Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1522102 (Melanoma)
 7,698 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A melanoma tumor-associated antigen (TAA), isolated from spent culture medium of human melanoma cell line UCLA-SO-M14, was purified to mean homogeneity to determine its physical and biochemical nature. Gel filtration and native polyacrylamide gel electrophoretic analyses of the 125I-labeled melanoma TAA revealed that the antigen had a molecular weight in the range of 180,000-190,000. However, ultracentrifugation of melanoma 125I-labeled TAA in a 5-20% sucrose density gradient revealed a sedimentation coefficient to be 4.96 +/- 0.24. Melanoma 125I-labeled TAA focused at a pH of 6.5 by isoelectric focusing. No carbohydrates were detectable by various colorometric methods in the highly purified melanoma TAA fraction, and melanoma TAA failed to bind with several lectins. Its antigenic activity was destroyed by the proteolytic enzymes but was not affected by the glycosidic enzymes or phospholipase A2. The results suggested that the melanoma TAA was most likely a lipoprotein that had a molecular weight of 180,000-190,000, a sedimentation coefficient of approximately 5, and a pl value of 6.5. The protein portion apparently formed the antibody binding site(s).
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PMID:Studies of a melanoma tumor-associated antigen detected in the spent culture medium of a human melanoma cell line by allogeneic antibody. III. Physicochemical properties. 658 6

A human melanoma cell line, M14 , adapted to grow in serum free synthetic media was examined for its expression and secretion of several serologically defined melanoma associated antigens (MAA) previously described in this laboratory. Melanoma associated antigen expression and secretion was identical to that of M14 cells grown in parallel in serum supplemented medium. Spent synthetic media was found to be an enriched serum free source for the initial isolation of 100 kilodalton secreted glycoprotein MAA. M14 melanoma cells grown in synthetic media were also shown to be adaptable to the double agar clonogenic assay facilitating the examination of clonal heterogeneity in functional studies of MAA in melanoma tumor biology. Recent investigations from this laboratory have focused on characterizing human melanoma associated antigens (MAA) found either as secreted or cell surface associated glycoproteins in human melanoma cell lines. In these studies, monoclonal and polyclonal antiserums to melanoma cell components have been developed to specifically identify these MAAs immunochemically and provide a means to study the structural biochemistry of these determinants. At this time we have identified two antigens on which our research efforts are targeted: 1) a 100,000 dalton secreted glycoprotein (100K) common to melanoma, sarcoma and neuroblastoma tumor cell lines, and 2) a 250,000 dalton-high molecular weight component glycoprotein-proteoglycan complex which is thus far restricted to melanoma cells. The ultimate goal of our efforts is two-fold. Initially, we hope to develop schemes to isolate these melanoma associated antigens in sufficient quantities to obtain detailed structural information on these molecules, and secondly, we wish to implicate these glycoproteins in functional aspects of the biology of metastatic human melanoma in vitro.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Antigenic expression of human melanoma cells in serum-free medium. 673 Nov 48

The inhibitory effect of saporin 6, a single-chain ribosome-inactivating protein (sc-RIP) purified from the seeds of Saponaria officinalis, on the proliferation of human primary (MeWo, WM 164, SK MEL 28, MEM), cloned (MEM A9, A12, A13) and metastatic (M14) melanoma cells has been tested by protein synthesis and colony formation assays in vitro. Results indicate a marked difference in the sensitivity of primary and metastatic cells to the action of saporin 6, the latter being significantly more affected, both in treated and in pretreated cultures, with a high and specific response evident after 24 h of treatment and progressively increasing up to 72 h of culture with the drug (IC50 = 0.82 microgram/ml). This effect, which was dose-dependent in exponentially growing cells, was partially reversed upon removal of the inhibitor from the culture medium. No inhibitory effect was evident in the MeWo primary cells at the highest saporin 6 concentration used: the p170 glycoprotein-mediated mechanism is not involved in such a resistance pathway.
Melanoma Res 1993 Oct
PMID:Diverse activity of sc-RIP saporin 6 on primary and metastatic melanoma cells in vitro. 829 94

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

Melanoma cells exhibit, both in vivo and in vitro, intrinsic drug resistance to various chemotherapeutic agents. Cultured human melanoma cells (M14) intrinsically express significant amounts of multidrug resistance-related protein (MRP1) and P-glycoprotein (P-gp) in the Golgi apparatus, but do not express these drug transporters on the plasma membrane. A panel of multidrug resistant (MDR) melanoma cell lines (M14Dx), showing different degrees of resistance to doxorubicin (DOX), were isolated. In M14Dx lines, the appearance of surface P-gp, but not of MRP1 or lung resistance related protein (LRP), occurred in cells grown in the presence of DOX concentrations higher than 60 nM. Furthermore, P-gp levels appeared to be dose-dependent. Flow cytometry, laser scanning confocal microscopy and cytotoxicity studies demonstrated that the activity of the drug extrusion system was related to both surface P-gp expression and resistance to DOX. In conclusion, P-gp, but not MRP1 or LRP, might play a pivotal role in the pharmacologically-induced MDR phenotype of melanoma cells.
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PMID:Induction of P-glycoprotein expression on the plasma membrane of human melanoma cells. 1095 45

