Yoshitaka Kuwahara

Gasdermin (Gsdm) localizing to mouse Chromosome 11 is predominantly expressed in upper gastrointestinal tract but significantly suppressed in human gastric cancer cells.

Amplification of proto-oncogenes associated with their over-expression is one of the critical carcinogenic events identified in human cancer cells. In many cases of human gastric cancer, a proto-oncogene ERBB-2 is co-amplified with CAB1 genes physically linked to ERBB-2, and both genes are over-expressed. The amplified region containing ERBB-2 and CAB1 was named 17q12 amplicon from its chromosomal location. The syntenic region corresponding to the 17q12 amplicon is well conserved in mouse. In this study we isolated and characterized a novel mouse gene that locates telomeric to the mouse syntenic region. Northern blot analysis using the mouse cDNA and a cloned partial cDNA of human homolog disclosed a unique expression pattern of the genes. They are expressed predominantly in the gastrointestinal (GI) tract and in the skin at a lower level. Moreover, in the GI tract, the expression is highly restricted to the esophagus and stomach. Thus, we named the mouse gene Gasdermin (Gsdm). This is the first report of a mammalian gene whose expression is restricted to both upper GI tract and skin. Interestingly, in spite of its expression in normal stomach, no transcript was detected by Northern blot analysis in human gastric cancer cells. These data suggest that the loss of the expression of the human homolog is required for the carcinogenesis of gastric tissue and that the gene has an activity adverse to malignant transformation of cells.

Alternative mechanisms of gene amplification in human cancers.

Gene amplification is a common phenomenon in cancer. Cytogenetic analyses have indicated that breakage‐fusion‐bridge (BFB) cycles drive intrachromosomal amplification of some oncogenes in a head‐to‐head manner in human cancers. However, the complex structures of an amplified sequence found in cancers are not always explained by the BFB model. At the 17q21 locus, which is not linked to common fragile sites, we discovered a recombination hot spot harboring amplicon repeats in tandem in a head‐to‐tail orientation, with the interamplicon junctions in each cancer cell being homogeneous. These findings clearly show the presence of alternative mechanisms other than BFB cycles in oncogene amplification.

Identification of the CAB2/hCOS16 Gene Required for the Repair of DNA Double-strand Breaks on a Core Amplified Region of the 17q12 Locus in Breast and Gastric Cancers

We previously reported that CAB1 and c‐ERBB‐2 genes were found to be located in a core amplified region of the 17q12 locus, which is frequently amplified in various cancers. During identification of this core region, CAB2, a human homologue of the yeast COS16 required for the repair of DNA double‐strand breaks was cloned. Autofluorescence analysis of cells transfected with its GFP fusion protein demonstrated that CAB2 translocates into vesicles, suggesting that overexpression of CAB2 may decrease intercellular Mn2+ by accumulating it in the vesicles, in the same way as yeast COS16. This is the first report identifying all of the genes on the core amplified region of the 17q12 locus in breast and gastric cancers.

Transurethral Resection in Saline Vaporization: Evaluation of Clinical Efficacy and Prostate Volume

OBJECTIVE To assess the efficacy and safety of transurethral resection in saline vaporization for symptomatic bladder outlet obstruction and the change in prostate volume. METHODS A total of 106 patients with symptomatic bladder outlet obstruction underwent transurethral resection in saline vaporization. The effectiveness of the treatment was evaluated using the International Prostate Symptom Score (IPSS), quality of life score, urinary peak flow, and prostate volume preoperatively and at 1, 3, 6, and 12 months postoperatively. To assess the treatment effect, the patients were divided into 3 groups according to the preoperative prostate volume: group 1 (<45 cm(3), n = 40), group 2 (≥ 45 but <65 cm(3), n = 34), and group 3 (≥ 65 cm(3), n = 32). RESULTS The mean perioperative hemoglobin loss was 1.2 g/dL. The mean IPSS, quality of life score, and prostate volume decreased significantly from 24.3, 5.2, and 52.8 cm(3) to 11.1, 2.7, and 29.9 cm(3), respectively (P < .01) and the mean urinary peak flow had increased significantly from 7.3 to 15.1 (P < .01) at 1 month. Moreover, the IPSS, quality of life score, and prostate volume had significantly decreased to 8.8, 2.3, and 26.1 cm(3) at 3 months (P < .05). The investigation of groups classified by prostate size demonstrated that the IPSS in group 3 continued at a significantly lower level than that in groups 1 and 2. The prostate volume decreased gradually and resulted in 52.8% volume reduction for ≤ 12 months. No significant complications were seen; however, irritative symptoms occurred frequently (11.3%). CONCLUSION Transurethral resection in saline vaporization was a safe and effective treatment option and was more efficacious for patients with a larger prostate. The bother scores and prostate volume gradually decreased for ≤ 12 months.

