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https://www.readbyqxmd.com/read/29866884/dna-methylation-regulates-the-neonatal-cd4-t-cell-response-to-pneumonia-in-mice
#1
Sharon McGrath-Morrow, Roland Ndeh, Kathryn A Helmin, Shang-Yang Chen, Kishore R Anekalla, Hiam Abdala-Valencia, Franco R D'Alessio, J Michael Collaco, Benjamin D Singer
Pediatric acute lung injury, usually due to pneumonia, has a mortality rate of more than 20% and an incidence that rivals that of all childhood cancers combined. CD4+ T-cells coordinate the immune response to pneumonia but fail to function robustly among the very young, which have poor outcomes from lung infection. We hypothesized that DNA methylation represses a mature CD4+ T-cell transcriptional program in neonates with pneumonia. Here, we found that neonatal mice (3-4 days old) aspirated with Escherichia coli bacteria had a higher mortality rate than juvenile mice (11-14 days old)...
June 4, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29796116/genome-wide-analysis-of-dna-methylation-in-bronchial-washings
#2
Sang-Won Um, Yujin Kim, Bo Bin Lee, Dongho Kim, Kyung-Jong Lee, Hong Kwan Kim, Joungho Han, Hojoong Kim, Young Mog Shim, Duk-Hwan Kim
Background: The objective of this study was to discover DNA methylation biomarkers for detecting non-small lung cancer (NSCLC) in bronchial washings and understanding the association between DNA methylation and smoking cessation. Methods: DNA methylation was analyzed in bronchial washing samples from 70 NSCLCs and 53 hospital-based controls using Illumina HumanMethylation450K BeadChip. Methylation levels in these bronchial washings were compared to those in 897 primary lung tissues of The Cancer Genome Atlas (TCGA) data...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29789542/rnf25-promotes-gefitinib-resistance-in-egfr-mutant-nsclc-cells-by-inducing-nf-%C3%AE%C2%BAb-mediated-erk-reactivation
#3
Jung Hee Cho, Yeon-Mi You, Young Il Yeom, Dong Chul Lee, Bo-Kyung Kim, Misun Won, Byoung Chul Cho, Minho Kang, Seulki Park, Suk-Jin Yang, Jang Seong Kim, Jung-Ae Kim, Kyung Chan Park
Non-small cell lung cancer (NSCLC) patients with EGFR mutations initially respond well to EGFR tyrosine kinase inhibitors (TKIs) but eventually exhibit acquired or innate resistance to the therapies typically due to gene mutations, such as EGFR T790M mutation or a second mutation in the downstream pathways of EGFR. Importantly, a significant portion of NSCLC patients shows TKI resistance without any known mechanisms, calling more comprehensive studies to reveal the underlying mechanisms. Here, we investigated a synthetic lethality with gefitinib using a genome-wide RNAi screen in TKI-resistant EGFR-mutant NSCLC cells, and identified RNF25 as a novel factor related to gefitinib resistance...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29776956/integrin-%C3%AE-3-inhibition-enhances-the-antitumor-activity-of-alk-inhibitor-in-alk-rearranged-nsclc
#4
Ka-Won Noh, Insuk Sohn, Ji-Young Song, Hyun-Tae Shin, Yu Jin Kim, Kyungsoo Jung, Minjung Sung, Mingi Kim, Sungbin An, Joungho Han, Se-Hoon Lee, Mi-Sook Lee, Yoon-La Choi
BACKGROUND: Anaplastic lymphoma kinase (ALK)-positive cancers are sensitive to small molecule ALK kinase inhibitors, but most cases experience failure following treatment. Hence, additional drug targets and combination therapeutic treatments are needed. We investigated gene expression that is regulated by the expression of ALK and explored its roles in cancer progression and therapeutic implication. PATIENTS AND METHODS: We screened ALK-rearranged non-small cell lung cancer (NSCLC) cases using immunohistochemistry and fluorescence in situ hybridization, and then conducted multiplex gene expression analysis...
