摘要:

Retinoids inhibit proliferation of melanocytes and melanoma cells and affect disorders of hypo- and hyperpigmentation. Such effects might involve retinoid-binding proteins, retinoid metabolites and nuclear retinoid receptors for transcriptional activation. We detected messenger RNA transcripts for the cellular retinol- and retinoic acid-binding proteins (CRBP, CRABP I and II) in cultured epidermal melanocytes. In the melanoma cell lines the major transcript was CRABP II. Nuclear retinoic acid (RA) receptor transcripts and the 9-cis-retinoic acid receptor transcript were detected in all cells. The endogenous concentrations of retinol (ROH) and its metabolite 3,4-didehydroretinol (ddROH) in melanocytes were five times those in melanoma cells. When cells were incubated with [3H]ROH the main metabolites in the melanocytes were [3H]ddROH (4%) and [3H]RA (0.4%). Formation of [3H]RA was only detected in one melanoma cell line. Both melanocytes and melanoma cells produced an unidentified metabolite when incubated with [3H]ROH and [3H]RA. Dissimilarities in the metabolism and endogenous concentration of retinoids between benign and malignant melanocytes might play a key role in differentiation and growth regulation

ISSN:0960-8931    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

We determined whether tumour sizein vivoand cell densityin vivomodulate the expression of themdr-1 gene in B16 melanoma cells. Cells were injected subcutaneously into syngeneic mice. Small (5 mm in diameter) and large (15 20 mm in diameter) tumours were harvested. Tumour cells from small subcutaneous tumours exhibited higher levels ofmdr-1 mRNA (measured using Northern blot and in situ hybridization) and P-glycoprotein (P-gp) (measured using immunohistochemistry and fluorescent activated cell sorter analysis), as well as greater in vitro resistance to doxorubicin (DXR) than cells from large subcutaneous tumours. Immunohistochemical studies using an antibody against proliferating cell nuclear antigen revealed that the small subcutaneous tumours contained a larger fraction of proliferating cells than the large tumours. To determine whether cell proliferation correlated with expression ofmdr-1, we plated B16-F10 cells to yield sparse and confluent monolayer cultures. The levels ofmdr-1 mRNA and P-gp and resistance to DXR and phosphotyrosine activity were higher in the sparse cultures than in the confluent cultures. These results demonstrate an intratumoral heterogeneity for the expression ofmdr-1 that directly correlates with intratumoral heterogeneity for cell division

ISSN:0960-8931    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

A significant correlation between the inactivation of the growth-regulating enzyme ribonucleotide reductase (RR) with the growth inhibition of four different tumour cell lines has been found for seven differentp-alkoxyphenol derivatives with varying lengths of alkyl side chain. In Novikoff hepatoma and human leukaemia cells, inactivation of RR by p-alkoxyphenols was monitored by electron paramagnetic resonance (EPR) spectroscopy of the catalytically essential tyrosyl radical in the subunit R2 of RR. A significant inhibition of cellular growth of Novikoff hepatoma cells, human leukaemia cells and two human melanoma cell lines (MeWo and M5) byp-alkoxyphenols was also observed by growth inhibition assays. Inactivation of RR in whole tumour cells as well as inhibition of cellular growth of tumour cell lines by p-alkoxyphenols both show an increase in inhibition with increasing length of the alkyl side chain; the most effective inhibitors are pisobutoxyphenol, p-butoxyphenol andp-propoxyphenol. The enzyme RR, and in particular the catalytically essential tyrosyl radical in the active site, is recognized as an important cellular target for growth inhibition of Novikoff hepatoma cells, human leukaemia cells and melanoma cells by p-alkoxyphenols. Thus, the most potent RR inhibitorsp-isobutoxyphenol,p-butoxyphenol andp-propoxyphenol may be considered as future antiproliferative drugs for the systemic treatment of melanoma as well as leukaemia and possibly other malignancies.

