摘要:

Estimates derived from linear models fitted to melanoma death rates at successive time periods for the contiguous states of the US suggest that, allowing for latitude, rates are higher in the coastal than in the interior states. The effect of latitude on melanoma death rates in the white population of the US is decreasing and will shortly be gone. This decrease is slower in the interior states than in the coastal ones. The deceleration of the rate change is most marked in the states with the highest rates, so that latitude may be regarded as a determinant of the initial rate for each state, while the subsequent change in rate is a function of that initial rate. Melanoma death rates appear to be stabilizing at levels that are unaffected by latitude.

ISSN:0960-8931    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The hyaluronan-rich matrix that surrounds many tumours and facilitates tumour cell growth and invasion is thought to be predominantly synthesized by normal stromal cells stimulated by tumour cell-derived factors. This study examines the possibility that the production of tumour cell-derived factors that stimulate fibroblast glycosaminoglycan (GAG) synthesis may be blocked by exposure to differentiation-inducing agents such as retinoic acid. We have demonstrated that Hs294T, C8161 and A375 human melanoma cell lines release factors into their medium that stimulate normal fibroblast GAG synthesis. Exposure of these melanoma cells to retinoic acid failed to mediate any significant reduction in growth over a 7-day period. Retinoic acid failed to block the tumour cell production of GAG-stimulating activities and even enhanced the activities produced by the C8161 cell line, particularly at low retinoic acid concentrations (48% stimulation at 10−9M retinoic acid;P<0.02). Addition of retinoic acid directly to fibroblast cultures exposed to fibroblast-conditioned medium resulted in an inhibition of GAG synthesis with a 33% inhibition observed at 10−5M. Addition of retinoic acid to fibroblast cultures exposed to the tumour cell-conditioned medium failed to inhibit the stimulation of GAG synthesis. Other differentiation-inducing agents, such as hexamethylene-bis-acetamide and butyrate, also failed to block the production of tumour cell-derived GAG-stimulating activities. These results demonstrate that retinoic acid and other differentiation-inducing agents fail to inhibit melanoma cell production of fibroblast GAG synthesis-stimulating factors or their action upon fibroblasts.

ISSN:0960-8931    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The question of whether melanoma tumours have classical oestrogen receptors (ERs) is unresolved, but epidemiological data clearly show a survival benefit for female patients with metastatic melanoma. The aims of this study were to examine to what extent the presence of ER in melanoma tumours might relate to disease progression and whether disease progression relates to patients' sex steroid status. Additionally, levels of two soluble adhesion molecules [circulating intercellular adhesion molecule-1 (sICAM-1) and circulating vascular cell adhesion molecule-1 (sVCAM-1)] were examined as independent, possibly prognostic indicators of disease progression. ER immunocytochemical assay identified only two lesions (out of 69 investigated) which had any evidence of the receptors, and staining in these lesions was very modest. No significant changes in oestrone or androstenedione levels were noted for male or female patients with disease progression. As expected, oestradiol levels reflected the menopausal status of the female patients but, for all post-menopausal female patients and male patients, there was no significant relationship to tumour stage. However, a significant decrease in sex hormone-binding globulin occurred with disease progression in male but not female patients, and sex differences in the levels of soluble adhesion molecules were also seen in advanced metastatic disease.

ISSN:0960-8931    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

We have previously shown that a novel monoclonal antibody, XMEL, exhibited reactivity with deep primary melanomas while showing no reactivity with other tumours and normal tissue. XMEL was raised against a part of the extracellular domain of Xmrk, a growth factor receptor presumed to mediate melanoma formation in theXiphophorusfish model. Here we investigate the range of XMEL immunohistochemical reactivity in paraffin sections from human common acquired and dysplastic naevi of both junctional and compound type. The strongest reactivity was observed with the compound dysplastic naevi. We conclude that the antigen recognized by XMEL acts early in the cascade of genetic alterations underlying progression into malignant melanoma. Our results also support the notion that the dysplastic naevus may play a role in progression of human malignant melanoma and may indeed represent the precursor stage.

