Restoration of IGFBP-rP1 increases radiosensitivity and chemosensitivity in hormone-refractory human prostate cancer.

We previously reported the tumor-suppressive activity of insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) through induction of apoptosis in human prostate cancer cells. The aim of this study was to investigate the effects of IGFBP-rP1 for radiosensitivity and chemosensitivity in hormone-refractory human prostate PC-3 cancer cells. Five assays were performed using PC-3 cells transfected with IGFBP-rP1 (PC-3rP1) and control cells transfected with an empty vector (PC-3N): PC-3rP1 and PC-3N were compared by clonogenic survival assay, cell cycle analysis and apoptotic assay for radiosensitivity. The number of colonies of PC-3rP1 cells significantly decreased after 4 and 8 Gy of irradiation, compared with those of PC-3N in the clonogenic survival assay. After 16 hr irradiation at 8 Gy, the percentage of apoptotic cells significantly increased in PC-3rP1 compared with PC-3N. Growth of PC-3rP1 was significantly lower than that of PC-3N after docetaxel treatment both in vitro and in vivo. These results indicate that restoration of IGFBP-rP1 to PC-3 cells increases both their radiosensitivity and chemosensitivity.

Restoration of FGF receptor type 2 enhances radiosensitivity of hormone-refractory human prostate carcinoma PC-3 cells.

BACKGROUND: This study was undertaken to investigate the radiosensitizing effects of fibroblast growth factor receptor 2IIIb (FGFR2IIIb) in androgen-independent human prostate carcinoma PC-3 cells devoid of normally resident epithelial cell FGFR2IIIb. MATERIALS AND METHODS: A clonal line of PC-3 cells expressing FGFR2IIIb was established by stable transfection. Clonogenic cell survival, apoptosis and cell cycle distribution with and without gamma-irradiation were then compared between FGFR2IIIb-expressing PC-3 cells and control cells mock-transfected with vector alone. RESULTS: Gamma-irradiation resulted in an increase of clonogenic cell death concurrent with enhanced apoptosis and cell cycle arrest in the G2/M-phase in both transfected and untransfected cells. A quantitative analysis of all three parameters indicated that cells expressing FGFR2IIIb were significantly more sensitive to irradiation than control cells. CONCLUSION: These results indicate that restoration of FGFR2IIIb to PC-3 cells enhances their sensitivity to irradiation through acceleration of apoptosis and cell cycle arrest.

Women's perception of male erectile dysfunction drugs in the general population.

OBJECTIVE: The aim of this study is to investigate trends in women's perception of male erectile dysfunction (ED) drugs in the general population. METHODS: We designed an online questionnaire survey and randomly invited an initial total of 2370 women to respond to it from a database population that included 450,000 men and women recruited through an Internet-based market research company. The 17 items of the questionnaire comprised 9 items related to socio-cultural background and 8 items related to the perception of ED drugs, ED itself, and sexual relations. RESULTS: A total of 1262 women (53.2% of those initially invited), ranging in age from 20 to 77 years, participated. Among the participants, 83.3% were aware of the existence of ED drugs, but only 12.0% showed some interest in them, 46.4% and 43.2% of the participants claimed to have an unfavorable image of ED drugs, and of men using ED drugs, respectively. Among the participants, 45.2% stated that if their partners suffered from ED at present or in the future, they would not desire their partners to use ED drugs, and 25.5% stated that they would not accept it. Multiple logistic regression analysis revealed that higher age had a negative impact on knowledge, interest and image of ED drugs, the image of men using ED drugs, and the importance of sexual relations. CONCLUSIONS: Our findings reveal that a high proportion of women have a negative perception of ED drugs and associated issues in Japan.

DNA methylation of the RIZ1 gene is associated with nuclear accumulation of p53 in prostate cancer.

