近日,，研究人員在發(fā)現(xiàn)一種罕見(jiàn)的皮膚癌病毒的根源四年后,，匹茲堡大學(xué)癌癥研究所（UPCI）大學(xué)醫(yī)學(xué)院的研究人員現(xiàn)在已經(jīng)確定了這種病毒，在動(dòng)物實(shí)驗(yàn)中,，可以針對(duì)有選擇性地激活一個(gè)分子殺死腫瘤細(xì)胞。這一研究成果將很快被測(cè)試患者的治療。
Moore醫(yī)學(xué)博士說(shuō)細(xì)胞癌（MCC）,，皮膚癌是常見(jiàn)于中老年人和免疫系統(tǒng)虛弱的人，并且不能輕易診斷出來(lái),，它仍然有一個(gè)非常差的預(yù)后,，相關(guān)研究論文在5月9日的Science Translational Medicine雜志上。
Moore博士指出：目前我們所做的基因組可以識(shí)別癌癥的分子原因,，然后指出針對(duì)性的治療方式,。
在2008年，研究團(tuán)隊(duì)第一次描述了新的Merkel細(xì)胞多瘤病毒（MCV）,，Merkel細(xì)胞癌,。在一年之內(nèi)，他們發(fā)現(xiàn)該病毒對(duì)大多數(shù)情況下腫瘤發(fā)展有作用,。Chang博士說(shuō)：病毒仍然主要存在于皮膚細(xì)胞中,，并在大多數(shù)情況下是沒(méi)有損害的。但是,，當(dāng)這種病毒發(fā)生突變時(shí),，它可以導(dǎo)致癌癥,。（生物谷：Bioon.com）
doi:10.1126/scitranslmed.3003713
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Survivin Is a Therapeutic Target in Merkel Cell Carcinoma
Reety Arora, Masahiro Shuda, Anna Guastafierro, Huichen Feng, Tuna Toptan, Yanis Tolstov, et al.
Merkel cell polyomavirus (MCV) causes ~80% of primary and metastatic Merkel cell carcinomas (MCCs). By comparing digital transcriptome subtraction deep-sequencing profiles, we found that transcripts of the cellular survivin oncoprotein [BIRC5a (baculoviral inhibitor of apoptosis repeat-containing 5)] were up-regulated sevenfold in virus-positive compared to virus-negative MCC tumors. Knockdown of MCV large T antigen in MCV-positive MCC cell lines decreased survivin mRNA and protein expression. Exogenously expressed MCV large T antigen increased survivin protein expression in non-MCC primary cells. This required an intact retinoblastoma protein–targeting domain that activated survivin gene transcription as well as expression of other G1-S–phase proteins including E2F1 and cyclin E. Survivin expression is critical to the survival of MCV-positive MCC cells. A small-molecule survivin inhibitor, YM155, potently and selectively initiates irreversible, nonapoptotic, programmed MCV-positive MCC cell death. Of 1360 other chemotherapeutic and pharmacologically active compounds screened in vitro, only bortezomib (Velcade) was found to be similarly potent, but was not selective in killing MCV-positive MCC cells. YM155 halted the growth of MCV-positive MCC xenograft tumors and was nontoxic in mice, whereas bortezomib was not active in vivo and mice displayed serious morbidity. Xenograft tumors resumed growth once YM155 treatment was stopped, suggesting that YM155 may be cytostatic rather than cytotoxic in vivo. Identifying the cellular pathways, such as those involving survivin, that are targeted by tumor viruses can lead to rapid and rational identification of drug candidates for treating virus-induced cancers.
