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Biomedical subjects

F Koba

Publications and source records attributed to F Koba.

At least 37 records · Page 2Linked to original sources

Impaired production of interleukin-2 after surgery.

The capacity of peripheral blood mononuclear cells (PBM) to produce interleukin-2 (IL-2) was studied serially before and following operation in patients undergoing various surgical procedures. In patients who had major surgery, significant decrease in IL-2 activity was observed 1, 3 and 6 days after operation as compared to that before surgery, although there was no significant change throughout the post-operative course in patients undergoing minor surgery. IL-2 activity returned to the pre-operative level by the 8th post-operative day. However, it remained significantly depressed 8 days after surgery in patients who had undergone major surgical procedures of more increasing severity. Distribution of T cell subsets, especially OKT4 positive cells, did not differ significantly from the pre-operative value throughout the post-operative course. However, the depressed production of IL-2 3 days after surgery could be abolished when adherent cells were removed from PBM by plastic adherence procedures. These results indicated that adherent cells, but not quantitative change in T cell subsets, might be responsible for the depression of IL-2 production after surgery.

Cell Adhesion↗

A trial of adjuvant combination chemoimmunotherapy for stage III carcinoma of stomach.

A chemoimmunotherapy program designed on the basis of experimental results was administered to 27 patients with stage III carcinoma of stomach following curative resection. The treatment regimen consisted of active immunotherapy with Vibrio cholerae neuraminidase (VCN)-treated autologous tumor cells admixed with bacillus Calmette-Guérin (BCG) and chemotherapy with drugs such as cyclophosphamide (CY), mitomycin C (MMC), and 5-fluorouracil (FU) which proved to enhance the immune response when administered at optimal dose and timing. Then, it was followed by long-term administration of tegafur (FT) and immunomodulators. This treatment significantly improved survival when compared to that of 41 historical control patients treated with surgery alone (P less than 0.001). As compared to 31 control patients concurrently treated with a bolus dose of MMC followed by long-term FT and immunomodulators, survival had a tendency, but not significantly, to be improved in patients treated with this therapy (P less than 0.1). However, the survival rate at 4.5 years was significantly higher than that of control patients (P less than 0.01). These results appeared to show that this type of adjuvant combination chemoimmunotherapy may be of benefit for this group of patients with gastric carcinoma.

Adult↗

Immunodepression after surgery: impaired production of interleukin 2.

The capacity of peripheral blood mononuclear cells to produce interleukin 2 (IL 2) was studied serially before and after various surgical procedures in 34 patients. In the group of 6 patients who had minor surgery and were categorized into class 1, IL 2 activity did not differ significantly from the preoperative value, throughout the postoperative course. In the group of 14 class 2 patients who underwent major surgery, however, significant decreases in IL 2 activity were observed 1, 3 and 6 days after operation as compared to findings before surgery. Preoperative levels were reverted to by the 8th postoperative day. The remaining 14 patients underwent major and extensive surgical procedures, and were put into class 3. Here too, were also significant decreases in the activity 1, 3 and 6 days after operation. The activity remained significantly depressed 8 days after surgery, in this group of patients. These results show that depression in the production of IL 2 in postoperative surgical patients correlates relatively well with the extent of the surgical procedures.

Animals↗

Combination chemoimmunotherapy for advanced gastric carcinoma.

Eighty-nine patients with advanced gastric carcinoma were treated with a combination chemo-immunotherapy regimen that consisted of active immunotherapy with Vibrio cholerae neuraminidase (VCN) treated autologous tumor cells admixed with BCG and drugs including cyclophosphamide, mitomycin C (MMC) and 5-fluorouracil, followed by long term tegafur (FT) and immunomodulators. This treatment significantly improved survival rate of patients in Stages III, IV and unresectable or recurrent carcinoma, compared to that of historical controls. As compared to controls treated with MMC followed by long term FT and immunomodulators concurrently, survival rate of those in Stage III tended to improve (P less than 0.1) and survival rate at 4.5 years in Stage III was significantly higher (p less than 0.01), although it was not improved in Stage IV. In patients with unresectable or recurrent tumor, survival time was not significantly lengthened with this therapy when compared with that in patients given BCG alone in the same treatment schedule (CCI-BCG group). However, none of 19 patients in CCI-BCG group survived more than 15 months, although 4 of 28 patients receiving this therapy survived. These results suggest that this combination chemo-immunotherapy is effective for a selected group of patients with advanced gastric carcinoma.