The retinoblastoma protein-interacting zinc finger gene, RIZ1, is thought to be a tumor suppressor gene. RIZ1 is inactivated by mutation, deletion and DNA methylation in several human cancers. In the present study, the relationship between DNA methylation of RIZ1 and mutation of p53 was investigated in prostate cancer (PCa). In total, 47 cases of node-negative PCa (stages I-III) were analyzed. DNA methylation of the RIZ1 gene was detected in 20 (42.6%) of the 47 PCa tissues by methylation-specific polymerase chain reaction. DNA methylation of the RIZ1 gene was not associated with clinicopathological features. DNA methylation of RIZ1 tended to be present more frequently in PCa specimens with a high Gleason score (16/30, 53.3%) than in those with a low Gleason score (4/17, 23.5%); however, this tendency was not statistically significant (P = 0.0675). Nuclear accumulation of p53 was observed in four (8.5%) of 47 PCa specimens by immunostaining. All four PCa specimens with nuclear accumulation of p53 were stage III disease and showed DNA methylation of RIZ1. However, of the remaining 43 cancers without nuclear accumulation of p53, DNA methylation of RIZ1 was observed in only 16 (37.2%) specimens (P = 0.0272). Of the three PCa cell lines, only the PC3 cell line showed loss of RIZ1 mRNA due to DNA methylation, and this loss was rectified by treatment with a demethylating agent, 5-Aza-2'-deoxycytidine. These results suggest that transcriptional inactivation of RIZ1 by aberrant DNA methylation may contribute to prostate carcinogenesis. Genetic alterations are likely associated with epigenetic alterations in PCa.

Lower urinary tract symptoms and risk of prostate cancer in Japanese men.

Our aim was to investigate whether or not men with lower urinary tract symptoms are at increased risk of prostate cancer. A total of 3511 men aged 50-79 years who underwent mass screening for prostate cancer between 2002 and 2004 for the first time, and completed the International Prostate Symptom Score (IPSS) questionnaire at the time of the prostate specific antigen (PSA) test, were enrolled in the present study. All men with PSA values greater than 4.0 ng/mL were advised and encouraged to undergo transrectal systematic sextant biopsy. The number of cancers subsequently detected was compared between men with IPSS scores of 0-7 and 8-35. Of the 3511 men, 219 (6.2%) had PSA values greater than 4 ng/mL, 178 (5.1%) underwent biopsy, and 51 (1.5%) were found to have prostate cancer. Although the PSA positivity rate for men with IPSS scores of 8-35 was significantly higher than that in the 0-7 group, there were no significant intergroup differences in the cancer detection rates for biopsied men and for total screened subjects. Multivariate logistic regression analysis revealed that prostate volume was the dominant predictor for the detection of prostate cancer, followed by PSA level, but the IPSS made no significant contribution. No significant difference was noted in the IPSS scores between men with cancer and the others of the same age group. Symptomatic Japanese men are not at higher risk of prostate cancer despite their higher PSA values compared with asymptomatic men of the same age group.

Transrectal ultrasound-guided 10-core biopsy of the prostate for Japanese patients.

To determine the utility of transrectal ultrasound (TRUS)-guided 10-core prostate biopsy (sextant plus 4 far lateral cores) for Japanese patients, we compared it with the standard sextant for detection of prostate cancer. The study patients were 564 consecutive Japanese men (median age 71 years) who underwent 10-core biopsy because of PSA values of > or = 2.0 ng/ml at Hiroshima University Hospital between March 2000 and December 2004. The overall cancer detection rate for the 10-core biopsy was 42.6% (240/564), which was significantly higher than the 36.3% (205/564) for the standard sextant biopsy (P=0.0330), with a 14.6% (35/240) improvement. The 10-core biopsy also detected a significant number of additional cancers in the sub-groups of patients with PSA values of 2 to approximately 10 ng/ml (P=0.0275), a prostate volume of > 20 cc (P=0.0440), or normal findings of digital rectal examination (P=0.0304). The 10-core biopsy scheme detected 9.6% and 2.1 to approximately 8.3% more cancers than the lateral sextant (apex, lateral mid portion, and lateral base) and the probable different combinations of 8-core biopsy designs, respectively. Compared to the standard sextant biopsy, the 10-core biopsy did not detect an increased proportion of clinically insignificant cancers. There was no severe morbidity, and only 2 patients (0.4%) were briefly hospitalized due to high fever. These results show that the TRUS-guided 10-core biopsy yields a better prostate cancer detection rate than the 6-core or 8-core protocol without severe complications. Therefore, it seems to be practicable for Japanese patients.

