Molecular urology最新文献

Background: Androgen ablation may improve the efficacy of radiation therapy.

Patients and methods: A total of 296 patients who had either (125)I (206; 70%) or (103)Pd (90; 30%) transperineal prostate brachytherapy (no external-beam radiation) had routine transrectal ultrasound-guided needle biopsy (minimum six cores) 2 years after treatment without regard to disease status. Neoadjuvant hormonal therapy (NHT: leuprolide acetate and flutamide) was used in 115 patients (39%) for 3 months prior to and 3 months after the implant.

Results: Of the 296 patients, 30 (10%) had positive prostate biopsies. Biopsies were positive in 4 of 115 (3.5%) v 26 of 181 (14%) of those who received or had not received NHT, respectively (P = 0.002). When patients were separated into low risk (PSA < or = 10 ng/mL, stage < or = T(2a), and Gleason score < or = 6) and high risk (all others), it was seen that low-risk patients did not benefit from NHT (3.8 v 7.7% positive biopsy rate; P = 0.5) whereas high-risk patients did (3.4% v 21.1%; P = 0.003).

Conclusion: Prostate brachytherapy yields high negative biopsy rates (90%) 2 years after treatment. Neoadjuvant hormonal therapy can improve the local control rates (as determined by biopsy) in patients undergoing (125)I or (103)Pd seed implantation. These results are most significant for patients who present with PSA >10 ng/mL, stage > or = T(2b) diseases, or Gleason score > or = 7 (high-risk status).

Currently, our understanding of the mechanism(s) of radiation-induced death of prostate cancer is limited. In-depth analysis of these processes would facilitate the design of more effective treatment strategies utilizing radiation therapy. An increasingly recognized form of radiation-induced death is postmitotic apoptosis. In this process, radiation damages the tumor cell s DNA. The cell then divides prior to completing DNA repair, an event that is lethal. In order to avoid this fate, the cancer cell may attempt to halt its cell-cycle machinery temporarily to repair its DNA prior to dividing. In the treatment of prostate cancer, radiation therapy currently is being evaluated in combination with androgen deprivation (AD). However, because AD can induce growth arrest, it may reduce the effectiveness of radiation through a reduction in postmitotic apoptosis. To study this effect, we examined the effect of AD on prostate cancer radiosensitivity as it is related to cell-cycle progression. Androgen-sensitive prostate cancer cells demonstrated increased resistance to radiation when deprived of androgenic stimuli. Thus, paradoxically, AD may reduce the radiosensitivity of prostate cancer by means of cell-cycle delay, which results in a reduction in postmitotic apoptosis.

Background and purpose: Recent reports suggest that reactive oxygen species; e.g., hydrogen peroxide (H(2)O(2)), could be the primary cause of various drug-induced renal injuries. We investigated the effects of H(2)O(2) on renal cells to understand its mode of action and to explore cytoprotection from such a fatal injury.

Materials and methods: Renal proximal tubular LLC-PK(1) cells were exposed to various concentrations of H(2)O(2), and cell viability was determined at specified times. Lipid peroxidation assay and Western blot analysis of heat shock proteins (Hsp70 and Hsp90) were performed to assess the cellular effects.

Results: The dose-response study showed that H(2)O(2) > or = 100 microM was severely cytotoxic. Even a 1-h exposure was sufficient to induce >95% cell death in 24 h. Lipid peroxidation was significantly (>50%) increased, while Hsp90, but not Hsp70, was partially degraded, to an approximately 85-kDa fragment, after a 3-h H(2)O(2) exposure. However, such cytotoxic cell death was remarkably ( approximately 90%) prevented by the antioxidants pyruvate or N-acetylcysteine (NAC), and Hsp90 remained intact.

Conclusion: Hydrogen peroxide-induced renal cell death involves increased lipid peroxidation and partial degradation of Hsp90. Both pyruvate and NAC are capable of detoxifying H(2)O(2) to maintain cell viability and Hsp90 integrity. Acute renal injuries associated with oxidative stress might preventable by appropriate antioxidants.

Although the incidence and death rates for cancer of the prostate (CaP) in Taiwan have been among the lowest in the world, they have increased remarkably in recent years. Because of the very low autopsy rate in this country, prostate specimens obtained via cystoprostatectomy may provide a unique opportunity to study the incidence and status of latent cancer. From January 1992 to December 1997, 49 prostate specimens were obtained from patients with transitional-cell carcinoma of the urinary bladder (48 cases) or pelvic melanoma (one case). Patients' ages ranged from 47 to 89, with a mean age of 67.8 years. No patient had any clinical indication of CaP, as assessed by digital rectal examination. Each prostate was prepared with whole-mount transverse serial sections at 3-mm intervals from the apex to the bladder neck. The stained slides reviewed by two pathologists to evaluate the frequency and pathological status of acinar cancer lesions and high-grade prostatic intraepithelial neoplasia (PIN). Of the 49 patients evaluated, 16 (33%) had evidence of adenocarcinoma, and 24 (49%) had high-grade PIN. The incidence of unsuspected CaP in patients aged 40 to 59, 60 to 69, and >/=70 years was 25%, 32%, and 37%, respectively. The frequency of high-grade PIN in patients aged 40 to 59, 60 to 69, and >/=70 years was 25%, 42%, and 64%, respectively. The incidence of high-grade PIN in the 16 patients with unsuspected CaP was significantly higher than in the 31 patients without this early cancer (75% v 36%). Of the 16 patients with unsuspected cancer, 5 had multiple tumors (3 patients with two and 2 with multiple foci). The mean volume of the 24 tumors was 0.0786 cm(3), with a range of 0.008 to 0.393 cm(3), but only 6 tumors exceeded 0.1 cm(3) in volume (0.112, 0.112, 0.164, 0.245, 0.262, and 0.393 cm(3)). Eighty-eight percent of these early cancers were low grade (Gleason score 2-4). All unsuspected CaP were organ confined. The frequency of unsuspected CaP in Taiwanese men is relatively higher than in Chinese, as previous reported by Dr. Gu. However, the incidence of this latent cancer is comparable to that of U.S. men of the same age. These findings, together with the high incidence of high-grade PIN, suggest that the initial step in the induction of CaP in indigenous Taiwanese is similar to that in U.S. men. The lower number of reports of CaP in Taiwan might be attributable to: (1) lower volume of latent cancer in the Taiwanese compared with U.S. men; (2) underestimation of the incidence rate of CaP in Taiwan; or (3) different genetic or environmental status leading to a different progression rate.

