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)

A human B-lymphoblastoid cell clone, L55-81, that produces human monoclonal antibody (MAb) to ganglioside G(M2) was established from peripheral blood B lymphocytes of a melanoma patient. L55-81 secretes IgMkappa light chain antibody in a serum-free medium. G(M2) specificity of the antibody was tested by immune adherence assay, TLC immunostaining, and ELISA. Anti-G(M2) antibody was shown to have the ability to kill the G(M2)-rich human melanoma cell line M14 in the presence of human or rabbit complement. A purified L55-81 MAb (>99.5% purity in protein concentration) was biotinylated and tested for its reactivity to various histological-type biopsied tumor and normal tissues in an avidin-biotin detection system. L55-81 MAb (20 microg/ml) reacted with several types of tumor tissues such as melanoma (7 of 10), colon carcinoma (4 of 5), ovary carcinoma (4 of 5), breast carcinoma (1 of 5), kidney carcinoma (1 of 5), and prostate carcinoma (1 of 5). None of the normal tissues derived from 24 different organs and adjacent normal tissues surrounding the cancerous tissues were stained. Production of the antibody in a serum-free medium, the cytotoxic potential with human complement, the inability to react to normal tissues, and the ability to target antigen-specific target cells make L55-81 a potential therapeutic agent for the treatment of cancers expressing ganglioside G(M2).
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PMID:Development of a human monoclonal antibody to ganglioside G(M2) with potential for cancer treatment. 897 Nov 73

The polar solvent N-methylformamide proved to be capable of enhancing the cytotoxic potential of various antitumoral compounds, both in vitro and in vivo. In many cases, this ability depended on the sequence of treatment, and the enhancement of the cytotoxic effect occurred only when N-methylformamide administration succeeded anticancer drug treatment. The results obtained in the present study indicate that N-methylformamide interferes with the mechanisms of intracellular transport and efflux of the antitumoral drug doxorubicin. In particular, laser scanning confocal microscopy observations performed on melanoma cells (M14) after N-methylformamide administration revealed evident alterations of the microtubular network, including numerous interruptions of the microtubules. Moreover, when doxorubicin-treated cells were recovered in the presence of the polar solvent, the normal efflux of the anthracyclinic antibiotic appeared to be hampered, and the drug was localized mainly in well delimited perinuclear regions. Double staining experiments demonstrated the colocalization of the doxorubicin molecules and the WGA-stained regions as well as a close structural relationship between them and the microtubule system. These results indicate that N-methylformamide interferes with the doxorubicin transport inducing a damage in the microtubular network and the consequent persistence and entrapment of the drug in the regions likely occupied by the Golgi apparatus of tumor cells. This finding could account for the chemosensitizing properties exerted by N-methylformamide.
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PMID:Influence of N-methylformamide on the intracellular transport of doxorubicin. 901 27

Availability of a standard human melanocyte cell line with unlimited growth potential and otherwise normal melanocytic properties will greatly facilitate research in melanocyte biology and in vitro studies on the etiology of pigmentary disorders and melanoma. Using a retroviral vector, E6 and E7 open reading frames of human papilloma virus type 16 (HPV 16) have been introduced into cultured normal human melanocytes. Cells selected by increased resistance to geneticin conveyed by the vector and expressing E6E7 mRNA have been cloned to ensure genetic homogeneity. Since their establishment as primary cells, cloned PIG1 cells have undergone more than twice the amount of population doublings of senescent parental cells. Moreover, in passage numbers when parental cells had become senescent, proliferation of clonal cells was retained at levels exceeding those of normal human melanocytes in third passage by 100%. Further characterization has revealed that the cells remain dependent on tetradecanoyl phorbol 13-acetate (TPA) for growth and do not proliferate in soft agar nor form tumors in nude mice. The antigenic profile of the cells was slightly altered as compared to parental cells, but was incomparable to that of M14 melanoma cells. Importantly, PIG1 cells contain more melanin pigment than parental cells.
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PMID:Generation of a human melanocyte cell line by introduction of HPV16 E6 and E7 genes. 902 34

