Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gamma-interferon (gamma IFN) was found to induce expression of the 150,000 M(r) cell surface and the 35,000 M(r) chromatin receptors for nerve growth factor (NGF) in the SW1116 colorectal carcinoma cell line that does not express NGF receptors. In the SW707 colorectal carcinoma cell line that expresses a low level of NGF receptors, gamma IFN stimulated expression of the cell surface and the nuclear receptors. Induction of NGF receptors in SW1116 cells resulted in internalization and nuclear translocation of 125I-NGF. When NGF bound to the chromatin, ribosomal RNA synthesis was inhibited. Two-dimensional gel electrophoresis of [35S]methionine-labeled chromatin proteins indicated significant changes in chromatin protein composition in cells treated and not-treated with gamma IFN. gamma IFN effectively stimulated the expression of NGF receptors in two colorectal carcinoma cell lines, but inhibited the expression in melanoma and breast carcinoma cells. It is suggested that gamma IFN, by modulating the expression of NGF receptors may affect the NGF-dependent growth of some tumor cell lines.
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PMID:Gamma-interferon-induced nerve growth factor receptors in colorectal carcinoma cell lines. 134 Feb 11

We have studied the cytokine regulation of cell surface and soluble intercellular adhesion molecule 1 (ICAM-1) expression on the human melanoma cell line A375M. Unstimulated cells express ICAM-1 on their cell surface but do not secrete significant levels of soluble ICAM-1. Interleukin 1, interleukin 6, tumor necrosis factor, and gamma-interferon all increased cell surface expression of ICAM-1. Tumor necrosis factor, interleukin 1, and gamma-interferon also caused the release of soluble ICAM-1. The serum of melanoma patients has been reported to contain elevated levels of soluble ICAM-1; however, the source of this ICAM-1 is unclear. The serum from nude mice bearing s.c. human melanoma tumors was found to contain soluble human ICAM-1. ICAM-1 levels showed a positive correlation with tumor weight. The release of ICAM-1 from melanoma tumors, in response to host-derived cytokines, may have relevance to immune recognition of the tumor.
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PMID:Soluble intercellular adhesion molecule 1 is released by human melanoma cells and is associated with tumor growth in nude mice. 134 68

Five clones derived from the same human malignant melanoma lesion were studied for their susceptibility to killing by human monocytes activated by exposure to interferon (IFN)-gamma and lipopolysaccharide. Melanoma clones were heterogeneous in their susceptibility to human monocyte cytotoxicity, with one clone (2/21) exhibiting extremely low levels of lysis. The different levels of susceptibility to monocyte cytotoxicity were not accounted for by susceptibility or resistance to monokines [tumor necrosis factor (TNF), interleukin (IL)-1 and IL-6] because: (a) these effector molecules had little (TNF) or no (IL-1 and IL-6) cytolytic activity under these conditions; and (b) anti-TNF antibodies had marginal effects on cytotoxicity. Monocytes bound less to resistant than to susceptible melanoma cells. Monocyte-resistant 2/21 melanoma cells expressed substantially lower levels of ICAM-1 and VLA-4 than susceptible cells. Anti-CD18 and, to a lesser extent, anti-ICAM-1 mAb inhibited binding and cytotoxicity of human monocytes on malignant melanoma whereas anti-VLA-4 had no inhibitory action. Transfection of the ICAM-1 gene under the control of a constitutive promotor resulted in high levels of expression of ICAM-1 in 2/21 melanoma cells and, concomitantly, in augmented susceptibility to activated monocyte cytotoxicity. The augmented killing of ICAM-1 transfected 2/21 cells was inhibited by anti-ICAM-1 mAb. These results demonstrate that the CD18-ICAM-1 adhesion pathway can play an important role in the expression of human monocyte cytotoxicity on melanoma target cells and that heterogeneity in expression of ICAM-1 can underlie differences in susceptibility to tumoricidal activity.
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PMID:Heterogeneous susceptibility of human melanoma clones to monocyte cytotoxicity: role of ICAM-1 defined by antibody blocking and gene transfer. 135 29

