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

Sera from 134 selected patients with various types of cancer were tested for soluble antigen-antibody complexes by the C1q binding method. Sera from 85 healthy blood bank donors served as normal controls. C1q binding activity (C1q BA) values above the 95th percentile for healthy subjects were found in 83% of sera from patients with neoplastic diseases. The incidence of abnormal C1q BA values among patients with malignant melanoma was 83%, with breast cancer 74%, with colon cancer 75%, with lung cancer 88%, with leukemia and lymphoma 85%, and with miscellaneous tumors 94%. High C1q BA values were found most frequently in sera of patients who had been diagnosed relatively recently (within 5 mo) and who had evident residual disease after surgical treatment. Recurrence or progression of tumor growth occurred significantly more frequently in lung cancer patients with high C1q BA. DNA was not detected in cancer patients' sera and treatment with DNase did not decrease in C1q BA. C1q BA in sera could not be explained by the presence of antiglobulin antibodies. Sucrose density gradient ultracentrifugation studies of the serum C1q BA in 4 cancer patients showed that the major binding activity was found between 19S and 7S.
 ...
PMID:The C1q binding test for soluble immune complexes: clinical correlations obtained in patients with cancer. 32 5

The growth inhibitory effect of 6-hydroxydopa, a cytotoxic analog of L-dopa, was studied in melanotic and amelanotic Cloudman melanoma, mouse fibroblast L929 and Chinese hamster ovary cells. A marked sensitivity of pigmented cells to 6-hydroxydopa was observed with a 10-fold increase in sensitivity of pigmented cells. Sensitivity correlated with the capacity of cells to incorporate radiolabeled exogenous L-dopa. The drug affected primarily DNA and RNA synthesis with greater inhibition observed in pigmented cells than the nonpigmented control cells. The mechanism of action may involve interaction with the melanocyte specific enzyme, tyrosinase, as a false substrate.
 ...
PMID:Selective toxicity of 6-hydroxydopa for melanoma cells. 42 70

Cultured human diploid skin fibroblasts incubated with [G-3H]benzo(a)pyrene yielded about 10 times more H2O-=soluble benzo(a)pyrene metabolites and DNA adducts of stationary growth phase than did proliferating cultures. This increased formation could be blocked by alpha-naphthoflavone. Trichloropropenoxide and cyclohexenoxide, inhibitors of the epoxide hydratase, inhibited predominantly the formation of DNA adducts. Cultures from older individuals formed significantly more benzo(a)pyrene metabolites and DNA adducts, but control cultures from patients with either lung cancer or melanoma did not. The age influence was not apparent when the ratio of DNA adducts to H2O-soluble metabolites was determined for each individual cell line. However, the proportion of DNA-bound material in the cells from patients with lung cancer was significantly increased compared to cells from melanoma patients or healthy individuals.
 ...
PMID:Metabolism and formation of DNA adducts of benzo(a)pyrene in human diploid fibroblasts. 42 49

The activity of a number of substituted alkylaminoanthraquinones was compared in transplanted murine tumor systems including P388 and L1210 leukemias, B16 melanoma, and colon carcinoma 26. The structure-activity relationships among this class of compounds are discussed. Several derivatives had very high antitumor activity in several tumor systems. Two of the most active derivatives, namely, 1,4-bis(2-[(2-hydroxyethyl)amino]ethylamino)-9,10-anthracenedione (bisalkylAAD) and 1,4-dihydroxy-5,8-bis(2-[(2-hydroxyethyl)amino]ethylamino)-9,10-anthracenedione (dihydroxybisalkylAAD), which had curative activity in the above-mentioned tumors, were compared in considerable detail. DihydroxybisalkylAAD showed distinct advantages over bisalkylAAD in several tumor systems and is tenfold more potent with respect to effective dose range. This last difference is important for two reasons. First, these aminoanthraquinones are strong and persistent blue dyes and the administration of lower doses would minimize a potential cosmetic drawback of these compounds. Second and most important, iv administration of dose levels of bisalkylAAD which are within the therapeutic dose range on intermittent dose schedules produced convulsions and immediate death. IV administration of dihydroxybisalkylAAD also caused acute toxicity, but, because of its increased potency relative to antitumor activity and delayed toxicity, this acute toxicity was apparent only at doses well above the therapeutic dose range. All of the aminoanthraquinones evaluated, regardless of their activity as antitumor agents in vivo, proved to be potent inhibitors of DNA and RNA synthesis in vitro and bound strongly to DNA as evidenced by deltaTm values (deltaTm = upward shift in DNA melting temperature). Thus, the strong antitumor activity of aminoanthraquinones would appear to be due to some mechanism other than, or in addition to, DNA binding and inhibition of nucleic acid synthesis.
 ...
PMID:Experimental antitumor activity of aminoanthraquinones. 42 24

The chemotherapeutic activity of thymidine (dThd) was tested against four human tumor xenografts growing in nude mice, including a melanoma, an oat cell carcinoma of the lung, a colon carcinoma, and a breast carcinoma. Tumor-bearing mice were given an infusion of dThd (1 g/kg/day) s.c. for 72 hr each week for three weeks. Tumor growth in the treated mice was compared to that in randomized concurrent control mice infused with media alone. A significant effect was found only for the melanoma, and it was cytostatic rather than cytotoxic. Even when melanomas of very small initial volume were treated, there were no complete regressions, and tumor growth resumed when dThd treatment was stopped. In culture, sustained dThd concentrations of greater than 3.2 mM were required to cause death of the melanoma cells; in the mice the dThd level during infusion ranged from 1 to 5 mM. This exposure to dThd, although failing to produce a tumor response, did produce significant toxicity in the nude mice in the form of myelosuppression and leukopenia. Flow cytometric analysis of marrow cells during the dThd infusion showed an accumulation of cells in S phase, but proliferation was not completely halted since cells with G2-M content of DNA were present in the marrow even after 72 hr of dThd exposure. This study failed to demonstrate a therapeutically useful effect of dThd on these tumors.
 ...
PMID:Activity of thymidine as a chemotherapeutic agent against human tumor xenografts in nude mice. 47 23

