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Amanda L Lumsden, Richard L Young, Nektaria Pezos, Damien J Keating
BACKGROUND: Huntingtin-associated Protein 1 (HAP1) is expressed in neurons and endocrine cells, and is critical for postnatal survival in mice. HAP1 shares a conserved "HAP1_N" domain with TRAfficking Kinesin proteins TRAK1 and TRAK2 (vertebrate), Milton (Drosophila) and T27A3.1 (C. elegans). HAP1, TRAK1 and TRAK2 have a degree of common function, particularly regarding intracellular receptor trafficking. However, TRAK1, TRAK2 and Milton (which have a "Milt/TRAK" domain that is absent in human and rodent HAP1) differ in function to HAP1 in that they are mitochondrial transport proteins, while HAP1 has emerging roles in starvation response...
October 13, 2016: BMC Evolutionary Biology
Moon Kyung Joo, Jong-Jae Park, Hoon Jai Chun
Homeobox genes, including HOX and non-HOX genes, have been identified to be expressed aberrantly in solid tumors. In gastrointestinal (GI) cancers, most studies have focused on the function of non-HOX genes including caudal-related homeobox transcription factor 1 (CDX1) and CDX2. CDX2 is a crucial factor in the development of pre-cancerous lesions such as Barrett's esophagus or intestinal metaplasia in the stomach, and its tumor suppressive role has been investigated in colorectal cancers. Recently, several HOX genes were reported to have specific roles in GI cancers; for example, HOXA13 in esophageal squamous cell cancer and HOXB7 in stomach and colorectal cancers...
October 7, 2016: World Journal of Gastroenterology: WJG
Aileen S W Li, Yusuke Marikawa
Valproic acid (VPA), an antiepileptic drug, is a teratogen that causes neural tube and axial skeletal defects, although the mechanisms are not fully understood. We previously established a gastrulation model using mouse P19C5 stem cell embryoid bodies (EBs), which exhibits axial patterning and elongation morphogenesis in vitro. Here, we investigated the effects of VPA on the EB axial morphogenesis to gain insights into its teratogenic mechanisms. Axial elongation and patterning of EBs were inhibited by VPA at therapeutic concentrations...
September 29, 2016: Reproductive Toxicology
T Rau
The pathogenesis of precursor lesions of gastrointestinal tumors is manifested in many ways. In the esophagus an aberrant genetic expression of intestinal transcription factors, such as CDX2 is initiated by local environment factors. During the subsequent dysplasia to carcinoma sequence, chromosomal gain and loss of genes occurs. A 4-color fluorescence in situ hybridization (FISH) assay can be applied in dysplasia as well as in Barrett's adenocarcinoma to define prognostic marker combinations. In the gastric carcinogenesis sequence the gene expression of CDX1 is regulatively dependent on an interplay between inflammation and promotor methylation...
September 14, 2016: Der Pathologe
Mio Matsui, Kosuke Tanaka, Naoki Higashiguchi, Hisato Okawa, Yoichi Yamada, Ken Tanaka, Soichiro Taira, Tomoko Aoyama, Misaki Takanishi, Chika Natsume, Yuuki Takakura, Norihisa Fujita, Takeshi Hashimoto, Takashi Fujita
Mild exposure to ultraviolet (UV) radiation is also harmful and hazardous to the skin and often causes a photosensitivity disorder accompanied by sunburn. To understand the action of UV on the skin we performed a microarray analysis to isolate UV-sensitive genes. We show here that UV irradiation promoted sunburn and downregulated filaggrin (Flg); fucoxanthin (FX) exerted a protective effect. In vitro analysis showed that UV irradiation of human dermal fibroblasts caused production of intracellular reactive oxygen species (ROS) without cellular toxicity...