The Wilms' tumor 1 gene (WT1) is a tumor suppressor gene whose alterations are linked to the genesis of Wilms¹ tumor. The gene is expressed in the urogenital organs and plays a key role in their development. Recent studies have shown that the WT1 gene product acts as a growth promoter of human leukemic cells. Because WT1 has been reported to be important in testicular development, we have investigated WT1 messenger RNA (mRNA) expression in testicular germ-cell tumors. Quantitative reverse transcription­polymerase chain reaction (RT-PCR) was used to examine the levels of WT1 mRNA in 34 patients with testicular germ-cell tumor, including 25 low-stage and 9 high-stage tumors. There were 23 seminomas and 11 nonseminomas. The WT1 mRNA was highly expressed in 6 of 9 high-stage lesions (67%) but only 5 of 25 low-stage cases (20%). A significant correlation was observed between the extent of WT1 mRNA expression and tumor stage (P = 0.017). There was no significant difference in WT1 mRNA expression between seminomas and nonseminomatous tumors. These results suggest that WT1 may be causal for the progression of testicular germ-cell tumors.

The treatment of residual prostate cancer after irradiation is often associated with significant morbidity and a high failure rate. Percutaneous transperineal interstitial microwave thermoablation is a minimally invasive procedure used experimentally in our institution to treat selected patients with failures of external-beam radiation therapy for prostate cancer. The aim is to ablate all residual intraprostatic cancer thermally. Patients were treated under general or epidural anesthesia with transrectal ultrasound guidance of transperineal placement of the microwave antennas. The rectum, urethra, and a developed space between the prostate and surrounding tissues were actively cooled. The minimal target temperature of the prostate was 65 degrees C for 15 min. The temperature was measured in all cases with interstitial prostatic thermosensors and in selected cases with online magnetic resonance scanning. Thirty-seven patients with apparently localized prostate cancer after failure of treatment for cure with external-beam therapy were subjected to this treatment, and 20 of these patients have at least 12 months of follow-up. The initial prostate specific antigen (PSA) concentration ranged from 0.2 to 120 ng/mL. At 12 months, 12 of 20 patients had no biochemical or histologic evidence of disease, and 11 of 14 patients with initial PSA concentration <10 ng/mL had no evidence of disease. Five of the thirty-seven patients were treated with 3 months of neoadjuvant androgen ablation because the volume of their prostates precluded adequate heating. The average volume decline was 28%, which allowed all men to be treated. Two of these patients have been followed for at lease 1 year, and neither shows evidence of recurrence. Side effects of treatment in all patients were modest. Preliminary results suggest that this treatment might be useful in selected patients as a salvage therapy after failure of radiation therapy for localized prostate cancer.

Prostate cancer survivors frequently seek natural remedies for elevated or rising PSA concentrations to forestall the necessity for more definitive modalities. PC-SPES is one of the most widely used of the complementary medicines. It consists of eight Chinese herbs, and although it contains no estrogen, it does exhibit some estrogenic effects. For this reason, UsToo was anxious to determine just how successful the product is and whether any side effects are present. A four-page survey form was designed and pretested on a dozen patients. After refinement, the form was sent to 200 PC-SPES users, mostly UsToo members, with anonymity assured. In only five cases did respondents not identify themselves. After 102 responses had been received, a compilation form was designed to simplify computer database entry of the survey results. This produced a spreadsheet of all 102 respondents' categorized answers. Final analysis followed, with emphasis on prostate specific antigen (PSA) concentrations before and after PC-SPES use, quality of life (QoL), side effects, dosage, and relation to concurrent treatment modalities. Graphs were then constructed on each respondent for study of slope data and PSA changes. Twenty respondents provided insufficient data for analysis; the remaining 82 surveys gave us a good picture of PC-SPES usage and results, as well as information on commingling of other modalities with PC-SPES. Beneficial effects were reported by 77% of the respondents, with 23% reporting more limited or marginal results. Side effects reported were breast tenderness and lowered libido, with three respondents also reporting leg edema. There were no reported cases of circulatory problems or thrombosis. Declines in PSA were reported of as much as 70 ng/mL that were sustained for as long as the respondents have been using PC-SPES, approaching 2 years in some cases. No clinically significant adverse effects were observed. For some men, PC-SPES provides an alternative to hormonal therapy; has a palliative effect when used by patients with advanced, metastatic disease; and overall has a reported 77% effectiveness, with 87% effectiveness when recommended dosages are adhered to.