Summary Melanoma represents a significant malignancy in humans and dogs. Different from genetically engineered models, sporadic canine melanocytic neoplasms share several characteristics with human disease that could make dogs a more relevant pre-clinical model. Canine melanomas rarely arise in sun-exposed sites. Most occur in the oral cavity, with a subset having intraepithelial malignant melanocytes mimicking the in situ component of human mucosal melanoma. The spectrum of canine melanocytic neoplasia includes benign lesions with some analogy to nevi, as well as invasive primary melanoma, and widespread metastasis. Growing evidence of distinct subtypes in humans, differing in somatic and predisposing germ-line genetic alterations, cell of origin, epidemiology, relationship to ultraviolet radiation and progression from benign to malignant tumors, may also exist in dogs. Canine and human mucosal melanomas appear to harbor BRAF, NRAS and c-kit mutations uncommonly, compared to human cutaneous melanomas, although both species share AKT and MAPK signaling activation. We conclude that there is significant overlap in the clinical and histopathological features of canine and human mucosal melanomas. This represents opportunity to explore canine oral cavity melanoma as a pre-clinical model.
BACKGROUNDSystemic treatment of metastatic melanoma is largely ineffective and alternative approaches are needed. Imatinib mesylate is an oral tyrosine kinase inhibitor that targets bcr‐Abl, c‐kit, platelet‐derived growth factor receptor (PDGFR)‐α, and PDGFR‐β, leading to remarkable clinical responses in several cancers. Signal transduction via c‐kit, PDGFR‐α, and PDGFR‐β has been demonstrated in malignant melanoma.METHODSThe primary objective of this Phase II study was to determine the response rate, response duration, and the frequency of 6‐month progression‐free survival in patients who could receive up to 2 prior therapeutic regimens. Initially, patients received imatinib at at dose of 400 mg twice orally each day. Based on Simon's optimal design, the study allowed entry of 21 patients; if there were ≥ 2 objective responses, accrual would then continue to a total of 41 patients.RESULTSTwenty‐six patients were enrolled. Patients experienced 29 episodes of Grade 3 and 2 episodes of Grade 4 toxicity (according to National Cancer Institute common toxicity criteria). No objective clinical responses were noted among the 25 evaluable patients. The median time to progression was 54 days and the median overall survival was 200 days. No patient was free of disease progression at 6 months. Paraffin‐embedded tumor specimens from 15 patients were tested for expression of imatinib responsive kinases by immunohistochemistry. Three tumors had moderate and 5 tumors had weak staining for c‐kit. Five tumor samples had weak staining for PDGFR‐α and ‐β.CONCLUSIONSImatinib is an inactive single agent in metastatic melanoma in a population of predominately pretreated patients. The levels of c‐kit and/or PDGFR‐α, ‐β expression in the current study were lower than previously reported. Alternative treatment strategies remain a priority for patients with advanced melanoma. Cancer 2006. © 2006 American Cancer Society.
With the proliferation of social networks and blogs, the Internet is increasingly being used to disseminate personal health information rather than just as a source of information. In this paper we exploit the wealth of user-generated data, available through the micro-blogging service Twitter, to estimate and track the incidence of health conditions in society. The method is based on two stages: we start by extracting possibly relevant tweets using a set of specially crafted regular expressions, and then classify these initial messages using machine learning methods. Furthermore, we selected relevant features to improve the results and the execution times. To test the method, we considered four health states or conditions, namely flu, depression, pregnancy and eating disorders, and two locations, Portugal and Spain. We present the results obtained and demonstrate that the detection results and the performance of the method are improved after feature selection. The results are promising, with areas under the receiver operating characteristic curve between 0.7 and 0.9, and f-measure values around 0.8 and 0.9. This fact indicates that such approach provides a feasible solution for measuring and tracking the evolution of health states within the society.
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