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Biomedical subjects

S Arinaga

Publications and source records attributed to S Arinaga.

At least 37 records · Page 2Linked to original sources
PubMed1993

Cytotoxic cell function and phenotypic analysis of peripheral blood mononuclear cells in cancer patients treated with low-dose interleukin-2 and mitomycin C.

We previously found that the ability of peripheral blood mononuclear cells (PBM) of cancer patients to generate lymphokine-activated killer (LAK) cells became remarkably augmented after mitomycin C administration. On the basis of the clinical findings, we designed a treatment regimen comprised of 12 mg/m2 mitomycin C i.v. on day 1 and 700 U/m2 recombinant interleukin-2 (IL-2) i.v. every 12 h from day 4 through day 8. Of 25 patients with advanced carcinoma, 9 had a partial response and 3 had a minor response. Cytotoxic cell function, including natural killer activity, lymphokine-activated killer (LAK) activity, and the ability to generate LAK cells, and lymphocyte subsets in PBM was measured 1 day before and after either the first or second course of this therapy. The relationship between these parameters and the clinical antitumor response to this treatment was examined. Although the cytotoxic activities were significantly augmented after either the first or second treatment course, no positive correlation was observed between the changes in these cytotoxic activities and the clinical response to this therapy, when patients who either showed a partial response or whose disease remission was partial or minor were defined as responders. Further, phenotypic analysis showed a significant increase in CD2+, CD3+, CD4+ and CD4+Leu8- cells after the first course, and CD25+ cells after either the first or second course of this treatment. The percentages of CD2+ and CD25+ cells were significantly elevated only in responders but not in nonresponders, suggesting the increase in these subsets was related to clinical response.

Aged↗
PubMed1993

A reliable operative procedure for preparing a sufficiently nourished gastric tube for esophageal reconstruction.

We developed a reliable procedure for obtaining sufficient blood flow at the anastomotic site of the gastric tube for esophageal reconstruction. By utilizing the junction between the left gastroepiploic and short gastric vessels via the splenic hilar vascular arcade, the distal portion of the gastric tube could be sufficiently nourished. The application of this technique resulted in a complete prevention of postoperative anastomotic leakage after antesternal esophageal reconstruction.

Aged↗
PubMed1992

A trial of adjuvant chemoimmunotherapy with mitomycin C and OK-432 for stage III gastric carcinoma.

We previously found that the ability to generate cytotoxic cells induced by in vitro activation of peripheral blood mononuclear cells (PBM) with OK-432, a bacterial immunopotentiator, was markedly increased following intravenous administration of a single dose of mitomycin C (MMC) in cancer patients. On the basis of this clinical finding, we designed a treatment regimen that consisted of MMC 12 mg/m2 intravenously on day 1 and OK-432 5 Klinische Einheit (KE) intradermally on days 6, 8, and 11, when the generation of OK-432 activated killer cells had been shown to be significantly augmented. Then, it was followed by long-term tegafur. Fifteen patients with stage III gastric carcinoma who had undergone curative resection were treated with the above regimen. The survival of these patients was significantly better than that of 26 comparable stage III patients concurrently treated with MMC 12 mg/m2 alone, followed by long-term tegafur (P less than 0.01). The results indicate that OK-432 combined with MMC may be effective against stage III gastric carcinoma, when these agents are used probably in an appropriate combination.

Carcinoma↗
PubMed1992

Immunohistochemical analysis of lymphocyte subsets infiltrating gastric carcinoma after mitomycin C administration.

The intensity of lymphoid cell infiltration and distribution of lymphocyte subsets in tumors were investigated immunohistochemically on tumor tissues obtained from 11 patients with gastric carcinoma, who had been treated with mitomycin C (MMC), 12 mg/m2, i.v. 5 days before operation. The results were compared with those obtained from 24 untreated patients as controls. In the tumor tissues from pretreated patients, the intensity of lymphoid infiltration was not significantly different from that of untreated patients. However, high-grade infiltration of CD4+ cells was observed in 55% of pretreated patients, whereas only 8% of control patients exhibited the high-grade infiltration (P < 0.02). Since the CD8+ cell infiltration was not significantly altered, the ratio of CD4+ to CD8+ cells was more frequently estimated to be more than 1 in patients pretreated with MMC, as compared to untreated controls (P < 0.02). Further, CD25+ cells in pretreated tumor tissues were more predominant than those in control tumor tissues (P < 0.05). These results suggest that MMC administration induces these alterations in lymphocyte subsets in tumor tissue in patients with gastric carcinoma.