ISSN:0960-8931    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Superantigens like the Staphylococcus enterotoxin A (SEA) can direct cytotoxic T lymphocytes expressing certain T cell receptor Vβ regions to lyse MHC class II-positive target cells. This superantigen-dependent cellular cytotoxicity (SDCC) has been extended to MHC class II-negative tumour cells by targeting T cells via conjugates of a tumour-specific monoclonal antibody (moAb) and a superantigen. In the present study the MHC class II-negative human melanoma cell lines G361 and MaRi were tested for susceptibility to SDCCin vitro. Antibodies recognizing the disialoganglioside GD3 and the CD10 antigen were linked to SEA either by a recombinant protein A–SEA fusion protein or an anti-κ moAb–SEA chemical conjugate. Specific lysis of melanoma cells was dose- and effector to target (E:T) cell ratio-dependent. Introduction of a point mutation into the SEA gene (producing SEAm9) in order to reduce MHC II affinity of the superantigen, which has already been shown to severely diminish superantigen-dependent binding and lysis of MHC class II-positive cells, did not influence antibody-targeted SDCC. Cytotoxicity was equal with both antibodies (anti-GD3 and anti-CD10) and independent of whether protein A–SEA, protein A–SEAm9 or anti-κ–SEA were used.

ISSN:0960-8931    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Interleukin-1α (IL-1α) induces cell motility in a variety of benign cell types and in some but not all malignant cell linesin vitro. This study characterizes the IL-1α-induced motility of an aggressive human melanoma cell line that expresses both type I and type II IL-1 receptors. We tested the effect of monoclonal antibodies including function-blocking moAbs against the type I and type II IL-1 receptors on melanoma cell motility to determine which receptor is involved in signal transduction of IL-1α-induced melanoma cell motility. IL-1α significantly increases MM-RU melanoma cell migration in a dose-dependent manner using modified Boyden chamber assays at concentrations 10 to 100 times less than concentrations that significantly inhibit cell growth. Computer-assisted time-lapse image analysis reveals that the motility is inhibited in a dose-dependent manner by neutralizing antibodies against IL-1α. Function-blocking monoclonal antibodies against either type I or type II IL-1 receptors show a significant inhibition of cytokine-induced enhanced cell migration. When both the anti-IL-1 receptor antibodies are added together, the motility response is completely blocked to control levels. Taken together the data indicate that the IL-1α-induced motility of MM-RU melanoma cells is mediated through both type I and type II IL-1 receptors. The significant inhibition of motility by neutralizing IL-1α or blocking either one or both of the IL-1 receptors indicates an integration of IL-1- induced signals in the induction of melanoma cell migration.

ISSN:0960-8931    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Uveal melanoma is characterized by an unpredictable clinical course, during which metastatic disease may occur after a prolonged and, at present, undefinable disease-free interval. Because of its relative rarity and the dispersion of cases, the possible genetic alterations implicated in the invasive and metastatic behaviour of this ocular neoplasm have not yet been characterized. The aim of this immunohistochemical retrospective study was to assess the expression of nm23 gene product, proposed to be a metastasis-suppressor gene, in uveal melanoma and to analyse its prognostic significance in relation to the various conventional histopathological parameters, currently considered the major prognostic indicators in this intra-ocular neoplasm. We analysed formalin-fixed paraffin-embedded samples excised from 33 patients with uveal melanoma. Of these, 22 (67%) were positive for monoclonal antibody nm23. This nm23 positivity was inversely associated with scleral invasion level (P= 0.001) and largest tumour diameter (P= 0.02), which represent the two most significant prognostic factors for metastasis. On the other hand, there was no correlation between nm23 expression and other prognostic markers such as cell type, intra-ocular location or clinical characteristics. These results may suggest a close relationship between nm23 gene expression and metastatic potential of uveal melanomas. In addition, analysis of nm23 gene expression on bioptic tissue may represent an extreme useful prognostic tool for metastatic progression of uveal melanomas.

