Melanoma Research Today is a free monthly online journal that collates and summarizes the latest research about Melanoma, including details on identification, causes, prevention, treatment.

Effectiveness of treatments for metastatic uveal melanoma.

Augsburger JJ, Corrêa ZM, Shaikh AH

Department of Ophthalmology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.

PURPOSE: To evaluate and comment on published peer-reviewed literature for evidence of effectiveness of treatments for metastatic uveal melanoma. DESIGN: Analytical nonexperimental study of published peer-reviewed data. METHODS: Literature search and analysis of pertinent articles published between January 1, 1980 and June 30, 2008. RESULTS: Of 80 identified publications, 12 (15.0%) were review articles without original information, 2 (2.5%) were review articles combined with case reports, 22 (27.5%) were case reports, 16 (20.0%) were retrospective descriptive case series reports, 3 (3.75%) were pilot studies of a novel intervention, 2 (2.5%) were prospective phase I clinical trials, 8 (10.0%) were prospective phase I/II clinical trials, and 15 (18.75%) were prospective phase II clinical trials. None of the articles reported a prospective, randomized phase III clinical trial. The largest reported unselected patient groups had a median survival of 3 to 4 months after detection of metastasis, whereas the largest selected patient groups showed substantially longer median survival times. CONCLUSIONS: Although median survival time after diagnosis of metastatic uveal melanoma tends to be substantially longer in selected patient subgroups subjected to aggressive invasive interventions than it is in unselected groups, much if not most of this apparent difference in survival is likely to be attributable to selection bias, surveillance bias, and publication bias rather than treatment-induced alteration of expected outcome. Published peer-reviewed articles do not provide compelling scientific evidence of any survival benefit of any method of treatment for any subgroup of patients with metastatic uveal melanoma.

Published 22 June 2009 in Am J Ophthalmol, 148(1): 119-27.
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Articles on Melanoma published 17 June 2009:

Autoimmune antibodies and recurrence-free interval in melanoma patients treated with adjuvant interferon.   J Natl Cancer Inst, 101(12): 869-77.

BACKGROUND: Appearance of autoantibodies and clinical manifestations of autoimmunity in melanoma patients treated with adjuvant interferon (IFN)-alpha2b was reported to be associated with improved prognosis. We assessed the association of the appearance of autoantibodies after initiation of treatment with recurrence-free interval in two randomized trials that compared intermediate doses of IFN with observation for the treatment of melanoma patients. METHODS: Serum levels of anticardiolipin, ... [Abstract] [Full-text]

Articles on Melanoma published 15 June 2009:

Caspases and inhibitor of apoptosis proteins in cutaneous and mucosal melanoma: expression profile and clinicopathologic significance.   Hum Pathol, 40(7): 950-6.

Malignant melanoma is characterized by apoptotic dysfunction, presumably due to abnormal expression of caspases and inhibitor of apoptosis proteins. However, the expression status and clinicopathologic significance of caspases and inhibitor of apoptosis proteins in cutaneous and particularly in mucosal melanomas have not been established. We investigated the expression of the major caspases (CASP3, 6, 7, 8, 9, and 10) and inhibitor of apoptosis proteins (survivin, CIAP1, CIAP2, XIAP, and Livin) ... [Abstract] [Full-text]

Articles on Melanoma published 5 June 2009:

Impaired interferon signaling is a common immune defect in human cancer.   Proc Natl Acad Sci U S A, 106(22): 9010-5.

Immune dysfunction develops in patients with many cancer types and may contribute to tumor progression and failure of immunotherapy. Mechanisms underlying cancer-associated immune dysfunction are not fully understood. Efficient IFN signaling is critical to lymphocyte function; animals rendered deficient in IFN signaling develop cancer at higher rates. We hypothesized that altered IFN signaling may be a key mechanism of immune dysfunction common to cancer. To address this, we assessed the ... [Abstract] [Full-text]

Articles on Melanoma published 4 June 2009:

IFN-alpha enhances peptide vaccine-induced CD8+ T cell numbers, effector function, and antitumor activity.   J Immunol, 182(12): 7398-407.

Type I IFNs, including IFN-alpha, enhance Ag presentation and promote the expansion, survival, and effector function of CD8(+) CTL during viral infection. Because these are ideal characteristics for a vaccine adjuvant, we examined the efficacy and mechanism of exogenous IFN-alpha as an adjuvant for antimelanoma peptide vaccination. We studied the expansion of pmel-1 transgenic CD8(+) T cells specific for the gp100 melanocyte differentiation Ag after vaccination of mice with gp100(25-33) peptide ... [Abstract] [Full-text]

Novel variants of muscle calpain 3 identified in human melanoma cells: cisplatin-induced changes in vitro and differential expression in melanocytic lesions.   Carcinogenesis, 30(6): 960-7.

Calpains are cysteine proteases comprising members ubiquitously expressed in human tissues and other tissue-specific isoforms. Alterations of calpain 3 (p94), the muscle-specific isoform that contains three peculiar sequences (NS, IS1 and IS2), are strictly associated to the limb-girdle muscular dystrophy type 2A, in which a myonuclear apoptosis has been documented. Our recent demonstration of a proapoptotic role of ubiquitous calpains in drug-induced apoptosis of melanoma cells prompted us to ... [Abstract] [Full-text]

Suppression of NF-kappaB activity by NDRG2 expression attenuates the invasive potential of highly malignant tumor cells.   Carcinogenesis, 30(6): 927-36.

Downregulation of the N-myc downstream-regulated gene 2 (NDRG2) gene is involved in the progression of aggressive forms of cancer, along with the poor prognosis of cancer patients. In the current study, we examined the effect of NDRG2 expression on the metastatic potential of HT1080 human fibrosarcoma and B16F10 murine melanoma cells in both in vitro and in vivo systems. In gelatin zymography, NDRG2 expression remarkably suppressed the matrix metalloproteinase (MMP)-9 activity and slightly ... [Abstract] [Full-text]

Articles on Melanoma published 2 June 2009:

Is completion lymph node dissection needed in case of minimal melanoma metastasis in the sentinel node?   Ann Surg, 249(6): 1003-7.

OBJECTIVE: The purpose of this study was to evaluate the micromorphometric Starz-classification in melanoma patients. SUMMARY BACKGROUND DATA: The micromorphometric Starz-classification suggests that melanoma patients with a sentinel node metastasis invading no more than 0.3 mm (S-I) or 0.31 to 1.0 mm (S-II) below the capsular level can be spared further surgery, while invasion of the metastasis of more than 1.0 mm (S-III) implies a need for completion dissection. METHODS: Seventy patients with ... [Abstract] [Full-text]

Safety and efficacy of isolated limb infusion with cytotoxic drugs in elderly patients with advanced locoregional melanoma.   Ann Surg, 249(6): 1008-13.

INTRODUCTION: The treatment of elderly patients with advanced metastatic melanoma confined to a limb remains controversial. Isolated limb infusion (ILI) is an effective minimally invasive alternative to isolated limb perfusion (ILP) and is therefore a potentially valuable therapeutic option for this group. METHODS: From our prospective database 185 patients with advanced metastatic melanoma of the limb treated with a single ILI between 1992 and 2007 were identified. In all patients a cytotoxic ... [Abstract] [Full-text]

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