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Biomedical subjects

Y Gunji

Publications and source records attributed to Y Gunji.

85 records · Page 5Linked to original sources

Randomly controlled study of chemotherapy versus chemoimmunotherapy in postoperative gastric cancer patients.

From September 1979 through March 1981, a total of 302 patients with gastric cancer and undergoing gastrectomy at the Department of Surgery at Chiba University Hospital and its 14 affiliated hospitals was studied for clinical effectiveness of immunotherapy with Nocardia rubra cell wall skeleton. The patients were stratified by gross stage of cancer and degree of operative curability. They were then assigned randomly to either chemotherapy group or chemotherapy plus immunotherapy group. Immunotherapy used was intradermal injection of 400 micrograms of N. rubra cell wall skeleton which was given weekly for the first month and monthly thereafter. After the specimen was examined microscopically, the patients were classified by histological stage of cancer and radicality of surgical intervention into curative or noncurative groups. The patients were surveyed for survival period in December 1981. The postoperative survival rate was compared in patients of histologically curative or noncurative resection cases between the two treatment groups. No statistical difference was detected between the groups in age, sex, or operative procedures that might influence the patient's survival. As a result, statistical intergroup difference in survival rates was not seen in patients of the curative group, probably due to a short observation period. However, the intergroup difference in survival rates was statistically significant in patients of the noncurative group (p less than 0.01). These results indicate the adjunctive effect of N. rubra cell wall skeleton as an immunotherapeutic agent in patients undergoing gastrectomy for gastric cancer.

Adult↗

P300 as indicator of effects of prophylactic cranial radiation.

In order to assess the late adverse effects of cranial radiation on the central nervous system, 33 children with acute lymphocytic leukemia were examined through event-related potential P300, brain response analysis. P300 latency was significantly prolonged in children who received both prophylactic cranial radiation and intrathecal methotrexate. Although a longitudinal study is necessary, we believe that P300 is useful in the assessment of the adverse effects of cranial radiation in children with acute lymphocytic leukemia.

Acoustic Stimulation↗

Antitumor effect of murine colon carcinoma cells retrovirally transduced with interleukin-4 and granulocyte macrophage-colony stimulating factor genes.

We have investigated the antitumor effect of murine colon carcinoma cells developed to produce cytokines. Retrovirally transduced cells were inoculated into syngeneic mice, and their survivals were examined. Inoculation of interleukin-4 (IL-4)- or granulocyte macrophage-colony stimulating factor (GM-CSF)-producing cells alone did not affect the survival of the mice. In the tumors derived from an admixture of IL-4 and GM-CSF producers, however, regression developed spontaneously, and prolonged survival of the challenged mice was consequently observed. Histological examination revealed predominant infiltration of neutrophils around the tumor of a mixed population of IL-4 and GM-CSF producers.

Animals↗

Lymph node metastasis with adenocarcinoma of the gastric cardia: clinicopathological analysis and indication for D1 dissection.

PURPOSE: To establish the indications for proximal resection with dissection of perigastric lymph nodes in order to treat adenocarcinoma of the gastric cardia. METHODS: We analyzed the clinicopathological features of 110 resected adenocarcinomas of the gastric cardia with respect to the appropriate operative method and extent of lymphadenectomy for treatment. RESULTS: Of the 110 patients, 93 underwent curative resection. The D2 group (total gastrectomy with dissection of extended regional lymph nodes) revealed higher morbidity and mortality rates compared to the D1 group (proximal resection with dissection of perigastric lymph nodes). The risk of lymph node metastasis was determined by depth of invasion, size of tumors, and gross findings of tumors. CONCLUSION: The appropriate operative method for adenocarcinoma of the gastric cardia requires: (i) tumor size less than 4 cm; and (ii) gross findings indicating a superficial type of lesion, which are recommended for proximal resection with dissection of perigastric lymph nodes.

Adenocarcinoma↗

Differential efficacy of suicide gene therapy by herpes simplex virus-thymidine kinase gene reflects the status of p53 gene in human esophageal cancer cells.

We examined the effect of herpes simplex virus-thymidine kinase gene (HSV-TK)-mediated suicide gene therapy on human esophageal cancer. Two human lines, T.Tn cells which bears truncated p53 and TE2 cells with wild-type p53, were transduced with the HSV-TK gene and tested for their sensitivities to a prodrug, ganciclovir (GCV). The transduced cells, T.Tn/TK and TE2/TK, increased in vitro sensitivity to GCV compared with that of respective wild-type cells. However, the growth suppression of T.Tn/TK tumors induced by GCV was marginal in nude mice and the tumors regrew thereafter. In contrast, the growth of TE2/TK tumors was significantly inhibited by GCV and all the tumors disappeared. The status of the p53 gene of tumor cells thereby may influence the efficacy of the HSV-TK/GCV system.

Animals↗

Copper metabolism after living donor liver transplantation for hepatic failure of Wilson's disease from a gene mutated donor.

There is a genetic problem in living donor liver transplantation, involving Wilson's disease, because the majority of donors have a kinship relationship. Recently, it was reported that the serum ceruloplasmin level is insufficient in some persons with one allele mutation. The recipient was a 13-year-old male child, and the donor was a 22-year-old woman, who was his sister by a different father. The gene analysis for Wilson's disease (ATP7B gene) was preoperatively carried out by the amplification refractory mutation system-PCR. Homozygous and heterozygous deletion of 2871 cytosine (C) were detected in the recipient and donor, respectively, in the ATP7B gene. Serum ceruloplasmin level was sufficient in the donor. The right hepatic lobe graft was transplanted to the recipient. Immediately after the liver transplantation, the copper metabolism improved to increase the serum ceruloplasmin levels up to the normal range, and decrease the urinary copper excretion. However, the serum ceruloplasmin levels gradually decreased below the normal base line, although the urine copper levels continued to be low without any clinical symptoms. We should perform gene analyses and confirm the serum ceruloplasmin levels in donors before living donor liver transplantation for Wilson's disease, to screen for their impairment of copper metabolism. After living donor liver transplantation for Wilson's disease, we should carefully follow-up the transition of serum ceruloplasmin levels in the recipient.

