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Zhou-Feng Chen, Zhi-Ming Huang, Hai-Bo Xue, Xiu-Qing Lin, Ren-Ping Chen, Meng-Jun Chen, Rui-Fang Jin
The mechanism underlying the metastasis of gastric cancer (GC) cells remains elusive. REG3A is considered an oncogene in various cancers, but in GC its role is unclear. Here, we report that the expression of REG3A was significantly increased in the tumor tissues of patients with GC compared with the matched normal tissues. Knockdown of REG3A induced by specific small interfering RNA (siRNA) significantly repressed the proliferation of GC cells for 24 h or 48 h. Moreover, knockdown of REG3A significantly suppressed the migration, invasion, and adhesion of GC cells in vitro...
2017: OncoTargets and Therapy
Katie S Lennard, Ryan W Goosen, Jonathan M Blackburn
The relevance of specific microbial colonisation to colorectal cancer (CRC) disease pathogenesis is increasingly recognised, but our understanding of possible underlying molecular mechanisms that may link colonisation to disease in vivo remains limited. Here, we investigate the relationships between the most commonly studied CRC-associated bacteria (Enterotoxigenic Bacteroides fragilis, pks+ Escherichia coli, Fusobacterium spp., afaC+ E. coli, Enterococcus faecalis & Enteropathogenic E. coli) and altered transcriptomic and methylation profiles of CRC patients, in order to gain insight into the potential contribution of these bacteria in the aetiopathogenesis of CRC...
2016: PloS One
Yelin Wu, Yanchun Quan, Yuanqi Liu, Keiwei Liu, Hongquan Li, Ziwei Jiang, Tian Zhang, Hu Lei, Katherine A Radek, Dongqing Li, Zhenhua Wang, Jilong Lu, Wang Wang, Shizhao Ji, Zhaofan Xia, Yuping Lai
Dysregulated inflammatory responses are known to impair wound healing in diabetes, but the underlying mechanisms are poorly understood. Here we show that the antimicrobial protein REG3A controls TLR3-mediated inflammation after skin injury. This control is mediated by REG3A-induced SHP-1 protein, and acts selectively on TLR3-activated JNK2. In diabetic mouse skin, hyperglycaemia inhibits the expression of IL-17-induced IL-33 via glucose glycation. The decrease in cutaneous IL-33 reduces REG3A expression in epidermal keratinocytes...
November 10, 2016: Nature Communications
Qing Li, Hao Wang, George Zogopoulos, Qin Shao, Kun Dong, Fudong Lv, Karam Nwilati, Xian-Yong Gui, Adeline Cuggia, Jun-Li Liu, Zu-Hua Gao
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignant tumor. Acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN) are both precursor lesions that lead to the development of PDAC. Reg family proteins (Reg1A, 1B, 3A/G, 4) are a group of calcium-dependent lectins that promote islet growth in response to inflammation and/or injuries. The aim of this study was to establish a role for Reg proteins in the development of PDAC and their clinical value as biomarkers. We found that Reg1A and Reg3A/G were highly expressed in the ADM tissues by immunohistochemistry...
November 22, 2016: Oncotarget
Mauro J Muraro, Gitanjali Dharmadhikari, Dominic Grün, Nathalie Groen, Tim Dielen, Erik Jansen, Leon van Gurp, Marten A Engelse, Francoise Carlotti, Eelco J P de Koning, Alexander van Oudenaarden
To understand organ function, it is important to have an inventory of its cell types and of their corresponding marker genes. This is a particularly challenging task for human tissues like the pancreas, because reliable markers are limited. Hence, transcriptome-wide studies are typically done on pooled islets of Langerhans, obscuring contributions from rare cell types and of potential subpopulations. To overcome this challenge, we developed an automated platform that uses FACS, robotics, and the CEL-Seq2 protocol to obtain the transcriptomes of thousands of single pancreatic cells from deceased organ donors, allowing in silico purification of all main pancreatic cell types...
