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https://www.readbyqxmd.com/read/29047229/enhanced-inflammation-and-attenuated-tumor-suppressor-pathways-are-associated-with-oncogene-induced-lung-tumors-in-aged-mice
#1
Neha Parikh, Ryan L Shuck, Mihai Gagea, Lanlan Shen, Lawrence A Donehower
Aging is often accompanied by a dramatic increase in cancer susceptibility. To gain insights into how aging affects tumor susceptibility, we generated a conditional mouse model in which oncogenic Kras(G12D) was activated specifically in lungs of young (3-5 months) and old (19-24 months) mice. Activation of Kras(G12D) in old mice resulted in shorter survival and development of higher-grade lung tumors. Six weeks after Kras(G12D) activation, old lung tissues contained higher numbers of adenomas than their young tissue counterparts...
October 18, 2017: Aging Cell
https://www.readbyqxmd.com/read/28972577/genome-wide-association-study-across-european-and-african-american-ancestries-identifies-a-snp-in-dnmt3b-contributing-to-nicotine-dependence
#2
D B Hancock, Y Guo, G W Reginsson, N C Gaddis, S M Lutz, R Sherva, A Loukola, C C Minica, C A Markunas, Y Han, K A Young, D F Gudbjartsson, F Gu, D W McNeil, B Qaiser, C Glasheen, S Olson, M T Landi, P A F Madden, L A Farrer, J Vink, N L Saccone, M C Neale, H R Kranzler, J McKay, R J Hung, C I Amos, M L Marazita, D I Boomsma, T B Baker, J Gelernter, J Kaprio, N E Caporaso, T E Thorgeirsson, J E Hokanson, L J Bierut, K Stefansson, E O Johnson
Cigarette smoking is a leading cause of preventable mortality worldwide. Nicotine dependence, which reduces the likelihood of quitting smoking, is a heritable trait with firmly established associations with sequence variants in nicotine acetylcholine receptor genes and at other loci. To search for additional loci, we conducted a genome-wide association study (GWAS) meta-analysis of nicotine dependence, totaling 38,602 smokers (28,677 Europeans/European Americans and 9925 African Americans) across 15 studies...
October 3, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28969043/isothiocyanates-suppress-the-invasion-and-metastasis-of-tumors-by-targeting-fak-mmp-9-activity
#3
Yun-Jeong Jeong, Hyun-Ji Cho, Fung-Lung Chung, Xiantao Wang, Hyang-Sook Hoe, Kwan-Kyu Park, Cheorl-Ho Kim, Hyeun-Wook Chang, Sang-Rae Lee, Young-Chae Chang
Isothiocyanates, which are present as glucosinolate precursors in cruciferous vegetables, have strong activity against various cancers. Here, we compared the anti-metastatic effects of isothiocyanates (benzyl isothiocyanate (BITC), phenethyl isothiocyanate (PEITC), and sulforaphane (SFN)) by examining how they regulate MMP-9 expression. Isothiocyanates, particularly PEITC, suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMP-9 activity and invasion in various cancer cell lines. By contrast, N-methyl phenethylamine, a PEITC analog without an isothiocyanate functional group, had no effect...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28900503/label-free-rapid-viable-enrichment-of-circulating-tumor-cell-by-photosensitive-polymer-based-microfilter-device
#4
Yoon-Tae Kang, Il Doh, Jiyoung Byun, Hee Jin Chang, Young-Ho Cho
We present a clinical device for simple, rapid, and viable isolation of circulating tumor cells (CTCs) from cancer patient bloods. In spite of the clinical importance of CTCs, the lack of easy and non-biased isolation methods is a big hurdle for implementing CTC into clinical use. The present device made of photosensitive polymer was designed to attach to conventional syringe to isolate the CTCs at minimal resources. Its unique tapered-slits on the filter are capable not only to isolate the cell based on their size and deformability, but also to increase sample flow rate, thus achieving label-free rapid viable CTC isolation...
