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Biomedical subjects

T Toge

Publications and source records attributed to T Toge.

At least 127 records · Page 7Linked to original sources
PubMed1991

Effect of the administration of bismuth nitrate on radiogenic thymoma induction in mice.

Metallothionein functions as a radical scavenger protecting cells from the indirect effect of radiations. We investigated the effect of bismuth nitrate, an efficient inducer of metallothionein, on acute and late effects of radiation in mice. Metallothionein contents were examined in several organs after the administration of bismuth nitrate. The content in bone marrow increased 2-fold in the treated as compared to the control mice. This treatment protected irradiated mice from bone marrow death and increased the number of endogenous spleen colonies. The metallothionein content in the ileum did not change after treatment with bismuth nitrate. Mice were not protected by bismuth nitrate when exposed to 9 Gy of X-rays. This suggests that this agent does not protect from gastrointestinal death. The incidence of X-ray-induced thymic lymphomas was lowered by the administration of bismuth nitrate in mice exposed to four fractionated doses of 1.3 Gy of X-rays. These results indicate that bismuth nitrate effectively modified both acute and late effects of X-rays by inducing metallothionein in the target tissues.

Animals↗
PubMed1991

[Study on the intra-tumor tissue concentration of zinostatin stimalamer in the liver following intra-arterial injection of zinostatin stimalamer (YM881) suspension].

A suspension of zinostatin stimalamer (YM881), an antitumor protein antibiotic in iodized poppy oil-fatty acid ester, was injected into the hepatic artery of 2 patients who received surgical treatment of hepatic tumors. Single doses of 4 mg of zinostatin stimalamer were injected into the hepatic artery by Seldinger's method. Two and 4 weeks after the dose, tissue samples were collected from the tumor and non-tumor regions close to and distant (normal tissues) from the tumor, and zinostatin stimalamer concentrations in these tissues were assayed by RIA. In one of the two patients, plasma concentrations of the drug were also assayed. Concentrations of zinostatin stimalamer in the tumor tissues (381.8 ng/g) were about 55 times greater than those in the normal tissue (6.9 ng/g) in patient No. 1 (week 4), and about 17 times in patients No. 2 (13.9 ng/g in the normal tissue and 229.8 ng/g in the tumor tissues in week 2). Plasma concentrations were assayed in patient No. 2, and were 510.3 ng/ml after one hr., 385.3 ng/ml after 3 hrs., 184.4 ng/ml after 6 hrs., and 45.4 ng/ml after 24 hrs., with a half life of 7.1 hrs. These results indicate that zinostatin stimalamer suspended in iodized poppy oil fatty acid ester persisted in the hepatic tumor tissues at the high concentrations, when injected into the hepatic artery, but was eliminated fairly rapidly from the plasma.

Aged↗
PubMed1991

[Prognostic significance of expression of c-ERBB-2 oncoprotein in breast cancer patients].

The c-erbB-2 oncogene, is a member of tyrosine kinase oncogene family and expected to play a role in the regulation of cell growth. In the present study, prognostic significance of the expression of c-erbB-2 oncoprotein was investigated by immunocytochemical assay with 130 primary breast cancer patients. The positive expression of c-erbB-2 oncoprotein was found in 53 out of 130 patients (40.8%). There was no significant correlation between expression of c-erbB-2 oncoprotein and conventional prognostic factors, estrogen receptor (ER), axillary lymph node metastasis and epidermal growth factor receptor (EGFR). Relapse free survival rate of the patients with positive c-erbB-2 expression was significantly worse than those with negative at 49 month after operation. Similar result was found in overall survival rate but the difference was not significant. Furthermore, when patients were stratified by regional nodal status, in the patients with lymph node metastasis, the prognosis of the patients with positive c-erbB-2 expression was significantly worse than those with negative, while no significant difference was found in the patients without lymph node metastasis. These results suggest that c-erbB-2 oncoprotein may act as a prognostic factor independently, predicting the prognosis of breast cancer patients.

Adult↗
PubMed1991

[5'-deoxy-5-fluorouridine (5'-DFUR), mitomycin C (MMC), etoposide and medroxy progesterone acetate (MPA) in a previously treated patient with advanced breast cancer].

An advanced breast cancer patient refractory to CAF (Cyclophosphamide, Adriamycin, 5-fluorouracil), 5-FU-Methotrexate sequential therapy and Tamoxifen was treated with the combination 5' DFUR, MMC, Etoposide and MPA. Complete response was obtained both against liver and lymph node metastases from 7 months after the initial treatment. A mild bone marrow suppression and appetite loss were observed as the side effect. It is suggested that the combination therapy may be useful for previously treated patients with advanced breast cancer.

