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https://www.readbyqxmd.com/read/28225782/chronic-treatment-of-non-small-cell-lung-cancer-cells-with-gefitinib-leads-to-an-epigenetic-loss-of-epithelial-properties-associated-with-reductions-in-microrna-155-and-200c
#1
Michiko Narita, Eri Shimura, Atsumi Nagasawa, Toshiki Aiuchi, Yukari Suda, Yusuke Hamada, Daigo Ikegami, Chizuru Iwasawa, Kazuhiko Arakawa, Katsuhide Igarashi, Naoko Kuzumaki, Yusuke Yoshioka, Takahiro Ochiya, Hideyuki Takeshima, Toshikazu Ushijima, Minoru Narita
BACKGROUND: The EGFR tyrosine kinase inhibitor gefitinib is used in therapy for non-small-cell lung cancer (NSCLC). However, its application is limited by resistance-accelerated disease progression, which is accompanied by the epithelial-to-mesenchymal transition (EMT). In the present study, we performed multiple expression analyses of microRNAs (miRNAs) and quantified the expression of several related EMT players in gefitinib-resistant NSCLC cells. METHODS AND RESULTS: To establish gefitinib-resistant NSCLC cells, gefitinib-sensitive HCC827 cells, which exhibit an in-frame deletion [E746-A750] in EGFR exon 19, were exposed to gefitinib for at least 1...
2017: PloS One
https://www.readbyqxmd.com/read/28225269/indazole-based-covalent-inhibitors-to-target-drug-resistant-epidermal-growth-factor-receptor
#2
Stefano Tomassi, Jonas Lategahn, Julian Engel, Marina Keul, Hannah Lea Tumbrink, Julia Ketzer, Thomas Mühlenberg, Matthias Baumann, Carsten Schultz-Fademrecht, Sebastian Bauer, Daniel Rauh
The specific targeting of oncogenic mutant epidermal growth factor receptor (EGFR) is a breakthrough in targeted cancer therapy and marks a drastic change in the treatment of non-small cell lung cancer (NSCLC). The recurrent emergence of resistance to these targeted drugs requires the development of novel chemical entities that efficiently inhibit drug-resistant EGFR. Herein, we report the optimization process for a hit compound that has emerged from a phenotypic screen resulting in indazole-based compounds...
February 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28223676/-multiple-salvage-radiotherapies-for-metachronous-lymph-node-metastasis-from-gastric-cancer-contributed-to-long-term-management-of-disease
#3
Naoto Hori, Shunsuke Kagawa, Satoru Kikuchi, Shinji Kuroda, Megumi Watanabe, Shuichi Sakamoto, Tetsuya Kagawa, Kazuya Kuwada, Tetsushi Kubota, Hiroyuki Kishimoto, Masahiko Nishizaki, Norihisa Katayama, Toshiyoshi Fujiwara
A 70-year-old man who underwent gastrectomy for Stage III C gastric cancer developed lymph node(LN)metastasis posterior to the pancreatic head 3 years after the radical surgery.He was first treated with radiotherapy(RT)followed by chemotherapy.The irradiated tumor regressed completely.However, the cancer relapsed in a single para-aortic LN and he was treated with RT to the lesion followed by chemotherapy.Although it completely regressed, later, lung metastasis was observed.The lung lesions were well suppressed by switching to docetaxel; however, the cancer relapsed again in a mediastinal LN, and it was not responsive to docetaxel...
February 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28223509/high-throughput-screening-of-rare-metabolically-active-tumor-cells-in-pleural-effusion-and-peripheral-blood-of-lung-cancer-patients
#4
Yin Tang, Zhuo Wang, Ziming Li, Jungwoo Kim, Yuliang Deng, Yan Li, James R Heath, Wei Wei, Shun Lu, Qihui Shi
Malignant pleural effusion (MPE), the presence of malignant cells in pleural fluid, is often the first sign of many cancers and occurs in patients with metastatic malignancies. Accurate detection of tumor cells in pleural fluid is crucial because the presence of MPE denotes an advanced stage of disease and directs a switch in clinical managements. Cytology, as a traditional diagnostic tool, has limited sensitivity especially when tumor cells are not abundant, and may be confounded by reactive mesothelial cells in the pleural fluid...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28223427/calcium-dependent-enhancement-by-extracellular-acidity-of-the-cytotoxicity-of-mitochondrial-inhibitors-against-melanoma
#5
Fumihito Noguchi, Shigeki Inui, Clare Fedele, Mark Shackleton, Satoshi Itami
Extracellular acidity is a hallmark of cancers and is independent of hypoxia. Since acidity potentiates malignant phenotypes, therapeutic strategies that enhance the targeting of oncogenic mechanisms in an acidic microenvironment should be effective. We report here that drugs which abrogate mitochondrial respiration show enhanced cytotoxicity against melanoma cells in a normoxic but acidic extracellular pH, independent from P53 mutations, BRAF (V600E) mutations and/or resistance against BRAF inhibitors. Conversely, the cytotoxicity against melanoma cells of mitochondrial inhibitors is impaired by a neutral or alkaline extracellular pH and in vivo systemic alkalinization with NaHCO3 enhanced subcutaneous tumor growth and lung metastasis of B16F10 cells in mice treated with the mitochondrial inhibitor phenformin...