Tumor cells often display alterations in their normal program of cellular differentiation. A promising approach for the treatment of cancer involves the induction of terminal differentiation and a loss of proliferative capacity in cancer cells. In human melanoma cells, the combination of mezerein (MEZ) and fibroblast interferon (IFN-beta), results in a rapid and irreversible suppression of cell growth with a concomitant increase in the synthesis of melanin. The induction of terminal differentiation is associated with alterations in the expression of several cellular genes, including fibronectin, ISG-15 and ISG-54, and changes in the expression of specific cell surface antigens, including intercellular adhesion molecule-1 (ICAM-1) and HLA Class I antigens. In the HO-1 human melanoma cell line, induction of terminal differentiation by MEZ plus IFN-beta results in an induction and/or increased expression of ICAM-1, HLA Class I antigens and HLA Class II antigens. IFN-beta and MEZ alone can modulate expression of these antigens to a lower extent than does the combination of compounds. Induction of terminal differentiation and the irreversible suppression of cell growth is not a prerequisite for antigenic modulation in HO-1 cells. This is indicated by the inability of immune interferon (IFN-gamma), a strong inducer of ICAM-1, HLA Class I antigens and HLA Class II antigens synthesis, or the combination of IFN-beta plus IFN-gamma which synergistically but reversibly suppresses HO-1 growth, to induce melanin synthesis or terminal differentiation in HO-1 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of the antigenic phenotype of human melanoma cells by differentiation-inducing and growth-suppressing agents. 135 50

A serum-dependent and two serum-independent variants of the Bowes melanoma cell line, RPMI7272, were transfected with plasmids containing a geneticin-resistance (neo) gene transcribed by the HSV thymidine kinase promoter and an SV40 T antigen gene under control of the mouse metallothionein I promoter. T-antigen increased the cloning efficiency of the serum-dependent cell line in soft-agar more than 50-fold, but cloning efficiency of serum-independent lines was not increased. Trypsinization of serum-independent lines required 100 times lower concentrations of trypsin than serum-dependent cells. Human metal-inducible T-antigen-producing (HMT) melanoma cells supported replication of transfected plasmids containing an SV40 origin of replication. Transient expression of interferon or plasminogen activator from such plasmids was 40-fold higher than in untransformed melanoma cells and could be enhanced 30-fold more by stimulation of transcription of the T antigen gene with cadmium chloride. HMT cells can be grown in suspension and thus may represent an attractive alternative to monkey kidney COS cells.
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PMID:Transformation of Bowes melanoma cells with SV40 T antigen. 136 20

The treatment of disseminated melanoma with monotherapy and combined chemotherapy is still associated with rather low objective response rates and significant toxicity. Therefore, more effective substances and regimens with less toxicity are desired in the pharmacologic treatment of metastatic melanoma. The initial high expectations placed in systemic cancer treatment with interferons (IFNs) were not fulfilled, but IFN-alpha as a single substance revealed an objective response rate of 10% to 15% in melanoma patients. Clinical and experimental results suggest that the antitumoral activity of IFNs is mainly related to their antiproliferative effect, whereas immunomodulatory effects were not substantiated in clinical investigations. Results of in vitro trials showed that type-I IFNs may produce antagonistic effects combined with some agents (eg, cisplatin) and synergistic effects combined with others (eg, vindesine and BCNU). Clinical trials with combined IFN and cytostatic drug therapy were started a few years ago and have yielded promising initial results. Several studies with an entire number of more than 200 patients have already been performed to evaluate the combination of IFN-alpha and dacarbazine. This regimen was effective in over 50% of the patients, leading to complete or partial remissions in 27% and stabilization of the disease in an additional 28%. Toxicity is significant but still manageable, especially with a new generation of antiemetic drugs (serotonin receptor blockers). Several clinical trials performed so far did not find an improved efficacy by adding IFN-alpha to cisplatin or to vinblastine. The combination of IFN-alpha and vindesine seems to be more favorable and superior to the response rates of single agents and was well tolerated in an ongoing trial in our clinic. Recently, a new generation of multidrug combinations including IFN-alpha has been initiated and several reports with overall response rates greater than 50% have been published. In conclusion, combined regimens with IFN-alpha and different cytostatic drugs seem to be superior to treatments with cytostatic drugs alone and rather safe in disseminated melanoma. Additional combinations of IFNs and cytostatic drugs should be evaluated in future in vitro studies and in clinical trials.
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PMID:Combined treatment of metastatic melanoma with interferons and cytotoxic drugs. 137 65

The interferons (IFNs) were identified as novel, endogenous antiviral agents in 1957. Shortly thereafter, antiproliferative and immunostimulatory activities were identified for these compounds. Based on these observations, partially purified IFNs entered clinical trials in the 1970s and recombinant IFNs in 1980. IFNs have demonstrated important clinical activity in hairy cell leukemia, melanoma, renal cell carcinoma, and Kaposi's sarcoma as monotherapy. Shortly after their introduction into clinical trials, however, preclinical studies demonstrated synergistic interactions between IFNs and cytotoxic drugs. Numerous preclinical trials have demonstrated a broad spectrum of interactions between IFNs and at least 20 cytotoxic agents both in vitro and in vivo. Early clinical trials suggest a benefit to combinations of fluorouracil and recombinant interferon alfa in refractory gastrointestinal malignancies. Combinations of IFNs and cytotoxic agents deserve further investigations; however, different principles apply for combining IFNs with cytotoxic drugs than for the design of combination chemotherapy regimens.
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PMID:Principles in the biomodulation of cytotoxic drugs by interferons. 137 5

