Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-three patients with advanced renal cell carcinoma were treated with subcutaneous injections of interleukin-2 (IL-2) and interferon-alpha (IFN-alpha). IFN-alpha (5-10(6) U/m2) was injected on day 1 of the 1st week of a treatment cycle of 6 weeks and high doses of IL-2 (20.10(6) IU/m2) on days 3, 4 and 5. In the 2nd and 3rd week IFN-alpha (dose as above) and low doses of IL-2 (5.10(6) IU/m2) were injected on days 1, 3 and 5. The treatment from the 4th to the 6th week corresponded to that of the 1st to 3rd week. In cases of remission or stable disease the treatment schedule was repeated as a rule once or twice. In 12 of the 23 cases nephrectomy had been carried out previously. Complete remission lasting 4 + months and partial remission lasting 2 months were achieved in two patients with lung and skeletal metastases. A stable state of the disease lasting 1-7 + months was observed in 11 cases. Ten patients showed progression of the disease after the first treatment cycle. Thus, the overall objective response rate was 9%. The side effects were only slight and corresponded to WHO toxicity grade I (n = 8) and grade II (n = 15). In two cases the first treatment cycle could not be finished.
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PMID:[Treatment of advanced renal cell carcinoma with subcutaneous administration of interleukin 2 and interferon-alpha]. 797 33

Biological response modifiers have been extensively investigated in the management of patients with cancer, but few data are available on tumors of the gastrointestinal tracts. To evaluate the feasibility and activity of the combination of interleukin 2 (IL-2) and beta-interferon (beta-IFN), 15 patients with colorectal cancer and 10 patients with hepatocellular carcinoma were treated with the following outpatient schedule: beta-IFN 3 x 10(6) U i.m. 3 times weekly from day 1 to day 14; IL-2 4.5 x 10(6) U s.c. every 12 for 5 consecutive days a week from day 7 to day 21, the cycles being repeated every 28 days. All of the patients had been previously treated with chemotherapy; 7 unresectable locally advanced, and 18 had metastatic disease. All of the treatment courses were administered in an outpatient setting. No grade 4 side effects were recorded. The worst side effects were grade 3 fever (4 patients) and asthenia (2 patients) requiring treatment discontinuation in 4 cases. Twenty-four patients were evaluated for response (14 with colorectal cancer and 10 with hepatocellular carcinoma). One partial response, 4 stable disease, 9 progressive disease were recorded among the colorectal patients; 4 stable disease and 6 progressive disease among the hepatocellular carcinoma patients. The median duration of stable disease was 3 months for hepatocellular carcinoma and 4 months for colorectal cancer patients. Our results suggest that the schedule is feasible in an outpatient setting. Its limited hematological toxicity makes it suitable to be combined with cytotoxic drugs.
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PMID:Home treatment with interleukin 2 and beta-interferon in patients with colorectal cancer and hepatocellular carcinoma. 805 92

A syngeneic in vitro system was developed for investigation of the binding of purified murine interleukin-2 (IL-2) activated natural killer (A-NK) cells to murine microvascular endothelial cells. This system is potentially useful as a model to investigate biochemical and molecular events underlying the binding of A-NK cells to microvascular endothelial cells within metastases in vivo that we have previously noted using electron microscopy. A-NK/endothelial cell binding in the syngeneic system was compared with the binding of allogeneic A-NK cells to the endothelial cells. Among test agents used to pretreat the A-NK cells for modulation of binding, lipopolysaccharide (LPS) most consistently enhanced binding. Additionally, test agents were also used in concurrent assays of A-NK cytolytic activity versus YAC-1 and P815 tumor cell targets. Polyinosinic: polycytidylic acid (poly IC), and gamma interferon (gamma IFN) were among the test agents which enhanced A-NK cell cytolytic activity.
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PMID:Interleukin-2 (IL-2) activated natural killer (A-NK) cells: binding to microvascular endothelial cells and BRM enhancement of cytolytic activity. 805 14

The antitumor efficacy of recombinant murine interleukin-1 alpha (rMuIL-1 alpha) was evaluated either alone or in combination with recombinant human hybrid interferon alpha A/D (IFN-alpha A/D) against the murine B16 F10 malignant melanoma. Treatment of subcutaneous tumor-bearing mice intraperitoneally with rMuIL-1 alpha resulted in a dose-dependent inhibition of tumor growth with the greatest activity obtained with the maximum tolerated dose of rMuIL-1 alpha (10 micrograms per treatment). Augmented tumor inhibition comparable to that seen in mice treated with a high dose of rMuIL-1 alpha was observed in subcutaneous tumor-bearing mice injected with the combination of IFN-alpha A/D and a low dose of rMuIL-1 alpha. Similar inhibition of subcutaneous tumor growth was obtained in T-cell-deficient nude or natural killer cell-deficient beige mice. In contrast, treatment of mice bearing B16F10 experimental pulmonary metastases with rMuIL-1 alpha resulted in no decrease in the number of metastases, and rMuIL-1 alpha did not potentiate the antimetastatic activity of IFN-alpha A/D. A synergistic induction of IL-6 was induced in mice treated with the combination of rMuIL-1 alpha plus IFN-alpha A/D but the level of IL-6 induced was not correlated with inhibition of tumor growth because this elevation of IL-6 was not observed in tumor-bearing nude mice. No direct antiproliferative activity was demonstrable in vitro against B16 F10 cells with rMuIL-1 alpha, IL-6, or rMuIL-1 alpha plus IL-6, and addition of these cytokines did not enhance the antiproliferative activity of IFN-alpha A/D.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enhanced antitumor efficacy in mice by combination treatment with interleukin-1 alpha and interferon-alpha. 806 95

