一项新的研究表明 鸦片类止痛药加速肿瘤细胞的生长
Opiate-based painkillers can increase tumor-cell proliferation, says new study

 

虽然两个世纪以来吗啡一直是治疗术后和慢性癌症疼痛的黄金标准药物,但越来越多的证据表明,阿片类止痛药可以刺激癌细胞的生长和扩散。两项新的研究推动了这一观点,并在细胞培养和小鼠模型中证明了,保护肺癌细胞不受鸦片剂的影响是如何减少细胞增殖、侵袭和迁移的。


这个报告2009年11月18日,在“分子靶和癌症治疗,”联席会议在波士顿的美国癌症研究协会提交,美国国家癌症研究所和欧洲癌症研究和治疗组织——突出μ阿片受体,在吗啡的作品,作为一个潜在的治疗目标。


“如果临床证实,这可能会改变我们为癌症患者做手术麻醉的方式,”帕特里克A.辛格尔顿博士说,他是芝加哥大学医学中心的助理教授,也是这两项研究的主要作者。“这也暗示了这种新型药物的潜在新应用,这类药物应该被探索。”


阿片类药物影响癌症复发的主张,是由一些不相关的临床和实验室研究提出的,逐渐得到了支持。它始于2002年的一项姑息治疗试验。在这项试验中,接受脊椎治疗而非全身疼痛缓解的患者存活时间更长。此后不久,辛格尔顿的同事、麻醉学家乔纳森•莫斯(Jonathan Moss)注意到,在同情用药方案中接受选择性阿片类阻滞剂的几名癌症患者比预期寿命更长。最近的两项回顾性研究发现,接受局部麻醉而不是全身麻醉的乳腺癌和前列腺癌患者复发更少。2009年2月,麻醉病人安全基金会强调了这个问题。


莫斯的姑息治疗患者服用甲基纳曲酮(MNTX),这是上世纪80年代由已故的芝加哥大学药理学家利昂•戈德堡(Leon Goldberg)为治疗阿片类药物引起的便秘而研制的药物。戈德堡修改了一种可以阻断吗啡的药物,使其不能再穿过包围大脑的保护屏障。因此,MNTX可以阻断吗啡的外周副作用,但不会干扰其对疼痛的作用,疼痛集中在大脑中。它在2008年获得了FDA的批准。

莫斯回忆说:“这些人都是晚期癌症患者,他们的预期寿命只有一到两个月,但也有一些人活了五到六个月。”这让我们怀疑这是否只是更好的胃肠道功能的结果,或者可能对肿瘤有影响。

 

Opiate-based painkillers can increase tumor-cell proliferation, says new study

Although morphine has been the gold-standard treatment for postoperative and chronic cancer pain for two centuries, a growing body of evidence is showing that opiate-based painkillers can stimulate the growth and spread of cancer cells. Two new studies advance that argument and demonstrate how shielding lung cancer cells from opiates reduces cell proliferation, invasion and migration in both cell-culture and mouse models.

The reports--to be presented November 18, 2009, at "Molecular Targets and Cancer Therapeutics," a joint meeting in Boston of the American Association for Cancer Research, the National Cancer Institute, and the European Organization for Research and Treatment of Cancer--highlight the mu opiate receptor, where morphine works, as a potential therapeutic target.

"If confirmed clinically, this could change how we do surgical anesthesia for our cancer patients," said Patrick A. Singleton, PhD, assistant professor of medicine at the University of Chicago Medical Center and principal author of both studies. "It also suggests potential new applications for this novel class of drugs which should be explored."

The proposition that opiates influence cancer recurrence, prompted by several unrelated clinical and laboratory studies, has gradually gained support. It started with a 2002 palliative-care trial in which patients who received spinal rather than systemic pain relief survived longer. Soon after that, Singleton's colleague, anesthesiologist Jonathan Moss, noticed that several cancer patients receiving a selective opiate blocker in a compassionate-use protocol lived longer than expected. Two recent retrospective studies found that breast and prostate cancer patients who received regional rather than general anesthesia had fewer recurrences. In February, 2009, the Anesthesia Patient Safety Foundation highlighted the issue.

Moss's palliative-care patients were taking methylnaltrexone (MNTX), developed in the 1980s for opiate-induced constipation by the late University of Chicago pharmacologist Leon Goldberg. Goldberg modified an established drug that blocks morphine so that it could no longer cross the protective barrier that surrounds the brain. So MNTX blocks morphine's peripheral side effects but does not interfere with its effect on pain, which is centered in the brain. It won FDA approval in 2008.

"These were patients with advanced cancer and a life expectancy of one to two months," Moss recalled, "yet several lived for another five or six. It made us wonder whether this was just a consequence of better GI function or could there possibly be an effect on the tumors."

https://www.news-medical.net/news/20091119/Opiate-based-painkillers-can-increase-tumor-cell-proliferation-says-new-study.aspx