Takuya Koie

Core 2 N-acetylglucosaminyltransferase-1 expression induces aggressive potential of testicular germ cell tumor.

We studied orchiectomy specimens from 130 patients immuhistochemically with testicular germ cell tumor (TGCT) using anti‐core 2 N‐acetylglucosaminyltransferase‐1 (C2GnT‐1) antibody. The incidence of C2GnT‐1 positivity in stage I disease (29.5%, 21/71) was significantly lower than that in higher stages (84.7%, 50/59) (P < 0.001, χ2 test). This significant difference was also found when the cases were divided into seminoma and NSGCT according to histopathological classification. Kaplan‐Meier plots and the log rank test showed that in the patients with stage I seminoma, C2GnT‐1‐positive cases had a higher risk for recurrence (P < 0.001). This was also the case with the patients with stage I NSGCT (P < 0.001). To determine whether C2GnT‐1 promotes aggressive behavior of cancer cells, a C2GnT‐1‐negative human TGCT cell line, JKT‐1, was stably transfected with a mammalian expression vector containing C2GnT‐1 cDNA. In vitro assays revealed that JKT‐1‐C2 cells are more invasive than mock transfectants, although there are no differences in proliferation activity. When orthotopically inoculated into athymic nude mice, JKT‐1‐C2 cells produced larger testicular tumors extending to the retroperitoneum with mesenteric metastasis, while mock transfectants produced small tumors without metastasis (P < 0.01, Mann‐Whitneys U‐test). When injected via the tail vein, JKT‐1‐C2 cells produced a number of metastatic lung foci. In contrast, mock transfectants produced a small number of nodules (p < 0.01, Mann‐Whitneys U‐test). These results strongly suggest that C2GnT‐1 enhances the metastatic potential of TGCT and may be a reliable biomarker for aggressive potential of TGCT.

An aggressive course of Xp11 translocation renal cell carcinoma in a 28-year-old man

Abstract:  Cases of renal cell carcinoma (RCC) associated with Xp11 translocations are rare and are reported predominantly in children. We report a case of a young man who developed an aggressive Xp11 translocation RCC. A 28‐year‐old man presented with back pain, fever and macroscopic hematuria. Computed tomography of the abdomen showed a heterogeneous mass in the left kidney. Left radical nephrectomy was performed. Hematoxylin–eosin staining revealed nested and papillary architecture, clear and eosinophilic cytoplasm and vesicles with prominent nucleoli. Immunohistochemical evaluation revealed that the tumor cells showed nuclear labeling for TFE3 protein. On the basis of these findings, the case was diagnosed as Xp11 translocation RCC. This tumor massively recurred and led to the patients death 2 years after the initial diagnosis. The utility of immunohistochemistry using antibodies against TFE3 in RCC occurring in young adults may be necessary for accurate diagnosis.

Effect of an Oral Adsorbent, AST-120, on Dialysis Initiation and Survival in Patients with Chronic Kidney Disease

The oral adsorbent AST-120 has the potential to delay dialysis initiation and improve survival of patients on dialysis. We evaluated the effect of AST-120 on dialysis initiation and its potential to improve survival in patients with chronic kidney disease. The present retrospective pair-matched study included 560 patients, grouped according to whether or not they received AST-120 before dialysis (AST-120 and non-AST-120 groups). The cumulative dialysis initiation free rate and survival rate were compared by the Kaplan-Meier method. Multivariate analysis was used to determine the impact of AST-120 on dialysis initiation. Our results showed significant differences in the 12- and 24-month dialysis initiation free rate (P < 0.001), although no significant difference was observed in the survival rate between the two groups. In conclusion, AST-120 delays dialysis initiation in chronic kidney disease (CKD) patients but has no effect on survival. AST-120 is an effective therapy for delaying the progression of CKD.

Invadopodia formation by bladder tumor cells.