In seven human melanoma cell lines and one human fibroblast strain some correlation of resistance to cell killing was found with two bifunctional alkylating agents (melphalan, chlorambucil) and three monofunctional agents (4(5)-(3,3-dimethyl-l-triazeno)imidazole-5(4)-carboxamide (DTIC), methylmethane sulphonate (MMS) and N-methyl-N1-nitro-N-nitrosoguanidine (MNNG), but little cross-resistance was found between these two groups of agents or with cytosine arabinoside (ara-C). In contrast to previous studies with rodent tumours, potentially synergistic (chloroquine, arginine) or antagonistic (ascorbic acid, leucine) compounds did not affect the toxicity of melphalan in a human melanoma cell line. In two melanoma lines DTIC induced patterns of DNA damage (inhibition of semi-conservative synthesis) and repair (strand breaks and repair synthesis) similar to, but not identical with, those induced by the methylating agent MMNG. These results suggest that a methylating species is derived from DTIC but has a different reactivity toward DNA compared with MNNG.
 ...
PMID:Cytotoxicity studies of human melanoma cells and fibroblasts. 48 82

The effects of purine deoxyribonucleosides on bromodeoxyurdine (BrdU) mutagenesis in Syrian hamster melanoma cells were determined. Both deoxyguanosine (dG) and deoxyadenosine (dA) were found to stimulate mutagenesis without changing the amount of BrdU in DNA. In addition, the stimulation of mutagenesis by dG and dA was suppressed by the addition of deoxycytidine (dC). These results suggest that BrdU mutagenesis involves the perturbation of dC metabolism, which perturbation is enhanced by dGTP and dATP. The mutagenic activity of dG in the absence of BrdU was tested, as was that of thymidine (dT), which we had shown previously to stimulate BrdU mutageneis. With dG alone, no increase above the spontaneous mutation frequency was detected. However, at extremely high concentration, dT in the absence of BrdU was slightly mutagenic, and the mutagenesis by dT was enhanced by dG and suppressed by dC.
 ...
PMID:Bromodeoxyuridine mutagenesis in mammalian cells is stimulated by purine deoxyribonucleosides. 53 35

Mutant cell lines resistant to hydroxyurea (HU), an inhibitor of the enzyme ribonucleotide reductase, were selected from a line of Syrian hamster melanoma cells. Mutant lines were selected for resistance to 0.3 mM HU, and from these lines, second-step mutants were selected for resistance to 1.9 mM HU. The HUr lines were tested ffor their responses to 5-bromodeoxyuridine (brdU), in terms of toxicity, mutagenesis, and incorporation of BrdU into DNA. All of the HUr lines showed increased resistance to the toxic effects of BrdU. in addition, the HUr lines all were resistant to BrdU mutagenesis. Overall, there was good correlation among the levels of resistance to HU toxicity, BrdU toxicity, and BrdU mutagenesis in the HUr lines. These tests were carried out under conditions such that the parental and HUr cells incorporated equal amounts of BrdU into nuclear DNA. Therefore, the resistance of the HUr cells to the effects of BrdU cannot be attributed to decreased incorporation of BrdU into DNA. These results suggest that the HUr cells have an lateration in ribonucleotide reductase activity that simultaneously confers resistance to HU and BrdU. The properties of the HUr cells suggest that the perturbation of deoxcytidine metabolism by BrdU. The properties of the HUr cells suggest that the perturbation of deoxcytidine metabolism by BrdU triphosphate inhibition of ribonucleotide reductase activity plays a key role in the toxic and mutagenic effects of BrdU in mammalian cells.
 ...
PMID:Resistance to bromodeoxyuridine mutagenesis and toxicity in mammalian cells selected for resistance to hydroxyurea. 54 27

In a malignant choroidal melanoma, basophilic deposits were seen as globules between cells, intracellularly and in the vessel lumina. They were observed primarily in necrotic or incipient necrotic areas. A battery of histochemical methods showed these deposits to consist of DNA and possibly small amounts of RNA. By electron microscopy, their origin was evidenced to be the nuclear chromatin. Their presence in the vessel lumina suggested removal by the circulation. The resulting influence on the production of antibodies is also mentioned.
 ...
PMID:DNA 'lakes' in a malignant choroidal melanoma. 54 18

Peritoneal macrophages from unstimulated nonimmune BALB/c mice exerted nonspecific cytostatic effects of tumor cells in vitro. Incubation of syngeneic B40 lymphoma or allogeneic B16 melanoma cells with peritoneal macrophages or with macrophage culture supernatant fluids (SF) resulted in decreased target cell DNA synthesis and growth; in contrast, nontumorigenic syngeneic 3T3 fibroblasts were stimulated by macrophages but SF exerted no significant effects. Lipopolysaccharide activation of macrophages did not induce cytotoxicity for any target cell tested, and did not enhance the observed tumoristatic effects. The level of tumor inhibition associated with macrophage culture SF was dependent upon the concentration of fetal calf serum present in the medium as well as upon the numbers of macrophages cultured. Inhibitory SF could be harvested continuously from macrophage cultures for at least 7 days with no appreciable loss of activity.
 ...
PMID:Tumoristatic effects of nonimmune BALB/c peritoneal macrophages on syngeneic lymphoma cells in vitro. 59 52


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>