It has been reported that UVA effects are partly mediated by production of reactive oxygen species. Moreover, oxidative stress increases protein damage, involving the occurrence of isoaspartyl residues, a product of protein deamidation/isomerization reactions. This work was undertaken in order to study the effects of UVA irradiation, mediated by oxidation, on sensitive protein targets. Melanoma cells exposed to UVA rays have been chosen as a model for monitoring the occurrence of L-isoaspartyl sites. A dramatic increase of these abnormal residues, specifically recognized and methylated by the enzyme L-isoaspartate(D-aspartate) O-methyltransferase (PCMT; EC 2.1.1.77), can be detected after exposure of M14 cells to raising doses of UVA. The effect of UVA on NO and TBARS accumulation, as well as on DNA fragmentation, has also been investigated. NO formation parallels the increase in isoaspartyl formation, while lipid peroxidation occurs only at the highest UVA doses. No DNA fragmentation has been detected under the employed experimental conditions. These results, as a whole, indicate that protein damages are one of the early events on UVA-induced cell injury. The endogenous activity of PCMT remains remarkably stable under UVA treatment, suggesting that this enzyme might play a crucial role in the repair and/or disposal of damaged proteins in UVA-irradiated cells.
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PMID:UVA irradiation induces L-isoaspartyl formation in melanoma cell proteins. 1142 84

Hyperthermia produces regression of human cancer. Because hyperthermia has produced only limited results, attention has focused on searching for substances able to sensitize tumour cells to the effects of hyperthermia. The flavonoid quercetin has been reported to be a hyperthermic sensitizer in ovarian and uterine cervical tumours and in leukaemia. Quercetin and tamoxifen inhibit melanoma cell growth. We therefore investigated whether quercetin and tamoxifen can sensitize M10, M14 and MNT1 human melanoma cells to hyperthermia. We observed that both quercetin and tamoxifen synergize with hyperthermia (42.5 degrees C) in reducing the clonogenic activity of M14 and MNT1 and in inducing apoptotic cell death in all three cell lines. As revealed by flow cytometric and Northern blot analyses, quercetin and tamoxifen reduced heat shock protein-70 expression at both protein and mRNA levels. Our results suggest that quercetin and tamoxifen can be usefully combined with hyperthermia in the therapy of recurrent and/or metastatic melanoma.
Melanoma Res 2001 Oct
PMID:Quercetin and tamoxifen sensitize human melanoma cells to hyperthermia. 1159 83

Resveratrol, a polyphenol present in many plant species, exhibits a wide range of biological and pharmacological activities both in vitro and in vivo. It has been shown to exert a potent chemopreventive effect in carcinogenesis models and to induce cell growth inhibition and apoptosis in human tumour cells, including melanoma cells. Malignant melanoma is considered to be a chemotherapy-refractory tumour, and the commonly used anticancer drugs do not seem to modify the prognosis of metastatic disease. To further evaluate the therapeutic potential of resveratrol in the treatment of melanoma, we selected three human melanoma cell lines with different levels of resistance to temozolomide (TMZ), an antitumour triazene compound. The cell lines were subjected to resveratrol treatment and analysed for cell growth inhibition, cell cycle perturbation and apoptosis induction. We found that resveratrol markedly impaired proliferation of both the TMZ-sensitive M14 and the TMZ-resistant SK-Mel-28 and PR-Mel cell lines. The latter cell line was two-fold more resistant to the drug than M14 and SK-Mel-28 cells. The sensitivity of normal human keratinocytes to resveratrol was found to be significantly higher than that of M14 and SK-Mel-28 cells and similar to that of the PR-Mel cell line. This suggests a possible good in vivo therapeutic index for resveratrol. Our results also show that the growth-inhibitory effect of resveratrol on melanoma cells is mainly due to its ability to induce S-phase arrest and apoptosis. Taken together, our data indicate that resveratrol is an interesting candidate for the treatment of advanced melanoma.
Melanoma Res 2004 Jun
PMID:In vitro antitumour activity of resveratrol in human melanoma cells sensitive or resistant to temozolomide. 1517 87

Melanoma cells exhibit a high level of intrinsic or acquired resistance to the cytotoxic agents often associated with the over-expression of drug transporters such as P-glycoprotein (P-gp). In this in vitro study, we investigated the possible relationship between P-gp and CD44, the cell adhesion molecule involved in metastasis and tumor progression of melanoma cells. CD44 expression appeared to be similar in the parental sensitive M14 WT cells and in their resistant counterparts M14 ADR cells. Double-labeling of cryosectioned cells showed that P-gp and CD44 were transported from the synthesis loci to the cell periphery by different vesicles and began to coalesce in proximity of the plasma membrane; thus, P-gp and CD44 seemed to reach together the cell surface. Moreover, P-gp and CD44 appeared to be associated with ERM proteins. The invasive activities of both M14 WT and M14 ADR cells were analyzed by the "transwell chamber invasion" assay. M14 WT cells revealed low capacity to traverse the filters, both in the absence (motility) and in the presence (invasion) of a Matrigel coating. In comparison, M14 ADR cells displayed significantly higher motility and invasion. SEM observations showed that sensitive cells employed lamellar cytoplasmic extrusions to pass through the filter pores whereas resistant cells elongated along the hole through globular processes. In conclusion, the results herein reported suggest that drug resistance in melanoma cells appears associated with a more aggressive behaviour. P-gp and CD44 might cooperate to confer this more invasive phenotype.
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PMID:Invasive properties of multidrug resistant human melanoma cells. 1610 Oct 31


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