2017: Theranostics
https://www.readbyqxmd.com/read/28881718/quercetin-inhibits-cr-vi-induced-malignant-cell-transformation-by-targeting-mir-21-pdcd4-signaling-pathway
#5
Poyil Pratheeshkumar, Young-Ok Son, Sasidharan Padmaja Divya, Lei Wang, Lilia Turcios, Ram Vinod Roy, John Andrew Hitron, Donghern Kim, Jin Dai, Padmaja Asha, Zhuo Zhang, Xianglin Shi
Hexavalent chromium [Cr(VI)] is an important human carcinogen associated with pulmonary diseases and lung cancer. Inhibition of Cr(VI)-induced carcinogenesis by a dietary antioxidant is a novel approach. Quercetin is one of the most abundant dietary flavonoids widely present in many fruits and vegetables, possesses potent antioxidant and anticancer properties. MicroRNA-21 (miR-21) is a key oncomiR significantly elevated in the majority of human cancers that exerts its oncogenic activity by targeting the tumor suppressor gene programmed cell death 4 (PDCD4)...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28862766/genomic-profiles-of-lung-cancer-associated-with-idiopathic-pulmonary-fibrosis
#6
Ji An Hwang, Deokhoon Kim, Sung-Min Chun, SooHyun Bae, Joon Seon Song, Mi Young Kim, Hyun Jung Koo, Jin Woo Song, Woo Sung Kim, Jae Cheol Lee, Hyeong Ryul Kim, Chang-Min Choi, Se Jin Jang
Little is known on the pathogenesis or molecular profiles of idiopathic pulmonary fibrosis-associated lung cancer (IPF-LC). This study was performed to investigate the genomic profiles of IPF-LC and to explore the possibility of defining potential therapeutic targets in IPF-LC. We assessed genomic profiles of IPF-LC using targeted exome sequencing (OncoPanel version 2) in 35 matched tumor/normal pairs surgically resected between 2004 and 2014. Germline and somatic variant calling was performed using GATK HaplotypeCaller and MuTect with GATK SomaticIndelocator, respectively...
September 1, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28860622/lsd1-modulates-the-non-canonical-integrin-%C3%AE-3-signaling-pathway-in-non-small-cell-lung-carcinoma-cells
#7
So-Young Lim, Iris Macheleidt, Priya Dalvi, Stephan C Schäfer, Martin Kerick, Luka Ozretić, Sandra Ortiz-Cuaran, Julie George, Sabine Merkelbach-Bruse, Jürgen Wolf, Bernd Timmermann, Roman K Thomas, Michal R Schweiger, Reinhard Buettner, Margarete Odenthal
The epigenetic writer lysine-specific demethylase 1 (LSD1) is aberrantly upregulated in many cancer types and its overexpression correlates with poor survival and tumor progression. In this study, we analysed LSD1 function in non-small cell lung cancer adenocarcinomas. Expression profiling of 182 cases of lung adenocarcinoma proved a significant correlation of LSD1 overexpression with lung adenocarcinoma progression and metastasis. KRAS-mutated lung cancer cell clones were stably silenced for LSD1 expression...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28838404/validation-of-alk-ros1-dual-break-apart-fish-probe-probe-in-non-small-cell-lung-cancer
#8
Sun Min Lim, Hyun Chang, Yoon Jin Cha, Shile Liang, Yan Chin Tai, Gu Li, Ekaterina Pestova, Frank Policht, Thomas Perez, Ross A Soo, Won Young Park, Hye Ryun Kim, Hyo Sup Shim, Byoung Chul Cho
BACKGROUND: ALK and ROS1 gene rearrangements are distinct molecular subsets of non-small-cell lung cancer (NSCLC), and they are strong predictive biomarkers of response to ALK/ROS1 inhibitors, such as crizotinib. Thus, it is clinically important to develop an effective screening strategy to detect patients who will benefit from such treatment. In this study, we aimed to validate analytical performance of Vysis ALK/ROS1 Dual Break Apart Probe Kit (RUO) in NSCLC. METHODS: Study population composed of three patient cohorts with histologically confirmed lung adenocarcinoma (patients with ALK rearrangement, patients with ROS1 rearrangement and patients with wild-type ALK and ROS1)...
