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https://www.readbyqxmd.com/read/28625657/synergy-between-next-generation-egfr-tyrosine-kinase-inhibitors-and-mir-34a-in-the-inhibition-of-non-small-cell-lung-cancer
#1
Jane Zhao, Adriana Guerrero, Kevin Kelnar, Heidi J Peltier, Andreas G Bader
OBJECTIVES: EGFR tyrosine kinase inhibitors (TKIs) are widely used to treat NSCLC, primarily patients with activating mutations, with more limited response in wild-type disease. However, even with EGFR-mutated disease, many patients fail to respond, most who initially respond fail to respond completely, and almost all develop resistance and inevitably progress. New therapeutic options that improve these outcomes could provide substantial clinical benefit. We previously demonstrated strong synergistic effects between erlotinib and the tumor suppressor microRNA miR-34a, sensitizing NSCLC cells with primary resistance (EGFR wild-type) and restoring sensitivity in cells with acquired resistance...
June 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28561721/managing-resistance-to-efgr-and-alk-targeted-therapies
#2
Christine M Lovly, Puneeth Iyengar, Justin F Gainor
Targeted therapies have transformed the management of non-small cell lung cancer (NSCLC) and placed an increased emphasis on stratifying patients on the basis of genetic alterations in oncogenic drivers. To date, the best characterized molecular targets in NSCLC are the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK). Despite steady advances in targeted therapies within these molecular subsets, however, acquired resistance to therapy is near universal. Recent preclinical models and translational efforts have provided critical insights into the molecular mechanisms of resistance to EGFR and ALK inhibitors...
2017: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/28559013/establishment-and-genomic-characterization-of-primary-salivary-duct-carcinoma-cell-line
#3
Jie Li, Yohitsugu Mitani, Pulivarthi H Rao, Laszlo Perlaky, Bin Liu, Randal S Weber, Adel K El-Naggar
OBJECTIVES: To develop and characterize in vitro salivary duct carcinoma as a surrogate for functional studies. MATERIALS AND METHODS: Cells were dispersed from tumor tissue fragments under sterile conditions in RPMI media. Disassociated cells were cultivated, immortalized with hTERT and propagated for more than 100 passages. Morphologic, linage, cytogenetic and genomic analyses were performed on different passages of cell line and primary tumor. Soft agar growth was performed...
June 2017: Oral Oncology
https://www.readbyqxmd.com/read/28474124/expressions-and-clinical-significance-of-cox-2-vegf-c-and-efgr-in-endometrial-carcinoma
#4
Shengnan Cai, Yue-Xiang Zhang, Ke Han, Yi-Qian Ding
OBJECTIVE: The article is to study the expressions of COX-2, VEGF-C, and EGFR in endometrial carcinoma as well as its clinical significances. MATERIALS AND METHODS: Clinical data of 183 patients with endometrial carcinoma who received surgery as initial treatment in the Nanjing Drum Tower Hospital Affiliated to the Nanjing University Medical School and the Nantong Maternal and Child Health Hospital Affiliated to the Nantong University from January 2005 to December 2010 were retrospectively investigated; 152 out of the 183 patients were closely followed up...
May 4, 2017: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/28473630/epidermal-growth-factor-receptor-inhibition-downregulates-helicobacter-pylori-induced-epithelial-inflammatory-responses-dna-damage-and-gastric-carcinogenesis
#5
Johanna C Sierra, Mohammad Asim, Thomas G Verriere, M Blanca Piazuelo, Giovanni Suarez, Judith Romero-Gallo, Alberto G Delgado, Lydia E Wroblewski, Daniel P Barry, Richard M Peek, Alain P Gobert, Keith T Wilson
OBJECTIVE: Gastric cancer is the third leading cause of cancer death worldwide and infection by Helicobacter pylori is the strongest risk factor. We have reported increased epidermal growth factor receptor (EGFR) phosphorylation in the H. pylori-induced human carcinogenesis cascade, and association with DNA damage. Our goal was to determine the role of EGFR activation in gastric carcinogenesis. DESIGN: We evaluated gefitinib, a specific EGFR inhibitor, in chemoprevention of H...
