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Biomedical subjects

T Toge

Publications and source records attributed to T Toge.

At least 199 records · Page 11Linked to original sources

Effects of intraperitoneal administration of OK-432 for patients with advanced cancer.

The effects of intraperitoneal administration of OK-432 on tumor cells in ascites, in relation to the infiltration of effector cells and on the immune responses of the host, particularly, with regard to immune suppressive mechanisms, were investigated in 25 patients with cancerous ascites. The effects of OK-432 depended on frequency of the repeated and continuous administrations through a tube placed in the peritoneum during laparotomy. Infiltrations of neutrophils and lymphocytes were observed in the ascites within a short period after the administration and monocyte infiltration followed. Disappearance of tumor cells correlated well with the infiltration of these cells. No marked changes in the proliferative responses of peripheral blood lymphocytes were noted and decreases in serum inhibitory factor levels in sera were observed in patients given larger doses of OK-432. A marked reduction in Concanavalin-A-induced suppressor cell activities was observed after OK-432 administration. OK-432 administration probably leads to a disappearance of tumor cells by enhancing peritoneal effector cell activities and by inhibiting the induction of suppressor cell activities, in a dose dependent manner.

Ascites↗

In vitro chemosensitivity tests on human tumor xenografts by clonogenic assay: the combined use of mitomycin C with alpha-interferon or gamma-interferon.

Using the human tumor clonogenic assay technique, the effects of Mitomycin C plus either alpha-interferon or gamma-interferon were studied against five human tumor xenografts serially transplanted into nude mice (three gastric and two colon cancers). When the survival fraction found with the drug combination was smaller than the multiplication of survival fractions with either drug alone, the combined effect was defined as synergism. Similarly, antagonistic effect was defined when the survival fraction of drug combination was larger than the larger one observed in either interferon or Mitomycin C alone. Four out of five human tumor xenografts (three gastric and one colon cancers) showed synergistic effects in combination of alpha-interferon with Mitomycin C. Though two gastric cancer xenografts exhibited synergistic effects in combination of gamma-interferon with Mitomycin C, antagonistic effects, which was not found in combination of alpha-interferon with Mitomycin C, were observed in one gastric cancer and one colon cancer xenografts.

Adenocarcinoma↗

[Assessment of the combined effects of mitomycin C with alpha-interferon or gamma-interferon by the clonogenic assay technique].

The combined effects of Mitomycin C (MMC) with alpha-interferon (HLBI) or gamma-interferon (TRP-2), which have become attractive drugs for use as Biological Response Modifiers, were investigated using the human tumor clonogenic assay technique. Tumors in this study were five human tumor xenografts serially transplanted into nude mice (three gastric cancer, two colon cancer). When the survival fraction occurring with the combination was smaller than that obtained by multiplication of the survival fractions occurring with either drug alone, the combined effect was considered to be synergism. Four out of five xenografts (three gastric cancer, one colon cancer) showed synergistic effects for the combination of MMC with alpha-interferon. Although two gastric cancer xenografts showed synergism for the combination of MMC with gamma-interferon, antagonistic effects were observed in one gastric cancer and one colon cancer xenograft.

Animals↗

[Postoperative adjuvant immunochemotherapy with bestatin for stomach cancer. Randomized controlled trial: first report].

The effectiveness of Bestatin combined with Mitomycin-C, FT-207 for treating gastric cancer was investigated in a prospective randomized controlled study. All patients had undergone gastrectomy during the period from November 1980 to July 1983. Three-year survival rates revealed no difference between groups given or not given Bestatin. The effectiveness of Bestatin was confirmed by postoperative changes revealed by liver function test, especially GOT and GPT. No side effect due to Bestatin was detected.

Adult↗

[Clinical studies on plasma exchange in advanced cancer patients with special reference to the postcentrifugal filter].

Plasma exchange was undertaken to remove the immunosuppressive factors in 25 advanced cancer patients who did not respond to immunochemotherapy. In the present studies, a postcentrifugal filter was tried, and the filtrated autologous plasma was replaced in 10 patients replaced by about 1000 ml in eight and by about 1600 ml in two. The improvement of subjective symptoms and reduction of tumors were observed in 15 (60%) and seven (28%) patients, respectively. It was suggested that immunosuppressive factors of a large molecular size could be selectively removed by the postcentrifugal filter.

Adult↗

[The role of the spleen in immunosuppression and the effects of splenectomy on prognosis in gastric cancer patients].

