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抗前列腺癌新药有苗头
http://www.100md.com 2001年7月26日 家庭医生医疗保健网
     路透社纽约健康消息-美国默克研究实验室以雷蒙德·琼斯博士为首的科学家们找到了一种新技术,能增强化疗药阿霉素杀伤前列腺癌细胞的能力。该技术通过诱使阿霉素选择性地把前列腺癌细胞作为攻击靶子,从而让医生在为病人设计化疗方案时,可以使用较低剂量的阿霉素,达到减少阿霉素副作用的目的。

    前列腺癌是一种男性肿瘤,有些类型的前列腺癌要依赖男性激素(雄激素)才能生长,因此,能够阻滞雄激素的药物就可以阻止癌的发展。而对于不依赖于雄激素的前列腺癌病人来说,目前仍没有延长生存期的治疗方法。

    阿霉素被用于治疗各种类型癌症的化疗已经有近三十年历史,但用于治疗对雄激素无依赖性的前列腺癌所需的剂量非常大,其副作用甚至会是致命的。琼斯博士的研究小组就是通过改进阿霉素,使它成为对肿瘤组织更有针对性的“前期药物”。

    新技术是依靠前列腺特异性抗原(PSA)实现的,PSA是一种由前列腺产生的蛋白,在患有前列腺癌时容易被激活。在鼠的实验中,研究员将阿霉素与一种特殊的肽配对。这种阿霉素-肽结合物会在体内循环,而且无论是在前列腺内还是在癌症扩散后在身体的其它部份,只要它与PSA接触,PSA蛋白就会打破了肽与阿霉素的连结,阿霉素被激活,杀灭前列腺癌细胞。根据实验报告,阿霉素-肽结合物对一种不产生PSA的前列腺癌作用不大。
, 百拇医药
    研究组在十一月的《自然医学杂志》上发表文章说,这种治疗在老鼠身上是成功的:阿霉素-肽结合物攻击肿瘤的功效比普通阿霉素高出了15倍,而且发生严重副作用的风险较小。普通阿霉素对心脏有较大的损害,但阿霉素-肽结合物残留在实验鼠心脏的药物水平比普通阿霉素要低。

    琼斯研究小组目前正在对阿霉素-肽结合物进行一期临床实验,以了解其在人体中用药是否安全。尽管这个早期试验的目的不在于测试新药的有效性,但根琼斯博士说,有两个病人已对治疗产生了圆满的反应。他对阿霉素-肽结合物能继续进行下一期的临床试验持“谨慎的乐观”的态度。

    Powerful Chemotherapy May Treat Prostate Cancer

    NEW YORK (Reuters Health) - Researchers have developed a way to supercharge the cancer-killing power of a chemotherapy drug, making it possible to destroy prostate cancer cells without causing debilitating side effects, according to new study results.
, 百拇医药
    Some forms of prostate cancer depend on the male hormones (androgens) to grow, so treatment with androgen-blocking compounds can stop the development of cancer.

    But for men with prostate cancer that does not depend on androgens, there is no treatment that will prolong survival. Chemotherapy can destroy androgen-independent prostate cancer, but the doses needed are so large that the side effects could be deadly.

    Dr. Raymond Jones and colleagues at Merck Research Laboratories in West Point, Pennsylvania, developed a way to coax the chemotherapy drug doxorubicin to selectively target prostate cancer cells, which would allow doctors to use lower doses of the drug.
, http://www.100md.com
    Doxorubicin has been used to treat various types of cancer for nearly 30 years, but the high doses needed to attack androgen-independent prostate cancer cause considerable toxic effects, according to Jones.

    In an interview with Reuters Health, the researcher said that he and his colleagues have modified the drug and made it a ‘‘prodrug‘‘ that is more targeted to tumor tissue.

    ``We made it more toxic to tumor tissue and less toxic to normal tissue,‘‘ he explained.
, http://www.100md.com
    The new approach depends on PSA, or prostate-specific antigen, a protein produced by the prostate that tends to be elevated when a man has prostate cancer. In experiments in mice, the researchers paired doxorubicin with a particular peptide. When the drug-peptide combo came into contact with PSA, the protein broke the bond between the peptide and the drug, allowing the medication to kill prostate cancer cells.

    The treatment appeared to be a success in mice, Jones and his colleagues report in the November issue of Nature Medicine. Compared to normal doxorubicin, the experimental drug was 15 times more effective at fighting tumors. The researchers tested the maximum amount each version of the drug that could be tolerated.
, 百拇医药
    The theory behind the treatment is that the drug-peptide combination will move through the body and will only be activated when it comes into contact with prostate cancer cells, either in the prostate gland or in other parts of the body if the disease has spread. This seems to be the case, since the modified version of doxorubicin did not have much of an effect on a type of prostate cancer that does not produce PSA, according to the report.

    And the modified drug appears to carry less of a risk of severe side effects, according to Jones‘ team. Ordinary doxorubicin can cause major damage to the heart, but mice treated with the modified version had lower levels of the drug in their heart than mice treated with the unmodified drug.
, http://www.100md.com
    Current care for androgen-independent prostate cancer focuses only on making a person more comfortable, not in slowing down or stopping the growth of cancer, Jones said. In referring to the experimental prodrug, he added, ``we hope that it increases longevity.‘‘

    Jones and his colleagues are currently testing the prodrug in Phase 1 clinical trials, which are designed to see whether a drug is safe to use in people. But even though this early trial is not meant to test the effectiveness of the drug, two patients have had a complete response to the treatment, according to Jones.

    Although it is impossible to know when or if the prodrug will ever be approved for use in people, Jones said he is ‘‘cautiously optimistic‘‘ that it would move on to the next phase of human testing., http://www.100md.com


    参见:首页 > 药学版 > 药物手册 > 西药大全一 > 抗病毒、抗肿瘤及免疫药物药理 > 抗肿瘤抗生素 > 阿霉素