ISSN:0960-8931    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

In a previous study, we showed by immunohistochemical analysis that basic fibroblast growth factor (bFGF) is expressed strongly and homogeneously in naevus-cell naevus (NCN), while that in malignant melanoma (MM) is heterogeneous and sometimes non-existent. In order to elucidate the role of bFGF in these pigmented tumours, the expression of its receptors must be determined. In this study, we performed an immunohistochemical analysis of FGF receptors 1, 2 and 3 (FGFR-1, FGFR-2 and FGFR-3, respectively) in NCN and MM and compared their expression and localization with those of bFGF. The expression of bFGF and its three receptors was also examined in melanoma cell lines. None of the 10 NCN that showed strong, homogeneous staining for bFGF expressed FGFR-1 or FGFR-3 proteins; six weakly expressed FGFR-2 protein. Ten primary and 10 metastatic MM showed heterogeneous expression for the three receptors, with larger populations of FGFR-3-negative cells in the primary than in the metastatic tumours. Western blot analysis showed homogeneous expression of bFGF protein in all four melanoma cell lines tested, while FGFR proteins had a heterogeneous distribution in the different cell lines. Cultured NCN and normal melanocytes showed no immunoreactive band for FGFR-1 protein, the only protein tested. Our results suggest that tumour-derived bFGF is involved in melanoma formation through an autocrine mechanism, but is involved mostly through a paracrine or other mechanism in NCN

ISSN:0960-8931    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Pigmented basal cell carcinoma (PBCC) is a tumour with distinct clinical features which occasionally may be difficult to differentiate from malignant melanoma (MM). The purpose of this study was to re-examine the epiluminescence microscopy (ELM) criteria for PBCC and to determine their statistical significance in the differential diagnosis of MM. Fifty histologically verified pigmented skin lesions (25 PBCCs and 25 MMs) were investigated using ELM for the presence of ELM criteria; their significance was determined by calculating the odds ratios. We found that individual ELM criteria have different weights of significance in the differential diagnosis of PBCC (leaf-like distribution of diffuse pigmentation, gradual thinning at the periphery and telangiectasia) and MM (pigment network, black and grey pigmentation, radial streaming, pseudopods, brown globules and black dots). Selected patterns of ELM criteria adjusted to the distinct types of pigmented skin lesions are characteristic features for preoperative diagnosis. The prevalence of distinct ELM criteria in PBCC and MM is of critical value in differentiating between the two types of lesions.

ISSN:0960-8931    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Transforming growth factor-β(TGFβ), which is secreted by cultured melanoma cells constitutively, inhibits the proliferation of normal melanocytes and of most melanoma cellsin vitro, but some melanoma cells from advanced stages of the disease develop resistance to TGFβ-dependent growth inhibition, without developing any change in TGFβcell surface binding.In vitroTGF p also downregulates the expression of HLA-DR molecules on melanoma cells, and upregulates the expression of theβ3 integrin subunit on some cell lines. Immunohistochemical analysis of 53 melanocytic lesions (12 naevi, 30 primary melanomas and 11 metastases) revealed a trend of increasing expression of TGFβand TGFβreceptor type III with tumour progression, and a significantly higher expression of both TGFβ(P< 0.0001) and the receptor (P< 0.05) in metastatic and thick (P< 1 mm) primary melanomas compared with thin (> 1 mm) primary melanomas. The expression of TGFβcorrelated with expression of a marker of proliferation, Ki67, and with HLA-DR andβ3 integrin subunit expression. Coexpression of the four molecules was observed in all metastases and in most thick primary melanomas. These findings argue against an inhibitory effect of TGFβon cell proliferation or HLA-DR antigen expression in melanoma, and suggest the upregulation of theβ3 subunit. TGFβprotein appears to be a biological marker of melanoma progressionin situ.

