Nature 479 , 141 (2011) doi:10.1038/nj7371-141d Published online 02 November 2011 This article was originally published in the journal Nature Graduates lured to non-science careers by pay and flexibility. University graduates with skills in science, technology, engineering and maths (STEM) are in high demand in non-STEM jobs in the United States, says a report, STEM , released on 20 October by Georgetown University in Washington DC. STEM graduates often work in health care and in managerial and professional jobs in sales or manufacturing. Co-author Nicole Smith, a Georgetown economist, says that non-STEM posts pay better than academia, which is a big draw. Women preferred non-STEM posts that offered flexibility and promotion. The report, which used data from about 20,000 graduates, says STEM departments should help university students to find work in their areas of study. http://www.nature.com/naturejobs/2011/111103/full/nj7371-141d.html ps. I think this is good for the society, no matter how you look at it.
Provider: Quertle (www.quertle.info) Content: text/plain; charset=UTF-8 TY- JOUR TI- A polymeric nanoparticle formulation of curcumin inhibits growth, clonogenicity and stem-like fraction in malignant brain tumors. AU- Lim, Kah Jing AU- Bisht, Savita AU- Bar, Eli E AU- Maitra, Anirban AU- Eberhart, Charles G PY- 2011 T2- Cancer biology therapy J2- Cancer Biol Ther UR- http://www.ncbi.nlm.nih.gov/pubmed/21193839 VL- 11 IS- 5 N2- Curcumin is a polyphenolic compound derived from the Indian spice turmeric. We used nanoparticle-encapsulated curcumin to treat medulloblastoma and glioblastoma cells. This formulation caused a dose-dependent decrease in growth of multiple brain tumor cell cultures, including the embryonal tumor derived lines DAOY and D283Med, and the glioblastoma neurosphere lines HSR-GBM1 and JHH-GBM14. The reductions in viable cell mass observed were associated with a combination of G2/M arrest and apoptotic induction. Curcumin also significantly decreased anchorage-independent clonogenic growth and reduced the CD133-positive stem-like population. Down-regulation of the insulin-like growth factor pathway in DAOY medulloblastoma cells was observed, providing one possible mechanism for the changes. Levels of STAT3 were also attenuated. Hedgehog signaling was blocked in DAOY cells but Notch signaling was not inhibited. Our data suggest that curcumin nanoparticles can inhibit malignant brain tumor growth through the modulation of cell proliferation, survival and stem cell phenotype. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- BMP-2 inhibits the tumorigenicity of cancer stem cells in human osteosarcoma OS99-1 cell line. AU- Wang, Lin AU- Park, Paul AU- Zhang, Huina AU- Marca, Frank La AU- Claeson, Amy AU- Valdivia, Juan AU- Lin, Chia-Ying PY- 2011 T2- Cancer biology therapy J2- Cancer Biol Ther UR- http://www.ncbi.nlm.nih.gov/pubmed/21178508 VL- 11 IS- 5 N2- Previously, based on high ALDH activity, we showed that cancer stem cells (CSCs) could be identified as ALDHbr cells from an aggressive human osteosarcoma OS99-1 cell line. In this study, we evaluate the impact of BMP-2 on CSCs.Three types of BMP receptors were expressed in freshly sorted ALDHbr cells. In vitro, growth of the sorted ALDHbr cells was inhibited by BMP-2. Using RT-PCR analysis, BMP-2 was found to down-regulate the expression of embryonic stem cell markers Oct3/4, Nanog, and Sox-2, and up-regulate the transcription of osteogenic markers Runx-2 and Collagen Type I. In vivo, all animals receiving ALDHbr cells treated with BMP-2 did not form significant tumors, while untreated ALDHbr cells developed large tumor masses in NOD/SCID mice. Immunostaining confirmed few Ki-67 positive cells were present in the sections of tumor containing ALDHbr cells treated with BMP-2. These results suggest that BMP-2 suppresses tumor growth by reducing the gene expression of tumorigenic factors and inducing the differentiation of CSCs in osteosarcoma. BMP-2 or BMP-2-mimetic drugs, if properly delivered to tumor and combined with traditional therapies, may therefore provide a new therapeutic option for treatment of osteosarcoma. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Pancreatic cancer spheres are more than just aggregates of stem marker-positive cells AU- Gaviraghi, Margherita AU- Tunici, Patrizia AU- Valensin, Silvia AU- Rossi, Marco AU- Giordano, Cinzia AU- Magnoni, Letizia AU- Dandrea, Mario AU- Montagna, Licia AU- Ritelli, Rossana AU- Scarpa, Aldo AU- Bakker, Annette PY- 2011 T2- Bioscience Reports J2- Biosci Rep UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990923/ VL- 31 IS- Pt 1 SP- 45-55 DO- 10.1042/BSR20100018 C2- 2990923 N2- Pancreatic cancer stem-like cells are described by membrane expression of CD24, CD44 and ESA (epithelial-specific antigen) and their capacity to grow as spheres in a serum-free medium containing well-defined growth factors. The capacity of a panel of four pancreatic cancer cell lines (PANC-1, CFPAC-1, PancTu-1 and PSN-1) to form spheres was tested. All cell lines with the exception of PancTu-1 developed spheres. Phenotypically, the sphere-growing cells showed an increased in vitro invasion capability. Both gene and protein expressions of markers of metastases and components of active hedgehog pathway signalling were assessed. Spheres clearly demonstrated increased expression of the above-mentioned markers when compared with their adherent counterpart. With the aim of identifying a minimum set of markers able to separate cells that have the capacity to form spheres from those incapable of forming spheres, a PCA (principal component analysis) of the multidimensional dataset was performed. Although PCA of the accepted stemness genes was unable to separate sphere-forming from sphere-incapable cell lines, the addition of the aggressiveness marker CD44v6 allowed a clear differentiation. Moreover, inoculation of the spheres and the adherent cells in vivo confirmed the superior aggressiveness (proliferation and metastasis) of the spheres over the adherent cells. In conclusion, the present study suggests that the sphere-growing cell population is not only composed of cells displaying classical stem membrane markers but also needs CD44v6-positive cells to successfully form spheres. Our results also emphasize the potential therapeutic importance of pathways such as CXCR4 and hedgehog for pancreatic cancer treatment. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Molecular epidemiology of human respiratory syncytial virus subgroups A and B identified in adults with hematological malignancy attending an Irish hospital between 2004 and 2009. AU- Salter, Aisling AU- Laoi, Bairbre Ni AU- Crowley, Brendan PY- 2011 T2- Journal of medical virology J2- J Med Virol UR- http://www.ncbi.nlm.nih.gov/pubmed/21181932 VL- 83 IS - 2 SP- 337-47 N2- Human respiratory syncytial virus (HRSV) is an important cause of respiratory infection in patients with hematological malignancy, particularly hematopoietic stem cell transplant recipients. This study investigated the genetic variability of the attachment (G) protein gene among HRSV isolates collected from adult patients with hematological malignancy. Between December 2004 and March 2009, 60 samples collected from 58 adults attending an Irish hospital were positive for HRSV by direct immunofluorescence. Nucleotide sequence analysis of the G gene showed a slightly higher frequency of HRSV subgroup A (52%) than HRSV subgroup B (48%). Genetic variability was higher among subgroup A viruses (up to 13% at nucleotide level) than among subgroup B viruses (up to 4%). Phylogenetic analysis revealed two genotypes of HRSV subgroup A, GA2 and GA5, which cocirculated between 2004/2005 and 2007/2008, although GA2 alone was identified in season 2008/2009. Genotype BA was the only genotype of HRSV subgroup B identified. Genotype-specific amino acid substitutions were identified, with two and seven changes for GA2 and GA5, respectively. Furthermore, one to four potential N-glycosylation sites were found among HRSV subgroup A isolates while two to three were identified in HRSV B isolates. Predicted O-glycosylation sites included 25-34 and 40-43 in HRSV subgroups A and B, respectively. The average synonymous mutation-to-non-synonymous mutation ratios (dS/dN) implied neutral selection pressure on both HRSV subgroup isolates. This study provides data for the first time on the molecular epidemiology of HRSV isolates over five successive epidemic seasons among patients attending an Irish hospital. J. Med. Virol. 83:337-347, 2011. 2010 Wiley-Liss, Inc. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- BMSC enhance the survival of paclitaxel treated squamous cell carcinoma cells in vitro. AU- Scherzed, Agmal AU- Hackenberg, Stephan AU- Froelich, Katrin AU- Kessler, Michael AU- Koehler, Christian AU- Hagen, Rudolf AU- Radeloff, Andreas AU- Friehs, Gudrun AU- Kleinsasser, Norbert PY- 2011 T2- Cancer biology therapy J2- Cancer Biol Ther UR- http://www.ncbi.nlm.nih.gov/pubmed/21127403 VL- 11 IS- 3 SP- 35-43 N2- The 5-year survival rate of patients suffering from head and neck squamous cell carcinoma (HNSCC) is unsatisfying despite the advances in carcinoma treatment. Recent studies suggest that stem cells can be used as a gene therapy carrier for cancer treatment. Stem cells produce different cytokines such as growth factors in a paracrine manner and cancer cells may show drug resistance in the presence of such growth factors. Reports in the literature concerning treatment of cancer using bone marrow derived stem cells (BMSC) are controversial, which led us to investigate the effects of paclitaxel on human HNSCC cell lines (FaDu and HLaC 78) cultivated simultaneously with BMSC in a transwell system (co-culture). Co-culture and HNSCC cell lines were treated with 10nM of paclitaxel for 24h. Morphology, viability and apoptosis were measured by microscopy, the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, and the Annexin V-propidium iodide test. The survival of HNSCC cell lines treated with paclitaxel in co-culture increased significantly compared to control cells. Apoptosis of HNSCC cell lines in co-culture was attenuated significantly. In conclusion, BMSC increase HNSCC resistance to treatment with paclitaxel in vitro. Tumor-stroma interactions are critical components of tumor biology including tumor invasion and metastatic potential. Therefore particular attention must be paid to the complex tumor-stroma interactions to fully understand how tumor cells become chemoresistant. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Systemic absorption of topical lidocaine in a bone marrow transplant recipient with hepatic sinusoidal obstruction syndrome. AU- Gabra, Bichoy H AU- Abidi, Muneer H AU- Al-Khadimi, Zaid AU- Edwards, David J AU- Ibrahim, Rami B PY- 2011 T2- American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists J2- Am J Health Syst Pharm UR- http://www.ncbi.nlm.nih.gov/pubmed/21200060 VL- 68 IS- 2 SP- 135-7 N2- Purpose A case of systemic lidocaine exposure in a bone marrow transplant recipient with severe hepatic sinusoidal obstruction syndrome (SOS) receiving treatment with lidocaine patch 5% is reported. Summary A 35-year-old Caucasian man with a history of refractory acute lymphoblastic leukemia was admitted for a third allogeneic, mismatched, peripheral blood hematopoietic stem cell transplant from an unrelated donor, with a conditioning regimen that included busulfan and fludarabine. The patient was receiving treatment with lidocaine patch 5% (two patches daily, which was started five months before another hospital admission for the treatment of vincristine-related peripheral neuropathy. Baseline laboratory findings were within normal limits except for disease-related neutropenia and thrombocytopenia. Twenty days after hematopoietic stem cell transplantation (HSCT), the patient developed signs and symptoms of severe hepatic SOS. His serum alanine transaminase concentration rose from 65 IU/L at baseline to 370 IU/L, and his serum aspartate transaminase concentration rose from 32 IU/L at baseline to 871 IU/L. His total bilirubin increased to 2.8 mg/dL, and his body weight increased by 15%. An abdominal ultrasound noted ascites and hepatomegaly without reversal of blood flow. The lidocaine patch was discontinued, but the patient's condition continued to deteriorate. He died 38 days after HSCT from complications of severe hepatic SOS. Conclusion A 35-year-old man developed hepatic SOS 20 days after his third HSCT. As a result of his hepatic impairment, the patient, who had been receiving lidocaine patch 5% for the treatment of neuropathic pain, experienced increased systemic exposure to lidocaine, which led to discontinuation of the patch. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Telomeres in cancer and ageing. AU- Donate, Luis E AU- Blasco, Maria A PY- 2011 T2- Philosophical transactions of the Royal Society of London. Series B, Biological sciences J2- Philos Trans R Soc Lond B Biol Sci UR- http://www.ncbi.nlm.nih.gov/pubmed/21115533 VL- 366 IS- 1561 SP- 76-84 N2- Telomeres protect the chromosome ends from unscheduled DNA repair and degradation. Telomeres are heterochromatic domains composed of repetitive DNA (TTAGGG repeats) bound to an array of specialized proteins. The length of telomere repeats and the integrity of telomere-binding proteins are both important for telomere protection. Furthermore, telomere length and integrity are regulated by a number of epigenetic modifications, thus pointing to higher order control of telomere function. In this regard, we have recently discovered that telomeres are transcribed generating long, non-coding RNAs, which remain associated with the telomeric chromatin and are likely to have important roles in telomere regulation. In the past, we showed that telomere length and the catalytic component of telomerase, Tert, are critical determinants for the mobilization of stem cells. These effects of telomerase and telomere length on stem cell behaviour anticipate the premature ageing and cancer phenotypes of telomerase mutant mice. Recently, we have demonstrated the anti-ageing activity of telomerase by forcing telomerase expression in mice with augmented cancer resistance. Shelterin is the major protein complex bound to mammalian telomeres; however, its potential relevance for cancer and ageing remained unaddressed to date. To this end, we have generated mice conditionally deleted for the shelterin proteins TRF1, TPP1 and Rap1. The study of these mice demonstrates that telomere dysfunction, even if telomeres are of a normal length, is sufficient to produce premature tissue degeneration, acquisition of chromosomal aberrations and initiation of neoplastic lesions. These new mouse models, together with the telomerase-deficient mouse model, are valuable tools for understanding human pathologies produced by telomere dysfunction. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Rationale for inhibition of the hedgehog pathway paracrine loop in pancreatic adenocarcinoma. AU- Dimou, Anastasios AU- Syrigos, Kostas AU- Saif, Muhammad Wasif PY- 2011 T2- JOP : Journal of the pancreas J2- JOP UR- http://www.ncbi.nlm.nih.gov/pubmed/21206093 VL- 12 IS- 1 SP- 1-5 N2- The role of hedgehog pathway in the biology of pancreatic adenocarcinoma is an emerging area of investigation and provides a novel field for treatment intervention. Recent studies have shown the activation of the hedgehog pathway in pancreatic cancer. Despite the initial assumption of an autocrine mechanism, it seems that the hedgehog pathway contributes to the molecular conversation between tumor and its microenvironment through a paracrine loop. Furthermore, members of the hedgehog pathway crosstalk with other pathways; they regulate tumor angiogenesis and are associated with cancer stem cells. In addition, there is preclinical evidence about the efficiency of hedgehog inhibitors both in vitro and in vivo and the first clinical trials with those compounds in the treatment of patients with pancreatic adenocarcinoma, are already under way. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Human acute myelogenous leukemia stem cells are rare and heterogeneous when assayed in NOD/SCID/IL2Rc-deficient mice AU- Sarry, Jean-Emmanuel AU- Murphy, Kathleen AU- Perry, Robin AU- Sanchez, Patricia V AU- Secreto, Anthony AU- Keefer, Cathy AU- Swider, Cezary R AU- Strzelecki, Anne-Claire AU- Cavelier, Cindy AU- Rcher, Christian AU- Mansat-De Mas, Vronique AU- Delabesse, Eric AU- Danet-Desnoyers, G AU- Carroll, Martin PY- 2011 T2- The Journal of Clinical Investigation J2- J Clin Invest UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3007135/ VL- 121 IS- 1 SP- 384-395 DO- 10.1172/JCI41495 C2- 3007135 N2- Human leukemic stem cells, like other cancer stem cells, are hypothesized to be rare, capable of incomplete differentiation, and restricted to a phenotype associated with early hematopoietic progenitors or stem cells. However, recent work in other types of tumors has challenged the cancer stem cell model. Using a robust model of xenotransplantation based on NOD/SCID/IL2Rc-deficient mice, we confirmed that human leukemic stem cells, functionally defined by us as SCID leukemia-initiating cells (SL-ICs), are rare in acute myelogenous leukemia (AML). In contrast to previous results, SL-ICs were found among cells expressing lineage markers (i.e., among Lin+ cells), CD38, or CD45RA, all markers associated with normal committed progenitors. Remarkably, each engrafting fraction consistently recapitulated the original phenotypic diversity of the primary AML specimen and contained self-renewing leukemic stem cells, as demonstrated by secondary transplants. While SL-ICs were enriched in the LinCD38 fraction compared with the other fractions analyzed, SL-ICs in this fraction represented only one-third of all SL-ICs present in the unfractionated specimen. These results indicate that human AML stem cells are rare and enriched but not restricted to the phenotype associated with normal primitive hematopoietic cells. These results suggest a plasticity of the cancer stem cell phenotype that we believe has not been previously described. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Lessons from the Niche for Generation and Expansion of Hematopoietic Stem Cells AU- Bowman, Teresa V. AU- Zon, Leonard I. PY- 2011 T2- Drug discovery today. Therapeutic strategies J2- Drug Discov Today Ther Strateg UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014625/ VL- 6 IS- 4 SP- 135-140 DO- 10.1016/j.ddstr.2009.06.003 C2- 3014625 N2- Hematopoietic Stem Cells (HSCs) are used clinically to treat human blood-related genetic diseases and leukemias, but the availability of this therapy is constrained by the limiting number of transplantable HSCs. Previous strategies to expand HSCs in vitro resulted in precocious differentiation and reduced transplant efficiency. In vivo analysis of the mechanisms utilized by fetal and adult niches to control HSCs can be mimicked for therapeutic use. This review summarizes the latest research on the in vivo HSC niche and the clinical applications of this knowledge to promote ex vivo expansion and direct de novo generation of HSCs. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Stem cell niches and other factors that influence the sensitivity of bone marrow to radiation-induced bone cancer and leukaemia in children and adults. AU- Richardson, Richard B PY- 2011 T2- International journal of radiation biology J2- Int J Radiat Biol UR- http://www.ncbi.nlm.nih.gov/pubmed/21204614 N2- Purpose: This paper reviews and reassesses the internationally accepted niches or 'targets' in bone marrow that are sensitive to the induction of leukaemia and primary bone cancer by radiation. Conclusions:The hypoxic conditions of the 10 m thick endosteal/osteoblastic niche where preleukemic stem cells and hematopoietic stem cells (HSC) reside provides a radioprotective microenvironment that is 2- to 3-fold less radiosensitive than vascular niches. This supports partitioning the whole marrow target between the low haematological cancer risk of irradiating HSC in the endosteum and the vascular niches within central marrow. There is a greater risk of induced bone cancer when irradiating a 50 m thick peripheral marrow adjacent to the remodelling/reforming portion of the trabecular bone surface, rather than marrow next to the quiescent bone surface. This choice of partitioned bone cancer target is substantiated by the greater radiosensitivity of: (i) Bone with high remodelling rates, (ii) the young, (iii) individuals with hypermetabolic benign diseases of bone, and (iv) the epidemiology of alpha-emitting exposures. Evidence is given to show that the absence of excess bone-cancer in atomic-bomb survivors may be partially related to the extremely low prevalence among Japanese of Paget's disease of bone. Radiation-induced fibrosis and the wound healing response may be implicated in not only radiogenic bone cancers but also leukaemia. A novel biological mechanism for adaptive response, and possibility of dynamic targets, is advocated whereby stem cells migrate from vascular niches to stress-mitigated, hypoxic niches. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Bcl-2 and Fas Expressions Correlate with Proliferative Specificity of Adipose-derived Stem Cells (ASCs) in Breast Cancer. AU- Razmkhah, Mahboobeh AU- Jaberipour, Mansooreh AU- Ghaderi, Abbas PY- 2011 T2- Immunological investigations J2- Immunol Invest UR- http://www.ncbi.nlm.nih.gov/pubmed/21204604 N2- The tumor microenvironment consists of a dynamic interaction with several cell types including infiltrating cells from the immune system, fibroblasts, adipose derived stem cells (ASCs), and an appropriate milieu for tumor cell growth, expansion and spreading. The aim of this study was to focus on ASCs function by isolating and characterizing them from both breast cancer and normal breast adipose tissues. Therefore, the expressions of Bcl-2 and Fas mRNAs in these cells were determined using real-time quantitative PCR (Q-PCR). Also the proliferative properties of ASCs were compared among different pathological states and normal ASCs utilizing the MTT assay. It was observed that, Bcl-2 mRNA had 5-fold more expression in ASCs of patients than in controls. In contrast, Fas had a lower expression of mRNA in ASCs of patients compared to the controls. ASCs isolated from patients with stage 3 breast cancer had a statistically significant higher rate of proliferation compared to stage 2 and normal ASCs (P-value 0.001). Based on these results, ASCs of the tumor microenvironment may contribute to tumor growth and progression and consequently protect tumor cells from the host immune response. Therefore these cells may be considered as therapeutic targets of cancer immunotherapy. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Loss of Function of E-Cadherin in Embryonic Stem Cells and the Relevance to Models of Tumorigenesis AU- Mohamet, Lisa AU- Hawkins, Kate AU- Ward, Christopher M PY- 2011 T2- Journal of Oncology J2- J Oncol UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005858/ VL- 2011 DO- 10.1155/2011/352616 C2- 3005858 N2- E-cadherin is the primary cell adhesion molecule within the epithelium, and loss of this protein is associated with a more aggressive tumour phenotype and poorer patient prognosis in many cancers. Loss of E-cadherin is a defining characteristic of epithelial-mesenchymal transition (EMT), a process associated with tumour cell metastasis. We have previously demonstrated an EMT event during embryonic stem (ES) cell differentiation, and that loss of E-cadherin in these cells results in altered growth factor response and changes in cell surface localisation of promigratory molecules. We discuss the implication of loss of E-cadherin in ES cells within the context of cancer stem cells and current models of tumorigenesis. We propose that aberrant E-cadherin expression is a critical contributing factor to neoplasia and the early stages of tumorigenesis in the absence of EMT by altering growth factor response of the cells, resulting in increased proliferation, decreased apoptosis, and acquisition of a stem cell-like phenotype. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Glioblastoma Stem Cells: A Neuropathologist's View AU- McLendon, Roger E AU- Rich, Jeremy N PY- 2011 T2- Journal of Oncology J2- J Oncol UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2971570/ VL- 2011 DO- 10.1155/2011/397195 C2- 2971570 N2- Glioblastoma (WHO Grade IV) is both the most common primary brain tumor and the most malignant.Advances in the understanding of the biology of the tumor are needed in order to obtain a clearer picture of the mechanisms driving these tumors.To neuropathologists, glioblastoma is a tumor that represents a complex system of migrating pleomorphic tumor cells, proliferating blood vessels, infiltrating inflammatory cells, and necrosis.This review will highlight how the glioma stem cell concept brings these elements together into a collective whole, interacting with microenvironmental influences in complex ways. Borrowing from chaos theory a vocabulary of self organizing systems and complex adaptive systemsthat seem useful in describing these pathologic features, a new paradigm of glioblastoma biology will be proposed that genetic changes should be understood in a three dimensional framework as they relate not only to the tumor cells themselves but also to the multicellular hierarchical unit, not isolated from, but responsive to, its local milieu.In this way we will come to better appreciate the impact our therapeutic interventions have on the regional phenotypic heterogeneity that exists within the tumor and the intercellular communications directing adaptation and progression. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Targeted Therapy of Ewing's Sarcoma AU- Subbiah, Vivek AU- Anderson, Pete PY- 2011 T2- Sarcoma J2- Sarcoma UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2968715/ VL- 2011 DO- 10.1155/2011/686985 C2- 2968715 N2- Refractory and/or recurrent Ewing's sarcoma (EWS) remains a clinical challenge because the disease's resistance to therapy makes it difficult to achieve durable results with standard treatments that include chemotherapy, radiation, and surgery. Recently, insulin-like-growth-factor-1-receptor (IGF1R) antibodies have been shown to have a modest single-agent activity in EWS. Patient selection using biomarkers and understanding response and resistance mechanisms in relation to IGF1R and mammalian target of rapamycin pathways are areas of active research. Since EWS has a unique tumor-specific EWS-FLI1 t(11;22) translocation and oncogenic fusion protein, inhibition of EWS-FLI1 transcription, translation, and/or protein function may be key to eradicating EWS at the stem-cell level. Recently, a small molecule that blocks the protein-protein interaction of EWS-FLI1 with RNA helicase A has been shown in preclinical models to inhibit EWS growth. The successful application of this first-in-class protein-protein inhibitor in the clinic could become a model system for translocation-associated cancers such as EWS. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Omental milky spots in screening gastric cancer stem cells. AU- Cao, L AU- Hu, X AU- Zhang, Y AU- Sun, X T PY- 2011 T2- Neoplasma J2- Neoplasma UR- http://www.ncbi.nlm.nih.gov/pubmed/21067262 VL- 58 IS- 1 SP- 20-6 N2- The existence of cancer stem and progenitor cells in solid tumors has been widely postulated. However, neither the cancer stem cells nor the cancer progenitor cells have been definitively identified and functionally characterized. Here we propose anew strategy to identify and isolate gastric cancer stem cells -using omental milky spots to screen gastric cancer stem cells in peritoneal metastasis mouse models of gastric cancer. In this study, we used the property that the macrophages in omental milky spots are cytotoxic against tumor cells and so able to screen and collect cancer stem cells. Our findings suggest that macrophages in omental milky spots have not only cytotoxic properties against tumor cells but also provide amicroenvironment within milky spots in which cancer stem cells are capable to survive and grow into micrometastasis. Omental milky spot become acancer stem cell niche in this situation. Further we studied the omental milky spots for screening gastric cancer cells (OMSS-GCCs) and found that omental milky spot enriched the volume of gastric cancer stem cells. Tumors were consistently generated after an injection of 1103 OMSS-GCCs. OMSS-GCCs high express CD133 and low express CD324. Omental milky spots are ahighly efficient natural filter for screening gastric cancer stem cells. Keywords: cancer stem cell, gastric cancer, omentum, omental milky spot. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- RPRT TI- Generation of Breast Cancer Stem Cells by the EMT. AU- Weinberg, RA PY- 2011 T2- National Technical Information Service UR- http://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+toxline:@term+@DOCNO+NTIS/12990012 DB- NTIS N2- The epithelial-mesenchymal transition (EMT) has been found by us to induce normal mammary epithelial cells (MECs) to acquire mesenchymal traits and, in addition, many of the characteristics of mammary epithelial stem cells. At the same time, induction of an EMT in breast cancer cells causes them to acquire to many of the attributes of cancer stem cells (CSCs). However, none of these observations demonstrate that the products of EMT are actually stem cells. To demonstrate this, we developed a protocol for the efficient expression of EMT-inducing transcription factors in vector-infected cells. We have now demonstrated in initial experiments that induction of an EMT in normal mouse MECs results in an approximately 100-fold increase in their ability to generate mammary ductal trees. Hence, an EMT can indeed increase the formation of normal mammary epithelial stem cells. Attempts to produce the parallel result with human breast cancer cells have not advanced as far. Since we can now produce large numbers of cells with properties of human breast cancer stem cells, we have used these to screen for drugs that preferentially kill human CSCs and have found two agents that preferentially eliminate CSCs. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Transmembrane potential of GlyCl-expressing instructor cells induces a neoplastic-like conversion of melanocytes via a serotonergic pathway AU- Blackiston, Douglas AU- Adams, Dany S AU- Lemire, Joan M AU- Lobikin, Maria AU- Levin, Michael PY- 2011 T2- Disease Models Mechanisms J2- Dis Model Mech UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3008964/ VL- 4 IS- 1 SP- 67-85 DO- 10.1242/dmm.005561 C2- 3008964 N2- SUMMARY: Understanding the mechanisms that coordinate stem cell behavior within the host is a high priority for developmental biology, regenerative medicine and oncology. Endogenous ion currents and voltage gradients function alongside biochemical cues during pattern formation and tumor suppression, but it is not known whether bioelectrical signals are involved in the control of stem cell progeny in vivo. We studied Xenopus laevis neural crest, an embryonic stem cell population that gives rise to many cell types, including melanocytes, and contributes to the morphogenesis of the face, heart and other complex structures. To investigate how depolarization of transmembrane potential of cells in the neural crests environment influences its function in vivo, we manipulated the activity of the native glycine receptor chloride channel (GlyCl). Molecular-genetic depolarization of a sparse, widely distributed set of GlyCl-expressing cells non-cell-autonomously induces a neoplastic-like phenotype in melanocytes: they overproliferate, acquire an arborized cell shape and migrate inappropriately, colonizing numerous tissues in a metalloprotease-dependent fashion. A similar effect was observed in human melanocytes in culture. Depolarization of GlyCl-expressing cells induces these drastic changes in melanocyte behavior via a serotonin-transporter-dependent increase of extracellular serotonin (5-HT). These data reveal GlyCl as a molecular marker of a sparse and heretofore unknown cell population with the ability to specifically instruct neural crest derivatives, suggest transmembrane potential as a tractable signaling modality by which somatic cells can control stem cell behavior at considerable distance, identify a new biophysical aspect of the environment that confers a neoplastic-like phenotype upon stem cell progeny, reveal a pre-neural role for serotonin and its transporter, and suggest a novel strategy for manipulating stem cell behavior. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Preponderance of cells with stem cell characteristics in metastasising mouse mammary tumours induced by deregulated EphB4 and ephrin-B2 expression. AU- Kaenel, Philip AU- Schwab, Caroline AU- Mlchi, Kathrin AU- Wotzkow, Carlos AU- Andres, Anne-Catherine PY- 2011 T2- International journal of oncology J2- Int J Oncol UR- http://www.ncbi.nlm.nih.gov/pubmed/21109936 VL- 38 IS- 1 SP- 151-60 N2- We have previously shown that EphB4 and ephrin-B2 are differentially expressed in the mammary gland and that their deregulated expression in the mammary epithelium of transgenic mice leads to perturbations of the mammary parenchyma and vasculature. In addition, overexpression of EphB4 and expression of a truncated ephrin-B2 mutant, capable of receptor stimulation but incapable of reverse signalling, confers a metastasising phenotype on NeuT initiated mouse mammary tumours. We have taken advantage of this transgenic tumour model to compare stem cell characteristics between the non-metastasising and metastasising mammary tumours. We analysed the expression of the proliferation attenuating p21waf gene, which was significantly increased in the metastasising tumours. Moreover, we compared the expression of CK-19, Sca-1, CD24 and CD49f as markers for progenitor cells exhibiting a decreasing differentiation grade. Sca-1 expressing cells were the earliest progenitors detected in the non-metastasising NeuT induced tumours. The metastasising NeuT/EphB4 tumours were enriched in CD24 expressing cells, whereas the metastasising NeuT/truncated ephrin-B2 tumours contained in addition significant amounts of CD49f expressing cells. The same cell populations were also enriched in mammary glands of single transgenic MMTV-EphB4 and MMTV-truncated ephrin-B2 females indicating that deregulated EphB4-ephrin-B2 signalling interferes with the homeostasis of the stem/progenitor cell pool before tumour formation is initiated. Since the same cell populations are enriched in the normal tissue, primary mammary tumours and metastases we conclude that these progenitor cells were the origin of tumour formation and that this change in the tumour origin has led to the acquisition of the metastatic tumour phenotype. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Targeting the Mechanisms of Resistance to Chemotherapy and Radiotherapy with the Cancer Stem Cell Hypothesis AU- Morrison, Ryan AU- Schleicher, Stephen M AU- Sun, Yunguang AU- Niermann, Kenneth J AU- Kim, Sungjune AU- Spratt, Daniel E AU- Chung, Christine H AU- Lu, Bo PY- 2011 T2- Journal of Oncology J2- J Oncol UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2958340/ VL- 2011 DO- 10.1155/2011/941876 C2- 2958340 N2- Despite advances in treatment, cancer remains the 2nd most common cause of death in the United States. Poor cure rates may result from the ability of cancer to recur and spread after initial therapies have seemingly eliminated detectable signs of disease. A growing body of evidence supports a role for cancer stem cells (CSCs) in tumor regrowth and spread after initial treatment. Thus, targeting CSCs in combination with traditional induction therapies may improve treatment outcomes and survival rates. Unfortunately, CSCs tend to be resistant to chemo- and radiation therapy, and a better understanding of the mechanisms underlying CSC resistance to treatment is necessary. This paper provides an update on evidence that supports a fundamental role for CSCs in cancer progression, summarizes potential mechanisms of CSC resistance to treatment, and discusses classes of drugs currently in preclinical or clinical testing that show promise at targeting CSCs. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Ewing's Sarcoma and Second Malignancies AU- Schiffman, Joshua D AU- Wright, Jennifer PY- 2011 T2- Sarcoma J2- Sarcoma UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2957850/ VL- 2011 DO- 10.1155/2011/736841 C2- 2957850 N2- Ewing's sarcoma (ES) is a rare tumor that is most common in children and young adults. Late effects of ES therapy include second cancers, a tragic outcome for survivors of such a young age. This paper will explore the frequencies and types of malignancies that occur after ES. Additionally, it will review how second malignancies have changed with the shift in treatment from high-dose radiation to chemotherapy regimens including alkylators and epipodophyllotoxins. The risk of additional cancers in ES survivors will also be compared to survivors of other childhood cancers. Finally, the possible genetic contribution to ES and second malignancies will be discussed. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Pathobiologic Markers of the Ewing Sarcoma Family of Tumors: State of the Art and Prediction of Behaviour AU- Pinto, Alfredo AU- Dickman, Paul AU- Parham, David PY- 2011 T2- Sarcoma J2- Sarcoma UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2957858/ VL- 2011 DO- 10.1155/2011/856190 C2- 2957858 N2- Over the past three decades, the outcome of Ewing sarcoma family tumor (ESFT) patients who are nonmetastatic at presentation has improved considerably.The prognosis of patients with metastatic disease at the time of diagnosis and recurrence after therapy remains dismal.Drug-resistant disease at diagnosis or at relapse remains a major cause of mortality among patients diagnosed with ESFT.In order to improve the outcome for patients with potential relapse, there is an urgent need to find reliable markers that either predict tumor behaviour at diagnosis or identify therapeutic molecular targets at the time of recurrence. An improved understanding of the cell of origin and the molecular pathways that regulate tumorigenicity in ESFT should aid us in the search for novel therapies for ESFT. The purpose of this paper is thus to outline current concepts of sarcomagenesis in ESFT and to discuss ESFT patterns of differentiation and molecular markers that might affect prognosis or direct future therapeutic development. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Quiescent, Slow-Cycling Stem Cell Populations in Cancer: A Review of the Evidence and Discussion of Significance AU- Moore, Nathan AU- Lyle, Stephen PY- 2011 T2- Journal of Oncology J2- J Oncol UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948913/ VL- 2011 DO- 10.1155/2011/396076 C2- 2948913 N2- Long-lived cancer stem cells (CSCs) with indefinite proliferative potential have been identified in multiple epithelial cancer types. These cells are likely derived from transformed adult stem cells and are thought to share many characteristics with their parental population, including a quiescent slow-cycling phenotype. Various label-retaining techniques have been used to identify normal slow cycling adult stem cell populations and offer a unique methodology to functionally identify and isolate cancer stem cells. The quiescent nature of CSCs represents an inherent mechanism that at least partially explains chemotherapy resistance and recurrence in posttherapy cancer patients. Isolating and understanding the cell cycle regulatory mechanisms of quiescent cancer cells will be a key component to creation of future therapies that better target CSCs and totally eradicate tumors. Here we review the evidence for quiescent CSC populations and explore potential cell cycle regulators that may serve as future targets for elimination of these cells. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Mesenchymal Stem Cells and the Origin of Ewing's Sarcoma AU- Lin, Patrick P AU- Wang, Yongxing AU- Lozano, Guillermina PY- 2011 T2- Sarcoma J2- Sarcoma UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2952797/ VL- 2011 DO- 10.1155/2011/276463 C2- 2952797 N2- The origin of Ewing's sarcoma is a subject of much debate. Once thought to be derived from primitive neuroectodermal cells, many now believe it to arise from a mesenchymal stem cell (MSC). Expression of the EWS-FLI1 fusion gene in MSCs changes cell morphology to resemble Ewing's sarcoma and induces expression of neuroectodermal markers. In murine cells, transformation to sarcomas can occur. In knockdown experiments, Ewing's sarcoma cells develop characteristics of MSCs and the ability to differentiate into mesodermal lineages. However, it cannot be concluded that MSCs are the cell of origin. The concept of an MSC still needs to be rigorously defined, and there may be different subpopulations of mesenchymal pluripotential cells. Furthermore, EWS-FLI1 by itself does not transform human cells, and cooperating mutations appear to be necessary. Therefore, while it is possible that Ewing's sarcoma may originate from a primitive mesenchymal cell, the idea needs to be refined further. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Bmi-1 Regulates Snail Expression and Promotes Metastasis Ability in Head and Neck Squamous Cancer-Derived ALDH1 Positive Cells AU- Yu, Cheng-Chia AU- Lo, Wen-Liang AU- Chen, Yi-Wei AU- Huang, Pin-I AU- Hsu, Han-Shui AU- Tseng, Ling-Ming AU- Hung, Shih-Chieh AU- Kao, Shou-Yen AU- Chang, Charn-Jung AU- Chiou, Shih Hwa PY- 2011 T2- Journal of Oncology J2- J Oncol UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948925/ VL- 2011 DO - 10.1155/2011/609259 C2- 2948925 N2- Recent studies suggest that ALDH1 is a putative marker for HNSCC-derived cancer stem cells. However, the regulation mechanisms that maintain the stemness and metastatic capability of HNSCC-ALDH1+ cells remain unclear. Initially, HNSCC-ALDH1+ cells from HNSCC patient showed cancer stemness properties, and high expression of Bmi1 and Snail. Functionally, tumorigenic properties of HNSCC-ALDH1+ cells could be downregulated by knockdown of Bmi-1. Overexpression of Bmi-1 altered in expression property ALDH1 cells to that of ALDH1+ cells. Furthermore, knockdown of Bmi-1 enhanced the radiosensitivity of radiation-treated HNSCC-ALDH1+ cells. Moreover, overexpression of Bmi-1 in HNSCC-ALDH1 cells increased tumor volume and number of pulmonary metastatic lesions by xenotransplant assay. Importantly, knock-down of Bmi1 in HNSCC-ALDH1+ cells significantly decreased distant metastases in the lungs. Clinically, coexpression of Bmi-1/Snail/ALDH1 predicted the worst prognosis in HNSCC patients. Collectively, our data suggested that Bmi-1 plays a key role in regulating Snail expression and cancer stemness properties of HNSCC-ALDH1+ cells. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- CXCR4-transfected human umbilical cord blood-derived mesenchymal stem cells exhibit enhanced migratory capacity toward gliomas. AU- Park, Soon A AU- Ryu, Chung Heon AU- Kim, Seong Muk AU- Lim, Jung Yeon AU- Park, Sang In AU- Jeong, Chang Hyun AU- Jun, Jin Ae AU- Oh, Ji Hyeon AU- Park, Sun Hwa AU- Oh, Wonil AU- Jeun, Sin-Soo PY- 2011 T2- International journal of oncology J2- Int J Oncol UR- http://www.ncbi.nlm.nih.gov/pubmed/21109930 VL- 38 IS- 1 SP- 97-103 N2- Mesenchymal stem cells (MSCs) can be used as a delivery vehicle for gene therapy against brain tumors, because these cells have a migratory capacity toward glioma cells. Soluble factors including chemokines or growth factors expressed and released by glioma cells mediate the tropism of MSCs for gliomas. Among them, stromal cell-derived factor-1 (SDF-1) has been identified as a key molecule related to the tropism of MSC in many cancers containing gliomas. In this study, we found that overexpression of the SDF-1 receptor, CXCR4, on human umbilical cord blood-derived MSCs (hUCB-MSCs) enhanced the migratory capacity of MSCs toward gliomas. We showed that hUCB-MSCs have the migration ability toward the glioma cell lines and primary glioma cells. SDF-1 treatment increased the migration capacity of hUCB-MSCs in a dose-dependent manner and inhibition of SDF-1 or CXCR4 by treatment with the anti-SDF-1 or the CXCR4 antagonist AMD3100 blocked the migration capacity of hUCB-MSCs toward glioma cells. Furthermore, CXCR4-overexpressed hUCB-MSCs (hMSCs-CXCR4) showed a stronger migration capacity toward glioma cells in vitro compared with control MSCs, and also exhibited enhanced migration to glioma cells in an intracranial human malignant glioma xenograft model. These results indicate that SDF-1/CXCR4 could be involved in recruitment of hUCB-MSCs to glioma cells and that overexpression of CXCR4 may be a useful tool for stem cell-based glioma therapy. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma AU- Monroe, Marcus M. AU- Anderson, Eric C. AU- Clayburgh, Daniel R. AU- Wong, Melissa H. PY- 2011 T2- Journal of Oncology J2- J Oncol UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2976506/ VL- 2011 DO- 10.1155/2011/762780 C2- 2976506 N2- Accumulating evidence suggests that self-renewal and differentiation capabilities reside only in a subpopulation of tumor cells, termed cancer stem cells (CSCs), whereas the remaining tumor cell population lacks the ability to initiate tumor development or support continued tumor growth. In head and neck squamous cell carcinoma (HNSCC), as with other malignancies, cancer stem cells have been increasingly shown to have an integral role in tumor initiation, disease progression, metastasis and treatment resistance. In this paper we summarize the current knowledge of the role of CSCs in HNSCC and discuss the therapeutic implications and future directions of this field. N1- Exported from www.Quertle.info. Search query: cancer stem cells . ER- TY- JOUR TI- TRANSLATIONAL IMPACT PY- 2011 T2- Disease Models Mechanisms J2- Dis Model Mech UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014347/ VL- 4 IS- 1 SP- 80-80 DO- 10.1242/dmm.006650 C2- 3014347 N2- N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Novel Perspectives on p53 Function in Neural Stem Cells and Brain Tumors AU- Hede, Sanna-Maria AU- Nazarenko, Inga AU- Nistr, Monica AU- Lindstrm, Mikael S. PY- 2011 T2- Journal of Oncology J2- J Oncol UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010739/ VL- 2011 DO- 10.1155/2011/852970 C2- 3010739 N2- Malignant glioma is the most common brain tumor in adults and is associated with a very poor prognosis. Mutations in the p53 tumor suppressor gene are frequently detected in gliomas. p53 is well-known for its ability to induce cell cycle arrest, apoptosis, senescence, or differentiation following cellular stress. That the guardian of the genome also controls stem cell self-renewal and suppresses pluripotency adds a novel level of complexity to p53. Exactly how p53 works in order to prevent malignant transformation of cells in the central nervous system remains unclear, and despite being one of the most studied proteins, there is a need to acquire further knowledge about p53 in neural stem cells. Importantly, the characterization of glioma cells with stem-like properties, also known as brain tumor stem cells, has opened up for the development of novel targeted therapies. Here, we give an overview of what is currently known about p53 in brain tumors and neural stem cells. Specifically, we review the literature regarding transformation of adult neural stem cells and, we discuss how the loss of p53 and deregulation of growth factor signaling pathways, such as increased PDGF signaling, lead to brain tumor development. Reactivation of p53 in brain tumor stem cell populations in combination with current treatments for glioma should be further explored and may become a viable future therapeutic approach. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Sulforaphane synergizes with quercetin to inhibit self-renewal capacity of pancreatic cancer stem cells. AU- Srivastava, Rakesh K AU- Tang, Su-Ni AU- Zhu, Wenyu AU- Meeker, Daniel AU- Shankar, Sharmila PY- 2011 T2- Frontiers in bioscience (Elite edition) J2- Front Biosci (Elite Ed) UR- http://www.ncbi.nlm.nih.gov/pubmed/21196331 VL- 3 SP- 515-28 N2- According to the cancer stem cell hypothesis, the aggressive growth and early metastasis of cancer may arise through dysregulation of self-renewal of stem cells. The objectives of this study were to examine the molecular mechanisms by which sulforaphane (SFN, an active compound in cruciferous vegetables) inhibits self-renewal capacity of pancreatic cancer stem cells (CSCs), and synergizes with quercetin, a major polyphenol and flavonoid commonly detected in many fruits and vegetables. Our data demonstrated that SFN inhibited self-renewal capacity of pancreatic CSCs. Inhibition of Nanog by lentiviral-mediated shRNA expression enhanced the inhibitory effects of sulforaphane on self-renewal capacity of CSCs. SFN induced apoptosis by inhibiting the expression of Bcl-2 and XIAP, phosphorylation of FKHR, and activating caspase-3. Moreover, SFN inhibited expression of proteins involved in the epithelial-mesenchymal transition (beta -catenin, vimentin, twist-1, and ZEB1), suggesting the blockade of signaling involved in early metastasis. Furthermore, the combination of quercetin with SFN had synergistic effects on self-renewal capacity of pancreatic CSCs. These data suggest that SFN either alone or in combination with quercetin can eliminate cancer stem cell-characteristics. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Shock therapy: modulating stem cells PY- 2011 T2- Disease Models Mechanisms J2- Dis Model Mech UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014330/ VL- 4 IS- 1 SP- 1-1 C2- 3014330 N2- N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Flow Cytometric Detection of the Classical Hodgkin Lymphoma: Clinical and Research Applications AU- Roshal, Mikhail AU- Wood, Brent L AU- Fromm, Jonathan R PY- 2011 T2- Advances in Hematology J2- Adv Hematol UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2993040/ VL- 2011 DO- 10.1155/2011/387034 C2- 2993040 N2- Classical Hodgkin lymphoma (CHL) is a relatively uncommon Bcell-derived neoplasm that presents with rare malignant cells in an abundant reactive background. The diagnosis of CHL currently relies on a combination of morphologic findings and immunohistochemical stains. With the exception of rare cases with dramatically increased malignant populations, isolation of pure viable tumor cells has not been historically possible. Recently, a reliable flow cytometric assay for direct detection and isolation of the malignant cells in this disease has been developed. This assay has proven useful diagnostically and has been clinically validated to have a very high sensitivity and nearly absolute specificity for the diagnosis of CHL in routine clinical samples. This paper describes the methodology for the flow cytometric detection of CHL in clinical samples as well as current state of evaluation of background lymphocytes as an adjunct diagnostic test. Also discussed are exciting research applications of the direct isolation of viable tumor cells in CHL. The current state of flow cytometric evaluation of nodular lymphocyte predominant Hodgkin lymphoma and T cell-rich large B cell lymphoma is also briefly discussed. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- CD133 negative cancer stem cells in glioblastoma. AU- Beier, Christoph P AU- Beier, Dagmar PY- 2011 T2- Frontiers in bioscience (Elite edition) J2- Front Biosci (Elite Ed) UR- http://www.ncbi.nlm.nih.gov/pubmed/21196345 VL- 3 SP- 701-10 N2- Glioblastomas (GBM) are paradigmatic for the investigation of cancer stem cells (CSC) in solid tumors. Recently, the discovery of CD133- CSC in addition to CD133+ CSC has substantially added to our understanding of the complexity of GBM CSC. This review gives an overview on our current knowledge on CD133- cells in GBM and describes five different hypothesizes on the nature of CD133- cells in GBM. In addition, we summarize the current knowledge on tumorigenic CD133- CSC, list available markers, describe the current controversies on the origin of CD133- CSC, and discuss how the heterogeneity of CSC may correspond to the molecular heterogeneity of GBM. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Complexity of tumor vasculature and molecular targeting therapies. AU- Furuya, Mitsuko AU- Nagahama, Kiyotaka AU- Ishizu, Akihiro AU- Otsuka, Noriyuki AU- Nagashima, Yoji AU- Aoki, Ichiro PY- 2011 T2- Frontiers in bioscience (Elite edition) J2- Front Biosci (Elite Ed) UR- http://www.ncbi.nlm.nih.gov/pubmed/21196334 VL- 3 SP- 549-61 N2- Malignant solid tumors require blood supply for their uncontrollable progression. Angiogenic blood vessels generally sprout from preexisting vascular cells. In addition, various types of precursor cells also participate in tumor neovascularization. They include endothelial progenitor cells, hematopoietic stem cells and mesenchymal stem cells that are stimulated and attracted into tumor lesion, in which a wide variety of proinflammatory factors are involved. Among key molecules, vascular endothelial growth factor (VEGF) works as a mastermind regulator. Humanized monoclonal antibodies targeting VEGF-mediated signaling pathways are currently used as the most pervasive drugs in several types of progressive tumors. Adverse effects of these drugs include hypertension and proteinuria. Such symptoms are widely observed in preeclamptic patients whose blood contain high amount of natural VEGF antagonist. Vasoactive G protein-coupled receptors (GPCRs)-mediated signalings such as renin-angiotensin system and chemokine axes are also noticed that they may become effective therapeutic targets. In this review, we discuss general view of angiogenic microenvironment in solid tumors, and highlight several key signaling molecules and inhibitory effects of them on the whole system. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Metastatic potential of tumor-initiating cells in solid tumors. AU- Adhikari, Amit S AU- Agarwal, Neeraj AU- Iwakuma, Tomoo PY- 2011 T2- Frontiers in bioscience : a journal and virtual library J2- Front Biosci UR- http://www.ncbi.nlm.nih.gov/pubmed/21196274 VL- 16 SP- 1927-38 N2- The lethality of cancer is mainly caused by its properties of metastasis, drug resistance, and subsequent recurrence. Understanding the mechanisms governing these properties and developing novel strategies to overcome them will greatly improve the survival of cancer patients. Recent findings suggest that tumors are comprised of heterogeneous cell populations, and only a small fraction of these are tumorigenic with the ability to self-renew and produce phenotypically diverse tumor cell populations. Cells in this fraction are called tumor-initiating cells (TICs) or cancer stem cells (CSCs). TICs have been identified from many types of cancer. They share several similarities with normal adult stem cells including sphere-forming ability, self-renewability, and expression of stem cell surface markers and transcription factors. TICs have also been proposed to be responsible for cancer metastasis, however, scarce evidence for their metastatic potential has been provided. In this review article, we have attempted to summarize the studies which have examined the metastatic potential of TICs in solid tumors. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Lung Cancer Stem Cell: New Insights on Experimental Models and Preclinical Data AU- Rivera, Caroline AU- Rivera, Sofia AU- Loriot, Yohann AU- Vozenin, Marie-Catherine AU- Deutsch, Eric PY- 2011 T2- Journal of Oncology J2- J Oncol UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010697/ VL- 2011 DO- 10.1155/2011/549181 C2- 3010697 N2- Lung cancer remains the leading cause of cancer death. Understanding lung tumors physiopathology should provide opportunity to prevent tumor development or/and improve their therapeutic management. Cancer stem cell (CSC) theory refers to a subpopulation of cancer cells, also named tumor-initiating cells, that can drive cancer development. Cells presenting these characteristics have been identified and isolated from lung cancer. Exploring cell markers and signaling pathways specific to lung CSCs may lead to progress in therapy and improve the prognosis of patients with lung cancer. Continuous efforts in developing in vitro and in vivo models may yield reliable tools to better understand CSC abilities and to test new therapeutic targets. Preclinical data on putative CSC targets are emerging by now. These preliminary studies are critical for the next generation of lung cancer therapies. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- DNA methyltransferase inhibitor CDA-2 synergizes with high-dose thiotepa and paclitaxel in killing breast cancer stem cells. AU- Lu, Zhihao AU- Jia, Jun AU- Di, Lijun AU- Song, Guohong AU- Yuan, Yanhua AU- Ma, Bo AU- Yu, Jing AU- Zhu, Yulin AU- Wang, Xiaoli AU- Zhou, Xinna AU- Ren, Jun PY- 2011 T2- Frontiers in bioscience (Elite edition) J2- Front Biosci (Elite Ed) UR- http://www.ncbi.nlm.nih.gov/pubmed/21196304 VL- 3 SP- 240-9 N2- It has been suggested that breast cancer stem cells (CSCs), which characterized by CD44+CD24-/low, may result in treatment failure in patients with breast cancer. It is possible therefore that that inhibiting such subpopulation might subsequently improve clinical outcome. In the present study, we found that the CD44+/CD24-/low CSCs, isolated from both human breast cell line MCF-7 and MDA-MB-231, were more resistant to thiotepa, paclitaxel and anthracycline, when compared with the non-breast cancer stem cell subset from the same cell lines, whereas the chemosensitivities were remarkably reversed by higher concentration of thiotepa and paclitaxel except for adriamycin. The percentage of CSCs was significantly decreased with an addition of DNA methyltransferase inhibitor CDA-2 and the expression of Smo, Shh, and Gli-1 of Hedgehog signaling pathway in CSCs was decreased. Of important findings, combination of thiotepa or paclitaxel with CDA-2 could significantly inhibit the proliferation of CSCs regardless of their dosages. These results unveiled that the selection of cytotoxic agents and increasing their dosage might be of great importance in the respect of eliminating CSCs. DNA methyltransferase inhibitor CDA-2 exhibited a synergistic effect with cytotoxic drugs, which might provide a conceptually new therapeutic strategy. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Ewing Sarcoma: An Eponym Window to History AU- Cripe, Timothy P. PY- 2011 T2- Sarcoma J2- Sarcoma UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995899/ VL- 2011 DO- 10.1155/2011/457532 C2- 2995899 N2- Ewing sarcoma was named after James R. Ewing, an eminent American pathologist at Cornell who described the first cases in 1921. Although he is best remembered for this singular achievement, Ewing's contributions to the study of cancer were far more profound and influential. He essentially launched oncology as a discipline with the publication of his seminal textbook and founded the major American cancer societies that exist today. His vision of comprehensive cancer centers still drives our research infrastructure. Since his initial report, these organizations have helped us achieve numerous milestones in understanding and treating patients with Ewing sarcoma. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Breast cancer stem cells: A new challenge for breast cancer treatment. AU- Jain, Prachi AU- Alahari, Suresh K PY- 2011 T2- Frontiers in bioscience : a journal and virtual library J2- Front Biosci UR- http://www.ncbi.nlm.nih.gov/pubmed/21196267 VL- 16 SP- 1824-32 N2- The biggest challenge for cancer research is relapses that occur in patients undergoing chemotherapy and radiotherapy, suggesting that some cells in tumors escape targeted treatment. Key questions are why relapses occur and why current therapies fail to remove all cancer cells. The cancer stem-cell hypothesisis based on the fact that not all cells within a tumor are similar. Other than tumorigenesis and metastasis, cancer stem cells have some properties that are similar to those of normal stem cells, such as self-renewal and differentiation. Accordingly, breast cancer stem cells may arise from mutation of normal mammary stem cells or progenitor cells. Cancer stem cell regulation involves several factors, such as Wnt, Notch, and Hedgehog, mutations of which endow cancer stem cells with the capacity for self-renewal. Moreover, epithelial mesenchymal transition and microRNAs recently have been shown to regulate the stemness of cancer cells. Targeting cancer stem cells could prevent relapse and provide new hope for cancer prevention. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Colon cancer stem cells: implications in carcinogenesis. AU- Sanders, Matthew A AU- Majumdar, Adhip P N PY- 2011 T2- Frontiers in bioscience : a journal and virtual library J2- Front Biosci UR- http://www.ncbi.nlm.nih.gov/pubmed/21196254 VL- 16 SP- 1651-62 N2- The cancer stem cell model was described for hematologic malignancies in 1997 and since then evidence has emerged to support it for many solid tumors as well, including colon cancer. This model proposes that certain cells within the tumor mass are pluripotent and capable of self-renewal and have an enhanced ability to initiate distant metastasis. The cancer stem cell model has important implications for cancer treatment, since most current therapies target actively proliferating cells and may not be effective against the cancer stem cells that are responsible for recurrence. In recent years great progress has been made in identifying markers of both normal and malignant colon stem cells. Proteins proposed as colon cancer stem cell markers include CD133, CD44, CD166, ALDH1A1, Lgr5, and several others. In this review we consider the evidence for these proteins as colon cancer stem cell markers and as prognostic indicators of colon cancer survival. Additionally, we discuss potential functions of these proteins and the implications this may have for development of therapies that target colon cancer stem cells. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Epigenetic mechanisms in acute myeloid leukemia. AU- Peters, Antoine H F M AU- Schwaller, Juerg PY- 2011 T2- Progress in drug research. Fortschritte der Arzneimittelforschung. Progrs des recherches pharmaceutiques J2- Prog Drug Res UR- http://www.ncbi.nlm.nih.gov/pubmed/21141731 VL- 67 SP- 197-219 N2- Acute leukemia is characterized by clonal expansion of hematopoietic stem and progenitor cells with blocked differentiation. Clinical and experimental evidences suggest that acute myeloid leukemia (AML) is the product of several functionally cooperating genetic alterations including chromosomal translocations leading to expression of leukemogenic fusion proteins. Several AML-associated lesions target chromatin regulators like histone methyltransferases or histone acetyltransferases, including mixed-lineage leukemia 1 (MLL1) or CREB bindung protein/p300. Molecular and biochemical studies start to provide useful insights into the mechanisms of targeting and mode-of-action of such leukemogenic fusion proteins resulting in aberrant gene expression programs and AML. Chromatin modulating mechanisms are also mediating the transforming activity of key drivers of leukemogenesis by aberrant recruitment of corepressors. Recent large-scale screening efforts demonstrated that both aberrant DNA promoter methylation and aberrantly expressed microRNAs play an important role in the pathogenesis of AML as well. Current efforts to therapeutically exploit the potential reversibility of epigenetic mechanisms are focused on small molecules that inhibit DNA methyltransferases or histone deacetylases. Several phase I/II clinical trials using such compounds have reported promising, but mostly transient, clinical responses. This underscores the need to further dissect the molecular players of epigenetic mechanisms driving induction, maintenance, and potential reversibility of leukemic state to develop efficient and long-lasting targeted therapeutic strategies. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Self-renewal mechanisms in neural cancer stem cells. AU- Mantamadiotis, Theo AU- Taraviras, Stavros PY- 2011 T2- Frontiers in bioscience : a journal and virtual library J2- Front Biosci UR- http://www.ncbi.nlm.nih.gov/pubmed/21196191 VL- 16 SP- 598-607 N2- The view that there are cancer-initiating stem cells has led to a concerted effort to understand the nature of these cells. As in many tissues, rare populations of cancer stem cells have been characterized in neural cancers, including glioblastoma, medulloblastoma and epyndymoma. The ability of stem cells to undergo both symmetric (self-renewal) and asymmetric (division to produce a more differentiated cell) cell division is what defines them as stem cells. Understanding the molecular genetic mechanisms governing the self-renewal and proliferation of these cells will be important in developing novel more effective strategies which will perhaps lead to better treatments for many cancers, including some of the most difficult to treat, such as the most common and aggressive brain cancer, glioblastoma. This review will focus on the molecular genetic mechanisms which have recently been identified as being important for neural stem cell self-renewal in brain cancer. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Evidence for cancer stem cells contributing to the pathogenesis of ovarian cancer. AU- Curley, Michael D AU- Garrett, Leslie A AU- Schorge, John O AU - Foster, Rosemary AU- Rueda, Bo R PY- 2011 T2- Frontiers in bioscience : a journal and virtual library J2- Front Biosci UR- http://www.ncbi.nlm.nih.gov/pubmed/21196176 VL- 16 SP- 368-92 N2- Ovarian cancer represents the most lethal gynecologic malignancy, primarily due to a lack of early detection, which results in most patients being diagnosed at an advanced stage of disease. Though the ovarian surface epithelium is thought to provide the primary site of tumorigenesis, the exact etiology of the various tumor types associated with this disease remain undefined. Recent evidence suggests that ovarian tumors, like other solid tumors, contain distinct populations of cells that are responsible for tumor initiation, maintenance and growth. These specialized cells, termed cancer stem cells, display some of the hallmarks of normal stem cells and are thought to evade current chemotherapeutic strategies, resulting in an increased risk of recurrence. Here we review evidence for the existence of cancer stem cells in ovarian malignancies and their contribution to the pathology of this disease, critically evaluate the methods used for ovarian cancer stem cell definition and isolation, and discuss their clinical relevance. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Immunotherapy targeting colon cancer stem cells. AU- Iovino, Flora AU- Meraviglia, Serena AU- Spina, Marisa AU- Orlando, Valentina AU- Saladino, Vitanna AU- Dieli, Francesco AU- Stassi, Giorgio AU- Todaro, Matilde PY- 2011 T2- Immunotherapy J2- Immunotherapy UR- http://www.ncbi.nlm.nih.gov/pubmed/21174560 VL- 3 IS- 1 SP- 97-106 N2- In the last 10 years, cancer stem cells have interested the scientific community because this small tumorigenic population is also associated with tumor progression in human patients and specific targeting of cancer stem cells could be a strategy to eradicate cancers currently resistant to conventional therapy. Clinical studies have recently demonstrated that adding immune therapy to chemotherapy has survival benefits in comparison with chemotherapy alone that can sensitize tumors to immune cell-mediated killing (e.g., increasing sensitivity of tumor cells to subsequent cytotoxicity by T cells via upregulation of death receptors DR5 and Fas). However, loss of MHC molecules is often observed in cancer cells, rendering tumor cells resistant to CD8 T-cell-mediated cytotoxicity. For this reason, we review the role of other T-cell subsets, such as T and NK cells that are able to efficiently recognize and kill tumor cells and that could be used in passive or active immunotherapy in cancer stem cell eradication. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Novel agents to improve outcome of allogeneic transplantation for patients with multiple myeloma. AU- Kortm, Martin AU- Knop, Stefan AU- Einsele, Hermann PY- 2011 T2- Future oncology (London, England) J2- Future Oncol UR- http://www.ncbi.nlm.nih.gov/pubmed/21174544 VL- 7 IS- 1 SP- 135-43 N2- Over the last few decades therapy for multiple myeloma has improved remarkably. In particular, the introduction of novel agents has allowed improved response rates prior to, and after, stem cell transplantation with extension of progression-free survival in high-risk patients. Nevertheless, most patients relapse, leaving multiple myeloma an incurable disease. Despite being the only treatment option that has real curative potential, allogeneic transplantation has not shown its superiority to autologous transplantation due to its high morbidity and mortality rates. This review highlights how novel agents might help to reduce treatment-related mortality and to improve tumor control prior to and post-allogeneic stem cell transplant, which will hopefully result in significantly improved long-term disease control, and maybe a cure following this treatment modality. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER - TY- JOUR TI- In Vitro and In Vivo Evidence for the Importance of Breast Cancer Resistance Protein Transporters (BCRP/MXR/ABCP/ABCG2). AU- Schwabedissen, Henriette E Meyer Zu AU- Kroemer, Heyo K PY- 2011 T2- Handbook of experimental pharmacology J2- Handb Exp Pharmacol UR- http://www.ncbi.nlm.nih.gov/pubmed/21103975 VL- 201 SP- 325-71 N2- The breast cancer resistance protein (BCRP/ABCG2) is a member of the G-subfamiliy of the ATP-binding cassette (ABC)-transporter superfamily. This half-transporter is assumed to function as an important mechanism limiting cellular accumulation of various compounds. In context of its tissue distribution with localization in the sinusoidal membrane of hepatocytes, and in the apical membrane of enterocytes ABCG2 is assumed to function as an important mechanism facilitating hepatobiliary excretion and limiting oral bioavailability, respectively. Indeed functional assessment performing mouse studies with genetic deletion or chemical inhibition of the transporter, or performing pharmacogenetic studies in humans support this assumption. Furthermore the efflux function of ABCG2 has been linked to sanctuary blood tissue barriers as described for placenta and the central nervous system. However, in lactating mammary glands ABCG2 increases the transfer of substrates into milk thereby increasing the exposure to potential noxes of a breastfed newborn. With regard to its broad substrate spectrum including various anticancer drugs and environmental carcinogens the function of ABCG2 has been associated with multidrug resistance and tumor development/progression. In terms of cancer biology current research is focusing on the expression and function of ABCG2 in immature stem cells. Recent findings support the notion that the physiological function of ABCG2 is involved in the elimination of uric acid resulting in higher risk for developing gout in male patients harboring genetic variants. Taken together ABCG2 is implicated in various pathophysiological and pharmacological processes. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Cancer Stem Cells: Repair Gone Awry? AU- Rangwala, Fatima AU- Omenetti, Alessia AU- Diehl, Anna Mae PY- 2011 T2- Journal of Oncology J2- J Oncol UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003969/ VL- 2011 DO- 10.1155/2011/465343 C2- 3003969 N2- Because cell turnover occurs in all adult organs, stem/progenitor cells within the stem-cell niche of each tissue must be appropriately mobilized and differentiated to maintain normal organ structure and function. Tissue injury increases the demands on this process, and thus may unmask defective regulation of pathways, such as Hedgehog (Hh), that modulate progenitor cell fate. Hh pathway dysregulation has been demonstrated in many types of cancer, including pancreatic and liver cancers, in which defective Hh signaling has been linked to outgrowth of Hh-responsive cancer stem-initiating cells and stromal elements.Hence, the Hh pathway might be a therapeutic target in such tumors. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Side population in MDA-MB-231 human breast cancer cells exhibits cancer stem cell-like properties without higher bone-metastatic potential. AU- Hiraga, Toru AU- Ito, Susumu AU- Nakamura, Hiroaki PY- 2011 T2- Oncology reports J2- Oncol Rep UR- http://www.ncbi.nlm.nih.gov/pubmed/21109989 VL- 25 IS- 1 SP- 289-96 N2- An increasing body of evidence suggests that cancers contain a small subset of their own stem-like cells called cancer stem cells (CSCs), which play critical roles in the initiation, maintenance and relapse of tumors. However, the role of CSCs in cancer metastasis, especially in metastasis to bone, has not been extensively studied. Side population (SP) has been shown to enrich CSCs in several types of cancer, including breast cancer. In the present study, we characterized the SP cells isolated from the human breast cancer cell line MDA-MB-231 in comparison to non-SP (NSP). Fluorescence-activated cell sorter analysis demonstrated the existence of SP in MDA-MB-231 cells, which was markedly reduced in the presence of fumitremorgin C, a specific inhibitor of ATP-binding cassette sub-family G member 2 (ABCG2). Quantitative RT-PCR analysis showed that ABCG2 mRNA expression was significantly higher in SP cells than in NSP cells. SP cells formed increased numbers of tumor-spheres in suspension culture. Furthermore, the tumor growth in the orthotopic mammary fat pad in nude mice was significantly accelerated in SP cells. On the other hand, the development of bone metastases determined by intracardiac injection into nude mice showed no difference between SP and NSP cells. SP abundance in the tumor cells isolated from the bone metastases was not increased either compared with that from the mammary tumors. These results suggest that the SP in MDA-MB-231 cells possesses some of the CSC-like properties but does not have higher metastatic potential to bone. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Angiogenic activity of mesenchymal stem cells in multiple myeloma. AU- Wang, Xiaofang AU- Zhang, Zhiqing AU- Yao, Cheng PY- 2011 T2- Cancer investigation J2- Cancer Invest UR- http://www.ncbi.nlm.nih.gov/pubmed/21166497 VL- 29 IS- 1 SP- 37-41 N2- The pathophysiology of multiple myeloma-induced angiogenesis is complex and involves both direct production of angiogenic cytokines by plasma cells and their induction within the microenvironment. In this research, we investigated whether mesenchymal stem cells participated in inducing the angiogenic response in multiple myeloma, and explored the mechanism by which MSCs influence myeloma angiogenesis. We detected the concentration of angiogenic factors (bFGF, HGF, and VEGF) in the conditioned medium of mesenchymal stem cells and the capillary formation ability of mesenchymal stem cells in vitro. We found that conditioned medium of MSCs derived from MM significantly promoted the proliferation, chemotaxis, and capillary formation of human umbilical vein endothelial cells compared with that from normal donors. ELISA and RT-PCR were used to detect the mRNA and protein levels of angiogenic factors (bFGF, HGF, and VEGF) in the conditioned medium. We found that mRNA and protein levels of angiogenic factors were elevated in MSCs from multiple myeloma compared with normal donors. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Combined treatment of tumor-tropic human neural stem cells containing the CD suicide gene effectively targets brain tumors provoking a mild immune response. AU- Lee, Se Jeong AU- Kim, Yonghyun AU- Jo, Mi-Young AU- Kim, Hyeong-Seok AU- Jin, Younggeon AU- Kim, Seung U AU- Jin, Juyoun AU- Joo, Kyeung Min AU- Nam, Do-Hyun PY- 2011 T2- Oncology reports J2- Oncol Rep UR- http://www.ncbi.nlm.nih.gov/pubmed/21109958 VL- 25 IS- 1 SP- 63-8 N2- Previous studies showed promise of coupling genetically engineered neural stem cells (NSCs) with blood-brain barrier permeable prodrugs as an effective anti-brain tumor therapy. Here, we further advance those findings by testing the suicide gene therapeutic system in syngenic glioblastoma immunocompetent mice. After intracranial injection of HB1.F3.CD, an immortalized human NSC cell line engineered to constitutively produce cytosine deaminase (CD), the prodrug 5-fluorocytosine (5-FC) was administered for five days, q.d., via intraperitoneal injection. The HB1. F3.CD hNSCs migrated specifically to the brain tumor site via the corpus callosum and significantly reduced the tumor volume (67%) by converting 5-FC into the cytotoxic 5-fluorouracil. A corresponding increase in F4/80-positive population was observed in the treatment group, although CD3-positive population remained unchanged compared to control. No toxic effects or morphological changes were observed in the spleen and the lymph nodes. The data suggest that the NSC-enzyme/prodrug treatment is an effective anti-tumor therapeutic strategy that specifically targets only the tumor site with little or no systemic side effects. In addition, the treatment modeled here successfully elicited a macrophagic immune response which seemed to have a synergistic role in reducing tumor volume, thus showing promise for treatment-mediated enhancement of inherent immune responses against brain tumors. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- The anti-diabetic drug metformin suppresses the metastasis-associated protein CD24 in MDA-MB-468 triple-negative breast cancer cells. AU- Vazquez-Martin, Alejandro AU- Oliveras-Ferraros, Cristina AU- Cuf, Silvia AU- Del Barco, Sonia AU- Martin-Castillo, Begoa AU- Lopez-Bonet, Eugeni AU- Menendez, Javier A PY- 2011 T2- Oncology reports J2- Oncol Rep UR- http://www.ncbi.nlm.nih.gov/pubmed/21109968 VL- 25 IS- 1 SP- 135-40 N2- CD24, a mucin-like adhesion molecule that enhances the metastatic potential of malignant cells, has been suggested to be a marker of poor prognosis in breast carcinomas. The tumor-initiating potential of CD44posCD24pos cell populations has been recently recognized and, accordingly, distant metastases are largely composed of CD24-positive cells in breast cancer patients refractory to treatment. Therefore, new therapeutic strategies aimed at down-regulating CD24 may negatively regulate the dissemination of tumor cells and formation of metastasis. Here, we reveal that suppression of CD24 protein expression is a crucial event in the molecular mechanisms underlying the growth-inhibitory effects of the anti-diabetic drug metformin in MDA-MB-468 triple-negative (basal-like) breast cancer cells. First, we confirmed that, among the different molecular classes of breast cancer, basal-like breast cancer cells were significantly more sensitive to the growth-inhibitory effects of metformin. Second, we observed a positive correlation between the growth inhibitory activity of metformin and the relative enrichment in cells bearing the CD44posCD24pos immunophenotype. Third, high-content indirect immunofluorescence imaging assays revealed that CD24 protein levels were drastically decreased in the presence of growth-inhibitory concentrations of metformin. Fourth, to preliminary assess the clinical relevance of metformin's anti-CD24 effects we took advantage of the recently developed ROCK online interface (http://rock.icr.ac.uk/), a publicly accessible portal that allows rapid integration of breast cancer functional and molecular profiling datasets. When we evaluated the impact of CD24 expression on distant metastasis-free survival (DMFS) in microarray gene expression breast cancer datasets, Kaplan-Meier survival analyses and log-rank tests comparing DMSF for CD24-high and CD24-low breast carcinomas revealed that patients with CD24-high tumors tended to have a shorter DMFS. These findings, altogether, suggest that the ability of metformin to suppress the oncogene, metastasis promoter and breast cancer stem cell marker CD24 may open a novel molecular avenue in the therapeutic management of highly-metastastic subgroups of triple-negative (basal-like) breast cancers naturally enriched with CD44posCD24pos tumor-initiating cell populations. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Description of the CD133+ subpopulation of the human ovarian cancer cell line OVCAR3. AU- Guo, Rongjiao AU- Wu, Qiuhua AU- Liu, Fenghua AU- Wang, Yifeng PY- 2011 T2- Oncology reports J2- Oncol Rep UR- http://www.ncbi.nlm.nih.gov/pubmed/21109969 VL- 25 IS- 1 SP- 141-6 N2- Cancer stem cells (CSCs) form a very rare population within tumors and possess the ability to proliferate and self-renew indefinitely. The cluster of differentiation (CD) 133+ ovarian CSCs (OCSCs) have been identified recently and their clinical implications are about to be clarified. In this context, we use the CD133 antigen as a marker of OCSCs in OVCAR3 cells and show that microRNAs (miRNAs) are aberrantly expressed in this subpopulation. The OCSCs in the OVCAR3 cell line were identified by the monoclonal mouse anti-CD133-1 antibody (clone CD133). Microarray and real-time reverse transcription-polymerase chain reaction (RT-PCR) analyses were used to identify miRNAs with altered expression in CD133+ cells. The expression levels of dysregulated miRNAs, namely, miR-204, miR-206, miR-223, miR-9, miR-100, and miR-200c, were examined using TaqMan PCR. The RNA and protein levels of stem cell-specific genes were examined by real-time RT-PCR and western blot analyses. Our results of microarray and real-time RT-PCR analyses revealed distinct miRNA expression profiles between CD133+ and CD133- OVCAR3 cells. The expression of stem cell-specific genes, namely, Oct3/4, Sox2, and Nanog, was higher in CD133+ cells than in CD133- cells while that of FoxD3, was lower in CD133+ cells than in CD133- cells. In conclusion, our data indicate that CD133 expression defines a tumor-initiating subpopulation of cells in the OVCAR3 cell line. The overall miRNA expression profile of CD133+ OVCAR3 cells was clearly distinct from that of CD133- OVCAR3 cells, indicating that miRNAs are involved in the development of this neoplasia and may serve as pertinent chemotherapeutic targets. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- A comparative study of the structural organization of spheres derived from the adult human subventricular zone and glioblastoma biopsies. AU- Vik-Mo, Einar Osland AU- Sandberg, Cecilie AU- Joel, Mrinal AU- Stangeland, Biljana AU- Watanabe, Yasuhiro AU- Mackay-Sim, Alan AU- Moe, Morten Carstens AU- Murrell, Wayne AU- Langmoen, Iver Arne PY- 2010 T2- Experimental cell research J2- Exp Cell Res UR- http://www.ncbi.nlm.nih.gov/pubmed/21199649 N2- Sphere forming assays have been useful to enrich for stem like cells in a range of tumors. The robustness of this system contrasts the difficulties in defining a stem cell population based on cell surface markers. We have undertaken a study to describe the cellular and organizational composition of tumorspheres, directly comparing these to neurospheres derived from the adult human subventricular zone (SVZ). Primary cell cultures from brain tumors were found to contain variable fractions of cells positive for tumor stem cell markers (CD133 (2-93%)/SSEA1 (3-15%)/CXCR4 (1-72%)). All cultures produced tumors upon xenografting. Tumorspheres contained a heterogeneous population of cells, but were structurally organized with stem cell markers present at the core of spheres, with markers of more mature glial progenitors and astrocytes at more peripheral location. Ultrastructural studies showed that tumorspheres contained a higher fraction of electron dense cells in the core than the periphery (36% and 19%, respectively). Neurospheres also contained a heterogeneous cell population, but did not have an organization similar to tumorspheres. Although tumorspheres clearly display irregular and neoplastic cells, they establish an organized structure with an outward gradient of differentiation. We suggest that this organization is central in maintaining the tumor stem cell pool. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Microarray-based Analysis of MicroRNA Expression in Breast Cancer Stem Cells. AU- Sun, Jian-Guo AU- Liao, Rong-Xia AU- Qiu, Jun AU- Jin, Jun-Yu AU- Wang, Xin-Xin AU- Duan, Yu-Zhong AU- Chen, Fang-Lin AU- Hao, Ping AU- Xie, Qi-Chao AU- Wang, Zhi-Xin AU- Li, De-Zhi AU- Chen, Zheng-Tang AU- Zhang, Shao-Xiang PY- 2010 T2- Journal of experimental clinical cancer research : CR J2- J Exp Clin Cancer Res UR- http://www.ncbi.nlm.nih.gov/pubmed/21192833 VL- 29 IS- 1 SP- 174 N2- ABSTRACT: Background This study aimed to determine the miRNA profile in breast cancer stem cells (BCSCs) and to explore the functions of characteristic BCSC miRNAs. Methods We isolated ESA+CD44+CD24-/low BCSCs from MCF-7 cells using fluorescence-activated cell sorting (FACS). A human breast cancer xenograft assay was performed to validate the stem cell properties of the isolated cells, and microarray analysis was performed to screen for BCSC-related miRNAs. These BCSC-related miRNAs were selected for bioinformatic analysis and target prediction using online software programs. Results The ESA+CD44+CD24-/low cells had up to 100- to 1000-fold greater tumour-initiating capability than the MCF-7 cells. Tumours initiated from the ESA+CD44+CD24-/low cells were composed of luminal epithelial and myoepithelial cells, indicating stem cell properties. We also obtained miRNA profiles of ESA+CD44+CD24-/low BCSCs. Most of the possible targets of potential tumourigenesis-related miRNAs were oncogenes, anti-oncogenes or regulatory genes. Conclusions We identified a subset of miRNAs that were differentially expressed in BCSCs, providing a starting point to explore the functions of these miRNAs. Evaluating characteristic BCSC miRNAs represents a new method for studying breast cancer-initiating cells and developing therapeutic strategies aimed at eradicating the tumourigenic subpopulation of cells in breast cancer. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Gene Expression Profiling Reveals New Aspects of PIK3CA Mutation in ERalpha-Positive Breast Cancer: Major Implication of the Wnt Signaling Pathway AU- Cizkova, Magdalena AU- Cizeron-Clairac, Graldine AU- Vacher, Sophie AU- Susini, Aurlie AU- Andrieu, Catherine AU- Lidereau, Rosette AU- Biche, Ivan PY- 2010 T2- PLoS ONE J2- PLoS One UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012715/ VL- 5 IS- 12 DO- 10.1371/journal.pone.0015647 C2- 3012715 N2- Background: The PI3K/AKT pathway plays a pivotal role in breast cancer development and maintenance. PIK3CA, encoding the PI3K catalytic subunit, is the oncogene exhibiting a high frequency of gain-of-function mutations leading to PI3K/AKT pathway activation in breast cancer. PIK3CA mutations have been observed in 30% to 40% of ER-positive breast tumors. However the physiopathological role of PIK3CA mutations in breast tumorigenesis remains largely unclear. Methodology/Principal Findings: To identify relevant downstream target genes and signaling activated by aberrant PI3K/AKT pathway in breast tumors, we first analyzed gene expression with a pangenomic oligonucleotide microarray in a series of 43 ER-positive tumors with and without PIK3CA mutations. Genes of interest were then investigated in 249 ER-positive breast tumors by real-time quantitative RT-PCR. A robust collection of 19 genes was found to be differently expressed in PIK3CA-mutated tumors. PIK3CA mutations were associated with over-expression of several genes involved in the Wnt signaling pathway (WNT5A, TCF7L2, MSX2, TNFRSF11B), regulation of gene transcription (SEC14L2, MSX2, TFAP2B, NRIP3) and metal ion binding (CYP4Z1, CYP4Z2P, SLC40A1, LTF, LIMCH1). Conclusion/Significance: This new gene set should help to understand the behavior of PIK3CA-mutated cancers and detailed knowledge of Wnt signaling activation could lead to novel therapeutic strategies. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Efficient Generation of Multipotent Mesenchymal Stem Cells from Umbilical Cord Blood in Stroma-Free Liquid Culture AU- Peters, Rowayda AU- Wolf, Monika J. AU- van den Broek, Maries AU- Nuvolone, Mario AU- Dannenmann, Stefanie AU- Stieger, Bruno AU- Rapold, Reto AU- Konrad, Daniel AU- Rubin, Arnold AU- Bertino, Joseph R. AU- Aguzzi, Adriano AU- Heikenwalder, Mathias AU- Knuth, Alexander K. PY- 2010 T2- PLoS ONE J2- PLoS One UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012708/ VL- 5 IS- 12 DO- 10.1371/journal.pone.0015689 C2- 3012708 N2- Background: Haematopoiesis is sustained by haematopoietic (HSC) and mesenchymal stem cells (MSC). HSC are the precursors for blood cells, whereas marrow, stroma, bone, cartilage, muscle and connective tissues derive from MSC. The generation of MSC from umbilical cord blood (UCB) is possible, but with low and unpredictable success. Here we describe a novel, robust stroma-free dual cell culture system for long-term expansion of primitive UCB-derived MSC. Methods and Findings: UCB-derived mononuclear cells (MNC) or selected CD34+ cells were grown in liquid culture in the presence of serum and cytokines. Out of 32 different culture conditions that have been tested for the efficient expansion of HSC, we identified one condition (DMEM, pooled human AB serum, Flt-3 ligand, SCF, MGDF and IL-6; further denoted as D7) which, besides supporting HSC expansion, successfully enabled long-term expansion of stromal/MSC from 8 out of 8 UCB units (5 MNC-derived and 3 CD34+ selected cells). Expanded MSC displayed a fibroblast-like morphology, expressed several stromal/MSC-related antigens (CD105, CD73, CD29, CD44, CD133 and Nestin) but were negative for haematopoietic cell markers (CD45, CD34 and CD14). MSC stemness phenotype and their differentiation capacity in vitro before and after high dilution were preserved throughout long-term culture. Even at passage 24 cells remained Nestin+, CD133+ and 95% were positive for CD105, CD73, CD29 and CD44 with the capacity to differentiate into mesodermal lineages. Similarly we show that UCB derived MSC express pluripotency stem cell markers despite differences in cell confluency and culture passages. Further, we generated MSC from peripheral blood (PB) MNC of 8 healthy volunteers. In all cases, the resulting MSC expressed MSC-related antigens and showed the capacity to form CFU-F colonies. Conclusions: This novel stroma-free liquid culture overcomes the existing limitation in obtaining MSC from UCB and PB enabling so far unmet therapeutic applications, which might substantially affect clinical practice. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Evi-1 is a transcriptional target of MLL oncoproteins in hematopoietic stem cells. AU- Arai, Shunya AU- Yoshimi, Akihide AU- Shimabe, Munetake AU- Ichikawa, Motoshi AU- Nakagawa, Masahiro AU- Imai, Yoichi AU- Goyama, Susumu AU- Kurokawa, Mineo PY- 2010 T2- Blood J2- Blood UR- http://www.ncbi.nlm.nih.gov/pubmed/21190993 N2- Ecotropic viral integration site-1 (Evi-1) is a nuclear transcription factor that plays an essential role in the regulation of hematopoietic stem cells (HSCs). Aberrant expression of Evi-1 has been reported in up to 10% of acute myeloid leukemia (AML) patients, and is a diagnostic marker that predicts a poor outcome. Although chromosomal rearrangement involving the Evi-1 gene is one of the major causes of Evi-1 activation, overexpression of Evi-1 is detected in a subgroup of AML without any chromosomal abnormalities, indicating the presence of other mechanisms for Evi-1 activation. In this study, we found that Evi-1 is frequently up-regulated in bone marrow cells transformed by MLL-ENL or MLL-AF9. Analysis of the Evi-1 gene promoter region revealed that MLL-ENL activates transcription of Evi-1. MLL-ENL-mediated up-regulation of Evi-1 occurs exclusively in the undifferentiated hematopoietic population, in which Evi-1 particularly contributes to the propagation of MLL-ENL-immortalized cells. Furthermore, gene expression analysis of human AML cases demonstrated the stem cell-like gene expression signature of Evi-1 high MLL-rearranged leukemia. Our findings indicate that Evi-1 is one of the targets of MLL oncoproteins, and is selectively activated in HSC-derived MLL leukemic cells. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- PC3 prostate tumor-initiating cells with molecular profile FAM65B(high)/MFI2(low)/LEF1(low) increase tumor angiogenesis. AU- Zhang, Kexiong AU- Waxman, David J PY- 2010 T2- Molecular cancer J2- Mol Cancer UR- http://www.ncbi.nlm.nih.gov/pubmed/21190562 VL- 9 IS- 1 SP- 319 N2- ABSTRACT: BACKGROUND: Cancer stem-like cells are proposed to sustain solid tumors by virtue of their capacity for self-renewal and differentiation to cells that comprise the bulk of the tumor, and have been identified for a variety of cancers based on characteristic clonal morphologies and patterns of marker gene expression. METHODS: Single cell cloning and spheroid culture studies were used to identify a population of cancer stem-like cells in the androgen-independent human prostate cancer cell line PC3. RESULTS: We demonstrate that, under standard culture conditions, ~10% of PC3 cells form holoclones with cancer stem cell characteristics. These holoclones display high self-renewal capability in spheroid formation assays under low attachment and serum-free culture conditions, retain their holoclone morphology when passaged at high cell density, exhibit moderate drug resistance, and show high tumorigenicity in scid immunodeficient mice. PC3 holoclones readily form spheres, and PC3-derived spheres yield a high percentage of holoclones, further supporting their cancer stem cell-like nature. We identified one gene, FAM65B, whose expression is consistently up regulated in PC3 holoclones compared to paraclones, the major cell morphology in the parental PC3 cell population, and two genes, MFI2 and LEF1, that are consistently down regulated. This molecular profile, FAM65B(high)/MFI2(low)/LEF1(low), also characterizes spheres generated from parental PC3 cells. The PC3 holoclones did not show significant enriched expression of the putative prostate cancer stem cell markers CD44 and integrin alpha2beta1. PC3 tumors seeded with holoclones showed dramatic down regulation of FAM65B and dramatic up regulation of MFI2 and LEF1, and unexpectedly, a marked increase in tumor vascularity compared to parental PC3 tumors, suggesting a role of cancer stem cells in tumor angiogenesis. CONCLUSIONS: These findings support the proposal that PC3 tumors are sustained by a small number of tumor-initiating cells with stem-like characteristics, including strong self-renewal and pro-angiogenic capability and marked by the expression pattern FAM65B(high)/MFI2(low)/LEF1(low). These markers may serve as targets for therapies designed to eliminate cancer stem cell populations associated with aggressive, androgen-independent prostate tumors such as PC3. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Vascular endothelial growth inhibitor (VEGI; TNFSF15) inhibits bone marrow-derived endothelial progenitor cell incorporation into Lewis lung carcinoma tumors. AU- Liang, Paulina H AU- Tian, Fang AU- Lu, Yi AU- Duan, Biyan AU- Stolz, Donna B AU- Li, Lu-Yuan PY- 2010 T2- Angiogenesis J2- Angiogenesis UR- http://www.ncbi.nlm.nih.gov/pubmed/21188501 N2- Bone marrow (BM)-derived endothelial progenitor cells (EPC) have a critical role in tumor neovascularization. Vascular endothelial growth inhibitor (VEGI) is a member of the TNF superfamily (TNFSF15). We have shown that recombinant VEGI suppresses tumor angiogenesis by specifically eliminating proliferating endothelial cells (EC). We report here that treatment of tumor bearing mice with recombinant VEGI leads to a significantly decreased population of BM-derived EPC in the tumors. We transplanted whole bone marrow from green fluorescent protein (GFP) transgenic mice into C57BL/6 recipient mice, which were then inoculated with Lewis lung carcinoma (LLC) cells. Intraperitoneal injection of recombinant VEGI led to significant inhibition of tumor growth and decrease of vasculature density compared to vehicle-treated mice. Tumor implantation yielded a decrease of BM-derived EPC in the peripheral blood, while VEGI-treatment resulted in an initial delay of such decrease. Analysis of the whole bone marrow showed a decrease of Lin(-)-c-Kit(+)-Sca-1(+) hematopoietic stem cell (HSC) population in tumor bearing mice; however, VEGI-treatment caused a significant increase of this cell population. In addition, the number of BM-derived EPC in VEGI-treated tumors was notably less than that in the vehicle-treated group, and most of the apoptotic cells in the VEGI-treated tumors were of bone marrow origin. These findings indicate that VEGI inhibits BM-derived EPC mobilization and prevents their incorporation into LLC tumors by inducing apoptosis specifically of BM-derived cells, resulting in the inhibition of EPC-supported tumor vasculogenesis and tumor growth. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Spheres derived from the human SK-RC-42 renal cell carcinoma cell line are enriched in cancer stem cells. AU- Zhong, Yong AU- Guan, Kaopeng AU- Guo, Sujuan AU- Zhou, Chunxia AU- Wang, Dongmei AU- Ma, Wenbo AU- Zhang, Youhui AU- Li, Changling AU- Zhang, Shuren PY- 2010 T2- Cancer letters J2- Cancer Lett UR- http://www.ncbi.nlm.nih.gov/pubmed/20846785 VL- 299 IS- 2 SP- 150-60 N2- Various types of malignant tumor have been found to contain a subpopulation of cancer stem cells (CSCs). In this study, we sought to enrich CSCs from the renal cell carcinoma (RCC) cell line SK-RC-42 using the sphere culture system and characterize their immunophenotype. We demonstrated that a subpopulation of SK-RC-42 cells were capable of growing as tumor spheres in serum-free medium supplemented with EGF and bFGF. The sphere-forming cells (SFCs) had many properties similar to CSCs: ability of self-renewing in vitro and in vivo, higher mRNA expression levels of several 'stemness' genes, stronger tumorigenicity and resistance to chemotherapeutic agents and irradiation compared with the monolayer adherent cells (MACs). The SFCs expressed high levels of MHC class I but low levels of MHC class II, CD80 and CD86. In contrast with MACs, the SFCs had lower expression levels of FasL and Fas, Her2 and hTERT and activating natural killer receptors. Finally, SK-RC-42 SFCs and MACs both expressed significant and comparable levels of the transcription factor forkhead box protein 3 (FoxP3) and membrane complement regulatory proteins (mCRPs). Taken together, these findings indicate that CSCs can be enriched from RCC by culturing the tumor cells as spheres. The immunophenotype of the SFCs demonstrated in this study suggests that CSCs might play an important role in the evasion of tumor growth from immune surveillance. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- The requirement for proteomics to unravel stem cell regulatory mechanisms. AU- Williamson, Andrew J K AU- Whetton, Anthony D PY- 2010 T2- Journal of cellular physiology J2- J Cell Physiol UR- http://www.ncbi.nlm.nih.gov/pubmed/21190214 N2- Stem cells are defined by their ability to self-renew and to differentiate, the processes whereby these events are achieved is the subject of much investigation. These studies include cancer stem cell populations, where eradication of this specific population is the ultimate goal of treatment. Whilst cellular signalling events and transcription factor complex-mediated changes in gene expression have been analysed in some detail within stem cells, full systematic understanding of the events promoting self-renewal or the commitment process leading to formation of a specific cell type require a systems biology approach. This in turn demands a need for proteomic analysis of post-translational regulation of protein levels, protein interactions, protein post-translational modification (e.g. ubiquitination, methylation, acetylation, phosphorylation) to identify networks for stem cell regulation. Furthermore, the phenomenon of induced pluripotency via cellular reprogramming also can be understood optimally using combined molecular biology and proteomics approaches; here we describe current research employing proteomics and mass spectrometry to dissect stem cell regulatory mechanisms. J. Cell. Physiol. 2010 Wiley-Liss, Inc. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Unravelling the Mystery of Stem/Progenitor Cells in Human Breast Milk AU- Fan, Yiping AU- Chong, Yap Seng AU- Choolani, Mahesh A AU- Cregan, Mark D AU- Chan, Jerry K Y PY- 2010 T2- PLoS ONE J2- PLoS One UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010984/ VL- 5 IS- 12 DO- 10.1371/journal.pone.0014421 C2- 3010984 N2- Background: Mammary stem cells have been extensively studied as a system to delineate the pathogenesis and treatment of breast cancer. However, research on mammary stem cells requires tissue biopsies which limit the quantity of samples available. We have previously identified putative mammary stem cells in human breast milk, and here, we further characterised the cellular component of human breast milk. Methodology/Principal Findings: We identified markers associated with haemopoietic, mesenchymal and neuro-epithelial lineages in the cellular component of human breast milk. We found 2.60.8% (meanSEM) and 0.70.2% of the whole cell population (WCP) were found to be CD133+ and CD34+ respectively, 27.89.1% of the WCP to be positive for Stro-1 through flow-cytometry. Expressions of neuro-ectodermal stem cell markers such as nestin and cytokeratin 5 were found through reverse-transcription polymerase chain reaction (RT-PCR), and in 4.170.2% and 0.90.2% of the WCP on flow-cytometry. We also established the presence of a side-population (SP) (1.80.4% of WCP) as well as CD133+ cells (1.70.5% of the WCP). Characterisation of the sorted SP and non-SP, CD133+ and CD133- cells carried out showed enrichment of CD326 (EPCAM) in the SP cells (50.68.6 vs 18.16.0, P-value ?=?0.02). However, culture in a wide range of in vitro conditions revealed the atypical behaviour of stem/progenitor cells in human breast milk; in that if they are present, they do not respond to established culture protocols of stem/progenitor cells. Conclusions/Significance: The identification of primitive cell types within human breast milk may provide a non-invasive source of relevant mammary cells for a wide-range of applications; even the possibility of banking one's own stem cell for every breastfeeding woman. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Self-Renewal of Acute Lymphocytic Leukemia Cells Is Limited by the Hedgehog Pathway Inhibitors Cyclopamine and IPI-926 AU- Lin, Tara L AU- Wang, Qiuju H AU- Brown, Patrick AU- Peacock, Craig AU- Merchant, Akil A AU- Brennan, Sarah AU- Jones, Evan AU- McGovern, Karen AU- Watkins, D Neil AU- Sakamoto, Kathleen M AU- Matsui, William PY- 2010 T2- PLoS ONE J2- PLoS One UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3011010/ VL- 5 IS- 12 DO- 10.1371/journal.pone.0015262 C2- 3011010 N2- Conserved embryonic signaling pathways such as Hedgehog (Hh), Wingless and Notch have been implicated in the pathogenesis of several malignancies. Recent data suggests that Hh signaling plays a role in normal B-cell development, and we hypothesized that Hh signaling may be important in precursor B-cell acute lymphocytic leukemia (B-ALL). We found that the expression of Hh pathway components was common in human B-ALL cell lines and clinical samples. Moreover, pathway activity could be modulated by Hh ligand or several pathway inhibitors including cyclopamine and the novel SMOOTHENED (SMO) inhibitor IPI-926. The inhibition of pathway activity primarily impacted highly clonogenic B-ALL cells expressing aldehyde dehydrogenase (ALDH) by limiting their self-renewal potential both in vitro and in vivo. These data demonstrate that Hh pathway activation is common in B-ALL and represents a novel therapeutic target regulating self-renewal and persistence of the malignant clone. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Inhalation aromatherapy in children and adolescents undergoing stem cell infusion: results of a placebo-controlled double-blind trial. AU- Ndao, Deborah H AU- Ladas, Elena J AU- Cheng, Bin AU- Sands, Stephen A AU- Snyder, Kathryn T AU- Garvin, James H, Jr AU- Kelly, Kara M PY- 2010 T2- Psycho-oncology J2- Psychooncology UR- http://www.ncbi.nlm.nih.gov/pubmed/21188734 N2- Objective: Though often lifesaving, stem cell transplantation (SCT) is a period of great distress for both child and parent.Methods: We conducted a double-blind, placebo-controlled randomized study evaluating the effect of the respiratory administration of bergamot essential oil on the anxiety, nausea, and pain of 37 pediatric patients with malignant and non-malignant disorders undergoing stem cell infusion and their parents. Patients were assessed at the time of recruitment, prior to infusion, upon infusion completion, and one hour post-infusion using the Spielberger State-Trait Anxiety Inventory (STAI) for parents and the STAIC, Children's Behavioral Style Scale (CBSS), visual analogue scale (VAS) for pain and nausea, and the Emotionality Activity Sociability and Impulsivity instrument (EASI) for children.Results: Children and adolescents in the treatment group experienced greater anxiety (p = 0.05) and nausea (p = 0.03) one hour post-infusion. Reported pain in both groups was no longer significant one hour post-infusion. Parental anxiety declined in both groups but did not reach statistical significance. Child's monitoring coping style was significantly predictive of transitory anxiety post-infusion (p = 0.01).Conclusions: Although this trial did not report a benefit of inhalation aromatherapy for reducing anxiety, nausea, or pain when added to standard supportive care, it provides the first experimental rather than descriptive report on testing a single therapeutic essential oil among children and adolescents undergoing stem cell infusion. Future research may consider exploring the cutaneous application of essential oil through massage or other psychoeducational counseling interventions among parents with elevated anxiety and patients with greater information seeking coping styles during SCT. Copyright 2010 John Wiley Sons, Ltd. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Role of Notch and its oncogenic signaling crosstalk in breast cancer. AU- Guo, Shanchun AU- Liu, Mingli AU- Gonzalez-Perez, Ruben R PY- 2010 T2- Biochimica et biophysica acta J2- Biochim Biophys Acta UR- http://www.ncbi.nlm.nih.gov/pubmed/21193018 N2- The Notch signaling plays a key role in cell differentiation, survival, and proliferation through diverse mechanisms. Notch signaling is also involved in vasculogenesis and angiogenesis. Moreover, Notch expression is regulated by hypoxia and inflammatory cytokines (IL-1, IL-6 and leptin). Entangled crosstalk between Notch and other developmental signaling (Hedgehog and Wnt), and signaling triggered by growth factors, estrogens and oncogenic kinases, could impact on Notch targeted genes. Thus, alterations of the Notch signaling can lead to a variety of disorders, including human malignancies. Notch signaling is activated by ligand binding, followed by ADAM/Tumor necrosis factor--converting enzyme (TACE) metalloprotease and -secretase cleavages that produce the Notch intracellular domain (NICD). Translocation of NICD into the nucleus induces the transcriptional activation of Notch target genes. The relationships between Notch deregulated signaling, cancer stem cells and the carcinogenesis process reinforced by Notch crosstalk with many oncogenic signaling pathways suggest that Notch signaling may be a critical drug target for breast and other cancers. Since current status of knowledge in this field changes quickly, our insight should be continuously revised. In this review, we will focus on recent advancements in identification of aberrant Notch signaling in breast cancer and the possible underlying mechanisms, including potential role of Notch in breast cancer stem cells, tumor angiogenesis, as well as its crosstalk with other oncogenic signaling pathways in breast cancer. We will also discuss the prognostic value of Notch proteins and therapeutic potential of targeting Notch signaling for cancer treatment. The number of words in the abstract: 245. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Characterization of spheres derived from canine mammary gland adenocarcinoma cell lines. AU- Michishita, Masaki AU- Akiyoshi, Rui AU- Yoshimura, Hisashi AU- Katsumoto, Takuo AU- Ichikawa, Hitoshi AU- Ohkusu-Tsukada, Kozo AU- Nakagawa, Takayuki AU- Sasaki, Nobuo AU- Takahashi, Kimimasa PY- 2010 T2- Research in veterinary science J2- Res Vet Sci UR- http://www.ncbi.nlm.nih.gov/pubmed/21190702 N2- There is increasing evidence for the presence of cancer stem cells in several solid tumors, and these cancer stem cells have a potential role in tumor initiation, aggression, and recurrence. The stem cell-like properties of spheres derived from canine mammary tumors remain largely elusive. We attempted to induce sphere formation using four cell lines of canine mammary adenocarcinoma, and characterized the spheres derived from a CHMp line in vitro and in vivo. The CHMp-derived spheres showed predominantly CD44(+)CD24(-) population, higher expression of stem cell-related genes, such as CD133, Notch3 and MDR, and higher resistance to doxorubicin compared with the CHMp-derived adherent cells. Xenograft transplantations in nude mice demonstrated that only 110(4)sphere cells were sufficient for tumor formation. Use of the sphere assay on these sphere-derived tumors showed that sphere-forming cells were present in the tumors, and were maintained in serial transplantation. We propose that spheres derived from canine mammary adenocarcinoma cell lines possess a potential characteristic of cancer stem cells. Spheres derived from canine mammary tumors could be a powerful tool with which to investigate novel therapeutic drugs and to elucidate the molecular and cellular mechanisms that underlie tumorigenesis. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Telomerase activity-independent function of TERT allows glioma cells to attain cancer stem cell characteristics by inducing EGFR expression. AU- Beck, Samuel AU- Jin, Xun AU- Sohn, Young-Woo AU- Kim, Jun-Kyum AU- Kim, Sung-Hak AU- Yin, Jinlong AU- Pian, Xumin AU- Kim, Sung-Chan AU- Nam, Do-Hyun AU- Choi, Yun-Jaie AU- Kim, Hyunggee PY- 2010 T2- Molecules and cells J2- Mol Cells UR- http://www.ncbi.nlm.nih.gov/pubmed/21193962 N2- Telomerase reverse transcriptase (TERT), the catalytic subunit of the enzyme telomerase, is robustly expressed in cancer cells. TERT enables cells to avoid chromosome shortening during repeated replication by maintaining telomere length. However, several lines of evidence indicate that many cancer cells exhibit shorter telomere length than normal tissues, implying an additional function of TERT in tumor formation and progression. Here, we report a telomerase activity-independent function of TERT that induces cancer stemness in glioma cells. Overexpression of TERT712, a telomerase activity-deficient form of TERT, in U87MG cells promoted cell self-renewal in vitro, and induced EGFR expression and formation of gliomas exhibiting cellular heterogeneity in vivo. In patients with glioblastoma multiforme, TERT expression showed a high correlation with EGFR expression, which is closely linked to the stemness gene signature. Induction of differentiation and TERT-knockdown in glioma stem cells led to a marked reduction in EGFR expression, cancer stemness, and anticancer drug resistance. Together, our findings indicate that TERT plays a crucial role in tumor progression by promoting cancer stemness through expression of EGFR. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Hedgehog signalling and therapeutics in pancreatic cancer. AU- Kelleher, Fergal C PY- 2010 T2- Carcinogenesis J2- Carcinogenesis UR- http://www.ncbi.nlm.nih.gov/pubmed/21186299 N2- Purpose: To conduct a systematic review of the role that the hedgehog signalling pathway has in pancreatic cancer tumourigenesis. Design: PUBMED search (2000-2010) and literature based references. Results: Firstly, in 2009 a genetic analysis of pancreatic cancers found that a core set of 12 cellular signalling pathways including hedgehog were genetically altered in 67-100% of cases. Secondly, in vitro and in-vivo studies of treatment with cyclopamine (a naturally occurring antagonist of the hedgehog signalling pathway component; Smoothened) has shown that inhibition of hedgehog can abrogate pancreatic cancer metastasis. Thirdly, experimental evidence has demonstrated that sonic hedgehog (Shh) is correlated with desmoplasia in pancreatic cancer. This is important because targeting the Shh pathway potentially may facilitate chemotherapeutic drug delivery as pancreatic cancers tend to have a dense fibrotic stroma that extrinsically compressed the tumour vasculature leading to a hypoperfusing intra-tumoural circulation. It is probable that patients with locally advanced pancreatic cancer will derive the greatest benefit from treatment with Smoothened antagonists. Fourthly, it has been found that ligand dependent activation by hedgehog occurs in the tumour stromal micro-environment in pancreatic cancer, a paracrine effect on tumourigenesis. Finally, in pancreatic cancer, cells with the CD44+CD24+ESA+ immunophenotype select a population enriched for cancer initiating stem cells. Shh is increased 46 fold in CD44+CD24+ESA+ cells compared with normal pancreatic epithelial cells. Medications that destruct pancreatic cancer initiating stem cells are a potentially novel strategy in cancer treatment. Conclusion: Aberrant hedgehog signalling occurs in pancreatic cancer tumourigenesis and therapeutics that target the trans-membrane receptor Smoothened abrogate hedgehog signalling and may improve the outcomes of patients with pancreatic cancer. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- CD133(+) niches and single cells in glioblastoma have different phenotypes. AU- Christensen, Karina AU- Schrder, Henrik Daa AU- Kristensen, Bjarne Winther PY- 2010 T2- Journal of neuro-oncology J2- J Neurooncol UR- http://www.ncbi.nlm.nih.gov/pubmed/21184132 N2- Putative CD133(+) brain tumor stem cells have been shown to be located in niches and as single cells. This is the first study providing insight into the different phenotypes of CD133(+) cells in glioblastoma according to localization. Paraffin sections were stained by double immunofluorescence with CD133 and the candidate stem cell markers Sox2, Bmi-1, EGFR, podoplanin and nestin, the proliferation marker Ki67 and the endothelial cell markers CD31, CD34, and VWF. Cell counting showed that the CD133(+) cells in the niches had a significantly higher expression of Sox2, EGFR and nestin compared to CD133(+) single cells, but only a 3% Ki67 labeling index versus 14% found for CD133(+) single cells. Only low endothelial cell marker expression was found in the niches or the CD133(-) tumor areas, while 43% CD133(+)/CD31(+) and 25% CD133(+)/CD34(+) single cells were found. CD133(+) blood vessels within CD133(+) niches were less proliferative and more often Bmi-1(+) than CD133(+) blood vessels outside niches. In conclusion, different CD133(+) cell phenotypes exist according to the in situ localization, and also the phenotype of CD133(+) blood vessels vary according to the localization. CD133(+) niches contain stem-like cells with a lower proliferation index than CD133(+) single cells, which have an endothelial differentiation profile suggesting a role in angiogenesis. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Side Population is not Necessary or Sufficient for a Cancer Stem Cell Phenotype in Glioblastoma Multiforme. AU- Broadley, Kate W R AU- Hunn, Martin K AU- Farrand, Kathryn J AU- Price, Kylie M AU- Grasso, Carole AU - Miller, Rose J AU- Hermans, Ian F AU- McConnell, Melanie J PY- 2010 T2- Stem cells (Dayton, Ohio) J2- Stem Cells UR- http://www.ncbi.nlm.nih.gov/pubmed/21184504 N2- There is strong evidence for the existence of cancer stem cells (CSC) in the aggressive brain tumor glioblastoma multiforme (GBM). These cells have stem-like self-renewal activity and increased tumor initiation capacity, and are believed to be responsible for recurrence due to their resistance to therapy. Several techniques have been used to enrich for CSC, including growth in serum-free defined media to induce sphere formation, and isolation of a stem-like cell using exclusion of the fluorescent dye Hoechst 33342, the side population (SP). We show that sphere formation in GBM cell lines and primary GBM cells enriches for a CSC-like phenotype of increased self-renewal gene expression in vitro and increased tumor initiation in vivo. However, the SP was absent from all sphere cultures. Direct isolation of the SP from the GBM lines did not enrich for stem-like activity in vitro, and tumor-initiating activity was lower in sorted SP compared to non-SP and parental cells. Transient exposure to doxorubicin enhanced both CSC and SP frequency. However, doxorubicin treatment altered the cytometric profile and obscured the SP demonstrating the difficulty of identifying SP in cells under stress. Doxorubicin-exposed cells showed a transient increase in SP, but the doxorubicin-SP cells were still not enriched for a stem-like self-renewal phenotype. These data demonstrate that the GBM SP does not necessarily contribute to self-renewal or tumor initiation, key properties of a CSC, and we advise against using SP to enumerate or isolate CSC. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Vascular Stem Cells and Tumor Angiogenesis. AU- Melero-Martin, Juan M AU- Dudley, Andrew C PY- 2010 T2- Stem cells (Dayton, Ohio) J2- Stem Cells UR- http://www.ncbi.nlm.nih.gov/pubmed/21184502 N2- Solid tumors are complex organs of cancer cells and a heterogeneous population of hematopoietic cells, mesenchymal cells and endothelial cells. While mutant tissue-resident stem cells that can perpetually self-renew have been proposed as the cancer-initiating cell for some tumors, non-tumor-forming stem and progenitor cells are also present within the tumor microenvironment. These adult stem cells do not form tumors when injected into experimental animals, but they may augment tumor growth through juxtacrine and paracrine regulation of tumor cells and by contributing to neovascularization. Thus, cancer cells may actively co-opt non-tumor-forming stem cells distally from the bone marrow or proximally from nearby tissue and subvert their abilities to differentiate and maintain tissue growth, repair and angiogenesis. This review will cover the roles of non tumor-forming vascular stem cells in tumor growth and angiogenesis. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI - Unregulated miR-96 Induces Cell Proliferation in Human Breast Cancer by Downregulating Transcriptional Factor FOXO3a AU- Lin, Huanxin AU- Dai, Ting AU- Xiong, Huaping AU- Zhao, Xiaohui AU- Chen, Xiuting AU- Yu, Chunping AU- Li, Jun AU- Wang, Xi AU- Song, Libing PY- 2010 T2- PLoS ONE J2- PLoS One UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3009749/ VL- 5 IS- 12 DO- 10.1371/journal.pone.0015797 C2- 3009749 N2- FOXO transcription factors are key tumor suppressors in mammalian cells. Until now, suppression of FOXOs in cancer cells was thought to be mainly due to activation of multiple onco-kinases by a phosphorylation-ubiquitylation-mediated cascade. Therefore, it was speculated that inhibition of FOXO proteins would naturally occur through a multiple step post-translational process. However, whether cancer cells may downregulate FOXO protein via an alternative regulatory mechanism is unclear. In the current study, we report that expression of miR-96 was markedly upregulated in breast cancer cells and breast cancer tissues compared with normal breast epithelial cells (NBEC) and normal breast tissues. Ectopic expression of miR-96 induced the proliferation and anchorage-independent growth of breast cancer cells, while inhibition of miR-96 reduced this effect. Furthermore, upregulation of miR-96 in breast cancer cells resulted in modulation of their entry into the G1/S transitional phase, which was caused by downregulation of cyclin-dependent kinase (CDK) inhibitors, p27Kip1 and p21Cip1, and upregulation of the cell-cycle regulator cyclin D1. Moreover, we demonstrated that miR-96 downregulated FOXO3a expression by directly targeting the FOXO3a 3-untranslated region. Taken together, our results suggest that miR-96 may play an important role in promoting proliferation of human breast cancer cells and present a novel mechanism of miRNA-mediated direct suppression of FOXO3a expression in cancer cells. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- MicroRNAs involved in neoplastic transformation of liver cancer stem cells. AU- Li, Ren AU- You, Nan AU- Wang, Xinchuan AU- Dou, Kefeng PY- 2010 T2- Journal of experimental clinical cancer research : CR J2- J Exp Clin Cancer Res UR- http://www.ncbi.nlm.nih.gov/pubmed/21176238 VL- 29 IS- 1 SP- 169 N2- ABSTRACT: BACKGROUND: The existence of cancer stem cells in hepatocellular carcinoma (HCC) has been verified by characterizing side population (SP) cells based on efflux of Hoechst 33342 dye from stem cells. Recent advances in microRNA (miRNA) biology have revealed that miRNAs play an important role in embryonic development and tumorigenesis. However, it is still unclear which miRNAs participate in the neoplastic transformation of liver cancer stem cells (LCSCs) during hepatocarcinogenesis. METHODS: To identify the unique set of miRNAs differentially regulated in LCSCs, we applied SP sorting to primary cultures of F344 rat HCC cancer cells treated with diethylnitrosamine (DEN) and normal syngenic fetal liver cells, and the stem-like characteristics of SP cells were verified through detecting expression of CD90.1, AFP and CK-7. Global miRNA expression profiles of two groups of SP cells were screened through microarray platform. RESULTS: A total of 68 miRNAs, including miR-10b, miR-21, miR-470*, miR-34c-3p, and let-7i*, were identified as overexpressed in SP of HCC cells compared to fetal liver cells. Ten miRNAs were underexpressed, including miR-200a* and miR-148b*. These miRNAs were validated using stem-loop real-time reverse transcriptase polymerase chain reaction (RT-PCR). CONCLUSIONS: Our results suggest that LCSCs may have a distinct miRNA expression fingerprint during hepatocarcinogenesis. Dissecting these relationships will provide a new understanding of the function of miRNA in the process of neoplastic transformation of LCSCs. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Bone Morphogenetic Protein 5 Regulates the Number of Keratinocyte Stem Cells from the Skin of Mice. AU- Kangsamaksin, Thaned AU- Morris, Rebecca J PY- 2010 T2- The Journal of investigative dermatology J2- J Invest Dermatol UR- http://www.ncbi.nlm.nih.gov/pubmed/21179110 N2- Understanding keratinocyte stem cell regulation is important in understanding the pathogenesis of wound healing and nonmelanoma skin cancer. We previously used a sensitive and quantitative assay for in vitro keratinocyte colony formation and mapped the keratinocyte stem cell locus (Ksc1) on mouse chromosome 9. Examination of the candidate genes in this locus disclosed a sequence variant in the gene for bone morphogenetic protein 5 (Bmp5). In this report, we used a naturally occurring mouse with a null mutation in this gene to probe stem cell properties in mouse epidermis. We found that the mutant keratinocytes had a significant reduction in the size and number of clonogenic keratinocytes. The mutant mice had a 50% reduction in the number of label-retaining cells when compared with their littermates. Addition of exogenous Bmp5 protein increased the number and size of keratinocyte colonies in the mutant as well as their wild-type littermates. Surprisingly, the mutant mice showed at least a 2-fold increase in skin tumor susceptibility over their littermates. We conclude that a naturally occurring mutation in Bmp5 affects keratinocyte stem cell proliferation, and skin tumor susceptibility, and is a candidate stem cell regulatory gene in the Ksc1 locus.Journal of Investigative Dermatology advance online publication, 23 December 2010; doi:10.1038/jid.2010.378. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Perforated mixed carcinoid-adenocarcinoma in transverse colon and at gastroenterostomy site: case report AU- Ihtiyar, Enver AU- Pa?ao?lu, Ozg l AU- Erkasap, Serdar AU- Karaka ?, Bar?? R AU- Ya?ar, Fatih N PY- 2010 T2- World journal of surgical oncology J2- World J Surg Oncol UR- http://www.wjso.com/content/8/1/110 VL- 8 IS- 1 SP- 110 DO- 10.1186/1477-7819-8-110 C2- 3014938 N2- Abstract: Goblet cell carcinoid of the large intestine is a rare neoplasm, usually located in ascending colon and rectum. A 60-year-old male patient underwent surgery after the diagnosis of acute abdomen. Exploratory laparotomy revealed perforation with a diameter of 1 cm at the site of the previously performed gastroenterostomy and dilatation of the right colic flexure, secondary to a solid obstructive mass located in the mid-portion of transverse colon. Histopathological investigation of the biopsies, taken from the gastroenterostomy site and the tumor, revealed mixed carcinoid-adenocarcinoma with carcinoid component, predominantly composed of goblet cells. Three cycles of FOLFOX-4 protocol was administered. Following respiratory distress secondary to pulmonary metastasis, the patient's condition deteriorated and subsequently died in the fourth postoperative month. Our aim with this paper is to point out that more cases should be reported for more effective diagnosis, histopathological study, clinical investigation, treatment and prognosis of this specific neoplasm. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- CXCR6, a Newly Defined Biomarker of Tissue-Specific Stem Cell Asymmetric Self-Renewal, Identifies More Aggressive Human Melanoma Cancer Stem Cells AU- Taghizadeh, Rouzbeh AU- Noh, Minsoo AU- Huh, Yang Hoon AU- Ciusani, Emilio AU- Sigalotti, Luca AU- Maio, Michele AU- Arosio, Beatrice AU- Nicotra, Maria R AU- Natali, Piergiorgio AU- Sherley, James L AU- La Porta, Caterina A M PY- 2010 T2- PLoS ONE J2- PLoS One UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3008677/ VL- 5 IS- 12 DO- 10.1371/journal.pone.0015183 C2- 3008677 N2- Background: A fundamental problem in cancer research is identifying the cell type that is capable of sustaining neoplastic growth and its origin from normal tissue cells. Recent investigations of a variety of tumor types have shown that phenotypically identifiable and isolable subfractions of cells possess the tumor-forming ability. In the present paper, using two lineage-related human melanoma cell lines, primary melanoma line IGR39 and its metastatic derivative line IGR37, two main observations are reported. The first one is the first phenotypic evidence to support the origin of melanoma cancer stem cells (CSCs) from mutated tissue-specific stem cells; and the second one is the identification of a more aggressive subpopulation of CSCs in melanoma that are CXCR6+. Methods/Findings: We defined CXCR6 as a new biomarker for tissue-specific stem cell asymmetric self-renewal. Thus, the relationship between melanoma formation and ABCG2 and CXCR6 expression was investigated. Consistent with their non-metastatic character, unsorted IGR39 cells formed significantly smaller tumors than unsorted IGR37 cells. In addition, ABCG2+ cells produced tumors that had a 2-fold greater mass than tumors produced by unsorted cells or ABCG2- cells. CXCR6+ cells produced more aggressive tumors. CXCR6 identifies a more discrete subpopulation of cultured human melanoma cells with a more aggressive MCSC phenotype than cells selected on the basis of the ABCG2+ phenotype alone. Conclusions/Significance: The association of a more aggressive tumor phenotype with asymmetric self-renewal phenotype reveals a previously unrecognized aspect of tumor cell physiology. Namely, the retention of some tissue-specific stem cell attributes, like the ability to asymmetrically self-renew, impacts the natural history of human tumor development. Knowledge of this new aspect of tumor development and progression may provide new targets for cancer prevention and treatment. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- High-Definition Mapping of Retroviral Integration Sites Defines the Fate of Allogeneic T Cells After Donor Lymphocyte Infusion AU- Cattoglio, Claudia AU- Maruggi, Giulietta AU- Bartholomae, Cynthia AU- Malani, Nirav AU- Pellin, Danilo AU- Cocchiarella, Fabienne AU- Magnani, Zulma AU- Ciceri, Fabio AU- Ambrosi, Alessandro AU- von Kalle, Christof AU- Bushman, Frederic D AU- Bonini, Chiara AU- Schmidt, Manfred AU- Mavilio, Fulvio AU- Recchia, Alessandra PY- 2010 T2- PLoS ONE J2- PLoS One UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3008730/ VL- 5 IS- 12 DO- 10.1371/journal.pone.0015688 C2- 3008730 N2- The infusion of donor lymphocytes transduced with a retroviral vector expressing the HSV-TK suicide gene in patients undergoing hematopoietic stem cell transplantation for leukemia/lymphoma promotes immune reconstitution and prevents infections and graft-versus-host disease. Analysis of the clonal dynamics of genetically modified lymphocytes in vivo is of crucial importance to understand the potential genotoxic risk of this therapeutic approach. We used linear amplification-mediated PCR and pyrosequencing to build a genome-wide, high-definition map of retroviral integration sites in the genome of peripheral blood T cells from two different donors and used gene expression profiling and bioinformatics to associate integration clusters to transcriptional activity and to genetic and epigenetic features of the T cell genome. Comparison with matched random controls and with integrations obtained from CD34+ hematopoietic stem/progenitor cells showed that integration clusters occur within chromatin regions bearing epigenetic marks associated with active promoters and regulatory elements in a cell-specific fashion. Analysis of integration sites in T cells obtained ex vivo two months after infusion showed no evidence of integration-related clonal expansion or dominance, but rather loss of cells harboring integration events interfering with RNA post-transcriptional processing. The study shows that high-definition maps of retroviral integration sites are a powerful tool to analyze the fate of genetically modified T cells in patients and the biological consequences of retroviral transduction. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Increased CCL2 and IL-8 in the bone marrow microenvironment in acute lymphoblastic leukemia. AU- de Vasconcellos, Jara Ferreira AU- Laranjeira, Angelo Brunelli Albertoni AU- Zanchin, Nilson Ivo Tonin AU- Otubo, Rosemary AU- Vaz, Thais Haline AU- Cardoso, Angelo Almeida AU- Brandalise, Silvia Regina AU- Yunes, Jos Andrs PY- 2010 T2- Pediatric blood cancer J2- Pediatr Blood Cancer UR- http://www.ncbi.nlm.nih.gov/pubmed/21182032 N2- BACKGROUND: The interactions of acute lymphoblastic leukemia (ALL) blasts with bone marrow (BM) stromal cells have a positive impact on leukemia cell survival. In the present study, we proposed to identify and investigate the role of molecules critically involved in leukemia-microenvironment crosstalk. PROCEDURE: Gene expression profiling analyses of BM mesenchymal stem cells (BMMSC) were performed following stimulation by ALL cells. CCL2 and IL-8 plasma levels were evaluated from ALL patients and controls. Expression of the CCL2 and IL-8 receptors in ALL was determined by RT-PCR. The biological effects of CCL2, IL-8 or its neutralizing antibodies in primary precursor-B ALL and BMMSC cells were evaluated using in vitro assays. RESULTS: Leukemia stimulation of BMMSC upregulated the expression of several inflammatory chemokines, including CCL2 and IL-8. The BM plasma levels of CCL2 and IL-8 in children at diagnosis were significantly higher than in healthy controls (P0.001). Functional studies revealed that CCL2 and IL-8 enhanced the capacity of BMMSC to support adhesion of ALL cells. CCL2 and IL-8 were also found to enhance BMMSC survival and to increase their proliferation. ALL cells were not directly affected by CCL2 or IL-8. CONCLUSIONS: The leukemic BM microenvironment had increased levels of CCL2 and IL-8. These chemokines are known to have suppressive effects in normal hematopoiesis. Our data indicate that CCL2 and IL-8 have a positive impact on BMMSC survival, proliferation, and adhesiveness to ALL cells. Leukemia-associated CCL2 and IL-8 upregulation may represent one possible mechanism of microenvironment perversion in favor of ALL cells. Pediatr Blood Cancer 2010 Wiley-Liss, Inc. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Frontiers in targeting glioma stem cells. AU- Frosina, Guido PY- 2010 T2- European journal of cancer (Oxford, England : 1990) J2- Eur J Cancer UR- http://www.ncbi.nlm.nih.gov/pubmed/21185169 N2- Patients with glioblastoma multiforme (GBM - WHO grade IV) seldom recover. This is due to the infiltrative nature of these tumours and the presence of cellular populations with ability to escape therapies and drive tumour recurrence and progression. In some cases, these resistant cells exhibit stem properties . This article aims at discussing relevant issues on GSC resistance to current therapies and outlines possible and promising avenues in regard to novel therapeutic strategies, such as pharmacological, immunological and viral interventions. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Generation of Induced Pluripotent Stem Cell Lines from Friedreich Ataxia Patients. AU- Liu, Jun AU- Verma, Paul J AU- Evans-Galea, Marguerite V AU- Delatycki, Martin B AU- Michalska, Anna AU- Leung, Jessie AU- Crombie, Duncan AU- Sarsero, Joseph P AU- Williamson, Robert AU- Dottori, Mirella AU- Pbay, Alice PY- 2010 T2- Stem cell reviews J2- Stem Cell Rev UR- http://www.ncbi.nlm.nih.gov/pubmed/21181307 N2- Friedreich ataxia (FRDA) is an autosomal recessive disorder characterised by neurodegeneration and cardiomyopathy. It is caused by a trinucleotide (GAA) repeat expansion in the first intron of the FXN gene that results in reduced synthesis of FXN mRNA and its protein product, frataxin. We report the generation of induced pluripotent stem (iPS) cell lines derived from skin fibroblasts from two FRDA patients. Each of the patient-derived iPS (FA-iPS) cell lines maintain the GAA repeat expansion and the reduced FXN mRNA expression that are characteristic of the patient. The FA-iPS cells are pluripotent and form teratomas when injected into nude mice. We demonstrate that following in vitro differentiation the FA-iPS cells give rise to the two cell types primarily affected in FRDA, peripheral neurons and cardiomyocytes. The FA-iPS cell lines have the potential to provide valuable models to study the cellular pathology of FRDA and to develop high-throughput drug screening assays. We have previously demonstrated that stable insertion of a functional human BAC containing the intact FXN gene into stem cells results in the expression of frataxin protein in differentiated neurons. As such, iPS cell lines derived from FRDA patients, following correction of the mutated gene, could provide a useful source of immunocompatible cells for transplantation therapy. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Identification of Therapeutic Targets for Quiescent, Chemotherapy-Resistant Human Leukemia Stem Cells AU- Saito, Yoriko AU- Kitamura, Hiroshi AU- Hijikata, Atsushi AU- Tomizawa-Murasawa, Mariko AU- Tanaka, Satoshi AU- Takagi, Shinsuke AU- Uchida, Naoyuki AU- Suzuki, Nahoko AU- Sone, Akiko AU- Najima, Yuho AU- Ozawa, Hidetoshi AU- Wake, Atsushi AU- Taniguchi, Shuichi AU- Shultz, Leonard D AU- Ohara, Osamu AU- Ishikawa, Fumihiko PY- 2010 T2- Science translational medicine J2- Sci Transl Med UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005290/ VL- 2 IS- 17 SP- 17ra9-17ra9 DO- 10.1126/scitranslmed.3000349 C2- 3005290 N2- Human acute myeloid leukemia (AML) originates from rare leukemia stem cells (LSCs). Because these chemotherapy-resistant LSCs are thought to underlie disease relapse, effective therapeutic strategies specifically targeting these cells may be beneficial. Here, we report identification of a primary human LSC gene signature and functional characterization of human LSC-specific molecules in vivo in a mouse xenotransplantation model. In 32 of 61 (53%) patients with AML, either CD32 or CD25 or both were highly expressed in LSCs. CD32- or CD25-positive LSCs could initiate AML and were cell cyclequiescent and chemotherapy-resistant in vivo. Normal human hematopoietic stem cells depleted of CD32- and CD25-positive cells maintained long-term multilineage hematopoietic reconstitution capacity in vivo, indicating the potential safety of treatments targeting these molecules. In addition to CD32 and CD25, quiescent LSCs within the bone marrow niche also expressed the transcription factor WT1 and the kinase HCK. These molecules are also promising targets for LSC-specific therapy. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- NEWS TI- MIT researchers help biotech start-up attack cancer stem cells AU- Carroll, John PY- 2010 T2- Fierce Biotech Researcher UR- http://www.fiercebiotechresearch.com/story/mit-researchers-help-biotech-start-attack-cancer-stem-cells/2010-12-21 JF- Fierce Biotech Researcher N2- N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- The potential of combinations of drug-loaded nanoparticle systems and adult stem cells for glioma therapy. AU- Roger, Mathilde AU- Clavreul, Anne AU- Venier-Julienne, Marie-Claire AU- Passirani, Catherine AU- Montero-Menei, Claudia N AU- Menei, Philippe PY- 2010 T2- Biomaterials J2- Biomaterials UR- http://www.ncbi.nlm.nih.gov/pubmed/21183214 N2- The prognosis of patients with malignant glioma remains extremely poor, despite surgery and improvements in radio- and chemo-therapies. Nanotechnologies hold great promise in glioma therapy as they protect the therapeutic agent and allow its sustained release. However, new paradigms permitting tumor-specific targeting and extensive intratumoral distribution must be developed to efficiently deliver nanoparticles. Modifications and functionalizations of nanoparticles have been developed to specifically track tumor cells. However, these nanoparticles have yielded few clinical results due to intra-patient heterogeneity and inter-patient variability. Stem cells with a specific tropism for brain tumors could be used as delivery vehicles for nanoparticles. Indeed, these cells have a natural tendency to migrate and distribute within the tumor mass and they can also incorporate nanoparticles. Stem cell therapy combined with nanotechnology could be a promising tool to efficiently deliver drugs to brain tumors. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- HER2 Phosphorylation Is Maintained by a PKB Negative Feedback Loop in Response to Anti-HER2 Herceptin in Breast Cancer AU- Gijsen, Merel AU- King, Peter AU- Perera, Tim AU- Parker, Peter J AU- Harris, Adrian L AU- Larijani, Banafsh AU- Kong, Anthony PY- 2010 T2- PLoS Biology J2- PLoS Biol UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3006345/ VL- 8 IS- 12 DO- 10.1371/journal.pbio.1000563 C2- 3006345 N2- Author Summary: HER2 (ErbB2) is a surface protein and member of the epidermal growth factor receptor (EGFR) family that is overexpressed in approximately one-fifth of breast cancers. HER2-positive breast tumours tend to be very aggressive, and patients with this type of tumour have a poor prognosis. A therapeutic monoclonal antibody called trastuzumab (Herceptin) has been designed to block HER2 signalling and is used as a treatment for patients with HER2-positive breast cancer. However, recent studies have shown that Herceptin does not decrease HER2 activation. This may be why patients invariably develop resistance if treated with Herceptin monotherapy. To date, no study has explained why Herceptin cannot abolish HER2 signalling despite being an anti-HER2 monoclonal antibody. We have found that Herceptin switches on a feedback loop that increases the production of the ADAM17 protein, a protease that in turn releases the growth factors that activate HER (ErbB) receptors. These growth factors activate HER2 and also the other members of the HER receptor familyEGFR, HER3 and HER4in such a way as to maintain HER2 activation and cell survival in HER2-positive breast cancer cells. We have found that when Herceptin is provided in combination with ADAM17 inhibitors, the feedback loop is abrogated in cells. Furthermore, a pan-HER inhibitor that decreases the activation of other HER receptors can also inhibit the feedback loop and decrease HER2 activation when used in combination with Herceptin. We further demonstrated that the combination therapy of Herceptin with a pan-HER inhibitor is more effective than Herceptin alone in an animal model of breast cancer. We believe our results offer treatment strategies that may help overcome acquired Herceptin resistance in patients with HER2-positive breast cancer. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- CD133 is a temporary marker of cancer stem cells in small cell lung cancer, but not in non-small cell lung cancer. AU- Cui, Fei AU- Wang, Jian AU- Chen, Duan AU- Chen, Yi-Jiang PY- 2010 T2- Oncology reports J2- Oncol Rep UR- http://www.ncbi.nlm.nih.gov/pubmed/21174061 N2- Lung cancer is the most common cause of cancer-related death worldwide. Current investigations in the field of cancer research have intensively focused on the 'cancer stem cell' or 'tumor-initiating cell'. While CD133 was initially considered as a stem cell marker only in the hematopoietic system and the nervous system, the membrane antigen also identifies tumorigenic cells in certain solid tumors. In this study, we investigated the human lung cancer cell lines A549, H157, H226, Calu-1, H292 and H446. The results of real-time PCR analysis after chemotherapy drug selection and the fluorescence-activated cell sorting analysis showed that CD133 only functioned as a marker in the small cell lung cancer line H446. The sorted CD133+ subset presented stem cell-like features, including self-renewal, differentiation, proliferation and tumorigenic capacity in subsequent assays. Furthermore, a proportion of the CD133+ cells had a tendency to remain stable, which may explain the controversies arising from previous studies. Therefore, the CD133+ subset should provide an enriched source of tumor-initiating cells among H446 cells. Moreover, the antigen could be used as an investigative marker of the tumorigenic process and an effective treatment for small cell lung cancer. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Tumor incidence in related hematopoietic stem cell donors. AU- Jeger, A AU- Favre, G AU- Lutz, J-M AU- Stern, M AU- Usel, M AU- Rovo, A AU- Rischewski, J AU- Tichelli, A AU- Gratwohl, A AU- Halter, J PY- 2010 T2- Bone marrow transplantation J2- Bone Marrow Transplant UR- http://www.ncbi.nlm.nih.gov/pubmed/21170092 N2- Late malignancies have been discussed as a potential risk for growth factor mobilized donors of hematopoietic stem cells. Little is known about the incidence and potential risk factors. This single center retrospective cohort study evaluated all HLA-identical sibling pairs with hematopoietic stem cell transplantation (HSCT) for a hematological malignancy, treated from 1974 to 2001 at the University Hospital of Basel. Three hundred eighteen pairs were identified, 291 donors (92%) could be contacted. Median observation time was 13.8 years (range 5-32 years). Sixteen (5%) donors had developed a total of 18 tumors, 17 recipients a secondary tumor. According to the age- and sex-adapted cancer incidence, 3.3 tumors in male and 6.8 in female donors were expected, 3 (relative risk (RR): 0.91, 95% confidence interval: 0.19-2.66) and 4 (RR: 0.58, 95% confidence interval: 0.16-1.48), respectively, were found in donors between 0 and 49 years. Between 50 and 69 years, 4.5 tumors in males and 4.8 in females were expected, 5 (RR: 1.11, 95% confidence interval: 0.36-2.59) and 6 (RR: 1.23, 95% confidence interval: 0.45-2.67), respectively, were observed. Tumors do occur in donors of hematopoietic stem cells at least at the rate as expected in a normal population; whether incidence exceeds expected rates needs to be determined in larger international cohorts.Bone Marrow Transplantation advance online publication, 20 December 2010; doi:10.1038/bmt.2010.291. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Consequences of Daily Administered Parathyroid Hormone on Myeloma Growth, Bone Disease, and Molecular Profiling of Whole Myelomatous Bone AU- Pennisi, Angela AU- Ling, Wen AU- Li, Xin AU- Khan, Sharmin AU- Wang, Yuping AU- Barlogie, Bart AU- Shaughnessy, John D AU- Yaccoby, Shmuel PY- 2010 T2- PLoS ONE J2- PLoS One UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3004797/ VL- 5 IS- 12 DO- 10.1371/journal.pone.0015233 C2- 3004797 N2- Background: Induction of osteolytic bone lesions in multiple myeloma is caused by an uncoupling of osteoclastic bone resorption and osteoblastic bone formation. Current management of myeloma bone disease is limited to the use of antiresorptive agents such as bisphosphonates. Methodology/Principal Findings: We tested the effects of daily administered parathyroid hormone (PTH) on bone disease and myeloma growth, and we investigated molecular mechanisms by analyzing gene expression profiles of unique myeloma cell lines and primary myeloma cells engrafted in SCID-rab and SCID-hu mouse models. PTH resulted in increased bone mineral density of myelomatous bones and reduced tumor burden, which reflected the dependence of primary myeloma cells on the bone marrow microenvironment. Treatment with PTH also increased bone mineral density of uninvolved murine bones in myelomatous hosts and bone mineral density of implanted human bones in nonmyelomatous hosts. In myelomatous bone, PTH markedly increased the number of osteoblasts and bone-formation parameters, and the number of osteoclasts was unaffected or moderately reduced. Pretreatment with PTH before injecting myeloma cells increased bone mineral density of the implanted bone and delayed tumor progression. Human global gene expression profiling of myelomatous bones from SCID-hu mice treated with PTH or saline revealed activation of multiple distinct pathways involved in bone formation and coupling; involvement of Wnt signaling was prominent. Treatment with PTH also downregulated markers typically expressed by osteoclasts and myeloma cells, and altered expression of genes that control oxidative stress and inflammation. PTH receptors were not expressed by myeloma cells, and PTH had no effect on myeloma cell growth in vitro. Conclusions/Significance: We conclude that PTH-induced bone formation in myelomatous bones is mediated by activation of multiple signaling pathways involved in osteoblastogenesis and attenuated bone resorption and myeloma growth; mechanisms involve increased osteoblast production of anti-myeloma factors and minimized myeloma induction of inflammatory conditions. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Challenges in the development of future treatments for breast cancer stem cells AU- Patel, Shyam A AU- Ndabahaliye, Anicia AU- Lim, Philip K AU- Milton, Russell AU- Rameshwar, Pranela PY- 2010 T2- Breast cancer : targets and therapy J2- Breast Cancer (London) UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3004231/ VL- 2 SP- 1-11 C2- 3004231 N2- The recurrence of tumors after years of disease-free survival has spurred interest in the concept that cancers may have a stem cell basis. Current speculation holds that as few as 0.1% of the tumor mass may be chemoresistant and radioresistant, harboring stem-like properties that drive tumor survival, development, and metastasis. There are intense investigations to characterize cancer stem cells on the basis of self-renewal and multi-lineage differentiation. Thus far, no successful targeted therapies have been developed and reached the clinic, but as these cells are isolated and characterized, insights may be unraveled. In this review, we discuss the controversy over the origins of the cancer stem cell hypothesis and the unforeseen factors that may facilitate breast cancer stem cell survival and metastasis. We discuss the role of tumor microenvironment, including carcinoma-associated fibroblasts, epigenetic factors, and the Th1/Th2 balance, in supporting breast cancer stem cells. In addition, we have incorporated ideas on the epithelial-to-mesenchymal transition in metastatic dissemination of epithelial malignancies. This area is relevant since breast cancer stem cells have been suggested to revert to a mesenchymal phenotype during the progression of cancer. Finally we discuss prospects on developing targeted therapy including novel treatment modalities such as oncolytic viral therapy, differentiation therapy, and nanotechnology. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Markers of Tumor-Initiating Cells Predict Chemoresistance in Breast Cancer AU- Gong, Chang AU- Yao, Herui AU- Liu, Qiang AU- Chen, Jingqi AU- Shi, Junwei AU- Su, Fengxi AU- Song, Erwei PY- 2010 T2- PLoS ONE J2- PLoS One UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3004932/ VL- 5 IS- 12 DO- 10.1371/journal.pone.0015630 C2- 3004932 N2- Purpose: Evidence is lacking whether the number of breast tumor-initiating cells (BT-ICs) directly correlates with the sensitivity of breast tumors to chemotherapy. Here, we evaluated the association between proportion of BT-ICs and chemoresistance of the tumors. Methods: Immunohistochemical staining(IHC) was used to examine the expression of aldehyde dehydrogenase 1 (ALDH1) and proliferating cell nuclear antigen, and TUNEL was used to detect the apoptosis index. The significance of various variables in patient survival was analyzed using a Cox proportional hazards model. The percentage of BT-ICs in breast cancer cell lines and primary breast tumors was determined by ALDH1 enzymatic assay, CD44+/CD24 phenotype and mammosphere formation assay. Results: ALDH1 expression determined by IHC in primary breast cancers was associated with poor clinical response to neoadjuvant chemotherapy and reduced survival in breast cancer patients. Breast tumors that contained higher proportion of BT-ICs with CD44+/CD24 phenotype, ALDH1 enzymatic activity and sphere forming capacity were more resistant to neoadjuvant chemotherapy. Chemoresistant cell lines AdrR/MCF-7 and SK-3rd, had increased number of cells with sphere forming capacity, CD44+/CD24 phenotype and side-population. Regardless the proportion of T-ICs, FACS-sorted CD44+/CD24 cells that derived from primary tumors or breast cancer lines were about 1060 fold more resistant to chemotherapy relative to the non- CD44+/CD24 cells and their parental cells. Furthermore, our data demonstrated that MDR1 (multidrug resistance 1) and ABCG2 (ATP-binding cassette sub-family G member 2) were upregulated in CD44+/CD24 cells. Treatment with lapatinib or salinomycin reduced the proportion of BT-ICs by nearly 50 fold, and thus enhanced the sensitivity of breast cancer cells to chemotherapy by around 30 fold. Conclusions: These data suggest that the proportion of BT-ICs is associated with chemotherapeutic resistance of breast cancer. It highlights the importance of targeting T-ICs, rather than eliminating the bulk of rapidly dividing and terminally differentiated cells, in novel anti-cancer strategies. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Non-Invasive In Vivo Imaging of Tumor-Associated CD133/Prominin AU- Tsurumi, Chizuko AU- Esser, Norbert AU- Firat, Elke AU- Gaedicke, Simone AU- Follo, Marie AU- Behe, Martin AU- Elssser-Beile, Ursula AU- Grosu, Anca-Ligia AU- Graeser, Ralph AU- Niedermann, Gabriele PY- 2010 T2- PLoS ONE J2- PLoS One UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3004948/ VL- 5 IS- 12 DO- 10.1371/journal.pone.0015605 C2- 3004948 N2- Background: Cancer stem cells are thought to play a pivotal role in tumor maintenance, metastasis, tumor therapy resistance and relapse. Hence, the development of methods for non-invasive in vivo detection of cancer stem cells is of great importance. Methodology/Principal Findings: Here, we describe successful in vivo detection of CD133/prominin, a cancer stem cell surface marker for a variety of tumor entities. The CD133-specific monoclonal antibody AC133.1 was used for quantitative fluorescence-based optical imaging of mouse xenograft models based on isogenic pairs of CD133 positive and negative cell lines. A first set consisted of wild-type U251 glioblastoma cells, which do not express CD133, and lentivirally transduced CD133-overexpressing U251 cells. A second set made use of HCT116 colon carcinoma cells, which uniformly express CD133 at levels comparable to primary glioblastoma stem cells, and a CD133-negative HCT116 derivative. Not surprisingly, visualization and quantification of CD133 in overexpressing U251 xenografts was successful; more importantly, however, significant differences were also found in matched HCT116 xenograft pairs, despite the lower CD133 expression levels. The binding of i.v.-injected AC133.1 antibodies to CD133 positive, but not negative, tumor cells isolated from xenografts was confirmed by flow cytometry. Conclusions/Significance: Taken together, our results show that non-invasive antibody-based in vivo imaging of tumor-associated CD133 is feasible and that CD133 antibody-based tumor targeting is efficient. This should facilitate developing clinically applicable cancer stem cell imaging methods and CD133 antibody-based therapeutics. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Stochastic acquisition of a stem cell-like state and drug tolerance in leukemia cells stressed by radiation. AU- Lee, Ga-Young AU- Shim, Jae-Seung AU- Cho, Bin AU- Jung, Joo-Young AU- Lee, Dong-Soon AU- Oh, Il-Hoan PY- 2010 T2- International journal of hematology J2- Int J Hematol UR- http://www.ncbi.nlm.nih.gov/pubmed/21170617 N2- A rare population of leukemia cells have the properties of leukemia stem cells (LSCs) and cause resistance to therapy, but their development is not clearly understood. In the current study, we show that a higher resistance to cytotoxic drug (Ara-C) can be developed in the subpopulation of promyelocytic leukemia cells that survived radiation treatment. These drug-tolerant leukemia cells (DTLs) are not observed immediately after radiation despite extensive genetic instability in the cells, but appear in 3weeks of recovery culture. Moreover, when the single cell-derived clones were examined by clonal trafficking, no correlation between radio-resistant and chemo-resistant leukemic clones was detected, indicating that the resistance is developed by active acquisition of the resistance without clonal predisposition. Interestingly, the DTLs mimicked the characteristics of LSCs exhibiting leukemia-initiating activities and lower levels of reactive oxygen species or a higher level expression of bmi-1 as well as higher resistance to retinoic acid-induced differentiation compared to parental leukemic cells. These studies show that an active reacquisition of stem cell-like properties can occur in the leukemia cells to develop resistance to treatments and that such reacquisition process of leukemic cells occurs in a stochastic manner triggered by radiation stress on leukemic cells. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- CD44(+)CD133(+) population exhibits cancer stem cell-like characteristics in human gallbladder carcinoma. AU- Shi, Chengjian AU- Tian, Rui AU- Wang, Min AU- Wang, Xin AU- Jiang, Jianxin AU- Zhang, Zhifa AU- Li, Xu AU- He, Zheng AU- Gong, Weiqiang AU- Qin, Renyi PY- 2010 T2- Cancer biology therapy J2- Cancer Biol Ther UR- http://www.ncbi.nlm.nih.gov/pubmed/20948317 VL- 10 IS- 11 N2- Cancer stem cells (CSCs)/tumor-initiating cells have been defined as a subset of tumor cells responsible for initiating and sustaining tumor development. Emerging evidence strongly supports the existence of CSCs in various solid tumors, but they have not yet been identified in human gallbladder carcinomas (GBC). In this study, we identified CSCs in primary GBC and in the cell line GBC-SD using the cell surface markers CD44 and CD133. The percentages of CD44(+)CD133(+) cells were 1.76-3.05% in primary tumors and 40.29% in GBC-SD cells. These cells showed stem cell properties, including selfrenewal, differentiation potential and high tumorigenicity. In vitro culture experiments revealed that CD44(+)CD133(+) GBC cells possessed a higher spheroid-colony forming ability in serum-free media than other subpopulations. When injected into nonobese diabetic/severe combined immunodeficient mice, these cells formed new tumors and generated CD44(+)CD133(+), CD44(-) and CD133(-) progeny. CD44(+)CD133(+) cells also showed a high degree of chemoresistance, possibly due to upregulation of the breast cancer resistance protein (ABCG2) and the transcription factor Gli1 in these highly tumorigenic cells. These results suggest that the CD44(+)CD133(+) population exhibited CSC-like characteristics and may thus provide a novel approach to the diagnosis and treatment of GBC. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- NKX2.2 suppresses self renewal of glioma-initiating cells. AU- Muraguchi, Teruyuki AU- Tanaka, Shingo AU- Yamada, Daisuke AU- Tamase, Akira AU- Nakada, Mitsutoshi AU- Nakamura, Hideo AU- Hoshii, Takayuki AU- Ooshio, Takako AU- Tadokoro, Yuko AU- Naka, Kazuhito AU- Ino, Yasushi AU- Todo, Tomoki AU- Kuratsu, Jun-Ichi AU- Saya, Hideyuki AU- Hamada, Jun-Ichiro AU- Hirao, Atsushi PY- 2010 T2- Cancer research J2- Cancer Res UR- http://www.ncbi.nlm.nih.gov/pubmed/21169405 N2- Glioblastoma (GBM) is the most aggressive and destructive form of brain cancer. Animal models that can unravel the mechanisms underlying its progression are needed to develop rational and effective molecular therapeutic approaches. In this study, we report the development of mouse models for spontaneous gliomas representing distinct progressive stages of disease that are governed by defined genetic alterations. Neural stem/progenitor cell (NPC)-specific constitutive Ras activation in vivo plus p53 deficiency led to development of primarily anaplastic astrocytoma (AA, grade III), whereas combined loss of p53 plus p16Ink4a/p19Arf led to development of GBM (grade IV) at 100% penetrance within 6 weeks. These glioma models showed enhanced stem cell properties (stemness) accompanied by malignant progression. Notably, we determined that in our models as well as in human specimens downregulation of the homeodomain transcription factor NKX2.2, which is essential for oligodendroglialdifferentiation, was correlated with increased tumor malignancy. Nkx2.2 overexpression by GBM-derived glioma-initiating cells (GICs) induced oligodendroglial differentiation and suppressed self-renewal capacity. By contrast, Nkx2.2 down-regulation in mouse NPCs accelerated GBM formation. Importantly, the inhibitory effects of NXK2.2 on GIC self-renewal were conserved in human cells. Thus, our mouse models offer pathobiologically significant advantages to investigate the nature of brain tumors, with improved opportunities to develop novel mechanism-based therapeutic approaches. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Using a Stem Cell-Based Signature to Guide Therapeutic Selection in Cancer. AU- Shats, Igor AU- Gatza, Michael L AU- Chang, Jeffrey T AU- Mori, Seiichi AU- Wang, Jialiang AU- Rich, Jeremy N AU- Nevins, Joseph PY- 2010 T2- Cancer research J2- Cancer Res UR- http://www.ncbi.nlm.nih.gov/pubmed/21169407 N2- Given the very substantial heterogeneity of most human cancers, it is likely that most cancer therapeutics will be active in only a small fraction of any population of patients. As such, the development of new therapeutics, coupled with methods to match a therapy with the individual patient, will be critical to achieving significant gains in disease outcome. One such opportunity is the use of expression signatures to identify key oncogenic phenotypes that can serve not only as biomarkers but also as a means of identifying therapeutic compounds that might specifically target these phenotypes. Given the potential importance of targeting tumors exhibiting a stem-like phenotype, we have developed an expression signature that reflects common biological aspects of various stem-like characteristics. The Consensus Stemness Ranking (CSR) signature is upregulated in cancer stem cell enriched samples, at advanced tumor stages and is associated with poor prognosis in multiple cancer types. Using two independent computational approaches we utilized the CSR signature to identify clinically useful compounds that could target the CSR phenotype. In vitro assays confirmed selectivity of several predicted compounds including topoisomerase inhibitors and resveratrol towards breast cancer cell lines that exhibit a high-CSR phenotype. Importantly, the CSR signature could predict clinical response of breast cancer patients to a neoadjuvant regimen that included a CSR-specific agent. Collectively, these results suggest therapeutic opportunities to target the CSR phenotype in a relevant cohort of cancer patients. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- The Therapeutic Implications of Plasticity of the Cancer Stem Cell Phenotype AU- Leder, Kevin AU- Holland, Eric C AU- Michor, Franziska PY- 2010 T2- PLoS ONE J2- PLoS One UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003707/ VL- 5 IS- 12 DO- 10.1371/journal.pone.0014366 C2- 3003707 N2- The cancer stem cell hypothesis suggests that tumors contain a small population of cancer cells that have the ability to undergo symmetric self-renewing cell division. In tumors that follow this model, cancer stem cells produce various kinds of specified precursors that divide a limited number of times before terminally differentiating or undergoing apoptosis. As cells within the tumor mature, they become progressively more restricted in the cell types to which they can give rise. However, in some tumor types, the presence of certain extra- or intracellular signals can induce committed cancer progenitors to revert to a multipotential cancer stem cell state. In this paper, we design a novel mathematical model to investigate the dynamics of tumor progression in such situations, and study the implications of a reversible cancer stem cell phenotype for therapeutic interventions. We find that higher levels of dedifferentiation substantially reduce the effectiveness of therapy directed at cancer stem cells by leading to higher rates of resistance. We conclude that plasticity of the cancer stem cell phenotype is an important determinant of the prognosis of tumors. This model represents the first mathematical investigation of this tumor trait and contributes to a quantitative understanding of cancer. N1- Exported from www.Quertle.info. Search query: cancer stem cells . ER- TY- JOUR TI- Basal-like breast cancers: the phenotypic disparity between the cancer-initiating cells and tumor histology. AU- Raouf, Afshin PY- 2010 T2- Breast cancer research : BCR J2- Breast Cancer Res UR- http://www.ncbi.nlm.nih.gov/pubmed/21172068 VL- 12 IS- 6 SP- 316 N2- ABSTRACT: Recent evidence suggests that a rare-cell population with a stem cell phenotype maintains breast tumors. Therefore, to devise breast cancer therapies that are more effective, we need to understand the unique biology of these cancer stem cells. Currently, very little is known about the origin of cancer stem cells and their relationship to the tumor phenotype. A recent study from Smalley's group demonstrates that targeting an inactivating Brca1 mutation to the luminal progenitors could yield basal-like breast cancers. This observation suggests that the inherent plasticity of the primitive cells can be hijacked by the tumorigenic processes to produce tumors with an unpredictable phenotype. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Immunohistochemical expression analysis of Cx43, Cx26, c-KIT and PlAP in contralateral testis biopsies of patients with non-seminomatous testicular germ cell tumor. AU- Steiner, Marianne AU- Weipoltshammer, Klara AU- Viehberger, Gerhard AU- Meixner, Eva-Maria AU- Lunglmayr, Gerhard AU- Schfer, Christian PY- 2010 T2- Histochemistry and cell biology J2- Histochem Cell Biol UR- http://www.ncbi.nlm.nih.gov/pubmed/21161545 N2- Non seminomatous testicular germ cell tumors (NSTGCTs) express fetal stem cell markers and display dysregulation of connexin 43 expression. Persistence of fetal spermatogonial characteristics was implicated in the emergence of testicular germ cell tumors. The objective of this study was to analyze the tubular architecture in contralateral testes of patients with NSTGCT. We studied morphologic alterations, expression patterns of markers for the integrity of the germinal epithelium (gap junction proteins connexin 43 and 26), as well as of the embryonic markers c-KIT and placental alkaline phosphatase (PlAP), both established markers to detect carcinoma in situ (CIS). In all samples, tubules showing maturation of germ cells up to spermatozoa were observed. In addition, tubules with alterations in tubular architecture and with impaired spermatogenesis occurred. In tubules showing aberrant spermatogenesis, connexin 43 (Cx43) signal was down-regulated and a shift of signal from gap junctions to the cytoplasm occurred. Concomitantly, Cx26 was found highly up-regulated in tubules with incomplete and aberrant germ cell maturation. All testes exhibited single spermatogonia with positive reaction for c-KIT and a significant positive correlation was found between the mean number of c-KIT positive spermatogonia per tubule and the percentage of tubules presenting severely impaired spermatogenesis. Our data show alterations of the normal architecture of the germinal epithelium and disturbances of spermatogenesis in the contralateral testes of patients with NSTGCT in all cases evaluated. The concomitant occurrence of c-KIT positive spermatogonia and defects in tubular architecture is in line with the hypothesis that patients with NSTGCT suffer from disturbed germ cell development. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Linking Transgene Expression of Engineered Mesenchymal Stem Cells and Angiopoietin-1-induced Differentiation to Target Cancer Angiogenesis. AU- Conrad, Claudius AU- Hsemann, Yves AU- Niess, Hanno AU- von Luettichau, Irene AU- Huss, Ralf AU- Bauer, Christian AU- Jauch, Karl-Walter AU- Klein, Christoph A AU- Bruns, Christiane AU- Nelson, Peter J PY- 2010 T2- Annals of surgery J2- Ann Surg UR- http://www.ncbi.nlm.nih.gov/pubmed/21169810 N2- OBJECTIVE:: To specifically target tumor angiogenesis by linking transgene expression of engineered mesenchymal stem cells to angiopoietin-1-induced differentiation. BACKGROUND:: Mesenchymal stem cells (MSCs) have been used to deliver therapeutic genes into solid tumors. These strategies rely on their homing mechanisms only to deliver the therapeutic agent. METHODS:: We engineered murine MSC to express reporter genes or therapeutic genes under the selective control of the Tie2 promoter/enhancer. This approach uses the differentiative potential of MSCs induced by the tumor microenvironment to drive therapeutic gene expression only in the context of angiogenesis. RESULTS:: When injected into the peripheral circulation of mice with either, orthotopic pancreatic or spontaneous breast cancer, the engineered MSCs were actively recruited to growing tumor vasculature and induced the selective expression of either reporter red florescent protein or suicide genes when the adoptively transferred MSC developed endothelial-like characteristics. The TK gene product in combination with the prodrug ganciclovir (GCV) produces a potent toxin, which affects replicative cells. The homing of engineered MSC with selective induction of TK in concert with GCV resulted in a toxic tumor-specific environment. The efficacy of this approach was demonstrated by significant reduction in primary tumor growth and prolongation of life in both tumor models. CONCLUSION:: This Trojan Horse combined stem cell/gene therapy represents a novel treatment strategy for tailored therapy of solid tumors. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Effective mobilization of hematopoietic progenitor cells in G-CSF mobilization defective CD26(-/-) mice through AMD3100-induced disruption of the CXCL12-CXCR4 axis. AU- Paganessi, Laura A AU- Walker, Andrew L AU- Tan, Lydia Luy AU- Holmes, Isaac AU- Rich, Elizabeth AU- Fung, Henry C AU- Christopherson, Kent W, 2nd PY- 2010 T2- Experimental hematology J2- Exp Hematol UR- http://www.ncbi.nlm.nih.gov/pubmed/21168468 N2- OBJECTIVE: We previously reported that inhibition or loss of CD26 (DPPIV/dipeptidylpeptidase IV) results in a defect in normal mobilization of hematopoietic stem and progenitor cells induced by granulocyte-colony stimulating factor (G-CSF). This suggests that CD26 is a necessary component of the mobilization pathway. Our goal in this study was to determine whether mobilization can be induced by the CXCR4 antagonist AMD3100 in mice lacking CD26 (CD26(-/-)). MATERIALS AND METHODS: Ten week old CD26(-/-) and C57BL/6 mice received a subcutaneous injection of AMD3100. One hour post-injection the mice were euthanized and peripheral blood and bone marrow were collected and evaluated. RESULTS: AMD3100 mobilizes hematopoietic progenitors into the peripheral blood of CD26(-/-) and mice. CONCLUSIONS: Our finding that AMD3100 rapidly mobilizes hematopoietic progenitor cells from the bone marrow into the periphery in CD26 deficient transgenic mice that otherwise exhibit a mobilization defect in response to G-CSF suggests that: (1) CD26 is downstream of G-CSF but upstream of the CXCL12-CXCR4 axis and (2) AMD3100 can be used as a single agent to mobilize hematopoietic stem and progenitor cells in normal donors or patients that have an intrinsic defect in their response to G-CSF treatment. Stem cell transplants are often the only curative treatment in some cancer patients. The ability to perform the transplant and its success is dependent on the ability to mobilize adequate numbers of hematopoietic progenitor cells. The use of AMD3100 as a single agent would give patients or donors an additional option for a successful stem cell transplant. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- The adult stem cell marker musashi-1 modulates endometrial carcinoma cell cycle progression and apoptosis via notch-1 and p21(WAF1/CIP1). AU- Gtte, Martin AU- Greve, Burkhard AU- Kelsch, Reinhard AU- Mller-Uthoff, Heike AU- Weiss, Kristin AU- Kharabi Masouleh, Behzad AU- Sibrowski, Walter AU- Kiesel, Ludwig AU- Buchweitz, Olaf PY- 2010 T2- International journal of cancer. Journal international du cancer J2- Int J Cancer UR- http://www.ncbi.nlm.nih.gov/pubmed/21165952 N2- The RNA-binding protein Musashi-1 has been proposed to maintain stem cell function during development and regenerative processes as a modulator of the Notch-1 signalling pathway. Musashi-1 expression is upregulated in endometrial carcinoma, however, its pathogenetic role in this tumor entity is unknown. Here we investigate the functional impact and mode of action of Musashi-1 on endometrial carcinoma cell behaviour in vitro. Aldehyde dehydrogenase-1 activity and side population (SP) measurement by Hoechst dye exclusion revealed that the Ishikawa endometrial carcinoma cell line contains a pool of putative cancer stem cells. Musashi-1 expression is 20.8-fold upregulated in SP+ compared to SP- and equally distributed between ALDH+ and ALDH- cell pools. siRNA-mediated knockdown of Musashi-1 mRNA expression lead to an altered expression of the signalling receptor Notch-1 and its downstream targets, the transcription factor Hes-1 and the cell cycle regulators p21(WAF1/CIP1) and cyclin B1, as determined by Western blotting and quantitative real-time PCR. Flow cytometric and ELISA analyses revealed that Musashi-1-mediated modulation of these factors exerted an antiproliferative effect on the cell cycle, and increased apoptosis in endometrial carcinoma cells. We conclude that Ishikawa cells contain a subpopulation of cells with stem cell-like properties. Musashi-1 modulates endometrial carcinoma cell cycle progression and apoptosis via the stemness-related factors Notch-1, Hes-1 and p21(WAF1/CIP1), thus emerging as a novel future target for endometrial carcinoma therapy. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Transglutaminase 2: A multi-tasking protein in the complex circuitry of inflammation and cancer. AU- Mehta, Kapil AU- Kumar, Aupam AU- Kim, Hong Im PY- 2010 T2- Biochemical pharmacology J2- Biochem Pharmacol UR- http://www.ncbi.nlm.nih.gov/pubmed/20599779 VL- 80 IS- 12 SP- 1921-9 N2- Metastasis of primary tumors to distant sites and their inherent or acquired resistance to currently available therapies pose major clinical challenge to the successful treatment of cancer. The identification of tumor-coded genes and how they contribute to the progression of cancer is required to improve patient outcomes. Recently, cells that have undergone the epithelial-mesenchymal transition (EMT), which share characteristics with cancer stem cells (CSC) have been implicated to play a role in drug resistance and metastasis of several types of cancer. In this review, we discuss the relationship among transglutaminase 2 (TG2), the EMT, and CSCs in inflammation and cancer. TG2 is a structurally and functionally complex protein implicated in such diverse processes as tissue fibrosis, wound healing, apoptosis, neurodegenerative disorders, celiac disease, atherosclerosis and cancer. Depending on the cellular context, TG2 can either promote or inhibit cell death. Increased expression of TG2 in several types of cancer cells has been associated with increased cell invasiveness, cell survival and decreased survival of patients with cancer. Down-regulation of TG2 by small interfering RNA (siRNA) or its inhibition by small molecule inhibitors has been shown to significantly enhances the therapeutic efficacy of anticancer drugs and inhibit metastatic spread. In addition, TG2-regulated pathways are involved in promoting or protecting normal and tumor cells from death-induced signaling. We discuss the contribution of TG2-regulated pathways to the development of drug resistance and progression to metastatic disease and the therapeutic potential of TG2 for treating advanced-stage cancer. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Large granular lymphocytic leukaemia pathogenesis and management. AU- Dearden, Claire PY- 2010 T2- British journal of haematology J2- Br J Haematol UR- http://www.ncbi.nlm.nih.gov/pubmed/21158751 N2- The WHO classification recognises three distinct disorders of large granular lymphocytes: T-cell large granular lymphocytic leukaemia (T-LGL), chronic lymphoproliferative disorders of NK-cells (CLPD-NK) and agressive NK-cell leukaemia. Despite the different cell of origin, there is considerable overlap between T-LGL and CLPD-NK in terms of clinical presentation and therapy. Many patients are asymptomatic and do not require treatment. Therapy, with immunosuppressant agents such as low dose methotrexate or ciclosporin, is usually indicated to correct cytopenias. In contrast, aggressive NK-cell leukaemia and the rare CD56(+) aggressive T-LGL leukaemia follow a fulminant clinical course, affect younger individuals and require more intensive combination chemotherapy followed by allogeneic stem cell transplant in eligible patients. The relative rarity of these disorders means that there have been few clinical trials to inform management. However, there is now considerable interest in the pathogenesis of the chronic LGL leukaemias and this has stimulated early trials to evaluate novel agents which target the dysregulated apoptotic pathways characteristic of this disease. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- CXCL12-CXCR4 Axis in Angiogenesis, Metastasis and Stem Cell Mobilization. AU- Liekens, S AU- Schols, D AU- Hatse, S PY- 2010 T2- Current pharmaceutical design J2- Curr Pharm Des UR- http://www.ncbi.nlm.nih.gov/pubmed/21158728 N2- Chemokines are key players in the attraction and activation of leukocytes and are thus implicated in the recruitment of immune cells at sites of infection and/or inflammation. They exert their action by binding to seven-transmembrane G protein-coupled receptors. The chemokine stromal cell-derived factor-1 (SDF-1)/CXCL12 represents the single natural ligand for the chemokine receptor CXCR4. CXCL12 possesses angiogenic properties and is involved in the outgrowth and metastasis of CXCR4-expressing tumors and in certain inflammatory autoimmune disorders, such as rheumatoid arthritis. CXCR4 expression on tumor cells is upregulated by hypoxia and angiogenic factors, such as vascular endothelial growth factor (VEGF). CXCR4 also acts as a co-receptor for entry of human immunodeficiency virus (HIV) in CD4(+) T cells. Finally, CXCL12/CXCR4 interactions were shown to play an important role in the migration of hematopoietic stem cells and their progenitors from, and their retention within, the bone marrow, a site characterized by high CXCL12 expression. As such, CXCR4 inhibitors may be utilized to inhibit HIV-1 infection, tumor growth and metastasis and to mobilize hematopoietic stem cells from the bone marrow in the circulation, where they can be collected for autologous stem cell transplantation. Here, we discuss the different aspects of CXCL12/CXCR4 biology as well as the development and anti-cancer/stem cell mobilizing activity of CXCR4 antagonists. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Cancer stem cell traits in squamospheres derived from primary head and neck squamous cell carcinomas. AU- Lim, Young Chang AU- Oh, Se-Yeong AU- Cha, Yun Yi AU- Kim, Sung-Hak AU- Jin, Xun AU- Kim, Hyunggee PY- 2010 T2- Oral oncology J2- Oral Oncol UR- http://www.ncbi.nlm.nih.gov/pubmed/21167769 N2- A subpopulation of cancer stem cells (CSCs), but not the majority of non-tumorigenic cancer cells, in a variety of human malignancies plays a critical role in cancer cell proliferation, invasion, metastasis, and tumor recurrence post-therapies. We report the isolation of sphere-forming cells (squamospheres) from primary head and neck squamous cell carcinomas (HNSCCs), and characterization of their CSC properties. Squamospheres appeared within 2 weeks after seeding as single-dissociated cells obtained from primary HNSCC specimens in serum-free culture conditions. Real-time RT-PCR and immunocytochemistry assays revealed that a number of stem cell markers, including CK5, OCT4, SOX2, and nestin, were up-regulated in HNSCC-driven squamospheres. Fluorescence-activated cell sorting (FACS) analysis showed that squamospheres contain enriched side population cells compared to serum-induced differentiated squamosphere cells. Furthermore, HNSCC-driven squamospheres appeared to be chemoresistant to cisplatin, 5-fluorouracil (FU), paclitaxel and doxetaxel, and showed increased levels of ABCG2, one of the ATP-binding cassette (ABC) transporters. Of particular interest, in sharp contrast to subcutaneous injection of 110(6) differentiated squamosphere cells, as few as 100 squamosphere cells were able to give rise to tumors in nude mice. Altogether, we assert that primary HNSCC-driven squamospheres possess CSC properties, and its functional analysis may provide a novel tool for investigating the tumorigenic process of HNSCC. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Targeting Wnt Signaling in Colon Cancer Stem Cells. AU- Medema, Jan Paul AU- De Sousa E Melo, Felipe AU- Vermeulen, Louis AU- Richel, Dirk J PY- 2010 T2- Clinical cancer research : an official journal of the American Association for Cancer Research J2- Clin Cancer Res UR- http://www.ncbi.nlm.nih.gov/pubmed/21159886 N2- The identification of cancer stem cell (CSC) populations in virtually all tumour types has widespread clinical consequences. CSCs are suggested to be the only cells within malignancies endowed with tumourigenic capacity and are therefore directly implicated in therapy resistance and minimal residual disease. The genetic and molecular mechanisms sustaining CSCs are only currently emerging. For instance, aberrant activation of the Wnt signaling pathway is crucial for many cancer types and especially those of the gastrointestinal tract. Indeed, Wnt signaling activity was shown to designate colon CSCs and is therefore an attractive target for new therapeutics. Here we review some of the latest developments that have been achieved to inhibit the Wnt pathway in the context of colon CSCs. Moreover, we discuss some of the pitfalls that can be anticipated and present new opportunities for therapeutic intervention. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- The Canonical NF-{kappa}B Pathway Governs Mammary Tumorigenesis in Transgenic Mice and Tumor Stem Cell Expansion. AU- Liu, Manran AU- Sakamaki, Toshiyuki AU- Casimiro, Mathew C AU- Willmarth, Nicole E AU- Quong, Andrew A AU- Ju, Xiaoming AU- Ojeifo, John AU- Jiao, Xuanmao AU- Yeow, Wen-Shuz AU- Katiyar, Sanjay AU- Shirley, L Andrew AU- Joyce, David AU- Lisanti, Michael P AU- Albanese, Christopher AU- Pestell, Richard G PY- 2010 T2- Cancer research J2- Cancer Res UR- http://www.ncbi.nlm.nih.gov/pubmed/21159656 VL- 70 IS- 24 SP- 10464-10473 N2- The role of mammary epithelial cell (MEC) NF-B in tumor progression in vivo is unknown, as murine NF-B components and kinases either are required for murine survival or interfere with normal mammary gland development. As NF-B inhibitors block both tumor-associated macrophages (TAM) and MEC NF-B, the importance of MEC NF-B to tumor progression in vivo remained to be determined. Herein, an MEC-targeted inducible transgenic inhibitor of NF-B (IBSR) was developed in ErbB2 mammary oncomice. Inducible suppression of NF-B in the adult mammary epithelium delayed the onset and number of new tumors. Within similar sized breast tumors, TAM and tumor neoangiogenesis was reduced. Coculture experiments demonstrated MEC NF-B enhanced TAM recruitment. Genome-wide expression and proteomic analysis showed that IBSR inhibited tumor stem cell pathways. IBSR inhibited breast tumor stem cell markers in transgenic tumors, reduced stem cell expansion in vitro, and repressed expression of Nanog and Sox2 in vivo and in vitro. MEC NF-B contributes to mammary tumorigenesis. As we show that NF-B contributes to expansion of breast tumor stem cells and heterotypic signals that enhance TAM and vasculogenesis, these processes may contribute to NF-B-dependent mammary tumorigenesis. Cancer Res; 70(24); 10464-73. 2010 AACR. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- TGF- Receptor Inhibitors Target the CD44(high)/Id1(high) Glioma-Initiating Cell Population in Human Glioblastoma. AU- Anido, Judit AU- Sez-Borderas, Andrea AU- Gonzlez-Junc, Alba AU- Rodn, Laura AU- Folch, Gerard AU- Carmona, Maria A AU- Prieto-Snchez, Rosa M AU- Barba, Ignasi AU- Martnez-Sez, Elena AU- Prudkin, Ludmila AU- Cuartas, Isabel AU- Ravents, Carolina AU- Martnez-Ricarte, Francisco AU- Poca, M Antonia AU- Garca-Dorado, David AU- Lahn, Michael M AU- Yingling, Jonathan M AU- Rodn, Jordi AU- Sahuquillo, Juan AU- Baselga, Jos AU- Seoane, Joan PY- 2010 T2- Cancer cell J2- Cancer Cell UR- http://www.ncbi.nlm.nih.gov/pubmed/21156287 VL- 18 IS- 6 SP- 655-68 N2- Glioma-initiating cells (GICs), also called glioma stem cells, are responsible for tumor initiation, relapse, and therapeutic resistance. Here, we show that TGF- inhibitors, currently under clinical development, target the GIC compartment in human glioblastoma (GBM) patients. Using patient-derived specimens, we have determined the gene responses to TGF- inhibition, which include inhibitors of DNA-binding protein (Id)-1 and -3 transcription factors. We have identified a cell population enriched for GICs that expresses high levels of CD44 and Id1 and tend to be located in a perivascular niche. The inhibition of the TGF- pathway decreases the CD44(high)/Id1(high) GIC population through the repression of Id1 and Id3 levels, therefore inhibiting the capacity of cells to initiate tumors. High CD44 and Id1 levels confer poor prognosis in GBM patients. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Non-stem cell origin for oligodendroglioma. AU- Persson, Anders I AU- Petritsch, Claudia AU- Swartling, Fredrik J AU- Itsara, Melissa AU- Sim, Fraser J AU- Auvergne, Romane AU- Goldenberg, David D AU- Vandenberg, Scott R AU- Nguyen, Kim N AU- Yakovenko, Stanislava AU- Ayers-Ringler, Jennifer AU- Nishiyama, Akiko AU- Stallcup, William B AU- Berger, Mitchel S AU- Bergers, Gabriele AU- McKnight, Tracy R AU- Goldman, Steven A AU- Weiss, William A PY- 2010 T2- Cancer cell J2- Cancer Cell UR- http://www.ncbi.nlm.nih.gov/pubmed/21156288 VL- 18 IS- 6 SP- 669-82 N2- Malignant astrocytic brain tumors are among the most lethal cancers. Quiescent and therapy-resistant neural stem cell (NSC)-like cells in astrocytomas are likely to contribute to poor outcome. Malignant oligodendroglial brain tumors, in contrast, are therapy sensitive. Using magnetic resonance imaging (MRI) and detailed developmental analyses, we demonstrated that murine oligodendroglioma cells show characteristics of oligodendrocyte progenitor cells (OPCs) and are therapy sensitive, and that OPC rather than NSC markers enriched for tumor formation. MRI of human oligodendroglioma also suggested a white matter (WM) origin, with markers for OPCs rather than NSCs similarly enriching for tumor formation. Our results suggest that oligodendroglioma cells show hallmarks of OPCs, and that a progenitor rather than a NSC origin underlies improved prognosis in patients with this tumor. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- -Catenin Mediates the Establishment and Drug Resistance of MLL Leukemic Stem Cells. AU- Yeung, Jenny AU- Esposito, Maria Teresa AU- Gandillet, Arnaud AU- Zeisig, Bernd B AU- Griessinger, Emmanuel AU- Bonnet, Dominique AU- So, Chi Wai Eric PY- 2010 T2- Cancer cell J2- Cancer Cell UR- http://www.ncbi.nlm.nih.gov/pubmed/21156284 VL- 18 IS- 6 SP- 606-18 N2- Identification of molecular pathways essential for cancer stem cells is critical for understanding the underlying biology and designing effective cancer therapeutics. Here, we demonstrated that -catenin was activated during development of MLL leukemic stem cells (LSCs). Suppression of -catenin reversed LSCs to a pre-LSC-like stage and significantly reduced the growth of human MLL leukemic cells. Conditional deletion of -catenin completely abolished the oncogenic potential of MLL-transformed cells. In addition, established MLL LSCs that have acquired resistance against GSK3 inhibitors could be resensitized by suppression of -catenin expression. These results unveil previously unrecognized multifaceted functions of -catenin in the establishment and drug-resistant properties of MLL stem cells, highlighting it as a potential therapeutic target for an important subset of AMLs. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- A malignant oligarchy: progenitors govern the behavior of oligodendrogliomas. AU- Pei, Yanxin AU- Wechsler-Reya, Robert J PY- 2010 T2- Cancer cell J2- Cancer Cell UR- http://www.ncbi.nlm.nih.gov/pubmed/21156279 VL- 18 IS- 6 SP- 546-7 N2- Recent studies have suggested that brain tumors arise from neural stem cells and are maintained by stem-like tumor-initiating cells (TICs). In this issue of Cancer Cell, Persson etal. report that oligodendrogliomas, unlike malignant astrocytomas, originate from-and are propagated by-cells that resemble oligodendrocyte progenitors. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Targeting cancer stem cells by inhibiting Wnt, Notch, and Hedgehog pathways. AU- Takebe, Naoko AU- Harris, Pamela J AU- Warren, Ronald Q AU- Ivy, S Percy PY- 2010 T2- Nature reviews. Clinical oncology J2- Nat Rev Clin Oncol UR- http://www.ncbi.nlm.nih.gov/pubmed/21151206 N2- Tumor relapse and metastasis remain major obstacles for improving overall cancer survival, which may be due at least in part to the existence of cancer stem cells (CSCs). CSCs are characterized by tumorigenic properties and the ability to self-renew, form differentiated progeny, and develop resistance to therapy. CSCs use many of the same signaling pathways that are found in normal stem cells, such as Wnt, Notch, and Hedgehog (Hh). The origin of CSCs is not fully understood, but data suggest that they originate from normal stem or progenitor cells, or possibly other cancer cells. Therapeutic targeting of both CSCs and bulk tumor populations may provide a strategy to suppress tumor regrowth. Development of agents that target critical steps in the Wnt, Notch, and Hh pathways will be complicated by signaling cross-talk. The role that embryonic signaling pathways play in the function of CSCs, the development of new anti-CSC therapeutic agents, and the complexity of potential CSC signaling cross-talk are described in this Review. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- CSPG Is a Secreted Factor that Stimulates Neural Stem Cell Survival Possibly by Enhanced EGFR Signaling AU- Tham, Muly AU- Ramasamy, Srinivas AU- Gan, Hui Theng AU- Ramachandran, Ashray AU- Poonepalli, Anuradha AU- Yu, Yuan Hong AU- Ahmed, Sohail PY- 2010 T2- PLoS ONE J2- PLoS One UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001889/ VL- 5 IS- 12 DO- 10.1371/journal.pone.0015341 C2- 3001889 N2- Understanding how autocrine/paracrine factors regulate neural stem cell (NSC) survival and growth is fundamental to the utilization of these cells for therapeutic applications and as cellular models for the brain. In vitro, NSCs can be propagated along with neural progenitors (NPs) as neurospheres (nsphs). The nsph conditioned medium (nsph-CM) contains cell-secreted factors that can regulate NSC behavior. However, the identity and exact function of these factors within the nsph-CM has remained elusive. We analyzed the nsph-CM by mass spectrometry and identified DSD-1-proteoglycan, a chondroitin sulfate proteoglycan (CSPG), apolipoprotein E (ApoE) and cystatin C as components of the nsph-CM. Using clonal assays we show that CSPG and ApoE are responsible for the ability of the nsph-CM to stimulate nsph formation whereas cystatin C is not involved. Clonal nsphs generated in the presence of CSPG show more than four-fold increase in NSCs. Thus CSPG specifically enhances the survival of NSCs. CSPG also stimulates the survival of embryonic stem cell (ESC)-derived NSCs, and thus may be involved in the developmental transition of ESCs to NSCs. In addition to its role in NSC survival, CSPG maintains the three dimensional structure of nsphs. Lastly, CSPG's effects on NSC survival may be mediated by enhanced signaling via EGFR, JAK/STAT3 and PI3K/Akt pathways. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- A rare case of metastatic renal carcinoid AU- Kato, Yoshiharu AU- Nakamura, Kogenta AU- Yamada, Yoshiaki AU- Nishikawa, Genya AU- Yoshizawa, Takahiko AU- Zennami, Kenji AU- Katsuda, Remi AU- Tobiume, Motoi AU- Aoki, Shigeyuki AU- Taki, Tomohiro AU- Honda, Nobuaki PY- 2010 T2- BMC urology J2- BMC Urol UR- http://www.biomedcentral.com/1471-2490/10/22 VL- 10 IS- 1 SP- 22 DO- 10.1186/1471-2490-10-22 C2- 3016340 N2- Abstract Background: Carcinoid is an endocrine cell tumor with low-grade atypia, which is generally a low-grade malignant cancer with a good prognosis. Metastatic renal carcinoid is even rarer than primary carcinoids. Case presentation: We present our experience of a patient with metastatic renal carcinoid from the gastrointestinal tract. Conclusions: The carcinoid tumor of the kidney in our patient, who had a history of liver metastasis from rectal carcinoid, was considered metastatic based on the pathological findings. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Identification of cancer stem cell markers in human malignant mesothelioma cells. AU- Ghani, Farhana Ishrat AU- Yamazaki, Hiroto AU- Iwata, Satoshi AU- Okamoto, Toshihiro AU- Aoe, Keisuke AU- Okabe, Kazunori AU- Mimura, Yusuke AU- Fujimoto, Nobukazu AU- Kishimoto, Takumi AU- Yamada, Taketo AU- Xu, C Wilson AU- Morimoto, Chikao PY- 2010 T2- Biochemical and biophysical research communications J2- Biochem Biophys Res Commun UR- http://www.ncbi.nlm.nih.gov/pubmed/21163253 N2- Malignant mesothelioma (MM) is an aggressive and therapy-resistant neoplasm arising from the pleural mesothelial cells and usually associated with long-term asbestos exposure. Recent studies suggest that tumors contain cancer stem cells (CSCs) and their stem cell characteristics are thought to confer therapy-resistance. However, whether MM cell has any stem cell characteristics is not known. To understand the molecular basis of MM, we first performed serial transplantation of surgical samples into NOD/SCID mice and established new cell lines. Next, we performed marker analysis of the MM cell lines and found that many of them contain SP cells and expressed several putative CSC markers such as CD9, CD24, and CD26. Interestingly, expression of CD26 closely correlated with that of CD24 in some cases. Sorting and culture assay revealed that SP and CD24(+) cells proliferated by asymmetric cell division-like manner. In addition, CD9(+) and CD24(+) cells have higher potential to generate spheroid colony than negative cells in the stem cell medium. Moreover, these marker-positive cells have clear tendency to generate larger tumors in mouse transplantation assay. Taken together, our data suggest that SP, CD9, CD24, and CD26 are CSC markers of MM and could be used as novel therapeutic targets. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- BCR-ABL kinase is dead; long live the CML stem cell. AU- Perl, Alexander AU- Carroll, Martin PY- 2010 T2- The Journal of Clinical Investigation J2- J Clin Invest UR- http://www.ncbi.nlm.nih.gov/pubmed/21157035 N2- Chronic myeloid leukemia (CML) is a hematopoietic disease characterized by expansion of myeloid blood cells. It is caused by the t(9;22) chromosomal translocation that results in the expression of the fusion tyrosine kinase BCR-ABL. Tyrosine kinase inhibitor (TKI) therapy has led to long-term remissions, but patients remain BCR-ABL+. There is agreement that TKIs do not kill CML stem cells; however, it is controversial whether this is because of a lack of BCR-ABL kinase inhibition in CML stem cells or because CML stem cells do not require BCR-ABL for survival. In this issue of the JCI, Corbin and colleagues provide definitive evidence that BCR-ABL is kinase active in CML stem cells and that TKIs inhibit this kinase activity without affecting CML stem cell survival. Rather, CML stem cells revert to a normal dependence on cytokines for survival and proliferation. These results demonstrate that the CML stem cell is not BCR-ABL addicted and have important implications for developing curative therapeutic approaches to CML. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- The HPB-AML-I cell line possesses the properties of mesenchymal stem cells AU- Ardianto, Bambang AU- Sugimoto, Takeshi AU- Kawano, Seiji AU- Kasagi, Shimpei AU- Jauharoh, Siti Na AU- Kurimoto, Chiyo AU- Tatsumi, Eiji AU- Morikawa, Keiko AU- Kumagai, Shunichi AU- Hayashi, Yoshitake PY- 2010 T2- Journal of Experimental Clinical Cancer Research J2- Journal of Experimental Clinical Cancer Research UR- http://www.jeccr.com/content/29/1/163 VL- 29 IS- 1 SP- 163 DO- 10.1186/1756-9966-29-163 C2- 3016278 N2- Abstract Background: In spite of its establishment from the peripheral blood of a case with acute myeloid leukemia (AML)-M1, HPB-AML-I shows plastic adherence with spindle-like morphology. In addition, lipid droplets can be induced in HPB-AML-I cells by methylisobutylxanthine, hydrocortisone, and indomethacin. These findings suggest that HPB-AML-I is similar to mesenchymal stem cells (MSCs) or mesenchymal stromal cells rather than to hematopoietic cells. Methods: To examine this possibility, we characterized HPB-AML-I by performing cytochemical, cytogenetic, and phenotypic analyses, induction of differentiation toward mesenchymal lineage cells, and mixed lymphocyte culture analysis. Results: HPB-AML-I proved to be negative for myeloperoxidase, while surface antigen analysis disclosed that it was positive for MSC-related antigens, such as CD29, CD44, CD55, CD59, and CD73, but not for CD14, CD19, CD34, CD45, CD90, CD105, CD117, and HLA-DR. Karyotypic analysis showed the presence of complicated abnormalities, but no reciprocal translocations typically detected in AML cases. Following the induction of differentiation toward adipocytes, chondrocytes, and osteocytes, HPB-AML-I cells showed, in conjunction with extracellular matrix formation, lipid accumulation, proteoglycan synthesis, and alkaline phosphatase expression. Mixed lymphocyte culture demonstrated that CD3+ T-cell proliferation was suppressed in the presence of HPB-AML-I cells. Conclusions: We conclude that HPB-AML-I cells appear to be unique neoplastic cells, which may be derived from MSCs, but are not hematopoietic progenitor cells. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Zinc Downregulates HIF-1 and Inhibits Its Activity in Tumor Cells In Vitro and In Vivo AU- Nardinocchi, Lavinia AU- Pantisano, Valentina AU- Puca, Rosa AU- Porru, Manuela AU- Aiello, Aurora AU- Grasselli, Annalisa AU- Leonetti, Carlo AU- Safran, Michal AU- Rechavi, Gideon AU- Givol, David AU- Farsetti, Antonella AU- D'Orazi, Gabriella PY- 2010 T2- PLoS ONE J2- PLoS One UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001454/ VL- 5 IS- 12 DO- 10.1371/journal.pone.0015048 C2- 3001454 N2- Background: Hypoxia inducible factor-1 (HIF-1) is responsible for the majority of HIF-1-induced gene expression changes under hypoxia and for the angiogenic switch during tumor progression. HIF-1 is often upregulated in tumors leading to more aggressive tumor growth and chemoresistance, therefore representing an important target for antitumor intervention. We previously reported that zinc downregulated HIF-1 levels. Here, we evaluated the molecular mechanisms of zinc-induced HIF-1 downregulation and whether zinc affected HIF-1 also in vivo. Methodology/Principal Findings: Here we report that zinc downregulated HIF-1 protein levels in human prostate cancer and glioblastoma cells under hypoxia, whether induced or constitutive. Investigations into the molecular mechanisms showed that zinc induced HIF-1 proteasomal degradation that was prevented by treatment with proteasomal inhibitor MG132. HIF-1 downregulation induced by zinc was ineffective in human RCC4 VHL-null renal carcinoma cell line; likewise, the HIF-1P402/P564A mutant was resistant to zinc treatment. Similarly to HIF-1, zinc downregulated also hypoxia-induced HIF-2 whereas the HIF-1 subunit remained unchanged. Zinc inhibited HIF-1 recruitment onto VEGF promoter and the zinc-induced suppression of HIF-1-dependent activation of VEGF correlated with reduction of glioblastoma and prostate cancer cell invasiveness in vitro. Finally, zinc administration downregulated HIF-1 levels in vivo, by bioluminescence imaging, and suppressed intratumoral VEGF expression. Conclusions/Significance: These findings, by demonstrating that zinc induces HIF-1 proteasomal degradation, indicate that zinc could be useful as an inhibitor of HIF-1 in human tumors to repress important pathways involved in tumor progression, such as those induced by VEGF, MDR1, and Bcl2 target genes, and hopefully potentiate the anticancer therapies. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER- TY- JOUR TI- Inactivation of p53 in breast cancers correlates with stem cell transcriptional signatures. AU- Mizuno, Hideaki AU- Spike, Benjamin T AU- Wahl, Geoffrey M AU- Levine, Arnold J PY- 2010 T2- Proceedings of the National Academy of Sciences of the United States of America J2- Proc Natl Acad Sci U S A UR- http://www.ncbi.nlm.nih.gov/pubmed/21149740 N2- Breast cancer comprises a heterogeneous set of diseases distinguishable from one another by pathologic presentation and molecular signatures. However, each breast cancer subtype is also heterogeneous. Some of the heterogeneity may be attributable to genetic instability, but recent data emphasize that developmental plasticity may also contribute. The p53 tumor suppressor could constitute a nodal control point underlying both sources of heterogeneity because it is frequently inactivated during malignant progression and has recently been shown to function as a potent barrier preventing fully differentiated cells from reverting to pluripotent stem cells after expression of appropriate oncogenes. Using archival microarray datasets, we tested the hypothesis that a p53 mutation could allow cells within a tumor to acquire a stem cell-like state by looking for coordinate expression of stem cell identity genes. We show that breast and lung cancers with p53 mutations do exhibit stem cell-like transcriptional patterns. Such tumors were also depleted for differentiation genes regulated by the polycomb repressor complex 2. These data are consistent with a model in which loss of p53 function enables acquisition of stem cell properties, which are positively selected during tumor progression. N1- Exported from www.Quertle.info. Search query:cancer stem cells . ER-
Molecular Trafficking Mechanisms of Multipotent Mesenchyma l Stem Cells Derived from Human Bone Marrow and Placenta Stem Cells and Development Molecular Trafficking Mechanisms of Multipotent Mesenchymal Stem Cells Derived from Human Bone Marrow and Placenta To cite this article: Gary Brooke, Hui Tong, Jean-Pierre Levesque, Kerry Atkinson. Stem Cells and Development. October 2008, 17(5): 929-940. doi:10.1089/scd.2007.0156. Published in Volume: 17 Issue 5: September 30, 2008 Online Ahead of Print: September 23, 2008 Online Ahead of Editing: June 18, 2008 Full Text: PDF for printing (521.9 KB) PDF w/ links (664.2 KB) Gary Brooke Adult Stem Cell and Haematopoietic Stem Cell Laboratories, Mater Medical Research Institute, Brisbane, Queensland, Australia. Hui Tong Adult Stem Cell and Haematopoietic Stem Cell Laboratories, Mater Medical Research Institute, Brisbane, Queensland, Australia. Jean-Pierre Levesque Adult Stem Cell and Haematopoietic Stem Cell Laboratories, Mater Medical Research Institute, Brisbane, Queensland, Australia. University of Queensland, Brisbane, Queensland, Australia. Kerry Atkinson Adult Stem Cell and Haematopoietic Stem Cell Laboratories, Mater Medical Research Institute, Brisbane, Queensland, Australia. University of Queensland, Brisbane, Queensland, Australia. We compared potential trafficking mechanisms used by human (h) multipotent mesenchymal stem cells (MSC) derived from bone marrow (bm) or placenta (p). Both hbmMSC and hpMSC expressed a broad range of cell surface adhesion molecules including 1-integrins (CD29) and CD44. Array data showed that both hbmMSC and hpMSC expressed mRNA for the cell adhesion molecules CD54 (ICAM-1), E-cadherin, CD166 (ALCAM), CD56 (NCAM), CD106 (VCAM-1), CD49a, b, c, e and f (integrins 1, 2, 3, 4 and 6), integrin 11, CD51 (integrin V), and CD29 (integrins 1). Functional binding of hpMSC, but not hbmMSC to VCAM-1 was demonstrated using recombinant chimeric constructs. Neither bone marrow nor placental MSC expressed ligands to endothelial selectins such as PSGL-1 or sialyl Lewis X (sLe x ) carbohydrates and neither were able to bind functionally to chimeric constructs of the endothelial selectins CD62E (E-selectin) and CD62P (P-selectin). Furthermore, MSC expressed a restricted range of transferases necessary for expression of sLe x , with no detectable expression of fucosyl transferases IV or VII. Placental MSC, but not hbmMSC, expressed mRNA for the chemokine receptors CCR1 and CCR3, and both hbmMSC and hpMSC expressed mRNA for CCR7, CCR8, CCR10, CCR11, CXCR4 and CXCR6. Intracellular chemokine receptor protein expression of CCR1, CCR3, CXCR3, CXCR4 and CXCR6 was detected in both hbmMSC and hpMSC. Cell surface expression of chemokine receptors was much more restricted with only CXCR6 displaying a strong signal on hbmMSC and hpMSC. Although cell surface expression of CXCR4 was not detected, MSC migrated in response to its ligand, CXCL12 (SDF-1). Thus, hbmMSC and hpMSC have an almost identical profile for cell surface adhesion and chemokine receptor molecules at the mRNA and protein levels. However, at the functional level, hpMSC likely utilise VLA-4-mediated binding in a superior manner to hbmMSC and thus may have superior engraftment properties to hbmMSC in vivo .
More recent approachis have focused on replacement of injured myocardium with healthy cardiomyocytes,and the induction of neovascularization and significant effort has been invested in the search for the optimal embryonic or adult progenitor cells with which to replace damaged cells. The angiogenic potential of vascular tissues emerges during organ growth and remains dormant within the postnatal, steady-state organism until elicited again during repair, regeneration,or neoplasia. Novel insights may be derived from investigation the trafficking mechanisms of the closely related hematopoietic cells or from an understanding of progenitor migration during embryogenesis.
Panminerva Med. 2010 Jun;52(2):97-110. Stem cells: the building blocks to repair the injured heart. Van Oorschot AA , Smits AM , Goumans MJ . Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands. Abstract Myocardial infarction is the major cause of death in western countries due to impaired function of the heart, which is the result of cardiomyocyte death and fibrotic scar formation. The endogenous regenerative capacity of the heart is unable to replenish this significant loss of tissue and conventional medical management cannot correct the underlying defects in cardiac muscle cell number. Recently, tremendous effort is being put into the development of cell transplantation protocol for heart repair, which has been put forward as an alternative therapy to reduce cell damage, cardiomyocyte death and improve tissue contraction. Unfortunately the ideal stem cell population for heart repair has not been identified to date, but several characteristics are defined which the ideal population should have namely, reduce cell damage, reduce cardiomyocyte death, induce differentiation into cardiomyocytes and endothelial cells, and improve tissue contraction. It is unclear whether this will be possible in one optimal population. Therefore the research focus is shifting towards improving the characteristics of the stem cell populations that are identified to date. In this review, we will give an overview of the different stem/progenitor cell populations and their application in cardiac repair and discuss current knowledge on issues like differentiation capacity, paracrine secretion profile, genetic modification of progenitor cells and their influence on cardiac remodeling.
Ugeskr Laeger. 2010 Sep 20;172(38):2613-6. Mathiasen AB , Srensen MH , Jrgensen E , Ekblond A , Kastrup J . Rigshospitalet, Kardiologisk Laboratorium 2014, Hjertecentret, 2100 Kbenhavn , Denmark. Abstract Treatment with stem cells with a regenerative potential is a new form of therapy that is being studied intensively. Mesenchymal stem cells or stromal cells (MSC) are a promising source of stem cells for regenerative therapy. MSC are easy to isolate and culture, expand in vitro and have a multipotent differentiation capacity. Clinical MSC studies on patients with ischaemic heart disease have shown improved left ventricular function and perfusion and also a reduction in infarct size and symptoms. In this short review we provide a status on MSC regenerative treatment in cardiovascular disease.
热门论文全文和相关文献见： http://www.sciencedirect.com/science?_ob=ArticleURL_udi=B6WSN-4KM3YVR-1_user=10_coverDate=08%2F25%2F2006_rdoc=1_fmt=high_orig=search_sort=d_docanchor=view=c_acct=C000050221_version=1_urlVersion=0_userid=10md5=019ed04a729cad1623a8d12a224a8fa2 Volume 126, Issue 4 , 25 August 2006, Pages 663-676 doi:10.1016/j.cell.2006.07.024 | How to Cite or Link Using DOI Cited By in Scopus (1655) Permissions Reprints Article Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors Kazutoshi Takahashi 1 and Shinya Yamanaka 1 , 2 , , 1 Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan 2 CREST, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan Received 24 April 2006; revised 18 June 2006; revised 20 July 2006. Published online: August 10, 2006. Available online 10 August 2006. 相关研究文献分析见： http://www.scopus.com/results/citedbyresults.url?sort=plf-fcite=2-s2.0-33747195353src=simp=tsid=-b_SVPt0pBxeQpfELYqrd0r%3a130sot=citesdt=asl=0origin=inwardtxGid=-b_SVPt0pBxeQpfELYqrd0r%3a12 Scopus: 1,661 Web SelectedSources 1661 Documents that cite: Takahashi K. , Yamanaka S. Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors (2006) Cell ,126(4),pp.663-676. var isAnyResultMarked = 'false'; Refine Results Close Source Title Stem Cells(82) Cell Stem Cell(77) Nature(60) Proceedings of the National Academy of Sciences of the United States of America(35) Cell(32) Author Name Hochedlinger, K.(19) Yamanaka, S.(17) Yamanaka, S.(16) Jaenisch, R.(13) Scholer, H.R.(12) Year 2010(391) 2009(651) 2008(440) 2007(155) 2006(24) Affiliation Kyoto University(67) Harvard Medical School(46) Massachusetts Institute of Technology(44) Harvard Stem Cell Institute(39) Harvard University(37) Subject Area Biochemistry, Genetics and Molecular Biology(1,129) Medicine(651) Multidisciplinary(119) Pharmacology, Toxicology and Pharmaceutics(106) Immunology and Microbiology(98) 文献计量分析结果见： http://www.gopubmed.org/web/gopubmed/1?WEB06a6npkpw811eIlIpI00h001000j100200010 844 documents semantically analyzed 1 2 Top Years Publications 2009 167 2010 144 2008 134 2007 79 2006 72 2005 52 2004 28 2003 24 2001 15 1998 14 2002 13 1999 13 2000 11 1997 8 1995 8 1994 7 1992 6 1986 5 1996 4 1993 3 1 2 1 2 Top Countries Publications USA 311 Japan 89 China 67 United Kingdom 49 Germany 44 France 22 South Korea 21 Canada 20 Spain 20 Israel 17 Singapore 16 Australia 16 Sweden 13 Italy 10 Iran 6 Taiwan 5 Belgium 5 Russia 4 Netherlands 4 Switzerland 4 1 2 1 2 3 ... 12 Top Cities Publications Boston 27 Kyoto 24 Cambridge, USA 24 Baltimore 17 Tokyo 16 Beijing 16 Cambridge 16 Singapur 16 Seoul 16 Shanghai 16 Los Angeles 15 Madison 14 Edinburgh 13 Toronto 12 New York 11 Guangzhou 10 Bethesda 9 Haifa 8 Davis 8 Barcelona 8 1 2 3 ... 12 1 2 3 ... 15 Top Journals Publications Stem Cells 62 Nature 43 Methods Mol Biol 31 Stem Cells Dev 27 Cell Stem Cell 25 J Biol Chem 20 Nat Biotechnol 18 Proc Natl Acad Sci U S A 16 Science 16 Blood 15 Differentiation 13 Biol Reprod 12 Development 10 J Cell Sci 10 Cloning Stem Cells 10 Cell 10 Mol Reprod Dev 10 P Natl Acad Sci Usa 10 Plos One 9 Exp Cell Res 9 1 2 3 ... 15 1 2 3 ... 195 Top Terms Publications stem cell development 745 stem cell differentiation 745 Fibroblasts 732 Animals 604 Mice 576 Cell Differentiation 484 Humans 450 Pluripotent Stem Cells 416 Cell Line 317 Cells, Cultured 309 Genes 306 Stem Cells 243 Embryonic Stem Cells 233 Transcription Factors 202 Tissues 193 POU domain, class 5, transcription factor 1 187 Proteins 182 Adult 163 Intercellular Signaling Peptides and Proteins 155 Cell Culture Techniques 153 1 2 3 ... 195 1 2 3 ... 217 Top Authors Publications Yamanaka S 11 Jaenisch R 7 Schler H 6 Meissner A 6 Pedersen R 5 Amit M 5 Bongso A 5 Choo A 5 Spielmann H 5 Park I 4 Sidhu K 4 Benvenisty N 4 Wernig M 4 Fong C 4 Richards M 4 Ichisaka T 4 Niwa H 4 Chin A 4 Takahashi K 4 Itskovitz-Eldor J 4 1 2 3 ... 217
April 08, 2010 The stem cell banking crisis Human embryonic stem cell research is being hampered by difficulties in distributing federally approved lines By Jef Akst Announcing The Scientist's Labbies Send us your lab's coolest videos, blogs, and other techy creations for a chance to win one of our 2010 multimedia awards By Jef Akst Hot paper in cancer biology The viral skinny By Edyta Zielinska NIH grants in danger? Obama's requested FY2011 NIH budget increase may not go far enough By The Scientist Community Energy-saving molecules A molecular lever switches the rotation of ATPase, giving cells control over whether they use energy, or produce it. Saita et al. 2010 J Biol Chem . Evaluated by N Nelson Plant knockouts get easier RNA gives plant scientists control over non-nuclear genomes: for the first time a synthetic riboswitch induces gene expression in chloroplasts. Verhounig et al. 2010 Proc Natl Acad Sci U S A . Evaluated by L Merendino J Joyard Gut bacteria are what we eat Intestinal microbes pick up genes from food-borne bacteria, possibly changing what our microbiota digests By Jef Akst Sizing up nanoparticles How to put nanoparticles to work in drug development By Kelly Rae Chi Down with reviews Review articles simply don't deserve all the citations they receive By Steven Wiley Wildlife manager or exterminator? Alaskan wildlife biologists are questioning the qualifications and management strategies of the new head of the Alaska Division of Wildlife Conservation By Lauren Urban Skates on thin ice A species of highly endangered fish is actually composed of two separate species, each in greater danger of extinction By Bob Grant Hot paper in genetics The closer By Edyta Zielinska News in a nutshell New science lab is launched; journal editor faces axe; women salaries fall short By Jef Akst Ancient aminos Was tubulin present in the primordial soup? By Alla Katsnelson Darwin to Joseph Hooker, 1844 Darwin describes his theory of natural selection in a letter to Hooker, comparing the experience to confessing a murder By Katherine Bagley
Dear Researcher , New Applied Biosystems TaqMan Protein expre ssion Assays enable fast, easy identification and relative protein quantification of pluripotency protein markers from limited quantities of cultured human embryonic stem cells (hESCs): Quantitate protein expre ssion using gold standard TaqMan 5' nuclease chemistry Correlate mRNA/miRNA expre ssion to protein expre ssion on the same real-time PCR platform Provide a more sensitive and quantitative readout than western blots or immunostaining Discover how Sincerely, Applied Biosystems Applied Biosystems 850 Lincoln Centre Dr. Foster City, CA 94404 United States www.appliedbiosystems.com FOR RESEARCH USE ONLY. NOT INTENDED FOR ANY ANIMAL OR HUMAN THERAPEUTIC OR DIAGNOSTIC USE, UNLESS OTHERWISE STATED. 2009 Life Technologies Corporation. All rights reserved. The trademarks mentioned herein are the property of Life Technologies Corporation or their respective owners. TaqMan is a registered trademark of Roche Molecular Systems, Inc. In compliance with federal regulations, we hereby disclose that this email communication is for commercial purposes. View the Applied Biosystems privacy policy. This message is brought to you as a registrant on The Scientist web site (The Scientist, 400 Market Street, Suite 1250, Philadelphia PA 19106 - 2501, USA). You have opted to receive relevant 3rd party e-mails through The Scientist . If you do not wish to receive these e-mails please visit Unsubscribe or, alternatively, log in to the My Scientist section of the website and edit your e-mail preferences.
http://www.pnas.org/content/early/2009/09/04/0908450106.abstract?sid=111e610d-c3fb-476d-b65b-f27b72b5622d Feeder-free derivation of induced pluripotent stem cells from adult human adipose stem cells Ning Sun a , Nicholas J. Panetta b , Deepak M. Gupta b , Kitchener D. Wilson a , Andrew Lee a , Fangjun Jia a , Shijun Hu a , Athena M. Cherry c , Robert C. Robbins d , e , Michael T. Longaker b , f , 1 and Joseph C. Wu a , e , g , 1 + Author Affiliations a Department of Radiology, b Division of Plastic and Reconstructive Surgery, Department of Surgery, c Department of Pathology, d Department of Cardiothoracic Surgery, e Cardiovascular Institute of Medicine, f Institute for Stem Cell Biology and Regenerative Medicine, and g Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305 Communicated by Mark M. Davis, Stanford University School of Medicine, Stanford, CA, July 31, 2009 (received for review April 2, 2009) Abstract Ectopic expression of transcription factors can reprogram somatic cells to a pluripotent state. However, most of the studies used skin fibroblasts as the starting population for reprogramming, which usually take weeks for expansion from a single biopsy. We show here that induced pluripotent stem (iPS) cells can be generated from adult human adipose stem cells (hASCs) freshly isolated from patients. Furthermore, iPS cells can be readily derived from adult hASCs in a feeder-free condition, thereby eliminating potential variability caused by using feeder cells. hASCs can be safely and readily isolated from adult humans in large quantities without extended time for expansion, are easy to maintain in culture, and therefore represent an ideal autologous source of cells for generating individual-specific iPS cells. differentiation pluripotency reprogramming Footnotes 1 To whom correspondence may be addressed. E-mail: joewu@stanford.edu or longaker@stanford.edu Author contributions: N.S., N.J.P., D.M.G., R.C.R., M.T.L., and J.C.W. designed research; N.S., N.J.P., D.M.G., K.D.W., A.L., F.J., S.H., and A.M.C. performed research; R.C.R., M.T.L., and J.C.W. contributed new reagents/analytic tools; N.S., N.J.P., K.D.W., A.L., F.J., S.H., A.M.C., and J.C.W. analyzed data; and N.S., K.D.W., M.T.L., and J.C.W. wrote the paper. http://www.sciencenet.cn/htmlpaper/20099111554215417275.shtm 脂肪干细胞更易变为iPS细胞 美国斯坦福大学研究人员9月7日说，与皮肤成纤维细胞相比，脂肪干细胞更容易转变为人工诱导多功能干细胞（iPS细胞），而且所转变的iPS细胞安全性更高，将来有望利用脂肪干细胞培育人体所需的各种器官。 iPS细胞是指体细胞经过基因重新编排，回归到胚胎干细胞的状态，从而具有类似胚胎干细胞的分化能力。培育iPS细胞涉及4种转录因子（Oct4、Sox2、Klf4和c-Myc）的表达，而在皮肤成纤维细胞中，这4种转录因子基本不表达或表达水平很低。 斯坦福大学研究人员发现，脂肪干细胞内两种转录因子的表达水平高于皮肤成纤维细胞，这表明，在初始状态下，脂肪干细胞更容易被诱导。 研究人员在脂肪干细胞和皮肤成纤维细胞中分别加入能够编码4种转录因子的基因后，约有万分之一的皮肤成纤维细胞转变为iPS细胞，而转变为iPS细胞的脂肪干细胞比例达到千分之二，是前者的20倍。利用脂肪干细胞培育的iPS细胞也通过了有关测试，它们能够分化成人体内的神经细胞、肌肉细胞以及肠上皮细胞等。 此外，利用脂肪干细胞培养iPS细胞不需要饲养细胞，这无疑提高了其安全性。所谓饲养细胞，是指在体外的细胞培养中，单个或少量的细胞不易生存与繁殖，必须加入其他活细胞才能使其快速繁殖，加入的细胞即为饲养细胞。 这项研究成果9月8日刊登在新一期美国《国家科学院院刊》（ PNAS ）上。负责这项研究的斯坦福大学干细胞生物学和再生医学研究所副主任迈克尔隆加克尔说，脂肪干细胞是一种伟大的自然资源，将来有望利用这种细胞培育人体所需的各种器官。 知识发现平台： http://arrowsmith.psych.uic.edu/cgi-bin/arrowsmith_uic/edit_b.cgi 检索策略：induced pluripotent stem cells and adipose stem cells 检索结果： Start A-Literature C-Literature B-list Filter Literature A-query: induced pluripotent stem cells C-query: adipose stem cells The B-list contains title words and phrases (terms) that appeared in both the A and the C literature. 0 articles appeared in both literatures. The results of this search are saved under id # 8403 and can be accessed from the start page after you leave this session. There are 183 terms on the current B-list (83 are predicted to be relevant), which is shown ranked according to predicted relevance. The list can be further trimmed down using the filters listed in the left margin. To assess whether there appears to be a biologically significant relationship between the AB and BC literatures for specific B-terms, please select one or more B-terms and then click the button to view the corresponding AB and BC literatures. Use Ctrl to select multiple B-terms. Rank Prob B-term 10.99adipose derived 20.99stem cell therapy 30.99adipose stromal 40.99adipose derived stromal 50.99ischemia induced angiogenesis 60.99derived stromal 70.99stem cell source 80.99adipose derived mesenchymal 90.99autologous adipose 100.99receptor human adipose 110.99human bone morphogenetic 120.99cell based therapy 130.99differentiation adipose 140.98human bone marrow 150.98osteogenic differentiation adipose 160.98cancer stem cell 170.98potential human adipose 180.98regeneration adipose 190.98infiltrating angiolipoma skeletal 200.98angiolipoma skeletal muscle 210.98regeneration adipose derived 220.98tissue regeneration adipose 230.98potential human bone 240.97murine adipose 250.97teratocarcinoma cell 260.97human bone 270.97teratocarcinoma 280.96adipocyte augment ischemia 290.96augment ischemia induced 300.96transplantation adipose stromal 310.96human adipose 320.96stromal derived factor-1 330.96fluorescent protein adipose 340.96primitive mesenchymal st-13 350.95fluid shear stress 360.95cell human bone 370.94bone cell able 380.94phenotype implication osteopenic 390.94cell able express 400.94able express osteoblastic 410.94implication osteopenic disorder 420.94source stem cell 430.94necrosis factor alpha 440.93simian virus t 450.92dna damage 460.92isolation mesenchymal stem 470.92infarction resistant adult 480.92myocardial infarction resistant 490.92chromosomal instability murine 500.92lost translation limiting 510.92yield myocardial infarction 520.92instability murine adipose 530.92adipose 540.89human adult bone 550.89retinoblastoma 560.88stromal 570.87cell dna damage 580.86carcinoma cell 590.86vivo adipose 600.82genotoxic 610.80leukemic 620.80liver failure 630.77chronic myelogenous leukemia 640.77signature 650.77cell source 660.76cardiomyopathy 670.72myelogenous leukemia 680.72lethally irradiated 690.72ischemia induced 700.71myeloproliferative 710.71acute leukemia 720.69carcinoma cell line 730.68dna damage induced 740.66teratoma 750.63aplastic anaemia 760.61genomic 770.55proliferative activity 780.51source cell 790.48diabetes 800.45myocardial infarction 810.42metaplasia 820.41ischemia 830.39carcinogenesis 840.35cell breast cancer 850.34leukemia 860.34spinal cord injury 870.33heart failure 880.32scar 890.31dedifferentiation 900.31autoimmune disease 910.30oncolytic 920.30melanoma cell 930.30infarction 940.30hyperthermia 950.28catalytic activity 960.26adhesion 970.24carcinoma 980.24wound 990.24efficient 1000.22cardiovascular disease 1010.22acute myocardial infarction 1020.22ischemic 1030.22|--ischemic tissue 1040.21aplasia 1050.20leukemia cell 1060.20functional recovery 1070.20stroke 1080.20induced tumor 1090.20sarcoma 1100.19hypoxia 1110.19lymphoma 1120.18related gene 1130.18mutation 1140.18source 1150.16signal 1160.15glioma 1170.15nodule 1180.15diabetic 1190.14anaemia 1200.14hippocampal 1210.14cytotoxicity 1220.11neurological disorder 1230.08heart disease 1240.08cytotoxic 1250.07anemia 1260.07inflammation 1270.06cancer 1280.05block 1290.05autoimmune 1300.05epilepsy 1310.05cell a critical 1320.05nervous 1330.04mass 1340.04breast cancer 1350.04neoplasia 1360.04suppression 1370.04cell lymphoma 1380.04death 1390.03melanoma 1400.03cell carcinoma 1410.03toxicity 1420.03resistance 1430.03h-1 1440.03stress 1450.02hope 1460.02neurogenic 1470.02tumor 1480.02strain 1490.02central nervous 1500.02dystrophy 1510.02null 1520.02exposure 1530.01arthritis 1540.01tumor induced 1550.01injury 1560.01endocrine 1570.01therapy 1580.01sensitivity 1590.01critical 1600.01disorder 1610.01presence 1620.01symptom 1630.00deficient 1640.00related 1650.00infection 1660.00inactivation 1670.00human disease 1680.00syndrome 1690.00normal 1700.00dysfunction 1710.00malignant 1720.00disease 1730.00activity 1740.00negative 1750.00view 1760.00sclerosis 1770.00history 1780.00loss 1790.00zone 1800.00lesion 1810.00impairment 1820.00pathogenesis 1830.00problem Restrict by semantic categories? Start A-Literature C-Literature B-list Filter Literature AB literature B-term BC literature induced pluripotent stem cell... ischemia induced angiogenesis adipose stem cells 1: Transplantation of adipose stromal cells, but not mature adipocytes, augments ischemia-induced angiogenesis .2007 Add to clipboard 1: Implantation of adipose-derived regenerative cells enhances ischemia-induced angiogenesis .2009 Add to clipboard 2: Transplantation of adipose stromal cells, but not mature adipocytes, augments ischemia-induced angiogenesis .2007 Add to clipboard Start A-Literature C-Literature B-list Filter Literature AB literature B-term BC literature induced pluripotent stem cell... stem cell therapy adipose stem cells 1: Stem cell therapy for ischemic heart disease: where are we?2009 Add to clipboard 2: Genetic Basis of Inherited Macular Dystrophies and Implications for Stem Cell Therapy .2009 Add to clipboard 3: 2006 Add to clipboard 1: A review of gene and stem cell therapy in cutaneous wound healing.2009 Add to clipboard 2: Stem cell therapy for urethral sphincter regeneration.2009 Add to clipboard 3: 2009 Add to clipboard 4: Muscle derived stem cell therapy for stress urinary incontinence.2008 Add to clipboard 5: Adipose-derived stem cell therapy for intervertebral disc regeneration: an in vitro reconstructed tissue in alginate capsules.2008 Add to clipboard 6: Advances in the understanding of sress urinary incontinence and the promise of stem-cell therapy .2007 Add to clipboard 7: Current concepts in adult stem cell therapy for stroke.2006 Add to clipboard 8: Stem cell therapy for neurologic disorders: therapeutic potential of adipose-derived stem cells.2005 Add to clipboard 9: Adult stem cell therapy for the heart.2004 Add to clipboard 10: Mesenchymal stem cell therapy in joint disease.2003 Add to clipboard 发现的新知识单元（用于科研选题参考） job id # 8403 started Fri Sep 11 06:35:57 2009 Max_citations: 50000 Stoplist: /var/www/html/arrowsmith_uic/data/stopwords_pubmed Ngram_max: 3 8403 Search ARROWSMITH A A_query_raw: induced pluripotent stem cells Fri Sep 11 06:36:18 2009 A query = induced pluripotent stem cells started Fri Sep 11 06:36:18 2009 A query resulted in 1067 titles 8403 Search ARROWSMITH C C_query_raw: adipose stem cells Fri Sep 11 06:36:40 2009 C: adipose stem cells 2217 A: pubmed_query_A 1067 AC: ( induced pluripotent stem cells ) AND ( adipose stem cells ) 23 C query = adipose stem cells started Fri Sep 11 06:36:46 2009 C query resulted in 2216 titles A AND C query resulted in 0 titles 2499 B-terms ready on Fri Sep 11 06:37:32 2009 Sem_filter: Disorders 183 B-terms left after filter executed Fri Sep 11 06:44:51 2009 Viewed B-terms Fri Sep 11 06:46:37 2009 ischemia induced angiogenesis B-list on Fri Sep 11 06:56:59 2009 1 adipose derived 2 stem cell therapy 3 adipose stromal 4 adipose derived stromal 5 ischemia induced angiogenesis 6 derived stromal 7 stem cell source 8 adipose derived mesenchymal 9 autologous adipose 10 receptor human adipose 11 human bone morphogenetic 12 cell based therapy 13 differentiation adipose 14 human bone marrow 15 osteogenic differentiation adipose 16 cancer stem cell 17 potential human adipose 18 regeneration adipose 19 infiltrating angiolipoma skeletal 20 angiolipoma skeletal muscle 21 regeneration adipose derived 22 tissue regeneration adipose 23 potential human bone 24 murine adipose 25 teratocarcinoma cell 26 human bone 27 teratocarcinoma 28 adipocyte augment ischemia 29 augment ischemia induced 30 transplantation adipose stromal 31 human adipose 32 stromal derived factor-1 33 fluorescent protein adipose 34 primitive mesenchymal st-13 35 fluid shear stress 36 cell human bone 37 bone cell able 38 phenotype implication osteopenic 39 cell able express 40 able express osteoblastic 41 implication osteopenic disorder 42 source stem cell 43 necrosis factor alpha 44 simian virus t 45 dna damage 46 isolation mesenchymal stem 47 infarction resistant adult 48 myocardial infarction resistant 49 chromosomal instability murine 50 lost translation limiting 51 yield myocardial infarction 52 instability murine adipose 53 adipose 54 human adult bone 55 retinoblastoma 56 stromal 57 cell dna damage 58 carcinoma cell 59 vivo adipose 60 genotoxic 61 leukemic 62 liver failure 63 chronic myelogenous leukemia 64 signature 65 cell source 66 cardiomyopathy 67 myelogenous leukemia 68 lethally irradiated 69 ischemia induced 70 myeloproliferative 71 acute leukemia 72 carcinoma cell line 73 dna damage induced 74 teratoma 75 aplastic anaemia 76 genomic 77 proliferative activity 78 source cell 79 diabetes 80 myocardial infarction 81 metaplasia 82 ischemia 83 carcinogenesis 84 cell breast cancer 85 leukemia 86 spinal cord injury 87 heart failure 88 scar 89 dedifferentiation 90 autoimmune disease 91 oncolytic 92 melanoma cell 93 infarction 94 hyperthermia 95 catalytic activity 96 adhesion 97 carcinoma 98 wound 99 efficient 100 cardiovascular disease 101 acute myocardial infarction 102 ischemic 103 ischemic tissue 104 aplasia 105 leukemia cell 106 functional recovery 107 stroke 108 induced tumor 109 sarcoma 110 hypoxia 111 lymphoma 112 related gene 113 mutation 114 source 115 signal 116 glioma 117 nodule 118 diabetic 119 anaemia 120 hippocampal 121 cytotoxicity 122 neurological disorder 123 heart disease 124 cytotoxic 125 anemia 126 inflammation 127 cancer 128 block 129 autoimmune 130 epilepsy 131 cell a critical 132 nervous 133 mass 134 breast cancer 135 neoplasia 136 suppression 137 cell lymphoma 138 death 139 melanoma 140 cell carcinoma 141 toxicity 142 resistance 143 h-1 144 stress 145 hope 146 neurogenic 147 tumor 148 strain 149 central nervous 150 dystrophy 151 null 152 exposure 153 arthritis 154 tumor induced 155 injury 156 endocrine 157 therapy 158 sensitivity 159 critical 160 disorder 161 presence 162 symptom 163 deficient 164 related 165 infection 166 inactivation 167 human disease 168 syndrome 169 normal 170 dysfunction 171 malignant 172 disease 173 activity 174 negative 175 view 176 sclerosis 177 history 178 loss 179 zone 180 lesion 181 impairment 182 pathogenesis 183 problem
知识发现平台： http://arrowsmith.psych.uic.edu/cgi-bin/arrowsmith_uic/show_sentences.cgi 检索策略：parkinson disease and embryonic stem cells 发现的相关研究报道： AB literature B-term BC literature Mitochondrial gene replacement... parkinson disease embryonic stem cells 1: Protection by the NDI1 gene against neurodegeneration in a rotenone rat model of Parkinson's disease .2008 Add to clipboard 2: 2004 Add to clipboard 3: Neuroprotective gene therapy for Parkinson's disease .2002 Add to clipboard 4: Mitochondrial ND1 sequence analysis and association of the T4216C mutation with Parkinson's disease .2000 Add to clipboard 1: The role of Lmx1a in the differentiation of human embryonic stem cells into midbrain dopamine neurons in culture and after transplantation into a Parkinson's disease model.2009 Add to clipboard 2: Cell replacement therapy for Parkinson's disease .2009 Add to clipboard 3: 2009 Add to clipboard 4: Nuclear transfer embryonic stem cells provide an in vitro culture model for Parkinson's disease .2009 Add to clipboard 5: Survival and early functional integration of dopaminergic progenitor cells following transplantation in a rat model of Parkinson's disease .2009 Add to clipboard 6: Granulocyte-macrophage colony-stimulating factor promotes survival of dopaminergic neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced murine Parkinson's disease model.2009 Add to clipboard 7: Multitracer assessment of dopamine function after transplantation of embryonic stem cell-derived neural stem cells in a primate model of Parkinson's disease .2009 Add to clipboard 8: Prospects of stem cell therapy for replacing dopamine neurons in Parkinson's disease .2009 Add to clipboard 9: Effects of GDNF pretreatment on function and survival of transplanted fetal ventral mesencephalic cells in the 6-OHDA rat model of Parkinson's disease .2009 Add to clipboard 10: Treatment of Parkinson's disease model mice with allogeneic embryonic stem cells : necessity of immunosuppressive treatment for sustained improvement.2009 Add to clipboard 11: Autologous neural stem cell transplantation: A new treatment option for Parkinson's disease ?2009 Add to clipboard 12: Bone marrow-derived mesenchymal stem cell therapy as a candidate disease-modifying strategy in Parkinson's disease and multiple system atrophy.2009 Add to clipboard 13: Parkinson's disease .2009 Add to clipboard 14: Future directions: use of interventional MRI for cell-based therapy of Parkinson disease .2009 Add to clipboard 15: Cells therapy for Parkinson's disease -so close and so far away.2009 Add to clipboard 16: The search for a curative cell therapy in Parkinson's disease .2008 Add to clipboard 17: From bench to bed: the potential of stem cells for the treatment of Parkinson's disease .2008 Add to clipboard 18: Comparison of the therapeutic potential of adult and embryonic neural precursor cells in a rat model of Parkinson disease .2008 Add to clipboard 19: Survival, differentiation, and migration of bioreactor-expanded human neural precursor cells in a model of Parkinson disease in rats.2008 Add to clipboard 20: DJ-1-binding compounds prevent oxidative stress-induced cell death and movement defect in Parkinson's disease model rats.2008 Add to clipboard 21: Embryonic stem cell-derived Pitx3-enhanced green fluorescent protein midbrain dopamine neurons survive enrichment by fluorescence-activated cell sorting and function in an animal model of Parkinson's disease .2008 Add to clipboard 22: Embryonic stem cells and Parkinson's disease : cell transplantation to cell therapy.2008 Add to clipboard 23: Therapeutic potentials of human embryonic stem cells in Parkinson's disease .2008 Add to clipboard 24: Human neural stem cells migrate along the nigrostriatal pathway in a primate model of Parkinson's disease .2008 Add to clipboard 25: 2008 Add to clipboard 26: Stem cells and Parkinson's disease : toward a treatment, not a cure.2008 Add to clipboard 27: Functional effect of FGF2- and FGF8-expanded ventral mesencephalic precursor cells in a rat model of Parkinson's disease .2008 Add to clipboard 28: Emerging restorative treatments for Parkinson's disease .2008 Add to clipboard 29: Parthenogenetic dopamine neurons from primate embryonic stem cells restore function in experimental Parkinson's disease .2008 Add to clipboard 30: 2008 Add to clipboard 31: Persistent dopamine functions of neurons derived from embryonic stem cells in a rodent model of Parkinson disease .2007 Add to clipboard 32: Benefits, risks and ethical considerations in translation of stem cell research to clinical applications in Parkinson's disease .2007 Add to clipboard 33: Neural-tube-derived neuroepithelial stem cells: a new transplant resource for Parkinson's disease .2007 Add to clipboard 34: Current advances in the treatment of Parkinson's disease with stem cells.2007 Add to clipboard 35: Stem cell therapy for Parkinson's disease .2007 Add to clipboard 36: 2007 Add to clipboard 37: The future of cell therapies in the treatment of Parkinson's disease .2007 Add to clipboard 38: Restorative cell therapy for Parkinson's disease : a quest for the perfect cell.2007 Add to clipboard 39: Stem cell transplantation: a promising therapy for Parkinson's disease .2007 Add to clipboard 40: Cell transplantation for patients with Parkinson's disease .2006 Add to clipboard 41: Activation of p53 signaling initiates apoptotic death in a cellular model of Parkinson's disease .2006 Add to clipboard 42: Transplantation of human embryonic stem cell-derived cells to a rat model of Parkinson's disease : effect of in vitro differentiation on graft survival and teratoma formation.2006 Add to clipboard 43: Embryonic stem cell-derived neuron models of Parkinson's disease exhibit delayed neuronal death.2006 Add to clipboard 44: Stem cell therapy for Parkinson's disease .2006 Add to clipboard 45: Enriched NCAM-positive cells form functional dopaminergic neurons in the rat model of Parkinson's disease .2006 Add to clipboard 46: Transplanted human neural precursor cells migrate widely but show no lesion-specific tropism in the 6-hydroxydopamine rat model of Parkinson's disease .2006 Add to clipboard 47: Potential application of embryonic stem cells in Parkinson's disease : drug screening and cell therapy.2006 Add to clipboard 48: Neural precursor cells differentiated from mouse embryonic stem cells relieve symptomatic motor behavior in a rat model of Parkinson's disease .2005 Add to clipboard 49: Stem cells may reshape the prospect of Parkinson's disease therapy.2005 Add to clipboard 50: Cripto as a target for improving embryonic stem cell-based therapy in Parkinson's disease .2005 Add to clipboard 51: Cell therapy for Parkinson's disease : problems and prospects.2005 Add to clipboard 52: Regenerative medicine in Parkinson's disease : generation of mesencephalic dopaminergic cells from embryonic stem cells .2005 Add to clipboard 53: Embryonic stem cells as a cell source for treating Parkinson's disease .2005 Add to clipboard 54: Stem cell-based therapy for Parkinson's disease .2005 Add to clipboard 55: Differentiation and migration of long term expanded human neural progenitors in a partial lesion model of Parkinson's disease .2004 Add to clipboard 56: The cellular repair of the brain in Parkinson's disease --past, present and future.2004 Add to clipboard 57: Cell transplantation for Parkinson's disease : present status.2004 Add to clipboard 58: Efficient induction of dopaminergic neurons from embryonic stem cells for application to Parkinson's disease .2004 Add to clipboard 59: Stem cell therapy for Parkinson's disease : where do we stand?2004 Add to clipboard 60: 2004 Add to clipboard 61: Retraction: efficient induction of dopaminergic neurons from embryonic stem cells for application to Parkinson's disease .2004 Add to clipboard 62: 2004 Add to clipboard 63: Embryonic and adult stem cells as a source for cell therapy in Parkinson's disease .2004 Add to clipboard 64: 2003 Add to clipboard 65: Stem cells for cell therapy in Parkinson's disease .2003 Add to clipboard 66: Transplantation of expanded neural precursor cells from the developing pig ventral mesencephalon in a rat model of Parkinson's disease .2003 Add to clipboard 67: Transfer of the von Hippel-Lindau gene to neuronal progenitor cells in treatment for Parkinson's disease .2003 Add to clipboard 68: Genetically modified human embryonic stem cells relieve symptomatic motor behavior in a rat model of Parkinson's disease .2003 Add to clipboard 69: Neurotrophic factor in the treatment of Parkinson disease .2003 Add to clipboard 70: Embryonic ventral mesencephalic grafts to the substantia nigra of MPTP-treated monkeys: feasibility relevant to multiple-target grafting as a therapy for Parkinson's disease .2002 Add to clipboard 71: Will embryonic stem cells be a useful source of dopamine neurons for transplant into patients with Parkinson's disease ?2002 Add to clipboard 72: The potential for circuit reconstruction by expanded neural precursor cells explored through porcine xenografts in a rat model of Parkinson's disease .2002 Add to clipboard 73: Stem cells in the treatment of Parkinson's disease .2002 Add to clipboard 74: Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease .2002 Add to clipboard 75: Effects of antioxidant pretreatment on the survival of embryonic dopaminergic neurons in vitro and following grafting in an animal model of Parkinson's disease .2002 Add to clipboard 76: Neural stem cells and Parkinson's disease .2002 Add to clipboard 77: Current state of stem cell research for the treatment of Parkinson's disease .2002 Add to clipboard 78: Role of cell therapy in Parkinson disease .2002 Add to clipboard 79: A clonal line of mesencephalic progenitor cells converted to dopamine neurons by hematopoietic cytokines: a source of cells for transplantation in Parkinson's disease .2001 Add to clipboard 80: Promotion of survival and regeneration of nigral dopamine neurons in a rat model of Parkinson's disease after implantation of embryonal carcinoma-derived neurons genetically engineered to produce glial cell line-derived neurotrophic factor.2000 Add to clipboard 信息分析平台： http://www.gopubmed.org/web/gopubmed/WEB10O00d000j100300.y 检索策略：parkinson disease and embryonic stem cells 信息分析结果如下： Top Years Publications 2007 25 2008 23 2004 20 2006 18 2009 17 2002 15 2003 10 2005 9 2001 5 2000 5 1997 2 1996 1 1 2 Top Countries Publications USA 40 Japan 22 United Kingdom 15 Sweden 15 Germany 12 South Korea 7 China 5 Switzerland 4 France 3 Israel 2 Canada 2 Netherlands 2 Spain 2 Belgium 1 Denmark 1 India 1 Australia 1 Italy 1 Mexico 1 Czech Republic 1 1 2 1 2 3 Top Cities Publications Lund 12 Kyoto 10 Cambridge 9 Belmont, MA, USA 7 New York 6 Denver 4 Cologne 4 London 3 Stockholm 3 Philadelphia 3 Bethesda 3 Seoul 3 San Francisco 2 Berne 2 Tochigi 2 Leipzig 2 Beijing 2 Madison 2 Los Angeles 2 Chicago 2 1 2 3 1 2 3 ... 6 Top Journals Publications Stem Cells 12 Brain Res 4 Rinsho Shinkeigaku 3 Neurosurg Focus 3 J Neurosurg 3 Nat Med 3 Cell Transplant 2 Proc Natl Acad Sci U S A 2 Stem Cells Dev 2 Eur J Neurosci 2 Parkinsonism Relat D 2 J Gerontol A-biol 2 Exp Neurol 2 Plos Biol 2 J Clin Invest 2 Cell Tissue Res 2 Expert Opin Biol Ther 2 Neurol Surg Tokyo 2 Regen Med 2 Neurochem Res 2 1 2 3 ... 6 1 2 3 ... 29 Top Authors Publications Barker R 7 Isacson O 7 Brundin P 6 Li J 5 Dunnett S 5 Beal M 4 Svendsen C 3 McKay R 3 Arenas E 3 Lindvall O 3 Morizane A 3 Tyers P 3 Hescheler J 3 Snchez Pernaute R 3 Schwarz J 3 Fukuda H 3 Takahashi J 3 Kim K 3 Chung S 3 Sasai Y 2 1 2 3 ... 29 1 2 3 ... 54 Top Terms Publications Parkinson Disease 150 Neurons 124 stem cell differentiation 123 Animals 122 stem cell development 121 Humans 112 Dopamine 87 Stem Cells 78 Stem Cell Transplantation 77 Cell Differentiation 69 Tissues 65 Tissue Therapy 57 Cell Transplantation 51 Rats 49 Mesencephalon 44 Patients 42 Mice 42 Embryonic Stem Cells 41 Therapeutics 39 Neurodegenerative Diseases 36 1 2 3 ... 54
Relaxing Restrictions on Stem Cell Research 2009年3月13日，Science报道（全文见图上的链接），美国总统巴拉克奥巴马签署一项行政命令，废除了由美国前总统乔治布什于2001年8月9日发布的限制干细胞研究规定，为干细胞研究松绑，实乃生物医学研究的一大幸事！
肿瘤干细胞的理论一直很诱人，按我的理解就是说，肿瘤里大部分细胞其实都是好的，只有极少数的真正坏的肿瘤干细胞，他们能无限增值扩散之后能产生新的肿瘤，他们正是肿瘤越长越大的动力源泉。这个理论很诱人，因为一旦找到能够把这些真坏的细胞分辨出来的marker，那就可以针对性设计药物，进而显著控制癌症甚至治愈癌症。无数青年才俊正在这一诱人前景的吸引下投身于寻找肿瘤干细胞，干掉肿瘤干细胞的梦想中，现在，他们的努力可能会付之东流。 HHMI的Sean Morrison（据说是干细胞研究的少掌门）12月4日的一篇Nature 跳出来说，至少在melanoma里面，有25%～27%的细胞都是能独立形成新的肿瘤，进而都可以被认为的传统意义上的坏细胞。而且四分之一的坏细胞和另外的好细胞表面的50种marker都不存在显著差别。 传统的肿瘤干细胞理论主要是基于NOD/SCID mice的实验，就是把一定数量的肿瘤细胞打到这些免疫缺陷的老鼠里，看看长出了多少个独立的肿瘤，进而统计出有多少细胞能够致瘤，结论是能够致瘤的癌细胞数量占总细胞数的极少部分，进而支持了肿瘤干细胞理论。但NOD/SCID mice模型有个严重的缺点，就是残留的NK细胞活性，现在Sean Morrison整了新的more severely immune-compromised mice, called NOD/SCID IL2R null . These mice are missing the gene for a receptor protein required for immune cells known as natural killer cells to function properly. The team found that 250,000 times as many melanoma cells formed tumors in this modified assay as compared to the standard NOD/SCID mice. 现在好了，没有NK细胞活性的新老鼠模型里，肿瘤干细胞一下子多了250，000倍！换句话说，就是打100个melonoma 细胞到这种老鼠模型里，有25个细胞能形成肿瘤；而如果打单一melanoma细胞到老鼠里，那么会有27%的老鼠产生肿瘤（这是个新方法）。 House最新一季的第一集正是拿cancer stem cell来忽悠，估计以后再想拿这个说事儿就得三思了。 还有，NK细胞可能真的是癌症免疫治疗的关键先生呢！ 新闻来源： http://www.hhmi.org/news/morrison20081204.html 中文版的： http://www.bioknow.cn/html/pages/779/paper_69779.htm Nature： http://www.nature.com/nature/journal/v449/n7159/full/7159xiiia.html Update！ 090908 Sean Morrison谈肿瘤干细胞理论 Some Cancers Follow a Cancer Stem Cell Model, Others Do Not http://www.cell.com/fulltext/S0092-8674(09)01030-7 我之前的日志有些草率了
癌症现在基本上被公认是基因病，是现代化社会的一大杀手。 当体内细胞分裂一次，基因复制出现些许差错，逐代积累，基因出错的几率越来越大，这也是为什么 癌症在老龄以后多发的原因 。 癌症 为多细胞生物所特有的疾病，单细胞生物并非没有基因出错的可能，只不过直接就被淘汰掉了。 癌症 是多细胞生物 的一种逆向进化， 癌细胞破坏了多细胞之间的平衡，极端利己主义 的大量疯长 ，最终导致整个生物体的崩溃。 使用化疗、放疗杀死 癌细胞 后 的病人，会在若干年后复发。这种现象促使了癌症干细胞的假设的提出。这个假设在近几年迅速发展，已经大大影响了癌症研究的方向。上周的 Economist 杂志，有一个非常科普的描述： http://www.economist.com/opinion/displaystory.cfm?story_id=12208016 Fig 1 Cancer stem cells targeted 同时，文中指出： This discovery is not a cure. But it does point the way towards oneor, at the least, towards better therapies. Some might be in action soon. For example, it seems that cancer stem cells are less vulnerable to radiation than other cancer cells, because their DNA-repair mechanisms are better. Radiotherapy might thus be made more effective against them by dosing them with existing drugs that inhibit DNA repair . Some existing drugs which are known to interfere with stem cells biochemical pathways could be used to attack them selectively. 专题文章： Cancer stem cells http://www.economist.com/science/displaystory.cfm?story_id=12202589 这次的生命科学会议，有一个干细胞的专题，其中就有人谈到了 癌症与干细胞的关系，我会在后文中给出。
标签: stem