In order to investigate the effects of in vivo treatment with interferon-alpha (IFN-alpha) on melanoma antigens, a clinical EORTC trial (No. 18852) was accompanied by an immunohistological study. Twenty patients with melanoma metastases of skin and soft tissues, eventually also of the lung, who were treated with systemic IFN-alpha, were evaluated for a comparison of metastases before (40) and during (42) treatment. Representative cryostat sections were studied immunohistologically with a panel of monoclonal antibodies against differentiation antigens (HMW-MAA, K-1-2, NKI-beteb, M-2-10-15), progression markers (transferrin receptor, ICAM-1, VLA-2), histocompatibility antigens (HLA-A, B, C, HLA-DR) and the proliferation-associated nuclear antigen Ki67. We found an overall reduction of the proliferation-associated antigen Ki-67 (p < 0.01), and an increase in expression of HLA-DR (p < 0.05) and ICAM-1 (trend) during treatment. The intensity of expression of HLA-A, B and C antigens as well as pigmentation (p < 0.01) was found to be increased. Early progression (< or = 8 weeks after onset of treatment) was associated with a lack of phenotypic changes. The data suggest an independent modulation of proliferation, pigmentation, and antigen expression by systemic treatment of metastatic melanoma with IFN-alpha.
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PMID:Effects of systemic interferon-alpha (IFN-alpha) on the antigenic phenotype of melanoma metastases. EORTC melanoma group cooperative study No. 18852. 810 70

Daily IFN-alpha/beta therapy was totally ineffective in inhibiting the development of visceral metastases in DBA/2 mice injected i.v. with the ESb lymphoma regardless of the number of tumor cells injected. The finding that IFN-alpha/beta therapy increased the survival time of ESb-immunized mice rechallenged with ESb cells suggested that cooperation between the immune system and IFN-alpha/beta was important. Adoptive transfer of Esb-immune spleen cells (but not normal cells) together with IFN-alpha/beta treatment did inhibit the development of ESb metastases in immunocompetent DBA/2 mice. Either treatment alone was ineffective. The anti-metastatic effect was specific for the ESb lymphoma as spleen cells from ESb-immunized mice together with IFN-alpha/beta treatment did not inhibit the development of metastases in mice challenged with IFN-alpha/beta-resistant 3C18 FLC. Depletion of CD8+ T cells (but not CD4+ T cells or B lymphocytes) prior to transfer eliminated the protective effect of ESb-immune splenocytes in IFN-alpha/beta-treated mice. As few as 1 x 10(6) ESb-immune spleen cells highly enriched for CD8+ cells increased the survival time of IFN-alpha/beta-treated ESb-challenged DBA/2 mice. The combined therapy of ESb-specific immune cells and IFN-alpha/beta resulted in long-term immunity to this tumor.
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PMID:Successful immunotherapy of the highly metastatic murine ESb lymphoma with sensitized CD8+ T cells and IFN-alpha/beta. 818 57

We have previously shown that an intact immune system was essential to the increase in survival time of IFN-alpha/beta-treated mice injected i.v. with an IFN-alpha/beta-resistant line of Friend erythroleukemia cells (FLC) highly metastatic to the liver and spleen. Here, we have investigated the early interactions of IFN alpha/beta with host cells prior to the development of the immune response. IFN alpha/beta treatment resulted in 50- to 100-fold inhibition of FLC multiplication in the liver and spleen of normal DBA/2 mice shortly after tumor inoculation, as evaluated by colony formation in agarose. IFN treatment was far less effective in inhibiting the multiplication of FLC in the livers of NK-cell-deficient DBA/2 beige mice, or in immunocompetent DBA/2 mice treated with antibody to asialo GMI, or silica, or in mice subjected to sub-lethal irradiation. Injection of antibody to CD4 or CD8 did not affect the early inhibitory action of IFN alpha/beta on FLC multiplication but did decrease survival time. Light- and electron-microscope examination of the livers of IFN-treated, FLC-injected mice confirmed the early inhibition of FLC multiplication in the liver and spleen. Our results indicate that IFN alpha/beta inhibits the development of FLC visceral metastases by acting first on host cells, such as NK cells and macrophages, and then continues to act in consort with the developing immune response.
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PMID:Interaction of IFN alpha/beta with host cells essential to the early inhibition of Friend erythroleukemia visceral metastases in mice. 818 64