A major cause of death in patients with bladder tumors is recurrence with metastasis. Bladder tumor metastasis is largely dependent upon the invasive capacity of tumor cells. Tumor cell invasion is mainly mediated by actin-rich protrusive membrane structures called invadopodia. The formation of invadopodia was observed in various types of invasive tumors such as breast cancer and melanomas. However, invadopodia formation so far has not been described in bladder tumor cells. We here report that human bladder tumor cells form functionally active invadopodia. By using a confocal laser scanning microscope, we demonstrated that invasive bladder tumor cell lines, YTS-1 and T24, with high Matrigel degradation activity form invadopodia but that noninvasive bladder tumor cell lines, RT4 and KK-47, form no detectable invadopodia. Invadopodia formed by YTS-1 cells had the ability to secrete matrix metalloproteases and degrade extracellular matrix to invade surrounding areas. Moreover, we observed that primary tumor cells obtained from patients with invasive bladder tumors also form invadopodia, validating the results from bladder tumor cell lines. Our results provide evidence that invasive human bladder tumor cells form invadopodia for tumor invasion.

Risk factors for erectile dysfunction in healthy Japanese men.

The aim of this study was to identify risk factors for erectile dysfunction (ED) in healthy men. A comprehensive risk factor investigation was carried out in a Japanese community. The subjects were 280 healthy male volunteers with an average age of 56 years (range: 20-83 years) who participated in the Iwaki Health Promotion Project in 2006. They were residents of Iwaki district, Hirosaki City, in northern Japan. The participants completed the five-item version of the International Index of Erectile Function (IIEF-5) and the International Prostate Symptom Score (I-PSS) surveys at the site of examination. We measured blood pressure and brachial-ankle pulse wave velocity (baPWV). We also measured risk factors for metabolic syndrome and sex hormones. We compared these risk factors with the IIEF-5 scores. Ninety-five participants (34%) scored 11 points or fewer on the IIEF-5 survey (severe/moderate ED), 154 (55%) scored 12-21 points (mild ED) and 31 (11%) scored 22 points or more (no ED). The prevalence of ED in the Japanese rural community was 89% (249/280). The severe/moderate ED group had significantly higher total I-PSS scores (p = 0.001), baPWV values (p < 0.001) and systolic blood pressure (p < 0.001) than the mild/no ED group. The same group had significantly lower free testosterone (p < 0.001) and dehydroepiandrosterone sulphate (p < 0.001) than the mild/no ED group. Logistic regression analysis revealed significant differences in baPWV (p = 0.003), total I-PSS (p = 0.015) and free testosterone (p = 0.003). Lower urinary tract symptoms, baPWV and free testosterone are independent risk factors for ED in healthy Japanese men.

Efficacy of SMART Stent Placement for Salvage Angioplasty in Hemodialysis Patients with Recurrent Vascular Access Stenosis

Vascular access stenosis is a major complication in hemodialysis patients. We prospectively observed 50 patients in whom 50 nitinol shape-memory alloy-recoverable technology (SMART) stents were used as salvage therapy for recurrent peripheral venous stenosis. Twenty-five stents each were deployed in native arteriovenous fistula (AVF) and synthetic arteriovenous polyurethane graft (AVG) cases. Vascular access patency rates were calculated by Kaplan-Meier analysis. The primary patency rates in AVF versus AVG at 3, 6, and 12 months were 80.3% versus 75.6%, 64.9% versus 28.3%, and 32.3% versus 18.9%, respectively. The secondary patency rates in AVF versus AVG at 3, 6, and 12 months were 88.5% versus 75.5%, 82.6% versus 61.8%, and 74.4% versus 61.8%, respectively. Although there were no statistically significant difference in patency between AVF and AVG, AVG showed poor tendency in primary and secondary patency. The usefulness of SMART stents was limited in a short period of time in hemodialysis patients with recurrent vascular access stenosis.

An Aggressive Signet Ring Cell Carcinoma of the Prostate in a Japanese Man

Signet ring cell carcinoma (SRCC) of the prostate is rare, with approximately 100 case reports to date. Here we report a very aggressive case of SRCC of the prostate in a Japanese man. The patient received estramustine, docetaxel, and carboplatin combination chemotherapy, followed by TS-1 and CPT-11 combination therapy. Unfortunately, the disease progressed, and he died of general metastatic disease treated over 16 month with systemic chemotherapy.