To elucidate the role of the spleen on the immunosuppression in gastric cancer patients, mechanism of the induction of suppressor cells in the spleen was investigated. Studies of tissue distribution of T cells using monoclonal antibodies revealed that spleen contained much higher proportion of OKT8 reactive T cells as compared with those in regional lymphnodes without metastasis. Lymphocytes released from the spleen during perfusion were taken to be representative of recirculating lymphocytes. Suppressor precursor cells were found to exist predominantly in perfusate from the spleen, while spontaneously activated suppressor cells were in the residual lymphocytes in the spleen after perfusion. Culture supernatants from splenic adherent cells induced suppressor cell activities as well as sera from splenic venous blood. These results suggest that suppressor precursor cells which could be mobilized slowly was more comparable to splenic lymphocytes and might be matured by factors released from splenic adherent cells, partly moving into peripheral blood. Furthermore, the effect of splenectomy on the prognosis of gastric cancer patients was investigated in randomized controlled trial. The patients who underwent total gastrectomy and had main location of the tumor on lesser curvature region were divided into two groups at random; splenectomy (+) and splenectomy (-) groups. A suggestive prolongation of survival time was observed in splenectomy (+) group. Thus, spleen seem to contribute to the immunosuppression in gastric cancer patients and splenectomy may lead to better prognosis.

Adult↗

The enhancement of tumor cell susceptibility to macrophage binding and cytolysis by p-aminobenzoic acid-N-xyloside sodium salt (K-247).

The enhancement of tumor cell susceptibility to macrophage binding and cytolysis by the pretreatment of tumor cells by p-aminobenzoic acid-N-xyloside sodium salt (K-247) was investigated in the C3H/He mouse-syngeneic tumor system. Binding and cytolytic activities of Corynebacterium parvum-activated macrophages were significantly enhanced when target MM-102 and MH-134 cells were pretreated with K-247 at doses of 200 or 400 micrograms/ml, while thioglycollate-elicited macrophages showed much lower binding and lytic activities against K-247 pretreated target cells. No enhancement of these activities were observed when target cells were pretreated with D-xylose, which had no anti-tumor activity. Furthermore, in a binding assay a significant reduction of macrophage binding to target cells by the K-247 pretreated cold competitors was observed. It is suggested that target cell susceptibility to macrophage cytolytic activity might be enhanced by pretreatment with K-247, involving an initially increased target binding.

4-Aminobenzoic Acid↗

[Significance of human Tr cell in gastric cancer --with special reference to suppressor cell activity].

Peripheral blood lymphocytes from gastric cancer patients and normal donors were divided into T, non T, Tr, and T non-r cell fractions. Suppressor cell activity of each fraction and surface antigen of T cell subsets were investigated. T and Tr cell fractions activated by concanavalin A (Con A) significantly depressed the lymphocyte proliferative responsiveness (LP) to phytohemagglutinin (PHA) of responder autologous lymphocytes, but non T and T non-r cell fractions didn't. LP response to PHA of responder autologous cells were depressed by Tr cell fraction from gastric cancer patients without Con A activation, but not from normal donors. The percentage of Tr cells in T cells increased from 8.9% to 18.2% in gastric cancer patients, and from 4.7% to 9.5% in normal donors when lymphocytes were activated by Con A for 24 hours. The percentages of Tr cells reacting with OKT3, 4, and 8 monoclonal antibodies were 72.5%, 29.0% and 43.4%, respectively. Therefore, Tr cell was relatively enriched by OKT8 cell. The percentage of Tr cells and suppressor cell activity increased when normal lymphocytes were incubated with sera from gastric cancer patients for 24 hours and suppression by T, Tr and T non-r cell fractions 23%, 8% and 5%, respectively. From these results it is suggested that Tr cells contain suppressor precursors which can be activated by Con A in vitro and matured suppressor cells which have been already activated in vivo, and that higher proportion of suppressor precursors is found in gastric cancer patients as compared with normal donors. Furthermore, it is indicated that cancer sera may contain factors which induce suppressor cell and induction of suppressor cell activity requires the interaction between Tr cell and T non-r cell.

Antigens, Surface↗

[Surgical treatment of Borrmann type 4 (diffuse) gastric cancer].

A total of 435 cases with stage II-IV gastric cancer resected in our department was investigated. Cases with Borrmann 4-type cancer showed the poorest prognosis in all stages compared with other types of cancer. None of three drugs-PS-K, FT-207 and Levamisole-was specifically effective on Borrmann 4-type cancer in two randomized controlled trials. A study of in-vitro lymphocyte responsiveness to mitogens suggested the presence of a suppressive factor in the serum of the patient with poorly differentiated cancer. An immunofluorescent study using monoclonal antibodies against large and small intestinal mucin antigens showed strong positivity in poorly differentiated cancers.

Female↗

[Increased cytotoxic effects of various anticancer drugs by alpha-interferon (HLBI) on human tumor xenografts in nude mice].

Since interferon (IFN) has a mechanism of action very different from chemotherapeutic agents, it is possible that a combination of two may be of therapeutic value. The authors studied increased cytotoxic effects of anticancer drugs by IFN on human tumors xenografts in nude mice. Tumor used in this study were "SH-10", "S-7379" (gastric cancer) and "O-7294" (malignant melanoma), serially transplanted subcutaneously. IFN was injected, 5 X 10(5) mu/mouse, every day for 2 weeks and a single drug was administered 3 times every fourth day. Cytotoxic effect was determined by tumor size on day 16 after treatment. Of the 7 drugs, MMC and ADM were most effective. Other drugs showed a slight inhibition of tumor growth by combination therapy with drugs and IFN.