February 21, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28221867/osimertinib-in-pretreated-t790m-positive-advanced-non-small-cell-lung-cancer-aura-study-phase-ii-extension-component
#6
James Chih-Hsin Yang, Myung-Ju Ahn, Dong-Wan Kim, Suresh S Ramalingam, Lecia V Sequist, Wu-Chou Su, Sang-We Kim, Joo-Hang Kim, David Planchard, Enriqueta Felip, Fiona Blackhall, Daniel Haggstrom, Kiyotaka Yoh, Silvia Novello, Kathryn Gold, Tomonori Hirashima, Chia-Chi Lin, Helen Mann, Mireille Cantarini, Serban Ghiorghiu, Pasi A Jänne
Purpose Osimertinib is an irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) selective for both EGFR-TKI sensitizing ( EGFRm) and T790M resistance mutations. AURA (NCT01802632) is a phase I/II clinical trial to determine the dose, safety, and efficacy of osimertinib. This article reports the results from the phase II extension component. Patients and Methods Patients with EGFR-TKI-pretreated EGFRm- and T790M-positive advanced non-small-cell lung cancer (NSCLC) received once-daily osimertinib 80 mg...
February 21, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28219421/regulation-of-voltage-gated-potassium-channels-attenuates-resistance-of-side-population-cells-to-gefitinib-in-the-human-lung-cancer-cell-line-nci-h460
#7
Seon Young Choi, Hang-Rae Kim, Pan Dong Ryu, So Yeong Lee
BACKGROUND: Side-population (SP) cells that exclude anti-cancer drugs have been found in various tumor cell lines. Moreover, SP cells have a higher proliferative potential and drug resistance than main population cells (Non-SP cells). Also, several ion channels are responsible for the drug resistance and proliferation of SP cells in cancer. METHODS: To confirm the expression and function of voltage-gated potassium (Kv) channels of SP cells, these cells, as well as highly expressed ATP-binding cassette (ABC) transporters and stemness genes, were isolated from a gefitinib-resistant human lung adenocarcinoma cell line (NCI-H460), using Hoechst 33342 efflux...
February 21, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28219203/-precision-first-line-therapy-for-advanced-non-small-cell-lung-cancer-patients-harboring-egfr-mutation
#8
D M Yuan, Y Song
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have become the preferred treatment option for advanced non-small-cell lung cancer (NSCLC) patients with activating mutations in epidermal growth factor receptor (EGFR) according to major practice guidelines. Gefitinib, elortinib and icotinib formed the cornerstone of first-line EGFR-TKIs in the clinical practice in our country. Now, with the continuously emerging of new types of EGFR-TKIs and ever-increasing publication of clinical trial results on afatinib, AZD9291 and other TKIs, we have more first-line choices for patients with EGFR mutations...
February 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28219202/-precision-treatment-after-resistance-to-first-generation-egfr-tki-in-patients-with-non-small-cell-lung-cancer
#9
C Pi, Y C Zhang, C R Xu, Q Zhou
Recently, with the research progress in molecular classification, the treatment of advanced non-small cell lung cancer (NSCLC) has been established as a model of anti-tumor treatment of precision medicine. The discovery of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) has transformed the treatment of NSCLC from platinum based doublet chemotherapy into era of target therapy. EGFR-TKI, such as erlotinib and gefitinib, have been recommended as standard first-line treatment of patients with EGFR mutation...
February 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28219199/-improving-the-internal-medical-care-to-set-up-a-leading-model-for-precision-medicine-development-in-lung-cancer
#10
B H Han
Lung cancer still remains the leading cause of cancer-related death worldwide. Recent development of molecular targeted therapies, especially the emergence of epidermal growth factor receptor (EGFR) inhibitors, has made an enormous progress for the treatment of non-small cell lung cancer (NSCLC). However, targeted therapy still faces many problems including acquired resistance. Several clinical trials have proved that targeted therapy can significantly improve the progression-free survival (PFS), but there are still many things needed to be improved...
