前列腺癌的基因治疗

基因治疗前列腺癌，虽然目前还够成熟，但利用腺病毒或逆转录病毒把基因导入癌细胞，已正在研究中，有的已被临床试验证明了其可行性和优越性，本文主要概述了体内外细胞因子基因重组产生肿瘤疫苗和矫正基因治疗，同时还探讨了其他几种基因治疗前列腺癌的方法。     

前列腺癌的基因治疗

基因治疗前列腺癌，虽然目前还不够成熟，但利用腺病毒或逆转录病毒把基因导入癌细胞，已正在研究中，有的已被临床试验证明了其可行性和优越性。本文主要概述了体内外细胞因子基因重组产生肿瘤疫苗和矫正基因治疗，同时也探讨了其他几种基因治疗前列腺癌的方法。     

前列腺癌的基因治疗展望

尽管绝大多数局部浸润和转移前列腺癌,初始对雄激素撤除有效,但最终预后不佳。近年来随着对癌症分子作用机制研究的深入,给临床医生提供了用基因治疗肿瘤的机会。癌症的基因治疗就是将基因转移至恶性肿瘤细胞内并进行表达,从而达到抑制癌细胞生长的目的。基因治疗包括:修正基因治疗、细胞减数基因治疗和免疫调节基因治疗。通常使用非病毒和病毒载体产生局部基因表达和治疗作用,但到目前为止,     

前列腺癌基因治疗的研究现状

前列腺癌在我国已成为较常见的肿瘤之一，诊断一旦明确则大多已失去手术时机，基因治疗中望成为前列腺癌的一种新疗法。本文主要介绍前列腺癌的癌基因和抑制基因与实验模型，以及基因治疗的载体和途径等研究现状。     

前列腺癌的基因治疗

0 引言 前列腺癌是一种老年男性高发病,许多局部复发和发生转移的患者,即使一开始已给予去势手术,其预后仍很差,并且转移灶往往对各种治疗发生耐受,外照时和放射性同位素治疗也只能缓解症状。从肿瘤的发生发展机制治疗恶性肿瘤,才是彻底根治的唯一途径,因此基因治疗已成为前列腺癌治疗的热点。目前前列腺癌的基因治疗已有了临床试验报告,临床实始研究更是深入,     

HSV-TK基因治疗在前列腺癌中的研究进展

HSV TK基因治疗应用于前列腺癌的研究进展迅速 ,成为最有希望进入临床应用的基因治疗方法之一。本文对HSV TK基因治疗的原理、效果、联合治疗乃至临床实验的研究作一综述。     

前列腺癌自杀基因治疗研究进展

随着分子生物学及其相关学科的发展 ,基因治疗已成为治疗恶性肿瘤的重要方法 ,其中自杀基因治疗便是研究的热门之一 ,如今 ,在前列腺癌的自杀基因治疗方面已取得较大进展 ,并显示其巨大潜力。本文就前列腺癌的自杀基因治疗作一综述。     

前列腺癌的基因治疗研究

一、概述 前列腺癌是男性最常见的肿瘤之一,由于其组织浸润性强、易早期转移,临床诊断时许多已处在进展期。手术、放疗、化疗、激素及免疫治疗不能很好的局部控制临床或病理上的T3期前列腺癌。因此,治疗干涉的目标应放在分子和细胞水平,利用DNA转移技术来扩大、改变或逆转基因表达最终阻止疾病发展。目前,从百余个已进入临床实验     

病毒载体介导的前列腺癌的基因治疗

本文综述了前列腺癌基因治疗领域近年的研究进展 ,探讨了目前介导基因治疗的病毒载体、治疗基因及特异性启动子的作用机理。     

Targeting of the VHL-hypoxia-inducible factor-hypoxia-induced gene pathway for renal cell carcinoma therapy

