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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
#1
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
https://www.readbyqxmd.com/read/28467805/paraoxonase-1-pon1-induces-metastatic-potential-and-apoptosis-escape-via-its-antioxidative-function-in-lung-cancer-cells
#2
Mark Borris D Aldonza, Yeon Sung Son, Hye-Jin Sung, Jung-Mo Ahn, Young-Jin Choi, Yong-In Kim, Sukki Cho, Je-Yoel Cho
Paraoxonase-1 (PON1) gene polymorphisms have been closely associated with the development of advanced cancers while PON1 secretion to the serum is linked with inhibition of oxidized high-density lipoprotein by its antioxidative function. Our group previously demonstrated that post-translational modification of serum PON1 in form of fucosylated PON1 is a potential biomarker of small cell lung cancer. Here, we interrogated the role of PON1 in the pathobiology of lung cancer (LC) by addressing cell-autonomous mechanisms using gain-of-function and loss-of-function approaches and protein expression profiling of tissue samples in our clinical biobank...
April 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28453567/performance-of-urine-cotinine-and-hypomethylation-of-ahrr-and-f2rl3-as-biomarkers-for-smoking-exposure-in-a-population-based-cohort
#3
Do-Hoon Lee, Sang-Hyun Hwang, Min Kyung Lim, Jin-Kyoung Oh, Da Young Song, E Hwa Yun, Eun Young Park
There is a growing body of evidence demonstrating an association between smoking and DNA methylation. Accordingly, DNA methylation is now considered a promising biomarker of smoking exposure. We evaluated the relationship between methylation markers (AHRR and F2RL3) and urine cotinine as well as self-reported smoking status. DNA methylation levels of AHRR and F2RL3 in blood as well as urine cotinine were measured in 330 adults (46 to 87 years of age). Pyrosequencing was performed to measure DNA methylation of AHRR and F2RL3 associated with smoking exposure...
2017: PloS One
https://www.readbyqxmd.com/read/28440514/silibinin-downregulates-mmp2-expression-via-jak2-stat3-pathway-and-inhibits-the-migration-and-invasive-potential-in-mda-mb-231-cells
#4
Hyo Joo Byun, Pramod Darvin, Dong Young Kang, Nipin Sp, Youn Hee Joung, Jong Hwan Park, Sun Jin Kim, Young Mok Yang
Worldwide, breast cancer (BCa) is the most common cancer in women. Among its subtypes, triple-negative breast cancer (TNBC) is an aggressive form associated with diminished survival. TNBCs are characterized by their absence, or minimal expression, of the estrogen and progesterone receptors, as well as the human epidermal growth factor receptor 2 (i.e. ER-/-, PR-/-, Her2-/Low). Consequently, treatment for this subtype of BCa remains problematic. Silibinin, a derivative of the flavonoid silymarin, is reported to have anticancer activities against hepatic and non-small cell lung cancers...
April 19, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28422737/generation-of-lung-cancer-cell-lines-harboring-egfr-t790m-mutation-by-crispr-cas9-mediated-genome-editing
#5
Mi-Young Park, Min Hee Jung, Eun Young Eo, Seokjoong Kim, Sang Hoon Lee, Yeon Joo Lee, Jong Sun Park, Young Jae Cho, Jin Haeng Chung, Cheol Hyeon Kim, Ho Il Yoon, Jae Ho Lee, Choon-Taek Lee
Tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib are effective against lung adenocarcinomas harboring epidermal growth factor receptor (EGFR) mutations. However, cancer cells can develop resistance to these agents with prolonged exposure; in over 50% of cases, this is attributable to the EGFR T790M mutation. Moreover, additional resistance mutations can arise with the use of new drugs. Cancer cell lines with specific mutations can enable the study of resistance mechanisms. In this study, we introduced the EGFR T790M mutation into the PC9 human lung cancer cell line-which has a deletion in exon 19 of the EGFR gene-by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas)9-mediated genome editing...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28370334/mir-27a-regulates-the-tgf-%C3%AE-signaling-pathway-by-targeting-smad2-and-smad4-in-lung-cancer
#6
Dong-Kyu Chae, Eunmi Ban, Young Sook Yoo, Eunice EunKyeong Kim, Ja-Hyun Baik, Eun Joo Song
The transforming growth factor-β (TGF-β) signaling pathway is associated with carcinogenesis and various biological processes. SMAD2 and SMAD4, which are putative tumor suppressors, have an important role in TGF-β signaling. The aberrant expression of these genes is implicated in some cancers. However, the mechanisms of SMAD2 and SMAD4 dysregulation are poorly understood. In this study, we observed that miR-27a was upregulated in lung cancer cell lines and patients. In addition, SMAD2 and SMAD4 genes were identified as targets of miR-27a by several target prediction databases and experimental validation...
