Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of autochthonous IFN- production was evaluated in immune reactions to Moloney murine sarcoma virus (M-MSV)-induced tumors which are characterized by spontaneous regression mainly caused by virus-specific CTL activity. A functional IFN- depletion, induced by repeated administration of mAb anti-IFN- at the site of virus inoculation, prevented tumor regression in M-MSV-injected mice. Moreover, this antibody inhibited in vitro both proliferation and differentiation of M-MSV-specific T lymphocytes obtained in bulk cultures, but not growth and lytic activity of the already differentiated virus-specific CTL clone CHM-14 stimulated with rIL-2 and relevant tumor Ag. In addition, in mice receiving mAb treatment the frequency of M-MSV-specific CTL precursors, evaluated by means of limiting dilution analysis, was strongly reduced in comparison with that of control mice injected only with virus. Because CTL secrete IFN- following antigenic stimulation, the possibility that non-T effector cells recruited by this lymphokine might mediate tumor regression was also considered. Adoptive immunotherapy experiments, performed in T cell-deficient (Tx + BM) and in sublethally irradiated mice, demonstrated that transfer of CHM-14 CTL clone, which secretes IFN-, was able to counteract M-MSV tumor growth despite the local mAb anti-IFN- treatment which may have prevented host cell recruitment. Moreover, repeated local rIFN- inoculations in Tx + BM mice did not counteract M-MSV tumor progression, thus confirming that other IFN- properties such as non-T cell recruitment, antiviral or anti-proliferative IFN- activities have little or no relevance when M-MSV-specific CTL are lacking. On the whole, these results indicate that in M-MSV-injected mice, tumor enhancement after mAb anti-IFN- treatment is principally caused by impaired differentiation of virus-specific CTL precursors.
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PMID:Monoclonal antibody against IFN-gamma inhibits Moloney murine sarcoma virus-specific cytotoxic T lymphocyte differentiation. 283 Mar 39

The biological activities and antitumor mechanism of an immunopotentiator, Ge-132, is reviewed herein. Ge-132 exhibited antitumor activity against certain syngeneic and allogeneic experimental tumors. It was shown that T-cells and macrophages were involved when tumor-bearing mice were protected by the compound. This protective effect could be transferred to tumor-bearing mice, not treated with the compound, by a macrophage fraction and serum specimens obtained from Ge-132-treated mice. Interferon gamma (IFN gamma) was detected in the circulation of Ge-132-treated mice and when sera obtained from Ge-132-treated mice were treated with anti-IFN gamma antiserum in vitro, the antitumor activity was abolished. On the other hand, in mice treated with anti-IFN gamma antiserum, Ge-132 did not induce serum IFN and failed to protect against death due to ascites tumor progression. The in vivo administration of monoclonal anti-Thy 1.2 antibody prevented the expression of the antitumor activity of Ge-132. However, serum specimens obtained from Ge-132-treated mice effectively inhibited the tumor growth of T-cell-depleted mice bearing ascites tumors. Since it has been reported that T-lymphocytes produce IFN gamma, this suggested that Ge-132 may first stimulate T-cells to produce IFN gamma in the expression of the observed antitumor efficacy. In addition, sera obtained from Ge-132-treated mice did not show any antitumor activity in mice depleted of macrophage functions. Additionally, passive transfer of macrophages from mice treated with these serum specimens to tumor-bearing mice also resulted in the inhibition of tumor growth. Pretreatment of these serum specimens with anti-IFN gamma antiserum effectively prevented the generation of cytotoxic macrophages. Also, tumor-bearing mice treated exogenously with this antiserum did not differ significantly in survival as compared to controls, despite the administration of Ge-132. Furthermore, the antitumor activity of Ge-132 was detected in NK cell-depleted mice. Therefore, the antitumor mechanism of Ge-132 in the murine ascites tumor system may be expressed as follows: (a) Ge-132 stimulates T-cells to induce IFN gamma when mice are treated orally with the compound, (b) IFN gamma activates macrophages to become cytotoxic, and (c) the cytotoxic macrophages eliminate tumor cells.
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PMID:Biological activities and antitumor mechanism of an immunopotentiating organogermanium compound, Ge-132 (review). 297 86

Recombinant human interferon alpha A/D (IFN alpha A/D) is known to be as active on murine cells as on human cells. We studied the antitumor effect of pure IFN alpha A/D on Meth-A sarcoma subcutaneously transplanted into female syngeneic BALB/c mice. When administered systematically (intraperitoneally), IFN alpha A/D was only marginally (but significantly, P less than 0.05) effective in inhibiting tumor growth. With intralesional injection, however, IFN alpha A/D strongly suppressed the growth of Meth-A sarcoma, even leading to complete tumor regression and to subsequent immunity to Meth-A sarcoma cells in the host mice when the treatment was started early after tumor transplantation and with a high IFN alpha A/D dose. We also found that treatment of mice with IFN alpha A/D increased the level of serum alpha 1-acid glycoprotein, one of the acute-phase proteins.
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PMID:Antitumor effect of recombinant human interferon alpha A/D on Meth-A sarcoma in mice. 308 32

