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https://www.readbyqxmd.com/read/27930974/mir-200c-enhances-sensitivity-of-drug-resistant-non-small-cell-lung-cancer-to-gefitinib-by-suppression-of-pi3k-akt-signaling-pathway-and-inhibites-cell-migration-via-targeting-zeb1
#1
Guohua Zhou, Fangli Zhang, Yu Guo, Jianfei Huang, Yaqiong Xie, Shuanglei Yue, Minghui Chen, Hao Jiang, Mengjie Li
Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is a major obstacle in the treatment of non-small cell lung cancer (NSCLC) patients. We explored the role of miR-200c in modulating the sensitivity of gefitinib-resistant NSCLC cells and examined the underlying mechanism. The gefitinib-resistant cell line PC-9-ZD and its parental PC-9 cells were used. Growth inhibition was detected by MTT assay. The cell apoptosis was detected by Annexin V/PI assay. Cell migration was assessed by wound-healing assay...
December 5, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27925186/up-regulation-of-transient-receptor-potential-melastatin-6-channel-expression-by-tumor-necrosis-factor-%C3%AE-in-the-presence-of-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor
#2
Chisa Furukawa, Naoko Fujii, Aya Manabe, Toshiyuki Matsunaga, Satoshi Endo, Hajime Hasegawa, Yoshinori Ito, Masahiko Yamaguchi, Yasuhiro Yamazaki, Akira Ikari
Anti-epidermal growth factor receptor (EGFR) drugs such as erlotinib and gefitinib cause a side effect of hypomagnesemia, but chemotherapy to treat this has not yet been developed. The transient receptor potential melastatin 6 (TRPM6) channel is involved in the reabsorption of Mg(2+) in the renal tubule. We reported previously that the expression of TRPM6 is up-regulated by epidermal growth factor (EGF) in renal tubular epithelial NRK-52E and HEK293 cells. EGF-induced elevation of TRPM6 expression was inhibited by erlotinib, gefitinib, and lapatinib...
December 7, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27924500/mir-124-modulates-gefitinib-resistance-through-snai2-and-stat3-in-non-small-cell-lung-cancer
#3
Fa-Yong Hu, Xiao-Nian Cao, Qin-Zi Xu, Yu Deng, Sen-Yan Lai, Jing Ma, Jun-Bo Hu
Gefitinib is used as a first-line treatment for advanced non-small cell lung cancer (NSCLC). Unfortunately, most NSCLC patients inevitably develop gefitinib resistance during treatment. In addition to EGFR mutation status, the mechanisms involved are largely unknown. In this study, we showed that miR-124, a tumor suppressor, was significantly down-regulated in gefitinib-resistant NSCLC patients and cell lines compared with gefitinib-sensitive patients and cell lines. In addition, the miR-124 depletion induced gefitinib resistance, and miR-124 overexpression sensitized gefitinib-resistant cells to gefitinib...
December 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/27920501/three-generations-of-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-developed-to-revolutionize-the-therapy-of-lung-cancer
#4
REVIEW
Haijun Zhang
Lung cancer, ~80%-85% of which is non-small-cell lung cancer (NSCLC), is the leading cause of cancer-related mortality worldwide. Sensitizing mutations in epidermal growth factor receptor (EGFR) gene (EGFRm(+)), such as exon 19 deletions and exon 21 L858R point mutations, are the most important drivers in NSCLC patients. In this respect, small-molecule EGFR tyrosine kinase inhibitors (TKIs) have been designed and developed, which launched the era of targeted, personalized and precise medicine for lung cancer...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27919956/expression-patterns-of-growth-and-survival-genes-with-prognostic-implications-in-advanced-pancreatic-cancer
#5
Dimitrios Pectasides, Vasiliki Kotoula, George Papaxoinis, Zoi Alexopoulou, Christos Dervenis, Epaminontas Samantas, Kleo Papaparaskeva, Elpida Charalambous, Chrysoula Gkakou, Christos Agalianos, Konstantine T Kalogeras, George Pentheroudakis, George Fountzilas
AIM: The aim of this study was to evaluate the mRNA expression pattern of growth- and survival-related genes and assess their prognostic significance in patients with advanced pancreatic cancer. PATIENTS AND METHODS: In total, 98 patients were included in this retrospective translational research study and were evaluated for Kirsten rat sarcoma viral oncogene homolog (KRAS) mutational status, and v-akt murine thymoma viral oncogene homolog 1 (AKT1), AKT serine/threonine kinase 2 (AKT2), AKT serine/threonine kinase 3 (AKT3), cyclin D1 (CCND1), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 1 (MAPK1), hepatocellular growth factor receptor (MET), avian myelomatosis viral oncogene homolog (MYC), nuclear factor kappa B subunit 1 (NFKb1), phosphatase and tensin homolog (PTEN) and mechanistic target of rapamycin (FRAP1) genes mRNA expression...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27918721/unconvincing-benefit-of-combination-therapy-with-gefitinib-and-pemetrexed-in-advanced-non-small-cell-lung-cancer
#6
Akiko Ota, Bishal Gyawali, Ayumu Matsuoka, Yuichi Ando
No abstract text is available yet for this article.