ISSN:0960-8931    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Experimental and clinical evidence suggests that tumour angiogenesis plays a role in the tendency for certain neoplasms, including cutaneous melanomas, to metastasize. We evaluated whether tumour vasculature is associated with the rate of metastases in patients with melanoma of the choroid or ciliary body. The study was based on a group of 63 patients enucleated between 1976 and 1984 with paraffin-embedded tissue blocks available for sectioning and with known survival status as of December 1988. Vessel endothelial cells were highlighted withUlex europaeusagglutinin I (UEA-I) conjugated with peroxidase. UEA-I-stained microvessels were counted at varying levels in the tumour (apex, centre and base) without knowledge of patient outcome. Patients with (n= 30) and without (n= 33) metastases had similar total vessel counts (P= 0.31). There was no evidence of greater vessel density in tumours that had metastasized, by level within the tumour. Similar results were obtained in multivariate analyses. Findings of this study suggest that tumour microvessel density is unrelated to patient survival in uveal melanoma.

ISSN:0960-8931    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Serum 5-S-cysteinyl dopa (5-S-CD), circulating intercellular adhesion molecule-1 (cICAM-1) and soluble interleukin-2 receptor (sIL-2R) have each been reported as useful markers for melanoma progression. To assess the clinical relevance of these three markers, we simultaneously assayed their serum levels in 30 Japanese melanoma patients. Pre-surgical serum levels of 5-S-CD, cICAM-1 and sIL-2R were elevated in six, 13 and five patients respectively. These abnormal values returned to normal after curative surgery in most of the patients, suggesting a direct relationship to the presence of the primary tumour. Pre-surgical values of these three markers, either individually or in combination, did not predict the development of subsequent metastases. The sequential measurements of the three markers in eight patients who had relapse after surgery showed that serum 5-S-CD is the most useful marker for disease progression, although it is dependent on the melanin-producing ability of individual recurrent tumours. sIL-2R seemed to reflectin vivoactivation of the host immune system and was a good indicator for predicting occult metastasis in selected cases. Circulating ICAM-1 levels were less relevant to the clinical disease course in our cases, although they tended to increase strikingly after liver metastasis. Our results in this limited number of cases show that the significance of the three markers varied with the individual and suggest that the simultaneous measurement of these markers may facilitate the early detection of metastases and proper therapeutic intervention.

ISSN:0960-8931    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The optimal dosing schedule for melphalan therapy of recurrent malignant melanoma in isolated limb perfusions has been examined using a physiological pharmacokinetic model with data from isolated rat hindlimb perfusions (IRHP). The study included a comparison of melphalan distribution in IRHP under hyperthermia and normothermia conditions. Rat hindlimbs were perfused with Krebs–Henseleit buffer containing 4.7° bovine serum albumin at 37 or 41.5°C at a flow rate of 4 ml/min. Concentrations of melphalan in perfusate and tissues were determined by high performance liquid chromatography with fluorescence detection. The concentration of melphalan in perfusate and tissues was linearly related to the input concentration. The rate and amount of melphalan uptake into the different tissues was higher at 41.5°C than at 37°C. A physiological pharmacokinetic model was validated from the tissue and perfusate time course of melphalan after melphalan perfusion. Application of the model involved the amount of melphalan exposure in the muscle, skin and fat in a recirculation system was related to the method of melphalan administration: single bolus > divided bolus > infusion. The peak concentration of melphalan in the perfusate was also related to the method of administration in the same order. Infusing the total dose of melphalan over 20 min during a 60 min perfusion optimized the exposure of tissues to melphalan whilst minimizing the peak perfusate concentration of melphalan. It is suggested that this method of melphalan administration may be preferable to other methods in terms of optimizing the efficacy of melphalan whilst minimizing the limb toxicity associated with its use in isolated limb perfusion.

ISSN:0960-8931    

出版商:OVID    

年代:1997

数据来源: OVID