灭活血小板可阻止癌细胞转移

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Fugitive Cancer Cells Can Be Blocked By Stopping Blood Cells That Aid Them, Study Shows
ScienceDaily (Mar. 10, 2008) — Cancer cells get a helping hand from platelets, specialized blood cells involved in clotting. Platelets shelter and feed tumor cells that stray into the bloodstream, making it easier for cancer to spread, or metastasize. Research at Washington University School of Medicine in St. Louis suggests that inactivating platelets could slow down or prevent metastasis.
每日科学（2008年3月10日）——血小板这种参与凝血的血液成分在癌症的发展中帮了它的忙。血小板们隐藏起来并且给那些进入血流的癌细胞提供养料，加速了其转移。圣路易斯的华盛顿大学医学中心的研究者们表示通过灭活血小板可以减慢或阻止癌症的转移。
In advance online publication in the Journal of Cellular Biochemistry, the scientists report that a combination of two platelet inhibitors reduced the number and size of breast cancer or melanoma tumors that grew in the bones of laboratory mice.
在线发表的《细胞生物化学》这本杂志中，研究者们报道了他们的研究成果：联合使用两种血小板抑制剂减少了患有乳腺癌或者黑色素瘤的小鼠体内肿瘤的数目以及肿瘤的大小。
One of the drugs was aspirin, a widely used inhibitor of platelet clotting. The other was an experimental drug, APT102, which also prevents platelet clotting, but by a different mechanism. Both drugs were needed to reduce bone tumors.
其中一种药物是阿斯匹林，一种广泛应用的抗血小板药物。另一种是目前正在试验阶段的药物APT102，一种通过另一途径抗血小板聚集的药物。
\"ast research has shown that tumor cells activate platelets and that mice with defective platelets have significantly fewer metastases,\" says Katherine Weilbaecher, M.D., assistant professor of medicine and of cell biology and physiology. \"We also know that platelets have several traits that can aid tumor cells, and we are working to break up that potentially lethal partnership.\"
细胞生物学和生理学助教授Katherine Weilbaecher说：“以前的试验研究已经证明了肿瘤细胞可以激活血小板，那些血小板有缺陷的小鼠体内肿瘤的转移程度比正常血小板功能的要低。我们同样知道血小板有几个特性可以帮助肿瘤的成长，我们目前正在致力于研究出有可能打破这种危险的合作关系的方法。”
Metastasis of cancer cells to sites away from the main tumor can cause pain and other symptoms and greatly increases the likelihood a patient will die of the disease. In fact, more than 90 percent of cancer deaths are the result of metastasis, which is difficult to control with current therapies.
癌症的转移会造成很多的痛苦以及引起一系列的症状增加患者的病死率。事实上，有超过90%的肿瘤患者就是死于转移的，而目前对于转移尚无有效的治疗方法。
Cancer cells that leave the primary tumor and circulate in the bloodstream can readily take advantage of platelets they encounter. The circulating tumor cells secrete factors that make platelets stick together, creating a shield of platelets that protects cancer cells from immune attack. In addition, platelets release growth factors that help tumor cells survive, and platelets' capacity to stick to particular sites enables companion tumor cells to settle in and proliferate in new areas.
那些进入血流将要转移的癌细胞可以很容易的利用血小板，这些癌细胞可以分泌一些物质使这些血小板聚集，为这些癌细胞形成一层坚实的盔甲使其避免免疫系统的识别。同时，血小板会释放生长因子以帮助癌细胞的生长，并且血小板黏附于某一部位的功能也可以使癌细胞在那个地方继续的繁殖。
Weilbaecher, an oncologist with the Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital, and colleagues, including 謟ge Ulu鏺an, a predoctoral trainee in molecular genetics, and Mark Eagleton, a research technician, tested the effect of aspirin and APT102 in mice that received an injection of either melanoma or breast cancer cells.
华盛顿大学医学部附属Barnes-Jewish医院Siteman肿瘤中心肿瘤学家Weilbaeche以及他的同事分子遗传学博士生謟ge Ulu鏺an，实验技术师Mark Eagleton，在被注射了乳腺癌或者黑色素瘤的小鼠身体内进行了阿斯匹林以及APT102的效果研究。
The cancer cells establish themselves in bones in as little as two days and proliferate to produce large bone tumors in less than two weeks. But the researchers found the bone tumors were smaller and fewer in mice that got a dose of aspirin and APT102 before inoculation with cancer cells and additional treatments twice a day for two days after that.