Aged↗
PubMed1992

Correlation of eosinophilia with clinical response in patients with advanced carcinoma treated with low-dose recombinant interleukin-2 and mitomycin C.

On the basis of our clinical findings that the ability of cancer patients to generate lymphokine-activated killer cells became markedly augmented after mitomycin C administration, we designed a treatment regimen comprising mitomycin C 12 mg/m2, i.v. on day 1 and recombinant interleukin-2 700 U/m2 (8000 IU/kg), i.v. every 12 h from day 4 through day 8. The treatment course was repeated at almost 7-day intervals. Altogether 33 patients with advanced carcinoma, including mainly gastrointestinal carcinoma, were treated with this regimen. Of these, 10 had a partial response (PR) and 4 had a minor response (MR). Since eosinophil counts peaked 1 day after either the first or second course of the therapy, the posttreatment values were compared to each pretreatment level, with regard to the clinical antitumor response to this treatment. When patients who showed PR were defined as responders, absolute eosinophil counts and the percentage of eosinophils in responders after both the first and second courses of the therapy were significantly greater than each pretreatment value or the posttreatment level in nonresponders. Further, these findings were almost identical, when both PR and MR were considered to be a true remission and therefore patients who exhibited PR or MR were defined as responders, although the difference between posttreatment levels of eosinophils in responders and nonresponders was not significant at the second course. These results indicate that eosinophilia induced by this treatment correlates with the clinical response to this therapy.

Aged↗
PubMed1992

Enhanced production of interleukin 1 and tumor necrosis factor by peripheral monocytes after lentinan administration in patients with gastric carcinoma.

The effect of intravenous administration of lentinan, an immunopotentiating polysaccharide, on the production of interleukin 1-alpha (IL 1-alpha), interleukin 1-beta (IL 1-beta) and tumor necrosis factor-alpha (TNF-alpha) by monocytes in peripheral blood mononuclear cells (PBM) was studied in patients with gastric carcinoma. Peripheral blood samples were obtained from 10 patients before and 3, 5 and 7 days after a single dose of 2 mg lentinan injection. The ability of monocytes in PBM to produce IL 1-alpha was significantly augmented 3 and 5 days after lentinan administration, as compared with that before treatment. IL 1-beta production was also significantly increased 3, 5 and 7 days after the drug injection. Further, the capacity to produce TNF-alpha was significantly enhanced 3, 5 and 7 days after the drug administration. Thus, it is likely that the augmentation of these cytokine's production may contribute to the antitumor action of lentinan in patients with gastric carcinoma.

Humans↗
PubMed1992

Enhanced induction of lymphokine-activated killer activity after lentinan administration in patients with gastric carcinoma.

In 15 patients with gastric carcinoma, peripheral blood mononuclear cells (PBM) were obtained serially before and 3, 5 and 7 days after lentinan administration. The generation of lymphokine-activated killer (LAK) activity, induced by in vitro activation of PBM with interleukin 2 (IL 2), was significantly augmented 5 days after a single intravenous dose of 2 mg lentinan, when compared with that before lentinan injection. Natural killer (NK) activity of PBM was also significantly enhanced 7 days after the drug injection. However, the distribution of lymphocyte subsets exhibited no significant change following lentinan administration.

Cell Separation↗
PubMed1990

Preoperative cell-mediated immune function and the prognosis of patients with gastric carcinoma.

The cell-mediated immune function of 83 patients with gastric carcinoma was assessed preoperatively and the results were compared to that of 52 patients with benign lesions. The data were subjected to an analysis in order to evaluate their prognostic significance. The abilities to induce allogeneic cytotoxicity and to produce interleukin 2 (IL2) in patients with stage IV carcinoma were significantly depressed, as compared to those in patients with benign lesions, whereas natural killer (NK) cell activity was not significantly impaired. There was no significant correlation among these immune functions. When the patients were stratified into two groups, those who had high (greater than the mean value in patients with benign lesions) and low (less than the same value) values of these immune reactivities, the survival of patients with high NK activity (greater than or equal to 43%) was significantly better, as compared to that of patients with low cytotoxicity (less than 43%). However, there was no correlation between the survival and allogeneic cytotoxicity in these patients. The high ability to produce IL2 (greater than or equal to 1.3 U/ml) correlated with the better survival in the patients, but not in the group of patients who underwent curative resection.

Cytotoxicity, Immunologic↗
PubMed1990

The effect of recombinant interleukin 2 in combination with mitomycin C on advanced cancer.