The administration of IFN containing sera (Ge-sera) obtained from Ge-132-treated mice (Ge-mice) or the passive transfer of macrophages (M phi) to mice bearing ascites tumors resulted in the inhibition of tumor growth. The cooperative role of Ge-sera and Ge-M phi in the display of Ge-132-antitumor activity was studied. When mice were pretreated with antimouse IFN gamma antiserum, no IFN-inducing and antitumor activities of the compound were detected. Cytotoxic activities were detected on peritoneal M phi of mice treated with Ge-sera, and passive transfer of these M phi to tumor-bearing mice resulted in the inhibition of tumor growth. When tumor-bearing mice were pretreated with substances toxic to M phi, there was no antitumor activity of Ge-sera observed. However, there was antitumor activity of Ge-sera in mice depleted of T-cells, even though the antitumor effects of the compound itself were not demonstrable in T-cell depleted mice. Therefore, a part of the antitumor activity of Ge-132 may appear to be expressed as follows: (1) Ge-132 stimulated T-cells to produce circulating lymphokine(s) which were inactivated by anti-IFN gamma treatment; (2) activated M phi were generated from resting M phi by such lymphokine(s); (3) the transplanted tumors were inhibited by these M phi.
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PMID:Cooperation of lymphokine(s) and macrophages in expression of antitumor activity of carboxyethylgermanium sesquioxide (Ge-132). 308 73

In a syngeneic C3H mammary adenocarcinoma model we studied gamma-interferon (gamma IFN) production during tumor evolution. The IFN production was induced by soluble tumor extracts on spleen cell cultures from tumor-bearing mice. A low level of IFN production was found in culture supernatants from small tumor-bearing mice (tumor diameter less than 10 mm, 12-15 days of tumor evolution). In advanced stages of tumor growth (diameter more than 15 mm, 20 days or more of tumor evolution), this ability was lost.
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PMID:In vitro immune interferon induction during tumor evolution. 309 17

The antitumor activities, resulting from the combined treatment of leukocyte interferon (IFN-alpha), with recombinant human immune interferon (IFN-gamma), against human tumor xenografts in nude mice, were studied. Nine human tumor xenografts, (7 from gastric carcinoma, 1 from gallbladder carcinoma and 1 from breast carcinoma), were serially transplanted into nude mice for the purpose of this experiment. Each human tumor xenograft was inoculated subcutaneously into BALB/c nu/nu nude mice and treatment was started after the estimated tumor had reached 100-300 mg. IFN was administered intramuscularly at a schedule of qd X 14. Treatment with either IFN-alpha or IFN-gamma alone, did not produce any antitumor effect against the various human tumor xenografts, however the combination of IFN-alpha with IFN-gamma resulted in achieving significant antitumor effects against the various human tumors. Inhibition of tumor growth was observed in 7 of the 9 tumors (77.8 per cent), and regression of the tumor was noted in 5 of the 9 tumors (55.6 per cent).
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PMID:Experimental studies on the combined effects of alpha and gamma interferons against human tumor xenografts transplanted into nude mice. 311 30

The in vivo anti-tumor effects of a recombinant human hybrid interferon alpha, rHuIFN-alpha A/D, and recombinant murine interferon gamma (rMuIFN-gamma) were evaluated against experimental hepatic metastases and s.c. tumor growth of the murine reticulum cell sarcoma M5076. The 2 interferons were equally active in preventing experimental hepatic metastases. However, the interferons differed in their relative ability to influence the growth of the same tumor when treatment was initiated following injection of tumor cells. Greater efficacy was obtained in the treatment of metastatic foci in the liver with rHuIFN-alpha A/D, while rMuIFN-gamma was more active in the therapy of an s.c. growing M5076 tumor. These results demonstrate that the same tumor growing at different sites can have different relative sensitivities to IFN-alpha and IFN-gamma.
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PMID:The anti-tumor effect of recombinant interferon alpha or gamma is influenced by tumor location. 312 22

