Sadaaki Sakamoto

Autocrine expression of neurotrophins and their receptors in prostate cancer

Abstract Previously, it has been demonstrated that the neurotrophins and their receptors are present in human prostate tissue, but neither their functional role nor localization is clearly understood. We studied the expression of neurotrophins and their receptors in prostate cancer. Between 1990 and 1999, 48 prostate cancer specimens were obtained from patients undergoing radical prostatectomy, of whom 25 received neoadjuvant hormonal therapy (NHT) and 23 were untreated. The specimens were analyzed immunohistochemically for neurotrophins (nerve growth factor, brain derived neurotrophic factor, neurotrophin 3, neurotrophin 4/5) and their receptors (TrkA, TrkB, TrkC, p75NTR). Immunohistochemical studies revealed that both benign and malignant prostate gland epithelial cells expressed the neurotrophins and their receptors to various degrees, but no obvious immunopositive reaction was observed in stromal cells. In benign epithelial cells, the neurotrophins were localized to secretory cells and the receptors were localized to basal cells. The neurotrophins, TrkA and TrkC were expressed to a similar extent in prostate cancer specimens obtained from patients both with and without NHT. In contrast, the expression of TrkB was down‐regulated and the expression of p75NTR was up‐regulated in prostate cancer after hormonal therapy. These findings suggest that neurotrophins are secreted by prostate cancer cells in an autocrine fashion. Neurotrophins may be involved, through their receptors, in the escape mechanism from cell death after androgen depletion found in prostate cancer.

Fungus ball formation of aspergillus in the bladder. an unusual case report.

An unusual case of fungus ball formation of Aspergillus in the bladder without any evidence of disseminated and renal aspergillosis is presented. A 49-year-old man whose chief complaint was progressively worsening dysuria after a stomach operation was admitted. Cystoscopy revealed many ball-like masses on the retrotrigone and left wall. Histological studies showed that these masses were composed of many Aspergilli. The uniqueness of the case and the route of infection are discussed.

Up-titration of vardenafil dose from 10 mg to 20 mg improved erectile function in men with spinal cord injury

Aim: Vardenafil is a highly selective phosphodiesterase type‐5 inhibitor for the treatment of erectile dysfunction (ED). Efficacy of vardenafil has been demonstrated in various ED populations, but that in Japanese patients with spinal cord injury (SCI) has not been assessed.

Mechanism of Accumulation of the Antitumor Protein Antibiotic Neocarzinostatin in Bladder Tissue: Intravenous Administration, Urinary Excretion, and Absorption into Bladder Tissue

Some aspects of the absorption, distribution, and excretion of neocarzinostatin (NCS), a proteinous antitumor antibiotic, were studied in rabbits. NCS was given intravenously (i.v.) via the auricular vein, or [14C]NCS was instilled directly into the cavity of the bladder by tubing. In both groups, ureterostomy was performed, so that the drug excreted in the urine did not pass through the bladder. The results showed extremely rapid renal clearance; namely, two-thirds of the total recovered was excreted in the first 5 min. It was also shown that drug infused into the bladder cavity could be recovered in urine from the ureterostomized ureter. Also, the level of biological activity of NCS in bladder tissues after i.v. administration is significantly lower when ureterostomy is performed. Thus, evidence is presented for the absorption of NCS into bladder tissue from the lumen of the bladder. The high levels of NCS in bladder tissue are due to this effect as well as to accumulation via the iliac artery. These data should encourage further trials of NCS in bladder cancer. A study of urine containing NCS derived from i.v. administration showed an increase in antibacterial activity upon incubation, followed by a decrease. These effects are probably due to proteolysis, as shown by the appearance of a low-molecular-weight fragment and by the absence of such an increase in the presence of inhibitors of proteolysis.