March 31, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28335269/galactosylated-liposomes-for-targeted-co-delivery-of-doxorubicin-vimentin-sirna-to-hepatocellular-carcinoma
#7
Hea Ry Oh, Hyun-Young Jo, James S Park, Dong-Eun Kim, Je-Yoel Cho, Pyung-Hwan Kim, Keun-Sik Kim
The combination of therapeutic nucleic acids and chemotherapeutic drugs has shown great promise for cancer therapy. In this study, asialoglycoprotein receptors (ASGPR) targeting-ligand-based liposomes were tested to determine whether they can co-deliver vimentin siRNA and doxorubicin to hepatocellular carcinoma (HCC) selectively. To achieve this goal, we developed an ASGPR receptor targeted co-delivery system called gal-doxorubicin/vimentin siRNA liposome (Gal-DOX/siRNA-L). The Gal-DOX/siRNA-L was created via electrostatic interaction of galactose linked-cationic liposomal doxorubicin (Gal-DOX-L) on vimentin siRNA...
July 30, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28326182/birt-hogg-dub%C3%A3-syndrome-a-case-report-and-a-review-of-the-literature
#8
REVIEW
Dea Kejlberg Jensen, Anders Villumsen, Anne-Bine Skytte, Mia Gebauer Madsen, Mette Sommerlund, Elisabeth Bendstrup
Background: Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal dominant inherited syndrome caused by mutations in the folliculin coding gene (FLCN). The clinical manifestations of the syndrome involve the skin, lungs, and kidneys. Because of the rarity of the syndrome, guidelines for diagnosis and management of the patients with BHDS are lacking. Objective: To present a case story and a review of the literature on BHDS in order to give an update on genetics, clinical manifestations, diagnosis, treatment, prognosis and follow-up strategies...
2017: European Clinical Respiratory Journal
https://www.readbyqxmd.com/read/28285687/met-exon-14-skipping-mutation-in-triple-negative-pulmonary-adenocarcinomas-and-pleomorphic-carcinomas-an-analysis-of-intratumoral-met-status-heterogeneity-and-clinicopathological-characteristics
#9
Dohee Kwon, Jaemoon Koh, Sehui Kim, Heounjeong Go, Young A Kim, Bhumsuk Keam, Tae Min Kim, Dong-Wan Kim, Yoon Kyung Jeon, Doo Hyun Chung
OBJECTIVES: MET mutations leading to exon 14 skipping rarely occur in non-small cell lung cancer (NSCLC). Recently, small molecule inhibitors targeting MET mutations showed clinical benefit. However, the clinicopathological characteristics of NSCLC harboring MET mutations, and the correlation among mutations, protein expression, and gene copy number of MET in NSCLC remain unclear. Therefore, we address these issues. MATERIALS AND METHODS: MET exon 14 skipping mutations were evaluated using real-time quantitative reverse-transcription-PCR (qRT-PCR) in 102 triple-negative (i...
April 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28230863/oncogenic-role-of-rab-escort-protein-1-through-egfr-and-stat3-pathway
#10
Un-Jung Yun, Jee Young Sung, Seog-Yun Park, Sang-Kyu Ye, Jaegal Shim, Jae-Seon Lee, Masahiko Hibi, Young-Ki Bae, Yong-Nyun Kim
Rab escort protein-1 (REP1) is linked to choroideremia (CHM), an X-linked degenerative disorder caused by mutations of the gene encoding REP1 (CHM). REP1 mutant zebrafish showed excessive cell death throughout the body, including the eyes, indicating that REP1 is critical for cell survival, a hallmark of cancer. In the present study, we found that REP1 is overexpressed in human tumor tissues from cervical, lung, and colorectal cancer patients, whereas it is expressed at relatively low levels in the normal tissue counterparts...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28223235/interleukin-32-inflammation-and-cancer
#11
REVIEW
Jin Tae Hong, Dong Ju Son, Chong Kil Lee, Do-Young Yoon, Dong Hun Lee, Mi Hee Park
Interleukin-32 (IL-32) is a novel cytokine involved in inflammation and cancer development. IL-32 gene consists of eight small exons, and IL-32 mRNA has nine alternative spliced isoforms, and was thought to be secreted because it contains an internal signal sequence and lacks a transmembrane region. IL-32 is initially expressed selectively in activated T cells by mitogen and activated NK cells and their expression is strongly augmented by microbes, mitogens, and other cytokines. The IL-32 is induced mainly by pathogens and pro-inflammatory cytokines, but IL-32 is more prominent in immune cells than in non-immune tissues...