We recently discovered that the ability of cancer patients to generate lymphokine-activated killer (LAK) cells became remarkably augmented after mitomycin C (MMC) administration. Based on our clinical findings, we designed a treatment regimen comprised of MMC 12 mg/m2 given intravenously on day 1 and recombinant interleukin 2 (rIL 2) 700 U/m2 given intravenously every 12 hr from day 4 through day 8, when the generation of LAK cells had been shown to be markedly increased. Ten patients with various advanced carcinomas for which standard therapy had failed or no standard therapy was available, were treated with this regimen. Of these ten, three had a partial response and three others had a minor response. Fevers were common and anemia occurred in four patients, but nevertheless, severe toxicity was not encountered. These results indicated that rIL 2 in combination with MMC might be effective against advanced carcinoma without causing severe toxicity when these drugs are used in an appropriate combination.

Aged↗
PubMed1989

Augmentation of the generation of lymphokine-activated killer cells after a single dose of mitomycin C in cancer patients.

The effect of mitomycin C administration on the generation of cytotoxic cells, induced by in vitro activation of peripheral blood mononuclear cells (PBM) with interleukin-2, was studied in patients with various carcinomas. The ability of PBM to generate lymphokine-activated killer (LAK) cell activity against Raji cell targets was significantly augmented 5 and 7 days after a single intravenous dose of 12 mg/m2 mitomycin C, when compared to that of PBM obtained before mitomycin C injection. Further, LAK cell activity against autologous tumor cells was also significantly increased after the drug administration. The distribution of lymphocyte subsets exhibited a significant increase in the percentage of CD3+ cells after injection, with the elevation of the CD4/CD8 ratio. Furthermore, the proportion of the CD4+ Leu8+ subpopulation, which identifies inducers of suppression, was significantly reduced. Thus, the decrease in the proportion of suppressor-inducer subsets of PBM might be at least partially, responsible for the augmented generation of LAK cells after mitomycin C administration.

Antigens, Differentiation↗
PubMed1988

Cell-mediated cytotoxic activity of spleen cells from patients with gastric carcinoma.

The cell-mediated cytotoxic activities of cells from the spleens (SP cells) of patients with gastric carcinoma were assayed in comparison with the activities of peripheral blood mononuclear cells (PBM cells) from the same patients, and from patients with benign lesions. The natural killer cell (NK) activity of the SP cells and their capacity to generate allogeneic cytotoxicity in mixed lymphocyte culture (MLC) were very similar to those of the PBM cells. The cytotoxic activity of SP cells induced by alloactivation in MLC, however, was significantly higher than that of the PBM cells from the same patient as well as from patients with benign lesions. The production of interleukin 2 (IL 2) and the ability to induce cytotoxic cells after activation with IL 2 (LAK) were therefore examined. Both the ability to produce IL 2 and to generate LAK cells were shown to be significantly increased in SP cells when compared to PBM cells. These results indicate that the spleen may be a potential reservoir for the precursors of these activated killer cells in patients with gastric carcinoma. Furthermore, it may play an important role in the defence against tumors in these patients.

Antibodies, Monoclonal↗
PubMed1988

A trial of postoperative adjuvant combination chemo-immunotherapy for stage IV gastric carcinoma.

A chemo-immunotherapy program was designed on the basis of our clinical findings, which revealed that the ability to generate cell-mediated cytotoxicity was remarkably augmented after adriamycin (AM) administration in cancer patients. Twenty patients with stage IV gastric carcinoma who had undergone noncurative resections were treated with the above regimen that consisted of active immunotherapy with autologous tumor cells, in combination with 30 mg of AM, given 7 days before the immunization, followed by long-term tegafur (FT) and immunomodulators. The survival of these patients was compared to that of 3 other groups of patients, namely; 30 patients treated with another chemo-immunotherapy regimen which comprised autologous tumor cells in combination with several anticancer drugs followed by long-term FT and immunomodulators (CCI1), 17 patients treated with mitomycin C followed by long-term FT and immunomodulators (CI), and 24 patients with comparable histories (HC). The first treatment group had significantly improved survival, as compared to the HC group (p less than 0.01) and the survival tended also to be more favorable, when compared to the CCI1 group (p less than 0.2) or the CI group (p less than 0.2). Moreover, the survival rate at 9 months was significantly higher than that of either the CCI1 group (p less than 0.01) or the CI group (p less than 0.01).

Adjuvants, Immunologic↗