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Biomedical subjects

K Orita

Publications and source records attributed to K Orita.

At least 325 records · Page 18Linked to original sources

In vitro synergistic effects of natural human tumor necrosis factor and natural human interferon-alpha.

Tumor necrosis factor and interferons are multifunctional cytokines. The present studies were undertaken to investigate the biologic interactions of highly purified natural human tumor necrosis factor and highly purified natural human interferon-alpha, which were derived from a B cell acute lymphatic leukemia line (BALL-1 cells) sensitized with hemagglutinating virus of Japan (HVJ). Combined treatment with natural human tumor necrosis factor and natural human interferon-alpha synergistically inhibited the in vitro proliferation of P4788 cells derived from a human colon cancer. Flow cytometric analysis of the cell cycle of asynchronous cells indicated that target cells treated with natural human tumor necrosis factor alone accumulate in the S phase. This accumulation in the S phase of the cell cycle was augmented by combined treatment with natural human tumor necrosis factor and natural human interferon-alpha. The growth inhibitions appeared to be a result of arrest in the S phase of the cell cycle. Combined treatment with these cytokines had potent cytostatic and cytotoxic effects on most of the tested malignant cell lines of human epithelial origin.

Cell Cycle↗

[Combined effect of human recombinant interferon alpha, beta and gamma on tumor cell growth and the cell cycle in vitro].

Antiproliferative effect and the effect on cell cycle distribution of human recombinant interferon (rHu-IFN)-alpha, -beta and -gamma in combination on a human colon cancer cell line were investigated in vitro. Combined treatment with rHuIFN-beta and rHuIFN-gamma had a marked antiproliferative effect. Combination of rHuIFN-beta (200U/ml) and rHuIFN-gamma (200JRU/ml) had a similar antitumor effect to rHuIFN-gamma (5,000JRU/ml). From the analysis of the cell cycle obtained by flow cytometry, rHuIFN-beta showed accumulation of the S phase, while rHuIFN-gamma revealed accumulation of the G1 phase. With the combination of rHuIFN-beta and rHuIFN-gamma, G2 + M phase decreased markedly and G1 phase increased. These results suggest that combined treatment with rHuIFN-beta and rHuIFN-gamma can be an effective therapy for human cancer.

Cell Cycle↗

[Combined effect of human recombinant interferon-beta and interferon-gamma against an experimental model of peritonitis carcinomatosa in nude mice].

The development of useful therapy for the peritonitis carcinomatosa of gastrointestinal cancer is an important theme in cancer therapy. We developed an experimental model of peritonitis carcinomatosa in nude mice transplanted intraperitoneally human colon cancer cells. In this study, we investigated combined effect of human recombinant interferon-beta (rIFN-beta) and recombinant interferon-gamma (rIFN-gamma) in vivo using this model. The result indicate that each rIFN-beta and rIFN-gamma showed a significant prolonged survival compared with the control group (mean survival days: 41.8 +/- 5.0 days). Furthermore, combined administration of rIFN-beta and rIFN-gamma showed a marked prolonged survival (mean survival days: 114.0 +/- 7.4 days) compared with rIFN-beta or rIFN-gamma alone. These results suggest that a combined treatment of rIFN-beta and rIFN-gamma may be useful against peritonitis carcinomatosa of gastrointestinal cancer.

Animals↗

Antitumor effect of recombinant human interferon-beta and interferon-gamma in combination against human colon cancer cell line in vitro and in nude mice.

The antiproliferative activity of recombinant human interferon (rIFN)-beta and rIFN-gamma, alone or in combination, against a human colon cancer cell line (RPMI 4788) was examined in vitro and in nude mice. rIFN-beta and rIFN-gamma interacted synergistically in vitro. In experimental pulmonary metastasis and intraabdominal carcinomatosis in nude mice, rIFN-beta and rIFN-gamma were administered iv and ip, respectively, alone or in combination, for 10 consecutive days beginning 2 days after RPMI 4788 cells were inoculated. In both models, rIFN-beta and rIFN-gamma alone had significant antitumor effects compared with the saline-control group. Combined administration of rIFN-beta and rIFN-gamma resulted in marked antitumor effects. In the pulmonary metastasis model, there were no pulmonary metastatic nodules in the group treated with the combination of rIFN-beta and rIFN-gamma (P less than 0.001), while there were 324.6 +/- 83.1 (mean +/- SD) nodules in the control group. In the intraabdominal carcinomatosis model, the mean survival time was 114.0 +/- 8.2 days (P less than 0.01) for the combination therapy group, but only 41.8 +/- 5.6 days for the control group. These results suggest that combined treatment with rIFN-beta and rIFN-gamma might be a promising therapy for pulmonary metastasis and intraabdominal carcinomatosis of human cancers.

Abdominal Neoplasms↗

Antitumor effect of human recombinant interferon-gamma alone and in combination with adriamycin on a human colon cancer cell line (RPMI 4788) in vitro and in nude mice.

The antitumor effect of recombinant human interferon-gamma (rIFN-gamma) and adriamycin (ADM), alone or in combination, against a human colon cancer cell line (RPMI 4788) was examined in vitro and in nude mice. In the in vitro study, antiproliferative activities of ADM were augmented additively or synergistically by combination with rIFN-gamma in a dose-dependent manner. Growth of RPMI 4788 cells (2 X 10(6)/mouse) transplanted subcutaneously into CD-1 nu/nu nude mice (day 0) was not inhibited significantly by 28 daily injections from day 10 of rIFN-gamma alone, but the antitumor effect of ADM was augmented synergistically by the simultaneous injection of rIFN-gamma. In an experimental model of pulmonary metastasis, in which RPMI 4788 cells (2 X 10(6)/mouse) were inoculated intravenously into BALB/c nu/nu nude mice (day 0), 10 or 21 daily injections from day 2 of rIFN-gamma alone had significant inhibitory effects against pulmonary metastasis in a dose-dependent manner. Furthermore, the inhibitory effect of ADM was augmented synergistically by daily injections of rIFN-gamma.

Animals↗