February 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28219421/regulation-of-voltage-gated-potassium-channels-attenuates-resistance-of-side-population-cells-to-gefitinib-in-the-human-lung-cancer-cell-line-nci-h460
#12
Seon Young Choi, Hang-Rae Kim, Pan Dong Ryu, So Yeong Lee
BACKGROUND: Side-population (SP) cells that exclude anti-cancer drugs have been found in various tumor cell lines. Moreover, SP cells have a higher proliferative potential and drug resistance than main population cells (Non-SP cells). Also, several ion channels are responsible for the drug resistance and proliferation of SP cells in cancer. METHODS: To confirm the expression and function of voltage-gated potassium (Kv) channels of SP cells, these cells, as well as highly expressed ATP-binding cassette (ABC) transporters and stemness genes, were isolated from a gefitinib-resistant human lung adenocarcinoma cell line (NCI-H460), using Hoechst 33342 efflux...
February 21, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28212561/the-tlr7-agonist-imiquimod-induces-anti-cancer-effects-via-autophagic-cell-death-and-enhances-anti-tumoral-and-systemic-immunity-during-radiotherapy-for-melanoma
#13
Jeong Hyun Cho, Hyo-Ji Lee, Hyun-Jeong Ko, Byung-Il Yoon, Jongseon Choe, Keun-Cheol Kim, Tae-Wook Hahn, Jeong A Han, Sun Shim Choi, Young Mee Jung, Kee-Ho Lee, Yun-Sil Lee, Yu-Jin Jung
Toll-like receptor (TLR) ligands are strongly considered immune-adjuvants for cancer immunotherapy and have been shown to exert direct anti-cancer effects. This study was performed to evaluate the synergistic anti-cancer and anti-metastatic effects of the TLR7 agonist imiquimod (IMQ) during radiotherapy for melanoma. The pretreatment of B16F10 or B16F1 cells with IMQ combined with γ-ionizing radiation (IR) led to enhanced cell death via autophagy, as demonstrated by increased expression levels of autophagy-related genes, and an increased number of autophagosomes in both cell lines...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28192899/comparison-of-the-mismatch-repair-system-between-primary-and-metastatic-colorectal-cancers-using-immunohistochemistry
#14
Jiyoon Jung, Youngjin Kang, Yoo Jin Lee, Eojin Kim, Bokyung Ahn, Eunjung Lee, Joo Young Kim, Jeong Hyeon Lee, Youngseok Lee, Chul Hwan Kim, Yang-Seok Chae
BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies worldwide. Approximately 10%-15% of the CRC cases have defective DNA mismatch repair (MMR) genes. Although the high level of microsatellite instability status is a predictor of favorable outcome in primary CRC, little is known about its frequency and importance in secondary CRC. Immunohistochemical staining (IHC) for MMR proteins (e.g., MLH1, MSH2, MSH6, and PMS2) has emerged as a useful technique to complement polymerase chain reaction (PCR) analyses...
March 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28192371/somatic-mutations-in-telomerase-promoter-counterbalance-germline-loss-of-function-mutations
#15
Lindley Maryoung, Yangbo Yue, Ashley Young, Chad A Newton, Cindy Barba, Nicolai S C van Oers, Richard C Wang, Christine Kim Garcia
Germline coding mutations in different telomere-related genes have been linked to autosomal-dominant familial pulmonary fibrosis. Individuals with these inherited mutations demonstrate incomplete penetrance of clinical phenotypes affecting the lung, blood, liver, skin, and other organs. Here, we describe the somatic acquisition of promoter mutations in telomerase reverse transcriptase (TERT) in blood leukocytes of approximately 5% of individuals with inherited loss-of-function coding mutations in TERT or poly(A)-specific ribonuclease (PARN), another gene linked to telomerase function...
