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。      

前列腺癌冷冻治疗并发症的防治进展

冷冻治疗作为前列腺癌的一种新兴治疗手段,与传统手术治疗相比,具有安全、微创、疗效确切及可重复治疗等特点,已成为前列腺癌治疗的主要手段之一。尤其在局限性前列腺癌及其放疗失败补救治疗方面,取得了显著的成效。然而,随着冷冻治疗技术在前列腺癌治疗中的广泛应用,其所呈现的并发症,如:勃起功能障碍、尿失禁、尿道损伤、直肠损伤、骨盆疼痛等,已越来越不容忽视。作者通过查阅国内外相关文献报道,对前列腺癌冷冻治疗的并发症及其防治做一综述。     

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。     

放射性125I粒子植入治疗前列腺癌的研究进展

随着放射性125I粒子植入技术的迅速发展,该项技术已逐渐成为治疗前列腺癌的重要方法。文章检索了近10年来有关放射性125I粒子植入治疗前列腺癌的文献报道,主要从125I粒子植入治疗前列腺癌的作用机制、适应证、处方剂量推荐、临床应用优势、应用现状及疗效评价、相关尿路不良反应治疗建议、粒子辐射防护等7个方面进行综述,并分析了目前125I粒子植入治疗前列腺癌相关研究及辐射防护方面存在的一些不足,旨在为临床安全应用125I粒子治疗前列腺癌提供更有力的依据和借鉴,丰富前列腺癌的治疗方法。     

Prostate cancer old problems and new approaches

In Part Three of this review, we begin with an analysis of prevention strategies for prostate cancer followed by a discussion of the clinical use of molecular techniques for the evaluation and treatment of patients with clinically localized prostate cancer. New developments in neutron and photon therapy of prostate cancer are addressed as well as the use of systemic radiotherapy for the treatment of bone metastases. Finally, we conclude with the role of hormonal therapy in the treatment of prostate cancer and the current status of development of chemo therapeutic regimens for the treatment of prostate cancer.     

前列腺癌:近期研究结果和新方向

虽然对临床局限性前列腺癌的最佳治疗手段尚未有定论，但针对不同患者应给予个体化治疗是目前前列腺癌临床治疗中的一致目标。近10年对前列腺癌的不断研究，临床上对前列腺癌的预防与早期诊断，以及依据治疗前各项实验室与影响学检查结果，对患者选择性地给予“等待观察”或积极治疗已取得了相当成就。本文就近10年来前列腺癌研究中一些最重要的研究结果与可能具显著发展前景的领域作一综述。     

前列腺癌的中医药诊治

作为常见的泌尿生殖肿瘤,前列腺癌的发病率和病死率逐年上升,西医治疗手段以手术、放化疗与内分泌治疗为主。中医诊治前列腺癌有其独特的优势和特色,论文从中医认识前列腺癌着手,总结前列腺癌的病因病机、辨证分析、方药应用、基础研究及数据挖掘,并对目前前列腺癌的中医诊治的问题进行分析与展望,以飨同道。     

Tumor focality in prostate cancer: implications for focal therapy

In recent years, there has been a growing interest in focal treatment for prostate cancer. Although widely used for the treatment of tumors of the breast and kidney, focal treatment for prostate cancer remains a controversial area. Criticism of focal prostate therapy has been based on the fact that prostate cancer is a multifocal disease. Until now, little attention has been paid to distinguishing between men with unifocal and those with multifocal disease because such information has little clinical relevance when treatment is aimed at the whole gland irrespective of the volume or number of cancers in the prostate. In this Review, we summarize existing knowledge and examine the issue of prostate cancer focality in the context of focal treatment.     

SPINK1在前列腺癌中的表达及其功能研究进展

前列腺癌是老年男性常见的恶性肿瘤之一,有关前列腺癌发生发展的机制以及治疗策略的选择是当前的研究重点。近年来,丝氨酸肽酶抑制剂1（serine protease inhibitor kazal type 1,SPINK1）被证明与多种肿瘤进展相关,其与前列腺癌同样关系密切。研究SPINK1在前列腺癌中的作用对于前列腺癌的治疗、预后评估、肿瘤复发等特性具有重大的理论意义。本文就SPINK1与前列腺癌的关系进行综述,希望能为前列腺癌发生发展机制研究提供参考。     

Optimal hormonal therapy for advanced prostatic carcinoma

Although the clinical presentation of stage D2 (M+) prostate cancer is decreasing because of screening, we are witnessing a new spectrum of advanced disease. According to our concept of incurable or advanced prostate cancer, more than half of currently diagnosed prostate cancer patients are potential candidates for hormonal therapy. Hormonal therapy has been the mainstay of treatment for advanced phases of prostate cancer for more than 50 years. However, the optimal form of this therapy is still an enigma. The choice of hormonal therapy for carcinoma of the prostate depends not only on the desired progression-free and overall survival, but also on the patient's quality of life, treatment costs, and treatment toxicities. At present, several important questions have been raised over the optimal treatment modalities for advanced prostate cancer. This review discusses some of the current challenges in the hormonal management of advanced prostate cancer.     

