Kunito Yamanaka

Expression of endothelial nitric oxide synthase in the Sertoli cells of men with infertility of various causes

Objective To investigate how endothelial nitric oxide (eNOS) expression in the seminiferous tubules might be related to spermatogenesis, by examining eNOS expression in testicular tissue of patients infertile from various causes.

Significance of lateral biopsy specimens during transrectal ultrasound‐guided prostate biopsies in Japanese men

Objectives:  Lateral biopsies are thought to have a better cancer detection rate compared with standard sextant biopsies. This study aimed to determine whether lateral peripheral zone biopsies in Japanese men who underwent transrectal ultrasound‐guided prostate biopsies provided a significantly higher cancer detection rate than sextant biopsies.

Growth Hormone Releasing Hormone Test for Infertile Men With Spermatogenetic Maturation Arrest

PURPOSE Growth hormone has an important role in the function of the male reproductive system. We investigated infertile men with impaired growth hormone secretion. MATERIALS AND METHODS Growth hormone status was studied in 8 fertile men and 9 infertile men with azoospermia due to spermatogenetic maturation arrest. Growth hormone releasing hormone, the specific stimulatory neurohormone, was used in the growth hormone stimulation test. A dose of 100 microg. of growth hormone releasing hormone was infused intravenously and serum growth hormone concentrations were measured at 0, 15, 30, 60, 90 and 120 minutes. Serum follicle-stimulating hormone, luteinizing hormone, prolactin, testosterone and estradiol were also measured before the test. RESULTS Serum follicle-stimulating hormone concentrations were significantly increased in the azoospermic group and basal levels of growth hormone were similar to those in the control group. Serum growth hormone concentrations increased after injection of growth hormone releasing hormone and the levels of growth hormone peaked after 30 minutes in both groups. At time 30 minutes growth hormone levels had decreased significantly more in the azoospermic group than in the controls. Men with azoospermia due to spermatogenetic maturation arrest had a low response to the growth hormone releasing hormone test. CONCLUSIONS Relative growth hormone insufficiency, which may be caused by reduced reactivity to growth hormone releasing hormone in pituitary growth hormone secretory cells, is strongly related to spermatogenic dysfunction.

A GIANT RENAL CYST IN A YOUNG MAN WITH INCREASED CARBOHYDRATE ANTIGEN 19–9 IN SERUM AND CYSTIC FLUID

Simple renal cysts are uncommon in patients younger than 30 years and most are benign. However, a few cases have been reported of carcinoma in the wall of renal cysts. Carbohydrate antigen 19-9 is well known as a serum marker for various cancers of digestive system. We describe a rare case of a giant renal cyst in a young man with increased carbohydrate antigen 19-9 in the serum and cystic fluid.

Sonic hedgehog and androgen signaling in tumor and stromal compartments drives epithelial–mesenchymal transition in prostate cancer

Abstract Objective. Sonic hedgehog (Shh) signaling, androgens and epithelial–mesenchymal transition (EMT) are related to prostate cancer (PCa) progression. The aim of this study was to investigate how Shh and androgen [dihydrotestosterone (DHT)] signaling act in prostate epithelial and stromal compartments and whether this signaling pathway drives EMT and promotes PCa progression. Material and methods. LNCaP, normal prostate fibroblast (NPF) and cancer-associated prostate fibroblast (CPF) cells were studied with DHT and/or the Shh signaling inhibitor cyclopamine. Real-time reverse transcription–polymerase chain reaction (RT-PCR) was performed to evaluate the expressions of a potential Shh target gene, osteonectin (ON) and EMT-associated markers (E-cadherin, N-cadherin and vimentin). Immunohistochemical studies using PCa prostatectomy samples were performed to assess the expression levels of ON, Gli-1, androgen receptor, Shh, E-cadherin, N-cadherin and vimentin. Results. While DHT enhanced cell proliferation in CPF more than LNCaP or NPF, cyclopamine inhibited cell proliferation enhanced by DHT in CPF. Real-time RT-PCR showed whereas both Shh and DHT induced N-cadherin and vimentin, DHT also induced the expression of osteonectin in LNCaP and cyclopamine blocked these expressions in osteonectin, N-cadherin and vimentin (p = 0.0084, 0.0002 and 0.0373, respectively). Immunohistochemistry showed that high expression of stromal, but, not epithelial, ON was significantly correlated with serum prostate-specific antigen (PSA) (p = 0.031), and high expression of Gli-1 and low expression of stromal ON with PSA recurrence (p = 0.0114 and p = 0.0005, respectively). Conclusions. Shh and androgen signaling in prostate tumor and stromal compartments drives EMT, and thus may play some role in PCa progression. Cyclopamine may be one therapeutic strategy for PCa.

A novel antireflux uretero-ileal anastomosis for urinary diversion: an experimental study

Objectives To assess a new antireflux valve technique in a dog model of urinary diversion, and thus provide a reliable and easily constructed antireflux system for an ileal reservoir.

Laparoscopic adrenalectomy: Troublesome cases

Among 143 cases of laparoscopic adrenalectomy carried out from 1993 to the present, 13 patients in whom the surgical manipulation presented problems were examined. Problems occurred due to the condition of the adrenal tumors themselves in six patients, whereas problems occurred due to the operative history in four patients. There were three patients with no operative history but with strong intraperitoneal adhesion. In patients with a history of laparotomy in other fields such as open cholecystectomy, gastrectomy or colostomy, operations were possible in most patients by examining the trocar site preoperatively. Patients with strong adhesion even without a history of surgery could be handled by full separation of the adhesion during surgery. In patients with bleeding in the adrenal tumors, large adrenal tumors, or tumors impacted in the liver, methods such as changing the sequence of separation procedures were required. In patients with a history of renal subcapsular hematomas due to extracorporeal shock wave lithotripsy (ESWL), it was not possible to understand the conditions of adrenal or perinephritic adhesion in preoperative imaging diagnosis, but resection was possible by changing the order of separation procedures and by using optimal instruments and devices. As with any surgery, including open surgeries, it is necessary to obtain knowledge on how to deal with variations in laparoscopic adrenalectomy to assure safe outcomes and to always consider effective methods for coping with unexpected difficulties.

