Katsuyuki Kuratsukuri

“Decoy” of androgen‐responsive element induces apoptosis in LNCaP cells

In an androgen‐dependent manner, the androgen receptor (AR) binds to the androgen‐responsive element (ARE) in the regulatory region of target genes. We hypothesize that an “ARE decoy,” a double‐stranded oligonucleotide containing the same DNA sequence as ARE, can inhibit prostatic proliferation by competitive inhibition of AR transcriptional activity.

Comparative Antitumor Activity of 5-Fluorouracil and 5’-Deoxy-5-Fluorouridine in Combination with Interferon-α in Renal Cell Carcinoma Cell Lines

Objectives: Although interferon-α (IFNα) and interleukin-2 are used in the treatment of advanced renal cell carcinoma (RCC), the rate of efficacy is about 15% and not satisfactory. Therefore, a more effective treatment is being investigated. In this study, we examined the combined effects of IFNα and 5-fluorouracil (5-FU) as well as 5-deoxy-5-fluorouridine (5′-DFUR), a produrg of 5-FU, in vitro. Materials and Methods: Four RCC cell lines (OCUU1, OCUU3, OCUU4, OCUU5) were established at our laboratory from RCC patients. OS-RC-2, RCC10RGB, TUHR14TKB, TUHR4TKB, A498 and Caki-1 were obtained from a commercial source. The sensitivity of the 10 RCC cell lines to 5-FU and 5′-DFUR was evaluated using MTT assay. The IC50 value for the cytostatics was expressed as the concentration at which growth was inhibited by 50% as compared with the control value. Thymidine phosphorylase (TP), the enzyme that converts 5′-DFUR into 5-FU and 5-FU into FdUMP, was estimated by ELISA. Results: When the 10 RCC cell lines were divided into the low TP expression group and high TP expression group at 2.0 U/ml protein, TP expression was not enhanced by IFNα in all 4 cell lines in the low TP expression group. Antitumor effects were not enhanced by IFNα in 3 out of 4 cell lines for 5-FU and in all 4 cell lines for 5′-DFUR. On the other hand, in the high TP expression group, TP expression was enhanced by IFNα in 5 out of 6 cell lines, and antitumor effects were enhanced by IFNα in 5 out of 6 cell lines for 5-FU and in all 6 cell lines for 5′-DFUR. In addition, there was a significant correlation between TP expression and sensitivity to 5-FU and 5′-DFUR in all RCC cell lines. Conclusions: These results suggested that TP may be useful as a predictive factor in combination therapy with IFNα and 5-FU or 5′-DFUR, which may be a promising treatment for advanced RCC.

Efficacy of naftopidil for nocturia in male patients with lower urinary tract symptoms: comparison of morning and evening dosing.

To examine the difference in improvement of lower urinary tract symptoms between morning and evening dosing of α1‐blocker naftopidil.

Galectin 9 and PINCH, novel immunotherapy targets of renal cell carcinoma: a rationale to find potential tumour antigens and the resulting cytotoxic T lymphocytes induced by the derived peptides

To analyse and then generalize the mechanism by which partial or complete response is achieved among a limited number of patients with metastatic renal cell carcinoma (RCC) treated with interferon or interleukin‐2.

Renal transplantation for the hemodialysis patient with axillofemoral bypass.

Background. Axillofemoral bypass grafts are used in the treatment of aortoiliac occlusive disease caused by atherosclerosis. There have been no previous reports on renal transplantation used as treatment for chronic renal failure after an axillofemoral bypass graft being placed because of atypical coarctation of the aorta. Methods. The patient was a 47-year-old woman who had received regular hemodialysis for 15 years. Axillofemoral bypass surgery was performed because of atypical coarctation of the aorta in October 1999. Three years after surgery, she underwent renal transplantation. Results. Renal transplantation was successful, and helical computed tomography demonstrated patent graft bypass and good nephrographic effects of the renal artery. Conclusions. Even though dialysis patients with atypical coarctation of the aorta are treated with an axillofemoral bypass, it is possible for them to undergo regular renal transplantation, if part of the external or internal iliac artery is intact.

Suppressive Effects of Eviprostat, a Phytotherapeutic Agent, on Lower Urinary Tract Symptoms in Prostate Cancer Patients Treated with Brachytherapy

Objectives: Eviprostat is an anti‐oxidant, anti‐inflammatory phytotherapeutic agent that is commonly used to treat lower urinary tract symptoms (LUTS) in benign prostatic hyperplasia in Japan and Germany. Prostate cancer patients treated with brachytherapy generally have complaints of LUTS for several months postoperatively.

