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J Laco, H Kovarikova, M Chmelarova, H Vosmikova, K Sieglova, I Bubancova, P Dundr, K Nemejcova, J Michalek, P Celakovsky, R Mottl, I Sirak, M Vosmik, I Marek, T Geryk, J Mejzlik, J Satankova, A Ryska
The aim of this study was a detailed clinicopathological investigation of sinonasal NUT midline carcinoma (NMC), including analysis of DNA methylation and microRNA (miRNA) expression. Three (5%) cases of NMC were detected among 56 sinonasal carcinomas using immunohistochemical screening and confirmed by fluorescence in situ hybridization. The series comprised 2 males and 1 female, aged 46, 60, and 65 years. Two tumors arose in the nasal cavity and one in the maxillary sinus. The neoplasms were staged pT1, pT3, and pT4a (all cN0M0)...
2018: Neoplasma
Chen Wang, Wenxia Ma, Rong Wei, Xiaoqin Zhang, Ningning Shen, Lifang Shang, Li E, Ying Wang, Lifang Gao, Xin Li, Bin Wang, Yaping Zhang, Aiping Du
Checkpoint with Forkhead-associated and Ring finger domains (CHFR) is a G2/M checkpoint and tumor-suppressor gene. Recent publications showed the correlation of CHFR promoter methylation with clinicopathological significance of non-small cell lung cancer (NSCLC), however, the results remain inconsistent. The aim of this study is to investigate the Clinicopathological significance of CHFR promoter methylation in NSCLC with a meta-analysis. A total of nine studies were included in the meta-analysis that 816 patients were involved...
December 12, 2017: Oncotarget
Zhulei Sun, Juncai Liu, Hong Jing, Shu-Xiao Dong, Jiang Wu
The Checkpoint with Forkhead-associated and Ring finger domains (CHFR) is a mitotic checkpoint and tumor-suppressor gene, its loss contributes tumorigenesis of epithelial cancers including colorectal carcinoma (CRC). The diagnostic and prognostic value of CHFR promoter hypermethylation in CRC remains unclear. This study aimed to conduct a meta-analysis and literature review and investigate clinicopathological significance of CHFR promoter hypermethylation in CRC. The following online database were used: PubMed, EMBASE, and Web of Science up to March 2017...
October 24, 2017: Oncotarget
Jing-Dong Zhou, Ting-Juan Zhang, Xi-Xi Li, Ji-Chun Ma, Hong Guo, Xiang-Mei Wen, Dong-Ming Yao, Wei Zhang, Jiang Lin, Jun Qian
CHFR acts as a tumor suppressor gene, which is frequently inactivated caused by its promoter hypermethylation in various solid tumors. Although a recent study showed that CHFR hypermethylation was a frequent event in acute myeloid leukemia (AML) and correlated with adverse clinical outcome, herein, we found that CHFR methylation was a rare event in patients with myeloid malignancies (including AML, chronic myeloid leukemia, and myelodysplastic syndromes), but its expression may serve as an independent prognostic biomarker in AML...
November 8, 2017: Journal of Cellular Physiology
M Overman, L Adam, K Raghav, J Wang, B Kee, D Fogelman, C Eng, E Vilar, R Shroff, A Dasari, R Wolff, J Morris, Enusha Karunasena, R Pisanic, N Azad, S Kopetz
Background: Hypermethylation of promoter CpG islands (CIMP) represents a unique pathway for the development of colorectal cancer (CRC), characterized by lack of chromosomal instability and a low rate of adenomatous polyposis coli (APC) mutations, which have both been correlated with taxane resistance. Similarly, small bowel adenocarcinoma (SBA), a rare tumor, also has a low rate of APC mutations. This phase II study evaluated taxane sensitivity in SBA and CIMP-high CRC. Patients and Methods: The primary objective was Response Evaluation Criteria in Solid Tumors version 1...
October 23, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Zhulei Sun, Juncai Liu, Hong Jing, Shu-Xiao Dong, Jiang Wu
The Checkpoint with Forkhead-associated and Ring finger domains (CHFR) is a mitotic checkpoint and tumor-suppressor gene, its loss contributes tumorigenesis of epithelial cancers including colorectal carcinoma (CRC). The diagnostic and prognostic value of CHFR promoter hypermethylation in CRC remains unclear. This study aimed to conduct a meta-analysis and literature review and investigate clinicopathological significance of CHFR promoter hypermethylation in CRC. The following online database were used: PubMed, EMBASE, and Web of Science up to March 2017...
July 20, 2017: Oncotarget
Leandro Castellano, Aleksandra Dabrowska, Loredana Pellegrino, Silvia Ottaviani, Paul Cathcart, Adam E Frampton, Jonathan Krell, Justin Stebbing
MicroRNA 26a (miR-26a) reduces cell viability in several cancers, indicating that miR-26a could be used as a therapeutic option in patients. We demonstrate that miR-26a not only inhibits G1-S cell cycle transition and promotes apoptosis, as previously described, but also regulates multiple cell cycle checkpoints. We show that sustained miR-26a over-expression in both breast cancer (BC) cell lines and mouse embryonic fibroblasts (MEFs) induces oversized cells containing either a single-large nucleus or two nuclei, indicating defects in mitosis and cytokinesis...