The anti-proliferative activity of human interferon (HuIFN) was enhanced by dipyridamole, 2,6-bis-(diethanolamino)-4,8-dipiperidinopyrimido-[5,4-d]-py rimidine, when tested against various human tumor cell lines, including KT (breast carcinoma), PLC/PRF/5 (hepatoma), MGC-I, U251-SP and T98 (glioma), HAC-2 and SHIN-3 (ovarian carcinoma), and MM-ICB (melanoma). The enhancement occurred irrespective of the kind of HuIFN used (alpha, beta or gamma) and the original degree of susceptibility of the cells to HuIFN. Even low doses down to 0.01 microM of dipyridamole that had no intrinsic anti-proliferative activity could enhance the effect of HuIFN. The enhancement of HuIFN effects seems not to be caused by induction of HuIFN production, because neither anti-viral activity nor HuIFN antigens were detected in culture medium in cells treated with dipyridamole. Mopidamole, a derivative of dipyridamole lacking one piperidine residue, produced little enhancement of the effects of HuIFN. Among ovarian cancer cell lines tested, the enhancement of the activity of HuIFN by dipyridamole for HAC-2 and SHIN-3 cells was equivalent to or greater than that for 3 chemotherapy agents (adriamycin, vincristine, and a camptothecin derivative). However, neither HOC-21 ovarian cancer cells nor HEC-1 endometrial adenocarcinoma cells were susceptible to any combinations. When MGC-1, U251-SP, and HAC-2 cells were injected into nude mice, the growth of tumors was more markedly inhibited by the subcutaneous administration of HuIFN in combination with oral administration of dipyridamole than by the HuIFN alone. Thus, this combination therapy seems to be worth trying for human cancer, although the enhancement of the effects of HuIFN by dipyridamole varied among the cell lines examined.
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PMID:Dipyridamole enhances an anti-proliferative effect of interferon in various types of human tumor cells. 137 1

The relationship between autocrine interferon (IFN) production and the expression of class I Major Histocompatibility Complex (MHC) membrane glycoproteins in vitro was investigated in a panel of murine transformed cells of nonhaemopoietic origin. The panel included 11 cell lines of H-2Kb haplotype derived from fibrosarcomas, carcinomas and melanoma, and from transformed fibroblasts. IFN activity was detected in the conditioned medium of nine cell lines; fibrosarcomas were among the high IFN producers, while the non-producers were a melanoma clone and a lung carcinoma cell line. A significant correlation was found between IFN production and the expression of H-2K/D glycoproteins, thus suggesting that long-term maintainment of MHC glycoprotein expression in vitro could be mediated by self produced IFN. Two IFN producer cell lines, MN/MCA1 and R80/17, were cultured in the presence of a blocking antiserum against IFN-alpha/beta: a significant decrease in H-2b expression was observed, thus indicating the existence of an autocrine IFN circuit. Taken together these findings suggest that release of IFN is a frequent event among transformed nonhaemopoietic cells, and that self-produced IFN contributes to the regulation of MHC antigen levels in solid tumours.
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PMID:Control of H-2 expression in transformed nonhaemopoietic cells by autocrine interferon. 138 3

Type I and II interferons (IFNs) stimulate the expression of the 202 and 2'-5' oligoadenylate synthetase (OASE) genes in L929, NIH 3T3 and LM-TK- fibroblastic cell lines. In two other cell lines, B16 melanoma and F9 teratocarcinoma, these cytokines induce OASE but not the 202 mRNA. In L929 cells, IFN-alpha induces the 202 mRNA at concentrations between 10 and 10(3) units/ml. To achieve maximal induction of the 202 mRNA, continuous exposure of L929 cells to IFN-alpha is necessary, whereas 30 minutes of exposure are sufficient to trigger maximal upregulation of the OASE transcript. The induction of the 202 mRNA is the consequence of both transcriptional and post-transcriptional events. Cycloheximide, a known inhibitor of protein synthesis, does not block the induction of 202 mRNA by IFN-alpha, demonstrating that new protein synthesis is not required for this effect. Protein kinase C, arachidonic acid metabolism via the cyclooxygenase or the lipoxygenase pathways and cAMP are not involved as second messengers in the induction of the 202 mRNA by IFN-alpha in L929 cells.
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PMID:Regulation of the 202 gene expression by interferons in L929 cells. 138 18


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