Expression of sphingosine-1 phosphate receptor in rat renal ischemia-reperfusion injury.

Sphingosine-1 phosphate receptor (S1PR) has come to the fore as a mediator of extracellular signaling through its interaction with G-protein-coupled receptors, which results in the induction of peripheral T-cell depletion. The mechanisms involved in renal ischemia-reperfusion (I/R) injury are complex, but appear to involve the early participation of bone marrow-derived cells, such as T lymphocytes. In this study, we investigated the expression of SIPR in a rat model of renal I/R injury. By means of a laparotomy, the right kidney was harvested and the left renal artery and vein were clamped. The kidney was reperfused after 90 min of ischemia, and rats were sacrificed at 0, 3, 6, 12 and 24 h after reperfusion. S1PR expression was analyzed by immunohistochemistry, and was observed only in endothelial cells of the normal kidneys. From 0 to 3 h after reperfusion, S1PR expression gradually became stronger in endothelial cells, reaching its peak intensity at 3 h after reperfusion. Twelve hours after reperfusion, necrosis had extended throughout the ischemic kidney, and nearly all the tubular epithelial cells had been destroyed. From 3 to 12 h after reperfusion, S1PR expression gradually weakened. At 24 h after reperfusion, levels of S1PR expression had almost reached those of the normal kidneys. In conclusion, S1PR was found to be expressed in a rat model of renal I/R injury. Several hours after achieving the maximum level of S1PR expression, the maximum level of renal I/R injury was observed. These results suggest a relationship between S1PR and renal I/R injury.

Palliative Treatment of Bone Metastases in Hormone-Refractory Prostate Cancer: Effects of Pamidronate on the Carboxyterminal Telopeptide of Type-I Collagen Level in Patients with Increasing Prostate-Specific Antigen Levels

Purpose: Bisphosphonates have been reported to be effective in reducing bone pain and skeletal-related events associated with bone metastases in hormone-refractory prostate cancer (HRPC). However, whether bone resorption is reduced primarily by these particular drugs is difficult to evaluate because patients with HRPC are usually treated with secondary or tertiary hormonal manipulations including second-line antiandrogens, high-dose diethylstilbestrol, or low-dose dexamethasone therapies, some of which may also be effective. Thus, we assessed changes in the level of the carboxyterminal telopeptide of type-I collagen (ICTP), a bone resorption marker, before and after pamidronate administration in HRPC patients with increasing prostate-specific antigen (PSA) levels. Patients and Methods: Twenty-one HRPC patients with bone metastases and increasing PSA levels were intravenously treated with pamidronate at a dose of 30 mg either every 2 or every 4 weeks. Pamidronate administration was started immediately after confirmation of three consecutive increases in the PSA level. Results: In 14 patients (67%), the ICTP levels decreased after the administration of pamidronate, despite increasing PSA levels. In 7 of these cases, the ICTP levels were lower than those recorded for 6 months or longer before the start of pamidronate administration. The characteristics of the responders were compared with those of the non-responders. Conclusion: In 67% of the HRPC patients with increasing PSA levels, pamidronate reduced the accelerated turnover of bone metabolism caused by metastases of prostate cancer.

A case of primary extragonadal seminoma arising in the perineum.

We report the first case of primary extragonadal seminoma arising in the perineum. A 34-year-old-man presented with a 2-cm painless mass in the perineum. He underwent surgical resection, and histology showed poorly differentiated adenocarcinoma. Three months later, local recurrence occurred. Whole evaluation including ultrasound and MRI of the testes were normal, so he underwent surgical wide excision, and pathology showed the tumor was pure seminoma. He received two courses of bleomycin, etoposide and cisplatin (BEP) therapy, and there has been no evidence of recurrence for 1 month.

Xanthogranulomatous pyelonephritis with acquired cystic disease of the kidney in a haemodialysis patient.

SUMMARY:  A 54‐year‐old‐female patient who had received regular haemodialysis therapy for 12 years was referred to our hospital for evaluation of a left renal mass. Imaging examinations revealed acquired cystic disease of the kidney (ACDK) and a tumour‐like lesion in the left kidney. Because of the preoperative diagnosis of the left renal cell carcinoma, the patient underwent a left nephrectomy. Pathological examination revealed xanthogranulomatous pyelonephritis. It was difficult to distinguish xanthogranulomatous pyelonephritis from renal cell carcinoma in our case, because it is very rare for xanthogranulomatous pyelonephritis to occur in ACDK.