December 5, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27918713/gefitinib-plus-pemetrexed-as-first-line-treatment-in-patients-with-nonsquamous-non-small-cell-lung-cancer-with-activating-epidermal-growth-factor-receptor-mutations
#7
Young Hak Kim
No abstract text is available yet for this article.
December 5, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27916828/enhancing-anticancer-effect-of-gefitinib-across-the-blood-brain-barrier-model-using-liposomes-modified-with-one-%C3%AE-helical-cell-penetrating-peptide-or-glutathione-and-tween-80
#8
Kuan-Hung Lin, Shu-Ting Hong, Hsiang-Tsui Wang, Yu-Li Lo, Anya Maan-Yuh Lin, James Chih-Hsin Yang
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), such as gefitinib, have been demonstrated to effectively treat the patients of extracranial non-small cell lung cancer (NSCLC). However, these patients often develop brain metastasis (BM) during their disease course. The major obstacle to treat BM is the limited penetration of anticancer drugs across the blood-brain barrier (BBB). In the present study, we utilized gefitinib-loaded liposomes with different modifications to improve gefitinib delivery across the in vitro BBB model of bEnd...
November 29, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27912836/epidermal-growth-factor-receptor-mutated-advanced-non-small-cell-lung-cancer-a-changing-treatment-paradigm
#9
REVIEW
Suchita Pakkala, Suresh S Ramalingam
Activating mutations in the epidermal growth factor receptor (EGFR) are present in approximately 15% of US patients with lung adenocarcinoma. EGFR tyrosine kinase inhibitors are associated with high response rate and progression-free survival for patients with non-small cell lung cancer with this genotype. Gefitinib, erlotinib, and afatinib are the EGFR tyrosine kinase inhibitors that are presently in clinical use. Understanding resistance mechanisms has led to the identification of a secondary mutational target, T790M, in more than half of patients, for which osimertinib has been approved...
February 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/27912760/update-on-recent-preclinical-and-clinical-studies-of-t790m-mutant-specific-irreversible-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors
#10
REVIEW
Bin-Chi Liao, Chia-Chi Lin, Jih-Hsiang Lee, James Chih-Hsin Yang
The first- and second-generation epidermal growth factor receptor tyrosine kinase inhibitors (1/2G EGFR-TKIs) gefitinib, erlotinib, and afatinib have all been approved as standard first-line treatments for advanced EGFR mutation-positive non-small cell lung cancer. The third-generation (3G) EGFR-TKIs have been developed to overcome the EGFR T790M mutation, which is the most common mechanism of acquired resistance to 1/2G EGFR-TKI treatment. This resistance mutation develops in half of the patients who respond to 1/2G EGFR-TKI therapy...
December 3, 2016: Journal of Biomedical Science
https://www.readbyqxmd.com/read/27909271/-epidermal-growth-factor-receptor-mutated-advanced-lung-adenocarcinoma-with-long-term-tumor-free-survival-by-chemotherapy-followed-by-tyrosine-kinase-inhibitor-treatment-after-reduction-surgery
#11
Atsushi Morio, Kazuki Nakahara, Toshirou Futagawa, Kenji Suzuki
A 67-year-old woman was detected stage III B adenocarcinoma of the left lung, with epidermal growth factor receptor(EGFR) -mutation. Since chest computed tomography showed enlarged lymph nodes in stations 7 and 1R-4R, radiochemotherapy was recommended. However, she declined radiochemotherapy and the chemotherapy after tumor reduction surgery was chosen. She underwent resection of the left lower lobe and lingular segment, and mediastinal lymph node dissection through a posterolateral thoracotomy by extended bronchoplasty(type C) due to the extranodal invasion of lymph nodes to the lingular segmental bronchus...
