Effects on rat testis of 1.95-GHz W-CDMA for IMT-2000 cellular phones

In recent years concern has arisen whether carrying a cellular phone near the reproductive organs such as the testes may cause dysfunction and particularly decrease in sperm development and production, and thus fertility in men. The present study was performed to investigate the effects of a 1.95 GHz electromagnetic field on testicular function in male Sprague-Dawley rats. Five week old animals were divided into 3 groups of 24 each and a 1.95-GHz wide-band code division multiple access (W-CDMA) signal, which is used for the freedom of mobile multimedia access (FOMA), was employed for whole body exposure for 5 hours per day, 7 days a week for 5 weeks (the period from the age of 5 to 10 weeks, corresponding to reproductive maturation in the rat). Whole-body average specific absorption rates (SAR) for individuals were designed to be 0.4 and 0.08 W/kg respectively. The control group received sham exposure. There were no differences in body weight gain or weights of the testis, epididymis, seminal vesicles, and prostate among the groups. The number of sperm in the testis and epididymis were not decreased in the electromagnetic field (EMF) exposed groups, and, in fact, the testicular sperm count was significantly increased with the 0.4 SAR. Abnormalities of sperm motility or morphology and the histological appearance of seminiferous tubules, including the stage of the spermatogenic cycle, were not observed. Thus, under the present exposure conditions, no testicular toxicity was evident.     

Angiosarcoma treated with radiotherapy: impact of tumor type and size on outcome

PURPOSE: Angiosarcoma is a rare and highly malignant vascular neoplasm. The purpose of this study was to elucidate the tumor characteristics and evaluate the efficacy of radiotherapy (RT) for angiosarcoma. MATERIALS AND METHODS: Thirty patients with angiosarcoma (20 males and 10 females, age range 4-89 years, median 66) who received RT from 1986 to 1999 were enrolled in the study. Twenty-four patients had angiosarcoma of the face and scalp (AFS), and 6 patients had angiosarcomas at other sites. AFS was classified into two categories (according to the macroscopic features): nodular AFS (14 patients) and endophytic AFS (10 patients). The median prescribed irradiation dose was 68 Gy. Surgery had been previously performed in 9 patients, and adjuvant immunotherapy using recombinant interleukin-2 (rIL-2) was combined during and after RT in 20 patients. Univariate analyses and calculation of survival by Kaplan-Meier methods were performed. RESULTS: Local tumor control was obtained in 17 patients (57%). However, 7 (47%) of them developed distant metastases. The median survival time for all patients was 8 months (7 months for AFS), and the 13-year overall survival rate was 25% (20% for AFS). Twenty-one patients died of angiosarcoma, with the cause of death local failure in 7 patients, distant failure in 7, and both in 7. Tumor type and size were found to be significant prognostic factors (p = 0.004 and p = 0.007, respectively), and age, total amount of rIL-2, gender, radiation dose, and surgery were not. Six patients (4 with nodular AFS and 2 with angiosarcoma in other parts) survived >2 years. No patient with endophytic AFS survived >2 years. Ten patients (33%) died of respiratory failure secondary to pulmonary metastases. High-dose rIL-2 administration suppressed the occurrence of distant metastases (p = 0.006). Two patients developed radiation dermatitis (Radiation Therapy Oncology Group Grade 4). CONCLUSION: RT, combined with complete resection or adjuvant rIL-2 immunotherapy, could be a promising treatment strategy, leading to prolonged survival in patients with angiosarcoma.     

A phase I/II trial of the oral antiangiogenic agent TSU-68 in patients with advanced hepatocellular carcinoma

Purpose

We studied the safety and effectiveness of TSU-68, an oral tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2, platelet-derived growth factor receptor and fibroblast growth factor receptor, in patients with advanced hepatocellular carcinoma (HCC).

Methods

Patients with unresectable or metastatic HCC were eligible for enrollment. In phase I, the safety, tolerability and pharmacokinetics were assessed in patients stratified based on liver function, from no cirrhosis to Child?CPugh class B. The safety and effectiveness were assessed in phase II at the dose determined in phase I.

Results

Twelve patients were enrolled in phase I. Dose-limiting toxicities were found with TSU-68 at the dose of 400?mg bid in Child?CPugh B patients, and 200?mg bid was established as the phase II dose. Phase II included 23 additional patients, and the safety and efficacy were evaluated in a total of 35 patients. One patient (2.9%) had a complete response. Two patients (5.7%) had a partial response, and 15 patients (42.8%) showed a stable disease. The median time to progression was 2.1?months, and the median overall survival was 13.1?months. Common adverse events were hypoalbuminemia, diarrhea, anorexia, abdominal pain, malaise, edema and AST/ALT elevation. The analysis of angiogenesis-related parameters suggests that serum-soluble vascular cell adhesion molecule-1 is a possible marker to show the response.

Conclusions

TSU-68 at a dose of 200?mg bid determined by stratification into liver function, showed promising preliminary efficacy with a high safety profile in patients with HCC who had been heavily pre-treated.     

Differentiation of mesenchymal stem cells and embryonic stem cells into steroidogenic cells using steroidogenic factor-1 and liver receptor homolog-1

Previously, we have demonstrated that mesenchymal stem cells could be differentiated into steroidogenic cells through steroidogenic factor-1 and 8bromo-cAMP treatment. Use of liver receptor homolog-1, another of the nuclear receptor 5A family nuclear receptors, with 8bromo-cAMP also resulted in the differentiation of human mesenchymal stem cells into steroid hormone-producing cells. The same approaches could not be applied to other undifferentiated cells such as embryonic stem cells or embryonal carcinoma cells, because the over-expression of the nuclear receptor 5A family is cytotoxic to these cells. We established embryonic stem cells carrying tetracycline-regulated steroidogenic factor-1 gene at the ROSA26 locus. The embryonic stem cells were first differentiated into a mesenchymal cell lineage by culturing on collagen IV-coated dishes and treating with pulse exposures of retinoic acid before expression of steroidogenic factor-1. Although the untreated embryonic stem cells could not be converted into steroidogenic cells by expression of steroidogenic factor-1 in the absence of leukemia inhibitory factor due to inability of the cells to survive, the differentiated cells could be successfully converted into steroidogenic cells when expression of steroidogenic factor-1 was induced. They exhibited characteristics of adrenocortical-like cells and produced a large amount of corticosterone. These results indicated that pluripotent stem cells could be differentiated into steroidogenic cells by the nuclear receptor 5A family of protein via the mesenchymal cell lineage. This approach may provide a source of cells for future gene therapy for diseases caused by steroidogenesis deficiencies.