The synthetic molecule muramyl tripeptide (CGP 19835A) encapsulated in liposomes is effective in increasing the survival of mice with spontaneous experimental lung metastases induced by the RENCA renal adenocarcinoma and B16 melanoma tumor models. The present study was aimed at extending the effects of CGP 19835A to another highly metastatic carcinoma model and at evaluating the efficacy of combination therapy with standard cytotoxic agents and other immunomodulators. C57BL/6 mice received whole tumor implants of PancO2, a spontaneously metastasizing pancreatic adenocarcinoma, subcutaneously in the hind leg. Therapeutic effects were measured by increased survival which is a direct function of the growth of spontaneous lung metastases in this system. No therapeutic efficacy was observed with CGP 19835A alone or in combination with any of a series of cytotoxic or biological agents, including cis-platinurn (cis-Pt), mitomycin C (MMC), adriamycin (ADR), cyclophosphamide (CP), interferon gamma (IFN gamma), and interleukin 2 (IL-2). In accord with previous studies, when the B16-F10 melanoma was used as an experimental metastatic tumor model, CGP 19835A, alone and in combination with CP, significantly reduced the number of pulmonary metastases. Cis-Pt, however, partially negated the effects of CGP 19835A when a combination of the two agents was used. The results indicate that CGP 19835A is an effective therapeutic agent in some models of spontaneous or experimental lung metastases, but not others, and that the effects of CGP 19835A are not enhanced by the accompanying cytotoxic drugs tested here.
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PMID:Analysis of the antimetastatic effects of synthetic muramyl tripeptide (CGP 19835A) encapsulated in liposomes in combination with other immunomodulatory agents and chemotherapeutic drugs. 819 65

Twenty-seven patients treated with high-dose rTNF alpha, IFN gamma and melphalan by isolated limb perfusion were histologically documented. There were 20 cases of melanoma-in-transit metastases and 7 cases of high-grade soft-tissue sarcoma. Biopsies were taken before IFN gamma, after IFN gamma, before TNF alpha and between 2 hr and 60 days after the TNF alpha perfusion. Immunohistochemistry was performed for adhesion molecules ICAM-I, ELAM-I (E selectin), VCAM-I and PECAM. During the first hours after beginning perfusion, the endothelial cells of the tumour capillaries appeared swollen. Significant tumour necrosis was already observed 3 hours after the perfusion in melanoma cases. The overall predominant feature was coagulative necrosis associated or not with haemorrhagic necrosis. TNF alpha induced increased expression of ELAM-I and VCAM-I adhesion molecules on intratumoral endothelial cells. The activated tumour vessels were progressively destroyed. Significant intravascular recruitment of polymorphonuclear cells (PMNs) was observed 3 hr after starting TNF alpha; it was followed by diapedesis and tumour colonization 3 days later. T lymphocytes and macrophages were detected during the first 7 days and B lymphocytes during the second week. Melanoma in transit metastases treated with alkylating agent alone did not show significant necrosis and did not express high levels of adhesion molecules (ELAM-I, VCAM-I) nor infiltration by PMN.
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PMID:Early endothelium activation and polymorphonuclear cell invasion precede specific necrosis of human melanoma and sarcoma treated by intravascular high-dose tumour necrosis factor alpha (rTNF alpha). 819 73

Interleukin (IL)-7 has been evaluated for its influence, alone or in combination with local hyperthermia (LH), on B16a melanoma-bearing mice. Six- to eight-week-old C57BL/6J male mice were inoculated s.c. with 5 x 10(5) tumor cells into the left hind limb. Mice were randomly divided into four groups, and treated s.c. with IL-7 (5 ng) or saline as control, twice a day for three weeks beginning eight days after tumor inoculation. LH, using hot water circulator at 43 +/- 0.2 degrees C for 30 min, was induced to the limb with tumor twice a week for two weeks. Size of the primary tumor was measured every other day for five weeks. Mice were sacrificed five weeks after tumor inoculation. The size of the primary tumor and the number of lung metastases were reduced in mice treated either with IL-7 or LH alone. As a control for IL-7, granulocyte colony stimulating factor (G-CSF) alone had no effect on primary tumor size or number of lung metastases. The greatest antitumor effect was observed in mice treated with IL-7 in combination with LH. Survival was prolonged significantly only in mice treated with IL-7 plus LH compared with that of mice treated with saline. Decreased natural killer (NK) cell activity, number of Thy1.2 cells, and ratio of L3T4+/Lyt2+ cells were associated with tumor growth. These parameters were restored in mice treated with IL-7 plus LH. Increases in levels of IL-1 alpha, IL-6, tumor necrosis factor (TNF alpha) and interferon (IFN gamma) were associated with an increase in the survival of tumor-bearing mice treated with IL-7 and/or LH. These results suggest that changes in T-cell, NK cell and cytokines such as IL-1 alpha, IL-6, TNF-alpha and IFN-gamma in response to IL7 and/or LH might account for prolonged survival of B16a melanoma-bearing mice and that IL-7 might be useful as a potential antitumor agent combined with other therapy in certain malignant solid tumors with metastases.
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PMID:Antitumor effect of interleukin 7 in combination with local hyperthermia in mice bearing B16a melanoma cells. 824 52


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