December 2016: Kyobu Geka. the Japanese Journal of Thoracic Surgery
https://www.readbyqxmd.com/read/27908825/egfr-mutation-subtypes-influence-survival-outcomes-following-first-line-gefitinib-therapy-in-advanced-asian-nsclc-patients
#12
Natalia Sutiman, Shao Weng Tan, Eng Huat Tan, Wan Teck Lim, Ravindran Kanesvaran, Quan Sing Ng, Amit Jain, Mei Kim Ang, Wan Ling Tan, Chee Keong Toh, Balram Chowbay
INTRODUCTION: Activating mutations in the EGFR gene have been shown to confer sensitivity to EGFR tyrosine kinase inhibitors (TKIs) in advanced NSCLC patients. However, wide inter-patient variability in treatment outcomes to EGFR TKIs in these patients remains unaccounted for. This study aimed to evaluate the influence of EGFR mutation types and subtypes on survival outcomes in advanced Asian NSCLC patients receiving first-line gefitinib therapy. METHODS: Patients with stage IIIB/IV, harboring EGFR mutations, receiving first-line gefitinib treatment and of Asian descent (N=383) were evaluated...
November 28, 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27907909/egfr-kinase-inhibitors-and-gastric-acid-suppressants-in-egfr-mutant-nsclc-a-retrospective-database-analysis-of-potential-drug-interaction
#13
Nesaretnam Barr Kumarakulasinghe, Nicholas Syn, Yu Yang Soon, Atasha Asmat, Huili Zheng, En Yun Loy, Brendan Pang, Ross Andrew Soo
BACKGROUND: Erlotinib and gefitinib are weak base drugs whose absorption and clinical efficacy may be impaired by concomitant gastric acid suppressive (AS) therapy, yet proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2As) are widely indicated in non-small cell lung cancer (NSCLC) patients for the prevention and treatment of erlotinib-induced gastrointestinal injury and corticosteroid-associated gastric irritation. We assessed the clinical relevance of this potential drug-drug interaction (DDI) in a retrospective cohort of EGFR-mutant NSCLC patients...
November 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27906420/the-effect-of-low-dosage-of-procaine-on-lung-cancer-cell-proliferation
#14
X-W Ma, Y Li, X-C Han, Q-Z Xin
OBJECTIVE: Non-small cell lung cancer (NSCLC) is the most common type of human lung cancer leading cause of cancer death worldwide. However, first-line drugs such as gefitinib and erlotinib showed great drug resistance in the clinical. MATERIALS AND METHODS: The cell proliferation was evaluated by MTT assay; gene expression was detected by qPCR assay. The protein expression was analyzed by Western blotting. RESULTS: Our results showed that in mouse models of lung cancer by A549 or NCI-H1975 xenograft, the local anesthetic drug Procaine (PCA) with 50 mg/kg specifically attenuated tumors compared with the vehicle-treated group...
November 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27903123/drug-priming-enhances-radiosensitivity-of-adamantinomatous-craniopharyngioma-via-downregulation-of-survivin
#15
Christina Stache, Christiane Bils, Rudolf Fahlbusch, Jörg Flitsch, Michael Buchfelder, Harald Stefanits, Thomas Czech, Udo Gaipl, Benjamin Frey, Rolf Buslei, Annett Hölsken
OBJECTIVE In this study, the authors investigated the underlying mechanisms responsible for high tumor recurrence rates of adamantinomatous craniopharyngioma (ACP) after radiotherapy and developed new targeted treatment protocols to minimize recurrence. ACPs are characterized by the activation of the receptor tyrosine kinase epidermal growth factor receptor (EGFR), known to mediate radioresistance in various tumor entities. The impact of tyrosine kinase inhibitors (TKIs) gefitinib or CUDC-101 on radiation-induced cell death and associated regulation of survivin gene expression was evaluated...