Prostate cancer screening: promise and peril--a review.

This review summarizes the current status of and recommendations for prostate cancer screening with prostate-specific antigen in light of recent reductions in prostate cancer incidence and mortality. It describes how the uncertain effectiveness of aggressive treatment for prostate cancer and a reservoir of unsuspected indolent cancers make prostate cancer fit poorly into conventional screening models. The large proportion of men with unsuspected prostate cancers that may not cause morbidity or mortality and are unlikely to benefit from aggressive treatment decrease the effectiveness of a screening program. In addition, indolent, unsuspected prostate cancers in the screening population accentuate the detrimental effects of length bias on studies evaluating the effectiveness of prostate cancer screening. Screening tests for prostate cancer will continue to improve, but chemoprevention or nutritional prevention with vitamins and micronutrients such as tocopherols or selenium may prove to be effective methods of reducing prostate cancer incidence and should be aggressively investigated.     

Prevention and management of osteoporosis in women with breast cancer and men with prostate cancer

Advances in cancer treatment have resulted in improved life expectancies for survivors of breast and prostate cancer. As the number of cancer survivors grows, the long-term side effects of treatment play an increasingly prominent role in the routine care of these patients. Due to similar management approaches, survivors of breast and prostate cancer are at increased risk for osteoporosis. This review summarizes the prevention and management of osteoporosis and osteopenia resulting from cancer treatment in survivors of breast and prostate cancer.     

Quality of life after therapy for localized prostate cancer

Given the lack of unequivocal survival data clearly favoring one treatment over another for localized prostate cancer, patients strongly consider quality-of-life effects when choosing treatment for this common malignancy. In the past 15 years, a sizeable body of literature assessing health-related quality-of-life (HRQOL) outcomes in localized prostate cancer has emerged. The goal of this article is to review the quality-of-life experience after treatment for localized prostate cancer. Specifically, I will briefly discuss how quality of life is measured and then review the quality of life effects of each of the commonly used treatment strategies in localized prostate cancer. Finally, I attempt to directly compare the quality-of-life effects of the various treatments to assist clinicians in advising patients with newly diagnosed localized prostate cancer.     

前列腺癌和乳腺癌的对比性研究

人体一些肿瘤的生长对某些激素有一定的依赖关系,激素阻断可抑制其生长,被称为激素相关性肿瘤,如甲状腺癌、乳腺癌、子宫内膜癌及前列腺癌等.其中前列腺癌和乳腺癌为人群中发病率较高的两种恶性肿瘤,在很多方面均具有类似的特点.将二者在各方面进行对比性研究,有利于总结前列腺癌治疗方案,提高治疗效果.     

Treatment strategy for elderly patients with prostate cancer

Because of both the indolent and aggressive nature of prostate cancers, it is not easy to select the best treatment for elderly patients with a high prevalence of comorbidities. Since the growth of prostate cancer is generally slow and all treatments adversely affect the quality of life to some degree, conservative treatment may well be the best option for elderly patients with prostate cancer. In fact, previous studies have indicated that the rate of prostate cancer death was not high in patients with low-intermediate risk of prostate cancer who were treated conservatively. However, it is also true that we often encounter elder patients with a locally advanced cancer who had not been exposed to PSA screening. Previous reports also support aggressive treatment such as hormonal therapy, external radiation and brachytherapy alone or in combination for healthy elderly men with high-risk prostate cancer. Thus, after a careful evaluation of the nature of the cancer and comorbidity, we found that both conservative and aggressive treatments are applicable for elderly patients with prostate cancer to maintain their quality of life.     

Multimodality Treatment for Patients with Node-Positive Prostate Cancer: the Role of Radiation Therapy

Prostate cancer is the secondary most frequently diagnosed cancer in the world. Although numerous prospective randomized trial have been conducted to guide the management of patients with localized or locally advanced prostate cancer, few clinical trials targeting node-positive prostate cancer have been reported. Therefore, there are still controversies in the optimal management of node-positive prostate cancer. Recently, efficacy of multimodality treatment, including radiation therapy (RT), for such patients has been reported in several articles. The results indicate potential benefit of RT both in adjuvant therapy after prostatectomy and in definitive therapy for node-positive prostate cancer. The aim in this article was to summarize the current evidence for RT and evaluate the role in multimodality treatment for patients with node-positive prostate cancer.     