September 2016: Journal of Pharmacological Sciences
Hao Zheng, Yuan Yang, Meng-Chao Wang, Sheng-Xian Yuan, Tao Tian, Jun Han, Jun-Sheng Ni, Jian Wang, Hao Xing, Wei-Ping Zhou
The caudal-type homeobox 1 (CDX1) transcription factor is a member of the caudal-related homeobox transcription factor gene family and has been reported to be down-regulated in a variety of cancers. However, the expression status and significance of CDX1 in hepatocellular carcinoma (HCC) is still controversial, and little is known about the role of CDX1 in HCC·In our previous study, we investigated the expression and clinical significance of CDX1 in HCC samples from 313 HCC patients. We found CDX1 was strikingly down-regulated in HCC samples...
September 2016: Surgical Oncology
Wendy Onstenk, Anieta M Sieuwerts, Bianca Mostert, Zarina Lalmahomed, Joan B Bolt-de Vries, Anne van Galen, Marcel Smid, Jaco Kraan, Mai Van, Vanja de Weerd, Raquel Ramírez-Moreno, Katharina Biermann, Cornelis Verhoef, Dirk J Grünhagen, Jan N M IJzermans, Jan W Gratama, John W M Martens, John A Foekens, Stefan Sleijfer
BACKGROUND: CTCs are a promising alternative for metastatic tissue biopsies for use in precision medicine approaches. We investigated to what extent the molecular characteristics of circulating tumor cells (CTCs) resemble the liver metastasis and/or the primary tumor from patients with metastatic colorectal cancer (mCRC). RESULTS: The CTC profiles were concordant with the liver metastasis in 17/23 patients (74%) and with the primary tumor in 13 patients (57%). The CTCs better resembled the liver metastasis in 13 patients (57%), and the primary tumor in five patients (22%)...
June 20, 2016: Oncotarget
Nils-Holger Zschemisch, Inga Brüsch, Anne-Sophie Hambusch, André Bleich
Genetic analysis in the IL10-deficient mouse model revealed a modifier locus of experimental inflammatory bowel disease (IBD) on chromosome 18, with the allele of the strain C3H/HeJBir (C3Bir) conferring resistance and the allele of C57BL/6J (B6) conferring susceptibility. Differential Cd14 expression was associated with this background specific susceptibility to intestinal inflammation. Polymorphisms of the Cd14 promoter were found to be likely causative for strain specific expression, and Cd14-knockout mice revealed a protective role of this gene-product in experimental IBD...
2016: PloS One
Ashish Kumar, M K Thakur
Previously, we reported differential expression of Presenilin (PS)1 and 2 and epigenetic modifications of their gene promoter in the cerebral cortex of mice during development. We identified the crucial role of DNA methylation and H3K9/14 acetylation in stage specific PS expression during brain development. Interestingly, we noted differential DNA methylation in putative binding sites of transcription factors considered pivotal for brain development. This prompted us to study the binding of transcription factors to cis-acting elements of PS1 and PS2 promoter in the cerebral cortex of mice during development...
August 15, 2016: Neuroscience Letters
Myrto Dimopoulou, Aart Verhoef, Bennard van Ravenzwaay, Ivonne M C M Rietjens, Aldert H Piersma
Embryotoxic responses are critically dependent on the timing of exposure during embryo development. Here, we examined the time- dependent developmental effects in rat embryos exposed to flusilazole (FLU), and their link to retinoic acid (RA) mediated pathways. To this end, we assessed the effects of 4h exposure of rat embryos in vitro to 300μM FLU during four developmental time windows (0-4, 4-8, 24-28 and 44-48h), evaluating morphological parameters, expression and localization of five genes directly or indirectly linked with the RA pathway...
September 2016: Reproductive Toxicology
Xiao Bing Tang, Tao Zhang, Wei Lin Wang, Zheng Wei Yuan, Yu Zuo Bai
Background. The objectives of this study were to determine the spatiotemporal distribution of human caudal-type homeobox proteins CDX1, CDX2 and CDX4 during development of the hindgut and anorectum in the embryo and to explore the possible roles of CDX genes during morphogenesis of the hindgut and anorectum. Methods. Embryos (89) were cut into sections serially and sagittally. From gestation weeks 4-9, CDX1, CDX2 and CDX4 proteins were detected on the caudal midline by immunohistochemical staining. Results...