May 4, 2017: Gut
https://www.readbyqxmd.com/read/28391340/targeting-the-tyrosine-kinase-signalling-pathways-for-treatment-of-immune-mediated-glomerulonephritis-from-bench-to-bedside-and-beyond
#6
Terry King-Wing Ma, Stephen P McAdoo, Frederick Wai Keung Tam
Glomerulonephritis (GN) affects patients of all ages and is an important cause of morbidity and mortality. Non-selective immunosuppressive drugs have been used in immune-mediated GN but often result in systemic side effects and occasionally fatal infective complications. There is increasing evidence from both preclinical and clinical studies that abnormal activation of receptor and non-receptor tyrosine kinase signalling pathways are implicated in the pathogenesis of immune-mediated GN. Activation of spleen tyrosine kinase (SYK), Bruton's tyrosine kinase (BTK), platelet-derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR) and discoidin domain receptor 1 (DDR1) have been demonstrated in anti-GBM disease...
January 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28367239/efficacy-of-second-line-tyrosine-kinase-inhibitors-in-the-treatment-of-metastatic-advanced-non-small-cell-lung-cancer-harboring-exon-19-and-21-egfr-mutations
#7
Zhen Zheng, Xiance Jin, Baochai Lin, Huafang Su, Hanbin Chen, Shaoran Fei, Lihao Zhao, Xia Deng, Deyao Xie, Congying Xie
Background: Although superior clinical benefits of first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the treatment of advanced non-small-cell lung cancer (NSCLC) had been reported with different sensitivity, the sensitivity of second-line TKIs in NSCLC patients with different EFGR mutations was unknown. The purpose of this study is to investigate the clinical outcome of second-line EGFR-TKIs in the treatment of NSCLC patients according to different EGFR genotypes. Methods: The treatment outcomes of 166 NSCLC patients with different EGFR mutations treated by second-line TKIs were retrospectively reviewed...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28336963/radiological-and-clinical-features-associated-with-epidermal-growth-factor-receptor-mutation-status-of-exon-19-and-21-in-lung-adenocarcinoma
#8
Zhang Shi, Xuan Zheng, Ruifeng Shi, Changen Song, Runhong Yang, Qianwen Zhang, Xinrui Wang, Jianping Lu, Yongwei Yu, Qi Liu, Tao Jiang
The exon 19 and 21 in Epidermal Growth Factor Receptor (EGFR) mutation are the most common subtype of lung adenocarcinoma, and the strongest predictive biomarker for progression-free survival and tumor response. Although some studies have shown differences in radiological features between cases with and without EFGR mutations, they lacked necessary stratification. This article is to evaluate the association of CT features between the wild type and the subtype (exon 19 and 21) of EGFR mutations in patients with lung adenocarcinoma...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28331934/microarray-analysis-of-differential-gene-expression-profile-between-human-fetal-and-adult-heart
#9
Zhimin Geng, Jue Wang, Lulu Pan, Ming Li, Jitai Zhang, Xueli Cai, Maoping Chu
Although many changes have been discovered during heart maturation, the genetic mechanisms involved in the changes between immature and mature myocardium have only been partially elucidated. Here, gene expression profile changed between the human fetal and adult heart was characterized. A human microarray was applied to define the gene expression signatures of the fetal (13-17 weeks of gestation, n = 4) and adult hearts (30-40 years old, n = 4). Gene ontology analyses, pathway analyses, gene set enrichment analyses, and signal transduction network were performed to predict the function of the differentially expressed genes...
March 22, 2017: Pediatric Cardiology
https://www.readbyqxmd.com/read/28326956/clinical-pathologic-and-genetic-features-of-wilms-tumors-with-wtx-gene-mutation
#10
Sanda Alexandrescu, Sara Akhavanfard, Marian H Harris, Sara O Vargas
Clinical and pathologic features of patients with WTX-mutated Wilms tumor (WT) have not been studied in detail. We characterize the clinical and pathologic findings in WT with WTX abnormalities and provide comparison with WT without WTX mutation. Clinical, gross, and microscopic features in 35 patients with WT were examined. Karyotype was examined in a subset of cases. All cases had been previously analyzed for WTX, WT1, and CTNNB1 aberrations via array comparative genomic hybridization; OncoMap 4 high throughput genotyping was performed on 18 cases...
