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https://www.readbyqxmd.com/read/28813624/tp53-mutational-status-and-ros-effect-the-expression-of-the-survivin-associated-radio-adaptive-response
#1
Jeffrey S Murley, Richard C Miller, Ralph R Weichselbaum, David J Grdina
A survivin-associated radio-adaptive response, characterized by increased radiation resistance or sensitization, was induced by exposure to 5 mGy of ionizing radiation and was correlated to the TP53 mutational status of exposed cells. Ten human cancer lines were investigated: colorectal carcinomas HCT116 and RKO [TP53 wild-type (WT)] and their respective TP53 null isogenic lines; breast adenocarcinomas MCF7 (TP53 WT) and MDA-MB-231 (TP53 Mut); lung carcinomas A549 (TP53 WT) and NCI-H1975 (TP53 Mut); and pancreatic carcinomas Hs766T (TP53 WT) and Panc-1 (TP53 Mut)...
August 16, 2017: Radiation Research
https://www.readbyqxmd.com/read/28812378/bevacizumab-in-advanced-lung-cancer-state-of-the-art
#2
Sandra Assoun, Solenn Brosseau, Christelle Steinmetz, Valérie Gounant, Gérard Zalcman
Despite recent advances in metastatic lung cancer treatment with the advent of immune checkpoint inhibitors and molecules targeting addictive genomic abnormalities, prognosis of most of the patients remains unfavorable. Combination approaches with older drugs, such as bevacizumab, should be thus envisioned. Bevacizumab is a monoclonal anti-VEGF antibody, approved by the US FDA and the EMA in first-line and maintenance settings of advanced nonsquamous non-small-cell lung cancer (NSCLC) treatment, in association with platinum-based chemotherapy...
August 16, 2017: Future Oncology
https://www.readbyqxmd.com/read/28807234/third-generation-egfr-tkis-in-egfr-mutated-nsclc-where-are-we-now-and-where-are-we-going
#3
REVIEW
A Russo, T Franchina, G R R Ricciardi, V Smiroldo, M Picciotto, M Zanghì, C Rolfo, V Adamo
The therapeutic landscape of Non Small Lung Cancer (NSCLC) has been profoundly changed over the last decade with the clinical introduction of Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (TKIs) and the discovery of EGFR activating mutations as the major predictive factor to these agents. Despite impressive clinical activity against EGFR-mutated NSCLCs, the benefit seen with 1st and 2nd generation EGFR TKIs is usually transient and virtually all patients become resistant. Several different mechanisms of acquired resistance have been reported to date, but the vast majority of patients develop a secondary exon 20 mutation in the ATP-binding site of EGFR, namely T790M...
September 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28806542/outcome-of-patients-with-lung-adenocarcinoma-with-transformation-to-small-cell-lung-cancer-following-tyrosine-kinase-inhibitors-treatment-a-systematic-review-and-pooled-analysis
#4
REVIEW
Elisa Roca, Cristina Gurizzan, Vito Amoroso, William Vermi, Vittorio Ferrari, Alfredo Berruti
BACKGROUND: Lung adenocarcinoma can transform to small-cell lung cancer (SCLC) when resistance to tyrosine kinase inhibitors (TKIs) develops. This phenomenon has repeatedly been described in several case reports and small patient series. The characteristics and treatment outcomes of this population, however, have not been comprehensively reported. METHODS: We performed a systematic review of the published literature to obtain explorative information on the clinical and pathological features and prognosis of the reported cases...
July 31, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28805682/alk-in-non-small-cell-lung-cancer-nsclc-pathobiology-epidemiology-detection-from-tumor-tissue-and-algorithm-diagnosis-in-a-daily-practice
#5
REVIEW
Paul Hofman
Patients with advanced-stage non-small cell lung carcinoma (NSCLC) harboring an ALK rearrangement, detected from a tissue sample, can benefit from targeted ALK inhibitor treatment. Several increasingly effective ALK inhibitors are now available for treatment of patients. However, despite an initial favorable response to treatment, in most cases relapse or progression occurs due to resistance mechanisms mainly caused by mutations in the tyrosine kinase domain of ALK. The detection of an ALK rearrangement is pivotal and can be done using different methods, which have variable sensitivity and specificity depending, in particular, on the quality and quantity of the patient's sample...