September 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28837649/integrative-analysis-for-the-discovery-of-lung-cancer-serological-markers-and-validation-by-mrm-ms
#9
Jihye Shin, Sang-Yun Song, Hee-Sung Ahn, Byung Chull An, Yoo-Duk Choi, Eun Gyeong Yang, Kook-Joo Na, Seung-Taek Lee, Jae-Il Park, Seon-Young Kim, Cheolju Lee, Seung-Won Lee
Non-small-cell lung cancer (NSCLC) constitutes approximately 80% of all diagnosed lung cancers, and diagnostic markers detectable in the plasma/serum of NSCLC patients are greatly needed. In this study, we established a pipeline for the discovery of markers using 9 transcriptome datasets from publicly available databases and profiling of six lung cancer cell secretomes. Thirty-one out of 312 proteins that overlapped between two-fold differentially expressed genes and identified cell secretome proteins were detected in the pooled plasma of lung cancer patients...
2017: PloS One
https://www.readbyqxmd.com/read/28811522/the-lichen-secondary-metabolite-atranorin-suppresses-lung-cancer-cell-motility-and-tumorigenesis
#10
Rui Zhou, Yi Yang, So-Yeon Park, Thanh Thi Nguyen, Young-Woo Seo, Kyung Hwa Lee, Jae Hyuk Lee, Kyung Keun Kim, Jae-Seoun Hur, Hangun Kim
Lichens are symbiotic organisms that produce various secondary metabolites. Here, different lichen extracts were examined to identify secondary metabolites with anti-migratory activity against human lung cancer cells. Everniastrum vexans had the most potent inhibitory activity, and atranorin was identified as an active subcomponent of this extract. Atranorin suppressed β-catenin-mediated TOPFLASH activity by inhibiting the nuclear import of β-catenin and downregulating β-catenin/LEF and c-jun/AP-1 downstream target genes such as CD44, cyclin-D1 and c-myc...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28776259/increased-egfr-expression-induced-by-a-novel-oncogene-cug2-confers-resistance-to-doxorubicin-through-stat1-hdac4-signaling
#11
Sirichat Kaowinn, Seung Won Jun, Chang Seok Kim, Dong-Myeong Shin, Yoon-Hwae Hwang, Kyujung Kim, Bosung Shin, Chutima Kaewpiboon, Hyeon Hee Jeong, Sang Seok Koh, Oliver H Krämer, Randal N Johnston, Young-Hwa Chung
BACKGROUND: Previously, it has been found that the cancer upregulated gene 2 (CUG2) and the epidermal growth factor receptor (EGFR) both contribute to drug resistance of cancer cells. Here, we explored whether CUG2 may exert its anticancer drug resistance by increasing the expression of EGFR. METHODS: EGFR expression was assessed using Western blotting, immunofluorescence and capacitance assays in A549 lung cancer and immortalized bronchial BEAS-2B cells, respectively, stably transfected with a CUG2 expression vector (A549-CUG2; BEAS-CUG2) or an empty control vector (A549-Vec; BEAS-Vec)...
August 3, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28766235/polymorphisms-in-epithelial-mesenchymal-transition-related-genes-and-the-prognosis-of-surgically-treated-non-small-cell-lung-cancer
#12
Yangki Seok, Hyo-Gyoung Kang, Shin Yup Lee, Ji Yun Jeong, Jin Eun Choi, Deuk Kju Jung, Cheng Cheng Jin, Mi Jeong Hong, Sook Kyung Do, Won Kee Lee, Ji Young Park, Kyung Min Shin, Seung Soo Yoo, Jaehee Lee, Sukki Cho, Seung Ick Cha, Chang Ho Kim, Sanghoon Jheon, Eung Bae Lee, Jae Yong Park
BACKGROUND: This study was conducted to determine whether single-nucleotide polymorphisms (SNPs) in EMT-related genes may influence the prognosis of NSCLC after surgery. METHODS: There were 88 SNPs in EMT-related genes evaluated in a discovery set of 376 patients who underwent curative surgery for NSCLC. Significantly, 14 SNPs were evaluated in a validation set of 428 patients. Luciferase assay and RT-PCR were conducted to examine functional relevance of polymorphisms...