Treatment of advanced renal cancer has made little progress in the past 30 yr. Most clinical efforts have incorporated cytokine-based therapy. The presumption has been that the cytokines may trigger a host immune response against the renal cancer. Only IFN-alpha and high-dose IL-2 seemed to have positive effects on patient outcomes. IFN has prolonged the lives of patients by a few months, and high-dose IL-2 is capable of inducing very prolonged remissions (>5 yr) for a small number of patients. Nephrectomy in the presence of metastatic disease has been established as an effective procedure for select patients, providing palliation and prolonging survival. Finally, enthusiasm has focused on the use of nonmyeloablative allogeneic stem cell transplantation and donor leukocyte infusion for the induction of graft versus tumor effects. Early results are both provocative and promising. A number of agents that target the critical gene products downstream from pVHL and hypoxia-inducible factor-1, such as vascular endothelial growth factor, PDGF, EGF receptor, and TGF-alpha, have recently become available. The new agents are capable of inhibiting specific cellular targets, and the biologic characteristics of clear cell carcinoma of the kidney support their application. If the correct targets are carefully selected for inhibition in tumors in which the targets are present (clear cell histologic features and loss of VHL expression), then results should resemble those others have observed with targeted therapy, such as the use of STI-571 (Gleevec; Novartis Pharmaceuticals, East Hanover, NJ) for treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors or anti-HER2/neu (Herceptin; Genentech, South San Francisco, CA) for treatment of breast cancer.     

Testosterone therapy and prostate carcinoma

Hypogonadism is a clinical and biochemical syndrome associated with a range of disease states that has significant effects on morbidity and mortality and also affects quality of life. Because of the increase in life expectancy and prostate carcinoma (PCa) survival, a significant increase in the number of men with hypogonadism who have undergone presumably curative treatment of PCa is anticipated. Despite the widespread belief regarding contraindication of testosterone administration to men with known or suspected PCa, there is no convincing evidence that the normalization of testosterone serum levels in men with low levels presents a deleterious effect on the evolution of the disease. In the few available case series describing testosterone replacement therapy (TRT) after treatment of PCa, no case of clinical or biochemical progression was observed. The available data suggest that TRT can be cautiously considered in selected hypogonadal men previously treated for curative intent of low-risk PCa and without evidence of active disease.     

Interstitial radiation therapy for carcinoma of the prostate

Pelvic lymph node dissection and iodine 125 implantation has been systematically utilized at Memorial Sloan-Kettering Cancer Center (MSKCC) since 1970 as one form of management of selected patients with stage B or stage C prostatic cancer. Experience with the technique is reviewed on the basis of previously published data and on the basis of a five-year follow-up of the first 100 patients. The operative procedure has been generally well tolerated, with a low morbidity, with a mortality rate of 0.67% (2/300), and with minimal adverse effects on urinary, rectal, and sexual functions. Thirty-six percent of the patients had regional lymph node metastasis, and such was associated with a 71% incidence of distant metastasis at five years. However, at five years 14% of patients with positive nodes remain free of evidence of neoplasm, and 38% of patients with negative lymph nodes have evidence of bone metastasis. At five years, 11% of patients have evidence of local recurrence only; 19%, distant metastasis only; and 32%, both local recurrence and distant metastasis. Five-year survival without stratification relative to lymph node involvement is 100% (16/16) for stage B1, 88% (23/26) for stage B2, 66% (6/10) for stage B3, 33% (2/6) for stage C1, 53% (17/32) for stage C2, and 1/1 for stage C3, but endocrine therapy has presumably contributed to such survival in those patients developing intractable local recurrence and/or symptomatic distant metastasis within the five-year follow-up.     

Targeting epitopes in prostate-specific membrane antigen for antibody therapy of prostate cancer

Prostate-specific membrane antigen (PSMA) is a target for immunotherapy of prostate cancer. It has been shown that antibodies against PSMA inhibited the in vivo growth of LNCaP tumor. In the present study, monoclonal antibodies against four epitopes in PSMA were raised. MAb 24.4E6 (IgG1), specific for the epitope (residues 638-657) in PSMA, significantly reduced the growth rate of established LNCaP tumor in SCID mice. Mouse IgG was detected in the tumor of mice treated with 24.4E6, but not with an unrelated MAb. These results suggest that this epitope may be the main target in PSMA for antibody therapy of prostate cancer.     

