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https://www.readbyqxmd.com/read/28634396/epigenetic-silencing-of-downstream-genes-mediated-by-tandem-orientation-in-lung-cancer
#1
Steffen Kiehl, Tobias Zimmermann, Rajkumar Savai, Soni S Pullamsetti, Werner Seeger, Marek Bartkuhn, Reinhard H Dammann
Epigenetic deregulation is of importance in tumorigenesis. In particular CpG islands (CGI), are frequently hypermethylated. Here, genome-wide DNA-methylation profiles of 480,000 CpGs in lung cancer cells were generated. It was observed that intra- and intergenic CGI exhibited higher methylation compared to normal cells. The functional annotation of hypermethylated CGI revealed that the hypermethylation was associated with homeobox domain genes and targets marked by repressive histone modifications. The strongest methylation variation was observed in transitional areas of CGI, termed shores...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634123/clinical-utility-of-chromosomal-aneusomy-in-individuals-at-high-risk-of-lung-cancer
#2
Anna E Barón, Severine Kako, William J Feser, Heather Malinowski, Daniel Merrick, Kavita Garg, Stephen Malkoski, Shannon Pretzel, Jill M Siegfried, Wilbur A Franklin, York Miller, Holly J Wolf, Marileila Varella-Garcia
INTRODUCTION: Low dose CT screening for lung cancer has a high false positive rate with frequent discovery of indeterminate pulmonary nodules. Noninvasive biomarkers are needed to reduce false positives and improve risk stratification. A retrospective longitudinal evaluation was performed to assess chromosomal aneusomy in sputum via fluorescence in situ hybridization (CA-FISH) in four nested case-control studies. METHODS: ROC analysis resulted in two grouped cohorts: High Risk (CO High Risk and CO Nodule; 68 Cases, 69 controls) and Screening (ACRIN/NLST and PLuSS; 97 Cases, 185 controls)...
June 17, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28631573/effects-of-mir-1236-3p-and-mir-370-5p-on-activation-of-p21-in-various-tumors-and-its-inhibition-on-the-growth-of-lung-cancer-cells
#3
Chuanchang Li, Qiangqiang Ge, Jiaxuan Liu, Qingsong Zhang, Chenghe Wang, Kai Cui, Zhong Chen
The mechanism of dsRNA-induced gene activation (RNAa) is being gradually unveiled. The plentiful evidence that it existed in mammalian species other than human demonstrated that dsRNA-mediated RNAa is a conservative phenomenon. Simultaneously, accumulating evidence suggested that microRNAs could activate gene expression by targeting promoter. Nevertheless, it is ambiguous whether microRNA-induced gene activation in different human cells is a common phenomenon. The study we performed verified that miR-1236-3p (miR-1236) and miR-370-5p can activate p21 expression in bladder cancer (BCa) T24, EJ cells, and non-small-cell lung carcinoma A549 cells, while in hepatocellular HepG2 cells both microRNAs cannot effectively induce the expression of P21(WAF1/CIP1) (p21)...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28631570/the-effect-of-rcan1-on-the-biological-behaviors-of-small-cell-lung-cancer
#4
Ningqiang Ma, Weiwei Shen, Hailin Pang, Ning Zhang, Hong Shi, Jianlin Wang, Helong Zhang
Bone is the third most common site of cancer metastasis. In total, 30%-40% of lung cancer cases can develop skeletal metastasis for which no effective therapy in clinic is available. RCAN1 (regulator of calcineurin 1) is an important regulator in angiogenesis which is vital to tumor growth. In this study, we investigated the changes of biological behaviors in SBC-5 and SBC-3 cells after the RCAN1 expression level was changed. Briefly, overexpression of RCAN1 significantly attenuated their malignancy, including decreased ability of proliferation, colony formation, migration, invasion, and bone adherence...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28631567/microrna-1285-5p-influences-the-proliferation-and-metastasis-of-non-small-cell-lung-carcinoma-cells-via-downregulating-cdh1-and-smad4
#5
Shixia Zhou, Zhongmian Zhang, Pengyuan Zheng, Wenchao Zhao, Na Han
Abnormal expression of microRNAs has been reported to regulate gene expression and cancer cell growth, invasion, and migration. Recently, upregulation of hsa-miR-1285 was demonstrated in bronchoalveolar lavage fluid samples from patients with lung cancer and downregulation in plasma level of stage-I lung cancer patients. However, the function and the underlying mechanism of miR-1285 in non-small-cell lung carcinoma have not been elucidated. In this study, we found that miR-1285-5p, the mature form of miR-1285, was significantly upregulated in human non-small-cell lung carcinoma cell lines A549 and SK-MES-1...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28629590/bulky-dna-adducts-tobacco-smoking-genetic-susceptibility-and-lung-cancer-risk
#6
Armelle Munnia, Roger W Giese, Simone Polvani, Andrea Galli, Filippo Cellai, Marco E M Peluso
The generation of bulky DNA adducts consists of conjugates formed between large reactive electrophiles and DNA-binding sites. The term "bulky DNA adducts" comes from early experiments that employed a (32)P-DNA postlabeling approach. This technique has long been used to elucidate the association between adducts and carcinogen exposure in tobacco smoke studies and assess the predictive value of adducts in cancer risk. Molecular data showed increased DNA adducts in respiratory tracts of smokers vs nonsmokers. Experimental studies and meta-analysis demonstrated that the relationship between adducts and carcinogens was linear at low doses, but reached steady state at high exposure, possibly due to metabolic and DNA repair pathway saturation and increased apoptosis...
