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Biomedical subjects

S Fuchimoto

Publications and source records attributed to S Fuchimoto.

At least 37 records · Page 2Linked to original sources
PubMed1991

Comparative antitumor activity of 5-fluorouracil and its prodrugs in combination with hyperthermia in vitro.

We investigated the antitumor activities of 5-fluorouracil (5-FU), 5'-deoxy-5-fluorouridine (5'-DFUR), 1-hexylcarbamoyl-5-fluorouracil (HCFU) and 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT-207) in combination with hyperthermia in vitro. The antitumor effect of 5-FU (10(-4) M) was slightly enhanced by combination with hyperthermia (42 degrees C) for 2h, and the effect was determined to be additive. Synergistic enhancement of antitumor activity was obtained by the concurrent use of hyperthermia (42 degrees C, 2h) and 5'-DFUR (10(-4) M) or HCFU (10(-5) M). However, the antitumor effect of FT-207 (10(-4) M) in combination with hyperthermia was comparable that of hyperthermia alone. The synergistic enhancement of antitumor activity was not obtained for all drugs when the cells were preheated at 42 degrees C for 2h. On the other hand, when cells were pretreated with drugs before heat exposure, weak interactions were obtained after 5-FU and 5'-DFUR treatment, and a synergistic interaction was obtained after HCFU treatment. It is speculated that the metabolites of 5'-DFUR and HCFU enhance the cytotoxicity of 5-FU, or might change the threshold concentration for a cytotoxic effect of 5-FU in cancer cells.

Antineoplastic Agents↗
PubMed1991

The possible involvement of free radical scavenging properties in the actions of cytokines.

Among the cytokines which show an antiproliferative effect on certain tumor cells, we investigated the free radical scavenging properties of tumor necrosis factor-alpha, interferon-alpha, and interferon-gamma. The scavenging properties were determined in vitro by the ability to reduce DPPH free radicals. All of these cytokines exhibited marked DPPH free radical scavenging ability.

Bepridil↗
PubMed1991

Production of hydroxyl radicals by tumor cells varies with cell type as measured by electron spin resonance spectrometry.

The hydroxyl radicals produced by two adherent cell lines, a human cancer cell and a mouse fibroblast, and six suspended human leukemia cell lines at different stages of differentiation were measured by electron spin resonance (ESR) spectrometry. The concentration of hydroxyl radicals detected in these tumor cells increased in proportion to temperature and cell number. The addition of the enzymes superoxide dismutase (SOD) and catalase (which do not permeate the cell membrane), reduced the amount of hydroxyl radicals detected. SOD decreased hydroxyl radicals somewhat but catalase eliminated hydroxyl radicals almost completely. These findings suggest that hydroxyl radicals are produced extracellularly consisted primarily of H2O2 but partially from superoxide radicals. Using the human leukemia cell lines at different stages of differentiation we demonstrated that cell differentiation may correlate with hydroxyl radical production. The earlier the stage of leukemic cell differentiation the more the greater the production of hydroxyl radicals. Moreover, the ability of SOD or catalase to eliminate hydroxyl radical activity correlated inversely with leukemic cell differentiation.

Animals↗
PubMed1991

[Clinical evaluation of intramuscular imipenem/cilastatin sodium in surgical infections].

A multi-center clinical study was carried out at the first Department of Surgery, Okayama University Medical School and its affiliated institutions to evaluate the efficacy and safety profiles of intramuscular imipenem/cilastatin sodium (IPM/CS) in surgical infections, which were mainly biliary tract infections and peritonitis. The following results were obtained: 1. The efficacy rate was 72.0% in a total of 25 evaluable patients and 81.8% in patients with cholecystitis. 2. The efficacy rates in patients with and without underlying diseases were 70.0% and 73.3%, respectively, and they were 71.4% in patients with mild or moderate infections and 75.0% in patients with severe infections. 3. Bacteriologically, the eradication rate was 100% for Gram-positive bacteria and 62.5% for Gram-negative bacteria, with an overall eradication rate of 78.6%. The eradication rate for monomicrobial infections was 71.4% and that for polymicrobial infections was 100%. 4. Out of 25 patients, one developed diarrhea as a drug-related adverse reaction, and laboratory abnormalities attributable to the treatment were observed in 5 patients. None of them was serious, however. 5. The overall usefulness rate was 60.0%, and the usefulness for cholecystitis (72.7%) was superior to that for cholangitis (33.3%).

