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)

Following severe hyperthermic treatment M-14 cells synthesize at high rate a new protein of about 66 kD, in addition to the three well known major HSPs (HSP 28, HSP 70 and HSP 90). This 66 kD protein is constitutively expressed at low levels and its rate of synthesis is not enhanced by mild hyperthermic exposures (40 degrees C for 2-4 h; 42 degrees C for 1-3 h), sufficient to induce the three major HSPs. The 66 kD protein is induced whenever the thermal dose administered to cells attains a threshold, roughly corresponding to a 50% reduction in survival. The 66 kDa protein is not induced by a variety of compounds (disulfiram, arsenate, cadmium) able to elicit a stress response in M-14 cells, as indicated by enhanced synthesis of the three major HSPs. Once induced by a treatment at 45 degrees C for 15 min, the rate of synthesis of the 66 kD protein remains above the control level for 16-20 h during recovery from the stress, while the synthesis of HSP 70 is shut off between 8 and 12 h. Immunoblotting and immunoprecipitation studies showed that the 66 kD protein shares immunological determinant(s) with HSP 70. Pulse-chase experiments demonstrated that the 66 kD protein is not a degradation product or a late post-transcriptional modification of HSP 70. It is proposed that the 66 kD protein is a previously unrecognized heat shock protein (HSP 66), characterized by an unusually high threshold for its induction.
Melanoma Res 1992 Dec
PMID:Identification of a 66 kD heat shock protein (HSP) induced in M-14 human melanoma cells by severe hyperthermic treatment. 129 85

Thirty patients with malignant melanoma and cerebral metastases confirmed by CT were studied. Metastases were classified according to their size: < or = 1 cm (group A), 1.1-4 cm (group B), and > 4 cm (group C), in order to assess the clinical course of the disease and predict the response to treatment with fotemustine. Group B lesions were the most common, independent of the site of the primary tumour, except for patients with rectal melanoma. Group C metastases were least common and were usually solitary. Asymptomatic patients usually had group A metastases, whereas those with non-specific complaints, hemisyndrome or neurobehavioural changes usually had group B metastases. The time from diagnosis of the primary tumour to discovery of disease in the CNS was significantly longer for those who had group A lesions, compared with those who had groups B or C lesions (P < 0.0001). Solitary lesions usually belonged to groups B or C, whereas multiple lesions belonged mainly to groups A or B. All the responders to fotemustine has mainly cortical, group A or group B lesions. Patients with group C lesions or leptomeningeal spread did not respond to fotemustine. Our findings suggest an association between the size of the cerebral metastatic lesion from malignant melanoma and clinical parameters characteristic of tumour behaviour.
Melanoma Res 1992 Dec
PMID:Cerebral metastatic melanoma: correlation between clinical and CT findings. 129 86

Although chemotherapy has been generally of limited clinical benefit in the treatment of metastatic malignant melanoma (MMM), fotemustine (FM) is a newly developed drug which is active against this disease. Twenty-four patients with histologically proven MMM were treated with fotemustine, with or without dacarbazine (DITC) according to different phase II trials. In the first schedule, three patients received FM alone on days 1, 8, 15 followed by a 5-week rest period. The second schedule consisted of FM administered on days 1 and 8 alternating with DTIC on days 15 and 16, followed by a 5-week rest period (19 patients). The third schedule, given to two patients, consisted of DTIC followed 4 h later by FM. The overall response rate was 8.3%. Response in those who were treated with alternating drugs, included one partial response (PR) in the brain which lasted 4 months, and one PR in brain metastases with complete response (CR) in lymph nodes for 4 months. Clinical and radiological evidence of regression was observed mainly in brain metastases (22.2%), reflecting the intracerebral activity of the drug. It seems that fotemustine is superior to any other drug currently available in the treatment of these metastases.
Melanoma Res 1992 Dec
PMID:Fotemustine--an advance in the treatment of metastatic malignant melanoma. 129 87

