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Methylation tumor

Shuji Nakamoto, Yusuke Kumamoto, Kazuharu Igarashi, Yoshiki Fujiyama, Nobuyuki Nishizawa, Shigenori Ei, Hiroshi Tajima, Takashi Kaizu, Masahiko Watanabe, Keishi Yamashita
BACKGROUND: Promoter DNA methylation of Cysteine dioxygenase type1 (CDO1) gene has been clarified as a molecular diagnostic and prognostic indicator in various human cancers. The aim of this study is to investigate the clinical relevance of CDO1 methylation in primary biliary tract cancer (BTC). METHODS: CDO1 DNA methylation was assessed by quantitative methylation-specific PCR in 108 BTC tumor tissues and 101 corresponding normal tissues. BTC was composed of extrahepatic cholangiocarcinoma (EHCC) (n = 81) and ampullary carcinoma (AC) (n = 27)...
2018: PloS One
Jiao Luo, Nyam-Osor Chimge, Beiyun Zhou, Per Flodby, Alessandra Castaldi, Amy L Firth, Yixin Liu, Hongjun Wang, Chenchen Yang, Crystal N Marconett, Edward D Crandall, Ite A Offringa, Baruch Frenkel, Zea Borok
Claudins are a family of transmembrane proteins integral to the structure and function of tight junctions (TJ). Disruption of TJ and alterations in claudin expression are important features of invasive and metastatic cancer cells. Expression of CLDN18.1, the lung-specific isoform of CLDN18, is markedly decreased in lung adenocarcinoma (LuAd). Furthermore, we recently observed that aged Cldn18 -/- mice have increased propensity to develop LuAd. We now demonstrate that CLDN18.1 expression correlates inversely with promoter methylation and with LuAd patient mortality...
October 16, 2018: International Journal of Cancer. Journal International du Cancer
Xiaohui Sun, Yiping Tian, Qianqian Zheng, Ruizhi Zheng, Aifen Lin, Tianhui Chen, Yimin Zhu, Maode Lai
AIM: To construct a model discriminating colorectal cancer (CRC) based on differential DNA methylation. MATERIALS & METHODS: The CRC-related methylation-modulated genes were retrieved from literature. The methylation levels of CpG sites in the promoter regions and the first exons of candidate genes were verified in The Cancer Genome Atlas data. A model for discriminating CRC based on methylation levels was established using least absolute shrinkage and selection operator regression...
October 16, 2018: Epigenomics
Vijay Ramaswamy, Michael D Taylor
Genomics has significantly advanced our knowledge of the biology of brain tumors, and refined our classification over the past 10 years. These advances have relied on the unbiased analysis of large cohorts of brain tumors, where they are clustered in an unbiased manner prior to ascribing clinical and biological features. Indeed, this has resulted in the identification of several layers of heterogeneity not previously appreciated by morphology alone. As such, the classification of unknown samples into known biological subgroups can be performed robustly using either gene expression or DNA methylation profiling...
2019: Methods in Molecular Biology
Yu-Feng Tian, Hui-Ching Wang, Chi-Wen Luo, Wen-Chun Hung, Yu-Han Lin, Tzu-Yi Chen, Chien-Feng Li, Chen-Yi Lin, Mei-Ren Pan
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease, which is characterized by its high invasiveness, rapid progression, and profound resistance to therapy. Gemcitabine is the first-line treatment option for pancreatic cancer patients, but the overall survival is quite low. Therefore, it is an urgent issue to identify new molecules for improved therapies, with better efficacy and less toxicity. Our previous data indicated that Euchromatic histone-lysine N-methyltransferase 2 (EHMT2) functions as a therapeutic target to override GEM resistance and promote metastasis in the treatment of pancreatic cancer...
2018: American Journal of Cancer Research
Feifei Huang, Yanyang Wu, Hong Tan, Tianyao Guo, Ke Zhang, Daiqiang Li, Zhongyi Tong
Non-small cell lung cancer (NSCLC) is one of the mostly deadly malignancies in the world. Nucleolin is a multifunctional protein that mainly regulates ribosome biogenesis but also has other functions including modulating the transcription of mRNAs and repressing RNA polymerase II. Nucleolin is overexpressed in various cancer cells, including NSCLC cells. It can confer resistance to apoptosis and promote cell migration and blood vessel formation by directly taking part in various tumor signal transduction pathways...