2017: Advances in Clinical Chemistry
https://www.readbyqxmd.com/read/28629464/mir-629-3p-may-serve-as-a-novel-biomarker-and-potential-therapeutic-target-for-lung-metastases-of-triple-negative-breast-cancer
#7
Jin Wang, Cailu Song, Hailin Tang, Chao Zhang, Jun Tang, Xing Li, Bo Chen, Xiaoming Xie
BACKGROUND: Different breast cancer subtypes show distinct tropisms for sites of metastasis. Notably, the lung is the most common site for the first distant recurrence in triple-negative breast cancer (TNBC). The identification of novel biomarkers for lung metastasis is of great importance to improving the outcome of TNBC. In this study, we sought to identify a microRNA (miRNA)-based biomarker and therapeutic target for lung metastasis of TNBC. METHODS: A total of 669 patients without de novo stage IV TNBC were recruited for this study...
June 19, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28626727/mast-cell-infiltration-in-human-brain-metastases-modulates-the-microenvironment-and-contributes-to-the-metastatic-potential
#8
Ananya Roy, Sylwia Libard, Holger Weishaupt, Ida Gustavsson, Lene Uhrbom, Göran Hesselager, Fredrik J Swartling, Fredrik Pontén, Irina Alafuzoff, Elena Tchougounova
Metastatic brain tumors continue to be a clinical problem, despite new therapeutic advances in cancer treatment. Brain metastases (BMs) are among the most common mass lesions in the brain that are resistant to chemotherapies, have a very poor prognosis, and currently lack any efficient diagnostic tests. Predictions estimate that about 40% of lung and breast cancer patients will develop BM. Despite this, very little is known about the immunological and genetic aberrations that drive tumorigenesis in BM. In this study, we demonstrate the infiltration of mast cells (MCs) in a large cohort of human BM samples with different tissues of origin for primary cancer...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28626632/synchronous-mucinous-and-non-mucinous-lung-adenocarcinomas-with-different-epidermal-growth-mutational-status
#9
Rita Linhas, David Tente, Margarida Dias, Ana Barroso
In recent years, the spread of more-sensitive diagnostic methods has resulted in an increase of synchronous multiple primary lung cancer diagnosis. Nevertheless, its occurrence is still rare. Distinction between synchronous lesions from second independent primary tumors is a problem when dealing with multiple lung tumors, particularly if the histological type is the same. We present a case report of a 78-year-old female patient referred to our institution due to pneumonia. A subsequent thoracic computed tomography (CT) was performed showing two suspicious lesions, one in the right upper lobe and the other in the right inferior lobe...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28625654/line-1-hypomethylation-is-associated-to-specific-clinico-pathological-features-in-stage-i-non-small-cell-lung-cancer
#10
Andrea Imperatori, Nora Sahnane, Nicola Rotolo, Francesca Franzi, Elisa Nardecchia, Laura Libera, Chiara Romualdi, Maria Cattoni, Fausto Sessa, Lorenzo Dominioni, Daniela Furlan
OBJECTIVES: We hypothesize that selected genetic and/or epigenetic changes associated with advanced tumours may help identifying early non-small cell lung cancers (NSCLCs) that recur after resection. Among epigenetic changes, long interspersed nuclear element-1 (LINE-1) hypomethylation is seen early during carcinogenesis and may act in concert with genetic alterations to cancer progression. LINE-1 hypomethylation and gene mutations frequently involved in lung cancer, were analysed to evaluate their prognostic role in resected stage I NSCLC...
June 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28625653/most-t790m-mutations-are-present-on-the-same-egfr-allele-as-activating-mutations-in-patients-with-non-small-cell-lung-cancer
#11
Noriko Hidaka, Eiji Iwama, Naoki Kubo, Taishi Harada, Kohta Miyawaki, Kentaro Tanaka, Isamu Okamoto, Eishi Baba, Koichi Akashi, Hiroyuki Sasaki, Yoichi Nakanishi
OBJECTIVES: The T790M and C797S mutations of the epidermal growth factor receptor gene (EGFR) confer resistance to first- and third-generation EGFR tyrosine kinase inhibitors (TKIs), respectively, in patients with non-small cell lung cancer (NSCLC) harboring activating mutations of EGFR. C797S has been identified in cis or in trans with T790M in tumor specimens from patients who experienced treatment failure with first- and third-generation EGFR-TKIs. The allelic relation between T790M and activating mutations of EGFR has not been well characterized, however...