Significance of Neoadjuvant Hormonal Therapy in Radical Retropubic Prostatectomy: A Retrospective Single-Surgeon Study

Purpose The purpose of this study was to evaluate whether neo-adjuvant hormonal therapy (NHT) prior to radical retropubic prostatectomy (RRP) for prostate cancer (PCa) is beneficial in terms of surgical outcomes and for preventing or delaying biochemical recurrence via single-surgeon case series study. Materials and Methods Fifty-three men underwent RRP by a single surgeon. The patients were divided into two groups according to whether or not NHT was performed prior to RRP. The study was analyzed retrospectively. We evaluated clinical parameters, surgical parameters, and biochemical recurrence rate. Group 1 (n=34) was treated with RRP only, while Group 2 (n=19) underwent RRP along with NHT. Results There were no significant differences in clinical, operation-related and pathological factors between the two groups (p>0.05). There was also no significant difference in biochemical recurrence rate between the two groups at the last follow-up, although Group 2 tended to have a lower PCa recurrence rate than Group 1 and the initial prostate-specific antigen (PSA) level was significantly higher in Group 2 than Group 1 (p=0.0496). Conclusion The present single-surgeon case series study revealed a trend toward a lower rate of PCa recurrence in NHT+RRP treated patients compared to those treated with RRP alone, but this did not reach statistical significance, despite the fact that NHT+RRP patients exhibited higher serum PSA levels preoperatively. Prospective studies with a longer duration of observation and a greater number of patients would be helpful in evaluating NHT more definitively.

Abstract 1407: Sonic hedgehog signaling and Androgens are linked in tumor-stromal interaction through Epithelial-Mesenchymal transition (EMT) in prostate cancer progression

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Backgrounds: Sonic hedgehog (Shh) signaling is known to relate to cancer progression but the detail about how to correlate and link with another signaling is debating. The purpose of this study is to investigate the link between Shh signaling, androgens and epithelial-mesenchymal transition (EMT) in prostate tumor-stroma interaction during prostate cancer (PCa) progression. Materials and Methods: We investigated cell proliferation in LNCaP PCa cells, Normal Prostate Fibroblasts (NPF), and Cancer-associated Prostate Fibroblasts (CPF) in the presence of representative androgen, dihydrotestosterone (DHT) and/or Shh signaling inhibitor, cyclopamine (Cyc). With these stimulators or inhibitors, real time RT-PCR was performed to investigate downstream transcriptional factors of Shh signaling, Gli-1, EMT markers (E-cadherin, N-cadherin, and Vimentin), and Osteonectin (ON), a possible Shh target gene shown in our previous work. Expression levels of AR, Gli-1, Ki-67, Shh, and ON in specimens from PCa patients were measured by immunohistochemical (IHC) staining and correlated with clinical data. Results: While significant cell proliferation was induced by DHT in LNCaP, NPF, and CPF, Cyc inhibited these enhanced growths. CPF tended to react to DHT more but less to Cyc than LNCaP or NPF. RT-PCR results showed Shh induced EMT and DHT induced the expression of Gli-1, ON and EMT, and those inductions were blocked by Cyc. IHC staining showed that Stromal ON (ONstr) had significant correlation with serum PSA (p=0.031), high Gleason Scores had significant correlation with Ki-67, and PSA recurrence was related significantly to Gli-1 expression and lower expression of ONstr, suggesting PCa recurrence had a significant correlation with Shh-Gli-1 signaling. Conclusions: Shh signaling is involved in tumor-stromal interaction through a link with Androgens and EMT, and thus plays a pivotal role in PCa progression. Cyclopamine may therefore be a possible therapeutic agent for blocking PCa progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1407. doi:1538-7445.AM2012-1407

Enhancement of Chemosensitivity in Human Bladder Cancer Cells by Adenoviral-Mediated p53 Gene Transfer

BACKGROUND Drug resistance is a major problem in tumor chemotherapy, and recent studies have suggested that the differential sensitivity of cancer cells to chemotherapy is associated with different susceptibilities to undergoing apoptosis. The aim of this study was to evaluate the effects of introduction of wild-type p53 or p21WAF1/CIP1 (p21) on chemosensitivity of bladder cancer cells. MATERIALS AND METHODS The human bladder cancer cell line HT1376, which contains mutant p53 and p21 genes, was used in this study. The effects of adenoviral-mediated p53 or p21 gene transfer on sensitivity of HT1376 cells to cisplatin were analyzed both in vitro and in vivo. RESULTS The introduction of wild-type p53 gene into HT1376 markedly enhanced the sensitivity to cisplatin in vitro. Direct injection of the p53-adenoviral vector into subcutaneous HT1376 tumors established in nude mice, followed by intraperitoneally administration of cisplatin, induced massive apoptotic destruction of the tumors. In contrast, the sensitivity of HT1376 to cisplatin was not increased by the introduction of the p21 gene either in vitro or in vivo. CONCLUSIONS These findings suggest that the combined regimen of adenoviral-mediated p53 gene transfer and cisplatin may become an efficient and powerful tool for treatment of bladder cancer.