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)

Theophyllin, an inhibitor of cAMP-degrading phosphodiesterase, stimulates melanin biosynthesis in cultures of RPMI 3460 hamster melanoma cells. Although theophylline does produce an initial transient elevation of intracellular cAMP levels, long-term treatment with theophylline produces a significant decrease in cAMP content. There is an inhibition of the theophylline stimulation by dibutyryl-cAMP; this is apparently caused by interference of dibutyryl-cAMP with the uptake and incorporation of theophylline, as shown by experiments with 3H-theophylline. An alternative theory is that theophylline, being a methylxanthine compound, is metabolized by the cell and possibly causes melanotic stimulation by becoming incorporated into cellular nucleic acids or by altering the normal nucleic acid metabolism. The following observations are consistent with this theory: (u) 3H-theophylline was incorporated into both trichloroacetic acid (TCA)-soluble and TCA-insoluble cell fractions; most of the insoluble label became soluble after digestion with ribonuclease and deoxyribonuclease. (2) These nuclease digests of the 3H-theophylline-labeled TCA-insoluble cell fractions contained 3H-labeled material that chromatographed differently from normal nucleotides on ion exchange thin layer sheets. (3) The acid-soluble pool of 3H label disappeared rapidly while both the insoluble label and the induction of melanogenesis remained stable for 50 hr after the removal of exogenous 3H-theophylline.
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PMID:Theophylline incorporation into the nucleic acids of theophylline-stimulated melanoma cells. 21 85

Several newly synthesized boron betaine analogs had antitumor activity in Ehrlich ascites, Walker 256 ascites carcinosarcoma, and Lewis lung screens and marginal activity in the B-16 melanotic melanoma screen. In vivo testing demonstrated that trimethylamine-cyanoborane inhibied Ehrlich ascites cell DNA and protein syntheses as well as gene modulation by chromatin protein phosphorylation and methylation. Trimethylamine-cyanoborane increased cyclic-AMP levels. In vitro testing showed that nuclear DNA polymerase, thymidylate synthetase, S-adenosylmethyltransferase, nonhistone chromatin methylation, deoxyribonuclease, ribonuclease, and cathepsin were inhibited by the boron analogs. These compounds did not demonstrate high antitumor activity at the doses employed, but blockage of methyl transfer from S-adenosylmethionine was established as a feasible method for controlling cell proliferation.
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PMID:Boron betaine analogs: antitumor activity and effects on Ehrlich ascites tumor cell metabolism. 22 87

The effect of I-RNA therapy was studied in a B16 melanoma-C57BL/6J mouse system. After having primary B16 isografts excised, mice receiving syngeneic lymphocytes incubated in vitro with specific guinea pig B16 I-RNA showed significantly improved survival as compared to control mice receiving untreated lymphocytes. This therapeutic effect was tumor specific and RNase sensitive. Significant cytotoxicity against B16 cells in vitro was consistently observed with lymphocytes prepared from B16 I-RNA treated animals, whereas lymphocytes from control animals or those treated with RNase-degraded B16 I-RNA or 3LL I-RNA had no effect. Results suggest that the combination of surgery and immunotherapy with I-RNA may be useful in preventing tumor recurrence in certain patients with cancer.
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PMID:Immunotherapy with RNA in cancer. 29 31

The effect of immune RNA treatment on the incidence of death from pulmonary metastases was studied in C57BL/6J mice after excision of a B16 murine melanoma. Immune RNA was extracted from the lymphoid tissues of guinea pigs immunized with B16 tumor and then incubated in vitro with normal C57BL/6J mouse splenocytes. Mice receiving intraperitoneal injections of these RNA-treated syngeneic splenocytes after the primary B16 isograft was resectioned showed significantly improved long-term survival (42 to 67 percent in three successive experiments) as compared to control mice (0 to 20 percent survival) receiving untreated splenocytes. The effect of RNA treatment was tumor-specific and ribonuclease sensitive. The results suggest that immunotherapy with immune RNA may be of benefit to certain patients after surgery for cancer.
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PMID:Prevention of death from metastases by immune RNA therapy. 69 19

In vivo experiments performed with NIH (nu/nu, bg/bg, xid/xid) triple immunodeficient (TD) mice revealed the striking ability of i.v. injected B16-F1 and B16-F10 murine melanoma cells to colonize not only the lungs but also the liver of TD mice. Subsequently, B16 melanoma cell cultures, which express very low levels of H-2Kb antigen, were cotransfected with plasmids pRSVneo, containing the neomycin resistance gene, and 6-2B1pMT, expressing the H-2Kb complentary DNA under the control of the metallothionein enhancer-promoter. Several neomycin-resistant clones were analyzed for H-2Kb and H-2Db expression by RNase protection and flow cytometry assays. All parental lines and transfected clones expressed normal levels of H-2Db mRNA, while only some of the transfected clones expressed easily detectable levels of H-2Kb mRNA. Moreover, in these clones H-2Kb expression could be enhanced in the presence of Zn2+, indicating that the metallothionein enhancer was functioning properly. Parental cells and transfected clones were injected i.v. in TD mice to assess the possible involvement of H-2Kb antigen in regulating the metastatic potential of B16 melanoma cells. We observed a remarkable correlation between expression of H-2Kb antigen and suppression of liver-specific metastases in TD mice. Identical results were obtained when we gave TD mice injections of mixed populations of transfectants expressing H-2Kb antigen, obtained by fluorescence-activated cell sorting. These experiments allowed us to rule out the possibility that the observed changes in metastatic potential were due to clonal variability among individual transfected clones. Taken together, the results of our in vivo studies with immunodeficient mice support the notion that specific major histocompatibility complex Class I molecules modulate the metastatic potential of malignant cells also by mechanisms which are independent of their well-established role in antigen presentation.
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PMID:Expression of a transfected H-2Kb gene in B16 cells correlates with suppression of liver metastases in triple immunodeficient mice. 161 80