June 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28624626/alternative-polyadenylation-patterns-for-novel-gene-discovery-and-classification-in-cancer
#12
Oguzhan Begik, Merve Oyken, Tuna Cinkilli Alican, Tolga Can, Ayse Elif Erson-Bensan
Certain aspects of diagnosis, prognosis, and treatment of cancer patients are still important challenges to be addressed. Therefore, we propose a pipeline to uncover patterns of alternative polyadenylation (APA), a hidden complexity in cancer transcriptomes, to further accelerate efforts to discover novel cancer genes and pathways. Here, we analyzed expression data for 1045 cancer patients and found a significant shift in usage of poly(A) signals in common tumor types (breast, colon, lung, prostate, gastric, and ovarian) compared to normal tissues...
June 15, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28624577/identification-of-an-immune-specific-class-of-hepatocellular-carcinoma-based-on-molecular-features
#13
Daniela Sia, Yang Jiao, Iris Martinez-Quetglas, Olga Kuchuk, Carlos Villacorta-Martin, Manuel Castro de Moura, Juan Putra, Genis Camprecios, Laia Bassaganyas, Nicholas Akers, Bojan Losic, Samuel Waxman, Swan N Thung, Vincenzo Mazzaferro, Manel Esteller, Scott L Friedman, Myron Schwartz, Augusto Villanueva, Josep M Llovet
BACKGROUND AND AIMS: Agents that induce an immune response against tumors by altering T-cell regulation have increased survival times of patients with advanced-stage tumors, such as melanoma or lung cancer. We aimed to characterize molecular features of immune cells that infiltrate hepatocellular carcinomas (HCCs) to determine whether these types of agents might be effective against liver tumors. METHODS: We analyzed HCC samples from 956 patients. We separated gene expression profiles from tumor, stromal, and immune cells using a non-negative matrix factorization algorithm...
June 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28624442/loss-of-fructose-1-6-bisphosphatase-induces-glycolysis-and-promotes-apoptosis-resistance-of-cancer-stem-like-cells-an-important-role-in-hexavalent-chromium-induced-carcinogenesis
#14
Jin Dai, Yanli Ji, Wei Wang, Donghern Kim, Leonard Yenwong Fai, Lei Wang, Jia Luo, Zhuo Zhang
Hexavalent chromium (Cr(VI)) compounds are confirmed human carcinogens for lung cancer. Our previous studies has demonstrated that chronic exposure of human bronchial epithelial BEAS-2B cells to low dose of Cr(VI) causes malignant cell transformation. The acquisition of cancer stem cell-like properties is involved in the initiation of cancers. The present study has observed that a small population of cancer stem-like cells (BEAS-2B-Cr-CSC) exists in the Cr(VI)-transformed cells (BEAS-2B-Cr). Those BEAS-2B-Cr-CSC exhibit extremely reduced capability of generating reactive oxygen species (ROS) and apoptosis resistance...
June 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28623290/tcrp1-transcriptionally-regulated-by-c-myc-confers-cancer-chemoresistance-in-tongue-and-lung-cancer
#15
Xiaoting Jia, Zhijie Zhang, Kai Luo, Guopei Zheng, Minying Lu, Ying Song, Hao Liu, Huisi Qiu, Zhimin He
Previously, we cloned a new gene termed 'tongue cancer resistance-associated protein 1' (TCRP1), which modulates tumorigenesis, enhances cisplatin (cDDP) resistance in cancers, and may be a potential target for reversing drug resistance. However, the mechanisms for regulating TCRP1 expression remain unclear. Herein, we combined bioinformatics analysis with luciferase reporter assay and ChIP assay to determine that c-Myc could directly bind to TCRP1 promoter to upregulate its expression. TCRP1 upregulation in multidrug resistant tongue cancer cells (Tca8113/PYM) and cisplatin-resistant A549 lung cancer cells (A549/DDP) was accompanied by c-Myc upregulation, compared to respective parental cells...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28623259/microrna-34a-encapsulated-in-hyaluronic-acid-nanoparticles-induces-epigenetic-changes-with-altered-mitochondrial-bioenergetics-and-apoptosis-in-non-small-cell-lung-cancer-cells
#16
Malav Trivedi, Amit Singh, Meghna Talekar, Grishma Pawar, Parin Shah, Mansoor Amiji
