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Sent on Friday, 2010 Apr 09 Search lung cancer and radiotherapy Click here to view complete results in PubMed. (Results may change over time.) To unsubscribe from these e-mail updates click here . PubMed Results Item 1 of 1 1. Diagnosis and treatment of pancreatic metastases of a papillary thyroid carcinoma. Borschitz T, Eichhorn W, Fottner C, Hansen T, Schad A, Schadmand-Fischer S, Weber MM, Schreckenberger M, Lang H, Musholt TJ. Thyroid . 2010 Jan;20(1):93-8. PMID: 20025539 Related citations
( NLM ). Do not reply directly to this message. Sender's message: Sent on Thursday, 2010 Apr 08 Search lung cancer and radiotherapy Click here to view complete results in PubMed. (Results may change over time.) To unsubscribe from these e-mail updates click here . PubMed Results Items 1 - 5 of 5 1. Oligometastases confined one organ from colorectal cancer treated by SBRT. Kang JK, Kim MS, Kim JH, Yoo SY, Cho CK, Yang KM, Yoo HJ, Seo YS, Lee DH, Kang HJ, Kim YH, Shin US. Clin Exp Metastasis . 2010 Apr 7. PMID: 20373133 2. Usefulness of dynamic contrast enhanced computed tomography in patients with non-small-cell lung cancer scheduled for radiation therapy. Lazanyi KS, Abramyuk A, Wolf G, Tokalov S, Zphel K, Appold S, Herrmann T, Baumann M, Abolmaali N. Lung Cancer . 2010 Apr 3. PMID: 20371133 3. Reduction of Cone-Beam CT scan time without compromising the accuracy of the image registration in IGRT. Westberg J, Jensen HR, Bertelsen A, Brink C. Acta Oncol . 2010;49(2):225-9. PMID: 20100157 Related citations 4. Optimal beam arrangement for stereotactic body radiation therapy delivery in lung tumors. Lim do H, Yi BY, Mirmiran A, Dhople A, Suntharalingam M, D'Souza WD. Acta Oncol . 2010;49(2):219-24. PMID: 19888895 Related citations 5. Use of a simplified geriatric evaluation in thoracic oncology. Cudennec T, Gendry T, Labrune S, Giraud V, Moulias S, Teillet L, Chinet T. Lung Cancer . 2010 Feb;67(2):232-6. Epub 2009 May 7. PMID: 19427054 Related citations
Sent on Wednesday, 2010 Apr 07 Search lung cancer and radiotherapy Click here to view complete results in PubMed. (Results may change over time.) To unsubscribe from these e-mail updates click here . PubMed Results Items 1 - 5 of 7 1. Significant activity of single agent vinorelbine against small-cell cancer of the bladder as second line chemotherapy: A case series and review of the literature. June RR, Dougherty DW, Reese CT, Harpster LE, Hoffman SL, Drabick JJ. Urol Oncol . 2010 Apr 2. PMID: 20363163 Related citations 2. Neoadjuvant treatment of soft-tissue sarcoma: a multimodality approach. Reynoso D, Subbiah V, Trent JC, Guadagnolo BA, Lazar AJ, Benjamin R, Pollock RE, Ludwig JA. J Surg Oncol . 2010 Mar 15;101(4):327-33. Review. PMID: 20187067 Related citations 3. Metastatic melanoma of the septum pellucidum mimicking a colloidal cyst of the third ventricle. A novel case. Cipri S, Mannino R, Cafarelli F. J Neurosurg Sci . 2009 Sep;53(3):125-9. PMID: 20075825 Related citations 4. Bruna A, Bourhis J. Bull Cancer . 2009;96 Suppl 1:65-8. Review. French. PMID: 19433375 Related citations 5. Taillade L, Alexandre I, Billemont B, Meric JB, Sultan-Amar V, Rixe O. Bull Cancer . 2009;96 Suppl 1:S45-55. Review. French. PMID: 19433373 Related citations
Advertisement Almac is a personalized medicine company with expertise in companion diagnostic development , Pharmacodynamic biomarker strategies , prognostic test development and drug target discovery. We utilize our experience, expertise and unique Cancer DSA technology to partner with customers enabling translational genomic solutions. To find out more visit www.almacgroup.com/diagnostics TABLE OF CONTENTS February 2010 Volume 10 Number 2 Advertisement Impact Factor 30.762 * Subscribe to Nature Reviews Cancer Recommend to your library In this issue Research Highlights Reviews Perspectives Correspondence Also this month Article series: Therapeutic resistance Featured article: Mitotic chromosomal instability and cancer: mouse modelling of the human disease JuanManuel Schvartzman, Rocio Sotillo Robert Benezra Biomarker Discovery Pilot Grants Biomarkers hold great promise for biomedical research, including diagnostics, drug discovery, and personalized medicine. To encourage biomarker research, RayBiotech is now accepting applications for pilot grants . Deadline for application is January 31, 2010. Details and applications available at: RayBiotech.com/Grant . Advertisement FREE CLASSIC NATURE MEDICINE ARTICLES Aminoglycoside antibiotics restore CFTR function by overcoming premature stop mutations Abstract | PDF Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells Abstract | PDF Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell Abstract | PDF Access more than 30 FREE articles from Nature Medicine here www.nature.com/nm/classics From the editors p77 | doi:10.1038/nrc2805 PDF RESEARCH HIGHLIGHTS Top Wildlife cancer: The details are not so devilish p79 | doi:10.1038/nrc2797 Genomic and transcriptomic analyses of Tasmanian devil facial tumour disease. PDF Systems biology: Network spreading p80 | doi:10.1038/nrc2794 Identification of a small transcription factor network that is responsible for the mesenchymal behaviour of glioma cells. PDF Metastasis: Motion capture p80 | doi:10.1038/nrc2796 Mutant p53 promotes cell migration and invasion through integrin recycling. PDF IN THE NEWS Cancer code cracked? p80 | doi:10.1038/nrc2800 Complete genomes of two individual cancers sequenced. PDF IN BRIEF Therapy | Genomic instability | Lymphoma | Tumorigenesis p81 | doi:10.1038/nrc2802 PDF Computational biology: Mutual ties p82 | doi:10.1038/nrc2798 Functional computational analysis of microarray data. PDF DNA damage response: DNA takes a break with SUMO p82 | doi:10.1038/nrc2801 PIAS1 and PIAS4 promote BRCA1 sumoylation and DNA repair. PDF Lymphomagenesis: Far, far away p83 | doi:10.1038/nrc2793 The Igh 3 regulatory region ( Igh3 RR ) can function over long distances to activate the transcription of translocated Myc . PDF Genome architecture: Reliable repositioning in cancer p84 | doi:10.1038/nrc2792 A new technique for diagnosing cancer from limited amounts of tissue. PDF Senescence: A key role for CDK2 p84 | doi:10.1038/nrc2799 CDK2 influences MYC- and Ras-induced senescence. PDF Angiogenesis: Regulating vessel size p85 | doi:10.1038/nrc2790 VEPTP and the ANG-TIE2 pathway regulate blood vessel size in tumour angiogenesis PDF Cancer JOBS of the week Research Scientist, Pharmacology / Toxicology Tekmira Pharmaceuticals Corporation Vancouver, BC Research Associate, Cancer Bioinformatics and Computational Biology of Drug Response Biomarkers University of Virginia Charlottesville, VA 22908 Postdoc Position in Integrative Genomics University Pompeu Fabra (Barcelona) Parc de Recerca Biomedica de Barcelona Research Associate, Signal Transduction and Cell Biology of Tumor Metastasis University of Virginia Charlottesville, VA 22908 Postdoctoral Fellowship in Growth Factor Signaling Dr. Reza Zarnegar University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15261 More Science jobs from Cancer EVENT James Watson Cancer Symposium 06.