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Biomedical subjects

Y Niitsu

Publications and source records attributed to Y Niitsu.

At least 289 records · Page 16Linked to original sources
PubMed1987

Cell cycle specificity of tumor necrosis factor and its receptor.

Phase specificity in the TNF cytotoxic effect and the number of TNF binding receptors was investigated using L-M cells incubated synchronously from the S phase. TNF cytotoxicity was observed to occur at various levels during the cell cycle, with peak effect in the G2-M phase. Analysis with 125I-labeled TNF to determine the number of receptors binding TNF in the various cell phases shewed a phase specificity with the maximum number occurring in the G2-M phase, similar to the peak in cytotoxicity. The results suggest the existence of a cell cycle specificity in the cytotoxicity of TNF which is apparently related to changes in the number of receptors capable of binding TNF.

Animals↗
PubMed1987

Transferrin receptors in human cancerous tissues.

The clinical significance of radioreceptor assay for transferrin receptors of human cancerous tissues was evaluated. Fresh surgical specimens from various carcinoma tissues were solubilized with 1% Triton X-100 and the extracts were mixed with 125I-labelled diferric transferrin. The free transferrin and the receptor-bound transferrin were separated by 15% polyethylene glycol precipitation. The % specific transferrin binding to gastric, colonic, lung and mammary carcinoma tissues ranged between 3.9 and 13.9%, whereas those for normal stomach and colon were less than 2%. The concentrations of transferrin receptors in these cancerous tissues ranged between 3.7 and 28.3 pmole/g tissues. It was concluded that the amounts of transferrin receptors were significantly increased in all of the tumor tissue extracts examined and may thereby provide a useful marker for the diagnosis of malignancies.

Humans↗
PubMed1987

[Analysis of the signalling pathway of TNF in normal cells and tumor cells].

The internalization process and intracellular distribution of 125I-labeled TNF, in L-M (murine tumorigenic fibroblasts, highly sensitive to TNF cytotoxicity) cells and in HEL (human embryonic lung cells, non-sensitive to TNF cytotoxicity) cells bearing TNF receptor, were elucidated by pulse-chasing and by Percoll density gradient centrifugation. Effect of TNF treatment on the RNA and protein synthesis of target cells was also studied using 3H-UDR and 35S-methionine incorporation. In both L-M and HEL cells, receptor-bound 125I-TNF was rapidly internalized and delivered to lysosomes within 15-30 min, followed by degradation and release into the culture medium. RNA synthesis and protein synthesis were not affected by TNF treatment in HEL cells, but marked stimulation (3.5 times and 4.2 times, respectively) was observed in L-M cells.

Animals↗
PubMed1987

[Tumor necrosis factor].

Tumor necrosis factor (TNF) is cytokine derived from macrophage and shows much promise for application in cancer therapy because of its marked antitumor effects and its high specificity to tumors. Recently, the gene encoding human TNF was expressed in E. coli and the recombinant TNF was purified to homogeneity by ion exchange chromatography, affinity chromatography, and gel filtration. Clinical study of rH-TNF has been launched because human recombinant TNF can be produced on a large scale. In spite of notable antitumor effects, little is known concerning the mechanism of action of cytotoxic activity. In this article, the mechanism of action of rH-TNF against tumors in vitro and in vivo is reviewed.

Animals↗
PubMed1987

[Anti-tumor effect and mechanism of action of the tumor necrosis factor (TNF)].

TNF is cytokine derived from macrophages and shows much promise for use in cancer therapy because of its marked antitumor effects and its high specificity to tumors. The clinical application (Phase I-II) of TNF has been started because human recombinant TNF (rH-TNF) can be produced on a large scale. In spite of notable antitumor effects, little is known concerning the mechanism of its cytotoxic action. In this article, the antitumor effects of rH-TNF against human and murine tumors, the mechanism of its action and the synergistic effects of rH-TNF in combination with IFN-gamma, various anticancer drugs or with hyperthermia are reviewed.