2016: PeerJ
Soichiro Sue, Wataru Shibata, Eri Kameta, Takeshi Sato, Yasuaki Ishii, Hiroaki Kaneko, Haruo Miwa, Tomohiko Sasaki, Toshihide Tamura, Masaaki Kondo, Shin Maeda
BACKGROUND: Helicobacter pylori induces chronic inflammation and intestinal metaplasia (IM) through genetic and epigenetic changes and activation of intracellular signaling pathways that contribute to gastric carcinogenesis. However, the precise mechanism of IM in gastric carcinogenesis has not been fully elucidated. We previously found that intestine-specific homeobox (ISX) mRNA expression increased in organoids cultured from Helicobacter-infected mouse mucosa. In this study, we elucidate the role of ISX in the development of IM and gastric carcinogenesis...
October 2016: Journal of Gastroenterology
Cheol Min Shin, Nayoung Kim, Hyun Chang, Joo Sung Kim, Dong Ho Lee, Hyun Chae Jung
BACKGROUND: Changes in CDX1/CDX2 in gastric mucosae following Helicobacter pylori eradication have not been clarified yet. AIMS: To evaluate the changes in CDX1/CDX2 expression after H. pylori eradication, in relation to the reversibility of intestinal metaplasia (IM). METHODS: Time course of CDX1/CDX2 expressions was investigated in 176 subjects with various gastroduodenal disorders. Among them, 132 patients were H. pylori positives; H. pylori were eradicated in 107 of them; 13 failed to eradicate; and 12 did not receive H...
April 2016: Digestive Diseases and Sciences
Da Hyun Jung, Jie-Hyun Kim, Yong Chan Lee, Sang Kil Lee, Sung Kwan Shin, Jun Chul Park, Hyun Soo Chung, Hyunki Kim, Hoguen Kim, Yong Hoon Kim, Jae Jun Park, Young Hoon Youn, Hyojin Park
PURPOSE: The importance of Helicobacter pylori eradication after endoscopic resection (ER) of gastric neoplasms remains controversial. In this study, we clarified the importance of H. pylori eradication for metachronous lesions after ER. MATERIALS AND METHODS: This study included 3,882 patients with gastric neoplasms who underwent ER. We included patients infected with H. pylori who received eradication therapy. Among them, 34 patients with metachronous lesions after ER and 102 age- and sex-matched patients (nonmetachronous group) were enrolled...
December 2015: Journal of Gastric Cancer
Chen Chen, Hao Peng, Xiaojie Huang, Ming Zhao, Zhi Li, Ni Yin, Xiang Wang, Fenglei Yu, Bangliang Yin, Yunchang Yuan, Qianjin Lu
Esophageal squamous cell carcinoma (ESCC) is the leading cause of cancer-related death worldwide. Previous studies have suggested that DNA methylation involved in the development of ESCC. However, the precise mechanisms underlying the regulation and maintenance of the methylome as well as their relationship with ESCC remain poorly understood. Herein, we used methylated DNA immunoprecipitation sequencing (MeDIP-Seq) and RNA-Seq to investigate whole-genome DNA methylation patterns and the genome expression profiles in ESCC samples...
January 26, 2016: Oncotarget
Stephanie Holst, Anna J M Deuss, Gabi W van Pelt, Sandra J van Vliet, Juan J Garcia-Vallejo, Carolien A M Koeleman, André M Deelder, Wilma E Mesker, Rob A Tollenaar, Yoann Rombouts, Manfred Wuhrer
Various cancers such as colorectal cancer (CRC) are associated with alterations in protein glycosylation. CRC cell lines are frequently used to study these (glyco)biological changes and their mechanisms. However, differences between CRC cell lines with regard to their glycosylation have hitherto been largely neglected. Here, we comprehensively characterized the N-glycan profiles of 25 different CRC cell lines, derived from primary tumors and metastatic sites, in order to investigate their potential as glycobiological tumor model systems and to reveal glycans associated with cell line phenotypes...