Adenovirus p16 gene therapy for prostate cancer

Surgery, radiation, or hormone deprivation alone does not adequately affect local control of clinical or pathologic stage T3 prostate cancer. Lack of local cancer control ultimately leads to a higher incidence of morbidity, distant metastasis, and decreased survival, with patients having disease-specific mortality exceeding 75%. Other novel therapies against this devastating and common disease are needed for the achievement of long-term local cancer control. For this purpose, therapeutic interventions should target prostate-cancer cells at the molecular and cellular level in ways not possible by current modalities of cancer treatment. Any strategy that can modify the biologic behavior of these cells may potentially have the most significant clinical impact. As prostate cancer represents an accumulation of genetic mutations that causes a prostate cell to lose the ability to control its growth, one new approach against prostate cancer may be gene therapy. Identification of key missing or mutated tumor-suppressor genes that, when replaced, may inhibit or destroy prostate-cancer cells may have the best chance of clinical success. One such gene appears to be tumor-suppressor gene p16 (also known as MTS1, INK4A, and CDKN2). Tumor-suppressor gene p16 is an important negative cell-cycle regulator whose functional loss may significantly contribute to malignant transformation and progression. Alterations in the p16 gene and its protein expression often occur in prostate cancer. An adenoviral vector containing wild-type p16 (Adp16) had a high transduction efficiency in prostate-cancer cells both in vitro and in vivo. Moreover, prostate tumors injected with Adp16 expressed p16 and the adenoviral vector expressed the transgene for up to 14 days. Wild-type p16 inhibited prostate-cancer proliferation in vitro and markedly suppressed tumors in vivo. Pathologic evaluation of the Adp16-treated tumors showed dose-dependent necrosis and fibrosis. Although the mechanism of p16 inhibition in cancer remains to be elucidated, senescence and apoptosis may both be important; however, the data suggest that p16-induced growth inhibition can function independently of the retinoblastoma gene product.     

Targeting autoimmune diabetes with gene therapy.

The autoimmune nature of insulin-dependent, or type 1, diabetes targets the beta-cells of the pancreas for destruction and results in a lifelong commitment to insulin replacement therapy. Although the number of formulations and dosing of insulin have become more sophisticated and more efficient in recent years, insulin therapy alone is unable to prevent nephropathy, retinopathy, or vascular and heart disease, which still occur in a large number of patients. Different approaches have been attempted to eliminate the requirement of exogenous insulin administration. Historically, these have included pancreatic and islet transplants, which were later combined with treatments intended to halt the destructive process directed against the islets. Despite significant advances made in all of these areas, each approach faces a hostile immunological response that frequently ends with the loss of the islets. Gene therapy-based approaches add a new dimension to the efforts aimed at specifically blocking the immunological attack against the islets in genetically at-risk individuals (autoimmunity) or the immunological response against transplanted allogeneic islets (rejection). This new technology may have an important role in the therapy and cure of type 1 diabetes.     

Decreased gene expression of steroid 5 alpha-reductase 2 in human prostate cancer: implications for finasteride therapy of prostate carcinoma

BACKGROUND: Steroid 5alpha-reductase 2 (SRD5A2) catalyzes the conversion of testosterone to the more potent androgen, DHT, in the prostate. The therapeutic influence of SRD5A2 inhibitor finasteride on prostate cancer is currently unknown. The direction and extent of changes in SRD5A2 expression in disease tissues is a relevant issue in this regard. METHODS: The expression differences of SRD5A2 in tissues representative of normal, benign, and malignant growth in the human prostate were examined in parallel by comparative analysis of relevant microarray gene expression data. Semiquantitative RT-PCR was used to further verify the gene expression differences of SRD5A2. RESULTS: Consistently decreased expression of SRD5A2 was observed in 25 prostate cancer samples when compared to 25 matched normal samples and nine BPH samples. Expression differences among these samples for six other genes were presented in parallel as indicators of the direction and extent of expression changes. These additional genes include SRD5A1, Hepsin (overexpressed in prostate cancer), AMACR (overexpressed in prostate cancer), Keratin 8 (epithelial marker), smooth muscle actin (stromal marker), Nell2 (overexpressed in BPH). Semiquantitative RT-PCR verified the expression differences for SRD5A2 in six normal, six BPH, and six prostate cancer samples. CONCLUSIONS: Results from this study, combined with those from previous studies, indicate an association of prostate cancer with reduced 5alpha-reductase enzymatic activity as a result of remarkably decreased expression of the SRD5A2 gene. The implications of this study for finasteride therapy of prostate cancer are discussed.