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https://www.readbyqxmd.com/read/27922681/cxcr4-promotes-cisplatin-resistance-of-non-small-cell-lung-cancer-in-a-cyp1b1-dependent-manner
#1
Songping Xie, Zhenbo Tu, Jie Xiong, Ganjun Kang, Lina Zhao, Weidong Hu, Haiyan Tan, Kingsley Miyanda Tembo, Qianshan Ding, Xinzhou Deng, Jie Huang, Qiuping Zhang
Chemoresistance is the main cause of treatment failure and high mortality in advanced lung cancer. Cisplatin, an important chemotherapeutic agent for lung cancer, has been observed to show enormously reduced chemotherapeutic efficacy owing to the development of chemoresistance. CXCR4, a stromal-derived-factor-1 specific chemokine receptor, is highly expressed in non-small cell lung cancer (NSCLC) tissues and participates in cancer progression by regulating cell growth, apoptosis or invasion. In this study, we therefore investigated whether CXCR4 plays a role in the cisplatin associated resistance in NSCLC...
December 2, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27922010/mek-inhibitors-block-growth-of-lung-tumours-with-mutations-in-ataxia-telangiectasia-mutated
#2
Michal Smida, Ferran Fece de la Cruz, Claudia Kerzendorfer, Iris Z Uras, Barbara Mair, Abdelghani Mazouzi, Tereza Suchankova, Tomasz Konopka, Amanda M Katz, Keren Paz, Katalin Nagy-Bojarszky, Markus K Muellner, Zsuzsanna Bago-Horvath, Eric B Haura, Joanna I Loizou, Sebastian M B Nijman
Lung cancer is the leading cause of cancer deaths, and effective treatments are urgently needed. Loss-of-function mutations in the DNA damage response kinase ATM are common in lung adenocarcinoma but directly targeting these with drugs remains challenging. Here we report that ATM loss-of-function is synthetic lethal with drugs inhibiting the central growth factor kinases MEK1/2, including the FDA-approved drug trametinib. Lung cancer cells resistant to MEK inhibition become highly sensitive upon loss of ATM both in vitro and in vivo...
December 6, 2016: Nature Communications
https://www.readbyqxmd.com/read/27920501/three-generations-of-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-developed-to-revolutionize-the-therapy-of-lung-cancer
#3
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/27920137/oncogenic-met-as-an-effective-therapeutic-target-in-non-small-cell-lung-cancer-resistant-to-egfr-inhibitors-the-rise-of-the-phoenix
#4
Livio Trusolino
Anecdotal reports have shown that concomitant inhibition of EGFR and MET can be clinically effective in patients with non-small cell lung cancer carrying EGFR mutations and MET amplification, but large phase III trials in genetically unselected individuals have failed to confirm the benefit of this combination therapy. A new study corroborates the evidence that lung cancer susceptibility to EGFR and MET blockade is sustained by genetically based activation of both targets and identifies a mutation in MET that confers acquired resistance to standard MET inhibitors hitting the active kinase, yet is vulnerable to other MET-directed compounds with a different binding mode...
December 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27919627/randomized-phase-2-trial-of-pharmacodynamic-separation-of-pemetrexed-and-intercalated-erlotinib-versus-pemetrexed-alone-for-advanced-nonsquamous-non-small-cell-lung-cancer
#5
Tianhong Li, Bilal Piperdi, William V Walsh, Mimi Kim, Laurel A Beckett, Rasim Gucalp, Missak Haigentz, Venu G Bathini, Huiyu Wen, Kaili Zhou, Patricia B Pasquinelli, Srikanth Gajavelli, Meera Sreedhara, Xianhong Xie, Primo N Lara, David R Gandara, Roman Perez-Soler
BACKGROUND: Pharmacodynamic separation of pemetrexed and erlotinib avoids negative cellular interactions and results in antitumor synergy in erlotinib-resistant non-small-cell lung cancer (NSCLC) cells, independent of EGFR (epidermal growth factor receptor) genotype. PATIENTS AND METHODS: Patients with platinum-treated metastatic nonsquamous NSCLC were randomly assigned 1:2 to pemetrexed alone (500 mg/m(2) provided intravenously on day 1) or pemetrexed followed by erlotinib (150 mg provided orally once daily on days 2-17) every 21 days...
October 28, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27917404/the-emerging-role-of-cdk5-in-cancer
#6
Karine Pozo, James A Bibb
Cdk5 is an atypical cyclin-dependent kinase that is well characterized for its role in the central nervous system rather than in the cell cycle. However Cdk5 has been recently implicated in the development and progression of a variety of cancers including breast, lung, colon, pancreatic, melanoma, thyroid and brain tumors. This broad pro-tumorigenic role makes Cdk5 a promising drug target for the development of new cancer therapies. Here we review the contribution of Cdk5 to molecular mechanisms that confer upon tumors the ability to grow, proliferate and disseminate to secondary organs, as well as resistance to chemotherapies...