October 12, 2018: Oncology Reports
Jae Yeon Choi, Hyun Jin Shin, In Hwa Bae
Cellular senescence, a distinctive type of irreversible growth arrest, develops in response to various stimuli. Bcl-w, an oncogene and member of the Bcl-2 family, has been reported to promote tumorigenicity in various cancer cells. Here, we sought to explore the potential role of Bcl-w in premature senescence, which has received relatively little research attention. Our findings demonstrate that Bcl-w enhances the activity of senescence-associated β-galactosidase (SA-β-gal) and promotes histone H3 tri-methylation at lysine 9 (H3K9me3) and expressions of p53, Notch2, p21, and p16-hallmarks of the senescent phenotype-in human U251 glioblastoma and H460 lung carcinoma cells...
October 11, 2018: Biochemical and Biophysical Research Communications
ZhaoFang Li, RongQiang Zhang, XiaoLi Yang, DanDan Zhang, BaoRong Li, Di Zhang, Qiang Li, YongMin Xiong
BACKGROUND: Osteoarthritis (OA) is a kind of chronic osteoarthropathy and degenerative joint disease. Epigenetic regulation in the gene expression dynamics has become increasingly important in OA. We performed a combined analysis of two types of microarray datasets (gene expression and DNA methylation) to identify methylation-based key biomarkers to provide a better understanding of molecular biological mechanisms of OA. METHODS: We obtained two expression profiling datasets (GSE55235, GSE55457) and one DNA methylation profiling data set (GSE63695) from the Gene Expression Omnibus...
October 14, 2018: Journal of Cellular Physiology
Yang Yang, Meng Wang, Bao Liu
Lung cancer is one of the most frequently diagnosed malignant tumors and the main reason for cancer-related death around the world, whereas nonsmall cell lung cancer that consists two subtypes: lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) is responsible for an estimated 85% of all lung cancers. The current study aimed to explore gene expression and methylation differences between LUAD and LUSC. EdgeR was used to identify differentially regulated genes between normal and cancer in the LUAD and LUSC extracted from The Cancer Genome Atlas (TCGA), respectively, whereas SAM was used to find genes with differential methylation between normal and cancer in the LUAD and LUSC, respectively...
October 14, 2018: Journal of Cellular Physiology
Tomonori Kamiya, Yusuke Tanimoto, Nana Fujii, Tomoe Negishi, Toshinori Suzuki, Tsutomu Hatano, Sakae Arimoto-Kobayashi
Previously we demonstrated the anti-tumorigenic, anti-mutagenic and anti-inflammatory effects of the juice of Vitis coignetiae (yamabudo), and identified caftaric acid as an anti-mutagenic component from the juice. In the present study, we investigated the isolation of anti-inflammatory components in yamabudo juice supposing that the anti-inflammatory components in yamabudo are also responsible for the anti-tumorigenic activity. The suppressing effect on nitric oxide production in mouse leukemic monocyte with LPS was used as a separation marker...
October 11, 2018: Food and Chemical Toxicology
Chang S Chan, Saurabh V Laddha, Peter W Lewis, Matthew S Koletsky, Kenneth Robzyk, Edaise Da Silva, Paula J Torres, Brian R Untch, Janet Li, Promita Bose, Timothy A Chan, David S Klimstra, C David Allis, Laura H Tang
The commonly mutated genes in pancreatic neuroendocrine tumors (PanNETs) are ATRX, DAXX, and MEN1. We genotyped 64 PanNETs and found 58% carry ATRX, DAXX, and MEN1 mutations (A-D-M mutant PanNETs) and this correlates with a worse clinical outcome than tumors carrying the wild-type alleles of all three genes (A-D-M WT PanNETs). We performed RNA sequencing and DNA-methylation analysis to reveal two distinct subgroups with one consisting entirely of A-D-M mutant PanNETs. Two genes differentiating A-D-M mutant from A-D-M WT PanNETs were high ARX and low PDX1 gene expression with PDX1 promoter hyper-methylation in the A-D-M mutant PanNETs...