Adjuvants, Immunologic↗

Depression of the generation of cell-mediated cytotoxicity after surgery.

Effects of surgery on generation of cell-mediated cytotoxicity in mixed cell cultures were studied in patients with various carcinomas, and the results were compared to those in patients with benign lesion. Peripheral mononuclear cells were cultured with the B-lymphoblastoid cell Raji in a mixed culture and the induced cytotoxicity was measured by 51Cr release assay. In 15 patients with various carcinomas, the capacity of peripheral mononuclear cells to generate cytotoxic cells was significantly depressed 1, 3 and 6 days after surgery, as compared to findings before surgery. Preoperative levels were reverted to by the 8th postoperative day. In 8 patients with benign lesion, significant decreases in cytotoxic cell activity were observed 3 and 6 days after operation and, on the 8th postoperative day, there was a significant increase in the generated cytotoxicity, as compared to the preoperative activity. Thus, postoperative depression of the generation of cell-mediated cytotoxicity may affect the host-tumor relationship in patients with carcinoma.

Adult↗

Depression of the generation of cell-mediated cytotoxicity by suppressor cells after surgery.

The effects of surgical operation on the generation of cell-mediated cytotoxicity in mixed cell cultures were studied in patients with various carcinomas or benign lesions. Peripheral blood mononuclear cells from patients were cultured with B lymphoblastoid cell line Raji in mixed culture, and the induced cytotoxicity was measured by 51Cr release assay. In 15 patients with various carcinomas, the capacity of cells to generate cytotoxic cells was significantly depressed 1, 3 and 6 days after surgery, as compared to that before surgery. It returned to the pre-operative level by the 8th post-operative day. In eight patients with benign lesions, significant decrease in cytotoxic cell activity was observed 3 and 6 days after operation. At the 8th day, however, there was a significant increase in the generated cytotoxicity. The depressed generation of cytotoxic cells 3 days after surgery could be abrogated by removal of adherent cells from the responding cell population. This effect could be partially reconstituted by addition of separated, autologous adherent cells back to the responding non-adherent cell culture. These results demonstrate that suppressor cells, presumably monocytes, may be responsible for the depressed generation of cytotoxic cells after surgery.

Cells, Cultured↗

[NK activity, TCGF production and generation of cell-mediated cytotoxicity in spleen cells from gastric cancer patients].

The in vitro cell-mediated immune reactivities of mononuclear cells separated from spleen (SPL) of gastric cancer patients were studied and, these were compared to those of peripheral blood mononuclear cells (PBL) from the same patient. The level of NK activity of SPL was slightly higher than that of PBL (p less than 0.2, by paired t test), as measured by 51Cr release assay using K562 cells as target. TCGF preparations, generated in cultures of PHA stimulated SPL or PBL, were also compared by quantitative assay. SPL produced in significantly larger amounts than PBL (p less than 0.05). Then, the generation of cell-mediated cytotoxicity in mixed cell culture was investigated in both cell populations. When these cells were cultured with B-lymphoblastoid cell line Raji, SPL had much more capacity to generate cytotoxic cells, compared to PBL (p less than 0.1). Moreover, SPL had significantly increased ability of induce concomitant cytotoxicity during sensitizing to normal allogeneic PBL in mixed lymphocyte culture as compared to PBL (p less than 0.005). These results appeared to demonstrate that SPL from gastric cancer patients had much more increased in vitro cell-mediated reactivities, when compared to those of PBL from these patients.

Cells, Cultured↗

[Intra-arterial infusion through 2 routes in liver (primary and metastatic cancer].

Patients with unresectable liver cancer (primary and metastatic) were treated with a newly-devised arterial infusion chemotherapy using Cis-DDP and its antidote Sodium thiosulfate (STS). The patients consisted of 4 with primary hepatoma and 1 with metastatic liver cancer originated from intestinal cancer. For the purpose of reducing unfavourable side effects without changing anticancer effect, Cis-DDP was infused into hepatic artery through the catheter while STS being administered systemically. According to Koyama and Saito's criteria, 2 of 5 patients showed partial response (PR) and the others showed no change (NC). The median survival time after onset of therapy was 6.6 months ranging from 2 to 11 months in all the patients. The myelosuppression and renal toxicity, which were considered to be the most serious side effects of Cis-DDP, were not found and liver function was not affected in all the patients. However, all the patients complained of nausea and vomiting. Thus, our experience has indicated that this newly devised infusion chemotherapy is a promising method for treating unresectable liver cancer, although further efforts are necessary for reducing the gastrointestinal toxicity.