August 12, 2017: Cancers
https://www.readbyqxmd.com/read/28805673/alk-status-assessment-with-liquid-biopsies-of-lung-cancer-patients
#6
REVIEW
Paul Hofman
Patients with advanced stage non-small cell lung carcinoma (NSCLC) harboring an anaplastic lymphoma kinase ALK gene rearrangement, detected from a tissue sample, can benefit from targeted ALK inhibitor treatment. However, while treatment is initially effective in most cases, relapse or progression occurs due to different resistance mechanisms including mutations in the tyrosine kinase domain of echinoderm microtubule-associated protein-like 4 (EML44)-ALK. The liquid biopsy concept has recently radically changed the clinical care of NSCLC patients, in particular for those harboring an epidermal growth factor receptor (EGFR) gene mutation...
August 12, 2017: Cancers
https://www.readbyqxmd.com/read/28804523/tri-methylation-of-h3k79-is-decreased-in-tgf-%C3%AE-1-induced-epithelial-to-mesenchymal-transition-in-lung-cancer
#7
Emilie Evanno, Julie Godet, Nathalie Piccirilli, Joëlle Guilhot, Serge Milin, Jean Marc Gombert, Benoit Fouchaq, Joëlle Roche
BACKGROUND: The epithelial-to-mesenchymal transition (EMT) enables epithelial cancer cells to acquire mesenchymal features and contributes to metastasis and resistance to treatment. This process involves epigenetic reprogramming for gene expression. We explored global histone modifications during TGF-β1-induced EMT in two non-small cell lung cancer (NSCLC) cell lines and tested different epigenetic treatment to modulate or partially reverse EMT. RESULTS: Loss of classical epithelial markers and gain of mesenchymal markers were verified in A549 and H358 cell lines during TGF-β1-induced EMT...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28803257/synthesis-and-biological-evaluation-of-4-o-acetyl-isoxanthohumol-and-its-analogues-as-antioxidant-and-antiproliferative-agents
#8
Monika Stompor, Marta Świtalska, Rafał Podgórski, Łukasz Uram, David Aebisher, Joanna Wietrzyk
Isoxanthohumol (2) and its 4'-O-monoacylated (3) and 7,4'-O-diacetylated (4) derivatives were synthesized and evaluated in vitro for their cytotoxic activity against several cancer cell lines of various origins: MCF-7 (breast), A549 (lung), MESSA (uterine sarcoma), LoVo (colon), drug-resistant human cancer cells (MESSA/DX and LoVo/DX), glioblastoma (U-118 MG), and also towards the non-cancerous cell line MCF-10A (normal breast cells). An antiproliferative assay indicates that 7,4'-di-O-acylisoxanthohumol (4) has similar cytotoxicity to its precursor, isoxanthohumol (2), against selected cell lines (A549, MES-SA, MES-SA/5DX, and U-118 MG)...
August 12, 2017: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/28801607/enhancing-nk-cell-mediated-cytotoxicity-to-cisplatin-resistant-lung-cancer-cells-via-mek-erk-signaling-inhibition
#9
Li Yang, MingJing Shen, Li Jun Xu, Xiaodong Yang, Ying Tsai, Peter C Keng, Yuhchyau Chen, Soo Ok Lee
Major progress has been made clinically in inhibiting the programmed death receptor 1 (PD-1)/PD-L1 interaction to enhance T cell-mediated immune function, yet the effectiveness of anti-PD-L1/PD-1 agents in enhancing natural killer (NK) cell's function remains largely unknown. Susceptibilities of cisplatin-resistant A549CisR and H157CisR cells vs. parental cells to the cytotoxic action of NK cells were examined. We found cisplatin-resistant cells more resistant to NK cell cytotoxicity than parental cells. There were constitutively higher expressions of PD-L1 in A549CisR and H157CisR cells than in parental cells in vitro, as well as in H157CisR cell-derived tumors than H157P cell-derived tumors...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28800787/mir-449a-suppresses-ldha-mediated-glycolysis-to-enhance-the-sensitivity-of-non-small-cell-lung-cancer-cells-to-ionizing-radiation
#10
Liang Li, Huijuan Liu, Lianjiang Du, Pan Xi, Qian Wang, Yanqin Li, Di Liu
MicroRNA dysregulation contributes to malignant progression, dissemination and profound treatment resistance in multiple cancers. MiR-449a is recognized as a tumor suppresser. However, roles of miR-449a in lung cancers initiation and progression are largely unrevealed. Our study aims to investigate roles and the underlying mechanism of miR-449a in modulating sensitivity to ionizing radiation (IR) in non-small cell lung cancers (NSCLC). Lung cancer cells were transfected with miR-449a mimics or negative control and exposed to IR, levels of target protein, glycolysis, cell viability, apoptosis and DNA damage were examined...