March 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28146588/the-frequency-and-clinical-impact-of-her2-alterations-in-lung-adenocarcinoma
#16
Eun Kyung Kim, Kyung A Kim, Chang Young Lee, Hyo Sup Shim
Human epidermal growth factor receptor 2 (HER2 or ErbB2) can be overexpressed, amplified and/or mutated in malignant tumors, and is a candidate for therapeutic targeting. However, molecular associations and clinical significances of these alterations were controversial in lung cancer. In this study, we investigated the frequency and clinicopathological significance of HER2 dysregulation in patients with lung adenocarcinoma. HER2 protein overexpression, gene amplification, and gene mutation were evaluated by immunohistochemistry (IHC), silver in situ hybridization, and direct sequencing, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28145643/analysis-of-fifty-hotspot-mutations-of-lung-squamous-cell-carcinoma-in-never-smokers
#17
Ha Youn Lee, Se Hoon Lee, Jae Kyung Won, Dong Soo Lee, Nak Jung Kwon, Sun Mi Choi, Jinwoo Lee, Chang Hoon Lee, Sang Min Lee, Jae Joon Yim, Chul Gyu Yoo, Young Whan Kim, Sung Koo Han, Young Sik Park
Smoking is the major risk factor for lung squamous cell carcinoma (SCC), although a small number of lung SCCs occurs in never-smokers. The purpose of this study was to compare 50 hotspot mutations of lung SCCs between never-smokers and smokers. We retrospectively reviewed the medical records of patients newly diagnosed with lung SCC between January 1, 2011 and December 31, 2013 in the Seoul National University Hospital. Formalin-fixed, paraffin-embedded tumor samples were used for analysis of hotspot mutations...
March 2017: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/28092948/oral-cell-dna-adducts-as-potential-biomarkers-for-lung-cancer-susceptibility-in-cigarette-smokers
#18
REVIEW
Stephen S Hecht
This perspective considers the use of oral cell DNA adducts, together with exposure and genetic information, to potentially identify those cigarette smokers at highest risk for lung cancer, so that appropriate preventive measures could be initiated at a relatively young age before too much damage has been done. There are now well established and validated analytical methods for the quantitation of urinary and serum metabolites of tobacco smoke toxicants and carcinogens. These metabolites provide a profile of exposure and in some cases lung cancer risk, but they do not yield information on the critical DNA damage parameter that leads to mutations in cancer growth control genes such as KRAS and TP53...
January 17, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28074012/reduced-abundance-of-the-e3-ubiquitin-ligase-e6ap-contributes-to-decreased-expression-of-the-ink4-arf-locus-in-non-small-cell-lung-cancer
#19
Cristina Gamell, Twishi Gulati, Yaara Levav-Cohen, Richard J Young, Hongdo Do, Pat Pilling, Elena Takano, Neil Watkins, Stephen B Fox, Prudence Russell, Doron Ginsberg, Brendon J Monahan, Gavin Wright, Alex Dobrovic, Sue Haupt, Ben Solomon, Ygal Haupt
The tumor suppressor p16(INK4a), one protein encoded by the INK4/ARF locus, is frequently absent in multiple cancers, including non-small cell lung cancer (NSCLC). Whereas increased methylation of the encoding gene (CDKN2A) accounts for its loss in a third of patients, no molecular explanation exists for the remainder. We unraveled an alternative mechanism for the silencing of the INK4/ARF locus involving the E3 ubiquitin ligase and transcriptional cofactor E6AP (also known as UBE3A). We found that the expression of three tumor suppressor genes encoded in the INK4/ARF locus (p15(INK4b), p16(INK4a), and p19(ARF)) was decreased in E6AP(-/-) mouse embryo fibroblasts...
January 10, 2017: Science Signaling
https://www.readbyqxmd.com/read/28042953/cervical-small-cell-neuroendocrine-tumor-mutation-profiles-via-whole-exome-sequencing
#20
Soo Young Cho, Minhye Choi, Hyo-Jeong Ban, Chang Hyeon Lee, Soojun Park, HanKyeom Kim, Young-Sik Kim, Young Seek Lee, Ji-Yun Lee
Cervical small cell neuroendocrine tumors (CSCNETs) are rare, aggressive neuroendocrine tumors (NETs). Reliable diagnostic and prognostic CSCNET markers are lacking, making diagnosis and prognosis prediction difficult, and treatment strategies limited. Here we provide mutation profiles for five tumor-normal paired CSCNETs using whole exome sequencing (WES). We expanded our assessment of frequently mutated genes to include publicly available data from 55 small intestine neuroendocrine tumors, 10 pancreatic neuroendocrine tumors, 42 small cell lung cancers, six NET cell lines, and 188 cervical cancers, along with our five CSCNETs...
January 31, 2017: Oncotarget
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