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)

Intrinsic and acquired resistance to chemotherapeutic agents represents the major clinical obstacle in the control of most tumours. In vitro studies have established that multiple mechanisms, including changes in drug uptake and efflux and in detoxifying enzymes, are responsible for drug resistance. Among the latter, glutathione S transferases (GST) have been recognized to play a relevant role. In the present study we have evaluated GST pi immunohistochemically as well as enzymatically in benign and malignant primary and metastatic lesions of the melanocyte lineage. A parallel analysis of the multiple drug resistance (MDRI) gene product was performed in a representative number of specimens. Results of this study demonstrate that while GST pi is constitutively expressed by the melanocyte lineage, independently from the transformed stage, MDRI p-glycoprotein is detected with a significantly lower frequency. These findings clearly indicate that GST pi represents the major detoxifying metabolic pathway of the melanocyte lineage and may be responsible for the high degree of inherent resistance of malignant melanoma to available cytostatic treatments.
Melanoma Res 1992 Nov
PMID:Expression of glutathione transferase pi in benign and malignant lesions of the melanocyte lineage. 136 63

Levels of glutathione peroxidase (GSH-PX), glutathione-S-transferase (GST), gamma-glutamyl transpeptidase (gamma GTP) and glutathione reductase (GR) activities in the B16-F10 metastatic melanoma cell line are higher than those in non-metastatic B-16 murine melanoma cells. An inverse relationship was observed between the level of reduced glutathione (GSH) and metastatic capacity. Interferon (IFN), an antitumour and antimetastic agent, reduced the experimental metastatic capacity of B16-F10 cells while increasing the intracellular GSH content. This was associated with a fall in activity of GSH-metabolizing enzymes. These results suggest a correlation of intracellular GSH and its metabolizing enzymes with malignant transformation.
Melanoma Res 1992 Dec
PMID:Intracellular glutathione and its metabolizing enzyme activities in a metastatic variant melanoma cell line. 136 79

Cell clones derived from a human melanoma metastasis selected for different integrin profiles were examined in vitro for invasive potential and biological and biochemical features potentially related to this process. Clones which expressed high levels of integrins showed high invasive potential, extracellular matrix degradation, and adhesion to gelatin-coated substrates. A correlation was also found between invasiveness and intracellular and extracellular plasminogen activator activity. Heparanase and collagenase type IV activities were apparently unrelated to invasiveness. gamma-Glutamyl transferase (GGT) activity was high in highly invasive clones, whereas melanin content was high in slightly invasive clones. Heterogeneity was also observed in cellular parameters such as cell dimensions, growth features and DNA index. The intrinsic biological and biochemical heterogeneity of a cell population derived from a single metastasis may be responsible for the different behaviour of clones, regardless of their invasive potential. Since slightly invasive cells are more differentiated than highly invasive cells, malignancy and differentiation are inversely correlated in such human melanoma clones.
Melanoma Res 1992 Dec
PMID:Biological and enzymatic features of human melanoma clones with different invasive potential. 136 80

Although most examples of cutaneous malignant melanoma are easily recognized by their clinical appearances, in some cases this serious neoplasm may clinically simulate other less serious forms of skin cancer or benign processes. This study was undertaken to assess both the sensitivity of clinical diagnosis of cutaneous malignant melanoma and the efficacy of biopsies of clinically unsuspected melanomas in yielding specimens on which complete and accurate histologic assessments could be made. A retrospective analysis of 1784 cases of histologically proven melanomas diagnosed between 1985 and 1990 was performed in search of lesions not clinically suspected. Biopsy techniques used to sample these lesions were subjected to critique of their efficacy in yielding specimens that could be accurately diagnosed and completely assessed histologically. Of 1784 histologically proven primary cutaneous melanomas, 583 were not clinically suspected, yielding a sensitivity of 67%. Clinical diagnosis included nevi (33%), no diagnosis (17%), multiple diagnoses (13%), basal cell carcinoma (12%), keratosis (9%), and lentigo (9%) among others. The biopsy methods used to sample these lesions were shave (56%), excisional (24%), punch (11%), curettage (2%), and undetermined (6%). Eighty-six percent of shave biopsies could be accurately assessed while only 32% of punches and no curettages provided sufficient material for both definitive and complete evaluation of melanomas. Eighteen percent of specimens histologically reviewed were considered inadequate for complete evaluation. In 34%, the actual diagnosis of melanoma was uncertain because of inability to assess diagnostic features as a consequence of the biopsy technique. Melanoma may be unsuspected clinically in a significant number of cases and may be mistaken for less serious cutaneous neoplasms.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Sensitivity of diagnosis of malignant melanoma: a clinicopathologic study with a critical assessment of biopsy techniques. 136 17