October 26, 2016: Cell Systems
Ying Ye, Ling Xiao, Su-Juan Wang, Wei Yue, Qiao-Shan Yin, Meng-Yao Sun, Wei Xia, Zhi-Yi Shao, Hong Zhang
Colorectal cancer (CRC) is one of the most common malignancies in the world. Previous studies have investigated the altered expression of regenerating islet-derived 3 alpha (REG3A) in various cancers. We aimed at exploring the biological function and the underlying molecular mechanism of REG3A in CRC. In this study, REG3A was found elevated in CRC compared with normal tissues. Further, high REG3A expression level was correlated with bigger tumor size, poorer differentiation, higher tumor stage and lower survival rate...
January 26, 2016: Oncotarget
Ashley L Kalinski, Rahul Sachdeva, Cynthia Gomes, Seung Joon Lee, Zalak Shah, John D Houle, Jeffery L Twiss
UNLABELLED: Although intra-axonal protein synthesis is well recognized in cultured neurons and during development in vivo, there have been few reports of mRNA localization and/or intra-axonal translation in mature CNS axons. Indeed, previous work indicated that mature CNS axons contain much lower quantities of translational machinery than PNS axons, leading to the conclusion that the capacity for intra-axonal protein synthesis is linked to the intrinsic capacity of a neuron for regeneration, with mature CNS neurons showing much less growth after injury than PNS neurons...
July 15, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Xiulan Liu, Jun Wang, Hongjie Wang, Guoxiao Yin, Yang Liu, Xiang Lei, Ming Xiang
Regenerating gene protein (REG) 3A is a 19 kD secretory pancreas protein with pro-growth function. Previously we demonstrated that overexpression of REG3A, acting as a key molecule for up-regulation of the JAK2/STAT3 pathway, contributed to inflammation-related pancreatic cancer (PaC) development. However the exact network associated with REG3A signaling still remains unclear. Here we determined that exposure of human PaC cells to cytokine IL-6 activated the oncogenic JAK2/STAT3 pathway, which directly upregulated REG3A expression, accelerated cell cycle progression by promoting CyclinD1 expression, and enhancing the expression of the anti-apoptosis Bcl family...
June 28, 2015: Cancer Letters
Kaori Kanemaru, Ayano Matsuyuki, Yoshikazu Nakamura, Kiyoko Fukami
Psoriasis is a chronic inflammatory skin disorder that is accompanied by an imbalance between the proliferation and differentiation of keratinocytes. A number of studies have suggested an association between obesity and severe psoriasis; however, it remains to be clarified whether obesity exacerbates psoriasis. To address this unsolved question, we induced psoriasiform dermatitis in mouse models for obesity. We found that obesity exaggerated the severity of psoriasiform dermatitis induced by topical application of the Toll-like receptor (TLR) 7 agonist, imiquimod...
June 2015: Experimental Dermatology
Yun-Suhk Suh, Jieun Yu, Byung Chul Kim, Boram Choi, Tae-Su Han, Hye Seong Ahn, Seong-Ho Kong, Hyuk-Joon Lee, Woo Ho Kim, Han-Kwang Yang
PURPOSE: The purpose of this study is to investigate differentially expressed genes using DNA microarray between advanced gastric cancer (AGC) with aggressive lymph node (LN) metastasis and that with a more advanced tumor stage but without LN metastasis. MATERIALS AND METHODS: Five sample pairs of gastric cancer tissue and normal gastric mucosa were taken from three patients with T3N3 stage (highN) and two with T4N0 stage (lowN). Data from triplicate DNA microarray experiments were analyzed, and candidate genes were identified using a volcano plot that showed ≥ 2-fold differential expression and were significant by Welch's t test (p < 0...
