Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tissue fragments from biopsies of six patients with malignant tumors of the lung were cultured in interleukin 2 (IL-2). Cultures of proliferating lymphocytes were isolated from all cases. Tumor cell lines (small cell carcinoma and adenocarcinoma) were established in parallel cultures from two of these patients. Lymphocytes that proliferated in vitro were virtually all mature T lymphocytes (greater than 95% T3+, T11+). The T8+ subset accounted for an average of 70% while T4+ cells averaged 20% of the cells in culture. HNK-1 antigen was presented on 23% of cells. Seventy-four percent of cells expressed Ia (HLA-DR) antigens. B cells did not proliferate under these conditions. In all cases the cells lysed K562 targets and were active in lectin-mediated cytolysis against human lymphoblasts. All cultures produced lymphokines (IL-2 and IFN-gamma) when stimulated with PHA. Lymphocytes grown from a tissue specimen with adenocarcinoma were capable of killing autologous tumor cells in vitro. Specific cytotoxicity has been maintained by these cultured lymphocytes for greater than 6 months. IL-2 activated peripheral blood cells in this case showed little specific cytotoxicity for autologous tumor cells. Lymphocytes from another specimen of adenocarcinoma also lysed this tumor, but cells from the other four specimens did not. Lymphocytes propagated from the specimen of small cell undifferentiated cancer did not lyse autologous tumor cells. These data show that primary lung tumors contain activated T cells which will respond to IL-2 in vitro. These tumor-infiltrating lymphocytes have demonstrable function, which can include cytolytic activity against autologous lung tumor.
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PMID:Functional characterization of T lymphocytes propagated from human lung carcinomas. 308 Feb 65

Human recombinant gamma interferon (rHuIFN-gamma) was found to induce tryptophan degradation in vitro in human cell cultures and in vivo in participants in phase I clinical trials. When human lung fibroblasts were treated with various concentrations of rHuIFN-gamma, they degraded tryptophan in a dose- and time-dependent manner. No tryptophan degradation was observed when cells were incubated in growth medium alone or in medium supplemented with human recombinant beta-interferon (rHuIFN-beta ser). Similarly human bladder carcinoma cells were induced to catabolize tryptophan after incubation with rHuIFN-gamma, but no activity was observed in untreated cells or cells treated with either rHuIFN-beta ser or human naturally produced alpha-interferon (HuIFN-alpha). When tryptophan plasma levels were measured in cancer patients who had received i.v. bolus injections of rHuIFN-gamma as part of a phase I clinical trial, decreased tryptophan levels were observed when compared with pretreatment values or values obtained from individuals who had received i.v. injections of HuIFN-alpha. Urine analyses were suggestive that plasma tryptophan degradation occurred via the kynurenine catabolic pathway in individuals who received rHuIFN-gamma. We conclude that tryptophan degradation is an activity induced in vitro and in vivo in response to exogenous IFN-gamma but not to IFN-alpha or IFN-beta. Tryptophan degradation may play an important role in the mechanism of antiproliferative, immunologic, and clinical side effects of IFN-gamma.
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PMID:Induction of tryptophan degradation in vitro and in vivo: a gamma-interferon-stimulated activity. 309 41

Combinations of interferon-alpha and interferon-gamma demonstrate synergistic antiviral and anti-proliferative activity in vitro. Therefore, we initiated a clinical study of combination interferon therapy in humans. Eighteen patients with metastatic solid tumors received daily intramuscular (IM) injections of recombinant interferon-alpha-A (IFN alfa-2a, Roferon-A; Hoffman-LaRoche, Nutley, NJ) and recombinant IFN-gamma (rIFN-gamma) for 6 weeks. The dose levels were 0.5, 1.0, 2.0, and 5.0 X 10(6) U/m2/d of each interferon. A minimum of two patients were entered sequentially at each dose level. Fever, chills, fatigue, and a greater than or equal to 50% drop in granulocyte counts were observed at all doses. Severity of symptoms corresponded to increasing dose levels. In contrast to the tachyphylaxis to these symptoms that usually develops in patients treated with the individual interferons, many patients on this study experienced persistent fever and worsening fatigue over 6 weeks. The maximum tolerated dose was 1 X 10(6) U/m2/d of each interferon. One patient with renal-cell carcinoma achieved a partial remission (duration, 3 months). Enzyme-linked immunoassay analysis in all four patients for whom complete data were available revealed that peak blood levels of IFN alfa-2a on day 22 were about tenfold higher than on day 1. Because of the possibility of cumulative toxicity, the recommended starting dose for further studies is 0.5 X 10(6) U/m2/d of each interferon, with escalation to 1.0 X 10(6) U/m2/d after 1 month if tolerance is acceptable. Phase II investigations to explore the antitumor efficacy of this regimen are planned.
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PMID:Phase I study of a combination of recombinant interferon-alpha and recombinant interferon-gamma in cancer patients. 309 4