Cell Line↗
PubMed1987

[The mechanism of action of tumor necrosis factor (TNF) on tumor vascularity--study using a transparent chamber].

Effects of human recombinant TNF on the tumor blood vessels and on the thrombus formation were investigated in relation to its mode of antitumor action against Meth-A sarcoma transplanted in BALB/c mice. The extent of the blood vessel lesion was evaluated by using transparent chamber placed in the mouse skin. Bleeding, hyperemia and congestion were observed at 1-2h, 4-6h and 24h after TNF (1 X 10(4)U/mouse) administration, respectively. In contrast, no histological changes in the normal blood vessels were observed microscopically following TNF injection. Thrombus formation was evoked in the tumor vessels 4h after TNF injection. However, when thrombus formation was prevented by heparin, no difference was observed among antitumor action of TNF against Meth-A fibrosarcoma necrotic response and the rate of complete cure. These results suggest that the direct effects of TNF causing lesions in the tumor blood vessels plays an important role in its antitumor action.

Animals↗
PubMed1987

[A case of pericarditis carcinomatosa showing good response following local transfer of lymphokine-activated killer (LAK) cells].

A good therapeutic response following local transfer of lymphokine-activated killer (LAK) cells was obtained in a patient with cardiac tamponade due to breast carcinoma. A 41-year-old female was admitted with complaints of dyspnea and tachycardia. She had undergone left mastectomy at the age of 37 years and had received continuous oral administration of tamoxifen. Chest roentgenogram revealed cardiomegaly (CTR = 65%) and cardiac echogram showed marked retention of pericardial effusion. The cytology of the effusion was class V (adenocarcinoma). Cardiac tamponade proved refractory to combination chemotherapy using adriamycin, cyclophosphamide and 5-fluorouracil, and the effect of paracentesis was only temporary. Autologous peripheral blood lymphocytes were obtained through the cubital vein and cultured in vitro with 2 units/ml of human recombinant IL-2, (TGP-3, Takeda Pharm. Co.). After 4 days of cultivation, LAK cells were transferred intrapericardially 3 times. The cumulative infusion dose was 1.2 X 10(8) cells and the amount of combined IL-2 administration was 100 units/each transfer. Twenty-four days after initial infusion of LAK cells, the effusion disappeared. After then, recurrence has not been observed for 287 days. This case is the first trial of LAK therapy against pericarditis carcinomatosa and seems to be a useful way of treating this uncontrollable state without any serious side effects.

Adenocarcinoma↗
PubMed1987

[Synergistic effects of human recombinant TNF and hyperthermia on in vitro cytotoxicity and artificial metastases].

Synergistic effects of hyperthermia on the cytotoxicity of TNF were examined, using L-M cells (mouse tumorigenic fibroblasts) and HEL cells (human embryonic lung cells) as targets. The sensitivity of L-M cells to TNF apparently increased when the culture temperature was raised from 37 degrees C to 38.5 degrees C or 40 degrees C, probably reflecting the increased turnover rate of the TNF-receptor complex. The anti-metastatic effects of a combined regimen of TNF (300U) and whole-body hyperthermia (40 degrees C, 30 min) was also examined in Balb/c mice injected with 1 X 10(6) Meth A F15 cells into a tail vein. No effects of TNF or hyperthermia alone were observed on artificial metastasis, while the combination of TNF and hyperthermia remarkably enhanced the inhibition of metastasis. These studies clearly suggest that combination of TNF with hyperthermia provides a significant synergistic effect against tumor.

Animals↗
PubMed1987

[Sequential methotrexate-5-fluorouracil (MTX-5-FU) treatment of patients with advanced gastric and colorectal cancer. Sequential Methotrexate-5-FU Study Group].