October 2015: Cancer Research and Treatment: Official Journal of Korean Cancer Association
Jun Wang, Hong Zhou, Yong Han, Xiulan Liu, Min Wang, Xin Wang, Guoxiao Yin, Xu Li, Ming Xiang
UNLABELLED: Pancreatic cancer (PaC) is the fifth leading cause of cancer death in the world, but the molecular mechanisms for its development remain unclear. Regenerating islet-derived protein 3-alpha (Reg3A) has been reported overexpressed in pancreatic inflammation and associated with PaC malignancies, thus believed as a potential target in inflammation-linked pancreatic carcinogenesis. Silencing of suppressor of cytokine signaling SOCS3, a well-known feedback inhibitor of cell proliferation, has been found in many human cancers...
December 2014: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Darragh P O'Brien, Neomal S Sandanayake, Claire Jenkinson, Aleksandra Gentry-Maharaj, Sophia Apostolidou, Evangelia-Ourania Fourkala, Stephane Camuzeaux, Oleg Blyuss, Richard Gunu, Anne Dawnay, Alexey Zaikin, Ross C Smith, Ian J Jacobs, Usha Menon, Eithne Costello, Stephen P Pereira, John F Timms
PURPOSE: Biomarkers for the early detection of pancreatic cancer are urgently needed. The primary objective of this study was to evaluate whether increased levels of serum CA19-9, CA125, CEACAM1, and REG3A are present before clinical presentation of pancreatic cancer and to assess the performance of combined markers for early detection and prognosis. EXPERIMENTAL DESIGN: This nested case-control study within the UKCTOCS included 118 single and 143 serial serum samples from 154 postmenopausal women who were subsequently diagnosed with pancreatic cancer and 304 matched noncancer controls...
February 1, 2015: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Richard Coffey, Hyeyoung Nam, Mitchell D Knutson
It is well known that iron overload can result in pancreatic iron deposition, beta-cell destruction, and diabetes in humans. Recent studies in animals have extended the link between iron status and pancreatic function by showing that iron depletion confers protection against beta-cell dysfunction and diabetes. The aim of the present study was to identify genes in the pancreas that are differentially expressed in response to iron deficiency or overload. Weanling male Sprague-Dawley rats (n = 6/group) were fed iron-deficient, iron-adequate, or iron-overloaded diets for 3 weeks to alter their iron status...
2014: PloS One
Tatsuro Murano, Ryuichi Okamoto, Go Ito, Toru Nakata, Shuji Hibiya, Hiromichi Shimizu, Satoru Fujii, Yoshihito Kano, Tomohiro Mizutani, Shiro Yui, Junko Akiyama-Morio, Yasuhiro Nemoto, Kiichiro Tsuchiya, Tetsuya Nakamura, Mamoru Watanabe
Notch signaling plays an essential role in the proliferation and differentiation of intestinal epithelial cells (IECs). We have previously shown that Notch signaling is up-regulated in the inflamed mucosa of ulcerative colitis (UC) and thereby plays an indispensable role in tissue regeneration. Here we show that in addition to Notch signaling, STAT3 signaling is highly activated in the inflamed mucosa of UC. Forced expression of the Notch target gene Hes1 dramatically enhanced the IL-22-mediated STAT3-dependent transcription in human IECs...
January 17, 2014: Biochemical and Biophysical Research Communications
Mindy Porterfield, Peng Zhao, Haiyong Han, John Cunningham, Kazuhiro Aoki, Daniel D Von Hoff, Michael J Demeure, J Michael Pierce, Michael Tiemeyer, Lance Wells
Sensitive and specific biomarkers for pancreatic cancer are currently unavailable. The high mortality associated with adenocarcinoma of the pancreatic epithelium justifies the broadest possible search for new biomarkers that can facilitate early detection or monitor treatment efficacy. Protein glycosylation is altered in many cancers, leading many to propose that glycoproteomic changes may provide suitable biomarkers. In order to assess this possibility for pancreatic cancer, we have performed an in-depth LC-MS/MS analysis of the proteome and MS(n)-based characterization of the N-linked glycome of a small set of pancreatic ductal fluid obtained from normal, pancreatitis, intraductal papillary mucinous neoplasm (IPMN), and pancreatic adenocarcinoma patients...
