前列腺癌的基因治疗研究进展

随着分子生物学及相关学科的发展，基因治疗可望成为治疗恶性肿瘤的重要方法，目前基因治疗应用于前列腺癌的临床前实验研究已取得较大进展，给晚期前列腺癌治疗带来新的希望。该文就前列腺癌基因治疗的几种策略作一综述。     

前列腺癌的基因治疗

面对治疗前列腺癌有限的几种治疗模式,其有限的成功率势必需要一种更加有效的治疗方案作为替代或补充,随着生物科技的迅速发展,前列腺癌基因治疗的研究也在不断的深入,基于前列腺癌的分子表达,通过基因介导以达到治疗的目的,在研究过程当中多种基因治疗方案已经取得了很大的发展,这些方法主要有以下几类：免疫基因治疗;细胞减数基因治疗;条件复制型腺病毒。我们相信这些新的治疗方案在不久的将来定将给患者带来巨大的福音,现对这一方法进行综述。     

基因治疗在前列腺癌中的应用

目前晚期前列腺癌局部和全身治疗手段都存在一定局限性，为此人们开始寻找其他方法，基因治疗的出现给晚期前列腺癌治疗带来新的希望，全文就当今前列腺癌基因治疗的情况进行了学习和总结。     

前列腺癌的基因治疗

面对治疗前列腺癌有限的几种治疗模式,其有限的成功率势必需要一种更加有效的治疗方案作为替代或补充,随着生物科技的迅速发展,前列腺癌基因治疗的研究也在不断的深入,基于前列腺癌的分子表达,通过基因介导以达到治疗的目的,在研究过程当中多种基因治疗方案已经取得了很大的发展,这些方法主要有以下几类:免疫基因治疗;细胞减数基因治疗;条件复制型腺病毒.我们相信这些新的治疗方案在不久的将来定将给患者带来巨大的福音,现对这一方法进行综述.     

前列腺癌靶向基因治疗实验研究的最新进展北大核心CSCD

由于去势抵抗性前列腺癌(castration-resistant prostate cancer,CRPC)缺乏有效的治疗方法催生了探索新治疗模式的需求,其中靶向基因治疗是治疗前列腺癌较理想的模式。但因缺乏令人满意的基因载体以及旁观者效应的降低而影响了其临床应用,为此世界各地的科学家进一步致力于靶向基因、载体、应用方法和治疗方案的实验研究,本文就CRPC靶向基因治疗的最新研究成果作一综述。     

前列腺癌自杀基因治疗中组织特异性启动子的研究进展

随着自杀基因治疗成为治疗恶性肿瘤的重要方法,其中组织特异性启动子是目前研究的热门之一.前列腺癌自杀基因治疗常用的组织特异性启动子有PSA及Probasin等,其中PSA,Probasin为雄激素依赖性,对于未经雄激素去势治疗的前列腺癌治疗效果较好;而PSMA为雄激素非依赖性,对于是否经过雄激素去势治疗的前列腺癌均有良好疗效,适用范围广.     

前列腺特异性启动子在慢病毒介导基因治疗中的研究进展

前列腺癌多发生于老年男性,其发病率和死亡率正在逐年上升。对于早期前列腺癌,采用阻断雄激素的去势治疗可以有效抑制肿瘤生长,但在治疗2～3年后大部分进展为去势抵抗性前列腺癌,这是导致患者死亡的主要原因。目前,对晚期尤其是去势抵抗性前列腺癌尚缺乏有效的治疗策略,随着生物技术的兴起与发展,针对恶性肿瘤的生物靶向治疗研究日趋深入和成熟,其中慢病毒介导的基因治疗成为研究的热点。运用特异性启动子调控相关基因的表达,可以进一步提高抗肿瘤的靶向性和安全性。本文就目前在基础研究中,前列腺特异性启动子在慢病毒介导下基因靶向治疗前列腺癌的研究现状进行综述。     

肝癌的基因治疗研究进展

肝癌的基因治疗是肿瘤基因治疗的研究热点之一，其治疗方案包括：肝癌的抑癌基因治疗，肝癌的反义基因治疗，肝癌的自杀基因治疗和肝癌的免疫基因治疗。本文对肝癌基因治疗各种方法的疗效、优缺点及前景作了总结。     