October 2016: Trends in Cancer
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
#7
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/27916691/therapeutic-effects-of-gold-nanoparticles-synthesized-using-musa-paradisiaca-peel-extract-against-multiple-antibiotic-resistant-enterococcus-faecalis-biofilms-and-human-lung-cancer-cells-a549
#8
S Vijayakumar, B Vaseeharan, B Malaikozhundan, N Gopi, P Ekambaram, R Pachaiappan, P Velusamy, K Murugan, G Benelli, R Suresh Kumar, M Suriyanarayanamoorthy
Botanical-mediated synthesis of nanomaterials is currently emerging as a cheap and eco-friendly nanotechnology, since it does not involve the use of toxic chemicals. In the present study, we focused on the synthesis of gold nanoparticles using the aqueous peel extract of Musa paradisiaca (MPPE-AuNPs) by green approach following a facile and cheap fabrication process. The green synthesized MPPE-AuNPs were bio-physically characterized by UV-Vis spectroscopy, FTIR, XRD, TEM, Zeta potential and EDX. MPPE-AuNPs were crystalline in nature, spherical to triangular in shape, with particle size ranged within 50 nm...
December 1, 2016: Microbial Pathogenesis
https://www.readbyqxmd.com/read/27914365/developing-piperlongumine-directed-glutathione-s-transferase-inhibitors-by-an-electrophilicity-based-strategy
#9
Hai-Bo Wang, Xiao-Ling Jin, Jia-Fang Zheng, Fu Wang, Fang Dai, Bo Zhou
We report a case of successful design of glutathione S-transferase (GST) inhibitors via a natural product-inspired and electrophilicity-based strategy. Based on this strategy, a novel piperlongumine analog (PL-13) bearing a para-trifluoromethyl group and an α-chlorine on its aromatic and lactam rings, respectively, surfaced as a promising GST inhibitor, thereby overcoming cisplatin resistance in lung cancer A549 cells.
November 15, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27913578/characterization-of-egfr-t790m-l792f-and-c797s-mutations-as-mechanisms-of-acquired-resistance-to-afatinib-in-lung-cancer
#10
Yoshihisa Kobayashi, Koichi Azuma, Hiroki Nagai, Young Hak Kim, Yosuke Togashi, Yuichi Sesumi, Masato Chiba, Masaki Shimoji, Katsuaki Sato, Kenji Tomizawa, Toshiki Takemoto, Kazuto Nishio, Tetsuya Mitsudomi
Lung cancers harboring common EGFR mutations respond to EGFR tyrosine kinase inhibitors (TKIs). We previously reported that tumors with exon 18 mutations are particularly sensitive to irreversible second-generation (2G) afatinib compared with 1G-TKIs. However, data on the mechanisms of acquired resistance to afatinib are limited. We established afatinib-resistant cells by transfecting Ba/F3 cells with common or exon 18 (G719A and Del18) mutations and subjecting them to chronic exposure to increasing concentrations of afatinib...
December 2, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27912836/epidermal-growth-factor-receptor-mutated-advanced-non-small-cell-lung-cancer-a-changing-treatment-paradigm
#11
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/27912826/diagnosis-and-treatment-of-anaplastic-lymphoma-kinase-positive-non-small-cell-lung-cancer
#12
REVIEW
Kathryn C Arbour, Gregory J Riely
Anaplastic lymphoma kinase (ALK) gene rearrangements occur in a small portion of patients with non-small cell lung cancer (NSCLC). These gene rearrangements lead to constitutive activation of the ALK kinase and subsequent ALK-driven tumor formation. Patients with tumors harboring such rearrangements are highly sensitive to ALK inhibitors, such as crizotinib, ceritinib, and alectinib. Resistance to these kinase inhibitors occurs through several mechanisms, resulting in ongoing clinical challenges. This review summarizes the biology of ALK-positive lung cancer, methods for diagnosing ALK-positive NSCLC, current FDA-approved ALK inhibitors, mechanisms of resistance to ALK inhibition, and potential strategies to combat resistance...