Adult↗
PubMed1991

Tumour necrosis factor-alpha induces translocation of protein kinase C in tumour necrosis factor-sensitive cell lines.

In this study we investigated whether the anti-proliferative effect of tumour necrosis factor-alpha (TNF-alpha) was associated with the activation of protein kinase C (PKC), using PANC-1 cells (TNF-alpha sensitive) and LoVo cells (TNF-alpha resistant). In combination with 12-0-tetradecanoylphorbol-13-acetate (TPA), a potent activator of PKC, TNF-alpha caused marked inhibition of the growth of LoVo cells. Inhibition of PANC-1 cell growth by TNF-alpha was blocked by pretreatment with TPA for 24 hr, along with down-regulation of PKC activity. Intracellular translocation of PKC from cytosol to membrane was induced by TNF-alpha treatment in PANC-1 cells but not in LoVo cells.

Cell Division↗
PubMed1990

Extragonadal sacrococcygeal seminoma--a case report.

We report herein, a rare case of a 32 year old man who presented with a massive sacrococcygeal tumor found by digital examination. A transrectal biopsy was performed, however, as massive anal bleeding occurred 1 day later, an abdominal perineal resection was carried out. Histologic examination subsequently revealed the giant tumor to be pure seminoma. Residual masses of seminoma were detected by CT examination 1 month postoperatively and, despite irradiation, the patient died 26 months after the operation. Although there have been reports of extragonadal seminoma being located in the retroperitoneum, mediastinum and pineal body, this is the first reported case of it being found in the sacrococcygeal region.

Adult↗
PubMed1990

Antitumor effect of recombinant human interleukin-1 beta alone and in combination with natural human tumor necrosis factor-alpha.

In order to investigate the antitumor effect of recombinant human interleukin-1 beta (IL-1 beta) alone and in combination with natural human tumor necrosis factor-alpha (nHuTNF-alpha), we used female BDF1 mice bearing Lewis lung carcinoma (3LL). IL-1 beta showed an antiproliferative effect against pulmonary metastatic tumors of 3LL in a dose-dependent manner. We observed 19.6 +/- 6.6, 18.6 +/- 5.3, 14.1 +/- 4.4 and 13.0 +/- 6.0 metastatic tumors at doses of 0.5, 1.0, 2.5 and 5.0 micrograms IL-1 beta/mouse/day by daily intravenous administration (the number of metastatic tumors of the control group was 26.3 +/- 8.2). Similar results were obtained by intraperitoneal administration, but in this case, mice showed a marked decrease of body weight. When IL-1 beta was administered in combination with nHuTNF-alpha, pulmonary metastatic tumors decreased much more than when IL-1 beta was administered alone. When the control group had 18.6 +/- 12.7 metastatic tumors, the nHuTNF-alpha group had 12.3 +/- 3.9 and the IL-1 beta group had 12.8 +/- 8.0, the group which was administered both cytokines had a significantly decreased number of 5.6 +/- 3.3 metastatic tumors. This antiproliferative effect of IL-1 beta in combination with nHuTNF-alpha was reduced by the intravenous administration of anti-asialo GM1 antibody and carrageenan. The number of metastatic tumors was increased from 8.9 +/- 8.0 to 18.8 +/- 11.4 by anti-asialo GM1 antibody and from 9.5 +/- 6.8 to 28.0 +/- 12.3 by carrageenan. It was suggested that asialo GM1-positive cells and macrophage were two of the most important effectors of the antiproliferative effect of IL-1 beta and TNF-alpha.

Animals↗
PubMed1990

Differing roles of protein kinase C on the antiproliferative effects of tumor necrosis factor alpha and beta on LoVo cells.

In this study we examined whether the antiproliferative effects of tumor necrosis factor (TNF)-alpha and beta were associated with the activation of protein kinase C (PKC), using the LoVo human colon cancer cell line which is resistant to both TNFs. In combination with 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent activator of PKC, TNF-alpha caused marked growth inhibition of LoVo cells, but TNF-beta had little antiproliferative effect. There was no difference in the effect when TPA was added 1 h before or 4 h after TNF-alpha administration. A PKC inhibitor, H-7, not only decreased the sensitivity of LoVo cells to TNF-alpha but also caused a slight promotion of cell proliferation and dose-dependently blocked the growth inhibition induced by TNF-alpha and TPA. These results suggested a possible regulatory function of PKC within the TNF-alpha-mediated intracellular signalling pathway. PKC may act at a later stage in the transduction pathway.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

Synergistic antiproliferative effect of the combination of natural human tumor necrosis factor-alpha and natural murine interferon-alpha/beta against colon-26 adenocarcinoma hepatic metastases in a murine model.