恶性肿瘤自杀基因治疗研究进展

经过数年的发展，目前国际上已有二百多个基因治疗项目应用于临床，其中恶性肿瘤的基因治疗占了２／３，而恶性肿瘤的自杀基因治疗又占恶性肿瘤基因治疗的五分之一以上。恶性肿瘤的自杀基因治疗已由最早的治疗卵巢癌（１９９１年），发展到多种肿瘤和疾病的治疗，如：脑瘤、恶性黑色素瘤、头颈部鳞癌、前列腺癌、多发性骨髓瘤、间皮瘤、柔脑膜瘤、中枢神经系统疾病及骨髓移植等各个方面［１］。所谓自杀基因（ｓｕｉｃｉｄｅｇｅｎｅ）是指在一定条件下，可以引起细胞自动死亡的基因。它有两类：一是基因表达产物本身对细胞有毒性作用，如白…     

前列腺癌的高剂量率近距离放射治疗

放疗是前列腺癌根治的重要治疗手段，前列腺癌的近距离放射是近20年来前列腺癌治疗领域的研究热点。多年来早期局限性前列腺癌的近距离放射以低剂量率放射粒子植入为主，但近年来美国各肿瘤治疗中心已逐渐开展了针对局限性前列腺癌的高剂量率（hish-dose-rate，HDR）近距离放射。多项研究结果显示前列腺癌具有低α/β比值，故大分割放射的高剂量率近距离放射对前列腺癌可能更具疗效。HDR近距离放射治疗通常与外放疗联合应用于局部晚期的前列腺癌根治，临床研究结果已初步证实了这一治疗方案的疗效；另外，单一HDR近距离放射治疗也可用于早期前列腺癌的治疗，但其疗效仍需临床研究的进一步支持。HDR近距离放射技术需要经过特殊训练的医师方能操作，以保证良好的治疗结果。     

Prostate cancer gene therapy and the role of radiation

Even though prostate cancer is detected earlier than in the pre-PSA era, prostate cancer is the second leading cause of cancer mortality in the American male. Prostate cancer therapy is not ideal, especially for high-risk localized and metastatic cancer; therefore, investigators have sought new therapeutic modalities such as angiogenesis inhibitors, inhibitors of the cell signaling pathway, vaccines, and gene therapy. Gene therapy has emerged as potential therapy for both localized and systemic prostate cancer. Gene therapy has been shown to work supra-additively with radiation in controlling prostate cancer in vivo. With further technological advances in radiation therapy, gene therapy, and the understanding of prostate cancer biology, gene therapy will potentially have an important role in prostate cancer therapy.     

Prostate cancer--treatment of hormone independent cancer]

At the present time in Japan, the androgen ablation therapy, such as the surgical castration, estrogen therapy, antiandrogen therapy and LHRH agonist therapy, is mainly used for the treatment of advanced prostate cancer as well as for early prostate cancer. Ten to twenty percent of advanced prostate cancer do not respond to the initial endocrine therapy. The most of advanced prostate cancer relapse to androgen independent state within several years after the initial endocrine therapy. This characteristic of prostate cancers to develop resistance to androgen ablation therapy is the main problem in the treatment of prostate cancer. We surveyed the literatures regarding the treatments of the hormone independent prostate cancer. The results of bilateral adrenalectomy or antiandrogen therapy for patients who had relapsed to standard hormone therapy was disappointing. These data showed that the absence of testes and adrenals is not sufficient to stop the progression of the hormone independent cancer cells. Theoretically, the chemotherapeutic agents will be expected to be active agents for the hormone independent prostatic cancer. However, none of the products available are particularly active and the objective response rate is less than 10%. Therefore, the least toxic agents should be used. The treatment of painful metastasis in the terminal stage patients with hormone independent prostate cancer should be positively achieved. The external beam irradiation is useful for palliation of local bone pain of prostate cancer. Analgesics including morphine should be also positively used for the relief of pain in the terminal stage patients with prostate cancer.     