May 18, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29775598/selective-cytotoxicity-of-the-nampt-inhibitor-fk866-toward-gastric-cancer-cells-with-markers-of-the-epithelial-mesenchymal-transition-due-to-loss-of-naprt
#5
Jooyoung Lee, Hyosil Kim, Jae Eun Lee, Su-Jin Shin, Sejin Oh, Sungjin Kwon, Hakhyun Kim, Yoon Young Choi, Michael A White, Soonmyung Paik, Jae-Ho Cheong, Hyun Seok Kim
BACKGROUND & AIMS: Markers of the epithelial-mesenchymal transition (EMT) in gastric tumor tissues are associated with poor outcomes of patients. We performed a screen to identify pharmacologic compounds that kill gastric cancer cells with EMT-associated gene expression patterns and investigate their mechanisms. METHODS: We identified 29 gastric cancer cell lines with gene expression signature previously associated with an EMT subtype, based on data from RNA sequence analyses, and confirmed their mesenchymal phenotypes of 7 lines (Hs746T, SNU1750, MKN1, SK4, SNU484, SNU668, and YCC11), based in invasive activity and protein markers...
May 15, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29774128/systematic-review-and-meta-analysis-of-selected-toxicities-of-approved-alk-inhibitors-in-metastatic-non-small-cell-lung-cancer
#6
Rubens Barros Costa, Ricardo L B Costa, Sarah M Talamantes, Jason B Kaplan, Manali A Bhave, Alfred Rademaker, Corinne Miller, Benedito A Carneiro, Devalingam Mahalingam, Young Kwang Chae
Introduction: Anaplastic lymphoma kinase ( ALK ) inhibitors are the mainstay treatment for patients with non-small cell lung carcinoma (NSCLC) harboring a rearrangement of the ALK gene or the ROS1 oncogenes. With the recent publication of pivotal trials leading to the approval of these compounds in different indications, their toxicity profile warrants an update. Materials and Methods: A systematic literature search was performed in July 2017. Studies evaluating US FDA approved doses of one of the following ALK inhibitors: Crizotinib, Ceritinib, Alectinib or Brigatinib as monotherapy were included...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29720381/whole-exome-and-transcriptome-analyses-integrated-with-microenvironmental-immune-signatures-of-lung-squamous-cell-carcinoma
#7
Jeong-Sun Seo, Ji Won Lee, Ahreum Kim, Jong-Yeon Shin, Yoo Jin Jung, Sae Bom Lee, Yoon Ho Kim, Samina Park, Hyun Joo Lee, In-Kyu Park, Chang Hyun Kang, Ji-Young Yun, Jihye Kim, Young T Kim
The immune microenvironment in lung squamous cell carcinoma (LUSC) is not well understood, with interactions between the host immune system and the tumor, as well as the molecular pathogenesis of LUSC, awaiting better characterization. To date, no molecularly targeted agents have been developed for LUSC treatment. Identification of predictive and prognostic biomarkers for LUSC could help optimize therapy decisions. We sequenced whole exomes and RNA from 101 tumors and matched noncancer control Korean samples...
May 2, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29717133/kinesin-light-chain-4-depletion-induces-apoptosis-of-radioresistant-cancer-cells-by-mitochondrial-dysfunction-via-calcium-ion-influx
#8
Jeong-Hwa Baek, Janet Lee, Hong Shik Yun, Chang-Woo Lee, Jie-Young Song, Hong-Duck Um, Jong Kuk Park, In-Chul Park, Jae-Sung Kim, Eun Ho Kim, Sang-Gu Hwang
Kinesins act as molecular microtubule-dependent motor proteins and have various important cellular functions related to cell division, intracellular transport, and membrane trafficking. However, the function of kinesin light chain 4 (KLC4) in cancer, especially radioresistance, has not been previously described. Thus, we investigated KLC4 function in lung cancer cells and radioresistant R-H460 cells by analyzing alterations in radiosensitivity after gene knockdown with siRNA and by evaluating cellular phenotypes and xenograft tumor growth...
