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https://www.readbyqxmd.com/read/28427160/biomarker-analysis-of-the-phase-3-torch-trial-for-first-line-erlotinib-versus-chemotherapy-in-advanced-non-small-cell-lung-cancer-patients
#1
Lucia Kim, Mauro Saieg, Massimo Di Maio, Ciro Gallo, Charles Butts, Fortunato Ciardiello, Ronald Feld, Dengxiao Cheng, Vittorio Gebbia, Marco Angelo Burgio, Yasmin Alam, Simona Signoriello, Antonio Rossi, Natasha Leighl, Paolo Maione, Alessandro Morabito, Geoffrey Liu, Ming-Sound Tsao, Francesco Perrone, Cesare Gridelli
BACKGROUND: The TORCH phase III trial compared the efficacy of first-line erlotinib followed by chemotherapy at progression (experimental arm) with the reverse sequence (standard arm) in unselected advanced non-small cell lung cancer (NSCLC) patients. Here we report biomarker analyses. METHODS: EGFR and KRAS mutation, expression of EGFR family members and of cMET and PTEN and EGFR and ABCG2 germline polymorphisms were tested on tumor tissue or blood samples to either confirm previously proposed predictive role or describe it in an explorative setting...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427146/microrna-200c-141-upregulates-serpinb2-to-promote-breast-cancer-cell-metastasis-and-reduce-patient-survival
#2
Tiefeng Jin, Hoe Suk Kim, Sul Ki Choi, Eun Hye Hwang, Jisu Woo, Han Suk Ryu, Kwangsoo Kim, Aree Moon, Woo Kyung Moon
The microRNA-200 (miR-200) family is associated with tumor metastasis and poor patient prognosis. We found that miR-200c/141 cluster overexpression upregulated SerpinB2 in the MDA-MB-231 triple-negative (TN) breast cancer cell line. We observed transcription factor (c-Jun, c-Fos, and FosB) upregulation, nuclear localization of c-Jun, and increased SerpinB2 promoter-directed chloramphenicol acetyltransferase activity in miR-200c/141 cluster-overexpressing cells relative to controls. Additionally, miR-124a and miR-26b, which directly target SepinB2, were downregulated compared to controls...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426106/afatinib-versus-gefitinib-in-patients-with-egfr-mutation-positive-advanced-non-small-cell-lung-cancer-overall-survival-data-from-the-phase-iib-lux-lung-7-trial
#3
L Paz-Ares, E-H Tan, K O'Byrne, L Zhang, V Hirsh, M Boyer, J C-H Yang, T Mok, K H Lee, S Lu, Y Shi, D H Lee, J Laskin, D-W Kim, S A Laurie, K Kölbeck, J Fan, N Dodd, A Märten, K Park
Background: In LUX-Lung 7, the irreversible ErbB family blocker, afatinib, significantly improved progression-free survival (PFS), time-to-treatment failure (TTF) and objective response rate (ORR) versus gefitinib in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Here, we present primary analysis of mature overall survival (OS) data. Patients and methods: LUX-Lung 7 assessed afatinib 40 mg/day versus gefitinib 250 mg/day in treatment-naïve patients with stage IIIb/IV NSCLC and a common EGFR mutation (exon 19 deletion/L858R)...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28425640/profiling-of-the-silica-induced-molecular-events-in-lung-epithelial-cells-using-the-rna-seq-approach
#4
Judy Y W Chan, Joseph C C Tsui, Patrick T W Law, Winnie K W So, Doris Y P Leung, Michael M K Sham, Stephen K W Tsui, Carmen W H Chan
Silicosis is a prolonged, irreversible and incurable occupational disease, and there is a significant number of newly diagnosed cases every year in Hong Kong. Due to the long latency of the disease, the diagnosis can be missed until detailed clinical examination at a later stage. For a better control of this deadly disease, detailing the pro-inflammatory and fibrotic events in the macrophage would be instrumental in understanding the pathogenesis of the disease and essential for the significant biomarkers discovery...
