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Biomedical subjects

K Orita

Publications and source records attributed to K Orita.

At least 217 records · Page 12Linked to original sources
PubMed1991

Mechanism of the combined antitumor effect of natural human tumor necrosis factor-alpha and natural human interferon-alpha on cell cycle progression.

We have studied the mechanism of the synergistic effect of the combination of tumor necrosis factor-alpha (TNF-alpha) and interferon-alpha (IFN-alpha) on cell cycle progression using two-parameter flow cytometry in vitro and an immunohistochemical staining method in vivo. The cells used were human colon cancer cell line RPMI 4788 in vitro and in vivo, and human breast cancer cell line MX-1 and human renal cancer cell line NAMKO-1 in vivo. In the in vitro experiment, the cell cycle progressed normally as time elapsed in the control group. However, in the group treated with TNF-alpha and IFN-alpha in combination (combination group), it appeared that the transition from the S phase to the G2/M phase was blocked, and the cells that accumulated in the S phase died. In the in vivo experiment with male nude mice of a CD-1 genetic background, the antitumor effect on all three kinds of cancer cells was significantly greater in the combination group than in the control group. The cell labeling index on staining with bromodeoxyuridine in the combination group became markedly larger and the mitotic index smaller than in the other groups. From these results, it was concluded that in the combination group, both in vitro and in vivo, tumor cells markedly accumulated in the S phase and their progression from the S phase to the G2/M phase in the cell cycle was inhibited.

Animals↗
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

Evaluation of preoperative and postoperative sodium and water loading in patients undergoing hepatectomy for liver cirrhosis complicated by hepatocellular carcinoma.

Evaluation of postoperative disturbance in the sodium and water balance was made in eight patients with compensated liver cirrhosis who had undergone segmental hepatectomy for hepatocellular carcinoma and had received unrestricted administration of sodium and water to maintain a normal urine output. On postoperative day 3, a significantly higher plasma atrial natriuretic peptide level and a significantly lower plasma aldosterone level were noted compared with postoperative day 1: the hormonal levels on postoperative day 3 were similar to the postinfusion levels obtained by the preoperative saline-loading test, which was performed to assess the physiological control of effective extracellular fluid and blood volume. Pulmonary artery and pulmonary wedge pressures were slightly, but significantly, higher on postoperative day 3 than on postoperative day 1. These results suggest that unrestricted fluid management prevents the depletion of effective extracellular fluid and blood volume on postoperative day 1, and permits their slight excess on postoperative day 3.

Adult↗
PubMed1991

In vitro induction of perforin mRNA and cytotoxic activities in human splenocytes by the streptococcal preparation, OK-432.

Mononuclear cells were isolated from a spleen excised during surgery and cultured with 0.05 KE (Klinische Einheit)/ml of the streptococcal preparation, OK-432, or 700 JRU (Japan Reference Units)/ml of recombinant interleukin-2 (rIL-2). When the cytotoxicity against K562 and Daudi cells was measured by four-hour 51Cr release assay, OK-432 induced about the same killing activity as that of rIL-2. The peak activity was observed on day 2. When the expression of human perforin messenger RNA (mRNA) was investigated by Northern blot analysis, a low-grade expression was seen in the splenocytes shortly after isolation (day 0). An expression 2.7-fold stronger than that seen on day 0 was produced after one day of culturing with OK-432. This enhanced expression decreased only slightly after the first day. The increases in expression of perforin mRNA on day 2 were similar for OK-432 and rIL-2. The results indicate the multicytokine inducer, OK-432, to induce perforin to about the same degree as rIL-2 does, and perforin to act as one of the effector molecules in the killing activity induced by OK-432.

Cytotoxicity, Immunologic↗
PubMed1991

Bracken as a risk factor in digestive tract tumors: state of the art.

The present knowledge of the risks of exposure to bracken fern (Pteridium aquilinum) is presented. The history of research on bracken toxicity is reviewed, covering the animal observations and chemical analysis, and focusing on the carcinogenic effects in various animal species and on the nature and biological properties of the known carcinogens. The implications of human exposure to bracken are inferred, the possible ways of contamination are discussed, and the existing epidemiological studies are commented. Bracken contribution to digestive tract tumors is deduced, and the need of further research on the plant toxicity and detailed epidemiological investigations with the exposed population is stressed.

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

Multicentre clinical trial of antirejection pulse therapy with deoxyspergualin in kidney transplant patients.

