Biomedical subjects
Publications and source records attributed to T Sakita.
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We performed a randomized controlled study of postoperative adjuvant immunochemotherapy with Nocardia rubra cell wall skeleton (N-CWS) and Tegafur for gastric carcinoma between September 1979 and March 1983. A total of 309 patients were entered into this trial. Of the 309 patients, there were 98 evaluable patients in the chemotherapy group and 115 evaluable patients in the immunochemotherapy group. In both groups, Tegafur was given as chemotherapy at a daily dose of 400 to 800 mg, starting at 24-29 days after gastrectomy. In the immunochemotherapy group, 400 micrograms of N-CWS was injected i.d. within the 2nd postoperative week. It was given weekly during the first month and subsequently monthly for as long as practicable. The patients were surveyed for length of survival in March 1985. The postoperative survival rate was analyzed for all cases, and for patients with various histopathological stages of carcinoma for comparison between the two treatment groups. No statistical difference was detected between the two groups in terms of age, sex, surgical curability, or stage of carcinoma. The overall survival rate for all patients was significantly higher in the immunochemotherapy group than in the chemotherapy group (p less than 0.05). With stage III plus IV disease, 53 patients from the chemotherapy group and 61 patients from the immunochemotherapy group were included for the analysis. As a consequence, a highly significant survival rate was observed in patients with stage III plus IV carcinoma in the immunochemotherapy group (p less than 0.005) as compared to the chemotherapy group. The overall 5-year (1800 days) survival rate after surgical treatment was 60.2% for the chemotherapy group and 73.2% for the immunochemotherapy group. In patients with stage III plus IV disease, the 5-year survival rates of the two treatment groups were 28.8% and 52.4%, respectively. Accordingly, the 50% survival period of patients with stage III plus IV cancer was 1800 days or more in the immunochemotherapy group, whereas it was only 722 days in the chemotherapy group. These results emphasize the effectiveness of N-CWS as an adjuvant immunotherapeutic agent in postoperative gastric cancer patients. The main side effects of N-CWS were skin lesions in the injected sites and fever, but these were temporary and not serious.
Splenic T cells obtained from tumor-bearing mice could be cultured with T cell growth factor (TCGF) for over 12 months. The TCGF-dependent lymphoid cell line strongly inhibited cell-mediated anti-tumor immunity directed against syngeneic tumor. However, the suppression was non-specific for the given tumor. The cell line expanded with TCGF expressed a phenotypic characterization of T cells defined by monoclonal anti-Thy-1.2 antibody.
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We cultured immunosuppressor T cells from gastric cancer patients using T-cell growth factor (TCGF) prepared from human tonsil or spleen. Peripheral blood lymphocytes cultured for 3-4 weeks with TCGF strongly inhibited the lymphocyte-proliferative response to alloantigen or PHA. Quantitative fluorescence measurement for immunological analysis of phenotypic characterization of the cells was made on a FACS-IV, using monoclonal antibodies (anti Leu-I, anti Leu-2a, anti Leu-3a, anti Leu-4, anti Leu-5, anti Leu-7, anti HLA-DR) and goat anti-human immunoglobulin. Immunosuppressor T cells grown in the presence of TCGF showed phenotype Leu-1+, 2a+, 3a-, 4+, 5+, 7-, HLA-DR+, human Ig-. Culture of immunosuppressor T cells activated by tumor cell antigen in vitro was successful only when the cells derived from patients with disseminated, nonresectable type of gastric carcinoma. Our findings suggest that TCGF-dependent immunosuppressor T cells are the result of a large tumor burden; this may explain the depression of in vitro or in vivo cell-mediated immune responses frequently found in such cancer patients.
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An analysis of 17,212 lesions from 15,933 patients with early gastric cancer collected from 110 major hospitals and institutes in Japan is presented. The percentage of patients with early gastric cancer was high among persons in their 60s and 50s. The sex ratio (F/M) was 0.5 but it was higher for younger people than for old people. Regarding distribution of the types of early gastric cancer, the depressed group (Types IIc, III) accounted for 73.9% and the elevated group (Types I, IIa) accounted for 15.3%. The elevated group was more frequent in the older age group. In regard to the type and invasion, slight invasion was prominent in types IIb and IIa, while deep invasion was prominent in IIa + IIc. The metastatic rate was 18.4% for IIa + IIc, 11.8% for I and 11% for IIc. The frequency of lymph node metastasis was 4% in intramucosal cancer, 18.9% in submucosal cancer and 11.4% in total. The type in which multiple cancers were most frequent was IIb, followed by IIa. The percentage of differentiated adenocarcinoma was 91.9% in the elevated group and was found more often among the aged. Undifferentiated adenocarcinoma occurred more often among the young. The relationship between site and histology, location and invasion, location and lymph node metastasis etc. were also investigated. We believe that these results should be very useful for detection and treatment of early gastric cancer. The rate of detection of small cancer is increasing year by year. This increase can be explained by the progress and widespread application of endoscopy, which will continue to play a large role in diagnosis and treatment of gastric cancer.
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An autopsy case a 75-year-old man, with papillary adenocarcinoma of the pancreas associated with wide-spread metastasis from a malignant lymphoma is reported. We discuss the markedly lower incidence of pancreatic cancer in syncronal association with lymphoma. We applied an immunoperoxidase method (PAP) in the diffuse large-cell lymphoma to determine the immunological phenotype and found mu heavy chains and lambda light chains in the lymphoma cells. This suggests that the tumor cells were derived from B-lymphocytes.
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A combined therapy of pepleomycin (NK-613) and radiation was performed in 15 cases of esophageal and cancer. Twelve cases out of 15 were inoperable, and 3 cases were operable. NK-631 was administered by drip intravenous injection at a dose of 5 mg per day for 3 consecutive days weekly, aiming at total dose of 60-120 mg. Tumor regression rates, which were measured by planimeter on esophagogram, were 42-92% (mean 72%): two cases were more than 90%, and more than 50% in 12 cases. An average of the survival period of 15 cases was 57 weeks with 7 cases (46.7%) of 1 year survival, 2 cases (13.3%) of 2 year survival. The side effects of NK-631 observed in the present study consisted of fever 6, stomatitis 2, skin rash 2, and reversible pneumonitis 2. This study suggests that NK-631 exhibit remarkable anti-tumor effects on esophageal carcinoma, and seem to be less toxic.
The effect of complete Freund's adjuvant (CFA), which is one of the strong immunoadjuvants, on the induction of either cytotoxic or suppressor T-cells against syngeneic tumors was investigated by an in vitro assay system. CFA did not show the apparent augmenting activity in the induction of cytotoxic T-cells against syngeneic tumors when it was administered i.p. to mice receiving s.c. inoculations of mitomycin C-treated tumor cells. The treated animals failed to develop stronger resistance against the second inoculum of the same viable tumor cells. Furthermore, CFA had an effect on the induction of suppressor T-cells in tumor-bearing hosts in which suppressor T-cells had been readily activated. Suppressor T-cells developed in syngeneic tumor-bearing mice treated with CFA was tumor specific. Tumor growth was enhanced when CFA was administered to mice given s.c. inoculations of the homologous tumor.