April 20, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28423659/targeting-hox-pbx-dimers-in-cancer
#5
REVIEW
Richard Morgan, Mohamed El-Tanani, Keith D Hunter, Kevin J Harrington, Hardev S Pandha
The HOX and PBX gene families encode transcription factors that have key roles in establishing the identity of cells and tissues in early development. Over the last 20 years it has become apparent that they are also dysregulated in a wide range of solid and haematological malignancies and have a predominantly pro-oncogenic function. A key mode of transcriptional regulation by HOX and PBX proteins is through their interaction as a heterodimer or larger complex that enhances their binding affinity and specificity for DNA, and there is growing evidence that this interaction is a potential therapeutic target in malignancies that include prostate, breast, renal, ovarian and lung cancer, melanoma, myeloma, and acute myeloid leukaemia...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423648/polyisoprenylated-cysteinyl-amide-inhibitors-disrupt-actin-cytoskeleton-organization-induce-cell-rounding-and-block-migration-of-non-small-cell-lung-cancer
#6
Elizabeth Ntantie, Jerrine Fletcher, Felix Amissah, Olufisayo O Salako, Augustine T Nkembo, Rosemary A Poku, Francis O Ikpatt, Nazarius S Lamango
The malignant potential of Non-Small Cell Lung Cancer (NSCLC) is dependent on cellular processes that promote metastasis. F-actin organization is central to cell migration, invasion, adhesion and angiogenesis, processes involved in metastasis. F-actin remodeling is enhanced by the overexpression and/or hyper-activation of some members of the Rho family of small GTPases. Therefore, agents that mitigate hyperactive Rho proteins may be relevant for controlling metastasis. We previously reported the role of polyisoprenylated cysteinyl amide inhibitors (PCAIs) as potential inhibitors of cancers with hyperactive small GTPases...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423155/the-role-of-genetic-testing-in-patients-with-breast-cancer-a-review
#7
Olivia M Valencia, Selyne E Samuel, Rebecca K Viscusi, Taylor S Riall, Leigh A Neumayer, Hassan Aziz
Importance: In the United States from 2009 to 2013, the incidence of breast cancer was the highest of any cancer and the death rate was second to that of lung cancer. Approximately 5% to 10% of breast cancers are inheritable. Observations: BRCA1 and BRCA2 germline mutations account for up to 30% of inheritable breast cancers and are the most commonly assessed mutations in patients presenting with early-onset breast cancer, triple-negative breast cancer, bilateral breast cancer, and a family history of breast cancer...
April 19, 2017: JAMA Surgery
https://www.readbyqxmd.com/read/28420235/garcinol-from-garcinia-indica-downregulates-cancer-stem-like-cell-biomarker-aldh1a1-in-nsclc-a549-cells-through-ddit3-activation
#8
Jinhan Wang, Liwen Wang, Chi-Tang Ho, Kunsheng Zhang, Qiang Liu, Hui Zhao
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and patients with NSCLC show high mortality rates still because of failure to clean up cancer stem cells (CSCs). The anticancer activity of phytochemical garcinol has been identified in various cancer cell models. However, the effect of garcinol on NSCLC cell lines is still not clear. Of the NSCLC cell lines we tested, A549 cells were the most sensitive to garcinol. Interestingly, Aldehyde Dehydrogenase 1 Family Member A1 (ALDH1A1) is preferentially expressed in A549 cells and downregulated by the addition of garcinol...
April 18, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28419994/degradation-of-mcl-1-through-gsk-3%C3%AE-activation-regulates-apoptosis-induced-by-bufalin-in-non-small-cell-lung-cancer-h1975-cells
#9
Xiao-Hong Kang, Jing-Hang Zhang, Qing-Qin Zhang, Yan-Hui Cui, Ying Wang, Wei-Zheng Kou, Zhan-Hui Miao, Ping Lu, Li-Fang Wang, Zhen-Ye Xu, Fei Cao
BACKGROUND/AIMS: Mcl-1, an anti-apoptotic Bcl-2 family member, is often overexpressed in non-small cell lung cancer (NSCLC). Bufalin has been reported to induce apoptosis in various tumor cells. However, there is no report showing that bufalin could downregulate Mcl-1 expression in NSCLC. METHODS: Cell proliferation was analyzed by cell counting kit-8 (CCK-8) assay in H1975 cells. Cell apoptosis was detected by flow cytometry. Mcl-1 mRNA was detected by RT-PCR. The expression of apoptosis-associated proteins in H1975 cells was detected by western blotting...
April 14, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28419414/association-between-aggressive-care-and-bereaved-families-evaluation-of-end-of-life-care-for-veterans-with-non-small-cell-lung-cancer-who-died-in-veterans-affairs-facilities
#10
Mary Ersek, Susan C Miller, Todd H Wagner, Joshua M Thorpe, Dawn Smith, Cari R Levy, Risha Gidwani, Katherine Faricy-Anderson, Karl A Lorenz, Bruce Kinosian, Vincent Mor
BACKGROUND: To the authors' knowledge, little is known regarding the relationship between patients' and families' satisfaction with aggressive end-of-life care. Herein, the authors examined the associations between episodes of aggressive care (ie, chemotherapy, mechanical ventilation, acute hospitalizations, and intensive care unit admissions) within the last 30 days of life and families' evaluations of end-of-life care among patients with non-small cell lung cancer (NSCLC). METHODS: A total of 847 patients with NSCLC (34% of whom were aged <65 years) who died in a nursing home or intensive care, acute care, or hospice/palliative care (HPC) unit at 1 of 128 Veterans Affairs Medical Centers between 2010 and 2012 were examined...