February 7, 2014: Journal of Proteome Research
Vanessa Fétaud-Lapierre, Catherine M Pastor, Manuel Jorge-Costa, Denis F Hochstrasser, Denis R Morel, Jean-Louis Frossard, Pierre Lescuyer
UNLABELLED: Acute pancreatitis is an inflammatory disease of the pancreas, which varies greatly in course and severity. Severe forms are associated with serious local and/or systemic complications, and eventually death. The pathobiology of acute pancreatitis is complex. Animal models have been developed to investigate pathobiological processes and identify factors determining disease course. We performed a time-course proteomic analysis using a rat model of severe necrotizing acute pancreatitis induced by taurocholate perfusion in the pancreatic ducts...
June 24, 2013: Journal of Proteomics
S Tonack, C Jenkinson, T Cox, V Elliott, R E Jenkins, N R Kitteringham, W Greenhalf, V Shaw, C W Michalski, H Friess, J P Neoptolemos, E Costello
BACKGROUND: The aims of our study were to identify serum biomarkers that distinguish pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC) patients from benign pancreatic disease patients and healthy subjects, and to assess the effects of jaundice on biomarker performance. METHODS: Isobaric tags for relative and absolute quantification were used to compare pooled serum and pancreatic juice samples from a test set of 59 and 25 subjects, respectively. Validation was undertaken in 113 independent subjects...
May 14, 2013: British Journal of Cancer
Atle van Beelen Granlund, Ann Elisabet Østvik, Øystein Brenna, Sverre H Torp, Bjørn I Gustafsson, Arne Kristian Sandvik
The regenerating islet-derived (REG) gene family encodes a group of proteins highly expressed in several human pathologies, many of which are associated with epithelial inflammation. All human family members, namely REG1A, REG1B, REG3A and REG4, are closely related in genomic sequence and all are part of the c-type lectin superfamily. REGs are highly expressed during inflammatory bowel disease (IBD)-related colonic inflammation and the in vivo expression pattern of REG1A and REG4 has been localised by using immunohistochemistry...
June 2013: Cell and Tissue Research
John F Bowyer, Tucker A Patterson, Upasana T Saini, Joseph P Hanig, Monzy Thomas, Luísa Camacho, Nysia I George, James J Chen
BACKGROUND: The meninges (arachnoid and pial membranes) and associated vasculature (MAV) and choroid plexus are important in maintaining cerebrospinal fluid (CSF) generation and flow. MAV vasculature was previously observed to be adversely affected by environmentally-induced hyperthermia (EIH) and more so by a neurotoxic amphetamine (AMPH) exposure. Herein, microarray and RT-PCR analysis was used to compare the gene expression profiles between choroid plexus and MAV under control conditions and at 3 hours and 1 day after EIH or AMPH exposure...
2013: BMC Genomics
Nobuyuki Matsumura, Hitoshi Zembutsu, Koji Yamaguchi, Kazuaki Sasaki, Tetsuhiro Tsuruma, Toshihiko Nishidate, Ryuichi Denno, Koichi Hirata
Although metastasis or relapse is a leading cause of death for patients with gastric cancer, the hematogenous spread of cancer cells remains undetected at the time of initial therapy. The development of novel diagnostic molecular marker(s) to detect circulating gastric cancer cells is an issue of great clinical importance. We obtained peripheral blood samples from 10 patients with gastric cancer who underwent laparotomy and 4 healthy volunteers. Microarray analysis consisting of 30,000 genes or ESTs was carried out using eight gastric cancer tissues and normal gastric mucosae...
July 2011: Experimental and Therapeutic Medicine
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