February 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28218907/the-link-a-lncrna-interacts-with-ptdins-3-4-5-p3-to%C3%A2-hyperactivate-akt%C3%A2-and-confer-resistance-to-akt%C3%A2-inhibitors
#11
Aifu Lin, Qingsong Hu, Chunlai Li, Zhen Xing, Guolin Ma, Cheng Wang, Jun Li, Yin Ye, Jun Yao, Ke Liang, Shouyu Wang, Peter K Park, Jeffrey R Marks, Yan Zhou, Jianwei Zhou, Mien-Chie Hung, Han Liang, Zhibin Hu, Hongbing Shen, David H Hawke, Leng Han, Yubin Zhou, Chunru Lin, Liuqing Yang
Phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3 or PIP3) mediates signalling pathways as a second messenger in response to extracellular signals. Although primordial functions of phospholipids and RNAs have been hypothesized in the 'RNA world', physiological RNA-phospholipid interactions and their involvement in essential cellular processes have remained a mystery. We explicate the contribution of lipid-binding long non-coding RNAs (lncRNAs) in cancer cells. Among them, long intergenic non-coding RNA for kinase activation (LINK-A) directly interacts with the AKT pleckstrin homology domain and PIP3 at the single-nucleotide level, facilitating AKT-PIP3 interaction and consequent enzymatic activation...
February 20, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28217439/egfr-targeted-therapy-in-lung-cancer-an-evolving-story
#12
C Bartholomew, L Eastlake, P Dunn, D Yiannakis
Specific oncogenes with driver mutations, such as the Epidermal Growth Factor Receptor (EGFR 1) gene can lead to non-small-cell lung cancer formation. Identification of these oncogenes, their driver mutations and downstream effects allow the targeting of these pathways by drugs. Such personalised therapy has become an important strategy in combating lung cancer and highlights the need to test for these mutations. Tyrosine Kinase Inhibitors (TKIs) against EGFR, such as Erlotinib, are able to halt these tumour promoting properties in non-small-cell lung cancers...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28215720/tackling-the-next-generation-of-resistance-in-egfr-mutant-lung-cancer
#13
EDITORIAL
Zofia Piotrowska, Lecia V Sequist
No abstract text is available yet for this article.
March 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28215024/pharmacogenomics-of-platinum-based-chemotherapy-in-non-small-cell-lung-cancer-focusing-on-dna-repair-systems
#14
REVIEW
Yi Xiong, Bi-Yun Huang, Ji-Ye Yin
Drug therapy for non-small cell lung cancer consists mainly of platinum-based chemotherapy regimens. However, toxicity, drug resistance, and high risk of death have been seen in the clinic, which means there is a need for optimizing the use of medications. Platinum resistance could be mediated by a series of DNA repair pathways, and therefore, these pathways should be taken into account for optimizing drug using. The goal of pharmacogenomics is to elucidate genetic factors, such as DNA repair genes, which might underlie drug efficacy and effectiveness, and to improve therapeutic effects or guide personalized therapy as well...
April 2017: Medical Oncology
https://www.readbyqxmd.com/read/28214878/mirna-26a-contributes-to-the-acquisition-of-malignant-behaviors-of-doctaxel-resistant-lung-adenocarcinoma-cells-through-targeting-ezh2
#15
Jing Chen, Yuejuan Xu, Leilei Tao, Yan Pan, Kai Zhang, Rui Wang, Long-Bang Chen, Xiaoyuan Chu
BACKGROUND/AIMS: Accumulating evidence revealed that microRNAs (miRNAs) have been demonstrated as critical molecules in tumor development and progression. MiR-26a, located in a fragile chromosomal region associated with various human cancer, has been reported to be involved in regulating various cellular process, such as proliferation, apoptosis and invasion through targeting multiple oncogene. Docetaxel-mediated chemotherapy has been applied in improving the survival and prognosis of patients with advanced lung adenocarcinoma (LAD)...
