Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm's potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause.

IDC-P in RP specimens was an independent risk factor for PFS and CSS and could predict clinical outcomes.

BACKGROUNDSperm cryopreservation before cancer chemotherapy is available for young patients with cancer. However, few patients bank their sperm. The authors evaluated by questionnaire the psychological impact of sperm cryopreservation.METHODSThe authors cryopreserved the sperm of 111 patients with cancer for free at the Yokohama City University (Yokohama, Japan). For the current study, questionnaires were mailed to 66 patients whose sperm had been cryopreserved. Fifty‐one patients (77.3%) with testicular carcinomas (n = 24), leukemia or malignant lymphoma (n = 19), or other cancers (n = 8) answered the questionnaire. The average age at collection and the period of sperm cryopreservation were 30.1 ± 6.0 (mean ± standard deviation) and 3.3 ± 2.2 years, respectively.RESULTSMany patients were informed of the deleterious effects of cancer chemotherapy and worried about infertility in the future. However, only half of the patients banked their sperm on their own initiative. Other patients followed their physician's instruction. Eighty percent of patients replied that sperm cryopreservation helped in the battle against cancer.Sperm banking especially was found to encourage every patient who banked sperm on their own initiative. After cancer chemotherapy, 70% of patients wanted to have a child. However, 60% of patients were worried about infertility in spite of having their sperm cryopreserved. No patients wanted to use cryopreserved sperm for fathering children if their spermatogenesis was restored. Sperm cryopreservation invigorated many patients with cancer after cancer treatments. The majority of patients recommended sperm cryopreservation to other cancer patients.CONCLUSIONSSperm cryopreservation encouraged young patients with cancer during and after cancer treatment. It should be recommended for all young patients with cancer. However, sperm cryopreservation did not eliminate their fear of infertility. Cancer 2005. © 2005 American Cancer Society.

The methylation status of 7 genes was examined in four cell lines, 36 samples of benign prostatic hyperplasia (BPH), 20 samples of prostatic intraepithelial neoplasia (PIN) and 109 samples of prostate cancer (PCa), using methylationspecific PCR (MSP): the pi-class glutathione S-transferase (GSTP1), retinoic acid receptor beta 2(RAR␤2), androgen receptor (AR), death-associated protein kinase (DAPK), tissue inhibitor of metalloproteinase-3 (TIMP-3), O 6 -methylguanine DNA methyltransferase (MGMT), and hypermethylated in cancer-1 (HIC-1). The frequencies of methylation in PCa were 88% for GSTP1, 78% for RAR␤2, 36% for DAPK, 15% for AR, 6% for TIMP-3, and 2% for MGMT, whereas the values were 11% for AR and DAPK, 6% for TIMP-3, 3% for GSTP1, and 0 for RAR␤2 and MGMT in BPH. Aberrant methylation of the GSTP1 and RAR␤2 genes was detected in 30% and 20% of PIN, respectively. Most samples of BPH and PCa were positive for HIC-1 methylation. Regarding accumulation of methylated cancerrelated genes, there were significant correlations between PCa and BPH as well as PIN and BPH. In the present study, a high frequency of aberrant promoter methylation of the GSTP1 and RAR␤2 genes was noted in PCa. Our findings suggest that methylation of cancer-related genes may be involved in carcinogenesis of the prostate.

Sirtuin 1 (SIRT1), originally identified as a longevity gene, is induced by caloric restriction, and regulates various cellular functions including DNA repair, cell survival and metabolism via the deacetylation of target proteins such as histone and p53. These functions are considered to act dualistically as preventing or facilitating cancer. This study aimed to clarify the expression and role of SIRT1 in endometrial carcinoma. Because a high-calorie diet was a well-known risk factor for endometrial carcinoma, we first hypothesized that SIRT1 might be downregulated in normal endometrial glandular cells of obese women. However, no correlation was observed between the expression of SIRT1 and body mass index (BMI). In contrast, regardless of BMI, the immunohistochemical expression of SIRT1 was significantly higher in endometrial carcinoma (108 cases) than in normal endometria (60 cases) (Po0.05), and its overexpression was associated with a shorter survival (Po0.05). Our experiments in vivo revealed that SIRT1 accelerated the proliferation of endometrial carcinoma cell lines (HHUA, HEC151, and HEC1B). SIRT1 overexpression significantly enhanced the resistance for cisplatin and paclitaxel in HHUA cells. Although p53 is an important target protein for SIRT1, the selective SIRT1 inhibitor (EX527) significantly suppressed the proliferation and cisplatin resistance of three endometrial carcinoma cell lines regardless of the p53 mutation status. In addition, SIRT1 overexpression in HHUA cells accelerated tumor growth and cisplatin resistance in nude mice, and EX527 significantly suppressed the growth of tumors of HHUA and HEC1B cells. No adverse effect of EX527 was observed in these mice. In conclusion, SIRT1 is involved in the acquisition of the aggressive behavior associated with endometrial carcinoma, and the SIRT1 inhibitor, EX527, may be a useful agent for the treatment of this malignancy.