Chemotherapy for bladder cancer with neocarzinostatin: Evaluation of systemic administration☆

Abstract Thirty patients with newly diagnosed bladder cancer were treated with i.v. neocarzinostatin. In 2 patients (6.7%) , the tumors disappeared completely. In 16 patients (53.3%) , a reduction to less than half of the initial size of the tumor was observed. In another 5 patients (16.7%) , the tumor was moderately reduced in size. In 6 patients (20%) , no effect was observed cystoscopically. Tumor growth was seen in 1 patient (3.3%) . Anorexia, general fatigue, slight weight loss and leukopenia appeared in most patients. Slight increase of S-GOT level was detected in 3 patients. However, these side effects were reversible and disappeared with the interruption of chemotherapy. All patients underwent transurethral resection after chemotherapy. Up to this date, although the periods of observation after treatment were 12–46 months, 5 recurrences (16.7%) have occurred. The recurrence rate was 3.3% (130) within 6 months , 6.7% (230) within 1 yr and 26.3% (519) within 2 yr . These results suggest that neocarzinostatin may be of value in treatment of bladder cancer.

An uptake of fluorescein isothiocyanate labeled neocarzinostatin into the cancer and normal cells

An uptake of fluorescein isothiocyanate labeled neocarzinostatin into normal and cancerous epithelial cells from bladder was investigated. Results showed that neocarzinostatin traversed the cell membrane into cytosol and nuclei, and it appeared to have a preferential cytotoxicity for the cancer cell.

Evaluation of cellular fluidity of peripheral blood lymphocytes from patients with urogenital cancers by a fluorescence polarization technique: PHA response and prognosis

Cellular fluidity of peripheral blood lymphocytes of 28 healthy donors, 24 patients with non-malignant urogenital diseases and 61 patients with urogenital cancers was measured after stimulation of phytohaemagglutinin (PHA) by a fluorescence polarization (P) method described by Cercek and Cercek and modified by us. P-values of lymphocytes without stimulation in each group were almost the same. The lymphocytes from healthy donors or patients with non-malignant diseases responded to PHA to a much greater extent than those from cancer patients. The stimulation index (SI), which quantifies the responsiveness of lymphocytes to PHA, was calculated based on the P-values. There was a significant difference in SI values between the control group, including healthy and non-malignant donors, and the malignant group (P < 0.005). In patients with malignant diseases, SI values were found to have close relations to the prognosis, stage, grade and lymphoid reaction. The present results indicate that the measurement of PHA response based on cellular fluidity of peripheral blood lymphocytes may be useful in diagnostic and prognostic evaluation of urogenital cancers.

A Simple Technique for Vesicourethral Anastomosis in Retropubic Radical Prostatectomy

Vesicourethral anastomosis during radical retropubic prostatectomy is often difficult. We present a new simple technique using a Nélaton catheter to aid in accurate suture placement for vesicourethral anastomosis.

A case of pseudodiphallia

A case of diphallia was presented. Roentogenographic and histological examination revealed pseudodiphallia without any other genitourinary anomalies.

Effect of Continuous Intravesical Infusion of Low-concentrated Mitomycin-C on Bladder Carcinogenesis in Rats Treated With N-butyl-N-4-hydroxybutyl-Nitrosamine

In the first experiment, histological changes of urinary bladder after long-term transvesical catheterization were evaluated in normal rats. No malignant changes of the bladder epithelium were detected in the two and four-week catheterization groups. However incidences of papilloma and papillary carcinoma developed in three of the five rats (60%) in the eight-week group. In a second experiment the therapeutic effect of continuous or intermittent administration of MMC on bladder carcinogenesis in rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was examined. MMC at a total dose of four mg. was administered for two weeks in both therapeutic groups. Continuous infusion was performed transvesically using an osmotic pump and a silicone catheter, on the basis that preliminary examination revealed the urinary delivery rate of MMC was constant for two weeks. In the intermittent group, MMC solution was instilled transurethrally with a venural catheter twice a week. The continuous infusion of low concentrated MMC reduced significantly (p less than 0.02) the incidence of tumor development in spite of extended catheterization (for eight weeks) into the bladder. However, the intermittent instillation of high concentrated MMC hardly inhibited the development of bladder tumors. We should consider the optimal concentration and time of a drug in intravesical chemotherapy based on the above findings.