Strategies for Prostate Cancer Gene Therapy

Gene therapy for prostate cancer is a relatively new experimental treatment modality and several different therapeutic approaches are being considered. Prostate cancer is the most commonly diagnosed cancer in males and has unique features that make it ideal for gene therapy. Although prostate cancer that is confined to the gland can be cured in many of the patients using local treatments (radical prostatectomy or irradiation therapy), the long-term failure rate of these therapies suggests that cancers can metastasize relatively early in the course of the disease. Once prostate cancer has metastasized there are no curative therapies. The greatest challenge in the treatment of advanced prostate cancer is to access and eliminate metastatic cells. Therefore, successful prostate cancer gene therapy will ultimately require an effective strategy to kill cancer cells both at the site of the primary tumor and at distant metastatic sites. In this article we review many aspects of gene therapy specifically relevant for prostate cancer. We discuss the unique advantages and disadvantages of nonviral and viral gene delivery systems. Evidence that gene delivery directly into tumors, in situ, is effective for prostate cancer is presented. We provide a broad review of three general approaches or strategies for prostate cancer gene therapy: corrective, cytoreductive, and immuno-modulatory gene therapy. Replacement of the tumor suppressor gene p53 is the best studied example of corrective gene therapy. The cytoreductive gene therapy that has been used most extensively is herpes simplex virus thymidine kinase (HSV-tk) combined with the prodrug ganciclovir. Immunomodulatory gene therapy approaches such as enhancement of cancer cell recognition, e.g. with antigen encoded gene vaccine approaches, and augmentation of the cellular immune response with specific immunomodulatory molecules such as interleukin-12 have the potential to effectively treat both local prostate cancer and distant metastases.     

前列腺癌干细胞相关肿瘤标志物的研究进展

前列腺癌(prostate cancer,PCa)是男性常见的恶性肿瘤。内分泌治疗是晚期前列腺癌的主要治疗方法,但该方法易使其发展成为激素难治性前列腺癌,且暂无切实有效的治疗方法。近年来的研究发现,前列腺癌干细胞在前列腺癌的发生、发展和转移中起着关键作用,因此前列腺癌干细胞的靶向治疗可能是根治前列腺癌的有效途径。靶向前列腺癌干细胞治疗需首先明确前列腺癌干细胞标志物,尤其是其特异标志物,才能更好地开展前列腺癌根治方案的研究。目前前列腺癌干细胞标志物的研究主要集中于CD44和CD133,但随着研究的不断深入其开始受到质疑,且发现了更多新的标志物,本文主要对前列腺癌干细胞领域研究较广和较新发现的肿瘤标志物进行综述。      

前列腺癌的内科治疗

前列腺癌的内科治疗可分为以下几步:在前列腺局部手术和(或)放疗或局部姑息性处理后,激素依赖性前列腺癌应进行一线内分泌治疗,经过14～30个月后,几乎所有患者都将逐渐发展为激素非依赖性前列腺癌(HIPC),包括雄激素非依赖性前列腺癌(AIPC)和激素难治性前列腺癌(HRPC),对AIPC可改用二线内分泌治疗,对HRPC应予以化疗.若出现骨转移应行抗骨转移治疗.综合合理应用内科治疗可提高前列腺癌治疗水平.     

Surgical and medical treatment for localized prostate cancer

With the advent of prostate-specific antigen (PSA) screening, prostate cancer is increasingly diagnosed in the early stage. For localized prostate cancer, radical prostatectomy is considered the most reliable curative therapy. Radiation therapy can also be curative in localized prostate cancer. Watchful waiting is a reasonable approach in adequately selected cases. More recently, several investigations reported the usefulness of primary hormone therapy for localized and locally advanced prostate cancer, especially for patients showing a favorable initial response. This article summarizes briefly reviews of various approaches in localized prostate cancer.     