May 2, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29684384/knockdown-of-poldip2-suppresses-tumor-growth-and-invasion-capacity-and-is-linked-to-unfavorable-transformation-ability-and-metastatic-feature-in-non-small-cell-lung-cancer
#9
Ying-Chieh Chen, Chih-Chi Kuo, Chih-Feng Chian, Ching Tzao, Shan-Yueh Chang, Yu-Lueng Shih, Ya-Wen Lin, Mu-Hsien Yu, Her-Young Su
The main problem in the treatment of non-small cell lung cancer (NSCLC) is metastasis. Epithelial-mesenchymal transition (EMT) is known as the critical signaling in tumor progression, metastasis, and also the drug resistance. In this study, we reported a novel gene Polymerase delta-interacting protein 2 (POLDIP2) was downregulated in NSCLC tissues and first demonstrated that overexpression of POLDIP2 increased the anchorage-independent growth (AIG) and invasiveness of H1299 cells. In addition, we examined that knockdown of POLDIP2 in H1299 and A549 cells reduced tumorigenicity and metastatic capacity in vitro and also in vivo...
July 1, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29667179/characteristics-of-genomic-alterations-of-lung-adenocarcinoma-in-young-never-smokers
#10
Wenxin Luo, Panwen Tian, Yue Wang, Heng Xu, Lu Chen, Chao Tang, Yang Shu, Shouyue Zhang, Zhoufeng Wang, Jun Zhang, Li Zhang, Lili Jiang, Lunxu Liu, Guowei Che, Chenglin Guo, Hong Zhang, Jiali Wang, Weimin Li
Non-small-cell lung cancer (NSCLC) has been recognized as a highly heterogeneous disease with phenotypic and genotypic diversity in each subgroup. While never-smoker patients with NSCLC have been well studied through next generation sequencing, we have yet to recognize the potentially unique molecular features of young never-smoker patients with NSCLC. In this study, we conducted whole genome sequencing (WGS) to characterize the genomic alterations of 36 never-smoker Chinese patients, who were diagnosed with lung adenocarcinoma (LUAD) at 45 years or younger...
April 18, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29575851/molecular-screening-of-small-biopsy-samples-using-next-generation-sequencing-in-korean-patients-with-advanced-non-small-cell-lung-cancer-korean-lung-cancer-consortium-klcc-13-01
#11
Bo Mi Ku, Mi Hwa Heo, Joo-Hang Kim, Byoung Chul Cho, Eun Kyung Cho, Young Joo Min, Ki Hyeong Lee, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Tae Jung Kim, Ho Yun Lee, Hojoong Kim, Kyung-Jong Lee, Myung-Ju Ahn
BACKGROUND: Non-small cell lung cancer (NSCLC) is a common type of cancer with poor prognosis. As individual cancers exhibit unique mutation patterns, identifying and characterizing gene mutations in NSCLC might help predict patient outcomes and guide treatment. The aim of this study was to evaluate the clinical adequacy of molecular testing using next-generation sequencing (NGS) for small biopsy samples and characterize the mutational landscape of Korean patients with advanced NSCLC...
May 2018: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/29561562/fluorometric-detection-of-egfr-exon-19-deletion-mutation-in-lung-cancer-cells-using-graphene-oxide
#12
Dong-Min Kim, Dong Ho Kim, Woong Jung, Kye Young Lee, Dong-Eun Kim
Mutations in epidermal growth factor receptor (EGFR) are known as biomarkers that cause non-small cell lung cancer. Particularly, approximately 45% of non-small cell lung cancer patients possess a deletion in exon 19 of the EGFR gene. A less invasive method for detecting the EGFR mutation is required; thus, we developed a simple polymerase chain reaction (PCR)-based method for detecting EGFR exon 19 deletion by using a quencher-free fluorescent probe DNA and graphene oxide (GO). In the presence of the exon 19 deletion mutation, the fluorophore-labeled DNA probe was designed to be fully complementary to the mutant sequences...