Nonfunctional pituitary macroadenoma manifested as muscular symptoms.

A 75-year-old man with a large pituitary adenoma presented with general muscular weakness, including difficulty in rising in the morning and forceless defecation and urination, and muscular pain, numbness and atrophy in the shoulder, neck and thigh. Testosterone replacement and subsequent resection of the pituitary tumor resulted in resolution of the symptoms. The value of pituitary imaging tests for men with hypogonadotropic hypogonadism is discussed.

Impact of radical perineal prostatectomy on urinary continence and quality of life: a longitudinal study of Japanese patients.

AIM: We used self-completed questionnaires to obtain a longitudinal assessment of urinary continence and urinary, bowel, and sexual domain-related quality of life (QOL) in Japanese patients undergoing radical perineal prostatectomy (RPP). METHODS: A total of 41 Japanese patients with a median age of 69 years who underwent RPP between February 2002 and February 2004 were included in the study. We measured QOL by the University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI) and assessed urinary continence on the basis of three different definitions of continence. The International Prostate Symptom Score (I-PSS) was also included to evaluate lower urinary tract symptoms (LUTS). RESULTS: When urinary continence was de fi ned as none, one, or two protective pads per day, 100%, 73%, 94%, 97%, or 100% of the patients were continent before, and 1, 3, 6, and 12 months after, RPP, respectively. When it was de fi ned as total control or occasional dribbling, the corresponding values were 97%, 70%, 84%, 94%, and 97%. Urinary function returned to the preoperative baseline level by 6 months postoperatively and scores for urinary bother had significantly surpassed the baseline by 12 months (P = 0.043). The I-PSS was significantly improved (P = 0.014), with a mean 4.7-unit decrease. Sexual function worsened significantly after surgery, and its recovery was less favorable. No significant change was observed in scores for bowel function or bowel bother. CONCLUSIONS: The majority of patients who undergo RPP rapidly regain urinary continence and QOL within 3-6 months. RPP has a favorable impact on LUTS.

Urological retroperitoneoscopic surgery for patients with prior intra-abdominal surgery.

OBJECTIVE: To determine whether previous intra-abdominal surgery is associated with surgical outcome in patients undergoing urological retroperitoneoscopic surgery. PATIENTS AND METHODS: One hundred seventeen cases of urological retroperitoneoscopic surgery, including 78 cases of retroperitoneoscopic radical nephrectomy (RN) for localized renal tumor and 39 cases of retroperitoneoscope-assisted radical nephroureterectomy (RNU) for upper urinary tract cancer, were evaluated. Thirty (38.5%) of the 78 patients who underwent RN and 13 (33.3%) of the 39 patients who underwent RNU had a history of intra-abdominal surgery. The patients were divided into two groups: those who had undergone prior intra-abdominal surgery (OP+) and those who had not (OP-). Patients' backgrounds, degree of surgical invasiveness, and period of convalescence were compared between the OP+ and OP- groups. RESULTS: There was no significant difference between the OP+ and OP- groups in terms of background, surgical invasiveness or convalescence, except for age in the patients who had undergone RN. Complications in the studied cases were unrelated to any history of intra-abdominal surgery. CONCLUSION: Previous intra-abdominal surgery is not associated with a negative outcome of urological retroperitoneoscopic surgery in patients with localized renal tumors and those with upper urinary tract cancer.