Uveal malignant melanoma (UM) is the most frequent primary intraocular tumour in adult humans. Because the survival rate of patients with UM has changed little in the past few decades, a better understanding of the molecular events governing UM development and the identification of markers indicating the potential for metastasis at the time of diagnosis are necessary to design improved and more specific treatments. In this study, we investigated UM tumour development by comparing two recently established UM cultures with different invasion potential by twodimensional gel electrophoresis. Protein features expressed differentially were identified by mass spectrometric analysis. Potential markers were assayed in both cultures and in long-term established UM cell lines (UW-1, OCM-1, SP6.5 and 92.1) by Western blotting and their role in invasion analysed using Matrigel membranes. Comparative analysis revealed that UM cultures with lowand high-grade invasion potential differ in their cellular metabolism and, more interestingly, in several cancer-associated proteins, including those implicated in cell adhesion and migration, proliferation and various oncogenes. Our data indicate a correlation between MUC18 and HMG-1 expression and the invasiveness of UM cells. We also demonstrate the expression and secretion of DJ-1 oncoprotein by UM cells. We suggest a possible role for MUC18 and HMG-1 proteins in UM cell invasion. The secretion of DJ-1 by UM cells, and the ability to detect this protein in UM patients' sera implicate it as a potential noninvasive biomarker for this malignancy. ' 2006 Wiley-Liss, Inc.Key words: uveal melanoma; invasion; proteomics; MUC-18; DJ-1 Uveal malignant melanoma (UM) is the most frequent intraocular tumour in adult humans.1 Unlike cutaneous melanoma, uveal melanoma disseminates mainly through the blood stream and preferentially establishes metastases in the liver. Metastatic liver disease is the leading cause of death in uveal melanoma and can develop after a long disease-free interval, which suggests the presence of occult micrometastatic disease at the time the primary eye tumour is diagnosed and treated.2 Unfortunately, advances in eye cancer treatment have not paralleled those made in the management of other types of cancer, and the survival rate of patients with uveal melanoma has changed little in the past few decades.3 A better understanding of the molecular events governing uveal melanoma development and the identification of markers indicating the potential for metastasis at the time of diagnosis are necessary to design improved and more specific treatments. Various clinical and molecular prognostic factors have been suggested in uveal melanoma, but none has proved to be sufficiently useful or viable for routine clinical use. 4,5 Currently, there are many challenging technologies and approaches to identify tumour markers for prognostic and therapeutic purposes.6 Transcriptional studies alone are not sufficient, with several investigators reporting a poor correlation between mRNA and p...
Introduction: More than 50% of patients with uveal melanoma end up developing metastases. Currently, there is no standard first-line treatment that facilitates proper management of the metastatic disease. Methods: A systematic review of the last 40 years in PubMed with an exhaustive and strict selection of studies was conducted, in which the unit of measurement was overall survival (OS) expressed in Kaplan–Meier curves or numerically. Results: After the selection process, 110 articles were included. Regional therapies, such as intra-arterial liver chemotherapy (OS: 2, 9–22 months), isolated liver perfusion (OS: 9, 6–27, 4 months), or selective internal radiation therapy (OS: 18 months in monotherapy and 26 months in combination with other therapies) showed some superiority when compared to systemic therapies, such as chemotherapy (OS: 4, 6–17 months), immunotherapy (OS: 5–19, 1 month), immunosuppression (OS: 11 months), or targeted therapy (OS: 6–12 months), without being significant. Conclusions: The results of this review suggest that there are no important differences in OS when comparing the different current treatment modalities. Most of the differences found seem to be explained by the heterogenicity of the different studies and the presence of biases in their design, rather than actual extensions of patient survival.
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