Regional perfusion therapy of melanoma is followed by an apparent decrease in lymph node metastases. When regional isolated perfusion is performed by cannulating the blood vessels at the iliac level, at least the middle and distal parts of the inguinal nodal zone are included. This is not the case with femoral perfusion. These two types of perfusion were therefore compared to determine whether iliac perfusion eradicates micrometastases present in the inguinal nodes. The regional node recurrence rate and time to regional node relapse of 97 patients treated with iliac perfusion were compared with those of 20 patients who received femoral perfusion. Prognostic factors such as sex, MD Anderson stage of disease, Breslow thickness and Clark level of the primary melanoma, and number of nodules of those with recurrent melanoma were equivalent in both groups. All patients were perfused with melphalan under normothermic conditions during the period 1978-1990. Five of 20 patients (25%) receiving femoral perfusion and 31 of 97 patients (32%) receiving iliac perfusion (P = 0.7, chi 2 test) developed inguinal node metastases after a median period of 25 (8-40) and 19 (2-71) months, respectively (Mann-Whitney U test, P = 0.9). There was no statistically significant difference in the 5-year survival rate (55% versus 62%, respectively; log rank test P = 0.5). Since no advantage could be seen in terms of reduction of inguinal node relapse for iliac perfusion, it is concluded that perfusion of the distal nodes is not the major cause of reduction of regional node metastases.(ABSTRACT TRUNCATED AT 250 WORDS)
Melanoma Res 1992 Dec
PMID:The role of regional isolated perfusion in the eradication of melanoma micrometastases in the inguinal nodes: a comparison between an iliac and femoral perfusion procedure. 129 88

We have recently described marked differences in cell migration rates and organization of actin in human melanoma cell lines isolated from various stages of tumor progression. Metastatic lines derived from lymph node metastases organized actin into stress fiber arrays and had high mean migration rates in vitro when compared to lines from other stages. Melanoma cells also reveal marked differences in localization of alpha-actinin and beta 1 integrins at stress fiber termination sites (focal contacts). Disruption of this organization is induced by antibodies against beta 1 integrins, alpha-actinin, recently postulated as having a role in linkage of actin to beta 1 integrins, is differentially expressed in melanoma cells by Northern blot analysis and a relatively high alpha-actinin to actin ratio is associated with stress fiber formation and increased cell migration. Furthermore, actin-binding protein, which cross-links actin filaments, is also significantly increased in lines exhibiting high migration rates. Control of migration and actin organization may be mediated by extracellular matrices and/or modulation of actin-associated proteins including alpha-actinin and actin binding protein. These findings provide evidence that an interaction of transmembrane adhesion molecules and elements of the cytoskeleton in melanoma cells may be responsible for differences in migration rates and capacity for metastasis.
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PMID:Actin organization and cell migration of melanoma cells relate to differential expression of integrins and actin-associated proteins. 129 73

Twenty-one intradermal nevi were studied by morphometric methods in an attempt to morphologically characterize the two types of nevus cell--epithelioids, type A, and fusiforms, type C--and to quantify the differences between them. Morphometric parameters of the intradermal nevi were compared with similar parameters of melanocytes and melanoma cells so that the maturation rates of the nevi cells could be established and to see if the parameters might indicate the degree of malignancy. Superficial nevus cells were differentiated from deep cells by their larger size and larger nuclear area. Nuclear area appeared to have potential for differentiating benign from malignant tumors. Decrease in cellular area appeared to indicate maturation rather than atrophy. Melanoma cells were differentiated by their larger size. Cell nuclear perimeter appeared to have confirmatory value, while cell perimeter was inconclusive.
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PMID:Application of morphometric methods to the cytologic study of intradermal nevi. 129 28

Tumor necrosis factor (TNF) induces synthesis of manganese superoxide dismutase (MnSOD). It was previously shown that overexpression of MnSOD protected some mammalian cells from TNF cytotoxicity. The purpose of this study was to establish whether MnSOD was increased in cells selected for resistance to cytolysis by TNF in combination with cycloheximide. Melanoma SK-MEL-109 and HeLa cell-resistant variants were selected by repeated treatments with TNF and cycloheximide. The SK-MEL-109 variants had relatively low levels of MnSOD that were inducible by TNF. Surprisingly, the HeLa variants had very low levels of MnSOD that were poorly inducible by either TNF or interleukin-1 alpha. Therefore, an elevated level of MnSOD was not required to protect these cells from TNF-mediated cytolysis. The HeLa variants were more sensitive than parental cells to superoxide radical (O2-) generating compounds, such as paraquat or xanthine/xanthine oxidase. Pretreatment of these variants with TNF did not provide protection against damage by superoxide radicals.
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PMID:Reduced expression of manganese superoxide dismutase in cells resistant to cytolysis by tumor necrosis factor. 131 74