Role of PPARgamma in the control of prostate cancer growth: a new approach for therapy

In several cases of prostate cancer, resistance to hormonal therapies is observed. Alternative therapeutic strategies for the treatment of prostate cancer are of great interest. Participation of the nuclear receptor PPARgamma in the physiopathology of the prostate, in particular in prostate cancer has been recently studied. PPARgamma is a member of the hormone nuclear receptor superfamily. As for most members of the family, its activity is regulated by ligands. PPARgamma has been shown to be over-expressed in several cancers, including prostate cancer. In vitro and in vivo studies have demonstrated anti-proliferative and pro-apoptotic actions of the PPARgamma agonists thiazolidinediones, suggesting that PPARgamma could be a promising therapeutical target for the treatment of cancer. No effects of PPARgamma agonists have been observed, however, in a large randomized clinical trial in the "rising PSA" group of prostate cancer patients. This suggests that PPARgamma activity is controled by other factors, in addition to its ligands, in prostate cancer. We have shown that PPARgamma activity is repressed by HDACs. Moreover, PPARgamma activity is enhanced in the presence of HDAC inhibitors. A combination treatment using HDAC inhibitors and PPARgamma agonists results in growth arrest of prostate tumors in mice. Furthermore, the combination therapy inhibits invasion of prostate cancer cells in vivo, through upregulation of the expression of the E-cadherin gene.     

Sequencing hormonal ablation and radiotherapy in prostate cancer: a molecular and therapeutic prespective (Review)

Current therapeutic modalities for advanced prostate cancer are palliative in nature, with no effective treatment increasing survival in patients with metastatic prostate cancer. Apoptosis as a molecular process of genetically regulated cell death has a critical endpoint that coincides with the goal of successful treatment of prostate cancer. Expression of key regulators of the apoptotic pathway such as bcl-2 and caspases within individual prostate tumors appear to correlate with the prostate cancer cell's sensitivity to traditional therapeutic modalities, including androgen ablation and radiotherapy. Androgen-dependent prostate tumors undergo apoptosis in response to androgen-ablation. Cancer regression after radiation occurs by disruption of the reproductive integrity of the tumor cells and via activation of the apoptotic pathway. Increasing the sensitivity of prostate tumor cells to die via apoptosis increases the efficacy of fractionated therapy by reducing tumor cell survival. Thus signaling interaction between androgen ablation and radiotherapy may be synergistic in maximally activating the apoptotic potential of prostate cancer cells. The role of molecular technology in identifying apoptosis regulation in association with combination hormonal ablation and radiotherapy for the treatment of advanced prostate cancer holds tremendous promise, as any approach significantly decreasing the apoptotic threshold may lead to total synergistic killing of tumor cells. This review is an attempt to summarize the current knowledge of the clinical consequences of sequencing androgen ablation and radiotherapy in the treatment of prostate cancer patients and the molecular parameters underlying a potential optimization of such a combination strategy.     

多学科综合治疗——改善高危前列腺癌患者的预后

手术和放疗是局限性前列腺癌主要的治疗方法,但对于高危前列腺癌单用局部治疗预后不佳,超过50％的患者会复发。手术、放疗、内分泌治疗和化疗的联合应用目前被认为是提高高危前列腺癌疗效的重要途径。本文总结了目前高危前列腺癌综合治疗的相关文献,期望能为我国高危前列腺癌综合治疗方案的选择提供借鉴和参考。     

Function and therapeutic implication of C-CAM cell-adhesion molecule in prostate cancer

Human neoplasms are often caused by cumulative alterations in oncogenes and tumor-suppressor genes. By identifying the early genetic changes involved in tumorigenesis, one can develop strategies to prevent and detect cancers at early stages, when treatment is most effective. C-CAM1, a cell-adhesion molecule (CAM) isoform (I), was recently shown to play a critical role in prostate cancer initiation and progression. Loss of C-CAM1 expression occurs early in the development of prostate cancer, suggesting that C-CAM1 may help maintain the differentiated state of the prostate epithelium. Reintroduction of C-CAM1 into cancer cells can reverse their cancerous growth. Thus, the C-CAM1 molecule itself or drugs that increase C-CAM1 expression are promising agents for prostate cancer treatment. The mechanisms by which C-CAM1 suppresses tumorigenesis are different from those of p53 and Rb. Therefore, C-CAM1 therapy is a new form of prostate cancer treatment. To exploit C-CAM1's therapeutic potential, a human C-CAM1 adenovirus expression vector (Ad-hu-C-CAM1) has been used to treat prostate tumor xenografts in nude mice. The preliminary results have shown great promise. In addition, while C-CAM gene therapy may have immediate application in prostate cancer treatment, the knowledge to be learned from mechanistic studies of C-CAM1-mediated tumor suppression may also help us design better strategies for prevention and treatment for prostate cancer.