Molecular urology最新文献

Purpose: A Phase II clinical study contrasted the endocrinologic and biochemical efficacy of Abarelix Depot, a gonadotropin-releasing hormone (GnRH) antagonist, with luteinizing hormone releasing-hormone (LHRH) superagonists, with or without additional antiandrogens, in men with prostate cancer.

Methods: This study was open-label and treated 242 men. Abarelix Depot 100 mg was administered by intramuscular injection to 209 men, and LHRH, with or without an antiandrogen, was administered to 33 men according to the formulation used. Serum concentrations of follicle-stimulating hormone (FSH) and other hormones were measured at baseline and at specified time points for the first 85 days of the study. Median serum concentrations of FSH at baseline were similar for the two treatment groups.

Results: Men treated with LHRH superagonists, with or without an antiandrogen, had a surge in the serum concentration of FSH on day 2 before FSH concentrations started to decline. Men in the Abarelix Depot group had an immediate and sustained decrease in the serum concentration of FSH.

Conclusion: Recent data suggest that FSH may be an independent growth factor for prostate cancer. The Abarelix Depot-induced decreased in FSH may have a role in the treatment of men with endocrine- responsive disease or for those men whose disease has escaped from hormone sensitivity.

Purpose: To explore more effective treatment for hormone-refractory prostate cancer, we investigated the potential antitumor effect of beta-glucan, a polysaccharide of the Maitake mushroom, on prostatic cancer cells in vitro.

Materials and methods: Human prostate cancer PC-3 cells were treated with various concentrations of the highly purified beta-glucan preparation Grifron-D(R) (GD), and viability was determined at 24 h. Lipid peroxidation (LPO) assay and in situ hybridization (ISH) were performed to unravel the antitumor mechanism of GD.

Results: A dose-response study showed that almost complete (>95%) cell death was attained in 24 h with GD > or = 480 microg/mL. Combinations of GD in a concentration as low as 30 to 60 microg/mL with 200 microM vitamin C were as effective as GD alone at 480 microg/mL, inducing >90% cytotoxic cell death. Simultaneous use with various anticancer drugs showed little potentiation of their efficacy except for the carmustine/GD combination (approximately 90% reduction in cell viability). The significantly (twofold) elevated LPO level and positive ISH staining of GD-treated cells indicated oxidative membrane damage resulting in apoptotic cell death.

Conclusion: A bioactive beta-glucan from the Maitake mushroom has a cytotoxic effect, presumably through oxidative stress, on prostatic cancer cells in vitro, leading to apoptosis. Potentiation of GD action by vitamin C and the chemosensitizing effect of GD on carmustine may also have clinical implications. Therefore, this unique mushroom polysaccharide may have great a potential as an alternative therapeutic modality for prostate cancer.

This paper provides our institutional data with respect to the prevalence of early neoplastic changes within the prostate gland and the age and race distribution of the patients. The changes examined were prostatic intraepithelial neoplasia (PIN) and preclinical (latent) cancers. The literature on the prevalence of these early lesions among different geographic and ethnic groups is summarized, and an abbreviated review of the more common molecular alterations reported at this early phase of prostatic neoplasia is offered.

Although conventional ultrasonography has proven to be clinically useful for depicting many types of cancerous lesions, it cannot distinguish reliably between cancerous and noncancerous tissue of the prostate. Therefore, conventional transrectal ultrasonography (TRUS) is used primarily for general evaluations of the gland and for guiding biopsies based on clearly imaged anatomic features such as the capsule, seminal vesicles, and urethra. Spectrum analysis extracts ultrasound signal parameters associated with biopsy-proven tissue types, and these parameters are then classified using neural network tools such as learning vector quantization, radial basis, and multilayer perceptron algorithms. Classification of cancerous and noncancerous prostate tissue using neural networks produces receiver operating characteristic (ROC) curves of 0.87 +/- 0.04 compared with 0.64 +/- 0.04 for conventional ultrasonography. To image the prostate using these methods, parameter values are computed at each pixel location, then translated into a score for the likelihood of cancer using a look-up table generated using the best classification algorithm. The score for cancer likelihood is expressed as a gray-scale or color value, and the resulting image may be useful to guide biopsies or therapy. Changes in parameter or score values over time potentially can be used to assess progression of disease or efficacy of therapy.