A multicenter cooperative study was conducted from July 1984 to March 1986 to evaluate the clinical efficacy of sequential MTX-5-FU treatment in 96 cases of advanced gastric cancer and 39 cases of colorectal cancer. 5-FU 600 mg/m2 i.v. was given and MTX 30 mg/m2 (A), 100 mg/m2 (B) and 300 mg/m2 (C) i.v. were given, and the administration interval between MTX and 5-FU was 1 to 3 h for the gastric cancer group, and 7 h for the colorectal cancer group. Leucovorin rescue of 10 mg/m2 p.o. was given 24 h after MTX administration. In the gastric cancer group, the response rate for Regimen A was 23.2% (CR 1 and PR 12) out of 56 evaluable cases, and for Regimen B, 40.5% (CR 1 and PR 14) out of 37 evaluable cases. In the colorectal cancer group, the response rate for Regimen A was 28.6% (PR 6) out of 21 evaluable cases and for Regimen B, 20.0% (PR 3) out of 15 cases. Median survival time for the gastric cancer group was 5.5 months with Regimen A and 7.6 months with Regimen B, and for the colorectal cancer group 10.9 months with Regimen A and 7.9 months with Regimen B. Main adverse effects were marrow impairment and gastrointestinal symptoms such as nausea, diarrhea, and stomatitis. In this study Regimen B showed relatively good results. In order to evaluate the biochemical modulation occurring with sequential MTX-5-FU treatment, a further phase III study in gastric cancer patients should be conducted.

Adult↗
PubMed1987

[The synergistic effect of human recombinant TNF in combination with various anti-cancer drugs].

The synergistic effect of human recombinant TNF in combination with various anti-cancer drugs was examined in vitro. In vitro treatment of L-M cells with TNF and mitomycin C (MMC), adriamycin (ADM), cytosine arabinoside (Ara-C), actinomycin D (ACD), daunorubicin (DM), cisplatin (CDDP), vincristine (VCR), or 5-fluorouracil (5-FU) revealed a synergistic cytotoxicity. However, the combination of TNF with bleomycin (BLM) failed to show such a synergistic effect.

Animals↗
PubMed1987

Serum transferrin receptor as a new index of erythropoiesis.

Serum transferrin receptors were measured by a sandwich radioimmunoassay procedure in patients with iron deficiency anemia, autoimmune hemolytic anemia and aplastic anemia. The mean circulating transferrin receptor concentration of normal subjects and patients with iron deficiency anemia, autoimmune hemolytic anemia and aplastic anemia are 253 +/- 82 ng/mL, 730 +/- 391 ng/mL, 1,426 +/- 1,079 ng/mL, and 182 +/- 39 ng/mL, respectively. The values for those with iron deficiency anemia and autoimmune hemolytic anemia were significantly higher than that of normal controls and the values for those with aplastic anemia were lower than that of normal controls. After iron supplementation in iron deficiency anemia, the serum transferrin receptor values increased twofold over those of pretreatment values. This increase parallels an increase in peripheral reticulocytes. Therefore, the number of circulating transferrin receptors in anemic patients may reflect the level of bone marrow erythropoiesis and is a potentially useful new index for red cell production.

Anemia↗
PubMed1986

A subclass of glutathione S-transferases as intracellular high-capacity and high-affinity steroid-binding proteins.

The distribution of glucocorticoids incubated with rat liver cytosol preparations or administered in vivo to adrenalectomized rats was analysed by chromatographic procedures. Corticosterone or dexamethasone was co-eluted with Yb-type GSH S-transferases in anion-exchange and gel-permeation chromatography systems, and these glucocorticoids also were bound to Yb forms in analyses by immunoadsorbent and lysyl-GSH affinity matrices. Pretreatment of cytosol with lysyl-GSH to extract GSH S-transferases or incubation with excess bilirubin, which is expected to compete with steroids for binding to the protein, yielded preparations that were devoid of this major steroid-binding component. In mixtures of the multiple rat GSH S-transferases, corticosterone preferentially interacted with Yb forms rather than Ya and Yc subgroups. All of the multiple Yb forms resolved by chromatofocusing procedures retained the steroid-binding capacity. It is suggested that these abundant proteins can account for a considerable share of intracellular glucocorticoid binding and represent a high-affinity non-saturable binding component with potential to function in steroid-hormone metabolism and action.

Animals↗