EFFECTS OF MELATONIN ON MAMMARY AND UTERINE TUMOR GROWTH

这项研究的长期目标是进一步阐明和理解 松果体主要激素褪黑素(MEL)的作用机制 抑制荷尔蒙反应性乳腺癌的增殖 在动物和人类乳腺癌模型中进行体内和体外实验。这个 拟议的研究将确定梅尔和/或松果体切除术对 女性致癌物诱发乳腺癌的发生与生长 老鼠。研究将解决这样的假设，即MEL是抑制性的，而 松果体切除对乳腺肿瘤的发生有促进作用。某些实验 将测试MEL是否是更有效的乳腺癌生长抑制剂 在启动或推广阶段给药时 致癌。此外，这些实验将决定是否存在 是对MEL抑制效应的反应的昼夜节律 人类乳腺癌的动物模型。更多的研究将 确定松果体摘除后是否更换每日MEL信号 大鼠减弱松果体摘除的促癌作用。血液水平 雌二醇(E_2)、催乳素(PRL)以及雌二醇和催乳素受体的结合 在肿瘤组织中的作用将与美罗华和/或 松果体切除术对乳腺肿瘤发生的影响。其他研究将测试这种影响。 MEL对已建立的致癌物诱导的乳腺癌生长的影响 正常和去垂体大鼠对雌二醇和/或催乳素的反应。其他来电 体外研究将直接确定MEL对生长的影响， 激素结合、雌激素磺基转移酶活性和丝裂原蛋白 致癌物诱导的乳腺癌细胞的合成/分泌以及 雌激素敏感的人类乳腺癌细胞。这些实验还将 检测人类MEL抑制的超微结构相关性 乳腺癌细胞在体外生长。相关研究将确定 MEL对致癌物诱导的人乳腺癌细胞生长的影响 对雌二醇和/或催乳素的反应。这项研究将增加我们对 神经内分泌、外周内分泌和细胞分子 MEL抑制乳腺癌生长的机制可能导致 美罗华作为一种新型抗肿瘤药物在卵巢癌治疗中的应用 荷尔蒙反应型人类乳腺癌。

The long range goal of this research is to further elucidate and understand the mechanisms by which melatonin (Mel), the major hormone of the pineal gland, inhibits the proliferation of hormone-responsive breast cancer in vivo and in vitro in both animal and human models of breast cancer. The proposed studies will determine the effects of Mel and/or pinealectomy on the development and growth of carcinogen-induced breast cancers in female rats. Studies will address the hypothesis that Mel is inhibitory while pinealectomy is stimulatory to mammary tumorigenesis. Certain experiments will test whether Mel is a more effective inhibitor of breast cancer growth when administered during either the initiation or promotional phases of carcinogenesis. Moreover, these experiments will determine whether there is a diurnal rhythm of responsiveness to the inhibitory effects of Mel in the animal models of human breast cancer. Additional studies will determine whether replacement of the daily Mel signal in pinealectomized rats attenuates the tumor-promoting effects of pinealectomy. Blood levels of estradiol (E2), prolactin (PRL) as well as E2 and PRL receptor binding in tumor tissue will be correlated with the effects of Mel and/or pinealectomy on mammary tumorigenesis. Other studies will test the effects of Mel on the growth of established carcinogen-induced breast cancers in intact and hypophysectomized rats in response to E2 and/or PRL. Other in vitro studies will determine the effects of Mel directly on the growth, hormone binding, estrogen sulfotransferase activity and mitogenic protein synthesis/secretion of carcinogen-induced breast cancer cells as well as estrogen-responsive human breast cancer cells. These experiments will also examine the ultrastructural correlates of the Mel's inhibition of human breast cancer cell growth in vitro. Related studies will determine the effects of Mel on carcinogen-induced and human breast cancer cell growth in response to E2 and/or PRL. This research will increase our understanding of the neuroendocrine, peripheral endocrine and cellular-molecular mechanisms by which Mel inhibits breast cancer growth and may lead to the use of Mel as a new antineoplastic agent in the treatment of hormone-responsive human breast cancer.