A combination of retinoic acid (RA) and human recombinant DNA-derived interferon-gamma (Hu-IFN-gamma) was tested with respect to the growth inhibitory action on several human mammary carcinoma cell lines (ZR-75.1, 734-B, MCF-7, and BT-20), a human lung carcinoma cell line (CCL-185), and a human laryngeal carcinoma cell line (HEP-2). The mammary carcinoma cell lines were all sensitive to Hu-IFN-gamma, and 2 of them (ZR-75.1 and 734-B) were also affected by RA. The combination of both substances led to a pronounced synergistic amplification of growth inhibition in ZR-75.1 and 734-B cells. RA also increased the antiproliferative activity of Hu-IFN-gamma in the RA-resistant BT-20 cells and to a less pronounced degree in MCF-7 cells. In contrast to these findings, no synergistic effects were observed between Hu-IFN-gamma and RA in CCL-185 and HEP-2 cells. Human recombinant DNA-derived interferon-alpha 2 amplified the action of RA only in BT-20 cells, but it did not act synergistically with RA in the other cell lines tested.
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PMID:Synergistic antiproliferative effect of human recombinant interferons and retinoic acid in cultured breast cancer cells. 309 46

To develop monoclonal antibodies (mAb) recognizing human melanoma-associated antigens (MAA) susceptible to modulation by immune interferon (IFN-gamma), hybridomas were constructed with splenocytes from a BALB/c mouse immunized with IFN-gamma-treated melanoma cells Colo 38. Screening of supernatants with control and IFN-gamma-treated melanoma cells showed that the mAb CL203 and CL207 display preferential reactivity with IFN-gamma-treated melanoma cells. The two mAb recognize the same (or spatially close) determinant on a 96,000 MAA which has a density of 0.36 X 10(6) antigenic sites/cell on untreated melanoma cells Colo 38 and of 1.39 X 10(6) and 1.54 X 10(6) on melanoma cells Colo 38 treated with IFN-gamma (final concentration, 200 U/ml) for 24 and 48 hr, respectively. The effect of IFN-gamma on the 96,000 MAA is dose- and time-dependent, reversible, and blocked by inhibitors of RNA and protein synthesis. Furthermore, the effect of IFN-gamma on the induction of the 96,000 MAA appears to be specific, inasmuch as IFN-alpha and IFN-beta do not induce the expression of the 96,000 MAA. The latter is also induced by IFN-gamma in a variety of carcinoma cell lines, but its level is markedly lower than on melanoma cells. Furthermore, the apparent m.w. of the antigen synthesized by the carcinoma cell lines in the presence of IFN-gamma ranges between 93,000 and 96,000. This molecular heterogeneity appears to reflect differences in the degree of glycosylation of the polypeptide moiety because the antigen synthesized by a variety of cell lines in the presence of tunicamycin has an apparent m.w. of 51,000.
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PMID:Characterization of a monoclonal antibody-defined human melanoma-associated antigen susceptible to induction by immune interferon. 311 85

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

Eight different human breast carcinoma cell lines, as well as clonally derived cell lines, were used to study the expression of four different monoclonal antibody (MAb)-defined tumor-associated antigens (TAAs) and the ability of recombinant human (rHu)-interferon (IFN)-alpha A and rHu-IFN-gamma to increase tumor-associated and/or normal cell-surface antigen expression. The different breast tumor cell lines expressed a wide range of antigenic phenotypes with respect to four different cell-surface TAAs. The cell lines could be divided into high and low antigen-expressing groups based on their constitutive levels of the four TAAs. In general, those breast tumor cell lines that expressed high levels of carcinoembryonic antigen, the MAb DF-3-defined 290-kD antigen, and the 90-kD antigen reactive with MAb B6.2 were poor candidates for antigen augmentation by rHu-IFN-alpha A or rHu-IFN-gamma. In contrast, breast cell lines that constitutively express low levels of these TAAs were found to be highly responsive to the ability of either of the rHu-IFNs to enhance MAb binding to the cell surface. Treatment with either of the rHu-IFNs increased the level of surface binding of MAbs as much as fourfold. The relative abilities of the IFNs to increase MAb binding to the surface of human breast tumor cells thus appeared to depend on the degree of constitutive surface antigen expression of the breast tumor cells. The high-molecular-weight TAA, TAG-72, is known not to be expressed on most cell lines but is expressed on the majority of human carcinoma biopsies. Most breast tumor cell lines employed in this study did not express the TAG-72 high-molecular-weight TAA. However, rHu-IFN-alpha A did substantially increase the level of expression of TAG-72 on the surface of breast tumor cells that were isolated from a pleural effusion. These studies may thus provide an important insight into the criteria used in the selection of carcinoma patients for IFN-mediated antigen augmentation when employing MAb-guided radioimmunolocalization or MAb-guided therapy.
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PMID:Enhancement of surface antigen expression on human breast carcinoma cells by recombinant human interferons. 313 Apr 26

