Personalisierte Therapiekonzepte beim malignen Melanom

Abstract

Metastatic melanoma is commonly regarded as one of the most difficult tumor entities to treat. Up to 2011 no systemic therapy had been able to achieve a prolongation of overall survival in controlled randomized trials. Cytotoxic chemotherapy resulted in objective remission in only a small subgroup of patients. The growing insight into the molecular pathology and the discovery of frequent mutations made it possible to define melanoma subgroups suitable for targeted therapies. In approximately 50% of melanomas activating mutations of the BRAF gene were identified and can be treated with specific inhibitors. Further mutations which can be approached by targeted therapies are found on the c-Kit and NRAS genes. Another promising approach is immunotherapy aimed to activate cytotoxic T cells. A monoclonal antibody directed against CTLA-4 was approved after convincing results in clinical trials and antibodies against PD-1 or PD-L1 are currently under clinical investigation. Through these achievements life prolonging therapies are available for melanoma patients for the first time.

Safety and toxicology of the intravenous administration of Ang2-siRNA plasmid chitosan magnetic nanoparticles

“…Melanoma is a form of superficial tumor, with a high malignancy and difficulty to treat (2). Currently, no effective prevention and treatment methods exist (3). The traditional surgical treatment methods lead to surgical trauma.…”

Construction of Ang2-siRNA chitosan magnetic nanoparticles and the effect on Ang2 gene expression in human malignant melanoma cells

“…In total, 0.15 g Fe 3 O 4 magnetic nanoparticles (Nanjing Emperor Nano Materials Co., Ltd., Nanjing, China) were dispersed in 20 ml 1.5% chitosan solution (relative molecular weight, 1.38x10 6 ; degree of deacetylation, 90%; Zhejiang Aoxing Biotechnology Co., Ltd., Kanmen, Zhejiang, China) subsequent to ultrasonic dispersal (JY98-IIIDN; Shanghai Shengke Instrument & Equipment Co., Ltd., Shanghai, China) and stirring. Subsequently, 80 ml liquid paraffin (Nujol; Hangzhou Yongxin Hardware Co., Ltd., Hangzhou, China) and petroleum ether mixture (Jining Huakai Resin Co., Ltd, Jining, China) containing 2 ml Span-80 (Jiangsu Haian Petrochemical Plant, Nantong, China) was added to 20 ml 1.5% chitosan solution.…”

“…Ang is expressed at a high level in malignant melanoma cells compared with normal tissues (5). Thus, it is possible to inhibit angiogenesis by blocking Ang expression and to inhibit the growth of malignant melanoma, therefore achieving a therapy for malignant melanoma (6).…”