In a group of four human tumor cell lines comprising one melanoma, one glioma, one teratocarcinoma and one neuroblastoma, the expression of the intercellular adhesion molecule-1 (ICAM-1) was found to be significantly increased following treatment with 10 microM of all-trans retinoic acid. In the melanoma and glioma cell lines HS 294T and HS 683, greater than 90% of the cells reacted with the anti-ICAM-1 monoclonal antibody (mAb) CL203.4 in the absence of treatment. Retinoic acid increased the cell surface expression of the molecule by 2-fold. In the teratocarcinoma and neuroblastoma cell lines, TERA-2 and SK-N-SH, the constitutive expression of ICAM-1 was weak, the percentage of cells stained above the background being less than 25%. Retinoic acid induced ICAM-1 expression in greater than 80% of the cells and increased the levels of expression by 2.5 to 3-fold. Immunoprecipitation studies in biosynthetically labeled cells as well as RNase protection analysis confirmed that retinoic acid treatment increased the amount of ICAM-1 at both the protein and mRNA level. The induction or stimulation occurred within 24 h, was maximal after 4 days and reversible.
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PMID:Regulation by retinoic acid of ICAM-1 expression on human tumor cell lines. 168 Mar 99

Our previous studies have demonstrated the production and release of a tumor-derived factor that promoted lipolysis in normal adipocytes. We further demonstrated that this in vitro lipolysis was correlated with the in vivo loss of total carcass lipids induced by the presence of the same tumor. This study identified and isolated this "lipolysis-promoting" factor (LPF), released into the extracellular environment (conditioned media) by the human A375 melanoma cell line, which appears to be responsible for the previously demonstrated induction of in vitro and in vivo lipolytic activity. Unlike previously described non-tumor-derived molecules, such as tumor necrosis factor-alpha/cachectin, which have been implicated in cancer cachexia, the LPF induces alterations in lipid metabolism similar to those observed in cancer patients. The biochemical nature of human tumor-derived LPF appears to be a heat-stable molecule with an apparent molecular weight of approximately 6000. The lipolysis-promoting activity was trichloroacetic acid precipitable, but not precipitable with protamine sulfate or extractable with chloroform:methanol. Its activity appears to be resistant to enzymatic treatments with protease K, trypsin, Pronase, RNase, and DNase, as well as to periodate oxidation. Immunochemically, LPF appears to be distinct from tumor necrosis factor-alpha/cachectin. Furthermore, in contrast to the mechanism of action of tumor necrosis factor-alpha/cachectin, the mechanism of "lipolysis promotion" by LPF appears to be by the induction of cellular lipase activity.
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PMID:Identification of a human tumor-derived lipolysis-promoting factor. 173 44

We have detected a 6-bp deletion in the untranslated first exon of a unique HRAS1 gene cloned from lymphocyte DNA of a familial melanoma patient. The deletion is without apparent functional consequence. Using an RNase protection assay, we have demonstrated the deletion in leukocyte DNAs of individuals unrelated to the patient. In these cases, the deletion marker is specifically associated with one class of common HRAS1 allele, thereby establishing the origin of the unique allele. We discuss the means by which DNA sequence heterogeneity at other loci may be rapidly analyzed.
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PMID:Allele-specific deletion in exon I of the HRAS1 gene. 257 74

In xiphophorine fish suffering from a genetically caused melanoma, both suppression of melanoma development and regression of the existing melanoma were observed after treatment of the fish with an "anti-melanoma immune RNA." This RNA was extracted from the lymphoid organs of guinea pigs immunized with fish melanoma. RNA from guinea pigs immunized with fish skin or liver and RNA from nonimmunized guinea pigs were ineffective. RNase treatment of the anti-melanoma immune RNA diminished its activity, although Pronase treatment did not. Analysis of antisera obtained from guinea pigs and rabbits immunized with either melanoma or normal skin of xiphophorine fish revealed differences in the immune responses induced by these tissues. The anti-melanoma sera recognized antigens in melanoma extracts, which were not present in skin extracts. These antigens were not recognized by the anti-skin sera. The results suggest specificity of the anti-melanoma immune RNA.
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PMID:Suppression of melanoma development and regression of melanoma in xiphophorine fish after treatment with immune RNA. 616 47

Immunofluorescence was used to examine antibodies to cellular antigens in the sera of patients with malignant melanoma. Sera from 60 melanoma patients and from 33 control individuals (13 normal subjects and 20 disease controls) were studied. Ninety % of the melanoma sera were found to have antinuclear antibodies when epithelial cell lines or melanoma lines were used as substrates for their detection, compared to 18% in the control group. Antinucleolar antibodies and anticytoplasmic antibodies were present in 32 and 17%, respectively, in malignant melanoma but none in the controls. Antinuclear and antinucleolar antibodies could be classified into different types according to different patterns of staining and susceptibility of antigens to digestion with DNase, RNase, and trypsin. Certain types of antibodies, such as those showing granular nuclear staining, appeared to be associated with less advanced stages of malignant melanoma, whereas those showing nucleolar and large speckled nuclear staining were associated with more advanced stages of the disease.
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PMID:Antinuclear, antinucleolar, and anticytoplasmic antibodies in patients with malignant melanoma. 633 6


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