这些癌症细胞在短短两天后就开始在骨骼中出现，两周后就复制产生了骨骼中的巨大肿瘤。但是试验者们发现，在那些注射癌细胞之前体内先注射阿斯匹林和APT102，并且以后注射癌细胞后每天注射2次，连着注射2天这两种药物的小鼠，体内肿瘤的数量以及大小都比对比组要少。
\"We only had a small amount of APT102 to test, so in this set of experiments, we gave only a few doses of the drugs to the mice,\" Ulu鏺an explains. \"At this point, we don't know if additional treatment would have further reduced the tumor burden, but it's clear that reducing platelet function had a positive result in this model of metastatic cancer.\"
Ulu鏺an解释说：“由于我们用于实验的APT102数量较小，所以在试验中，我们给这些小鼠注射的APT102的剂量是低于其治疗量的。因此，我们不知道是否加大APT102的剂量会使肿瘤受到更强的抑制，但是有一点是明确的，降低血小板的功能在这种癌症转移模型中可以抑制其转移。”
By themselves neither aspirin nor APT102 lessened the amount and size of bone tumors in the mice, possibly because cancer cells can activate platelets in several different ways, making a dual approach more effective, according to Weilbaecher.
Weilbaecher解释说，之所以单独的阿斯匹林或者APT102不能使肿瘤的数量和体积减小，可能是由于肿瘤细胞是通过多条途径激活血小板的，这就使得联合应用两种药物变得更加有效。
\"Aspirin prevents platelets from making thromboxane, a substance that facilitates clotting,\" Weilbaecher says. \"APT102 is an especially interesting drug because it gets rid of a compound called ADP, which tumor cells release and which stimulates platelets to clump. So APT102 prevents platelet activation in response to tumor cells.\"
Weilbaecher说：“阿斯匹林可以阻止血小板生成凝血噁烷，即一种可以促进凝血的物质。APT102是一种十分有趣的药物，它可以减少一种叫做ADP的物质，这种物质是由肿瘤细胞释放出来的，并可以促进血小板的生成。所以说APT102抑制了由肿瘤细胞造成的血小板活化。”
APT102 is produced by APT Therapeutics Inc., a St. Louis-based biopharmaceutical company. The company donated the drug but did not fund the research project. Co-authors Soon Seog Jeong and Ridong Chen are employees of APT Therapeutics and provided expertise about the bioactivity and dosing of APT102.
APT102是由APT Therapeutics Inc制造的，一座位于圣路易斯的生物制药厂。这家药厂研发了这种药物，但是并没有给该药物的临床试验研究提供经费。这篇论文的合作作者Soon Seog Jeong、 Ridong Chen是这家药厂的员工，他们提供了这种药物的生物学活性以及剂量方面的专业意见。
The researchers noted that the drug combination would likely be well tolerated because it did not cause excessive bleeding in the mice, as might be expected from platelet inhibitors. The research group plans to continue to study the process of metastasis and the role played by platelets.
研究者们发现这两种药物的联合应用的耐受性是很好的，在实验动物中并没有出血这种血小板抑制剂常见的副反应的发生。研究组将继续研究转移的生物学过程以及血小板在其中所发挥的作用。
In collaboration with Michael Naughton, M.D., assistant professor of medicine, Weilbaecher is also involved in a clinical trial of women with advanced breast cancer to test aspirin and Plavix? another antiplatelet drug, to see if the drug combination affects the number of tumor cells that circulate in the blood. The trial is open only to breast cancer patients undergoing treatment at the Siteman Cancer Center.
在于医学助教授Michael Naughton的合作研究中，Weilbaecher将会参与一项在进展期乳腺癌患者群体中使用阿斯匹林以及另一种抗血小板药物Plavix联合作用下对于循环血液中癌细胞的作用的研究。这项研究的对象只是针对于在Siteman医学中心接受治疗的乳腺癌患者。