The increased incidence of disease, the relative unresponsiveness of advanced tumour to conventional therapies, and high socioeconomic costs make the malignant melanoma an aggressive cancer. During the last decade, several new biological agents have been developed, some of which have shown significant activity in the treatment of disease. However, the impact on the management of melanoma patients is still far from being conclusive. Among biological response modifiers (BRMs), interferons (IFNs) have generated a great deal of interest and have been extensively employed, although incorrectly. IFNs have been used without a specific rationale and at antiproliferative rather than biologically active doses; no extensive laboratory monitoring has been performed. In this paper data available in the current literature are reviewed and the efficacies of the different IFNs, used alone or in combination and in various treatment regimens, are compared in order to understand what is the place of IFNs in the management of patients with metastatic melanoma. Results are encouraging but still disappointing with the most effective treatment, with an overall response rate of 28.5% (10.5% complete responses). However, these results need confirmation. In conclusion, IFN is effective in the therapy of advanced melanoma, but improved response rates are necessary before it may be suitable for general, rather than investigative, use. Alternative biotherapeutical approaches and strategies are suggested.
Melanoma Res
PMID:Role of interferons in the therapy of melanoma. 138 54

The pigmented human melanoma cell line, MM418, became demelanized when treated continuously with a nontoxic level of halistanol trisulphate (HTS), a C29 steroidal detergent isolated from a marine sponge. Nontoxic levels of halistanol or of a range of anionic, cationic and neutral detergents had no such effect. Control MM418 cells varied greatly in size, appearance and pigmentation; HTS-treated cells were smaller than controls, had a uniform, generally bipolar appearance, and lacked pigment. HTS induced only minor changes in cell ultrastructure, with fewer mature melanosomes being found in treated cells. Suppression of melanin synthesis was apparent within 24 h of addition of HTS, as judged by inhibited incorporation of the false precursor, 5[125I]-2-thiouracil. Reversal of inhibition occurred within the same period after removal of HTS. Tyrosinase activity gradually decreased to 25% of the control value during a 19-day treatment with HTS, and expression of two carbohydrate-dependent tyrosinase epitopes, 5C12 and 2B7, was abolished. Expression of one other melanosomal protein and of vimentin was not affected. The results suggest that HTS inhibits maturation of tyrosinase to a form associated with melanin synthesis.
Melanoma Res
PMID:Reversible depigmentation of human melanoma cells by halistanol trisulphate, a novel marine sterol. 138 55