May 5, 2017: Nucleic Acids Research
Jan Laco, Marcela Chmelařová, Hana Vošmiková, Kateřina Sieglová, Ivana Bubancová, Pavel Dundr, Kristýna Němejcová, Jaroslav Michálek, Petr Čelakovský, Radovan Mottl, Igor Sirák, Milan Vošmik, Aleš Ryška
The aim of the study was detailed clinicopathological investigation of SMARCB1/INI1-deficient sinonasal carcinomas, including molecular genetic analysis of mutational status and DNA methylation of selected protooncogenes and tumor suppressor genes by means of next generation sequencing (NGS) and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). A total of 4/56 (7%) cases of SMARCB1/INI1-deficient carcinomas were detected among 56 sinonasal carcinomas diagnosed over a 19year period using immunohistochemical screening...
February 2017: Pathology, Research and Practice
Hua Shi, Xiaojing Wang, Jianbo Wang, Jundi Pan, Junwei Liu, Bin Ye
BACKGROUND: The association between the hypermethylation of CHFR gene and gastric cancer risk has been investigated by a number of studies. However, the sample size of the majority of these studies was very small. To get a more a convincing conclusion, here we performed a meta-analysis of the previously published studies to assess the association between CHFR methylation and the risk of gastric cancer. METHODS: Eligible studies were identified by searching the MEDLINE/PubMed, Embase, and Web of Science databases before May 2016 without any language restriction...
2016: OncoTargets and Therapy
Myungjin Kim, Young Eun Kwon, Jae Oh Song, Sung Jun Bae, Jae Hong Seol
SIRT1, the NAD(+)-dependent protein deacetylase, controls cell-cycle progression and apoptosis by suppressing p53 tumour suppressor. Although SIRT1 is known to be phosphorylated by JNK1 upon oxidative stress and subsequently down-regulated, it still remains elusive how SIRT1 stability and activity are controlled. Here, we have unveiled that CHFR functions as an E3 Ub-ligase of SIRT1, responsible for its proteasomal degradation under oxidative stress conditions. CHFR interacts with and destabilizes SIRT1 by ubiquitylation and subsequent proteolysis...
November 24, 2016: Scientific Reports
Haniyeh Eyvani, Farima Moghaddaskho, Majid Kabuli, Ali Zekri, Majid Momeny, Javad Tavakkoly-Bazzaz, Kamran Alimoghaddam, Ardeshir Ghavamzadeh, Seyed H Ghaffari
AIMS: Cell cycle dysregulation is important in tumorigenesis. Transcriptional silencing of cell cycle regulatory genes, due to DNA methylation, is a common epigenetic event in malignancies. As2O3 has been shown to induce cell cycle arrest and also to be a potential hypomethylating agent. Our study aimed to investigate DNA methylation patterns of cell cycle regulatory genes promoters, the effects of Arsenic trioxide (As2O3) on the methylated genes and cell cycle distribution in colorectal cancer (CRC) cell lines...
December 15, 2016: Life Sciences
Maria Costales, Alejandro López-Hernández, Cristina García-Inclán, Blanca Vivanco, Fernando López, José Luis Llorente, Mario A Hermsen
OBJECTIVE: To identify epigenetic events in intestinal-type sinonasal adenocarcinoma (ITAC) and sinonasal squamous cell carcinoma (SNSCC) and to evaluate their relation to clinicopathologic features and follow-up data. STUDY DESIGN: Retrospective study. SETTING: Academic research hospital. SUBJECTS AND METHODS: The methylation status of 23 genes in 50 ITACs and 32 SNSCCs was analyzed by methylation-specific multiplex ligation-dependent probe amplification and its relation to clinicopathologic features and follow-up data...
November 2016: Otolaryngology—Head and Neck Surgery
Kai Ma, Baoping Cao, Mingzhou Guo
Esophageal cancer is one of the most common malignancies in the world. Squamous cell carcinoma accounts for approximately 90 % of esophageal cancer cases. Genetic and epigenetic changes have been found to accumulate during the development of various cancers, including esophageal squamous carcinoma (ESCC). Tobacco smoking and alcohol consumption are two major risk factors for ESCC, and both tobacco and alcohol were found to induce methylation changes in ESCC. Growing evidence demonstrates that aberrant epigenetic changes play important roles in the multiple-step processes of carcinogenesis and tumor progression...
2016: Clinical Epigenetics
Janek Kibat, Thomas Schirrmann, Matthias J Knape, Saskia Helmsing, Doris Meier, Michael Hust, Christoph Schröder, Daniela Bertinetti, Gerhard Winter, Khalid Pardes, Mia Funk, Andrea Vala, Nathalia Giese, Friedrich W Herberg, Stefan Dübel, Jörg D Hoheisel
Many diagnostic and therapeutic concepts require antibodies of high specificity. Recombinant binder libraries and related selection approaches allow the efficient isolation of antibodies against almost every target of interest. Nevertheless, it cannot be guaranteed that selected antibodies perform well and interact specifically enough with analytes unless an elaborate characterisation is performed. Here, we present an approach to shorten this process by combining the selection of suitable antibodies with the identification of informative target molecules by means of antibody microarrays, thereby reducing the effort of antibody characterisation by concentrating on relevant molecules...