February 3, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28214773/the-usefulness-of-bone-biomarkers-for-monitoring-treatment-disease-a-comparative-study-in-osteolytic-and-osteosclerotic-bone-metastasis-models
#16
Marta Martín-Fernández, Karmele Valencia, Carolina Zandueta, Cristina Ormazábal, Susana Martínez-Canarias, Fernando Lecanda, Concepción de la Piedra
BACKGROUND: The skeleton is the most common site of colonization by metastatic cancers. Zoledronic acid (ZA) has been shown to be effective for the treatment of bone metastases regardless of whether the bone lesions are osteolytic or osteoblastic. Biochemical markers of bone turnover may be useful tools to quantify the degree of bone remodeling in the presence of bone metastases. The aim of this work was to establish the correlation between tumor dispersion (bioluminescence) and biochemical markers of bone turnover in two osteolytic and osteoblastic metastasis models in mice...
February 16, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28214344/neferine-potentiates-the-antitumor-effect-of-cisplatin-in-human-lung-adenocarcinoma-cells-via-a-mitochondria-mediated-apoptosis-pathway
#17
Kalai Selvi Sivalingam, Poornima Paramasivan, Ching Feng Weng, Viswanadha Vijaya Padma
Cisplatin is one of the most potent chemotherapeutic agents for the treatment of many types of solid tumors but its efficacy is often limited by the development of resistance and dose limiting toxicity. Neferine is an alkaloid isolated from seed embryo of Nelumbo nucifera, it has recently been shown to have anticancer effects in various human cancer cell lines. The present investigation is designed to study the chemosensitizing ability of neferine with cisplatin in A549 cells. Neferine potentiates the cisplatin induced apoptosis through the exploration of characteristic apoptotic morphological changes, induced sub-G0/G1 cell cycle arrest, ROS hypergeneration, significant loss of cellular antioxidant enzymes as well as loss of mitochondrial membrane potential (ΔΨM)...
February 18, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28213330/drug-discovery-strategies-in-the-field-of-tumor-energy-metabolism-limitations-by-metabolic-flexibility-and-metabolic-resistance-to-chemotherapy
#18
REVIEW
N D Amoedo, E Obre, R Rossignol
The search for new drugs capable of blocking the metabolic vulnerabilities of human tumors has now entered the clinical evaluation stage, but several projects already failed in phase I or phase II. In particular, very promising in vitro studies could not be translated in vivo at preclinical stage and beyond. This was the case for most glycolysis inhibitors that demonstrated systemic toxicity. A more recent example is the inhibition of glutamine catabolism in lung adenocarcinoma that failed in vivo despite a strong addiction of several cancer cell lines to glutamine in vitro...
February 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28213007/effect-of-dasatinib-on-emt-mediated-mechanism-of-resistance-against-egfr-inhibitors-in-lung-cancer-cells
#19
Yuichi Sesumi, Kenichi Suda, Hiroshi Mizuuchi, Yoshihisa Kobayashi, Katsuaki Sato, Masato Chiba, Masaki Shimoji, Kenji Tomizawa, Toshiki Takemoto, Tetsuya Mitsudomi
OBJECTIVE: The epithelial to mesenchymal transition (EMT) is associated with acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in certain non-small cell lung cancers that harbor EGFR mutations. Because no currently available drugs specifically kill cancer cells via EMT, novel treatment strategies that overcome or prevent EMT are needed. A recent report suggested that dasatinib (an ABL/Src kinase inhibitor) inhibits EMT induced by transforming growth factor (TGF)-beta in lung cancer cells (Wilson et al...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28213001/predictive-factors-for-egfr-tyrosine-kinase-inhibitor-retreatment-in-patients-with-egfr-mutated-non-small-cell-lung-cancer-a-multicenter-retrospective-sequence-study
#20
Gee-Chen Chang, Chien-Hua Tseng, Kuo-Hsuan Hsu, Chong-Jen Yu, Cheng-Ta Yang, Kun-Chieh Chen, Tsung-Ying Yang, Jeng-Sen Tseng, Chien-Ying Liu, Wei-Yu Liao, Te-Chun Hsia, Chih-Yen Tu, Meng-Chih Lin, Ying-Huang Tsai, Meng-Jer Hsieh, Wen-Shuo Wu, Yuh-Min Chen
BACKGROUND: Acquired resistance occurs in most non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations experiencing a response to EGFR-tyrosine kinase inhibitor (TKI) initially. We investigated EGFR-TKI retreatment in patients who had previously received EGFR-TKI followed by chemotherapy. MATERIALS AND METHODS: This was a retrospective multicenter study. Patients with locally advanced or metastatic adenocarcinoma or TTF-1 (+) NSCLC, positive EGFR sensitive mutation, and EGFR-TKI reuse after initial EGFR-TKI followed by chemotherapy were enrolled...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
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