March 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28214899/therapeutic-targeting-of-epithelial-plasticity-programs-focus-on-the-epithelial-mesenchymal-transition
#11
REVIEW
Reem Malek, Hailun Wang, Kekoa Taparra, Phuoc T Tran
Mounting data points to epithelial plasticity programs such as the epithelial-mesenchymal transition (EMT) as clinically relevant therapeutic targets for the treatment of malignant tumors. In addition to the widely realized role of EMT in increasing cancer cell invasiveness during cancer metastasis, the EMT has also been implicated in allowing cancer cells to avoid tumor suppressor pathways during early tumorigenesis. In addition, data linking EMT to innate and acquired treatment resistance further points towards the desire to develop pharmacological therapies to target epithelial plasticity in cancer...
2017: Cells, Tissues, Organs
https://www.readbyqxmd.com/read/28159516/tumor-targeted-ph-redox-dual-sensitive-unimolecular-nanoparticles-for-efficient-sirna-delivery
#12
Guojun Chen, Yuyuan Wang, Ruosen Xie, Shaoqin Gong
A unique pH/redox dual-sensitive cationic unimolecular nanoparticle (NP) enabling excellent endosomal/lysosomal escape and efficient siRNA decomplexation inside the target cells was developed for tumor-targeted delivery of siRNA. siRNA was complexed into the cationic core of the unimolecular NP through electrostatic interactions. The cationic core used for complexing siRNA contained reducible disulfide bonds that underwent intracellular reduction owing to the presence of high concentrations of reduced glutathione (GSH) inside the cells, thereby facilitating the decomplexation of siRNA from the unimolecular NPs...
February 1, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28120720/the-role-of-epidermal-growth-factor-receptor-in-the-management-of-gastrointestinal-carcinomas-present-status-and-future-perspectives
#13
Malik Quasir Mahmood, Shakti Dhar Shukla, Kamal Dua, Madhur D Shastri
BACKGROUND: The global burden of gastrointestinal cancers, including colorectal, stomach, and esophageal cancers is rising steadily. Several therapeutic approaches have been considered for the treatment of GI carcinomas. However, none showed to halt or cure the disease. There is a need to develop effective targeted molecular therapies; mainly to overcome the adverse effects of currently used treatment regimens, as well as, to benefit a large proportion of cancer patients who do not respond well to chemotherapeutics...
January 24, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27993518/design-synthesis-and-biological-evaluation-of-novel-1-oxo-1-2-3-4-tetrahydropyrazino-1-2-a-indole-3-carboxamide-analogs-in-mcf-7-and-mda-mb-468-breast-cancer-cell-lines
#14
Ye Jin Kim, Jae Sung Pyo, Young-Suk Jung, Jae-Hwan Kwak
A series of novel 1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-3-carboxamide analogs were designed and synthesized for developing pyrazinoindolone scaffolds as anti-breast cancer agents. Compounds 1h and 1i, having a furan-2-yl-methylamide and benzylamide group, respectively, exhibited more potent cytotoxicity in MDA-MB-468 triple-negative breast cancer (TNBC) cells than compounds possessing aliphatic groups. Compounds 2a and 2b, as (R)-enantiomers of 1h and 1i, also had inhibitory activity against MDA-MB-468 cells...