Recurrence after local prostate cancer treatment detectable only by a rise in serum prostate specific antigen (PSA) is a very common problem facing clinicians. Given that the majority of these men are relatively young and otherwise healthy, treatment of PSA-only recurrence requires approaches that not only improve survival but also preserve quality of life. For radical prostatectomy patients, a PSA-only recurrence is broadly defined as persistent or rising PSA in the postoperative period. For radiation-treated patients, the 1997 American Society for Therapeutic Radiology and Oncology guidelines specify three consecutive elevations of PSA after the post-treatment nadir PSA is achieved. Traditional hormonal therapy is the mainstay of systemic treatment for PSA-only recurrence, although nontraditional approaches such as intermittent and oral-only hormonal therapy are under study.

Background: Transrectal high-intensity focused ultrasound (HIFU) is under investigation as a minimally invasive therapeutic option for elderly men with prostatic cancer.

Methods: From November 1996 to April 1999, 315 HIFU treatments with the Ablatherm (EDAP/TMS) were performed. A questionnaire including 50 theoretically possible adverse events was developed. Every patient complaint was recorded, including the physician's and patient's assessment, before and after therapy. Start date, end date, and period of every complaint were analyzed.

Results: As major adverse events after primary HIFU, there were six cases of stress incontinence grade 1. After repeat treatments with HIFU, rectourethral fistulas occurred in five patients, stress incontinence grade 1 in eight, and, after additive transurethral resection, grade 2 in one and grade 3 in two patients. Post-HIFU rectal mucosa burn decreased from 15% in 1996 to 0 within the last year. In all treatments, obstruction was avoided by suprapubic urinary diversion. Urinary tract infections (UTIs) were recorded initially in 58% of patients but later in only 8%.

Conclusion: Transrectal HIFU proved to be a secure, minimally invasive therapeutic option for elderly men to avoid hormonal ablation or to postpone its first use.

Since the first suggested use of nuclear magnetic resonance (NMR) for detecting cancer, followed by the demonstration of the feasibility of imaging based on the NMR signal in 1973, magnetic resonance imaging (MRI) has become the modality of choice for a variety of clinical applications. Subsequently, the use of NMR spectroscopy (MRS) to detect the presence of different metabolites in vivo has provided unique opportunities for obtaining physiological and biochemical information. More recently, improvements in NMR equipment (magnet, electronics, computers, gradients coils, radiofrequency coils) and pulse sequences (software) have further improved these capabilities. The distinctions between MRI and MRS have begun to blur as new techniques emerge that combine imaging and spectroscopy, generating MRS images of a variety of metabolites. This review provides a brief overview of recent developments in MRS studies pertinent to the clinical evaluation of prostate cancer. The paper has been divided into three parts: a brief qualitative theoretical section about MRS, a review of in vitro studies, and a discussion of the clinical studies of the human prostate.

Prostate-specific membrane antigen (PSMA) is a potential target in prostate cancer patients because it is very highly expressed and because it has been reported to be upregulated by androgen deprivation. This overview addresses the expression of the PSMA gene in terms of the promoter and enhancer and how that may play a role in gene therapy. We also review PSMA as a target for antibodies for imaging and treatment and the development of a novel hybrid T-cell receptor that combines the specificity of anti-PSMA antibodies with that of T-cell receptor activation when introduced into primary lymphocytes by retroviral-mediated gene transfer. We also discuss our recent findings on the expression of a PSMA-like gene and how that understanding allows specific targeting of PSMA.