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Ho Pan Sham, Mark Bazett, Momir Bosiljcic, Hyungjun Yang, Beryl Luk, Hong T Law, Vijay Morampudi, Hong B Yu, Jim Pankovich, Simon Sutcliffe, Brian Bressler, John K Marshall, Richard N Fedorak, Jenny Chen, Michelle Jones, Hal Gunn, Shirin Kalyan, Bruce A Vallance
Background: Current ulcerative colitis (UC) treatments are focused on symptom management primarily via immune suppression. Despite the current arsenal of immunosuppressant treatments, the majority of patients with UC still experience disease progression. Importantly, aggressive long-term inhibition of immune function comes with consequent risk, such as serious infections and malignancy. There is thus a recognized need for new, safe and effective treatment strategies for people living with UC that work upstream of managing the symptoms of the disease...
2018: Frontiers in Immunology
Satoshi Kondo, Shota Mizuno, Tadahiro Hashita, Takahiro Iwao, Tamihide Matsunaga
OBJECTIVE AND DESIGN: The primary component in gut mucus is mucin 2 (MUC2) secreted by goblet cells. Fluctuations in MUC2 expression are considered a useful indicator for evaluating mucosal damage and protective effect of various agents using animal studies. However, there are few in vitro studies evaluating mucosal damage using MUC2 as the indicator. Hence, we attempted to establish a novel in vitro model with MUC2 as the indicator for evaluating drug-induced mucosal damage and protective effect using enterocytes derived from human iPS cells...
October 13, 2018: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Anna Astashchanka, Thomas M Shroka, Britta M Jacobsen
PURPOSE: Tumors that secrete large volumes of mucus are chemotherapy resistant, however, mechanisms underlying this resistance are unknown. One protein highly expressed in mucin secreting breast cancers is the secreted mucin, Mucin 2 (MUC2). While MUC2 is expressed in some breast cancers it is absent in normal breast tissue, implicating it in breast cancer. However, the effects of MUC2 on breast cancer are largely unknown. This study examined the role of MUC2 in modulating breast cancer proliferation, response to chemotherapy and metastasis...
October 13, 2018: Breast Cancer Research and Treatment
Aldona Kasprzak, Elżbieta Siodła, Małgorzata Andrzejewska, Jacek Szmeja, Agnieszka Seraszek-Jaros, Szczepan Cofta, Witold Szaflarski
AIM: To determine tissue expression (mRNA, protein) of two types of mucins [mucin 1 (MUC1) and mucin 2 (MUC2)] in patients with colorectal cancer (CRC). METHODS: Expression of membrane-bound mucin (MUC1) and secretory mucin (MUC2) in CRC (mRNA, protein) were analyzed in tissue material including fragments of tumors obtained from CRC patients ( n = 34), and fragments of normal colorectal tissue from the same patients (control). The analysis was conducted using real-time quantitative polymerase chain reaction (RT-qPCR) (transcripts), immunohistochemistry (IHC) (apomucins), and the modern approach for morphometric analysis of IHC reaction (HSV filter software)...
September 28, 2018: World Journal of Gastroenterology: WJG
Milosz Wiktorowicz, Damian Mlynarski, Radoslaw Pach, Romana Tomaszewska, Jan Kulig, Piotr Richter, Marek Sierzega
BACKGROUND: Aberrantly expressed mucin glycoproteins (MUC) play important roles in pancreatic ductal adenocarcinoma (PDAC), yet their use as a diagnostic aid in fine-needle aspiration biopsy (FNAB) is poorly documented. The aim of this study was to investigate the rationale and feasibility of mucin (MUC1, MUC2, MUC3, MUC4, MUC5AC, and MUC6) expression profiling by RT-PCR for diagnostic applications in cytology. METHODS: Mucin expression was examined by RT-PCR and immunohistochemistry in specimens resected from patients with pancreatic (n = 101), ampullary (n = 23), and common bile duct (n = 10) cancers and 33 with chronic pancreatitis...