A new methoxymorpholinyl derivative of Adriamycin (ADR), FCE 23762 (MRD), has recently been selected for phase I clinical trials for its reduced cardiotoxicity and for its cytotoxic activity against a broad spectrum of solid tumors and leukemias that are sensitive or resistant to ADR. The purpose of the present study was to compare the in vitro antitumor activity of MRD and ADR on human melanoma lines with different chemosensitivity to triazene compounds, among which dacarbazine remains a reference drug in the treatment of melanoma. Both MRD and ADR were tested in vitro on three melanoma lines, MI13443-MEL, SK-MEL-28, and M14, previously screened for their chemosensitivity to the triazene compound p-(3-methyl-1-triazeno) benzoic acid, potassium salt (MTBA). The three lines were also analyzed for P-170 expression, total glutathione (GSH) content, and GSH-related enzyme activity. All melanomas, whether sensitive or resistant to MTBA, were susceptible to anthracycline treatment. The cytotoxic activity of MRD was comparable with that of ADR, and no substantial difference was found in cell growth inhibition between the two drugs. When the relative chemosensitivity of the three lines was considered, SK-MEL-28 was found to be slightly less sensitive to MRD treatment than the other tumors. This finding seems to correlate with the higher GSH-peroxidase activity of this melanoma relative to that of the MI13443 and M14 lines. These results show a homogeneous response of melanoma lines to MRD treatment in vitro, suggesting that phase I clinical trials concerning this drug, which in vivo appears to be activated to a more cytotoxic metabolite, could be extended to metastatic melanomas, including those completely resistant to triazene compounds.
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PMID:In vitro antitumor activity of 3'-desamino-3'(2-methoxy-4-morpholinyl) doxorubicin on human melanoma cells sensitive or resistant to triazene compounds. 918 41

L-buthionine-S,R-sulfoximine (BSO) selectivley inhibits glutathione (GSH) synthesis. Malignant melanoma may be uniquely dependent on GSH and its linked enzymes, glutathione S-transferase (GST) and GSH-peroxidase, for metabolism of reactive orthoquinones and peroxides produced during melanin synthesis. We compared the in vitro effects of BSO on melanoma cell lines and fresh melanoma specimens (n = 118) with breast and ovarian cell lines and solid tumors (n = 244). IC50 values (microM) for BSO on melanoma, breast and ovarian tumor specimens were 1.9, 8.6, and 29, respectively. The IC90 for melanoma was 25.5 microM, a level 20-fold lower than steady state levels achieved clinically. The sensitivity of individual specimens of melanoma correlated with their melanin content (r = 0.63). BSO synergistically enhanced BCNU activity against melanoma cell lines and human tumors. We followed GSH levels, GST enzyme activity, GST isoenzyme profiles and mRNA levels after BSO. BSO (50 microM) treatment for 48 hr resulted in a 95% decrease in ZAZ and M14 melanoma cell line GSH levels, and a 60% decrease in GST enzyme activity. GST-mu protein and mRNA levels were significantly reduced in both cell lines. GST-pi expression was unaffected. These data suggest that BSO action on melanoma may be related to GSH depletion, diminishing the capacity to scavenge toxic metabolites produced during melanin synthesis. We report here for the first time that BSO enhancement of alkylator action may be related in part to down regulation of GST. BSO may be a clinically useful adjunct in the treatment of malignant melanoma.
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PMID:Selective and synergistic activity of L-S,R-buthionine sulfoximine on malignant melanoma is accompanied by decreased expression of glutathione-S-transferase. 926 31

We studied the relation between tumour vascular density and tumour growth rate, metastatic incidence and vascular permeability factor (VPF) mRNA levels in a human xenograft model described previously. Vascular density was determined by automated image analysis. Xenografts derived from cell lines BLM and MV3 showed the highest mean vascular density (MVD), the highest in vivo growth rate, high VPF mRNA levels and rapid development of lung metastases. Xenografts of cell lines M14, Mel57 and MV1 showed a significantly lower degree of vascularization, lower in vivo growth rates and lower levels of VPF mRNA, but formed lung metastases with a similar incidence as those of BLM and MV3. Xenografts from cell line 1F6 did not form lung metastases, whereas tumours derived from a spontaneous mutant of 1F6, designated 1F6m, gave rise to lung metastases to the same extent as Mel57, M14 and MV1 tumours. MVD values in 1F6 and 1F6m xenografts, VPF mRNA levels and in vivo growth rates of 1F6 and 1 F6m xenografts, however, were similar. In conclusion, in the melanoma xenograft model vascular density is correlated with in vivo growth rate and with in vitro VPF mRNA levels, but not with the ability to metastasize.
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PMID:Vascular density in melanoma xenografts correlates with vascular permeability factor expression but not with metastatic potential. 930 53