Adenocarcinoma↗
PubMed1991

[Loco-regional cancer therapy for hepatic metastasis].

UNLABELLED: We undertook a clinical evaluation of chemotherapy for hepatic metastasis of gastric, colorectal and breast cancer. Between 1980 and 1989, chemotherapy for hepatic metastasis of gastric cancer was performed in 96 cases. Between 1973 and 1989, chemotherapy for hepatic metastasis of colorectal cancer and breast cancer was performed in 40 and 14 cases. RESULTS: (1) In hepatic metastasis of gastric cancer, the 50% survival period was 149 days in local injection therapy, 132 days in arterial infusion therapy and 117 days with no chemotherapy. There was no significant difference in the survival period in gastric cancer. (2) In hepatic metastasis of colorectal cancer, the 50% survival period was 445 days in arterial infusion therapy, 206 days in local injection therapy and 96 days with no chemotherapy. The survival period with hepatic metastasis of colorectal cancer that had undergone chemotherapy was longer than for no chemotherapy. (3) In hepatic metastasis of breast cancer, arterial infusion therapy was more effective, and the survival period was prolonged significantly.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

[LAK cell adoptive immunotherapy and its problems].

Clinical efficacy of lymphokine-activated killer (LAK) cell adoptive immunotherapy (AIT) in combination with plasma exchange and interleukin (IL-2) was investigated in 24 patients with advanced cancer. Partial response (PR) was found in 4 patients (20%), including 1 primary liver tumor, 1 metastatic lung tumor from renal cancer and 2 malignant pleural effusions from gastric and lung cancer. Based on these results new AIT in combination with plasma exchange, OK-432, IL-2 and cyclophosphamide was designed to target liver and lung tumors, in which LAK cells and other drugs were administered through the catheter located in the feeding artery of the tumor. Out of ten patients treated, 1 (10%) with metastatic liver tumor from gallbladder cancer was evaluated as PR. It is suggested that a strategy to enhance tumor accumulation and recognition of LAK cells should be attempted for development of gastrointestinal cancer therapy with AIT.

Aged↗
PubMed1991

[Combination of a biscoclaurine alkaloid, cepharanthine, and anticancer agents: effects and mechanism in human gastric and pancreatic carcinoma cell lines].

A biscoclaurine alkaloid, cepharanthine (CE) potentiated antitumor activity of doxorubicin (ADM) against human carcinoma cell lines, K 562 (myelogenous leukemia), PH 101 (pancreas cancer) and SH 101 (gastric cancer). The effect of CE was irreversible and ADM activity was potentiated only in the presence of CE. While, CE could not augment anticancer activities of mitomycin C (MMC) or 5-fluorouracil (5-FU). We also found an increase of cellular plasma membrane potential in the presence of CE. In physiological condition, ADM was charged positively, while MMC or 5-FU was neutrally charged compound. Thus, we suggest that CE can potentiate the activity of positively charged anticancer drugs by increasing plasma membrane potential. Since electronegative plasma membrane potential exerts a net driving force which attracts and retains positively charged compound, it may be accompanied with an increase of drug accumulation.

Alkaloids↗
PubMed1990

[The preoperative and postoperative carcinoembryonic antigen test in the diagnosis, staging, and prognosis of gastric cancer. Tumor Marker Committee, Japanese Foundation for Multidisciplinary Treatment of Cancer].

Preoperative and postoperative carcinoembryonic antigen (CEA) levels were studied in 3,532 patients with Surgically treated gastric cancer in 52 institutions from 1980 to 1981. These patients had disease resectable with curative intent and were followed for a minimum of 5 years or until death. Among 2,749 Stage I cases, 33 had recurrence and proved to be histologically stage I. A pair matching case control study between these 33 cases and matched 33 stage I controls without recurrence proved that the preoperative CEA level was relatively higher in cases with recurrence (p = 0.079). In Stage II and III cases, an analysis of variance using a cut off level as a block factor was performed. Among 315 Stage II cases, preoperative CEA levels were significantly higher in cases with recurrence than in cases without recurrence. In 468 Stage III cases, no correlations between preoperative CEA levels and high risks of cancer recurrence were detected. In Stage I and Stage II cases, CEA levels significantly increased at the time of recurrence. In conclusion, preoperative high serum CEA levels might be considered one of the risk factors for recurrence of Stage I and II gastric cancers, and monitoring the postoperative CEA levels might be useful in early detection of recurrence.

Analysis of Variance↗
PubMed1990

Relationship between epidermal growth factor receptor status and various prognostic factors in human breast cancer.