Adult↗

Effect of operation on cell-mediated immune response to autologous tumor extract in cancer patients.

Utilizing lymphocyte proliferation assay, effects of operation on cell-mediated immune response to autologous tumor extract were studied in 33 patients with gastric or colon carcinoma. To evaluate the lymphocyte proliferation response to autologous tissue extract preoperatively, the lymphocytes were left in culture for 24-30 hours before addition of the extract while 3 M KCl extract of autologous tissue was being processed. A significant level (P less than 0.001) of correlation was observed between stimulation index values to autologous tumor extract added at the initiation of culture and after a 24-30-hour period of incubation. Using this type of assay system, lymphocyte proliferation response to autologous tumor extract was examined immediately before operation and 1, 2, and 4 weeks after operation serially. Data comparing the responses of 20 patients who had curative resection and 13 patients who underwent noncurative resection appeared to fall into three categories in each group. The clinical courses of these patients in each category might clarify the significance of changes in the response following operation.

Colonic Neoplasms↗

Indirect macrophage migration inhibition response to 3-M KCl extract of gastric carcinoma.

With the use of indirect macrophage migration inhibition (MMI) test, the MMI response to 3-M KCl extract from gastric carcinoma or adjacent normal tissue was studied in patients with gastric carcinoma, in patients with other types of carcinoma, and in normal controls. The migration index (MI) of less than 75, which was 2 SD below the mean MI of normal controls, was considered positive. Twelve (23%) of 52 patients with gastric carcinoma showed positive response to autologous tumor extract, whereas only 2 (6%) of 35 patients responded to autologous normal tissue extract (P less than 0.03). Positive response to allogeneic gastric carcinoma extract occurred in 4 (9%) of 47 patients with gastric carcinoma and in none of 25 patients with other types of carcinoma. None of 39 patients with gastric carcinoma and 19 patients with nongastric carcinoma responded to allogeneic normal tissue extract. These results appeared to show a lower degree of sensitivity but a relatively higher degree of specificity in the indirect MMI test, as compared to those in the direct leukocyte migration inhibition test, for detection of the cell-mediated immune response to tumor-associated antigens in patients with gastric carcinoma.

Cell Migration Inhibition↗

Sequential combination chemoimmunotherapy for various malignant tumors: clinical and laboratory results.

A chemoimmunotherapy program designed on the bases of the results of animal experiments was designed for 139 patients with various advanced malignant tumors. The treatment regimen consisted of cyclophosphamide (CY) 200 mg intravenously on day 1, Vibrio cholerae neuraminidase (VCN) treated autologous tumor cells admixed with BCG 5 to 10 mg intradermally on day 4 and mitomycin C (MMC) 10 to 16 mg and 5-fluorouracil (FU) 500 mg intravenously on day 7, of each course. Thereafter, maintenance treatment was started on day 14 with tegafur (FT) 600 mg and immunostimulants, such as OK432, PSK or levamisole. In the group of patients with gastric carcinoma, as compared to historical control patients, this treatment significantly improved survival in those with stage III disease (p less than 0.02), stage IV disease (p less than 0.05) and recurrent or unresectable tumor (p less than 0.001). Immune reactivities as measured by PPD skin test and PHA lymphocyte blastogenesis increased slightly following the therapy. After completion of the treatment, cellular immunity to autologous tumor extract could be detected in vitro by macrophage migration inhibition technique in 12 of 42 patients. The relationship of immune reactivity before or after therapy to patient survival was examined. Analysis of survival curves according to PPD skin test showed significant prolongation of survival in patients with positive reaction as compared to those with negative response following the treatment.

Adjuvants, Immunologic↗

Relationship between lymphocyte proliferation and migration inhibitory factor production in response to autologous tumor extract in cancer patients.

In forty-nine patients with various carcinomas, cell-mediated immune response to 3M KCl extract of autologous tumor was studied with the use of both lymphocyte proliferation (LP) assay and macrophage migration inhibition (MMI) assay simultaneously. There was no correlation between stimulation index in LP assay and migration index in MMI assay in these simultaneous tests. The results of this study indicate dissociation between cell proliferation and migration inhibitory factor production of lymphocytes in response to autologous tumor extract in patients with various carcinomas.

Breast Neoplasms↗