January 2016: Molecular & Cellular Proteomics: MCP
Yong-guo Zhang, Shaoping Wu, Rong Lu, David Zhou, Jingsong Zhou, Geert Carmeliet, Elaine Petrof, Erika C Claud, Jun Sun
The breakdown of the intestinal barrier is a common manifestation of many diseases. Recent evidence suggests that vitamin D and its receptor VDR may regulate intestinal barrier function. Claudin-2 is a tight junction protein that mediates paracellular water transport in intestinal epithelia, rendering them "leaky". Using whole body VDR(-/-) mice, intestinal epithelial VDR conditional knockout (VDR(ΔIEC)) mice, and cultured human intestinal epithelial cells, we demonstrate here that the CLDN2 gene is a direct target of the transcription factor VDR...
2015: Scientific Reports
Anna Karpathakis, Harpreet Dibra, Chistodoulos Pipinikas, Andrew Feber, Tiffany Morris, Joshua Francis, Dahmane Oukrif, Dalvinder Mandair, Marinos Pericleous, Mullan Mohmaduvesh, Stefano Serra, Olagunju Ogunbiyi, Marco Novelli, TuVinh Luong, Sylvia L Asa, Matthew Kulke, Christos Toumpanakis, Tim Meyer, Martyn Caplin, Matthew Meyerson, Stephan Beck, Christina Thirlwell
PURPOSE: Small intestinal neuroendocrine tumors (SINET) are the commonest malignancy of the small intestine; however, underlying pathogenic mechanisms remain poorly characterized. Whole-genome and -exome sequencing has demonstrated that SINETs are mutationally quiet, with the most frequent known mutation in the cyclin-dependent kinase inhibitor 1B gene (CDKN1B) occurring in only ∼8% of tumors, suggesting that alternative mechanisms may drive tumorigenesis. The aim of this study is to perform genome-wide molecular profiling of SINETs in order to identify pathogenic drivers based on molecular profiling...
January 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Yuichiro Hatano, Katsunori Semi, Kyoichi Hashimoto, Myeong Sup Lee, Akihiro Hirata, Hiroyuki Tomita, Toshiya Kuno, Manabu Takamatsu, Koji Aoki, Makoto M Taketo, Young-Joon Kim, Akira Hara, Yasuhiro Yamada
The forced reduction of global DNA methylation suppresses tumor development in several cancer models in vivo. Nevertheless, the mechanisms underlying these suppressive effects remain unclear. In this report, we describe our findings showing that a genome-wide reduction in the DNA methylation levels induces cellular differentiation in association with decreased cell proliferation in Apc (Min/+) mouse colon tumor cells in vivo. Colon tumor-specific DNA methylation at Cdx1 is reduced in the DNA-hypomethylated tumors accompanied by Cdx1 derepression and an increased expression of intestinal differentiation-related genes...
July 2015: Carcinogenesis
Emir Ahmed Sajjad, Katarzyna Sikora, Tomasz Paciejewski, Filip Garbicz, Wiktor Paskal, Milena Szacht, Wieslawa Grajkowska, Pawel Krzysztof Włodarski
Mesenchymal chondrosarcoma is a rare tumor of cartilaginous origin characterized by its bimorphic pattern composed of highly undifferentiated small round cells separated by islands of well-differentiated hyaline cartilage. It exhibits higher malignancy and earlier occurrence in comparison to classic chondrosarcomas. Recently identified HEY1-NCOA2 and IRF2BP2-CDX1 gene fusions confirm their distinct molecular origin and pose a promising diagnostic marker. The majority of cases arise from craniofacial bones. In this study, we present a rare case of mesenchymal chondrosarcoma encompassed within the brain parenchyma of the frontal lobe without any dural or bone attachment...
September 2015: Clinical Neuropathology
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