September 25, 2016: New Biotechnology
Berta Luzón-Toro, Marta Bleda, Elena Navarro, Luz García-Alonso, Macarena Ruiz-Ferrer, Ignacio Medina, Marta Martín-Sánchez, Cristina Y Gonzalez, Raquel M Fernández, Ana Torroglosa, Guillermo Antiñolo, Joaquin Dopazo, Salud Borrego
BACKGROUND: The molecular mechanisms leading to sporadic medullary thyroid carcinoma (sMTC) and juvenile papillary thyroid carcinoma (PTC), two rare tumours of the thyroid gland, remain poorly understood. Genetic studies on thyroid carcinomas have been conducted, although just a few loci have been systematically associated. Given the difficulties to obtain single-loci associations, this work expands its scope to the study of epistatic interactions that could help to understand the genetic architecture of complex diseases and explain new heritable components of genetic risk...
2015: BMC Medical Genomics
Lin-Yu Lu, Xiaochun Yu
DNA damage response is required for male fertility. DNA damage repair mediates recombination between homologous chromosomes in meiotic prophase, which is essential for proper chromosome segregation during meiotic division. Interestingly, some DNA damage response proteins are also required for the survival of premeiotic germ cells, but their roles in these cells are still unclear. CHFR was recently shown to participate in DNA damage response, but it remains to be established if CHFR is required for male fertility...
2015: Cell Cycle
Li Gao, Fang Liu, Hui Zhang, Junzhong Sun, Yigai Ma
The CpG island of the promoter region of the checkpoint with fork-head associated and ring finger gene (CHFR), a mitotic checkpoint gene with tumor-suppressor functions, is hypermethylated in various human cancers. The objective of this study was to evaluate the frequency of aberrant CHFR promoter methylation in acute myeloid leukemia (AML) patients in an attempt to improve prognostication. CHFR promoter methylation levels were analyzed in 358 newly diagnosed AML cases and 30 healthy donors by the use of quantitative methylation-specific polymerase chain reaction...
February 2016: Genes, Chromosomes & Cancer
Seth A Brodie, Ge Li, Donald Harvey, Fadlo R Khuri, Paula M Vertino, Johann C Brandes
The mitotic checkpoint protein CHFR has emerged as a major mediator of taxane resistance in cancer. Here we show that CHFR's PAR-binding zinc finger domain (PBZ) mediates a protein interaction with poly-ADP ribosylated PARP1 leading to stabilization of CHFR. Disruption of the CHFR-PARP1 interaction through either PARP1 shRNA-mediated knockdown or overexpression of a PBZ domain peptide induces loss of CHFR protein expression. In an attempt to exploit this observation therapeutically, and to develop compounds with synthetic lethality in combination with taxanes, we performed a high-throughput computational screen of 5,256,508 chemical structures against the published crystal structure of the CHFR PBZ domain to identify candidate small molecule CHFR protein-protein interaction inhibitors...
October 13, 2015: Oncotarget
Zifang Quan, Ni Ye, Zhongxiang Hao, Caifang Wen, Hong Liao, Manli Zhang, Lu Luo, Sanjie Cao, Xintian Wen, Rui Wu, Qigui Yan
The aim of the present study was to investigate the promoter methylation status and mRNA expression of goat tumor‑associated genes, in addition to the mRNA expression of DNA methyltransferase genes in enzootic nasal tumors (ENT). Methylation‑specific polymerase chain reaction and SYBR Green reverse transcription‑quantitative polymerase chain reaction were used to detect the methylation status and the mRNA expression levels of DNA methyltransferases (DNMTs), O6‑methylguanine‑DNA methyltransferase (MGMT), the tumor suppressor genes P73, P53, GADD45G, CHFR and THBS1, the transcription factor CEBPA, the proto‑oncogenes KRAS, NRAS and C‑myc and EGFR in 24 nasal tumor tissue samples and 20 normal nasal epithelia tissue samples...
October 2015: Molecular Medicine Reports
Haiyan Chen, Tingguo Zhang, Yan Sheng, Cheng Zhang, Yunfei Peng, Xiao Wang, Cuijuan Zhang
DNA methylation is considered as a significant mechanism that silences tumor suppressor genes (TSGs) and could be used in the early diagnosis of cancer. Histone modifications often work together with DNA methylation; however, how these epigenetic alterations regulate TSGs remains unclear. Here, we determined the methylation status of ten TSGs (3OST2, ppENK, CHFR, LKB1, THBS1, HIC1, SLIT2, EDNRB, COX2, and CLDN7) in hepatocellular carcinoma (HCC) and corresponding noncancerous tissues. Methylation profiling revealed that four genes had very high frequencies of methylation in HCCs, but interestingly, similar high frequencies were also detected in corresponding noncancerous tissues (97...
2015: Journal of Cancer
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