To prevent the development of hepatic metastases after surgery for colorectal cancer, it is important to inhibit the growth of any micrometastases which occur during the operation. We used a hepatic metastasis model in mice to investigate the effects of combination therapy with natural human tumor necrosis factor-alpha (nHuTNF-alpha) and natural murine interferon-alpha/beta (nMuIFN-alpha/beta). Decreased formation of hepatic metastases by murine colon-26 carcinoma was recognized following a single injection of nHuTNF-alpha, nMuIFN-alpha/beta, or both. These inhibitory effects were synergistic. NK activity was also measured, because notaral lerller cells not only have an anti-tumor effect but are also a representative of the host immune system. Both nHuTNF-alpha and nMuIFN-alpha/beta were able to activate NK cells, and the combination of the cytokines more significantly augmented NK activity. The in vivo elevation of NK activity induced by nHuTNF-alpha, nMuIFN-alpha/beta, or their combination may be one of the mechanisms of their antiproliferative effect on experimental hepatic metastases of murine colon-26 carcinoma.

Adenocarcinoma↗
PubMed1990

Effect of selected splenic irradiation on growth of meth A-fibrosarcoma in mice and partial characterization of splenic effector and suppressor cell populations.

Meth A-fibrosarcoma bearing BALB/c mice were subjected to selected splenic irradiation (2.0-4.0 Gy) on days 7 and 14 of tumor growth. Tumor growth was recorded by serial measurement. Irradiation given on day 7 caused regression of tumor, but irradiation given on day 14 did not show tumor regression. Antitumor activity in the Winn assay was detected in spleen cells 3 days after irradiation, but was not detected 7 days after. The cell surface phenotypes were analyzed on days 3, 7 and 14 of splenic irradiation using monoclonal antibodies (anti-Thy1.2 antibody, anti-Lyt1 antibody, anti-Lyt2 antibody, anti-L3T4 antibody) by flow cytometry. Thy 1.2, Lyt1, and L3T4 cells were increased on day 3 of splenic irradiation, but were not on days 7 and 14. Lyt2-cells did not show increase on days 3, 7 and 14. It was possibly suggested that selected splenic irradiation induced tumor regression was caused by the ability of irradiation to preferentially eliminate suppressor T cells, thereby allowing effector T-cells to become relatively dominant.

Animals↗
PubMed1990

Primary non-Hodgkin's lymphoma of the rectum: a case report.

A rare gastrointestinal tract neoplasm, primary non-Hodgkin's B-cell lymphoma in a 39-year-old, asymptomatic woman is described. The tumor was originally localized in the rectum without evidence of any other lymphoma-involved organ and treated by curative surgical procedure associated with postoperative chemotherapy.

Adult↗
PubMed1990

Increased mitochondrial uptake of rhodamine 123 during interferon-gamma stimulation in Molt 16 cells.

The positively charged rhodamine analog rhodamine 123 accumulates specifically in the mitochondria of living cells. Mitochondria-specific interaction of this molecules is apparently dependent on the high transmembrane potential maintained by functional mitochondria (1, 2, 3). The application of such potential-dependent probes in conjunction with flow cytometry allows the monitoring of mitochondrial membrane potential in living cells (4, 5, 6). In the present work, the uptake of rhodamine 123 by Molt 16 cells stimulated by IFN-gamma or IFN-beta was measured by flow cytometry. Marked elevations in mitochondria-associated probe fluorescence have been observed in cells as early as 30-60 min after exposure of IFN-gamma but not observed by IFN-beta exposure. This results suggest that the IFN-gamma and -beta induced biological functions are different in the control of energy metabolism and energy requirements at the cellular level.

Biological Transport, Active↗
PubMed1990

A comparison of the antitumor effects of natural human tumor necrosis factors alpha and beta: the roles of arachidonic acid metabolism and intracellular cAMP.