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
#13
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/27911863/correlation-of-long-non-coding-rna-h19-expression-with-cisplatin-resistance-and-clinical-outcome-in-lung-adenocarcinoma
#14
Qi Wang, Ningning Cheng, Xuefei Li, Hui Pan, Chunyu Li, Shengxiang Ren, Chunxia Su, Weijing Cai, Chao Zhao, Limin Zhang, Caicun Zhou
The acquired drug resistance would influence the efficacy of cisplatin-based chemotherapy in non-small-cell lung cancer. The present study aimed to investigate the correlation of long non-coding RNA (lncRNA) H19 with cisplatin-resistance and clinical outcome in lung adenocarcinoma. In our study, the expression of H19 in cisplatin-resistant A549/DDP cells was unregulated. Knockdown of H19 restored the response of A549/DDP cells to cisplatin. H19-mediated chemosensitivity enhancement was associated with metastasis, induction of G0/G1 cell-cycle arrest, cell proliferation, and increased apoptosis...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911857/yap1-regulates-abcg2-and-cancer-cell-side-population-in-human-lung-cancer-cells
#15
Yuyuan Dai, Shu Liu, Wen-Qian Zhang, Yi-Lin Yang, Phillip Hang, Hui Wang, Li Cheng, Ping-Chih Hsu, Yu-Chen Wang, Zhidong Xu, David M Jablons, Liang You
A small population of cancer cells called cancer-initiating cells or cancer stem cells (CSCs) are involved in drug resistance, metastasis, and cancer relapse. Finding pathways that regulate CSC is very important for clinical therapy. ATP-binding cassette sub-family G member 2 (ABCG2) plays a role in side population (SP) cell formation and contributes to chemotherapy resistance in common forms of cancer. Yes-associated protein 1 (YAP1) is a major transcriptional effector of the Hippo pathway, which plays important roles in organ size control and tumorigenesis...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27910964/osimertinib-a-third-generation-tyrosine-kinase-inhibitor-targeting-non-small-cell-lung-cancer-with-egfr-t790m-mutations
#16
C E McCoach, A Jimeno
Oncogenic driver mutations in the epidermal growth factor receptor (EGFR) gene have provided a focus for effective targeted therapy. Unfortunately, all patients eventually develop resistance to frontline therapy with EGFR tyrosine kinase inhibitors (TKIs). The majority of patients develop a large subclonal population of tumor cells with a T790M mutation that renders these cells resistant to first-generation TKIs. Osimertinib is a third-generation EGFR TKI that was designed to overcome resistance from T790M mutations...
October 2016: Drugs of Today
https://www.readbyqxmd.com/read/27910741/topotecan-liposomes-a-visit-from-a-molecular-to-a-therapeutic-platform
#17
Shivani Saraf, Ankit Jain, Pooja Hurkat, Sanjay Kumar Jain
Topotecan (TPT), a potent anticancer camptothecin analog, is well described for the treatment of ovarian cancer, but has also anticancer activity against small-cell and non-small-cell lung cancer, breast cancer, and acute leukemia. Various nanocarriers, including liposomes, have been exploited for targeted delivery of TPT. However, there are a number of challenges with TPT delivery using TPT liposomes (TLs), such as low encapsulation efficiency, physiological pH labile E ring (hydrolysis), accelerated blood clearance, multidrug resistance, and cancer metastases...
2016: Critical Reviews in Therapeutic Drug Carrier Systems
https://www.readbyqxmd.com/read/27908756/a-novel-curcumin-derivative-which-inhibits-p-glycoprotein-arrests-cell-cycle-and-induces-apoptosis-in-multidrug-resistance-cells
#18
Vanessa Lopes-Rodrigues, Ana Oliveira, Marta Correia-da-Silva, Madalena Pinto, Raquel T Lima, Emília Sousa, M Helena Vasconcelos
Cancer multidrug resistance (MDR) is a major limitation to the success of cancer treatment and is highly associated with the overexpression of drug efflux pumps such as P-glycoprotein (P-gp). In order to achieve more effective chemotherapeutic treatments, it is important to develop P-gp inhibitors to block/decrease its activity. Curcumin (1) is a secondary metabolite isolated from the turmeric of Curcuma longa L.. Diverse biological activities have been identified for this compound, particularly, MDR modulation in various cancer cell models...
November 19, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27906433/microrna-185-5p-modulates-chemosensitivity-of-human-non-small-cell-lung-cancer-to-cisplatin-via-targeting-abcc1
#19
K Pei, J-J Zhu, C-E Wang, Q-L Xie, J-Y Guo
OBJECTIVE: MicroRNA-185-5p (miR-185-5p) dysregulation is found in various human cancers. Our purpose is to investigate the association of miR-185-5p expression with the sensitivity of non-small cell lung cancer (NSCLC) to cisplatin. MATERIALS AND METHODS: Real-time PCR or Western blot assay was performed to detect the expression of mature miR-185-5p and ATP-binding cassette, subfamily C, member 1 (ABCC1) protein. Cell lines with abnormal expression of miR-185-5p were generated using miR-185-5p inhibitor and mimics...
November 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27906420/the-effect-of-low-dosage-of-procaine-on-lung-cancer-cell-proliferation
#20
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
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