Relationship between epidermal growth factor receptor (EGFR) status and various prognostic factors was investigated in 91 human breast cancer tissues. Epidermal growth factor receptor was measured by biochemical competitive binding assay using iodine 125 epidermal growth factor (125I)-EGF. The EGFR status was not correlated with axillary lymph node involvement, tumor size, stage, and histologic type, but significantly correlated with histologic grading (P less than 0.05) and lymphatic invasion (P less than 0.01). Between EGFR and estrogen receptor (ER) status, a clear inverse relationship was observed (P less than 0.01). The Ki-67-positive stained cell rate, which reveals the proportion of cycling cells, was significantly higher in EGFR-positive tumor tissues than in EGFR-negative cases. Furthermore, preliminary postoperative survey demonstrated a high tendency of recurrence rate of patients with EGFR-positive tumors as compared with those with EGFR-negative tumors. These data suggest that EGFR status may be important for the prediction of biologically high malignant potential.

Antigens, Neoplasm↗
PubMed1990

The analysis of lymphocyte surface receptors recognized by wheat germ agglutinin for negative regulation of immune responses in cancer patients.

The population of peripheral blood lymphocytes expressing surface receptors for a lectin, wheat germ agglutinin (WGA), which has been shown to recognize the same receptors as the soluble immune suppressor factor (SISF) elaborated from suppressor cells on the lymphocyte surface, was analyzed by using fluorescein isothiocyanate-conjugated WGA on flow cytometry in cancer patients. It was found that the populations of WGA+ lymphocytes in cancer patients were significantly higher than those in either normal volunteers or patients with benign disease and increased with progress of the tumor. The populations decreased after treatment in patients who underwent curative resection of the tumor and in responders of immunochemotherapy but not in those who received non-curative surgery or in non-responders. It was suggested that the increase of receptors for SISF on the lymphocyte surface might play an important role in the negative regulation of immune responses in cancer patients and that WGA might be a useful parameter for immunosuppression.

Antigens, Surface↗
PubMed1990

A new experimental trial using repeated heating every 24 hours for local hyperthermic therapy with bleomycin in vivo.

This report presents the effect of repeated heating every 24 hrs using bleomycin (BLM) which, although seemingly contrary to the usual agreement that hyperthermia should be carried out with a long interval due to thermotolerance, holds many possibilities. FM3A cells on the foot pad of C3H mouse were immersed in a heated water bath at 43 and 44 degrees C for 30 min. The effect of repeated heating was appreciated by an improved growth curve and 50 day survival compared to mice which received heating twice with a 96-hr interval. Repeated heating every 24 hrs 5 times with BLM suppressed tumor growth significantly as compared to heating twice with a 96-hr interval without BLM. The longest survival time was obtained by the repeated heating with BLM among all protocols. There is therefore a good possibility that more effective results could be obtained clinically by repeated heating over a short period.

Animals↗
PubMed1990

Interference of the induction of suppressor cells by a streptococcal preparation, OK-432 through the blocking of suppressor inducer T-cells.

The effect of OK-432 on suppressor inducer T cells in the generation of suppressor cells was investigated to determine its mechanism of action as an immunopotentiating agent. Suppressor cell activities induced by sera from patients with advanced cancer (stage III, IV or recurrence) were found to be as high as those induced by Con-A. Suppressor activity induced by Con-A or serum from cancer patients resided in CD8+ T cells, although CD4+ T-cells were required for the induction of suppressor cells. Significant increases in the CD4+2H4+ T cell population after stimulation with either Con-A or sera from the advanced cancer patients were observed when compared with stimulation by normal serum. Stimulation with Con-A induced suppressor cells as well as a significant increase of CD4+2H4+ T-cells. The presence of OK-432 during the generation of suppressor cells, however, significantly reduced the suppressor activity and apparently blocked the increase of CD4+2H4+ T-cells. Thus, it is suggested that OK-432 may interfere with the induction of suppressor cells through the blocking of CD4+2H4+ suppressor inducer T-cells.

Antibodies, Monoclonal↗
PubMed1990

Antineoplastic effect of erbstatin on human mammary and esophageal tumors in athymic nude mice.

The growth of MCF-7, a human mammary carcinoma, in athymic nude mice was inhibited by intraperitoneal administration of erbstatin for 14 days in combination with an iron chelator, foroxymithine, which inhibits the decomposition of erbstatin. Another human mammary carcinoma, Br-10, was not affected. Foroxymithine alone had no anti-tumor activity. In four esophageal tumors, erbstatin retarded tumor growth. There were no side-effects in any erbstatin-treated group. Levels of epidermal growth factor receptors were not changed throughout treatment with erbstatin at any dose. Erbstatin, a tyrosine kinase inhibitor, may have an antineoplastic effect against human mammary and esophageal tumors.