We compared the antiproliferative efficacies of the natural human tumor necrosis factors alpha (nHuTNF-alpha) and beta (nHuTNF-beta). A phospholipase A2 inhibitor reduced the antitumor effects of both nHuTNF-alpha and nHuTNF-beta, but the inhibitory effect was more marked for nHuTNF-alpha than for nHuTNF-beta. Two other arachidonate metabolism pathways were also examined. A cyclo-oxygenase inhibitor moderately reduced nHuTNF-alpha-induced cell growth inhibition but did not affect nHuTNF-beta-induced growth inhibition, while a lipoxygenase inhibitor slightly reduced the antitumor effects of both types of nHuTNF. A third arachidonate metabolism pathway, cytochrome P450-dependent reductase inhibitor, did not affect nHuTNF-dependent growth inhibition. Exogenous cAMP and forskolin enhanced nHuTNF-alpha-induced growth inhibition but had no effect on nHuTNF-beta-induced growth inhibition. The stimulation of cancer cells by nHuTNF-alpha resulted in a significant elevation of intracellular cAMP concentrations, whereas nHuTNF-beta caused no such elevation. Additional studies demonstrated that combined nHuTNF-alpha and nHuTNF-beta (at similar unit concentrations, so that nHuTNF-beta was present at a molar concentration 1.4-fold greater than nHuTNF-alpha) showed an antitumor activity comparable to that of nHuTNF-alpha alone. These findings suggest the antiproliferative effect of nHuTNF-alpha to be both quantitatively and qualitatively distinguishable from that of nHuTNF-beta.

Arachidonic Acid↗
PubMed1989

The laser treatment of hemorrhoids: results of a study on 1816 patients.

Laser is an effective, simple and harmless clinical procedure used for the treatment of hemorrhoids, as an alternative to medical therapy or surgery. In this report, we describe our experience of applying carbon dioxide laser to hemorrhoids in a total 1816 consecutive patients. The results lead us to conclude that the laser treatment of hemorrhoids is effective in pain alleviation from the first session and that patients so treated have a much more comfortable postoperative course.

Female↗
PubMed1989

Preventive and antiproliferative effects of tumor necrosis factor against experimental hepatic metastases of mouse colon-26 tumor.

This investigation was undertaken in order to assess both the preventive and antiproliferative effects of tumor necrosis factor (TNF) in a hepatic metastasis model, by means of inoculation of mouse colon-26 tumor cells into the portal vein via the superior mesenteric vein in male CDF1 mice, aged 5 weeks. Continuous 10-day administration of natural human TNF-alpha (nHuTNF-alpha) following the tumor cell inoculation caused no reduction but rather an increase in the number of hepatic metastases. However, pretreatment with this preparation daily for 10 days before the inoculation caused a remarkable decrease in the number of hepatic metastases. This prophylactic effect was reversed by the intravenous administration of anti-asialo GM1 antibody 24 h before the inoculation. The result of immunoperoxidase staining of liver specimens suggested that organ-associated natural killer cells might play a role in the metastatic inhibition. An apparent antiproliferative effect on metastatic liver tumors was also recognized following injection of nHuTNF-alpha from the 10th day after the inoculation. Thus, TNF appears to have important effects upon the host immune system, acting against liver metastases.

Animals↗
PubMed1989

Differences in intracellular calcium mobilization by interferon-beta and interferon-gamma in RPMI-4788 cells.

Human interferon (IFN) stimulates a 1.5- to 1.7-fold transient increase in the concentration of cytoplasmic-free calcium ion ([Ca2+]i) within 10-20 s upon exposure of RPMI-4788 cells to IFN. This early event of IFN-induced [Ca2+]i mobilization was measurable by loading the cells with Fura-2AM, a fluorescent Ca2+ indicator. The mobilization induced by IFN-beta or IFN-gamma was dependent on the concentration of each IFN. The increased [Ca2+]i gradually returned to its resting level within 60 s. The addition of EGTA (0.5-10 mM) to medium induced a marked decrease in the amount of [Ca2+]i mobilized by IFN-beta and a partial decrease by IFN-gamma. This finding suggests that the mechanisms of [Ca2+]i mobilization by IFN-beta and IFN-gamma might be different. While IFN-beta-induced mobilization may be mainly from an influx of the extracellular calcium ion ([Ca2+]o), IFN-gamma-induced mobilization may be a summation of an influx of [Ca2+]o and a release from intracellular Ca2+ stores.

Calcium↗