A number of growth factors can stimulate the proliferation of human malignant melanoma cell lines. We investigated the effects of exogenous growth factors including basic fibroblast growth factor (bFGF), epidermal growth factor, transforming growth factor-alpha, insulin, insulin-like growth factor-I (IGF-I), acidic fibroblast growth factor, platelet-derived growth factor, transforming growth factor-beta and nerve growth factor on six human metastatic melanoma cell lines. The mitogenic activity of each growth factor was tested using the [3H]thymidine incorporation assay. There was a variable response of the different cell lines to most growth factors. All of the melanoma cell lines tested responded to IGF-I. Furthermore, the effects of growth factors were additive, a combination of bFGF and IGF-I having the greatest effect on three melanoma cell lines tested. The quantitative radioimmunoassay for bFGF and [125I]bFGF binding assay revealed that all of these melanoma cell lines produced bFGF and expressed high affinity receptors for bFGF. A 20-mer antisense oligodeoxynucleotide against the AUG initiation site of the bFGF coding region inhibited the proliferation of Mel-Tang by 40% (p less than 0.0001) and that of SK-MEL-5 by 20% (p less than 0.005), suggesting that these cell lines are at least under partial autocrine control of proliferation by bFGF. The presence of bFGF receptors on a high percentage of melanoma cell lines makes these a potential target for melanoma therapy.
Melanoma Res 1992 May
PMID:Basic fibroblast growth factor production and growth factor receptors as potential targets for melanoma therapy. 132 54

In this study we have compared the effects of different pro-opiomelanocortin (POMC) peptides on melanogenesis and metastasis and their relationship to MSH receptor expression in B16F1 melanoma cells. All peptides, apart from beta-endorphin, increased melanogenesis and the order of potency was Nle4DPhe7-alpha-MSH greater than alpha-MSH greater than ACTH[1-39] greater than des-acetyl alpha-MSH greater than ACTH[1-24]. A similar order of potency was found for metastasis, except for ACTH [1-24], which had a relatively greater effect on metastasis. These findings suggest that the effects on melanogenesis and metastasis are mediated via the same receptor. The results of ligand binding studies also indicated the presence of a single receptor with a KD value for Nle4DPhe7-alpha-MSH of 62 +/- 16pM. This was consistent with crosslinking studies using [125I] Nle4DPhe7-alpha-MSH which produced a single 50-55 kD band on analysis by SDS-PAGE. However, the relative binding affinities of the different peptides, measured by displacement of [125I]-Nle4DPhe7-alpha-MSH, did not closely correlate with the relative potencies in stimulating melanogenesis and metastasis. This suggests that receptor activation and the subsequent biological response is not determined solely by binding affinity.
Melanoma Res 1992 May
PMID:MSH receptor expression and the relationship to melanogenesis and metastatic activity in B16 melanoma. 132 55

The relationship between lung colonization and signal transduction was investigated for six B16 melanoma variants. A range of experimental metastatic potential (as determined by lung colonization), forskolin-stimulated cyclic AMP accumulation and FCS-stimulated protein kinase C activity was found. The major findings were that: (1) cells with the highest agonist-stimulated cyclic AMP production were those with the highest level of membrane-associated protein kinase C activity; (2) clones which differed in protein kinase C levels and distribution did so in the presence but not in the absence of foetal calf serum; and (3) no simple relationship was seen between either signal transduction system and lung colonization for all six variants. Altered ras expression was also excluded as an explanation for the differences in signal transduction and lung colonization potential which were observed. We conclude that differences in signal transduction in vitro between these cells do not relate simply to lung colonization potential in vivo.
Melanoma Res 1992 Sep
PMID:Signal transduction in murine B16 melanoma cells. 133 18


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