August 1, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28747957/acn9-regulates-the-inflammatory-responses-in-human-bronchial-epithelial-cells
#13
Jae Hoon Jeong, Jeeyoung Kim, Jeongwoon Kim, Hye-Ryeon Heo, Jin Seon Jeong, Young-Joon Ryu, Yoonki Hong, Seon-Sook Han, Seok-Ho Hong, Seung-Joon Lee, Woo Jin Kim
BACKGROUND: Airway epithelial cells are the first line of defense, against pathogens and environmental pollutants, in the lungs. Cellular stress by cadmium (Cd), resulting in airway inflammation, is assumed to be directly involved in tissue injury, linked to the development of lung cancer, and chronic obstructive pulmonary disease (COPD). We had earlier shown that ACN9 (chromosome 7q21), is a potential candidate gene for COPD, and identified significant interaction with smoking, based on genetic studies...
July 2017: Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/28747562/isothiocyanates-suppress-the-invasion-and-metastasis-of-tumors-by-targeting-fak-mmp-9-activity
#14
Yun-Jeong Jeong, Hyun-Ji Cho, Fung-Lung Chung, Xiantao Wang, Hyang-Sook Hoe, Kwan-Kyu Park, Cheorl-Ho Kim, Hyeun-Wook Chang, Sang-Rae Lee, Young-Chae Chang
Isothiocyanates, which are present as glucosinolate precursors in cruciferous vegetables, have strong activity against various cancers. Here, we compared the anti-metastatic effects of isothiocyanates (benzyl isothiocyanate (BITC), phenethyl isothiocyanate (PEITC), and sulforaphane (SFN)) by examining how they regulate MMP-9 expression. Isothiocyanates, particularly PEITC, suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMP-9 activity and invasion in various cancer cell lines. By contrast, N-methyl phenethylamine, a PEITC analog without an isothiocyanate functional group, had no effect...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28744021/thy-1-cancer-associated-fibroblasts-adversely-impact-lung-cancer-prognosis
#15
Mark J Schliekelman, Chad J Creighton, Brandi N Baird, Yulong Chen, Priyam Banerjee, Neus Bota-Rabassedas, Young-Ho Ahn, Jonathon D Roybal, Fengju Chen, Yiqun Zhang, Dhruva K Mishra, Min P Kim, Xin Liu, Barbara Mino, Pamela Villalobos, Jaime Rodriguez-Canales, Carmen Behrens, Ignacio I Wistuba, Samir M Hanash, Jonathan M Kurie
Cancer-associated fibroblasts (CAFs) regulate diverse intratumoral biological programs and can promote or inhibit tumorigenesis, but those CAF populations that negatively impact the clinical outcome of lung cancer patients have not been fully elucidated. Because Thy-1 (CD90) marks CAFs that promote tumor cell invasion in a murine model of Kras(G12D)-driven lung adenocarcinoma (Kras(LA1)), here we postulated that human lung adenocarcinomas containing Thy-1(+) CAFs have a worse prognosis. We first examined the location of Thy-1(+) CAFs within human lung adenocarcinomas...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28709031/bisphenol-a-induces-cox-2-through-the-mitogen-activated-protein-kinase-pathway-and-is-associated-with-levels-of-inflammation-related-markers-in-elderly-populations
#16
Heewon Song, Joonwoo Park, Phuong T C Bui, KeunOh Choi, Myung Chan Gye, Yun-Chul Hong, Jin Hee Kim, Young Joo Lee
Bisphenol A (BPA) is a well-known endocrine-disrupting chemical, and it is one of the highest volume chemicals produced worldwide. Even though several in vivo and in vitro studies showed positive associations of BPA exposure with pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin (IL)-6, the mechanism by which BPA induces inflammation is unclear. We investigated the mechanism by which BPA induces inflammation (expression of inflammation-related genes, changes in oxidative stress, and cell proliferation and migration) and evaluated the effect of BPA exposure on inflammation-related markers in epidemiologic studies using repeat urine and serum samples from elderly subjects...
