Using genetically manipulated mice to study the pathophysiologic consequences of castration-induced prostatic cell death

使用基因操纵小鼠研究去势诱导的前列腺细胞死亡的病理生理后果

• 批准号: nhmrc : 250318
• 负责人: Prof John Hayball
• 金额: $ 30.36万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2003
• 资助国家: 澳大利亚
• 起止时间: 2003-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/using-genetically-manipulated-cell-death/76392
• 关键词: Using; genetically; manipulated; mice; study

Prostate cancer is the second leading cause of cancer death among Australian men. The disease is incurable once it spreads beyond the confines of the prostate gland. Hormonal treatments can keep the cancer at bay for a number of years until they are no longer effective. Hormonal treatments cause shrinkage of prostate cancer because they interfere the function of the male hormone, testosterone, which encourages growth of prostate cancer. Hence, there is a need for other treatments that may improve the quality of life and survival of prostate cancer patients. It appears that a cancer patient can make immune cells known as T cells, which can recognise his own tumour but which are prevented from destroying the tumour. Using a mouse model of prostate cancer, we wish to understand how prostate tumours act to prevent immune destruction in circumstances that are common to the treatment of human prostate cancer. For example, hormonal treatments produce dead prostate cancer cells that will be cleared by the body's professional scavenger cells in a way that suppresses an active immune response against the tumour. To learn how the removal of dead cells suppresses the immune response, we propose to perturb the normal clearance of dead prostate cells by at least two means. First, we will study mice that have an inherited deficiency in the removal of dead cells. Second, these mice will be given a growth factor to produce an excess of immune stimulating cells known as dendritic cells in the prostate gland. The dendritic cell is the main type of cell that initiates immune responses. We will investigate whether the greater number of dendritic cells, which were put into the prostate gland by the growth factor, can remove the dead prostate cells in a way that excites rather than suppresses the anti-tumour immune response. Positive results obtained from these studies may lead to the design of new treatments for advanced prostate cancer.

前列腺癌是澳大利亚男性癌症死亡的第二大原因。这种疾病一旦扩散到前列腺以外就无法治愈。激素治疗可以使癌症在海湾数年，直到他们不再有效。激素治疗会导致前列腺癌缩小，因为它们干扰了男性激素睾丸激素的功能，睾丸激素会促进前列腺癌的生长。因此，需要可以改善前列腺癌患者的生活质量和存活率的其他治疗。癌症患者似乎可以产生被称为T细胞的免疫细胞，这种细胞可以识别自己的肿瘤，但不能破坏肿瘤。使用前列腺癌的小鼠模型，我们希望了解前列腺肿瘤如何在人类前列腺癌治疗常见的情况下防止免疫破坏。例如，激素治疗会产生死亡的前列腺癌细胞，这些细胞将被身体的专业清道夫细胞清除，从而抑制对肿瘤的主动免疫反应。为了了解死亡细胞的去除如何抑制免疫反应，我们建议通过至少两种方法干扰死亡前列腺细胞的正常清除。首先，我们将研究在去除死细胞方面具有遗传缺陷的小鼠。第二，这些小鼠将被给予生长因子，以在前列腺中产生过量的免疫刺激细胞，称为树突状细胞。树突状细胞是启动免疫反应的主要细胞类型。我们将研究是否更多的树突状细胞，这是由生长因子进入前列腺，可以消除死亡的前列腺细胞的方式，刺激而不是抑制抗肿瘤免疫反应。从这些研究中获得的积极结果可能会导致晚期前列腺癌的新治疗方法的设计。