April 16, 2018: Analyst
https://www.readbyqxmd.com/read/29559559/anaplastic-lymphoma-kinase-mutation-alk-f1174c-in-small-cell-carcinoma-of-the-prostate-and-molecular-response-to-alectinib
#13
Benedito A Carneiro, Sahithi Pamarthy, Ami N Shah, Vinay Sagar, Kenji Unno, HuiYing Han, Ximing J Yang, Rubens B Costa, Rebecca J Nagy, Richard B Lanman, Timothy M Kuzel, Jeffrey S Ross, Laurie Gay, Julia A Elvin, Siraj M Ali, Massimo Cristofanilli, Young K Chae, Francis J Giles, Sarki A Abdulkadir
Purpose: Small cell carcinoma of the prostate (SCCP) is an aggressive disease that can arise de novo or by transdifferentiation from prostate adenocarcinoma. Alterations in anaplastic lymphoma kinase ( ALK ) gene are involved in neuroblastoma, lung cancer, and other malignancies, but its role in SCCP has not been documented. We describe a patient with refractory de novo SCCP with ALK F1174C-activating mutation who obtained clinical benefit from treatment with ALK inhibitor. Experimental Design: Next-generation sequencing (NGS) was used to analyze primary and circulating tumor DNA (ctDNA)...
March 20, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29549897/detection-of-ret-rearranged-during-transfection-variants-and-their-downstream-signal-molecules-in-ret-rearranged-lung-adenocarcinoma-patients
#14
Jeong-Oh Kim, Jung-Young Shin, Min Young Kim, Kyoung Hwa Son, Chan Kwon Jung, Tae-Jung Kim, Su Young Kim, Jae Kil Park, Sook Whan Sung, Sang Ju Bae, Hyun Jung Min, Jin-Hyoung Kang
BACKGROUND: We screened resected tumor tissues from patients with lung cancer for EGFR mutations, ALK rearrangements, and rearranged during transfection (RET) gene variants (including RET rearrangements and the Kinesin Family Member 5B (KIF5B)-RET fusion gene) using various methods including reverse transcription polymerase chain reaction (RT-PCR), transcript assays, fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC). We also examined the protein expression of associated downstream signaling molecules to assess the effect of these variants on patient outcome...
March 2018: Surgical Oncology
https://www.readbyqxmd.com/read/29548312/delayed-diagnosis-of-birt-hogg-dub%C3%A3-syndrome-due-to-marked-intrafamilial-clinical-variability-a-case-report
#15
E C Sattler, O K Steinlein
BACKGROUND: Birt-Hogg-Dubé syndrome is a genetic syndrome caused by mutations in the FLCN gene. The main symptoms are lung bullae and pneumothorax, benign and malignant kidney tumors, and facial fibrofolliculoma. The risk of pneumothorax is considerable between ages 20-40 years, but decreases markedly after this age range and first-time pneumothorax after age 50 years is rare. Fibrofolliculomas usually occur between ages 35 and 45 years, while the risk for kidney cancer increases steadily with age, starting in young adulthood...
March 16, 2018: BMC Medical Genetics
https://www.readbyqxmd.com/read/29517858/clinicopathological-features-of-younger-aged-%C3%A2-50-years-lung-adenocarcinoma-patients-harboring-the-eml4-alk-fusion-gene
#16
Takuro Kometani, Kenji Sugio, Atsushi Osoegawa, Takashi Seto, Yukito Ichinose
BACKGROUND: The EML4-ALK fusion gene has recently been identified as a driver mutation in a subset of non-small cell lung cancers. In subsequent studies, EML4-ALK has been detected in a low percentage of patients, and was associated with a lack of EGFR or KRAS mutations, younger age, and adenocarcinoma with acinar histology. Cases with the EML4-ALK fusion gene were examined to clarify the clinicopathological characteristics of young adenocarcinoma patients. METHODS: Between December 1998 and May 2009, 85 patients aged ≤ 50 with lung adenocarcinoma were treated at our hospital...