Adenocarcinoma↗

[Local immunotherapy for cancer].

As for the non-specific cancer immunotherapy concerned, the effect is limited and local use of immunopotentiators which could collect effector cells around tumor tissues might be the best way of cancer immunotherapy. Intratumoral or intraperitoneal administration of large-dose of OK-432 (100 KE) has been investigated since many years with favorable results. Side effects were minimum with a few days continuing slight fever elevation. From the immunohistological examinations using monoclonal antibodies, participation of killer T cells and NK cells was confirmed after intratumoral administration of large-dose OK-432. On the other hand, after intraperitoneal administration of OK-432, neutrophil leucocytes appeared at first on the 2nd to 4th day and they were followed by lymphocytes on the 4th to 5th day and finally appeared lot of macrophages on the 6th and later days. From the results of in vitro and in vivo experiments, these macrophages seemed to play the leading role in the cytostatic activities after intraperitoneal OK-432 administration. As for the fear of introducing suppressor cells after large-dose OK-432 administration, detailed studies on suppressor activities before and after operation for gastric cancer patients revealed no particular increase of suppressor cell activities after intratumoral and intraperitoneal administration of 100 KE OK-432 as compared with curative resection cases with no OK-432 administration.

Adjuvants, Immunologic↗

Concanavalin A-induced and spontaneous suppressor cell activities in peripheral blood lymphocytes and spleen cells from gastric cancer patients.

In 173 gastric cancer patients, activities of Concanavalin-A-induced suppressor cells (Con-AS) and spontaneous suppressor cells (SpS) in peripheral blood lymphocytes (PBL), splenic vein lymphocytes (SVL), and spleen cells (SCs) were investigated. Suppressions by Con-AS in PBL were significantly effective in patients of Stages III and IV, while suppressions by SpS were effective in patients with recurrent tumors. Thus, in PBLs of cancer patients, suppressor precursors, which are considered to be activated in vitro by Concanavalin-A, seemed to appear with the advances of the disease, and SpS activities, which could be already activated in vivo, seemed to increase in the terminal stage. In SCs, increased activities of Con-AS, but normal activities of SpS, were observed, and these suppressor-cell populations consisted of glass nonadherent cells. Suppressor activities of SCs would be due to suppressor T-cells, not to other types of cells. Furthermore, Con-AS existed in the medium-sized lymphocytes, which were fractionated on the basis of cell size, while SpS in the large-sized lymphocytes. A higher proportion of T-cells, bearing Fc receptors for IgG, was observed in the larger-sized lymphocyte fractions. Cell numbers in the large-sized lymphocyte fraction tended to increase with the advances of tumors. From these results, it is suggested that higher presence of suppressor precursors and the increase of SpS activities may occur in cancer patients, depending on the tumor advancing.

Adult↗

Effects of Levamisole in adjuvant immunochemotherapy for gastric cancer; a prospective randomized controlled study.

The effectiveness of Levamisole combined with Mitomycin-C, FT-207 and PS-K for treating gastric cancer was investigated in a prospective randomized controlled study. All patients had undergone gastrectomy during the years from August 1977 to November 1980. Five year survival rates revealed no difference between groups given or not given Levamisole. In those with positive lymph node metastases plus obvious serosal invasion, there was a significant elevation in the survival rate at four years after gastrectomy. The effectiveness of Levamisole was confirmed by postoperative changes in the PPD skin test, lymphocyte blastogenesis to PHA and serum inhibition index.

Adjuvants, Immunologic↗

Treatment of renal cancer patients by transcatheter embolization and its effects on lymphocyte proliferative responses.

The effects of transcatheter embolization on lymphocyte proliferation in patients with renal cancer were investigated. Prognosis was good in 12 patients who underwent preoperative transcatheter embolization and 2 of 5 patients with distant metastases survived for 2 years or more. The remaining 9 patients underwent transcatheter embolization as a conservative procedure and 4 of 7 with distant metastases survived more than 1 year. Lymphocyte response to phytohemagglutinin before treatment in the presence of autologous or homologous serum was significantly lower in all patients than in healthy persons (p less than 0.01 and less than 0.05, respectively). The response after transcatheter embolization decreased slightly only in the presence of autologous serum for a short interval but recovered to the pre-treatment level 1 month after embolization. However, only in the presence of autologous serum was the response significantly higher at 2 months after nephrectomy than before treatment in patients who underwent preoperative transcatheter embolization (p less than 0.05). The serum inhibitory factor levels changed in inverse proportion to the post-treatment lymphocyte response. In patients who underwent preoperative transcatheter embolization the serum inhibitory factors essentially disappeared 2 months after nephrectomy.

Adult↗