Efficacy of Testosterone Treatment in Hemodialysis Patients as Assessed by Aging Males’ Symptoms Scores: A Pilot Study

Numerous reports point to the beneficial effects of testosterone replacement therapy for patients with late-onset hypogonadism (LOH) syndrome. The aim of this study was to evaluate the effect of intramuscular injection of testosterone enantholactam acid ester on Aging Males’ Symptoms (AMS) scores in hemodialysis patients with LOH. A total of 24 male patients with LOH (total AMS scores ≥27) were randomized into groups receiving intramuscular injections of either placebo or testosterone enantholactam acid ester at the dose of 250 mg for 6 months. In all, 13 and 11 participants from the active treatment and placebo groups, respectively, completed this study. An intramuscular injection of either placebo or testosterone enantholactam acid ester was given every 2 weeks. Self-administered AMS questionnaires were completed at the start, at Week 12 and at Week 24. The total AMS score was significantly more improved in the treatment group than in the placebo group (p = .049) during the 24-week period. The change in the mean of total AMS score was +1% in the placebo group and −13.2% in the treatment group. The mean somato-vegetative domain scores decreased significantly only in the treatment group, and not in the placebo group (−1.21 vs. −2.43, p = .028). Although a large-scale study is needed, testosterone treatment may be effective in male patients with hemodialysis who have poor health-related quality of life resulting from LOH.

Sufficient Volume Ablation with Photoselective Vaporization of the Prostate Delivers 5-Year Durability and Improves Symptom Relief for Larger Prostates

OBJECTIVES To assess the long-term durability of photoselective vaporization of the prostate (PVP) for symptomatic benign prostatic enlargement (BPE) or benign prostatic obstruction (BPO) and treatment efficacy for large BPE. METHODS Four hundred fifty-seven patients with symptomatic BPE underwent PVP between January 2006 and April 2009. Efficacy was evaluated with the International Prostate Symptoms Score (IPSS), Quality of Life (QOL) score, urinary peak flow (Qmax), postvoid residual volume (PVR), and prostate volume. Parameters were checked preoperatively, and at 1, 3, and 5 years postoperatively. One hundred fifty-three patients completed 5-year follow-up. To assess treatment effects, patients were divided into two groups according to the preoperative prostate volume: group A (<60 mL, n=104) and group B (>60 mL, n=49). RESULTS Mean IPSS, QOL score, Qmax, and PVR improved significantly and were maintained for 5 years with no significant differences; at year 1, prostate volume had decreased significantly from 54.0 mL to 30.6 mL (43% of volume ablation) and remained at that level until year 5. Investigations according to prostate size demonstrate that IPSS and QOL scores in group B remained at significantly lower levels, and Qmax in group B improved more than in group A. 1.1% of patients needed transurethral resection of the prostate due to BPO recurrence. CONCLUSIONS PVP is effective and provides durable results for 5 years, with sustained symptom relief and improved urinary flow rate, as well as a 43% volume reduction of prostate volume. Our data indicate PVP is more efficacious for larger prostates under sufficient volume ablation.

Photoselective vaporization of the prostate: pursuing good indications based on the results of 400 Japanese patients

Study Type – Therapy (individual cohort)

PHOTOSELECTIVE VAPORIZATION OF THE PROSTATE FOR THE TREATMENT OF BENIGN PROSTATIC HYPERPLASIA: INITIAL EXPERIENCE IN 250 JAPANESE PATIENTS

RESULTS: : In all 250 patients, PVP was performed successfully. Mean operation time was 70 minutes (range 17 to 218). No major complication occurred intraoperatively and no blood transfusions were necessary. Immediate postoperative serum sodium values were normal. At 1, 3 and 6 months after surgery mean IPSS decreased from 20.9 preoperatively to 9.6, 8.9 and 8.3, the mean QOL score improved from 5.2 to 2.4, 2.2 and 2.0, the mean Qmax (ml/s) increased from 8.4 to 16.9, 16.4 and 16.8, and the mean Vres (ml) decreased from 137 to 31, 24.5 and 31.4, respectively. Mean PSA value (ng/ml) decreased