Adenosine Triphosphatases↗

Electroporation-mediated transfer of cytokine genes into human esophageal tumors produces anti-tumor effects in mice.

Electroporation facilitates transfer of chemicals or plasmid DNA from extracellular milieu into cells by increasing the permeability of the cell membrane. Delivery of electric pulses to established tumors thereby can improve the susceptibility of tumors to an anti-cancer agent administered. We examined whether electroporation-mediated transfer of cytokine genes into solid tumors could produce anti-tumor effects in the tumor-bearing mice. Plasmid DNA containing cytokine genes were injected into human esophageal T.Tn tumors developed in nude mice and electric pulses were then delivered. Administration of murine GM-CSF or human IL-2 gene followed by electroporation significantly suppressed the subsequent growth of T.Tn tumors and prolonged the survival of the inoculated mice. In contrast, electroporation-mediated introduction of a control gene, human GM-CSF gene, whose products do not bind to murine GM-CSF receptors, did not achieve any anti-tumor effects. In vivo transfection of cytokine genes with electroporation could be a possible therapeutic strategy for established solid tumors.

Animals↗

Study of irradiation effects on cytokine secretion from retrovirally-transduced tumor cells: a model for tumor vaccination.

We have examined the effects of irradiation on the cytokine secretion from genetically modified human esophageal and gastric carcinomas. Both cell lines were transduced retrovirally to secrete interleukin-2, interleukin-6 and granulocyte-macrophage colony-stimulating factor, respectively. The metabolism of all the transduced cells was partially inhibited by 6 Gy, and greatly inhibited by 20 Gy irradiation. Cytokine productions, however, was not affected by 6 Gy in many cases, and continued to be detected even after 60 Gy irradiation. The analysis of the dose and time of irradiation in each cytokine producer is useful for the designing of tumor vaccine using cytokine gene transfer.

Cell Division↗

Inhibition of experimental lung metastasis of murine colon carcinoma cells depends on the amount of interleukin-2 secreted from the transduced cells.

We examined the antitumor effect of low and high interleukin-2 (IL-2) producers of murine colon carcinoma cells (Colon 26) which were generated by transduction with IL-2 gene in an experimental lung metastasis model using syngeneic mice. Intravenous injection of the low IL-2 producer cells formed multiple lung metastatic foci and the survival of the mice was not different from that of the mice injected with wild-type cells. However, the mice administrated with the high producer cells survived significantly longer. Subcutaneous inoculation of the low producers, although it caused the development of local tumors at the inoculation sites in some of the mice tested, inhibited lung metastasis of wild-type cells subsequently inoculated and prolonged the survival of the mice rechallenged with Meth A cells, syngeneic fibrosarcoma cells. In contrast, inoculation of the high producers did not cause the development of subcutaneous tumors and inhibited the experimental metastasis of parental but not Meth A cells inoculated thereafter. Thus, the amount of secreted IL-2 from tumor cells differentially influences antitumor effects by inducing tumor specific and nonspecific immunity.

Animals↗

Induction of T cell dependent acquired immunity in syngeneic mice by the combined expression of interleukin-4 and granulocyte macrophage-colony stimulating factor gene in murine colon carcinoma cells.

The inoculation of cytokine-producing tumor cells into syngeneic animals can produce antitumor effects. We previously reported that injection of a mixed population of murine colon carcinoma (Colon 26) cells transduced with interleukin-4 (IL-4) gene with granulocyte macrophage-colony stimulating factor (GM-CSF) gene developed subcutaneous tumors in syngeneic mice, but these tumors thereafter regressed spontaneously (Oncology 1997;54:69-73). In this study, we found the generation of tumor-specific acquired immunity in the mice which had rejected the tumors of a mixed population of IL-4 and GM-CSF producer cells, and that the immunity was mediated by mature T cells. Moreover, local secretion of both IL-4 and GM-CSF in the vicinity of tumors was found to be crucial for this rejection. These data suggest that enhanced host defense brought about by the combined expression of IL-4 and GM-CSF genes in tumor cells is a potential therapeutic strategy.

Animals↗

Inhibition of peritoneal dissemination of murine colon carcinoma cells by administrating retrovirus harboring IL-2 gene.

We have examined the antitumor effect of the retrovirally expressed interleukin-2 (IL-2) gene in murine colon carcinoma cells (Colon 26) on a disseminated model within the peritoneal cavity. Intraperitoneal injection of IL-2-producing Colon 26, but not wild-type cells, into syngeneic mice did not cause animal death and conferred T-cell-dependent, tumor-specific protective immunity on the inoculated mice. Direct administration of the retrovirus harboring IL-2 gene into the peritoneal cavity of the mice that had intraperitoneal tumor of wild-type cells significantly prolonged the survival of the mice compared with that of the mice that received control retrovirus. In the surviving mice treated with the retrovirus we also observed the induction of protective immunity with tumor specificity. Integrated retrovirus DNA was not detected in any organs examined. Thus, in vivo IL-2 gene transfer by retrovirus enabled tumor-bearing mice to generate antitumor immunity without unnecessary retroviral insertion into host genome.

Adenocarcinoma↗