April 17, 2017: Cancer
https://www.readbyqxmd.com/read/28418919/znf452-facilitates-tumor-proliferation-and-invasion-via-activating-akt-gsk3%C3%AE-signaling-pathway-and-predicts-poor-prognosis-of-non-small-cell-lung-cancer-patients
#11
Xiupeng Zhang, Haijing Zhou, Yong Zhang, Lin Cai, Guiyang Jiang, Ailin Li, Yuan Miao, Qingchang Li, Xueshan Qiu, Enhua Wang
ZNF452 is a zinc-finger protein family member which contains an isolated SCAN (SRE-ZBP, CTfin51, AW-1 and Number 18 cDNA) zinc-finger domain. Despite the SCAN N-terminus domain is known to play a role in transcriptional regulation of genes involved in cell survival and differentiation, there are no precise cellular functions that have been assigned to ZNF452. In the present study, we found that either endogenous or exogenous ZNF452 was overexpressed in the cytoplasm of NSCLC cells and positive ratio of ZNF452 in NSCLC samples (50...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416753/synergistic-effects-of-the-immune-checkpoint-inhibitor-ctla-4-combined-with-the-growth-inhibitor-lycorine-in-a-mouse-model-of-renal-cell-carcinoma
#12
Xiezhao Li, Peng Xu, Chongshan Wang, Naijin Xu, Abai Xu, Yawen Xu, Takuya Sadahira, Motoo Araki, Koichiro Wada, Eiji Matsuura, Masami Watanabe, Junxia Zheng, Pinghua Sun, Peng Huang, Yasutomo Nasu, Chunxiao Liu
Renal cell carcinoma (RCC) management has undergone a major transformation over the past decade; immune checkpoint inhibitors are currently undergoing clinical trials and show promising results. However, the effectiveness of immune checkpoint inhibitors in patients with metastatic RCC (mRCC) is still limited. Lycorine, an alkaloid extracted from plants of the Amaryllidaceae family, is touted as a potential anti-cancer drug because of its demonstrative growth inhibition capacity (induction of cell cycle arrest and inhibition of vasculogenic mimicry formation)...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416483/sfk-fak-signaling-attenuates-osimertinib-efficacy-in-both-drug-sensitive-and-drug-resistant-models-of-egfr-mutant-lung-cancer
#13
Eiki Ichihara, David Westover, Catherine B Meador, Yingjun Yan, Joshua A Bauer, Pengcheng Lu, Fei Ye, Amanda Kulick, Elisa De Stanchina, Robert McEwen, Marc Ladanyi, Darren Cross, William Pao, Christine M Lovly
Mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), such as osimertinib, are active agents for the treatment of EGFR-mutant lung cancer. Specifically, these agents can overcome the effects of the T790M mutation, which mediates resistance to first and second-generation EGFR TKI, and recent clinical trials have documented their efficacy in patients with EGFR-mutant lung cancer. Despite promising results, therapeutic efficacy is limited by development of acquired resistance...
April 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28415992/women-epidemiology-lung-cancer-welca-study-reproductive-hormonal-occupational-risk-factors-and-biobank
#14
Isabelle Stücker, Diane Martin, Monica Neri, Pierre Laurent-Puig, Hélène Blons, Martine Antoine, Anne Guiochon-Mantel, Sylvie Brailly-Tabard, Marianne Canonico, Marie Wislez, Jean Trédaniel
BACKGROUND: Lung cancer aetiology and clinical aspects have been mainly studied in men, although specific risk factors probably exist in women. Here we present the rationale, design and organization of the WELCA study (Women Epidemiology Lung CAncer) that has been launched to investigate lung cancer in women, focusing particularly on hormonal and occupational factors. METHODS/DESIGN: WELCA is a population based case-control study and planned to recruit 1000 cases and 1000 controls in three years, based on study power calculation...
April 17, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28415726/pge2-ep3-src-signaling-induces-egfr-nuclear-translocation-and-growth-through-egfr-ligands-release-in-lung-adenocarcinoma-cells
#15
Lorenzo Bazzani, Sandra Donnini, Federica Finetti, Gerhard Christofori, Marina Ziche
Prostaglandin E2 (PGE2) interacts with tyrosine kinases receptor signaling in both tumor and stromal cells supporting tumor progression. Here we demonstrate that in non-small cell lung carcinoma (NSCLC) cells, A549 and GLC82, PGE2 promotes nuclear translocation of epidermal growth factor receptor (nEGFR), affects gene expression and induces cell growth. Indeed, cyclin D1, COX-2, iNOS and c-Myc mRNA levels are upregulated following PGE2 treatment. The nuclear localization sequence (NLS) of EGFR as well as its tyrosine kinase activity are required for the effect of PGE2 on nEGFR and downstream signaling activities...
