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Biomedical subjects

T Shuin

Publications and source records attributed to T Shuin.

152 records · Page 9Linked to original sources

Experimental gene therapy against subcutaneously implanted glioma with a herpes simplex virus-defective vector expressing interferon-gamma.

We investigated the feasibility of local treatment or tumor vaccination with a herpes simplex virus (HSV) type 1-defective vector. The vector was engineered to express murine interferon-gamma (IFN-gamma) for experimental gene therapy against mouse glioma Rous sarcoma virus (RSV). The murine IFN-gamma gene was driven by the cytomegalovirus promoter. The helper virus (tsk) was thermosensitive; consequently, this vector could only proliferate at 31 degrees C. A high level of murine IFN-gamma expression was confirmed in vitro and in vivo by immunohistochemistry using anti-mouse IFN-gamma monoclonal antibody. This engineered vector (dvHSV/MulFN-gamma) inhibited the proliferation of mouse glioma RSV cells in vitro, and an intratumoral (i.t.) local injection of the vector caused i.t. necrosis in vivo. The immunological effect of dvHSV/MulFN-gamma was also examined in a mouse glioma RSV cell implantation model. A subcutaneous (s.c.) implant of 1 x 10(6) mouse glioma RSV cells after treatment with dvHSV/MulFN-gamma was rejected. However, the implant after treatment with an engineered HSV-defective vector containing an antisense nucleotide sequence of the murine IFN-gamma gene was not rejected. In addition, in another group of mice in which RSV cells treated with dvHSV/MulFN-gamma were implanted into a femoral (s.c.) region and nontreated RSV cells were implanted into a contralateral femoral (s.c.) region, the implanted RSV cells were rejected. The rejection of the implanted mouse glioma RSV was blocked by anti-asialo GM1, which was known to inhibit natural killer cell activity. These results revealed that the HSV-defective vector could realize a high efficiency of transfection to glioma cells through short-time treatment, and that the IFN-gamma gene transferred to the cells had the effect of tumor vaccination, which was suggested be related to natural killer cells. In conclusion, dvHSV/MulFN-gamma may be useful for the gene therapy of malignant glioma through either i.t. local injection or a practical tumor vaccination with ex vivo gene transfer.

Animals↗

Stimulation of motility of human renal cell carcinoma by SPARC/Osteonectin/BM-40 associated with type IV collagen.

SPARC is known to be important in development and tissue remodelling. Here, we examined the effects of SPARC (secreted protein, acidic and rich in cysteine; osteonectin) derived from a rat osteosarcoma cell line on migration of renal cell carcinoma (RCC) by a Boyden chamber assay. YCR RCC cells migrated through type IV collagen-coated filters without stimuli (basal level). SPARC in the lower compartment stimulated chemotactic activity to 120% of the basal level, whereas premixing of YCR with purified SPARC before inoculation reduced their migration to 72% of the basal level. Furthermore, SPARC mixed with type IV collagen more efficiently stimulated their migration in a concentration-dependent manner (up to 170% of the basal level). This suggests that SPARC bound to type IV collagen plays a role in tumor invasion.

Animals↗

AgNOR staining of cell imprint preparations of human bladder cancer.

OBJECTIVE: To determine the clinical usefulness of argyrophilic nuclear organizer region (AgNOR) staining as applied to cell imprint preparations in bladder cancer. STUDY DESIGN: The study group consisted of 59 bladder cancers (13 grade 1, 24 grade 2 and 22 grade 3). The staining time, quality of staining, relationship of AgNOR counts to tumor grade and interobserver variations in AgNOR counts were compared in cell imprint preparations and paraffin-embedded tissue sections. Interobserver variation was compared by calculating the coefficients of variation (CVs) and correlation coefficients between two independent observers. RESULTS: Following an optimal staining time of 30 minutes, the AgNOR dots of cell imprint preparations were highly distinct. In contrast, the optimal staining time was variable, and the AgNOR dots often were observed to aggregate in paraffin-embedded tissue sections. The mean AgNOR count was significantly higher in imprint preparations. AgNOR counts from the imprint preparations showed a stronger relationship to tumor grade. The CVs of AgNOR scores in the cell imprints was significantly smaller, and the correlation coefficient was significantly greater. CONCLUSION: AgNOR staining of cell imprint preparations is a more objective method than paraffin-embedded tissue sections in human bladder cancer.

Coloring Agents↗

Combination radiotherapy of urinary bladder carcinoma with chemohyperthermia.

The combination therapy of urinary bladder cancer with radiation and hyperthermia with bleomycin was investigated. Immediately following daily external irradiation (40 Gy/4 weeks), patients were irrigated with a solution of warmed saline (intravesical temperature, 42-43 degrees C) containing 30 micrograms/ml bleomycin. Of a total of 56 patients, complete responses were observed in 25, and partial responses in 21. Among T2-T3 cases, an 84% response rate was noted in combination therapy, whereas a 56% response rate was observed after radiation alone (50-70 Gy). The side-effects of the combination therapy were limited to reversible bladder irritation, and bladder capacity could be maintained within normal limits. These results suggest that combination therapy represents an effective conservative therapy for the management of bladder cancer.

Administration, Intravesical↗

The complementary role of beta-catenin in diagnosing various subtypes of renal cell carcinomas and its up-regulation in conventional renal cell carcinomas with high nuclear grades.

beta-catenin is a kind of cytoplasmic protein involved in cell adhesion and signal transduction. This study investigated its expression in various subtypes of renal cell carcinomas (RCCs) using an immunohistochemical staining method. beta-catenin expression was assessed from staining frequency and staining score. Staining score was performed by evaluating both staining percentage and intensity. All subtypes of RCCs reacted positively with beta-catenin. However, the positive frequency and staining score in papillary and chromophobe RCCs were significantly higher than those in conventional RCCs (p < 0.05). In addition, in conventional RCCs, the positive frequency and staining score of beta-catenin showed a significant difference between nuclear grades I/II and grade III (p < 0.05). Therefore, it may indicate that beta-catenin can serve as a complementary tool to distinguish conventional RCCs from chromophobe RCCs. In conventional RCCs with low nuclear grades, beta-catenin expression is generally down-regulated, while it appears to be preserved in those with high nuclear grades.

Adult↗

The activity of topoisomerases is related to the grade and stage in human renal cell carcinoma.

Human renal cell carcinomas are quite resistant to chemotherapy. There are no good anticancer agents effective for this disease. Recently, many anticancer agents were found to act as topoisomerase inhibitors and this is closely correlated with their anticancer activity. To assess the efficacy of anticancer agents as topoisomerase inhibitors on renal cell carcinomas, we examined the activity of topoisomerase I and topoisomerase II in 60 primary human renal cell carcinomas using DNA relaxation or DNA decatenation. Significant topoisomerase I and topoisomerase II activities were observed in 39(65%) or 22(36.7%) cases respectively. Topoisomerase II positive cases were more frequent in higher grade cancers (p < 0.01). The topoisomerase I positive rate did not differ in all grades. Our results showed that human renal cell carcinomas had significant topoisomerase I or topoisomerase II activities that were targets for some topoisomerase inhibitors. Therefore these agents could be good candidates for the chemotherapy of human renal cell carcinomas.

Biomarkers, Tumor↗