-11.04.10 Suzhou, China More science events from REVIEWS Top Barrett's oesophagus and oesophageal adenocarcinoma: time for a new synthesis Brian J. Reid, Xiaohong Li, Patricia C. Galipeau Thomas L. Vaughan p87 | doi:10.1038/nrc2773 The public health importance of Barrett's oesophagus lies in its association with oesophageal adenocarcinoma, the incidence of which is rising steadily. However, 95% of oesophageal adenocarcinomas arise in individuals without a prior diagnosis of Barrett's oesophagus. What strategies can be used to reduce late diagnosis of oesophageal adenocarcinoma? Abstract | Full Text | PDF Mitotic chromosomal instability and cancer: mouse modelling of the human disease Juan-Manuel Schvartzman, Rocio Sotillo Robert Benezra p102 | doi:10.1038/nrc2781 The inability to faithfully segregate chromosomes to two daughter cells during mitosis leading to aneuploidy is a widespread phenomenon in solid tumours that is thought to promote tumorigenic progression. This Review discusses how mitotic chromosomal instability might arise in tumours and what its consequences might be. Abstract | Full Text | PDF Fibroblast growth factor signalling: from development to cancer Nicholas Turner Richard Grose p116 | doi:10.1038/nrc2780 Fibroblast growth factors (FGFs) and their receptors have been shown to drive tumorigenesis and tumour progression. However, FGF signalling can also be tumour suppressive, and understanding the mechanisms that underlie these context-specific effects will be important to rationally target FGF signalling for therapeutic benefit. Abstract | Full Text | PDF PERSPECTIVES Top OPINION Article series: Therapeutic resistance Targeting the cancer kinome through polypharmacology Zachary A. Knight, Henry Lin Kevan M. Shokat p130 | doi:10.1038/nrc2787 It is becoming clear that targeting individual kinases is not sufficient to block the growth of most cancers. This Perspective discusses some of the strategies being used to identify new therapeutic combinations of kinase targets. Abstract | Full Text | PDF | Supplementary information OPINION Instructive role of the vascular niche in promoting tumour growth and tissue repair by angiocrine factors Jason M. Butler, Hideki Kobayashi Shahin Rafii p138 | doi:10.1038/nrc2791 The precise mechanisms whereby anti-angiogenesis therapy blocks tumour growth or causes vascular toxicity are unknown. This article proposes that endothelial cells establish a vascular niche that promotes tumour growth and tissue repair through an angiocrine mechanism. Abstract | Full Text | PDF | Supplementary information OPINION Article series: Therapeutic resistance ABC transporters in cancer: more than just drug efflux pumps Jamie I. Fletcher, Michelle Haber, Michelle J. Henderson Murray D. Norris p147 | doi:10.1038/nrc2789 Multidrug transporter proteins contribute to chemoresistance through the efflux of anticancer drugs from cancer cells. However, evidence also points to their importance in cancer beyond drug efflux. Is there more to this family than meets the eye? Abstract | Full Text | PDF CORRESPONDENCE Top Correspondence: Parallel progression of tumour and metastases Serge Koscielny Maurice Tubiana p156 | doi:10.1038/nrc2627-c1 Full Text | PDF Correspondence: Tumour cell dissemination and growth of metastasis Christoph A. Klein p156 | doi:10.1038/nrc2627-c2 Full Text | PDF Advertisement FREE ARTICLES FROM SciBX Pulmonary disease: Inhibiting HDAC7 in cystic fibrosis Full text | PDF Cancer: Targeting IDH1 in brain cancer Full text | PDF Musculoskeletal disease: New therapeutics for Spinal Muscular Atrophy Full text | PDF
TABLE OF CONTENTS Volume 102, Issue 1 Published online 5January2010 (1-235) In this issue Minireview Clinical Studies Translational Therapeutics Molecular Diagnostics Epidemiology Letters to the Editor Also new today Advance online publication Advertisment Book now for BAPRAS' world class plastic surgery course on Melanoma and Sarcoma 23-24 Apr 2010 Manchester UK Covering the latest innovations and techniques in the treatment of skin cancer, the course is aimed at specialist trainees and established surgeons. CME/EACCME coursesinplasticsurgery.org.uk Sign up for e-alerts Recommend to your library Web feed Subscribe Advertisement British Journal of Cancer publishes high quality original papers and reviews that make a significant contribution to increasing understanding of the causes of cancer and to improving the treatment and survival of patients. Visit the journal online at www.bjcancer.com to view the latest research and access selected articles FREE of charge. British Journal of Cancer has an impact factor of 4.846* * 2008 Journal Citation Reports (Thomson Reuters, 2009) Minireview Top Metabolic assessment of the action of targeted cancer therapeutics using magnetic resonance spectroscopy MBeloueche-Babari, Y-LChung, N M SAl-Saffar, MFalck-Miniotis and M OLeach Br J Cancer 2010 102: 1-7; advance online publication, November 24, 2009; 10.1038/sj.bjc.6605457 Abstract | Full Text Biomarkers of angiogenesis and their role in the development of VEGF inhibitors NMurukesh, CDive and G CJayson Br J Cancer 2010 102: 8-18; advance online publication, December 15, 2009; 10.1038/sj.bjc.6605483 Abstract | Full Text Clinical Studies Top A quality-adjusted survival analysis (Q-TWiST) of rituximab plus CVP vs CVP alone in first-line treatment of advanced follicular non-Hodgkin's lymphoma RMarcus, RAultman and FJost Br J Cancer 2010 102: 19-22; advance online publication, November 17, 2009; 10.1038/sj.bjc.6605443 Abstract | Full Text Enhancing fraction measured using dynamic contrast-enhanced MRI predicts disease-free survival in patients with carcinoma of the cervix S BDonaldson, D LBuckley, J PO'Connor, S EDavidson, B MCarrington, A PJones and C M LWest Br J Cancer 2010 102: 23-26; advance online publication, November 17, 2009; 10.1038/sj.bjc.6605415 Abstract | Full Text Short-term health-related quality of life consequences in a lung cancer CT screening trial (NELSON) K A Mvan den Bergh, M LEssink-Bot, G J J MBorsboom, ETh Scholten, MProkop, H Jde Koning and R Jvan Klaveren Br J Cancer 2010 102: 27-34; advance online publication, November 24, 2009; 10.1038/sj.bjc.6605459 Abstract | Full Text Assessment of residual tumour by FDG-PET: conventional imaging and clinical examination following primary chemotherapy of large and locally advanced breast cancer JDose-Schwarz, RTiling, SAvril-Sassen, SMahner, ALebeau, CWeber, MSchwaiger, FJnicke, MUntch and NAvril Br J Cancer 2010 102: 35-41; advance online publication, November 17, 2009; 10.1038/sj.bjc.6605427 Abstract | Full Text Age of onset in familial breast cancer as background data for medical surveillance ABrandt, J LorenzoBermejo, JSundquist and KHemminki Br J Cancer 2010 102: 42-47; advance online publication, November 10, 2009; 10.1038/sj.bjc.6605421 Abstract | Full Text Diagnostic accuracy systematic review of rectal bleeding in combination with other symptoms, signs and tests in relation to colorectal cancer MOlde Bekkink, CMcCowan, G AFalk, CTeljeur, F AVan de Laar and TFahey Br J Cancer 2010 102: 48-58; advance online publication, November 24, 2009; 10.1038/sj.bjc.6605426 Abstract | Full Text Quality-of-life findings from a randomised phase-III study of XELOX vs FOLFOX-6 in metastatic colorectal cancer TConroy, MHebbar, JBennouna, MDucreux, MYchou, GLldo, AAdenis, RFaroux, CRebischung, LKockler and J YDouillard Br J Cancer 2010 102: 59-67; advance online publication, November 17, 2009; 10.1038/sj.bjc.6605442 Abstract | Full Text Sorafenib in patients with advanced biliary tract carcinoma: a phase II trial CBengala, FBertolini, NMalavasi, CBoni, EAitini, CDealis, SZironi, RDepenni, AFontana, CDel Giovane, GLuppi and PConte Br J Cancer 2010 102: 68-72; advance online publication, November 24, 2009; 10.1038/sj.bjc.6605458 Abstract | Full Text Long-term activation of the pro-coagulant response after neoadjuvant chemoradiation and major cancer surgery MByrne, J VReynolds, J SO'Donnell, MKeogan, BWhite, MByrne, SMurphy, S GMaher and G PPidgeon Br J Cancer 2010 102: 73-79; advance online publication, December 1, 2009; 10.1038/sj.bjc.6605463 Abstract | Full Text Costs of managing adverse events in the treatment of first-line metastatic renal cell carcinoma: bevacizumab in combination with interferon- 2a compared with sunitinib GMickisch, MGore, BEscudier, GProcopio, SWalzer and MNuijten Br J Cancer 2010 102: 80-86; advance online publication, November 17, 2009; 10.1038/sj.bjc.6605417 Abstract | Full Text Collagen and calcium-binding EGF domains 1 is frequently inactivated in ovarian cancer by aberrant promoter hypermethylation and modulates cell migration and survival C ABarton, B SGloss, WQu, A LStatham, N FHacker, R LSutherland, S JClark and P MO'Brien Br J Cancer 2010 102: 87-96; advance online publication, November 24, 2009; 10.1038/sj.bjc.6605429 Abstract | Full Text Translational Therapeutics Top A small molecule inhibitor of XIAP induces apoptosis and synergises with vinorelbine and cisplatin in NSCLC E JDean, TWard, CPinilla, RHoughten, KWelsh, GMakin, MRanson and CDive Br J Cancer 2010 102: 97-103; advance online publication, November 10, 2009; 10.1038/sj.bjc.6605418 Abstract | Full Text A novel inhibitor of the PI3K / Akt pathway based on the structure of inositol 1,3,4,5,6-pentakisphosphate MFalasca, DChiozzotto, H YGodage, MMazzoletti, A MRiley, SPrevidi, B V LPotter, MBroggini and TMaffucci Br J Cancer 2010 102: 104-114; 10.1038/sj.bjc.6605408 Abstract | Full Text Pre-treatment with chemotherapy can enhance the antigenicity and immunogenicity of tumours by promoting adaptive immune responses W MLiu, D WFowler, PSmith and A GDalgleish Br J Cancer 2010 102: 115-123; advance online publication, December 8, 2009; 10.1038/sj.bjc.6605465 Abstract | Full Text Metastatic colorectal cancer cells from patients previously treated with chemotherapy are sensitive to T-cell killing mediated by CEA / CD3-bispecific T-cell-engaging BiTE antibody TOsada, DHsu, SHammond, AHobeika, GDevi, T MClay, H KLyerly and M AMorse Br J Cancer 2010 102: 124-133; advance online publication, December 1, 2009; 10.1038/sj.bjc.6605364 Abstract | Full Text In vitro activity of pertuzumab in combination with trastuzumab in uterine serous papillary adenocarcinoma KEl-Sahwi, SBellone, ECocco, MCargnelutti, FCasagrande, MBellone, MAbu-Khalaf, NBuza, F ATavassoli, PHui, D-ASilasi, MAzodi, P ESchwartz, T JRutherford, SPecorelli and A DSantin Br J Cancer 2010 102: 134-143; advance online publication, November 17, 2009; 10.1038/sj.bjc.6605448 Abstract | Full Text Immunophenotype and molecular characterisation of adenocarcinoma of the small intestine M JOverman, JPozadzides, SKopetz, SWen, J LAbbruzzese, R AWolff and HWang Br J Cancer 2010 102: 144-150; advance online publication, November 24, 2009; 10.1038/sj.bjc.6605449 Abstract | Full Text Prognostic and predictive value of TOPK stratified by KRAS and BRAF gene alterations in sporadic, hereditary and metastatic colorectal cancer patients IZlobec, FMolinari, MKovac, M PBihl, H JAltermatt, JDiebold, HFrick, MGermer, MHorcic, MMontani, GSinger, HYurtsever, AZettl, LTerracciano, LMazzucchelli, PSaletti, MFrattini, KHeinimann and ALugli Br J Cancer 2010 102: 151-161; advance online publication, November 24, 2009; 10.1038/sj.bjc.6605452 Abstract | Full Text Molecular Diagnostics Top PTEN status in advanced colorectal cancer treated with cetuximab F VNegri, CBozzetti, C ALagrasta, PCrafa, M PBonasoni, RCamisa, GPedrazzi and AArdizzoni Br J Cancer 2010 102: 162-164; advance online publication, December 1, 2009; 10.1038/sj.bjc.6605471 Abstract | Full Text Prognostic effect of activated EGFR expre ssion in human colon carcinomas: comparison with EGFR status R LRego, N RFoster, T CSmyrk, MLe, M JO'Connell, D JSargent, HWindschitl and F ASinicrope Br J Cancer 2010 102: 165-172; advance online publication, December 8, 2009; 10.1038/sj.bjc.6605473 Abstract | Full Text Reporting of prognostic studies of tumour markers: a review of published articles in relation to REMARK guidelines SMallett, ATimmer, WSauerbrei and D GAltman Br J Cancer 2010 102: 173-180; advance online publication, December 8, 2009; 10.1038/sj.bjc.6605462 Abstract | Full Text Pemphigus vulgaris antigen mRNA quantification for the staging of sentinel lymph nodes in head and neck cancer JSolassol, VBurcia, VCostes, JLacombe, AMange, EBarbotte, Dde Verbizier, CCartier, MMakeieff, LCrampette, NBoulle, TMaudelonde, BGuerrier and RGarrel Br J Cancer 2010 102: 181-187; advance online publication, December 8, 2009; 10.1038/sj.bjc.6605470 Abstract | Full Text Inhibition of endogenous SPARC enhances pancreatic cancer cell growth: modulation by FGFR1-III isoform expre ssion GChen, XTian, ZLiu, SZhou, BSchmidt, DHenne-Bruns, MBachem and MKornmann Br J Cancer 2010 102: 188-195; advance online publication, November 17, 2009; 10.1038/sj.bjc.6605440 Abstract | Full Text Notch1 regulates the functional contribution of RhoC to cervical carcinoma progression SSrivastava, BRamdass, SNagarajan, MRehman, GMukherjee and SKrishna Br J Cancer 2010 102: 196-205; advance online publication, December 1, 2009; 10.1038/sj.bjc.6605451 Abstract | Full Text Gene set enrichment analysis provides insight into novel signalling pathways in breast cancer stem cells MMurohashi, KHinohara, MKuroda, TIsagawa, STsuji, SKobayashi, KUmezawa, ATojo, HAburatani and NGotoh Br J Cancer 2010 102: 206-212; advance online publication, December 8, 2009; 10.1038/sj.bjc.6605468 Abstract | Full Text Epidemiology Top Relation of risk of contralateral breast cancer to the interval since the first primary tumour CRubino, RArriagada, SDelaloge and M GL Br J Cancer 2010 102: 213-219; advance online publication, November 17, 2009; 10.1038/sj.bjc.6605434 Abstract | Full Text Second solid cancers after radiotherapy for breast cancer in SEER cancer registries ABerrington de Gonzalez, R ECurtis, EGilbert, C DBerg, S ASmith, MStovall and ERon Br J Cancer 2010 102: 220-226; advance online publication, November 24, 2009; 10.1038/sj.bjc.6605435 Abstract | Full Text Birth characteristics and the risk of childhood rhabdomyosarcoma based on histological subtype SOgnjanovic, S ECarozza, E JChow, E EFox, SHorel, C CMcLaughlin, B AMueller, SPuumala, PReynolds, JVon Behren and LSpector Br J Cancer 2010 102: 227-231; advance online publication, December 8, 2009; 10.1038/sj.bjc.6605484 Abstract | Full Text Letters to the Editor Top SUN vs BEV IFN in first-line mRCC therapy: no evidence for a statistically significant difference in progression-free survival MNuijten and GMickisch Br J Cancer 2010 102: 232-233; 10.1038/sj.bjc.6605446 Abstract | Full Text Reply: SUN vs BEV IFN in first-line mRCC therapy: no evidence for a statistically significant difference in progression-free survival J SThompson Coon, ZLiu, MHoyle, GRogers, CGreen, TMoxham, KWelch and KStein Br J Cancer 2010 102: 234-235; 10.1038/sj.bjc.6605447 Abstract | Full Text
TABLE OF CONTENTS January 2010 Volume 10 Number 1 Impact Factor 30.762 * Subscribe to Nature Reviews Cancer Recommend to your library In this issue Comment Research Highlights Reviews Analysis Perspectives Also this month Article series: Epigenetics and genetics Senescence Featured article: Leukaemogenesis: more than mutant genes Jianjun Chen, Olatoyosi Odenike Janet D. Rowley Find over 5,000 vacancies across scientific disciplines as well as the latest job market news, career advice and more, only at... ATTENTION EMPLOYERS! Stay up to date with Naturejobs advertising deadlines and upcoming features: naturejobs.com/ealerts or telephone: US: + 1 800 989 7718 EUR: +44 (0) 20 7843 4961 Advertisement The Spanish Association Against Cancer supports cancer research as it is one of its main priorities in the fight against cancer, being truly aware of the importance of this field of activity to improve diagnosis, treatment and the future of patients. Through its Scientific Foundation offers funding for various lines of work in translational research. More info: www.todocancer.com Advertisement The University of Miami, Scripps Florida and Nature Publishing Group present MIAMI 2010 WINTER SYMPOSIUM Targeting Cancer Invasion and Metastasis February 21-24, 2010 Miami Beach, FL, USA This meeting will focus on recent advances in our knowledge of basic molecular pathways of invasion, migration and immune surveillance and how that knowledge can be translated into new clinical concepts for diagnosis and therapy. Register Today: www.nature.com/natureconferences/miami/mws2010 From the editors p1 | doi:10.1038/nrc2788 The importance of understanding basic biology. PDF Comment: Systemic inflammation as a confounding factor in cancer biomarker discovery and validation. p4 | doi:10.1038/nrc2777 PDF RESEARCH HIGHLIGHTS Top Signalling: Different strokes p4 | doi:10.1038/nrc2777 Signals from EphB receptors that trigger cell proliferation and migration are mediated by two distinct downstream pathways. PDF Immunology: Inflammatory transformation p5 | doi:10.1038/nrc2776 PDF Tumorigenesis: Them's the breaks kid p5 | doi:10.1038/nrc2784 Hyperactive AID can result in widespread genomic damage and lymphoma. PDF Metastasis: Self-renewal migrates onwards p6 | doi:10.1038/nrc2778 How does ZEB1 regulate self-renewal and migration? PDF Signalling: All roads lead to YAP1 p6 | doi:10.1038/nrc2779 Several papers find that YAP1 has many important roles in tumorigenesis and tumour progression. PDF IN BRIEF Therapy | Genetics | Therapy | Metabolism p7 | doi:10.1038/nrc2786 PDF Senescence: A family trait p8 | doi:10.1038/nrc2783 TAp63 induces senescence and suppresses tumour growth in vivo . PDF Metabolism: An oncogenic change of function p8 | doi:10.1038/nrc2785 Missense mutations of IDH1 confer oncogenic gain-of-function properties. PDF Cancer JOBS of the week Temporary Senior Publishing Administrator Adecco London, United Kingdom Postdoctoral Fellowship Opportunities Vanderbilt University Medical Center Nashville, Tennessee 4 Year PhD Studentships at Chemical Biology Centre Doctoral Training Centre Inmperial College London London, UK, SW7 2AZ Postdoctoral Researcher University of Pennsylvania School of Medicine Philadelphia, PA Postdoctoral Fellow University of Maryland, Baltimore 655 W. Baltimore Street, Baltimore, MD 21201 More Science jobs from Cancer EVENT Cancer Molecular Markers 03.-05.02.10 San Fran, US More science events from REVIEWS Top Integrins in cancer: biological implications and therapeutic opportunities Jay S. Desgrosellier David A. Cheresh p9 | doi:10.1038/nrc2748 The integrins regulate a diverse array of cellular functions that are crucial to the initiation, progression and metastasis of solid tumours. This Review discusses the exciting developments in targeting integrins, including the recent initiation of a Phase III trial for an integrin antagonist in patients with glioblastoma. Abstract | Full Text | PDF Article series: Epigenetics and genetics Leukaemogenesis: more than mutant genes Jianjun Chen, Olatoyosi Odenike Janet D. Rowley p23 | doi:10.1038/nrc2765 Epigenetic modifications, including DNA methylation and histone modifications, as well as microRNAs, contribute to the development of acute leukaemias. This Review describes the current understanding of epigenetic changes (including microRNA regulation) in acute leukaemias, with a particular focus on those characterized by balanced chromosomal aberrations. Abstract | Full Text | PDF | Supplementary information From pathogenesis to treatment of chronic lymphocytic leukaemia Thorsten Zenz, Daniel Mertens, Ralf Kppers, Hartmut Dhner Stephan Stilgenbauer p37 | doi:10.1038/nrc2764 Many factors, including genetic and epigenetic alterations, antigenic drive and the microenvironment, are crucial in the initiation and progression of chronic lymphocytic leukaemia (CLL). How will our growing understanding of CLL biology lead to the translation of therapeutic targets and prognostic markers into clinical practice? Abstract | Full Text | PDF Article series: Senescence Senescence in tumours: evidence from mice and humans Manuel Collado Manuel Serrano p51 | doi:10.1038/nrc2772 Oncogene-induced senescence was first seen in cultured cells. However, since the initial in vitro observation of this phenomenon, it has been shown to occur in both mouse and human tumours. What do we know about tumour cell senescence in vivo , and how might this be exploited therapeutically? Abstract | Full Text | PDF ANALYSIS Top Article series: Epigenetics and genetics A census of amplified and overexpressed human cancer genes Thomas Santarius, Janet Shipley, Daniel Brewer, Michael R. Stratton Colin S. Cooper p59 | doi:10.1038/nrc2771 This article proposes a weight-of-evidence based classification system for identifying individual genes in an amplified region of the genome that contribute to cancer development. The 77 genes identified using this approach have been further subdivided into different gene classes. Abstract | Full Text | PDF | Supplementary information PERSPECTIVES Top OPINION Emerging roles of ATF2 and the dynamic AP1 network in cancer Pablo Lopez-Bergami, Eric Lau Ze'ev Ronai p65 | doi:10.1038/nrc2681 Cooperation among transcription factors is central for their ability to execute specific transcriptional programmes. This Perspective summarizes the emerging role of the transcription factor ATF2 as part of the AP1 complex in tumorigenesis. Abstract | Full Text | PDF | Supplementary information Advertisement British Journal of Cancer presents: Breast cancer: Improved care through effective management of febrile neutropenia An examination of the increasing use of intensive adjuvant regimens for breast cancer, and the increased rates of febrile neutropenia associated with these regimens. Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. The contents of the Natureevents Directory are now live. 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TABLE OF CONTENTS Volume 101, Issue 12 Published online 8December2009 (1947-2078) In this issue Editorial Minireview Clinical Studies Translational Therapeutics Molecular Diagnostics Genetics and Genomics Letters to the Editor Corrigendum Author Index Keyword Index Also new today Advance online publication Sign up for e-alerts Recommend to your library Web feed Subscribe Advertisement British Journal of Cancer publishes high quality original papers and reviews that make a significant contribution to increasing understanding of the causes of cancer and to improving the treatment and survival of patients. Visit the journal online at www.bjcancer.com to view the latest research and access selected articles FREE of charge. British Journal of Cancer has an impact factor of 4.846* * 2008 Journal Citation Reports (Thomson Reuters, 2009) Editorial Top Regarding: Epoetin treatment in patients with cancer chemotherapy induced anaemia: the impact of initial haemoglobin and target haemoglobin levels on survival, tumour progression and thromboembolic events GSchwarzer Br J Cancer 2009 101: 1947-1948; 10.1038/sj.bjc.6605474 Abstract | Full Text Minireview Top Epidermal growth factor receptor expre ssion escapes androgen regulation in prostate cancer: a potential molecular switch for tumour growth A MTraish and AMorgentaler Br J Cancer 2009 101: 1949-1956; advance online publication, November 3, 2009; 10.1038/sj.bjc.6605376 Abstract | Full Text Clinical Studies Top Vitamin D receptor polymorphisms and prognosis of patients with epithelial ovarian cancer STamez, CNorizoe, KOchiai, DTakahashi, AShimojima, YTsutsumi, NYanaihara, TTanaka, AOkamoto and MUrashima Br J Cancer 2009 101: 1957-1960; advance online publication, November 10, 2009; 10.1038/sj.bjc.6605414 Abstract | Full Text Epoetin- treatment in patients with cancer chemotherapy-induced anaemia: the impact of initial haemoglobin and target haemoglobin levels on survival, tumour progression and thromboembolic events MAapro, BOsterwalder, AScherhag and H UBurger Br J Cancer 2009 101: 1961-1971; advance online publication, September 29, 2009; 10.1038/sj.bjc.6605255 Abstract | Full Text Phase I / II study of sequential therapy with irinotecan and S-1 for metastatic colorectal cancer TYoshioka, SKato, MGamoh, NChiba, TSuzuki, NSakayori, SKato, HShibata, HShimodaira, KOtsuka, YKakudo, STakahashi and CIshioka Br J Cancer 2009 101: 1972-1977; advance online publication, November 17, 2009; 10.1038/sj.bjc.6605432 Abstract | Full Text Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: a phase II trial PBougnoux, NHajjaji, M NFerrasson, BGiraudeau, CCouet and OLe Floch Br J Cancer 2009 101: 1978-1985; advance online publication, November 17, 2009; 10.1038/sj.bjc.6605441 Abstract | Full Text Metronomic chemotherapy with daily, oral etoposide plus bevacizumab for recurrent malignant glioma: a phase II study D AReardon, ADesjardins, J JVredenburgh, SGururangan, J HSampson, SSathornsumetee, R EMcLendon, J EHerndon, II, J EMarcello, JNorfleet, A HFriedman, D DBigner and H SFriedman Br J Cancer 2009 101: 1986-1994; advance online publication, November 17, 2009; 10.1038/sj.bjc.6605412 Abstract | Full Text Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma D AReardon, GDresemann, STaillibert, MCampone, Mvan den Bent, PClement, EBlomquist, LGordower, HSchultz, JRaizer, PHau, JEasaw, MGil, JTonn, AGijtenbeek, USchlegel, PBergstrom, SGreen, AWeir and ZNikolova Br J Cancer 2009 101: 1995-2004; advance online publication, November 10, 2009; 10.1038/sj.bjc.6605411 Abstract | Full Text Translational Therapeutics Top Glycogen synthase kinase-3: a new therapeutic target in renal cell carcinoma VBilim, AOugolkov, KYuuki, SNaito, HKawazoe, AMuto, MOya, DBilladeau, TMotoyama and YTomita Br J Cancer 2009 101: 2005-2014; advance online publication, November 17, 2009; 10.1038/sj.bjc.6605437 Abstract | Full Text In vivo high-resolution fluorescence microendoscopy for ovarian cancer detection and treatment monitoring WZhong, J PCelli, IRizvi, ZMai, B QSpring, S HYun and THasan Br J Cancer 2009 101: 2015-2022; advance online publication, November 17, 2009; 10.1038/sj.bjc.6605436 Abstract | Full Text Molecular Diagnostics Top Self-production of tissue factor-coagulation factor VII complex by ovarian cancer cells NYokota, SKoizume, EMiyagi, FHirahara, YNakamura, KKikuchi, WRuf, YSakuma, ETsuchiya and YMiyagi Br J Cancer 2009 101: 2023-2029; advance online publication, November 10, 2009; 10.1038/sj.bjc.6605406 Abstract | Full Text Tumour formation by single fibroblast growth factor receptor 3-positive rhabdomyosarcoma-initiating cells MHirotsu, TSetoguchi, YMatsunoshita, HSasaki, HNagao, HGao, KSugimura and SKomiya Br J Cancer 2009 101: 2030-2037; advance online publication, November 3, 2009; 10.1038/sj.bjc.6605407 Abstract | Full Text Epac inhibits migration and proliferation of human prostate carcinoma cells MGrandoch, ARose, Mter Braak, VJendrossek, HRbben, J WFischer, MSchmidt and A AWeber Br J Cancer 2009 101: 2038-2042; advance online publication, November 17, 2009; 10.1038/sj.bjc.6605439 Abstract | Full Text Genetics and Genomics Top Absence of truncating BRIP1 mutations in chromosome 17q-linked hereditary prostate cancer families A MRay, K AZuhlke, G RJohnson, A MLevin, J ADouglas, E MLange and K ACooney Br J Cancer 2009 101: 2043-2047; advance online publication, November 24, 2009; 10.1038/sj.bjc.6605433 Abstract | Full Text Evaluation of a candidate breast cancer associated SNP in ERCC4 as a risk modifier in BRCA1 and BRCA2 mutation carriers. Results from the Consortium of Investigators of Modifiers of BRCA1 / BRCA2 (CIMBA) AOsorio, R LMilne, GPita, PPeterlongo, THeikkinen, JSimard, GChenevix-Trench, A BSpurdle, JBeesley, XChen, SHealey, KConFab 9 , S LNeuhausen, Y CDing, F JCouch, XWang, NLindor, SManoukian, MBarile, AViel, LTizzoni, C ISzabo, LForetova, MZikan, KClaes, M HGreene, PMai, GRennert, FLejbkowicz, OBarnett-Griness, I LAndrulis, HOzcelik, NWeerasooriya, OCGN 23 , A-MGerdes, MThomassen, D GCruger, M ACaligo, EFriedman, BKaufman, YLaitman, SCohen, TKontorovich, RGershoni-Baruch, EDagan, HJernstrm, M SAskmalm, BArver, BMalmer, SWE-BRCA 37 , S MDomchek, K LNathanson, JBrunet, TRamn y Cajal, DYannoukakos, UHamann, HEBON 37 , F B LHogervorst, SVerhoef, EB GmezGarca, J TWijnen, Avan den Ouweland, EMBRACE 37 , D FEaston, SPeock, MCook, C TOliver, DFrost, CLuccarini, D GEvans, FLalloo, REeles, GPichert, JCook, SHodgson, P JMorrison, FDouglas, A KGodwin, GEMO 59 60 61 , O MSinilnikova, LBarjhoux, DStoppa-Lyonnet, VMoncoutier, SGiraud, CCassini, LOlivier-Faivre, FRvillion, J-PPeyrat, DMuller, J-PFricker, H TLynch, E MJohn, SBuys, MDaly, J LHopper, M BTerry, AMiron, YYassin, DGoldgar, Breast Cancer Family Registry 37 , C FSinger, DGschwantler-Kaulich, GPfeiler, A-CSpiess, Thomas v OHansen, O TJohannsson, TKirchhoff, KOffit, KKosarin, MPiedmonte, G CRodriguez, KWakeley, J FBoggess, JBasil, P ESchwartz, S VBlank, A EToland, MMontagna, CCasella, E NImyanitov, AAllavena, R KSchmutzler, BVersmold, CEngel, AMeindl, NDitsch, NArnold, DNiederacher, HDeiler, BFiebig, RVaron-Mateeva, DSchaefer, U GFroster, TCaldes, Mde la Hoya, LMcGuffog, A CAntoniou, HNevanlinna, PRadice and JBentez on behalf of CIMBA Br J Cancer 2009 101: 2048-2054; advance online publication, November 17, 2009; 10.1038/sj.bjc.6605416 Abstract | Full Text Letters to the Editor Top Regarding: High-intensity-focused ultrasound in the treatment of primary prostate cancer: the first UK series T SClark Br J Cancer 2009 101: 2055; 10.1038/sj.bjc.6605453 Abstract | Full Text Reply to TS Clark: High-intensity-focused ultrasound in the treatment of primary prostate cancer: the first UK series H UAhmed and MEmberton Br J Cancer 2009 101: 2056; 10.1038/sj.bjc.6605454 Abstract | Full Text Regarding: High-intensity-focused ultrasound in the treatment of primary prostate cancer: the first UK series SEggener, MGonzalgo and OYossepowitch Br J Cancer 2009 101: 2057-2058; 10.1038/sj.bjc.6605455 Abstract | Full Text Reply to S Eggener, M Gonzalgo and O Yossepowitch: High-intensity-focused ultrasound in the treatment of primary prostate cancer: the first UK series H UAhmed and MEmberton Br J Cancer 2009 101: 2059; 10.1038/sj.bjc.6605456 Abstract | Full Text Evolutionary game theory: lessons and limitations, a cancer perspective J WMcEvoy Br J Cancer 2009 101: 2060-2061; advance online publication, November 17, 2009; 10.1038/sj.bjc.6605444 Abstract | Full Text Reply: Evolutionary game theory: lessons and limitations, a cancer perspective DDingli, F A C CChalub, F CSantos, SVan Segbroeck and J MPacheco Br J Cancer 2009 101: 2062-2063; advance online publication, November 17, 2009; 10.1038/sj.bjc.6605445 Abstract | Full Text Corrigendum Top Profiling of high-grade central osteosarcoma and its putative progenitor cells identifies tumourigenic pathways A-MCleton-Jansen, J KAnninga, I HBriaire-de Bruijn, SRomeo, JOosting, R MEgeler, HGelderblom, A H MTaminiau and P C WHogendoorn Br J Cancer 2009 101: 2064; 10.1038/sj.bjc.6605482 Abstract | Full Text Author Index Top Author Index for Volume 101 Br J Cancer 2009 101: 2065-2074; 10.1038/sj.bjc.6605475 Abstract | Full Text Keyword Index Top Keyword Index for Volume 101 Br J Cancer 2009 101: 2075-2078; 10.1038/sj.bjc.6605476 Abstract | Full Text Advertisement Ensure your access to British Journal of Cancer If you are unable to access the articles in this Table of Contents e-alert, your library may not subscribe to this journal. 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Abstract: An important signal pathway was proposed by researchers study Gcn5. They have lauched some association trials in oder to indentify the role of Gcn5 , TRF1 and USP 22 in this signal pathway.At last, the researchers show that depletion of Gcn5 leads to chromosomal fusion and damage in mouse embryonic cell lines and also reduces the level of TRF1.This finds maybe help us explain the mechnism of producing of highly metastatic cancer. Keywords: Gcn5, TRF1, USP22, metastatic cancer A team of researchers at The University of Texas MD Anderson Cancer Center (USA) have found that a protein that opens the genomic door for DNA repair and gene expression is also a multitasking workhorse that protects the tips of chromosomes and has a role in a protein-destruction complex. Instead of being a really important tool dedicated just to regulation of gene transcription, Gcn5 is more like a Swiss Army knife that performs different functions depending on what needs to be done in the cell, said the senior author, Dr Sharon Dent. The researchers document a chain of events that starts with depletion of Gcn5, which leads to decreased activity by another protein that protects a third protein from destruction. The TRF1 protein protects telomeres, dense structures at the end of chromosomes that, similar to the compressed plastic tips on the ends of a shoelace, keep the chromosome ends intact. Variation in the gene that expresses the middle protein in this model, ubiquitin specific protease 22 ( USP22 ), is part of an 11-gene signature associated with highly metastatic cancers and poor prognosis. Dent said, Our results indicate that the Gcn5 complex regulates not just gene transcription but also protein stability. They also suggest that the role of USP 22 in highly aggressive cancers might be due to these new functions. Gcn5 was previously known for its role in a complex of proteins that loosens chromatin to allow access to DNA by the cells DNA repair machinery and by transcription factors that launch the process of gene expression. Years ago, a student in my lab found that mice deficient in Gcn5 died early during embryonic development, Dent also noted, The reason they died, in part, was that telomeres were fusing together. There was no reason to think Gcn5 would have anything at all to do with telomeres, so these fusions were quite puzzling. Another research group discovered that USP22 is active in the same protein complex in which Gcn5 operates. USP22 protects proteins by peeling off ubiquitin molecules that attach to the proteins and mark them for destruction by the proteasome complex. A literature review revealed that TRF1 carries a ubiquitin mark that makes it vulnerable to degradation by the proteasome. Dent stated, TRF1 normally resides at the telomeres and tells the cell that this is a normal chromosome end and you should leave it alone. If you dont have enough TRF1, the cell now thinks these chromosomal ends are abnormal and tries to fix them The team hypothesized that USP22 protects telomeres by knocking ubiquitins off of TRF1, sparing it from destruction. Our model is of a pathway in which depletion of Gcn5 reduces USP22 activity, causing greater TRF1 ubiquination, which leads to TRF1 destruction and that leads to telomere problems, Dent said. In the Molecular Cell paper, the researchers show that depletion of Gcn5 leads to chromosomal fusion and damage in mouse embryonic cell lines and also reduces the level of TRF1. They then demonstrate that USP22 interacts with TRF1 and is required for that protein to remain stable. Additional experiments identified that USP22 protects TRF1 by the removal of ubiquitin. The team continue to look for new proteins and cellular processes that are impaired in cells lacking GCN5 or USP22. Dent added, There must be a reason why USP22 is over expressed in highly metastatic cancers, and we are encouraged that we will be able to provide important clues for this process. Source: Atanassov BS, Evrard YA, Multani AS et al . Gcn5 and SAGA regulate shelterin protein turnover and telomere maintenance. Mol. Cell 35(3), 352364 (2009). 摘要：基于 Gcn5 的研究，研究人员提出了一个重要的信号通路。为了证明 Gcn5,TRF1 和 USP22 在这个信号通路的作用，他们开展了一系列的相关试验。最终， 研究者发现了在鼠的胚胎周期中 Gcn5 耗尽，会导致染色体融合和破坏，也减少了 TRF1 的水平。这个发现可能会帮助我们来解释转移癌产生的机理。 关键词： Gcn5, TRF1, USP22, 转移癌 美国 *** 癌症中心的一组研究人员，发现了一种为 DNA 修复和基因表达开启基因组之门的蛋白，它也是一种多功能的分子，可以保护染色体末端，也参与蛋白的破坏。 . Sharon Dent 博士说：除了 Gcn5 的一个只是专注于基因转录的调节真正重要的途径之外，在细胞里它更像一把瑞士军刀，依靠的是什么需要被做，它就可以开展不同的功能。 研究人员证明了一条竞争性链：从 Gcn5 损耗开始，它会导致另一个蛋白的活性降低，这个蛋白可以避免三分之一的蛋白破坏。 TRF1 蛋白保护染色体末端的端粒，一种密集的结构，类似于鞋带的被包裹的塑料末端，从而保持染色体末端的完整性。在这种模式下，表达的中等分子量蛋白的表达变异，辅基特殊蛋白酶 22 （ USP22 ），是相关高转移癌和预后不良的 11- 基因的部分。 Dent 说，我们的结果表明 Gcn5 综合体不只调节基因转录而且调节蛋白的稳定性。他们也表明 USP22 在高发性癌的作用可能由于这些新的功能。 Gcn5 先前认为它在蛋白的复合体中的作用就是通过 DNA 修复结构和转录因素放松 chromatin 接近 DNA ，从而开展基因表达的进程。多年前，一个我们实验室的学生发现缺乏 Gcn5 早在胚胎发育时期就死啦， Dent 也注意到，它们死的原因，部分是因为染色体一起融合。没有原因认为 Gcn5 和染色体有相关性，所以这些融合是令人相当迷惑的。 又一个研究组发现 USPS22 在 Gcn5 作用的同样蛋白综合体中是有活性的。 USPS22 保护蛋白，就是通过剥下结合在蛋白上的辅酶分子，对于破坏的分子通过蛋白酶复合物做标记。一篇学术报告揭示 TRF1 载有一个辅酶标记，这种辅酶标记使它容易被蛋白酶降解。 Dent 说， TRF1 正常地存在于染色体，并告诉细胞这是一个正常的染色体，应该保留它。如果你没有足够的 TRF1 ，细胞就认为这些染色体末端是不正常的，并试图组装它们 这个小组假设 USP22 保护端粒通过敲除 TRF1 的辅酶，避免破坏它。 Dent 说我们的模型是一个通路， Gcn5 消耗 USP22 活性减少 TRF1 辅酶增多 TRF1 破坏产生端粒难题。 在《分子细胞》论文中，研究者展示了在鼠的胚胎周期中 Gcn5 耗尽，会导致染色体融合和破坏，也减少了 TRF1 的水平。接着他们证明了 USP22 和 TRF1 相互作用，也为蛋白保持稳定所需要。其他的试验鉴定了 USP22 通过辅酶的除去来保护 TRF1. 这个组，在缺乏 Gcn5 或 USPS22 的细胞里，继续寻找新的蛋白和修复的细胞进程。 Dent 补充说：在转移酶中，为什么 USP22 高度表达，一定有原因。我们有信心我们将能为这个进程提供重要的线索。
Abstract: An important signal pathway was proposed by researchers study Gcn5. They have lauched some association trials in oder to indentify the role of Gcn5 , TRF1 and USP 22 in this signal pathway.At last, the researchers show that depletion of Gcn5 leads to chromosomal fusion and damage in mouse embryonic cell lines and also reduces the level of TRF1.This finds maybe help us explain the mechnism of producing of highly metastatic cancer. Keywords: Gcn5, TRF1, USP22, metastatic cancer A team of researchers at The University of Texas MD Anderson Cancer Center (USA) have found that a protein that opens the genomic door for DNA repair and gene expression is also a multitasking workhorse that protects the tips of chromosomes and has a role in a protein-destruction complex. Instead of being a really important tool dedicated just to regulation of gene transcription, Gcn5 is more like a Swiss Army knife that performs different functions depending on what needs to be done in the cell, said the senior author, Dr Sharon Dent. The researchers document a chain of events that starts with depletion of Gcn5, which leads to decreased activity by another protein that protects a third protein from destruction. The TRF1 protein protects telomeres, dense structures at the end of chromosomes that, similar to the compressed plastic tips on the ends of a shoelace, keep the chromosome ends intact. Variation in the gene that expresses the middle protein in this model, ubiquitin specific protease 22 ( USP22 ), is part of an 11-gene signature associated with highly metastatic cancers and poor prognosis. Dent said, Our results indicate that the Gcn5 complex regulates not just gene transcription but also protein stability. They also suggest that the role of USP 22 in highly aggressive cancers might be due to these new functions. Gcn5 was previously known for its role in a complex of proteins that loosens chromatin to allow access to DNA by the cells DNA repair machinery and by transcription factors that launch the process of gene expression. Years ago, a student in my lab found that mice deficient in Gcn5 died early during embryonic development, Dent also noted, The reason they died, in part, was that telomeres were fusing together. There was no reason to think Gcn5 would have anything at all to do with telomeres, so these fusions were quite puzzling. Another research group discovered that USP22 is active in the same protein complex in which Gcn5 operates. USP22 protects proteins by peeling off ubiquitin molecules that attach to the proteins and mark them for destruction by the proteasome complex. A literature review revealed that TRF1 carries a ubiquitin mark that makes it vulnerable to degradation by the proteasome. Dent stated, TRF1 normally resides at the telomeres and tells the cell that this is a normal chromosome end and you should leave it alone. If you dont have enough TRF1, the cell now thinks these chromosomal ends are abnormal and tries to fix them The team hypothesized that USP22 protects telomeres by knocking ubiquitins off of TRF1, sparing it from destruction. Our model is of a pathway in which depletion of Gcn5 reduces USP22 activity, causing greater TRF1 ubiquination, which leads to TRF1 destruction and that leads to telomere problems, Dent said. In the Molecular Cell paper, the researchers show that depletion of Gcn5 leads to chromosomal fusion and damage in mouse embryonic cell lines and also reduces the level of TRF1. They then demonstrate that USP22 interacts with TRF1 and is required for that protein to remain stable. Additional experiments identified that USP22 protects TRF1 by the removal of ubiquitin. The team continue to look for new proteins and cellular processes that are impaired in cells lacking GCN5 or USP22. Dent added, There must be a reason why USP22 is over expressed in highly metastatic cancers, and we are encouraged that we will be able to provide important clues for this process. Source: Atanassov BS, Evrard YA, Multani AS et al . Gcn5 and SAGA regulate shelterin protein turnover and telomere maintenance. Mol. Cell 35(3), 352364 (2009). 摘要：基于 Gcn5 的研究，研究人员提出了一个重要的信号通路。为了证明 Gcn5,TRF1 和 USP22 在这个信号通路的作用，他们开展了一系列的相关试验。最终， 研究者发现了在鼠的胚胎周期中 Gcn5 耗尽，会导致染色体融合和破坏，也减少了 TRF1 的水平。这个发现可能会帮助我们来解释转移癌产生的机理。 关键词： Gcn5, TRF1, USP22, 转移癌 美国 *** 癌症中心的一组研究人员，发现了一种为 DNA 修复和基因表达开启基因组之门的蛋白，它也是一种多功能的分子，可以保护染色体末端，也参与蛋白的破坏。 . Sharon Dent 博士说：除了 Gcn5 的一个只是专注于基因转录的调节真正重要的途径之外，在细胞里它更像一把瑞士军刀，依靠的是什么需要被做，它就可以开展不同的功能。 研究人员证明了一条竞争性链：从 Gcn5 损耗开始，它会导致另一个蛋白的活性降低，这个蛋白可以避免三分之一的蛋白破坏。 TRF1 蛋白保护染色体末端的端粒，一种密集的结构，类似于鞋带的被包裹的塑料末端，从而保持染色体末端的完整性。在这种模式下，表达的中等分子量蛋白的表达变异，辅基特殊蛋白酶 22 （ USP22 ），是相关高转移癌和预后不良的 11- 基因的部分。 Dent 说，我们的结果表明 Gcn5 综合体不只调节基因转录而且调节蛋白的稳定性。他们也表明 USP22 在高发性癌的作用可能由于这些新的功能。 Gcn5 先前认为它在蛋白的复合体中的作用就是通过 DNA 修复结构和转录因素放松 chromatin 接近 DNA ，从而开展基因表达的进程。多年前，一个我们实验室的学生发现缺乏 Gcn5 早在胚胎发育时期就死啦， Dent 也注意到，它们死的原因，部分是因为染色体一起融合。没有原因认为 Gcn5 和染色体有相关性，所以这些融合是令人相当迷惑的。 又一个研究组发现 USPS22 在 Gcn5 作用的同样蛋白综合体中是有活性的。 USPS22 保护蛋白，就是通过剥下结合在蛋白上的辅酶分子，对于破坏的分子通过蛋白酶复合物做标记。一篇学术报告揭示 TRF1 载有一个辅酶标记，这种辅酶标记使它容易被蛋白酶降解。 Dent 说， TRF1 正常地存在于染色体，并告诉细胞这是一个正常的染色体，应该保留它。如果你没有足够的 TRF1 ，细胞就认为这些染色体末端是不正常的，并试图组装它们 这个小组假设 USP22 保护端粒通过敲除 TRF1 的辅酶，避免破坏它。 Dent 说我们的模型是一个通路， Gcn5 消耗 USP22 活性减少 TRF1 辅酶增多 TRF1 破坏产生端粒难题。 在《分子细胞》论文中，研究者展示了在鼠的胚胎周期中 Gcn5 耗尽，会导致染色体融合和破坏，也减少了 TRF1 的水平。接着他们证明了 USP22 和 TRF1 相互作用，也为蛋白保持稳定所需要。其他的试验鉴定了 USP22 通过辅酶的除去来保护 TRF1. 这个组，在缺乏 Gcn5 或 USPS22 的细胞里，继续寻找新的蛋白和修复的细胞进程。 Dent 补充说：在转移酶中，为什么 USP22 高度表达，一定有原因。我们有信心我们将能为这个进程提供重要的线索。
http://www.sciencenet.cn/htmlnews/2009/8/222895.shtm 新方法可阻止人类结肠癌细胞生长和转移 瑞士的一个研究小组8月27日称，他们发现了一种可以阻止人类结肠癌细胞生长和转移的新方法，并在动物实验中获得了成功。相关研究发表在当日出版的《欧洲分子生物学学会期刊》（ EMBO Molecular Medicine ）上。 据介绍，早期结肠癌的发病部位大多位于肠壁，相对容易治疗。但在日常病例中大多数结肠癌在发现时已到了难以医治的晚期。一家设在瑞士日内瓦的研究小组发现，在结肠癌发展为晚期的过程中，刺猬蛋白信号通路（HH-GLI或Hedgehog-GLI）发挥了重要作用。HH-GLI是一种细胞之间用于传递信息的信号通路，一般被用来确定细胞存活、发育以及位置等信息。 负责此项研究的瑞士日内瓦大学阿瑞尔鲁伊斯阿尔塔巴教授说，先前已有相关研究提出，HH-GLI在结肠癌中具有重要作用的假设，但遭到了不少学者的否认。此次，研究人员通过实验证明了HH-GLI在结肠癌生存和发育中的重要作用，并在结肠癌上皮细胞中发现了具有活性的刺猬蛋白。此外，他们还发现转移性肿瘤也必须依靠HH-GLI才能维持生长。因此，识别出HH-GLI并将其作为标靶，就为结肠癌的治疗提供了一种新途径。 具体来说就是运用RNA介入和环耙明阻断癌变组织中Hedgehog信号传导通路，以影响其后续基因表达，从而达到阻止癌细胞生长、转移和复发的目的。 研究人员发现，通过遗传学或者药理学的手段阻断HH-GLI的方法还可以防止癌细胞的自我更新，这种疗法对癌症转移和复发的控制也同样有效。在对小鼠的实验中经过环耙明阻断治疗后，小鼠体内原先存在的肿瘤逐渐消失。患癌小鼠在接受治疗一年之后仍然健康，未见复发或其他不适症状。 鲁伊斯阿尔塔巴称，这项研究证明了HH-GLI在人类结肠癌细胞中的重要作用，为癌症的治疗开创了一个新局面，提供了一种既能消除肿瘤又能防止其复发和产生副作用的新方法。 http://www.physorg.com/news170536330.html 'Hedgehog' pathway may hold key to anti-cancer therapy August 26th, 2009
标签: cancer