Molecular mechanisms of apoptosis in prostate cancer

Prostate cancer is the most frequently diagnosed noncutaneous cancer in men in Western countries. As in the normal prostate, the initial stages of prostate cancer progression depend on androgens that increase proliferation and inhibit apoptosis. Androgen-deprivation therapy is the major course of treatment in recurrent and metastatic prostate cancer. However, in most cases prostate cancer progresses to an apoptosis-resistant androgen-independent stage for which there is no available therapy. It is therefore important to understand the molecular mechanisms underlying prostate cancer progression, and how prostate cancer cells evade apoptotic mechanisms that give rise to their uncontrolled growth behavior. Here, we have reviewed the most important signaling pathways implicated in prostate cancer apoptosis and cell growth and how they may be deregulated during prostate cancer progression.     

转移性前列腺癌的内分泌治疗

雄激素与正常前列腺细胞与前列腺癌细胞的生长存在密切关系。目前，内分泌治疗目前仍是转移性前列腺的最有效治疗手段，其目的在于减少或消除雄激素对前列腺生长的促进作用，从而缓解转移性前列腺癌的症状。转移性前列腺癌的内分泌治疗通常包括手术去势与药物去势。药物去势通过使用雌激素类药物、抗雄激素类药物或黄体素释放激素类似物等药物以阻断雄激素与雄激素受体的结合或减少体内雄激素的产生。以非甾体类抗雄激素药物联合手术去势或LHRH类似物为方案的雄激素完全阻断治疗可阻断睾丸和肾上腺分泌的所有睾酮对前列腺的作用，但其效果是否优于单一药物去势治疗尚无定论。二线内分泌治疗，包括抗雄激素药物撤停、抗雄激素药物治疗、雌激素药物治疗、P450酶抑制剂治疗及皮质类固醇类药物治疗对初始内分泌治疗失效后的“激素非依赖性”前列腺癌仍具一定疗效，且因其毒副作用较少，应于全身化疗前优先采用。     

Recent advances in the treatment of prostate cancer

As new evidence for prostate cancer treatment has emerged in the last few years, longstanding controversies in the treatment of prostate cancer have resurfaced. A number of long-held tenets of prostate cancer therapy have been revisited, sometimes with surprising and challenging results. Although neoadjuvant hormonal therapy prior to radical prostatectomy decreases positive surgical margin rates, longer follow-up is needed to support survival improvement of this combined modality therapy. Androgen deprivation combined with radiation therapy appears to improve disease-free survival (and survival in one series) in patients with locally advanced cancer. Another approach to locally advanced prostate cancer using three-dimensional conformal radiation therapy may improve long term outcome. The data are currently insufficient to conclude that interstitial low dose rate brachytherapy is equivalent to conventional treatments: patients with small tumor volumes and low Gleason grade seem to obtain more benefit, whereas for large tumors with higher gleason grades this approach seems inferior to conventional treatments. In advanced prostate cancer recent data suggest that immediate hormonal therapy improves survival. In this group of patients the use of maximum androgen blockade remains controversial but may adversely affect quality of life compared to orchiectomy alone. Intermittent hormonal therapy may improve quality of life, although effect upon survival is unknown. Chemotherapy in combination with androgen deprivation is currently being studied as front-line therapy in advanced prostate cancer. Palliative benefit of chemotherapy for hormone refractory prostate cancer remains an important endpoint; survival advantage has not been seen in any randomized trials. Suramin may delay disease progression in hormone refractory prostate cancer. Many aspects of prostate cancer treatment will remain controversial until results of large, randomized trials with longer follow-up are available.     

Gene-based therapy in prostate cancer

Prostate cancer is one of the commonest causes of illness and death from cancer. Radical prostatectomy, radiotherapy, and hormonal therapy are the main conventional treatments. However, gene therapy is emerging as a promising adjuvant to conventional strategies, and several clinical trials are in progress. Here, we outline several approaches to gene therapy for prostate cancer that have been investigated. Methods of gene delivery are described, particularly those that have commonly been used in research on prostate cancer. We discuss efforts to achieve tissue-specific gene delivery, focusing on the use of tissue-specific gene promoters. Finally, the present use of gene therapy for prostate cancer is evaluated. The ability to deliver gene-therapy vectors directly to prostate tissue, and to regulate gene expression in a tissue-specific manner, offers promise for the use of gene therapy in prostate cancer.