August 11, 2017: Oncology Research
https://www.readbyqxmd.com/read/28800469/immunotherapy-in-ovarian-endometrial-and-cervical-cancer-state-of-the-art-and-future-perspectives
#11
REVIEW
Jole Ventriglia, Immacolata Paciolla, Carmela Pisano, Sabrina Chiara Cecere, Marilena Di Napoli, Rosa Tambaro, Daniela Califano, Simona Losito, Giosuè Scognamiglio, Sergio Venanzio Setola, Laura Arenare, Sandro Pignata, Chiara Della Pepa
The tumors of the female genital tract represent a leading cause of morbidity and mortality among women worldwide. Substantial progresses have been made in ovarian cancer, with the increasing knowledge about BRCA mutated tumors and the recent development of PARP inhibitors, and in cervical cancer, thanks to extensive screening and widespread of vaccination against Human Papilloma Virus. Nevertheless many needs remain unmet, advanced stage diseases are still incurable and cervical and endometrial carcinoma, as well as platinum-resistant ovarian carcinoma, can certainly be classifiable among the cancers with poor sensitivity to conventional chemotherapy...
July 31, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28799237/anticancer-efficacy-of-the-hypoxia-activated-prodrug-evofosfamide-is-enhanced-in-combination-with-proapoptotic-receptor-agonists-against-osteosarcoma
#12
Vasilios Liapis, Aneta Zysk, Mark DeNichilo, Irene Zinonos, Shelley Hay, Vasilios Panagopoulos, Alexandra Shoubridge, Christopher Difelice, Vladimir Ponomarev, Wendy Ingman, Gerald J Atkins, David M Findlay, Andrew C W Zannettino, Andreas Evdokiou
Tumor hypoxia is a major cause of treatment failure for a variety of malignancies. However, hypoxia also leads to treatment opportunities as demonstrated by the development of compounds that target regions of hypoxia within tumors. Evofosfamide is a hypoxia-activated prodrug that is created by linking the hypoxia-seeking 2-nitroimidazole moiety to the cytotoxic bromo-isophosphoramide mustard (Br-IPM). When evofosfamide is delivered to hypoxic regions of tumors, the DNA cross-linking toxin, Br-IPM, is released leading to cell death...
August 10, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28797845/the-hsp90-inhibitor-nvp-auy922-attenuates-intrinsic-pi3k-inhibitor-resistance-in-kras-mutant-non-small-cell-lung-cancer
#13
Kang-Seo Park, Hannah Yang, Junyoung Choi, Seyoung Seo, Deokhoon Kim, Chang Hoon Lee, Hanwool Jeon, Sang-We Kim, Dae Ho Lee
More than 25% of non-small cell lung cancers (NSCLCs) carry mutations in KRAS, one of the most common oncogenic drivers in this disease. KRAS-mutant NSCLC responds poorly to currently available therapies; therefore, novel treatment strategies are needed. Here, we describe a particularly promising targeted therapeutic strategy against KRAS mutation-harboring NSCLC intrinsically resistant to treatment by PI3K inhibition. We found that intrinsic resistance to PI3K inhibition derived from RAF/MEK/ERK and RSK activation, bypassing blockage of the PI3K/AKT/mTOR pathway...
August 7, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28797843/blockade-of-stearoyl-coa-desaturase-1-activity-reverts-resistance-to-cisplatin-in-lung-cancer-stem-cells
#14
Maria Elena Pisanu, Alessia Noto, Claudia De Vitis, Stefania Morrone, Giosuè Scognamiglio, Gerardo Botti, Federico Venuta, Daniele Diso, Ziga Jakopin, Fabrizio Padula, Alberto Ricci, Salvatore Mariotta, Maria Rosaria Giovagnoli, Enrico Giarnieri, Ivano Amelio, Massimiliano Agostini, Gerry Melino, Gennaro Ciliberto, Rita Mancini
Poor prognosis in lung cancer has been attributed to the presence of lung cancer stem cells (CSCs) which resist chemotherapy and cause disease recurrence. Hence, the strong need to identify mechanisms of chemoresistance and to develop new combination therapies. We have previously shown that Stearoyl-CoA-desaturase 1 (SCD1), the enzyme responsible for the conversion of saturated to monounsaturated fatty acids is upregulated in 3D lung cancer spheroids and is an upstream activator of key proliferation pathways β-catenin and YAP/TAZ...
August 7, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28795492/treatment-of-alk-rearranged-non-small-cell-lung-cancer-a-review-of-the-landscape-and-approach-to-emerging-patterns-of-treatment-resistance-in-the-australian-context
#15
M Itchins, P L Chia, S A Hayes, V M Howell, A J Gill, W A Cooper, T John, P Mitchell, M Millward, S J Clarke, B Solomon, N Pavlakis
Since the identification of anaplastic lymphoma kinase (ALK) gene rearrangements in non-small cell lung cancer (NSCLC) in 2005, the treatment of ALK-rearranged NSCLC (ALK+ NSCLC) has evolved at a rapid pace. This molecularly distinct subset of NSCLC has uniquely important biology, clinicopathologic features and mechanisms of drug resistance which impact on the choice of treatment for a patient with this disease. There are multiple ALK tyrosine kinase inhibitors now available in clinical practice with efficacy data continuing to emerge and guide the optimal treatment algorithm...