We have studied whether N-methylformamide can affect the expression pattern of adhesion molecules and the attachment behaviour of M14 human melanoma cells. The role of N-methylformamide on experimental and spontaneous pulmonary metastases from M14 cells in nude mice was also investigated. We demonstrate that N-methylformamide in vitro pretreatment of M14 cells, although inducing a significant increase in the expression of alpha2beta1, alpha6beta1 and alpha(v)beta3 integrin receptors, slightly modifies alpha5beta1 heterodimer and beta1 subunit expression. After this modulation, enhancement of cell adhesion to laminin, collagen I, vitronectin and fibrinogen, which is blocked by specific anti-integrin antibodies, also occurs. No changes in binding to fibronectin are observed. In vitro N-methylformamide pretreatment also results in an increased number of experimental nodules and in a decrease in spontaneous metastases. Moreover, in vivo treatment with N-methylformamide significantly reduces the number of spontaneous metastases. Collectively, these data show that N-methylformamide modulates the expression of some adhesion receptors, cell adhesion to laminin, collagen I, vitronectin and fibrinogen as well as the metastatic behaviour of M14 cells. Our data also suggest that the effect of N-methylformamide might be evaluated in combination with antineoplastic agents for the treatment of human melanoma.
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PMID:N-methylformamide induces changes on adhesive properties and lung-colonizing potential of M14 melanoma cells. 946 Sep 90

The aim of the present study was to explore whether nitric oxide (NO) interferes with the attachment of human melanocytes to the extracellular matrix (ECM) components. Consequently, the effects have been investigated of the NO-releasing compounds 3-morpholino-sydnonimine (SIN-1) and S-nitroso-glutathione (GSNO) on the in vitro adhesion of human melanocytic cells to fibronectin. The NO donors induced a concentration-dependent reduction in the adhesion of both 51CrO4(2-)-labelled melanocytes and melanoma cells to fibronectin. Pigmented M14 melanoma cells were more susceptible to the effect of SIN-1 (half-maximal inhibiting effect at about 0.5 mM) than normal human melanocytes and also than the non-pigmented melanoma cells Mel57 (half-maximal inhibiting effects between 0.9 and 2 mM). This effect of SIN-1 also appeared to be related to the melanin content of normal melanocytes, whereas GSNO was significantly less active. Both flow cytometric analysis and immunocytochemical staining showed expression of neuronal NO synthase in all cell lines. The results of this study suggest that aberrant in vivo production of NO during infection and inflammation may contribute to loss of melanocytes in, for example, vitiligo, by reducing de novo attachment of melanocytes to the ECM. These findings could also be important for understanding the process of metastasis.
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PMID:Effect of nitric oxide on the adhesion of human melanocytes to extracellular matrix components. 949 65

We assessed the antiproliferative effects of human recombinant interferon-alpha2a (IFNalpha2a) and 13-cis-retinoic acid (13cis-RA) on two human melanoma cell lines (JR8 and M14). Both cell lines showed a very modest sensitivity to IFNalpha2a and 13cis-RA as single agents. In JR8 cells, the combination of the two compounds consistently produced simple additive effects. In contrast, different effects of the combination were recorded in the M14 cell line depending on the treatment schedule. Specifically, an additive interaction was observed when IFNalpha2a and 13cis-RA were given in sequence, independently of the order of drug administration, whereas a supra-additive antiproliferative effect was seen when cells were simultaneously exposed to the two drugs. Exposure to 1000 IU/ml IFNalpha2a markedly increased the nuclear expression of signal transducers and activators of transcription (STAT) proteins in both cell lines. By itself 10 microM 13cis-RA did not affect STAT protein expression or modify the extent of activation of such proteins by IFNalpha2a. Results from our study showed an enhancement of the antiproliferative activity of IFNalpha2a and 13cis-RA when given in combination and suggest that such an enhancement is not mediated by a concomitant effect of 13cis-RA on STAT protein activation.
Melanoma Res 1998 Feb
PMID:Combined effects of interferon-alpha2a and 13-cis-retinoic acid on human melanoma cell growth and STAT protein expression. 950 74

Eighty-six lymph nodes at measured distances from a primary tumor were removed from 68 patients with malignant melanoma. The ability of lymph-node lymphocytes (LNL) from these nodes to modulate proliferation of a melanoma cell line (UCLA-SO-M14) in vitro was tested. LNL from the majority of lymph nodes (66%) inhibited M14 growth, but LNL from 34% of nodes stimulated growth of the cell line. Peripheral blood mononuclear cells always inhibited M14 growth. Distance of a node from the primary tumor was found to be an important determinant of LNL activity. This was demonstrated using pairs of nodes from individual patients. In 86% of cases, LNL from nodes located nearer to the tumor inhibited M14 growth less than LNL from more distant nodes. Stimulation of M14 growth was commonest with LNL from nodes located near to the tumor. CD8+ T cells were largely responsible for M14 growth inhibition, whereas CD4+ cells were associated with stimulation of M14 growth. Removal of CD4+ lymphocytes from growth stimulatory LNL resulted in a CD4-depleted LNL preparation that inhibited M14 cell proliferation. The environment in lymph nodes located dose to tumors may thus favor growth of metastatic tumor cells.
Melanoma Res 1997 Aug
PMID:Lymphocytes from lymph nodes at different distances from human melanoma vary in their capacity to inhibit/enhance tumor cell growth in vitro. 957 18


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