杀灭病毒，阻止癌症
From 自明知识
研究人员首次指出：每年130万例之多的癌症，通过靶向杀灭其引发病毒，有一天可能会得到成功地治疗，甚至得到预防。纽约市耶希瓦大学艾伯特•爱因斯坦医学院的科学家们声称，这一研究发现能够为战胜先期病毒感染相关的人类癌症铺平道路。在这些癌症中，肝癌由乙型肝炎病毒和丙型肝炎病毒引发，子宫颈癌由人乳头状瘤病毒引发，淋巴瘤由EB病毒引发。 他们说，他们的关键是在这些病毒引发癌症之前，找到并且杀灭它们。
在这样的尝试中，研究人员使用了一项被认为是放射免疫疗法的技术，该技术系将与抗体（类似感染搜寻--摧毁导弹的蛋白质分子）相固定的放射性同位素（释放辐射的不稳定元素）注入体内。研究人员发现：这些抗体一旦进入体内，就锁定了他们的靶点---病毒抗原，而且放射性同位素在不损伤周围健康组织的情况下，破坏了邻近的癌细胞。 病毒抗原是由病毒感染细胞产生的蛋白质，其能够引起那些感染细胞出现异常，开始失控地分裂增殖，从而发生癌变。抗体是存在结合位点的免疫蛋白，其能够将相似的迷惑部分与外源性病毒或细菌抗原上相应的结合位点相结合，从而使它们失去功能（触发其他的免疫应答）。
虽然，典型引发癌症的病毒的问题是它们往往隐藏在无法触及的细胞内部，而不是在细胞的表面。然而，爱因斯坦医学院的研究人员却找到了解决这个问题的办法。据爱因斯坦医学院微生物学和免疫学系主任，合作的资深研究作者Arturo Casadeval说，“我们有一个预感：快速生长的肿瘤可能会超越血供而过度增长，致使产生坏死的肿瘤细胞，这些坏死细胞可能在存活的肿瘤细胞之间释放他们的病毒抗原。所以我们希望，通过将固定于同位素的抗体注射到血液中，送至深达肿块内部，然后它们将会与这些目前暴露的抗原相结合。于是，放射性同位素发出的辐射冲击将会破坏邻近的肿瘤细胞。”
研究人员将放射性同位素铼-18附在攻击E6（一种实际上由所有子宫颈癌细胞产生的病毒抗原）的抗体上，利用小鼠检测了他们的理论。他们还通过将铼-18附在以HBx（一种通过癌性肝细胞制成的病毒抗原）为靶点的抗体上，从而制备出对抗肝癌的相似武器。他们采用适当的放射免疫疗法，对注射了人类宫颈癌细胞和肝癌细胞的小鼠进行了治疗。据研究人员在PLoS ONE中报道称，在这两种情况下，与未治疗的小鼠的结果相比，该疗法明显减慢了肿瘤生长。在种植了宫颈癌的小鼠中，肿瘤不仅停止生长，而且一些肿瘤居然缩小了。爱因斯坦医学院微生物学和免疫学系以及核医学系的副教授、资深研究合著者-- Ekaterina Dadachova说，“放射免疫疗法不仅在治疗这些肿瘤中发挥作用，此外，放射还被完全限制于癌肿，使得健康组织不受损害。”
应用放射免疫疗法治疗感染性疾病的先驱者Dadachova，先前曾经首次成功地将其应用于一种引起肺炎的链状球菌的治疗。去年，她和她的同事指出：该疗法也能够通过靶向作用于HIV感染细胞表面的几个病毒蛋白，而应用于帮助阻止艾滋病病毒。她说，“我们的研究已经基本上表明：放射免疫疗法能够帮助治疗由病毒引发的癌症。而且，令人兴奋的是，该疗法也有望实现癌症的预防！在乙型或丙型肝炎病毒、人类乳头瘤病毒或其他已知的引发癌症病毒的慢性感染人群中，放射免疫疗法有可能在病毒感染细胞转变为癌细胞之前将它们消灭。”
Kill the Virus, Stop the Cancer
Researchers show that some cancers can be slowed and perhaps blocked by knocking out the viruses that trigger them.
By Lisa Stein
Researchers have for the first time shown that as many as 1.3 million cases of cancer a year may one day be successfully treated or even prevented by targeting and destroying the viruses that cause them.
Scientists at the Albert Einstein College of Medicine of Yeshiva University in New York City say the finding could pave the way for conquering human cancers that are linked to preexisting viral infections, among them liver cancer (caused by the hepatitis B and C viruses), cervical cancer (from human papillomavirus) and lymphomas caused by the Epstein–Barr virus.
They key, they say, is to find and destroy the viruses before they turn cancerous. In an attempt to do this, the researchers used a technique known as radioimmunotherapy in which radioisotopes (unstable elements that release radiation) mounted on antibodies (protein molecules akin to infection search-and-destroy missiles) are injected into the body. Once inside, researchers found that the antibodies zeroed in on their targets—viral antigens—and the radioisotopes destroyed nearby cancer cells without damaging surrounding healthy tissue.
Viral antigens are proteins produced by virus-infected cells that can cause those cells to go berserk and start multiplying out of control, thereby becoming cancerous. Antibodies are immune proteins with binding sites that can fit like puzzle pieces into corresponding sites on foreign viral or bacterial antigens and disable them (triggering other immune responses). The problem with viruses that typically cause cancer, though, is that they tend hide out of reach—inside of rather than on the surface of cells. The Einstein researchers, however, found a way around that.
"We had a hunch that rapidly growing tumors can 'outgrow' their blood supply, resulting in dead tumor cells that might spill their viral antigens amongst the living cancer cells," said co-senior study author Arturo Casadevall, chair of Einstein's Microbiology & Immunology department. "So we hoped that by injecting antibodies hitched to isotopes into the blood that they'd be carried deep into the tumor mass and would latch onto these now-exposed antigens. Then the blast of radiation emitted by the radioisotope would destroy the…tumor cells nearby."
The researchers tested their theory on mice, attaching the radioisotope rhenium 18 to antibodies that attack E6, a viral antigen produced by virtually all cervical cancer cells. They prepared a similar weapon against liver cancer by piggybacking rhenium 18 on antibodies that target HBx, a viral antigen made by cancerous liver cells. The mice, which had been injected with human cervical and liver cells, were treated with the appropriate radioimmunotherapy.
In both cases, researchers report in PLoS ONE the therapies significantly slowed tumor growth compared with results in untreated mice. In the animals with cervical cancer, the tumors not only stopped growing but some actually shrunk.
"Radioimmunotherapy not only worked against these cancers but, in addition, the radioactivity was confined entirely to the tumor masses, leaving healthy tissues undamaged," said senior study co-author Ekaterina Dadachova, an associate professor of nuclear medicine and of microbiology and immunology at Einstein.
Dadachova, a pioneer in the use of radioimmunotherapy against infectious diseases, previously successfully turned it on a streptococcal bacterium that causes pneumonia. Last year, she and her colleagues showed that the therapy could also be used to help halt HIV by targeting one of several viral proteins on the surface of HIV-infected cells.
"Our study has shown in principle that radioimmunotherapy can help in treating cancers caused by viruses—and, just as exciting, the approach also holds promise for cancer prevention, she said. "In people chronically infected with hepatitis B or C, human papillomaviruses or other viruses known to cause cancer, radioimmunotherapy could potentially eliminate virus-infected cells before they're able to transform into cancer cells."
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