August 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28794650/treating-egfr-mutation-resistance-in-non-small-cell-lung-cancer-role-of-osimertinib
#16
REVIEW
Valentina Mazza, Federico Cappuzzo
The discovery of mutations in EGFR significantly changed the treatment paradigm of patients with EGFR-mutant non-small cell lung cancer (NSCLC), a particular group of patients with different clinical characteristics and outcome to EGFR-wild-type patients. In these patients, the treatment of choice as first-line therapy is first- or second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, erlotinib, or afatinib. Inevitably, after the initial response, all patients become refractory to these drugs...
2017: Application of Clinical Genetics
https://www.readbyqxmd.com/read/28794639/kiaa1522-overexpression-promotes-tumorigenicity-and-metastasis-of-esophageal-cancer-cells-through-potentiating-the-erk-activity
#17
Zhi-Hui Xie, Jing Yu, Li Shang, Yi-Qing Zhu, Jia-Jie Hao, Yan Cai, Xin Xu, Yu Zhang, Ming-Rong Wang
Esophageal squamous cell carcinoma (ESCC) is a highly malignant tumor associated with a poor prognosis, and the molecular mechanisms underlying its formation and progression remain poorly understood. KIAA1522 is upregulated in various tumor tissues, but its function is unknown. Alterations in KIAA1522 expression and its implication in ESCC are currently unclear. In this study, an immunohistochemical analysis of ESCC tissues showed that KIAA1522 was highly expressed in 46% (157/342) of ESCC specimens and that its expression was inversely correlated with the degree of differentiation (P=0...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28793867/the-effect-of-nullomer-derived-peptides-9r-9s1r-and-124r-on-the-nci-60-panel-and-normal-cell-lines
#18
Abdelkrim Alileche, Greg Hampikian
BACKGROUND: Nullomer peptides are the smallest sequences absent from databases of natural proteins. We first began compiling a list of absent 5-amino acid strings in 2006 (1). We report here the effects of Nullomer-derived peptides 9R, 9S1R and 124R on the NCI-60 panel, derived from human cancers of 9 organs (kidney, ovary, skin melanoma, lung, brain, lung, colon, prostate and the hematopoietic system), and four normal cell lines (endothelial HUVEC, skin fibroblasts BJ, colon epithelial FHC and normal prostate RWPE-1)...
August 9, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28791631/erbb-receptors-and-cancer
#19
Zhixiang Wang
The ErbB receptor family, also known as the EGF receptor family or type I receptor family, includes the epidermal growth factor (EGF) receptor (EGFR) or ErbB1/Her1, ErbB2/Her2, ErbB3/Her3, and ErbB4/Her4. Among all RTKs, EGFR was the first RTK identified and the first one linked to cancer. Thus, EGFR has also been the most intensively studied among all RTKs. ErbB receptors are activated after homodimerization or heterodimerization. The ErbB family is unique among the various groups of receptor tyrosine kinases (RTKs) in that ErbB3 has impaired kinase activity, while ErbB2 does not have a direct ligand...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28791524/histological-analysis-of-anti-cancer-drug-loaded-targeted-mn-zns-quantum-dots-in-metastatic-lesions-of-4t1-challenged-mice
#20
Ibrahim Birma Bwatanglang, Faruq Mohammad, Nor Azah Yusof, Nurul Elyani Mohammed, Nadiah Abu, Noorjahan Banu Alitheen, Jaafar Abdullah, Mohd Zubir Hussein, Yusuf Abba, Noraini Nordin, Nur Rizi Zamberi
5-Fluororaucil (5-FU) as anti-cancer drug was reported to induce thymidine synthase (TS) overexpression and cancer cell resistance. To improve its therapeutic efficacy and selective targeting, here we developed a targeted delivery system mediated by the active ligand-folate receptor chemistry to deliver the 5-FU drug selectively into the tumor microenvironment. The preparation was achieved by exploring chitosan (CS)-biopolymer based system with folic acid (FA)-conjugation. The 5-FU@FACS-Mn:ZnS quantum dots (QDs) based on the histological assessment conducted in the 4T1 challenged mice showed an improved tumor remission in the liver, spleen and lungs...
August 8, 2017: Journal of Materials Science. Materials in Medicine
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