December 2016: Neurosurgical Focus
https://www.readbyqxmd.com/read/27900074/afatinib-induced-acute-fatal-pneumonitis-in-metastatic-lung-adenocarcinoma
#16
Sang Hoon Yoo, Jin Ah Ryu, Seo Ree Kim, Su Yun Oh, Gu Sung Jung, Dong Jae Lee, Bong Gyu Kwak, Yu Hyun Nam, Kyung Hyun Kim, Young Jun Yang
Afatinib is an oral tyrosine kinase inhibitor (TKI) that inhibit Endothelial Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), and HER4. The common side effects of EGFR TKI are rash, acne, diarrhea, stomatitis, pruritus, nausea, and loss of appetite. Drug induced pneumonitis is the less common adverse effects of EGFR TKI. Afatinib, 2nd generation EGFR TKI is anticipated to overcome drug resistance from 1st generation EGFR TKI according to preclinical study, and several studies are being conducted to compare clinical efficacy between 1st and 2nd EGFR TKI...
November 2016: Korean Journal of Family Medicine
https://www.readbyqxmd.com/read/27898252/advanced-non-small-cell-lung-cancer-nsclc-with-activating-egfr-mutations-first-line-treatment-with-afatinib-and-other-egfr-tkis
#17
Wolfgang Brückl, Amanda Tufman, Rudolf Maria Huber
Based on the results of several randomised controlled trials, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have now replaced platinum-based chemotherapy as first-line therapy for advanced non-small cell lung cancer (NSCLC) harboring an activating EGFR mutation. Areas covered: This review describes the EGFR pathway and its abnormalities in NSCLC and discusses the differential molecular and clinical activity of first and next-generation EGFR TKIs in the first-line treatment of tumors with an activating EGFR mutation, with a special focus on the second-generation agent afatinib...
November 29, 2016: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/27895763/small-cell-lung-cancer-transformation-and-the-t790m-mutation-a-case-report-of-two-acquired-mechanisms-of-tki-resistance-detected-in-a-tumor-rebiopsy-and-plasma-sample-of-egfr-mutant-lung-adenocarcinoma
#18
Greta Alì, Rossella Bruno, Mirella Giordano, Irene Prediletto, Letizia Marconi, Simonetta Zupo, Franco Fedeli, Alessandro Ribechini, Antonio Chella, Gabriella Fontanini
The present study describes the case of a 45-year-old man diagnosed with metastatic lung adenocarcinoma, which harbored a deletion within exon 19 of the epidermal growth factor receptor (EGFR) gene. The patient was subsequently treated with gefitinib (250 mg/day orally from May 2013 to March 2014), but developed acquired resistance to the drug following 11 months of treatment. Tumor burden molecular analysis was performed on a tumor rebiopsy and plasma sample, and histological analysis was also performed on the tumor rebiopsy...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27895753/drug-resistance-analysis-of-gefitinib-targeted-therapy-in-non-small-cell-lung-cancer
#19
Shuliang Liu, Hongji Yang, Xingping Ge, Lingfei Su, Aifeng Zhang, Liang Liang
The aim of the study was to examine the drug resistance analysis of gefitinib-targeted therapy in non-small cell lung cancer (NSCLC). In total, 156 NSCLC patients without surgical treatment were selected, including 117 cases of adenocarcinoma (75%), to receive single gefitinib 0.25 g/day or combined with platinum chemotherapy. Computed tomography was used to evaluate tumor growth for the response and non-response groups. The chemotherapy regimen was changed or combined with radiotherapy in the non-response group...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27895663/mir-30a-5p-overexpression-may-overcome-egfr-inhibitor-resistance-through-regulating-pi3k-akt-signaling-pathway-in-non-small-cell-lung-cancer-cell-lines
#20
Fei Meng, Fengfeng Wang, Lili Wang, S C Cesar Wong, William C S Cho, Lawrence W C Chan
Lung cancer is one of the most common deadly diseases worldwide, most of which is non-small cell lung cancer (NSCLC). The epidermal growth factor receptor (EGFR) mutant NSCLCs frequently respond to the EGFR tyrosine kinase inhibitors (EGFR-TKIs) treatment, such as Gefitinib and Erlotinib, but the development of acquired resistance limits the utility. Multiple resistance mechanisms have been explored, e.g., the activation of alternative tyrosine kinase receptors (TKRs) sharing similar downstream pathways to EGFR...
2016: Frontiers in Genetics
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