ISSN:0960-8931    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Using microdialysis of human melanoma transplants In athymic mice we have shown that interstitial glutathione levels decreased during treatment with buthionine sulphoximine (BSO) and recovered after cessation of treatment. The cysteine concentrations also decreased, while 5-Scysteinyldopa tended to increase during BSO treatment. Restoration of the glutathione levels was not seen after eitherN-acetylcysteine (NAC) or L-2-oxothiazolidine-4-carboxylate (OTC) injections, given on the third day of BSO treatment. These results were to be expected since NAC and OTC were given during the BSO treatment, and BSO is a specific and potent inhibitor of glutathione synthesis. Cysteine levels, however, increased after the NAC injection but remained unaltered after the OTC injection, while 5-Scysteinyldopa remained unaltered after both the NAC and the OTC injections.

ISSN:0960-8931    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

DNA ploidy and S-phase fraction (SPF) were measured by flow cytometry on tumours from 80 patients with disseminated malignant melanoma. All patients received a fourdrug chemotherapy regimen (dacarbazine, vincristine, bleomycin and lomustine) plus interferon. Specimens were taken for analysis from the latest metastases biopsied before the start of the treatment. In 13 patients we also analysed sequential samples taken after the treatment at the time of progression. DNA aneuploidy was observed in 65% of the patients. Among the 40 responders there were 26 with aneuploid tumours (65%). Aneuploidy did not reach statistical significance as a prognostic sign in the unstratified study population, but when stratified by response groups, DNA aneuploidy was a significant prognostic factor for a better response (P= 0.04). SPF could be calculated in 76 tumours. Out of 40 responding patients (complete or partial response), 23 had tumours with an SPF higher than the median. Accordingly, patients with a high SPF survived longer than those with a low SPF, with median survival times of 9.8 months and 8.7 months, respectively (P= 0.18). We conclude that DNA aneuploidy and a high SPF are associated with longer survival in patients with disseminated melanoma treated with a chemoimmunotherapy regimen. Based on our findings we claim that, among patients receiving chemoimmunotherapy, high SPF and aneuploidy are not signs of unfavourable prognosis, which is in contrast to previous observations in melanoma patients receiving heterogeneous therapy.

ISSN:0960-8931    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The aim of this study was to estimate the incidence of melanoma in the Paris region in 1994 and analyse the main clinical and histological characteristics of these lesions. It took the form of a prospective inquiry, mailed to public and private pathology laboratories, to count as accurately as possible the number of new cases diagnosed by pathologists in the region during the 1994 calendar year. In all, 1089 newly diagnosed Clark level I to V melanomas (excluding precancerous melanosis of Dubreuilh) were studied. Parameters recorded included age, sex, Clark level and Breslow's thickness. The incidence per 100000 inhabitants was 9.93 for melanoma and 8.62 for invasive melanoma. The female to male ratio was 1.6. Clark level I or thin (< 0.75 mm) melanomas represented 64.8% of the lesions. At the time of diagnosis, the females were significantly younger than the males (P= 0.004). Breslow's thickness increased with age and was significantly lower in women (P= 0.00005), especially those between 40 and 49 years old. The incidence of melanoma in the Paris region in 1994 was close to that observed during the preceding 5 years in England, Scotland and the French department of Haut-Rhin. It was 2.32 times higher for males and 1.69 times higher for females than the rates estimated for France for the period 1978 1982.

ISSN:0960-8931    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Melanoma risk differs by sun-sensitive phenotype, of which self-reported skin type (tendency to burn, inability to tan) is an indicator. If self-reports of skin type are influenced by the amount of sun exposure subjects have had, the two principal determinants of risk are linked, and stratifying by skin type would bias the estimated effect of sun exposure. Our objective was to determine whether teenagers changed their self-reports of skin type after being sunburnt. A random sample (n= 364) of 14-15 year old schoolchildren of northern European ancestry self-assessed and selfreported their skin type before and after their summer holidays. Their responses had high correlation coefficients (girls 0.71, boys 0.54) for repeatability at 4 months, but subjects who sunburnt less (more) frequently than usual that summer revised their skin type assessment to be less (more) sun-sensitive afterwards. We conclude that these 14-15 year olds were influenced by a recent experience of sunburn when reporting their skin type. A more objective measure of phenotype is needed.

ISSN:0960-8931    

出版商:OVID    

年代:1997

数据来源: OVID