October 2017: Environmental Research
https://www.readbyqxmd.com/read/28684234/roflumilast-treatment-inhibits-lung-carcinogenesis-in-benzo-a-pyrene-induced-murine-lung-cancer-model
#17
Chang Dong Yeo, Young Ae Kim, Hwa Young Lee, Jin Woo Kim, Seung Joon Kim, Sang Haak Lee, Young Kyoon Kim
Roflumilast, a potent and selective inhibitor of phosphodiesterase-4 (PDE4), has been used in treatment of COPD. PDE4 inhibitor is associated with inhibition of chronic airway inflammation, oxidative stress, and mesenchymal markers in B(a)P-induced lung tumors. The aim of this study was to assess whether roflumilast alone or added to inhaled budesonide might have dose-dependent inhibition on lung carcinogenesis induced by carcinogen B(a)P in mice. Female A/J mice were given a single dose of benzo(a)pyrene. Administration of roflumilast (1mg/kg or 5mg/kg) via oral gavage and aerosolized budesonide (2...
July 4, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28611104/cisplatin-increases-sensitivity-to-fgfr-inhibition-in-patient-derived-xenograft-models-of-lung-squamous-cell-carcinoma
#18
Clare E Weeden, Aliaksei Z Holik, Richard J Young, Stephen B Ma, Jean-Marc Garnier, Stephen B Fox, Phillip Antippa, Louis B Irving, Daniel P Steinfort, Gavin M Wright, Prudence A Russell, Matthew E Ritchie, Christopher J Burns, Benjamin Solomon, Marie-Liesse Asselin-Labat
Lung squamous cell carcinoma (SqCC) is a molecularly complex and genomically unstable disease. No targeted therapy is currently approved for lung SqCC, although potential oncogenic drivers of SqCC have been identified, including amplification of the fibroblast growth factor receptor 1 (FGFR1). Reports from a recently completed clinical trial indicate low response rates in patients treated with FGFR tyrosine kinase inhibitors, suggesting inadequacy of FGFR1 amplification as a biomarker of response, or the need for combination treatment...
August 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28566434/jun-mediated-downregulation-of-egfr-signaling-is-associated-with-resistance-to-gefitinib-in-egfr-mutant-nsclc-cell-lines
#19
Kian Kani, Carolina Garri, Katrin Tiemann, Paymaneh D Malihi, Vasu Punj, Anthony L Nguyen, Janet Lee, Lindsey D Hughes, Ruth M Alvarez, Damien M Wood, Ah Young Joo, Jonathan E Katz, David B Agus, Parag Mallick
Mutations or deletions in exons 18-21 in the EGFR) are present in approximately 15% of tumors in patients with non-small cell lung cancer (NSCLC). They lead to activation of the EGFR kinase domain and sensitivity to molecularly targeted therapeutics aimed at this domain (gefitinib or erlotinib). These drugs have demonstrated objective clinical response in many of these patients; however, invariably, all patients acquire resistance. To examine the molecular origins of resistance, we derived a set of gefitinib-resistant cells by exposing lung adenocarcinoma cell line, HCC827, with an activating mutation in the EGFR tyrosine kinase domain, to increasing gefitinib concentrations...
August 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28542649/evaluation-of-connectivity-map-discovered-celastrol-as-a-radiosensitizing-agent-in-a-murine-lung-carcinoma-model-feasibility-study-of-diffusion-weighted-magnetic-resonance-imaging
#20
Hong Young Jun, Tae-Hoon Kim, Jin Woo Choi, Young Hwan Lee, Kang Kyoo Lee, Kwon-Ha Yoon
This study was designed to identify potential radiosensitizing (RS) agents for combined radio- and chemotherapy in a murine model of human lung carcinoma, and to evaluate the in vivo effect of the RS agents using diffusion-weighted magnetic resonance imaging (DW-MRI). Radioresistance-associated genes in A549 and H460 cells were isolated on the basis of their gene expression profiles. Celastrol was selected as a candidate RS by using connectivity mapping, and its efficacy in lung cancer radiotherapy was tested...
2017: PloS One
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