A panel of monoclonal antibodies (mAbs) to bovine fibronectin (FN) is described which modulates either heparin binding or cell adhesion to FN, or both. A combination of competitive exclusion and binding to proteolytic fragments identified epitopes in the Hep II, Hep III/I and CBF (cell binding fragment) regions of FN. mAb A17, which bound to the CBF region, strongly inhibited the cell adhesion of BHK-21 fibroblasts, primary corneal fibroblasts and endothelial cells, and NM4 mammary adenocarcinoma cells, to FN at mAb concentrations as low as 1 microgram/ml. This mAb was not so effective at inhibiting the adhesion of B16 mouse melanoma cells. Adhesion of B16 cells to FN was more sensitive to inhibition by mAbs binding to Hep II (A2, A9, A32, A35). Of these, A32 and A35 significantly increased the binding of 35S-heparin to FN, whereas A2 and A9 did not affect it. mAbs A2, A9 and A32 showed good binding to HBF, the 40 kDa proteolytic fragment of human FN which contains both Hep II and IIICS (type III connecting segment). These mAbs inhibited B16 cell adhesion to the HBF (heparin binding fragment) by 30-50%, the greatest inhibition being shown by mAb A32. Two synthetic peptides from the HBF, CS1 (peptide 1) from the IIICS region and peptide I from the Hep II region, also inhibited B16 cell adhesion to HBF by approximately 70 and 30%, respectively. These results suggest that maximal cell adhesion to the HBF involves both CS1 and Hep II. The inhibitory effects of the two peptides were linearly additive in combination, whereas the inhibitory mAbs A2, A9 and A32 showed synergistic additive effects with each of the peptides. This points to the existence of an additional important cell binding site in Hep II, other than peptide I. Recent independent evidence for an additional cell binding site in Hep II supports this view. Melanoma cellular receptor(s) for the Hep II region may be cell surface proteoglycans but do not appear to bind to areas of Hep II with high affinity for soluble heparin, as the latter was not an inhibitor of B16 cell adhesion to the HBF. The increased effectiveness of A32 in inhibiting cell adhesion, compared to A2 and A9, may be due to conformational effects which increase the binding of soluble heparin, but reduce affinity for the cellular receptor. These results are discussed in context with other reports in the literature.
 ...
PMID:Anti-fibronectin antibodies that modify heparin binding and cell adhesion: evidence for a new cell binding site in the heparin binding region. 138 58

The non-subungual area of the hand is a rare anatomical site for malignant melanoma, lesions in this site comprising only 0.37% of 8,584 cutaneous melanomas in the Sydney Melanoma Unit database. This is approximately the same frequency of melanoma as is found on the subungual region of the hand, which represents a much smaller surface area. Not only is the sub-site distribution on the hand unusual but in addition the histogenetic types of melanoma found on the dorsum of the hand are not those commonly encountered on sun exposed skin. In this study, comparison is made between melanomas occurring on the non-subungual areas of the hand and those on the foot, an anatomically similar surface area. Comparison is also made between melanomas arising on the dorsal non-subungual surface of the hand and those on the face, a region with an equivalent surface area and similar sun exposure. The results of surgical treatment of 31 melanomas of the non-subungual region of the hand are reviewed.
 ...
PMID:Non-subungual melanomas of the hand. 962 Feb 2

Melanoma of the anorectum is a rare malignancy. At Armed Forces Institute of Pathology (AFIP), 11 cases were diagnosed over a 10 year period (1981-1990) constituting 14.2% of all primary malignant melanomas. The anorectum was the commonest site for noncutaneous melanomas (45.8%). The age group commonly affected was the fifth to seventh decade (72.7%). Most of the tumours were extensive involving both anal canal and rectum. The proportion of anorectal melanoma is much higher in our study as compared to western reports (0.4-1.6%). The distribution of noncutaneous melanomas in our population also differs, with a relatively lower proportion of ocular melanomas (33.3%) which are the commonest (80%) in western studies (JPMA 42: 155, 1992).
 ...
PMID:Anorectal melanoma in northern Pakistan. 140 31

The existence of a distinct pool of glutathione in the nucleus of cultured human melanoma cells was demonstrated. Melanoma cell nuclei contained 13-35 pmol of glutathione/10(6) nuclei, or approximately 0.4-1.3% of the total cellular glutathione. This nuclear glutathione pool resisted depletion by buthionine sulfoximine, an agent that inhibits glutathione synthesis, but was rapidly and reversibly depleted by subtoxic concentrations of Adriamycin plus carmustine, two agents that promote oxidation of glutathione without permitting its regeneration through enzymatic reduction of glutathione disulfide. The ability of Adriamycin plus carmustine to deplete this small but significant pool of glutathione in the cell nucleus may explain why these agents potentiate the cytotoxic effects of the DNA-alkylating agent melphalan to a much higher degree than does buthionine sulfoximine at concentrations that are equipotent in depleting cytosolic glutathione.
 ...
PMID:Depletion of a discrete nuclear glutathione pool by oxidative stress, but not by buthionine sulfoximine. Correlation with enhanced alkylating agent cytotoxicity to human melanoma cells in vitro. 141 60


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