September 25, 2018: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
Eduardo R Cobo, Ravi Holani, France Moreau, Kiminori Nakamura, Tokiyoshi Ayabe, Jennifer R Mastroianni, Yoshihiro Eriguchi, Andre Ouellette, Kris Chadee
No abstract text is available yet for this article.
October 2018: Infection and Immunity
Angel Fernandez-Flores, Itziar Eraña, Jesus Cuevas
BACKGROUND: Mammary Paget disease and extramammary Paget disease (EMPD) have different prognoses. Because they are indistinguishable on histopathological grounds, they must be distinguished on a topographical basis. OBJECTIVE: To study cases of Paget disease of the breast, which show similarities to EMPD. METHODS: Cases were selected by 2 different approaches: (1) those with an exceptionally good evolution and no evidence of subjacent tumor and (2) those expressing MUC5AC...
October 2018: American Journal of Dermatopathology
Minna Wu, Yaqi Wu, Jianmin Li, Yonghua Bao, Yongchen Guo, Wancai Yang
Gut dysbiosis is associated with colitis-associated colorectal carcinogenesis, and the genetic deficiency of the Muc2 gene causes spontaneous development of colitis and colorectal cancer. Whether there are changes of gut microbiota and a linkage between the changes of microbiota and intestinal pathology in Muc2-/- mice are unclear. Muc2-/- and Muc2+/+ mice were generated by backcrossing from Muc2+/- mice, and the fecal samples were collected at different dates (48th, 98th, 118th, 138th, and 178th day). Gut microbiota were analyzed by high-throughput sequencing with the universal 16S rRNA primers (V3⁻V5 region)...
September 18, 2018: International Journal of Molecular Sciences
Jaudah Al-Maghrabi, Shabnum Sultana, Wafaey Gomaa
Background/Aim: The objective of this study was to investigate the relationship between MUC2 immunostaining and clinicopathological characteristics in a subset of colorectal carcinomas (CRCs). Materials and Methods: A total of 128 CRCs, 50 local nodal metastases, and 42 normal colonic mucosae were retrieved from the archives at the Department of Pathology at King Abdulaziz University, Jeddah, Saudi Arabia. Immunohistochemistry was performed using anti-MUC2 antibody...
September 18, 2018: Saudi Journal of Gastroenterology: Official Journal of the Saudi Gastroenterology Association
Xuanxuan Yang, Luo Zhang, Xing Song, Wenting He, Dachuan Zhang, Qicheng Lu, Jun Wu, Changping Wu, Jingting Jiang
The aim of the present study is to investigate the expression and function of miR-613 in colon cancer (CC) and illuminate the molecular mechanisms underlying miR-613-regulated CC progression. Our data demonstrated that miR-613 was upregulated in CC tissue samples (P = 0.009) and human CC cell lines (HCT-116 and Lovo; P = 0.001 and P = 0.003, respectively), which also promoted the proliferation, invasion and migration of CC cells (P < 0.05). The dual-luciferase reporter assay confirmed that Atonal homolog1 (ATOH1) was the target mRNA of miR-613...
October 12, 2018: Biochemical and Biophysical Research Communications
Melissa Shizue de A Yamashita, Eduardo O Melo
Transgenic livestock have been studied with a well-known interest in improving quantitative and qualitative traits. In order to direct heterologous gene expression, it is indispensable to identify and characterize a promoter suitable for directing the expression of the gene of interest (GOI) in a tissue-specific way. The gastrointestinal tract is a desirable target for gene expression in several mammalian models. Throughout the surface of the intestinal epithelium, there is an intricate polymer network, formed by gel-forming mucins (especially MUC2 and MUC5AC, of which MUC2 is the major one), which plays a protective role due to the formation of a physical, chemical and immunological barrier between the organism and the environment...
September 14, 2018: Cell and Tissue Research
Atsushi Uchida, Masayoshi Ozawa, Yumi Ueda, Yoko Murai, Yuka Nishimura, Hiromi Ishimatsu, Yoshimi Okouchi, Kazuya Ishiguro, Yoshitaka Hamada, Rumiko Sasamoto, Masashi Watanabe, Naoki Sano, Ryoichi Miyamoto, