Recently ‘breast cancer’ has arisen as a hot topic around. The popular singer Yao Beina, and the famous actress Chen Xiaoxu, who played the role of Daiyu in the famous drama ‘the Dream of the Red Mansion’, are both victims of the terrible disease. Cancer actually is a leading cause of death worldwide, and according to WHO, there are 521,000 deaths caused by breast cancer in the year 2012. Breast cancer is among the notorious top 5 killers, besides there are lung cancer, liver cancer, gastric cancer, and colorectal cancer. About 20-25% of human breast cancers are distinguished by amplification of the human epidermal growth factor recerptor-2 (HER2) gene, and are associated with more aggressive tumor growth and worse clinical outcome in patients. In September 1998, the United States Food and Drug Administration (FDA) approved trastuzumab as the first targeted therapy for HER-2 positive metastatic breast cancer (MBC), and it has since improved the overall prognosis for patients with HER2-positive MBC. Trastuzumab is a recombinant humanized monoclonal antibody that selectively targets the extra-cellular domain of the HER2 receptor. The mechanisms through which trastuzumab is believed to kill tumor cells include inhibition of constitutive HER2 signaling and disruption of HER2/HER3 interactions in HER2-overexpressing cells, resulting in inhibition of cellular proliferation, leading to antibody-dependent cell mediated cytotoxicity. Although trastuzumab has had a major impact in the treatment of patients withHER2-positive MBC, a subset of patients do not respond to treatment, and most patients who are initially responsive to treatment ultimately experience disease progression. A wave of further research thus has been set off to develop alternative and additional approaches to target HER2. These included the development of small molecule kinase inhibitors and other monoclonal antibodies that bind to different sites on HER2 than trastuzumab. Despite the advances in HER2 targeted therapy, the tumor in these patients will eventually progress, underscoring the need for them. In the meantime, since the introduction of classic cytotoxic agents, clinical outcomes have been significantly improved for most cancers. However, off-target collateral damage of healthy tissues is a well-recognized side effect of cytotoxics. The concept of antibody-drug conjugates thus evolved as a means either to improve the tumor selectivity of cytotoxic drugs or to confer higher potency to monoclonal antibodies that display preferential binding to tumor cells but lack sufficient cytotoxicity. In February 2013, ado-trastuzumab emtansine (T-DM1) received regulatory approval from FDA for treatment of refractory HER2-positive MBC. T-DM1 is an antibody-drug conjugate composed of trastuzumab connected to emtansine which is shown to have anti-tumor activities. The available clinical data demonstrate its improved efficacy and safety compared with traditional chemotherapy. Although this therapy is highly promising, de novo and acquired resistance to T-DM1 occurs. Understanding the mechanism of resistance is crucial to circumventing it, and there’s still an unknown long way to go. Therefore, it’s essential for people to prevent the tumor rather than to treat it. Healthy lifestyle should be encouraged and followed. As the saying goes, early to bed, early to rise, makes a man healthy, wealthy and wise. References: 1. Peddi et al, Therapeutic Advances in Medical Oncology, 2014. 2. Lambert et al , Journal of Medicinal Chemistry, 2014. 3. Jeyakumar et al , Clinical Medicine Insights: Oncology, 2012. see the original post on my space: http://blog.chinadaily.com.cn/blog-309597-26542.html
tea was the second alcoholic beverage behind water and has been consumed for thousands of years.tea was known for numerous health benefits. Cabrera et al., 2006 , Clement, 2009, Ruxton, 2009 have reported its beneficial activities such as anticancers, reduce incidence of cardiovacular events and stroke, beneficial effects for people with type 2 diabetes and antioxidants. the compositional changes between tea catogories has been investigated for decades. recently, a high resolution mass spectrometry was applied to identify thousands of metabolites rapidly. these data processed with multivariated analysis can provide the biochemial profile changes during fermentation of tea and consequently monitor the quality of tea products. additionally, identification of the key metabolites might give a possible way to clarify tea products into categories based on chemistry features.
http://www.gopubmed.org/web/gopubmed/2?WEB01wk71quvwwbp3I2gIxI00h01000j100200010 8,331 documents semantically analyzed 1 2 Top Years Publications 1990 22 1989 16 1987 5 1988 4 1985 3 1984 3 1986 1 1983 1 1982 1 1975 1 1 2 1 2 3 4 5 Top Countries Publications USA 4,028 United Kingdom 535 Germany 460 Japan 436 Italy 372 France 300 Canada 280 China 231 Spain 151 Netherlands 146 Australia 145 Belgium 106 Switzerland 92 India 75 Israel 74 South Korea 72 Greece 64 Sweden 63 Austria 51 Finland 45 1 2 3 4 5 1 2 3 ... 42 Top Cities Publications Houston 306 Boston 254 Bethesda 232 New York 231 London 196 Philadelphia 154 Baltimore 140 Los Angeles 126 Chicago 106 Toronto 101 Tokyo 86 Paris 81 Rochester, MN, USA 79 St. Louis 78 Milan 72 Seattle 71 Cleveland 67 Rome 67 Durham 66 Stanford 64 1 2 3 ... 42 1 2 3 ... 90 Top Journals Publications Cancer Res 194 Clin Cancer Res 185 P Natl Acad Sci Usa 97 Blood 90 Mol Cancer Ther 83 Curr Opin Oncol 77 J Immunol 74 Gene Ther 73 Semin Oncol 68 J Clin Oncol 65 Expert Rev Anticancer Ther 65 Int J Cancer 62 J Control Release 55 Bioconjugate Chem 54 Gan To Kagaku Ryoho 53 J Biol Chem 53 Mol Ther 52 Hum Gene Ther 52 Oncogene 50 J Virol 48 1 2 3 ... 90 1 2 3 ... 802 Top Terms Publications Humans 6,657 Animals 3,775 Neoplasms 3,416 Therapeutics 3,074 Patients 2,794 Genes 2,776 Pharmaceutical Preparations 2,395 Proteins 2,361 Mice 1,890 Antineoplastic Agents 1,792 Drug Therapy 1,365 Antibodies 1,317 antigen binding 1,317 Phosphotransferases 1,239 Evaluation Studies as Topic 1,235 Drug Delivery Systems 1,234 signal transduction 1,212 Tissues 1,179 Mutation 1,165 Intercellular Signaling Peptides and Proteins 1,089 1 2 3 ... 802 1 2 3 ... 1663 Top Authors Publications Puri R 31 Curiel D 23 Kantarjian H 22 Kawakami K 22 Weissleder R 21 Pastan I 21 Lanza G 20 Awada A 19 Wickline S 19 Scheinberg D 18 Kawakami M 18 Wen P 16 Goldenberg D 15 Kreitman R 15 Russell S 14 Ciardiello F 13 Cortes J 13 Harrington K 13 Kerbel R 12 Arap W 12 1 2 3 ... 1663 进入二十一世纪后的抗肿瘤药物研发战略是在继续深入发展细胞毒性药物的基础上同时逐渐引入分子靶向性药物的开发。迄今为止，很多靶向药物已经在临床起了极其重要甚至是奇迹般的作用。有些已经按照循证医学的原则进入了国际肿瘤学界公认的标准治疗方案和规范。更多、更有希望的药物也在快马加鞭地研制和早期临床试验中。所有这些都使我们有理由相信，目前肿瘤的药物治疗正处于从单纯细胞毒性攻击到分子靶向性调节的过度时期，应是前程无量。 为达到这一目的，我们需更多地了解靶向药物极其治疗的分子生物学基础；了解大多数实体肿瘤都有多靶点、多环节调控过程的特点；了解目前的转化性研究还远远未能解释所发生的一切临床现象；了解各个民族、性别，各种环境、条件都可能对治疗有不同的反应。希望不久的将来，随着对人类基因组学中功能性基因组和支配肿瘤的基因组的深入了解并结合高新技术如高通量药物筛选等手段的有效运用，肿瘤的治疗必将跨入一个全新的时代。
标签: targeted