May 2018: Thoracic Cancer
https://www.readbyqxmd.com/read/29502124/a-prospective-observational-study-evaluating-the-correlation-of-c-met-expression-and-egfr-gene-mutation-with-response-to-erlotinib-as-second-line-treatment-for-patients-with-advanced-metastatic-non-small-cell-lung-cancer
#17
Cheol-Kyu Park, In-Jae Oh, Yoo-Duk Choi, Tae-Won Jang, Jeong-Eun Lee, Jeong-Seon Ryu, Shin-Yup Lee, Young-Chul Kim
OBJECTIVES: We aimed to evaluate the prevalence and predictive role of c-MET expression and EGFR mutation in the efficacy of erlotinib in non-small-cell lung cancer (NSCLC). METHODS: We prospectively recruited 196 patients with stage IV or recurrent NSCLC treated with erlotinib after failure of first-line chemotherapy. Immunohistochemistry was used to evaluate c-MET overexpression, silver in situ hybridization (SISH) to assess gene copy number, and real-time polymerase chain reaction to detect EGFR mutations, respectively, in tumor tissue...
March 2, 2018: Oncology
https://www.readbyqxmd.com/read/29496169/ophiopogonin-d-modulates-multiple-oncogenic-signaling-pathways-leading-to-suppression-of-proliferation-and-chemosensitization-of-human-lung-cancer-cells
#18
Jong Hyun Lee, Chulwon Kim, Seok-Geun Lee, Woong Mo Yang, Jae-Young Um, Gautam Sethi, Kwang Seok Ahn
BACKGROUND: Ophiopogonin D (OP-D), a steroidal glycoside obtained from the Chinese medicinal plant Ophiopogonin japonicas (the root portion), has been traditionally used to treat fever, inflammation, cough, sputum etc. However, the detailed molecular mechanism(s) underlying its therapeutic actions is still unknown. HYPOTHESIS: Because nuclear factor-κB (NF-κB), PI3K/AKT, and activator protein-1 (AP-1) signaling cascades have significant functions in cell proliferation, inflammation, and angiogenesis in tumor cells, we hypothesized that OP-D may disrupt these signaling cascades to exert its anticancer effects in human lung-cancer cells...
February 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29487705/mutations-in-dna-repair-genes-are-associated-with-increased-neo-antigen-load-and-activated-t-cell-infiltration-in-lung-adenocarcinoma
#19
Young Kwang Chae, Jonathan F Anker, Preeti Bais, Sandeep Namburi, Francis J Giles, Jeffrey H Chuang
Mutations in DNA repair genes lead to increased genomic instability and mutation frequency. These mutations represent potential biomarkers for cancer immunotherapy efficacy, as high tumor mutational burden has been associated with increased neo-antigens and tumor infiltrating lymphocytes. While mismatch repair mutations have successfully predicted response to anti-PD-1 therapy in colorectal and other cancers, they have not yet been tested for lung cancer, and few have investigated genes from other DNA repair pathways...
January 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29484424/knockdown-of-end-binding-protein-1-induces-apoptosis-in-radioresistant-a549-lung-cancer-cells-via-p38-kinase-dependent-cox-2-upregulation
#20
Jeong-Hwa Baek, Ji-Hye Yim, Jie-Young Song, Hong-Duck Um, Jong Kuk Park, In-Chul Park, Jae-Sung Kim, Chang-Woo Lee, Eun-Hee Hong, Eun Ho Kim, Sang-Gu Hwang
The role of end-binding protein 1 (EB1) in lung cancer tumorigenesis and radiotherapy remains poorly understood. In the present study, we observed that EB1 was highly expressed in lung tumor tissues compared with normal non-tumor tissues based on immunohistochemical analysis of lung cancer tissue samples obtained from human tissue microarrays. EB1 was also highly overexpressed in radioresistant lung and cervical cancer cells, which exhibited increased cell death after EB1 silencing. The cytotoxicity induced by EB1 gene knockdown was due to the activation and generation of reactive oxygen species by p38 mitogen-activated protein kinase...
April 2018: Oncology Reports
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