Malignant melanoma is the most lethal cutaneous neoplasm. Awareness, detection, and treatment along with sophistication of both the physician and patient are integral components to early recognition and cure of the disease. Diagnosis of melanoma at its earliest stage is crucial to outcome. This article discusses in depth the clinical presentation and evaluation, patterns of growth, and pathologic staging of the neoplasm and regional lymph nodes. Treatment approaches and outcomes are presented.
[Show abstract][Hide abstract] ABSTRACT: Therapies directed against receptor tyrosine kinases are effective in many cancer subtypes, including lung and breast cancer. We used a phosphoproteomic platform to identify active receptor tyrosine kinases that might represent therapeutic targets in a panel of 25 melanoma cell strains. We detected activated receptors including TYRO3, AXL, MERTK, EPHB2, MET, IGF1R, EGFR, KIT, HER3, and HER4. Statistical analysis of receptor tyrosine kinase activation as well as ligand and receptor expression indicates that some receptors, such as FGFR3, may be activated via autocrine circuits. Short hairpin RNA knockdown targeting three of the active kinases identified in the screen, AXL, HER3, and IGF1R, inhibited the proliferation of melanoma cells and knockdown of active AXL also reduced melanoma cell migration. The changes in cellular phenotype observed on AXL knockdown seem to be modulated via the STAT3 signaling pathway, whereas the IGF1R-dependent alterations seem to be regulated by the AKT signaling pathway. Ultimately, this study identifies several novel targets for therapeutic intervention in melanoma.
Molecular Cancer Research 06/2011; 9(6):801-12. DOI:10.1158/1541-7786.MCR-10-0512 · 4.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to identify a real-world US population having undergone surgery for malignant melanoma and describe treatment patterns, health care resource utilization, and costs for patients who subsequently received interferon alfa-2b (IFN) therapy or other standard of care chemotherapies.
A retrospective cohort study was conducted using administrative claims from MarketScan(®) databases among melanoma patients diagnosed between 2004 and 2008 who had surgery and were subsequently treated with IFN or other chemotherapies. Health care resource utilization and costs of services (converted to 2009 dollars) were evaluated. Cost refers to the amount paid to providers associated with the health service.
Of 18,075 subjects with melanoma surgery claims, 1525 (8.4%) were treated with IFN and 1194 (6.6%) with other chemotherapies. Median duration (days) and number of doses of IFN therapy were 29 and 20, respectively. Approximately half of patients who received IFN discontinued therapy within or after the one-month induction phase. For IFN therapy patients, average total cost per patient for the last melanoma-related surgery prior to start of therapy, including costs of the surgery itself, pathology, anesthesia, and hospital care, was $2219. The average total cost per patient related to IFN therapy was $1188; this included costs for drug, office visits, blood work, and infusions. Other chemotherapy costs ranged from $146 to $2678.
There is an unmet treatment need, considering that this study observed that melanoma patients on IFN therapy post-surgery do not complete the recommended one-year course of treatment which may compromise its full therapeutic benefits. Further study to investigate reasons for discontinuation may be warranted. In addition, costs associated with adjuvant IFN therapy in post-surgical treatment of disease are likely acceptable.
ClinicoEconomics and Outcomes Research 06/2012; 4(1):169-76. DOI:10.2147/CEOR.S32349
[Show abstract][Hide abstract] ABSTRACT: Melanoma is a life threatening condition, which mostly effects cocassions despite the advancements in current chemotherapeutic techniques. The aim of present study is to investigate the apoptotic inducing potential of oleanolic acid (OA) in A375 human melanoma cells. The anti-proliferative effects of OA (12.5–200 μM) were assessed by cell growth and XTT assay. The morphological and nuclear damage studies were carried out by Wright-Giemsa and DAPI staining, respectively. Further, the apoptotic inducing potential of OA in A375 cells were measured by DNA fragmentation ELISA. The results showed a dose-responsive effect of OA by inhibiting the cell growth significantly (P < 0.05) at 24 and 48 h with a decrease in cell viability (XTT data). The significant morphological changes included cellular annihilation, which was observed in A375 cells when compared to the control cells. Quantitative dose-dependent increase in apoptotic-DNA fragments in ELISA and nuclear fragments in DAPI results, further demonstrated the potential of this triterpenoid to induce apoptotic cell death at a concentration, particularly higher than 50 μM. Thus, we conclude that OA has wielded both anti-proliferative and apoptotic inducing potentials against A375 melanoma cells and can be a better choice for its progression.
Biomedicine and Preventive Nutrition 04/2014; 4(2). DOI:10.1016/j.bionut.2013.09.003
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