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This research considers the treatment of malignant melanoma. Data were collected from patient records for 78 individuals treated within the Yale Cancer Center Melanoma Unit. The patients were diagnosed with malignant melanoma prior to 1994 and progressed to stage I11 or N disease before their deaths.Due to the rapid progression of malignant melanoma, treatments are initiated at the time of diagnosis. Results of experimental Extreme Drug Resistance (EDR) tests subsequently become available. Physicians are warned the test results are not intended to guide therapy; however, assay directed therapies arguably result in better outcomes with other cancers. Thus, the question arises of whether the use of these tests might benefit patients in this context.This study evaluates the treatment decisions made using a multi-disciplinary approach within the Yale Cancer Center Melanoma Unit regarding patients with malignant melanoma relative to information contained in EDR tests conducted by Oncotech Inc. Within this comparison, three specific outcomes consistent with hypotheses of the study were assessed: the utilization of test results, drug toxicity and cost effectiveness and survival.Results were found to suggest that the initial treatment decisions of the Yale Cancer Center Melanoma Unit were in accord with tests results that were received henceforth for 74 of 78 patients. Two of those patients were in terminal stages of the disease thus treatments were unchanged; however two patients received a change in therapy.It is suggested that physicians made use of the tests as they became available. However, only two patients with therapies altered by the test results were shown to face reduced costs, drug toxicity, or have the benefit of improved survival. From the patient data collected, four patients receiving drugs to which their tumors exhibited EDR were found to exhibit shorter survival times. Literature review studies conducted to evaluate physician treatment approach and patient preference rate favorably the consideration of quality of life issues. The principle finding of this observational study which focuses upon the development of the Yale Cancer Center Melanoma Unit, suggest that a multidisciplinary approach to the treatment of malignant melanoma may offer quality of life benefits to the patient.

No / Prohormone convertases (PCs) are endoproteases that process many substrates in addition to hormone precursors. Although overexpression of PCs is linked to carcinogenesis in some solid tumors, the role of subtilisin-kexin isoenzyme-1 (SKI-1) in this context is unknown. We show that SKI-1 is constitutively expressed in human pigment cells with higher SKI activity in seven out of eight melanoma cell lines compared with normal melanocytes. SKI-1 immunoreactivity is also detectable in tumor cells of melanoma metastases. Moreover, tissue samples of the latter display higher SKI-1 mRNA levels and activity than normal skin. From various stimuli tested, 12-O-tetradecanoylphorbol-13-acetate and tunicamycin affected SKI-1 expression. Importantly, SKI-1 inhibition by the cell-permeable enzyme inhibitor decanoyl-RRLL-chloromethylketone (dec-RRLL-CMK) not only suppressed proliferation and metabolic activity of melanoma cells in vitro but also reduced tumor growth of melanoma cells injected intracutaneously into immunodeficient mice. Mechanistic studies revealed that dec-RRLL-CMK induces classical apoptosis of melanoma cells in vitro and affects expression of several SKI-1 target genes including activating transcription factor 6 (ATF6). However, ATF6 gene silencing does not result in apoptosis of melanoma cells, suggesting that dec-RRLL-CMK induces cell death in an ATF6-independent manner. Our findings encourage further studies on SKI-1 as a potential target for melanoma therapy.