October 12, 2018: Nature Communications
Yunjiao Zhang, Rui Sha, Lan Zhang, Wenbin Zhang, Peipei Jin, Weiguo Xu, Jianxun Ding, Jun Lin, Jing Qian, Guangyu Yao, Rui Zhang, Fanchen Luo, Jie Zeng, Jie Cao, Long-Ping Wen
Chemo-PTT, which combines chemotherapy with photothermal therapy, offers a viable approach for the complete tumor eradication but would likely fail in drug-resistant situations if conventional chemotherapeutic agents are used. Here we show that a type of copper (Cu)-palladium (Pd) alloy tetrapod nanoparticles (TNP-1) presents an ideal solution to the chemo-PTT challenges. TNP-1 exhibit superior near-infrared photothermal conversion efficiency, thanks to their special sharp-tip structure, and induce pro-survival autophagy in a shape- and composition-dependent manner...
October 12, 2018: Nature Communications
Nabih Lolak, Suleyman Akocak, Silvia Bua, Claudiu T Supuran
A series of novel ureido benzenesulfonamides incorporating 1,3,5-triazine moieties were obtained by reacting 4-isocyanato-benzenesulfonamide (2) with 2-amino-4,6-dicholoro-1,3,5-triazine (4). The 4-(3-(4,6-dichloro-1,3,5-triazin-2-yl)ureido) benzenesulfonamide (5) was subsequently derivatized by reaction with various nucleophiles such as, morpholine, ammonia, methyl amine, dimethyl amine, and piperidine. The ureido benzenesulfonamides incorporating triazinyl moieties were investigated as inhibitors of four selected physiologically relevant human carbonic anhydrase (hCA, EC 4...
October 5, 2018: Bioorganic Chemistry
Tsuyoshi Hamada, Jonathan A Nowak, Yohei Masugi, David A Drew, Mingyang Song, Yin Cao, Keisuke Kosumi, Kosuke Mima, Tyler S Twombly, Li Liu, Yan Shi, Annacarolina da Silva, Mancang Gu, Wanwan Li, Katsuhiko Nosho, NaNa Keum, Marios Giannakis, Jeffrey A Meyerhardt, Kana Wu, Molin Wang, Andrew T Chan, Edward L Giovannucci, Charles S Fuchs, Reiko Nishihara, Xuehong Zhang, Shuji Ogino
Background: Evidence indicates not only carcinogenic effect of cigarette smoking but also its immunosuppressive effect. We hypothesized that the association of smoking with colorectal cancer risk might be stronger for tumors with lower anti-tumor adaptive immune response. Methods: During follow-up of 134 981 participants (3 490 851 person-years) in the Nurses' Health Study and Health Professionals Follow-up Study, we documented 729 rectal and colon cancer cases with available data on T-cell densities in tumor microenvironment...
October 11, 2018: Journal of the National Cancer Institute
Keigo Yokoi, Hiroki Harada, Kazuko Yokota, Satoru Ishii, Toshimichi Tanaka, Nobuyuki Nishizawa, Masashi Shimazu, Ken Kojo, Hirohisa Miura, Takahiro Yamanashi, Takeo Sato, Takatoshi Nakamura, Masahiko Watanabe, Keishi Yamashita
BACKGROUND: Cysteine dioxygenase type 1 (CDO1) acts as a tumor suppressor gene, and its expression is regulated by promoter DNA methylation in human cancer. The metabolic product mediated by CDO1 enzyme increases mitochondrial membrane potential (MMP), putatively representing chemoresistance. The aim of this study is to investigate the functional relevance of CDO1 gene in colon cancer with chemotherapy. PATIENTS AND METHODS: We investigated 170 stage III colon cancer patients for CDO1 methylation by using quantitative methylation-specific polymerase chain reaction (PCR)...
