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Inhibiting crosstalk between MET signaling and mitochondrial dynamics and morphology: a novel therapeutic approach for lung cancer and mesothelioma.
Abstract The receptor tyrosine kinase MET is frequently involved in malignant transformation and inhibiting its activity in MET-dependent cancers is associated with improved clinical outcomes. Emerging evidence also suggests that mitochondria play an essential role in tumorigenesis and Dynamin Related Protein (DRP1), a key component of the mitochondrial fission machinery, has emerged as an attractive therapeutic target. Here, we report that inhibiting MET activity with the tyrosine kinase inhibitor MGCD516 attenuates viability, migration, and invasion of non-small cell lung cancer (NSCLC) and malignant pleural mes...
Source: Cancer Biology and Therapy - October 12, 2018 Category: Cancer & Oncology Authors: Wang J, Mirzapoiazova T, Carol Tan YH, Pang KM, Pozhitkov A, Wang Y, Wang Y, Mambetsariev B, Wang E, Nasser MW, Batra SK, Raz D, Reckamp K, Kulkarni P, Zheng Y, Salgia R Tags: Cancer Biol Ther Source Type: research

Synergistic effect of targeting dishevelled-3 and the epidermal growth factor receptor-tyrosine kinase inhibitor on mesothelioma cells in vitro.
Authors: Moriyama G, Tanigawa M, Sakai K, Hirata Y, Kikuchi S, Saito Y, Kyoyama H, Matsuda K, Seike M, Gemma A, Uematsu K Abstract It was previously revealed that Wnt signaling is activated in mesothelioma cells. Although epidermal growth factor receptor (EGFR) is expressed in mesothelioma cells, EGFR-tyrosine kinase inhibitors (TKIs) are not effective for mesothelioma treatment. However, in non-small cell lung cancer, the blocking of Wnt signaling has been identified to enhance the anticancer effect of EGFR-TKIs. To confirm the anticancer effect of blocking Wnt signaling in combination with EGFR-TKI treatment in m...
Source: Oncology Letters - February 7, 2018 Category: Cancer & Oncology Tags: Oncol Lett Source Type: research

Inhibition of autophagy potentiates pemetrexed and simvastatin-induced apoptotic cell death in malignant mesothelioma and non-small cell lung cancer cells
In this study, we determined whether autophagy could be induced by pemetrexed and simvastatin cotreatment in malignant mesothelioma and NSCLC cells. Furthermore, we determined whether inhibition of autophagy drives apoptosis in malignant mesothelioma and NSCLC cells. Malignant mesothelioma MSTO-211H and A549 NSCLC cells were treated with pemetrexed and simvastatin alone and in combination to evaluate their effect on autophagy and apoptosis. Cotreatment with pemetrexed and simvastatin induced greater caspase-dependent apoptosis and autophagy than either drug alone in malignant mesothelioma and NSCLC cells. 3-Methyladenine (...
Source: European Respiratory Journal - October 30, 2015 Category: Respiratory Medicine Authors: Kim, H.-R., Cho, K.-H., Hwang, K.-E., Jeong, E.-T. Tags: 11.1 Lung Cancer Source Type: research

Pemetrexed induces apoptosis in malignant mesothelioma and lung cancer cells through activation of reactive oxygen species and inhibition of sirtuin 1.
Authors: Hwang KE, Kim YS, Hwang YR, Kwon SJ, Park DS, Cha BK, Kim BR, Yoon KH, Jeong ET, Kim HR Abstract Pemetrexed is a multitargeted antifolate used for the treatment of malignant mesothelioma and non-small cell lung cancer (NSCLC). However, the mechanism by which pemetrexed induces apoptosis remains unclear. In the present study, we investigated the involvement of reactive oxygen species (ROS) and sirtuin 1 (SIRT1) in pemetrexed-induced apoptosis in MSTO-211 malignant mesothelioma cells and A549 NSCLC cells. Pemetrexed enhanced caspase-dependent apoptosis, induced intracellular ROS generation, and downregulate...
Source: Oncology Reports - March 5, 2015 Category: Cancer & Oncology Tags: Oncol Rep Source Type: research