The mAb CL 207 recognizes a 96-kDa melanoma-associated Ag. The latter is not modulated by antibody but is highly susceptible to induction by immune IFN-gamma on human carcinoma and melanoma cells. The mAb CL 207 does not mediate C- and cell-dependent lysis of human carcinoma and melanoma cells. Conjugation of daunomycin with mAb CL 207 causes a slight reduction of its immunoreactivity and affinity but does not affect its serologic specificity or the toxicity of daunomycin. In combination with IFN-gamma, the daunomycin-mAb CL 207 conjugate displays a selective in vitro and in vivo toxic effect on tumor cells that express the 96-kDa MAA. The synergistic effect of IFN-gamma and daunomycin-mAb CL 207 conjugate is specific. The in vivo toxicity is influenced by the interval between injection of human tumor cells into nude mice and that of IFN-gamma and daunomycin-mAb CL 207 conjugate. The present results suggest that the 96-kDa melanoma-associated Ag may be a useful model to investigate the combined use of IFN-gamma and mAb for the selective destruction of tumor cells.
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PMID:Synergistic in vitro and in vivo anti-tumor effect of daunomycin-anti-96-kDa melanoma-associated antigen monoclonal antibody CL 207 conjugate and recombinant IFN-gamma. 313 32

The expression of intercellular adhesion molecule-1 (ICAM-1) on primary human fibroblasts, a human fibrosarcoma, chondrosarcoma, and adenocarcinoma cell line in response to IL-1, TNF-alpha, or IFN-gamma was studied using an ELISA with anti-ICAM-1 mAb. The induction of ICAM-1 by these cytokines was neutralized by cytokine-specific antisera as well as some steroids and the glycosylation inhibitor, tunicamycin. Cyclohexamide up-regulated the expression of ICAM-1 on chondrosarcoma cells but had little or no effect on carcinoma cells. These data indicate different mechanisms in the regulation and expression of ICAM-1 on the various cell types and provide some insight into the anti-inflammatory effects of some pharmacologic agents.
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PMID:Induction of intercellular adhesion molecule 1 on primary and continuous cell lines by pro-inflammatory cytokines. Regulation by pharmacologic agents and neutralizing antibodies. 313 61

The effect of recombinant gamma-interferon (IFN-gamma) on established human colon carcinoma cell lines as well as fresh tumor cells from colon carcinoma patients has been investigated with respect to growth inhibition, enhancement of HLA expression, and modulation of immunogenicity. A direct antiproliferative activity of IFN-gamma was observed in five of seven cell lines tested, with a reduction of [3H]thymidine incorporation between 30 and 90%. Depending on the cell line, the IFN-gamma doses required for maximal inhibition varied between 20 and 2 X 10(4) units/ml. Independent of this effect, IFN-gamma enhanced the expression of HLA-A,B,C antigens in all cells investigated and induced expression of HLA-DR in three of seven carcinoma cell lines. Antigenic modulation of Class I and II major histocompatibility complex antigens was paralleled by an enhancement of the in vitro immunogenicity in three of four established carcinoma lines and in three of three cases, using cells derived from primary tumor cultures. Induction or enhancement of both proliferative and cytolytic T-cell responses was obtained in allogeneic and in autologous mixed-lymphocyte tumor cell cultures.
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PMID:Differential gamma-interferon response of human colon carcinoma cells: inhibition of proliferation and modulation of immunogenicity as independent effects of gamma-interferon on tumor cell growth. 316 Apr 56


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