Therapies targeting epigenetic changes for cancer treatment are in Phase I/II trials; however, all of these target only nuclear DNA. Emerging evidence suggests presence of methylation marks on mitochondrial DNA (mtDNA); but their contribution in cancer is unidentified. Expression of genes encoded on mtDNA are altered in cancer cells, along with increased glycolytic flux. Such glycolytic flux and elevated reactive oxygen species is supported by increased antioxidant; glutathione. MicroRNA-34a can translocate to mitochondria, mediate downstream apoptotic effects of tumor suppressor P53, and inhibit the antioxidant response element Nrf-2, resulting in depleted glutathione levels...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28623122/a-randomized-phase-ii-study-comparing-nivolumab-with-carboplatin-pemetrexed-for-patients-with-egfr-mutation-positive-nonsquamous-non-small-cell-lung-cancer-who-acquire-resistance-to-tyrosine-kinase-inhibitors-not-due-to-a-secondary-t790m-mutation-rationale
#17
Hidetoshi Hayashi, Yasutaka Chiba, Kazuko Sakai, Tomonobu Fujita, Hiroshige Yoshioka, Daisuke Sakai, Chiyoe Kitagawa, Tateaki Naito, Koji Takeda, Isamu Okamoto, Tetsuya Mitsudomi, Yutaka Kawakami, Kazuto Nishio, Shinichiro Nakamura, Nobuyuki Yamamoto, Kazuhiko Nakagawa
Antibodies to programmed cell death-1 (PD-1), such as nivolumab, have shown promising clinical activity in patients with advanced non-small-cell lung cancer (NSCLC), but their efficacy appears to be less pronounced in patients with such tumors harboring epidermal growth factor receptor gene (EGFR) mutations. Recent findings suggest that patients with EGFR mutation-positive NSCLC who develop resistance to tyrosine kinase inhibitors (TKIs) due to mechanisms other than acquisition of the secondary T790M mutation of EGFR are more likely to benefit from nivolumab treatment, possibly as a result of a higher level of expression of the PD-1 ligand PD-L1, than are patients who are T790M-positive...
May 25, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28621837/pediatric-follicular-thyroid-carcinoma-indolent-cancer-with-low-prevalence-of-ras-mutations-and-absence-of-pax8-pparg-fusion-in-a-japanese-population
#18
Huy Gia Vuong, Tetsuo Kondo, Naoki Oishi, Tadao Nakazawa, Kunio Mochizuki, Akira Miyauchi, Mitsuyoshi Hirokawa, Ryohei Katoh
BACKGROUND: Pediatric follicular thyroid carcinomas are uncommon and their clinicopathological features and molecular profiles are still unknown. In this present study, we aimed to investigate the clinicopathological aspects of a large series of follicular thyroid carcinomas (FTCs) in pediatric patients and to analyse the point mutations in codons 12, 13 and 61 of NRAS, HRAS and KRAS genes and the rearrangements of PAX8-PPARG. METHODS: A total of 41 pediatric FTCs less than 21 years of age were enrolled in the present study...
June 16, 2017: Histopathology
https://www.readbyqxmd.com/read/28621229/the-role-of-nrf2-keap1-axis-in-colorectal-cancer-progression-and-chemoresistance
#19
Mohammad Reza Sadeghi, Farhad Jeddi, Narges Soozangar, Mohammad Hossein Somi, Nasser Samadi
Colorectal cancer is the third common cancer after lung and genital cancers worldwide with more than 1.2 million new cases diagnosed annually. Although extensive progress has been made in the treatment of colorectal cancer, finding novel targets for early diagnosis and effective treatment of these patients is an urgent need. Nuclear factor-erythroid 2-kelch-like ECH-associated protein 1 signaling pathway plays a key role in protecting cells from the damage of intracellular oxidative stress and extracellular oxidizing agents...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28620129/up-regulation-of-irf-3-expression-through-gata-1-acetylation-by-histone-deacetylase-inhibitor-in-lung-adenocarcinoma-a549-cells
#20
Lu-Lu Wang, Lan-Bo Zhou, Jin Shu, Nan-Nan Li, Hui-Wen Zhang, Rui Jin, Li-Li Zhuang, Guo-Ping Zhou
Interferon regulatory factor 3 (IRF-3) is an important transcription factor for interferon genes. Although its functional activation by viral infection has been widely explicated, the regulatory mechanism of IRF-3 gene expression in cancer cells is poorly understood. In this study, we demonstrated treatment of lung adenocarcinoma A549 cells with trichostatin A (TSA) and valproic acid (VPA), two different classes of histone deacetylase inhibitors, strongly stimulated IRF-3 gene expression. Truncated and mutated IRF-3 promoter indicated that a specific GATA-1 element was responsible for TSA-induced activation of IRF-3 promoter...
June 6, 2017: Oncotarget
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