The present randomized comparative clinical trial was carried out to confirm the efficacy of a newly developed immunosuppressive drug, 15-deoxyspergualin (DSG), and also to find its optimal dose for antirejection pulse therapy. The study included 66 patients with rejection which had occurred within 6 months after renal transplantation. They were treated with DSG at 3, 5 or 7 mg/kg/day for 5 days. The overall percentage of efficacy was 73% and the percentage of efficacy was the highest in the 3-mg/kg group (82%). The incidence of adverse reaction tended to be dose-dependent. From these results, the optimal dose of DSG was judged to be 3-5 mg/kg/day for antirejection pulse therapy, and at doses in this range the percent efficacy could be expected to be 80% or more.

Graft Rejection↗
PubMed1991

[Effect of Euro-Collins' or UW solution on the early graft function following cadaveric kidney transplantation].

From November 1985 to March 1990, 55 cadaveric kidney transplants were performed under cyclosporine therapy. All kidneys were harvested from non-heart beating donors and cold stored after being flushed with EC solution (Group I, n = 27) or UW solution (Group II, n = 28). Warm ischemic time (min) in groups I and II were 7.1 +/- 3.3 and 6.9 +/- 2.3, respectively. Cold ischemic times (hr) in groups I and II were 6.9 +/- 2.4 and 8.4 +/- 2.8, respectively. Mean numbers of days for postoperative dialysis were 14.0 +/- 7.9 in group I and 7.9 +/- 5.8 in group II (p less than 0.05). One-month creatinine (mg/dl) was 2.9 +/- 2.8 in group I and 1.75 +/- 1.0 in group II (NS). One-month graft survivals (%) in groups I and II were 81.4% and 92.8%, respectively. In conclusion, UW solution has provided beneficial effect of preservation on ischemic damaged kidney and appears to be method of choice in non-heart beating cadaveric kidney transplantation.

Adenosine↗
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↗
PubMed1991

[Immune response in cancer patients treated with adjuvant immunochemotherapy].

In order to evaluate the immune response in cancer patients treated with adjuvant immunochemotherapy, a committee was organized in Japanese research Society for Surgical Cancer Immunology. Skin reactions, subsets of PBL, HLA, immunosuppressor (IAP), Immunoactivity (NK activity and lymphoblastogenesis with PHA), general nutritional condition and performance status were picked up and discussed as to how these reactions influence the prognosis of patients. For example, 395 cases of gastric cancer (excluded stage I, non-chemotherapy and absolute non-curative resection) collected from the committee's hospital were divided into two groups, according to a statistical "cut off point", i.e., more than 5.9g/dl of TP, 4.0g/dl of Alb, and 1500/mm3 of PBL, and values less than these. The five-year survival rate was significantly high in the former group. In the group that kept high counts of these parameters after operation, the 5-year survival rate was significantly high in cases which received immunotherapy. In conclusion, immunoparameters paralleled to the stage of disease and prognosis. When the parameters remained at high levels after operation, the immunotherapy group showed good survival compared to the non-immunotherapy group. Immunotherapy is not valuable in patients with high IAP levels and poor nutritional condition.

Humans↗
PubMed1990

Application of an interleukin 2 slow delivery system to the immunotherapy of established murine colon 26 adenocarcinoma liver metastases.

We evaluated the antitumor effect of an interleukin 2 (IL-2) slow delivery system, the IL-2 minipellet, using a murine hepatic metastasis model. The IL-2 minipellet consists of atelocollagen derived from natural bovine skin together with 1 x 10(6) units of recombinant IL-2. Administration of the IL-2 minipellet was performed into the spleens of BALB/c mice after translocation of the spleens to the s.c. position. Administration produced detectable serum IL-2 levels for 72 h. The IL-2 minipellet was evaluated for its efficacy against hepatic metastases from colon 26 adenocarcinoma in the BALB/c mice. Both the administration of the IL-2 minipellet alone and its combination with the injection of 5 x 10(7) lymphokine-activated killer cells resulted in significant reductions of the number of metastatic nodules. Moreover, increased survival of mice bearing colon 26 adenocarcinoma was noted in these two treatment groups. To investigate the mechanism of the IL-2 minipellet activity, we tested the lytic potential of splenocytes obtained after administration of the IL-2 minipellet in a 51Cr release assay. Cytotoxicity against YAC-1 cells and colon 26 cells was significantly augmented on Day 2 after minipellet administration. These results demonstrated that local administration of the IL-2 minipellet into the hepatic circulation was extremely effective against metastatic liver cancer.

Adenocarcinoma↗