A synergistic antitumor effect of natural human tumor necrosis factor-beta (TNF-beta) in combination with hyperthermia was found, in comparison with that of TNF-alpha, using an in vitro antiproliferative assay on a human colon cancer cell line (RPMI4788) and an in vivo tumor growth inhibition assay on Meth A sarcoma cells. In vitro combined treatment with TNF-beta (10,000 U/ml) and hyperthermia (at 43 degrees for 60 min) synergistically inhibited the proliferation of the cells. Combined effects of TNF-alpha or natural human interferon-alpha or -gamma (IFN-alpha, -gamma) and hyperthermia were also examined, and furthermore, the combinations of TNFs and IFNs were examined in combination with hyperthermia at 42 degrees; their antiproliferative effects were further augmented by hyperthermia. In vivo growth of Meth A sarcoma cells (5 x 10(5)), transplanted subcutaneously into BALB/c mice, was inhibited significantly (P less than 0.05) with the combination of TNF-alpha or -beta (2 x 10(5) U/mouse) and hyperthermia (at 43 degrees for 60 min) as compared to either a single intravenous injection of TNF-alpha or -beta alone or the hyperthermia alone. The influence of TNF-beta and hyperthermia on the cell cycle was examined. Flow cytometric analysis showed that RPMI4788 cells treated with TNF-alpha or -beta accumulated in the S phase of the cell cycle, and that hyperthermia (at 42 degrees for 60 min) alone had no influence on the cell cycle and did not augment the S phase accumulation of the cells treated with TNF-alpha or -beta.
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PMID:Hyperthermic enhancement of the antitumor effect of natural human tumor necrosis factor-alpha and -beta: an in vitro and in vivo study. 314 36

Friend erythroleukemia cells (FLC) (H-2d) injected intravenously into adult syngeneic DBA/2 or allogeneic C57B1/6 (H-2b) or C3H (H-2k) mice lodge in the liver but only multiply in the liver of syngeneic mice. Our results indicated that endogenous IFN-alpha/beta was a crucial factor in preventing the multiplication of FLC in the liver of adult allogeneic mice. (a) Treatment of allogeneic adult C57B1/6 or C3H mice with polyclonal antibody to mouse IFN-alpha/beta (but not antibody to IFN-gamma) completely abrogated the resistance to the multiplication of FLC in the liver and 87% of tumor-injected, antibody-treated C57B1/6 mice died with extensive tumor involvement of the liver. In contrast, after intravenous inoculation FLC do not multiply at all (or very rarely) in the liver of adult C57B1/6 mice left untreated or treated with a variety of control globulins, and no deaths occurred. (b) 8 h after intravenous inoculation of FLC, poly(A)+ RNA hybridizable with specific DNA probes for mouse IFN-alpha or -beta (but not -gamma) was present in the liver of injected C57B1/6 mice. Using the expression of the Mx protein as an indicator of the presence of IFN-alpha/beta, we showed that Mx+ congenic C57B1/6 mice injected with FLC exhibited a marked increase in the expression of the Mx protein in the liver, spleen, kidney and lung, and this increase was blocked by treatment of mice with antibody to IFN-alpha/beta. The possibility that different host mechanisms are elicited depending on the site of tumor growth in allogeneic mice is discussed. IFN-alpha/beta appears to be of particular importance in determining the resistance of the liver to FLC in allogeneic mice.
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PMID:Antibody to mouse interferon alpha/beta abrogates resistance to the multiplication of Friend erythroleukemia cells in the livers of allogeneic mice. 317 80

The in vivo anti-tumor activity of 2 recombinant cytokines, interleukin-2 (rIL-2) and human hybrid interferon alpha (rHuIFN-alpha A/D), were tested using the murine reticulum cell sarcoma M5076. Experimental hepatic metastases, following i.v. injection of tumor cells, and tumor growth and spontaneous metastases, following s.c. injection of tumor cells, were inhibited to a greater extent in mice treated with a combination of these cytokines than in animals treated with either one alone. When used in conjunction with surgical removal of the s.c. tumor, treatment of mice with both cytokines significantly prolonged survival of tumor-bearing animals. Injection of normal mice with a combination of cytokines, but not with either cytokine alone, resulted in a marked increase in cytotoxic activity of hepatic effector cells. The effector cells in these mice appeared to be NK cells since this enhanced cytotoxicity was markedly reduced in animals treated in vivo with anti-asialo GM1 or in NK-deficient beige mice. Furthermore, no in vivo efficacy was observed in M5076-bearing beige mice treated with these cytokines. Thus, injection of mice with rIL-2 and rHuIFN-alpha A/D results in the induction of an NK-cell-like population in the liver with enhanced cytotoxic activity that correlates with the observed anti-tumor activity in vivo in this murine model. These results suggest that combinations of cytokines, in particular IFN-alpha and IL-2, can be effectively used in combination for the treatment of tumors and/or metastases.
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PMID:In vivo anti-tumor activity of combinations of interferon alpha and interleukin-2 in a murine model. Correlation of efficacy with the induction of cytotoxic cells resembling natural killer cells. 349 83


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