October 11, 2018: Annals of Surgical Oncology
George Jour, Varshini Vasudevaraja, Victor G Prieto, Matija Snuderl, Carlos A Torres-Cabala, Rami Al-Rohil, Erik P Sulman, Leomar Y Ballester, Phyu P Aung
Superficial/cutaneous malignant peripheral nerve sheath tumor is a rare soft tissue neoplasm that shares morphological, immunohistochemical, and molecular features with spindle/desmoplastic melanoma. We aimed to identify a methylome signature to distinguish these two entities. We analyzed 15 cases of spindle/desmoplastic melanoma and 15 cases of cutaneous malignant peripheral nerve sheath tumor in 23 men and 7 women. DNA from formalin-fixed, paraffin-embedded tissues was extracted and processed using the Illumina Infinium Methylation EPIC array interrogating 866,562 CpG sites...
October 11, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Nooshin Salehi, Adam K Yuan, Gizelle Stevens, Ruby Koshy, Walter F Klein
BACKGROUND Anti-N-methyl D-Aspartate (anti-NMDA) receptor encephalitis is a rare autoimmune panencephalitis that typically presents with acute psychiatric disturbances and neurological deficits. Anti-NMDA receptor encephalitis is associated with certain tumors, most commonly ovarian teratomas. First-line therapy typically involves immunotherapy and tumor resection, if present, with up to 53% of patients experiencing improvement within 4 weeks. Cardiac arrhythmias and increased intracranial pressure have been reported in anti-NMDA receptor encephalitis, but these complications have usually been self-limited...
October 12, 2018: American Journal of Case Reports
Vijay Pandey, Baocheng Wang, Chakrabhavi Dhananjaya Mohan, Ainiah Rushdiana Raquib, Shobith Rangappa, Venkatachalaiah Srinivasa, Julian E Fuchs, Kesturu S Girish, Tao Zhu, Andreas Bender, Lan Ma, Zhinan Yin, Basappa, Kanchugarakoppal S Rangappa, Peter E Lobie
Human BCL-2-associated death promoter (hBAD) is an apoptosis-regulatory protein mediating survival signals to carcinoma cells upon phosphorylation of Ser99, among other residues. Herein, we screened multiple small-molecule databases queried in a Laplacian-modified naive Bayesian-based cheminformatics platform and identified a Petasis reaction product as a site-specific inhibitor for hBAD phosphorylation. Based on apoptotic efficacy against mammary carcinoma cells, N -cyclopentyl-3-((4-(2,3-dichlorophenyl) piperazin-1-yl) (2-hydroxyphenyl) methyl) benzamide (NPB) was identified as a potential lead compound...
October 11, 2018: Proceedings of the National Academy of Sciences of the United States of America
Henry D McCann, Charlotte E Johnson, Rachel J Errington, D Mark Davies, Elaine A Dunlop, Andrew R Tee
To find new anti-cancer drug therapies, we wanted to exploit homeostatic vulnerabilities within Tuberous Sclerosis Complex 2 (TSC2)-deficient cells with mechanistic target of rapamycin complex 1 (mTORC1) hyperactivity. We show that nelfinavir and mefloquine synergize to selectively evoke a cytotoxic response in TSC2-deficient cell lines with mTORC1 hyperactivity. We optimize the concentrations of nelfinavir and mefloquine to a clinically viable range that kill cells that lack TSC2, while wild-type cells tolerate treatment...
October 10, 2018: Cancers
Chin-Sheng Hung, Sheng-Chao Wang, Yi-Ting Yen, Tzong-Huei Lee, Wu-Che Wen, Ruo-Kai Lin
Lung and breast cancer are the leading causes of mortality in women worldwide. The discovery of molecular alterations that underlie these two cancers and corresponding drugs has contributed to precision medicine. We found that CCND2 is a common target in lung and breast cancer. Hypermethylation of the CCND2 gene was reported previously; however, no comprehensive study has investigated the clinical significance of CCND2 alterations and its applications and drug discovery. Genome-wide methylation and quantitative methylation-specific real-time polymerase chain reaction (PCR) showed CCND2 promoter hypermethylation in Taiwanese breast cancer patients...
October 10, 2018: International Journal of Molecular Sciences
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