March 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414317/p16-controls-epithelial-cell-growth-and-suppresses-carcinogenesis-through-mechanisms-that-do-not-require-rb1-function
#16
M Sen, N Akeno, A Reece, A L Miller, D S Simpson, K A Wikenheiser-Brokamp
The p16/RB1 tumor suppressor pathway is inactivated in the vast majority, if not all, human cancers. The current paradigm is that p16 and RB1 function in a linear pathway to suppress tumorigenesis; however p16 is preferentially lost in human cancers suggesting that p16 has critical tumor suppressive functions not mediated through RB1. Carcinomas arise from transformed epithelial cells and account for 80% of adult malignancies highlighting the need to understand p16/RB1 pathway function in organ epithelia. Lung cancer is the leading cause of cancer deaths and is associated with p16/RB1 pathway deregulation...
April 17, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28410216/friend-leukemia-virus-integration-1-promotes-tumorigenesis-of-small-cell-lung-cancer-cells-by-activating-the-mir-17-92-pathway
#17
LingyuLi, Wei Song, Xu Yan, Ailing Li, Xiaoying Zhang, Wei Li, Xue Wen Lei Zhou, Dehai Yu, Ji-Fan Hu, Jiuwei Cui
Small cell lung cancer (SCLC) is regarded as the most devastative type of human lung malignancies. The rapid and disseminated growth pattern remains the primary cause of poor clinical prognosis in patients with SCLC. However, the molecular factors that drive rapid progression of SCLC remain unclear. Friend leukemia virus integration 1 (FLI1), an Ets transcription factor family member, has been previously reported to act as a major driver of hematological malignancies. In this study, we explored the potential role of FLI1 in SCLC...
March 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28408326/emp1-emp-2-and-emp3-as-novel-therapeutic-targets-in-human-cancer
#18
REVIEW
Wang Yi-Wen, Cheng Hong-Ling, Ding Ya-Rou, Chou Lien-Hsuan, Chow Nan-Haw
The epithelial membrane protein genes 1, 2, and 3 (EMP1, EMP2, and EMP3) belong to the peripheral myelin protein 22-kDa (PMP22) gene family, which consists of at least seven members: PMP22, EMP1, EMP2, EMP3, PERP, brain cell membrane protein 1, and MP20. This review addresses the structural and functional features of EMPs, detailing their tissue distribution and functions in the human body, their expression pattern in a variety of tumors, and highlighting the underlying mechanisms involved in carcinogenesis...
April 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28407697/cytosolic-hsp90%C3%AE-and-its-mitochondrial-isoform-trap1-are-differentially-required-in-a-breast-cancer-model
#19
Evangelia Vartholomaiou, Marta Madon-Simon, Stéphane Hagmann, Guillaume Mühlebach, Wolfgang Wurst, Thomas Floss, Didier Picard
The Hsp90 family of molecular chaperones includes the cytosolic isoforms Hsp90α and Hsp90β, and the mitochondrial isoform Trap1. Hsp90α/β support a large number of client proteins in the cytoplasm and the nucleus whereas Trap1 regulates oxidative phosphorylation in mitochondria. Many of the associated proteins and cellular processes are relevant to cancer, and there is ample pharmacological and genetic evidence to support the idea that Hsp90α/β and Trap1 are required for tumorigenesis. However, a direct and comparative genetic test in a mouse cancer model has not been done...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28406480/wdr79-promotes-the-proliferation-of-non-small-cell-lung-cancer-cells-via-usp7-mediated-regulation-of-the-mdm2-p53-pathway
#20
Yang Sun, Lanqin Cao, Xunan Sheng, Jieying Chen, Yu Zhou, Chao Yang, Tanggang Deng, Hongchang Ma, Peifu Feng, Jing Liu, Weihong Tan, Mao Ye
WD repeat protein 79 (WDR79) is a member of the WD-repeat protein family and functions as a scaffold protein during telomerase assembly, Cajal body formation and DNA double strand break repair. We have previously shown that WDR79 is frequently overexpressed in cell lines and tissues derived from non-small cell lung cancer (NSCLC) and it accelerates cell proliferation in NSCLC. However, the detailed mechanism underlying the role of WDR79 in the proliferation of NSCLC cells remains unclear. Here, we report the discovery of a molecular interaction between WDR79 and USP7 and show its functional significance in linking the Mdm2-p53 pathway to the proliferation of NSCLC cells...
April 13, 2017: Cell Death & Disease
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