Animals↗
PubMed1990

Analysis of clonal evolution in a tumor consisting of pSV2neo-transfected mouse fibrosarcoma clones.

The process of clonal evolution was analyzed in a line of methylcholanthrene-induced mouse fibrosarcomas. The tumor cells were transfected with pSV2neo gene and 22 clones were randomly isolated. Genetically tagged clones were mixed and inoculated into syngeneic mice. Southern blot analysis revealed that one of the clones, no. 11, dominated both in tumors in situ and in lung metastatic nodules. No. 11 clone and other clones were similar in growth rates in vitro and in vivo, in spontaneous and experimental metastatic abilities, in immunogenicity, and in the capacity of intercellular communication in vitro. Although no. 11 clone overgrew other clones in vivo, this was not the case when clones were mixed and maintained in vitro. We conclude that clonal interactions in vivo may be responsible for the dominance of no. 11 clone in the tumor. It is likely that the preferential metastasis of no. 11 clone to the lung may be a simple reflection of the proliferative advantage of the dominant clone in the tumor in situ.

Animals↗
PubMed1990

Induction of growth factor-receptor and metalloproteinase genes by epidermal growth factor and/or transforming growth factor-alpha in human gastric carcinoma cell line MKN-28.

We examined the effects of epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) on EGF receptor (EGFR) phosphorylation and the expression of mRNAs for oncogenes, growth factors, their receptors and metalloproteinase genes by MKN-28 gastric carcinoma cells which express EGF, TGF-alpha and EGFR genes. Both EGF and TGF-alpha stimulated EGFR phosphorylation, EGF and TGF-alpha induced FOS, MYC and ERBB-2 oncogene expression. Interestingly, EGF increased the expression of mRNAs for TGF-alpha and EGFR. On the other hand, TGF-alpha increased TGF-alpha mRNA but decreased the expression of mRNAs for EGFR and TGF-beta. Furthermore, mRNAs for interstitial collagenase, stromelysin and procollagen type I genes were also enhanced after treatment with EGF and TGF-alpha. These results indicate that EGF and TGF-alpha successively evoke cascade phenomena which favor tumor progression, invasion and extracellular matrix formation, acting as autocrine growth regulators for gastric carcinomas.

Carcinogens↗
PubMed1990

[Clinical studies of in vitro chemosensitivity test evaluated by ATP assay of gastrointestinal cancer].

In order to determine the most effective anticancer agent for individual human tumor, we have performed several chemosensitivity tests, such as human tumor clonogenic assay (HTCA), succinic dehydrogenase inhibition test (SDI-T), nude mouse isotope assay (NM-IA) and subrenal capsule assay (SRCA). In this study, an novel in vitro chemosensitivity test (ATP-assay) measuring ATP amounts of cancer cells was carried out in 69 fresh gastro-intestinal tumors obtained at surgery. As the results, the evaluable rate of ATP assay was 87.0%. The positive rate of ATP assay against all tumors were 13.3% in mitomycin-C (MMC), 11.7% in adriamycin (ADM), 13.3% in 5-fluorouracil (5-FU) and 18.3% in cis-diamminedichloroplatinum (CDDP), respectively. Overall predictive accuracy rate was 82.8%. The comparative study of the survival rates of the patients with stage IV gastric cancer, receiving sensitive anticancer agents assayed by ATP assay, and those receiving negative anticancer agents revealed that the survival rate of the patients treated with sensitive drugs was longer with Kaplan-Meier analysis. From these results, it seems reasonable to conclude that ATP assay is of value in determining the chemosensitivity of gastrointestinal cancer in each patient.

Adenosine Triphosphate↗
PubMed1990

Lymphocyte subpopulations in peripheral blood and the spleen from gastric cancer patients.

Lymphocyte subpopulations in peripheral blood and the spleen from gastric cancer patients were identified by either single or two color analysis with fluorescence activated cell sorter-IV (FACS-IV) using monoclonal antibodies. The absolute and percentages of CD3+ (mature T) cells and CD4+ (helper/inducer T) cells in peripheral blood from the advanced cancer patients were significantly lower than those from normal healthy controls. In peripheral blood, a significant decrease of CD4+ cells was due to the decrease of CD4+ CD45RA+ (suppressor inducer T) cells, while CD8+ CD11b+ (suppressor T) cells tended to increase with progress of the disease. CD4+ CD45RA+ cells located more predominantly in peripheral blood and spleen than in the splenic vein, while CD8+ CD11b+ cells were more predominant in the splenic vein.

Antibodies, Monoclonal↗