December 5, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27754054/os-15-02-matrix-metalloproteinase-2-knockout-protects-from-angiotensin-ii-induced-vascular-injury-in-part-via-inhibition-of-egfr-and-erk1-2-activation
#15
Pierre Paradis, Tlili Barhoumi, Muhammad Oneeb Rehman Mian, Julio C Fraulob-Aquino, Asia Rehman, Nourredine Idris-Khodja, Ernesto L Schiffrin
OBJECTIVE: Matrix metalloproteinase 2 (MMP2) is involved in cardiovascular disease. Whether MMP2 plays a role in hypertension and vascular damage is unknown. We hypothesized that Mmp2 knockout will prevent angiotensin (Ang) II-induced hypertension and vascular injury. DESIGN AND METHOD: Mmp2 knockout (Mmp2) and wild-type (WT) mice were infused with Ang II (1000 ng/kg/min, SC) for 14 days. Systolic blood pressure (SBP) was measured by telemetry, and mesenteric artery (MA) endothelial function and vascular remodeling by pressurized myography...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27753039/a-rapid-and-sensitive-method-for-detection-of-the-t790m-mutation-of-egfr-in-plasma-dna
#16
Hideharu Kimura, Shingo Nishikawa, Hayato Koba, Taro Yoneda, Takashi Sone, Kazuo Kasahara
Epidermal growth factor receptor (EGFR) T790M mutation is associated with resistance to EGFR tyrosine kinase inhibitors' (EGFR-TKIs) in non-small cell lung cancer (NSCLC). The aims of this study are to develop a blood-based, non-invasive approach to detecting the EGFR T790M mutation in advanced NSCLC patients, using PointMan™ EGFR DNA Enrichment Kit which is a novel method for selective amplification of genotype specific sequences.Pairs of blood samples and tumor tissues were collected from NSCLC patients with an EGFR activating mutation and who were resistant to EGFR-TKI treatment...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27726288/erlotinib-induces-the-human-non-small-cell-lung-cancer-cells-apoptosis-via-activating-ros-dependent-jnk-pathways
#17
Fenglian Shan, Zewei Shao, Shenghua Jiang, Zhaozhong Cheng
Although erlotinib (ERL) has drawn more and more attention toward its anticancer properties effect, the underlying mechanisms of ERL's anticancer properties effect remain unclear yet. So, the aim of this research was to explore the underlying anticancer mechanisms of ERL and to explore whether the reactive oxygen species (ROS)-dependent c-Jun N-terminal kinase (JNK) pathway contributed to the anticancer properties provided by ERL. In our study, we used MTT assay to detect the anticell growth ability of ERL on human non-small-cell lung cancer cell lines (A549)...
November 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27642974/os-15-02-matrix-metalloproteinase-2-knockout-protects-from-angiotensin-ii-induced-vascular-injury-in-part-via-inhibition-of-egfr-and-erk1-2-activation
#18
Pierre Paradis, Tlili Barhoumi, Muhammad Oneeb Rehman Mian, Julio C Fraulob-Aquino, Asia Rehman, Nourredine Idris-Khodja, Ernesto L Schiffrin
OBJECTIVE: Matrix metalloproteinase 2 (MMP2) is involved in cardiovascular disease. Whether MMP2 plays a role in hypertension and vascular damage is unknown. We hypothesized that Mmp2 knockout will prevent angiotensin (Ang) II-induced hypertension and vascular injury. DESIGN AND METHOD: Mmp2 knockout (Mmp2) and wild-type (WT) mice were infused with Ang II (1000 ng/kg/min, SC) for 14 days. Systolic blood pressure (SBP) was measured by telemetry, and mesenteric artery (MA) endothelial function and vascular remodeling by pressurized myography...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27633965/interaction-of-treatment-and-biomarker-in-advanced-nsclc
#19
Pingfu Fu, Afshin Dowlati, Nathan Pennell, Neelesh Sharma, Qizhi Yi, Balazs Halmos
PURPOSE: There has been a long-standing interest in the investigation of interactions in science. The objective of the study is to evaluate interaction between EGFR mutation and treatment from randomized, phase II study of chemotherapy versus chemotherapy plus erlotinib in patients with progressive NSCLC following clinical benefit from erlotinib. MATERIALS AND METHODS: Forty-six patients with advanced stage NSCLC and progression from erlotinib were randomized to receive chemotherapy (pemetrexed or docetaxel) or chemotherapy plus erlotinib between 2008 and 2012...
September 16, 2016: Reviews on Recent Clinical Trials
https://www.readbyqxmd.com/read/27519631/tamoxifen-has-a-proliferative-effect-in-endometrial-carcinoma-mediated-via-the-gper-egfr-erk-cyclin-d1-pathway-a-retrospective-study-and-an-in%C3%A2-vitro-study
#20
Lizhi Zhang, Yanmin Li, Lan Lan, Rong Liu, Yanhong Wu, Quanxin Qu, Ke Wen
Tamoxifen has been widely used to treat breast cancer as an endocrine therapy. However, tamoxifen is known to enhance the risk of developing endometrial cancer. We want to examine the effect of tamoxifen on endometrial cancer. In our retrospective study, we found that high grade, high stage, and lymph node metastasis were more common in tamoxifen users. In vitro 4-hydroxytamoxifen (OHT) induced cell proliferation and cell cycle promotion in type I and type II endometrial cancer cell lines, and this proliferation was blocked by GPER silencing...
December 5, 2016: Molecular and Cellular Endocrinology
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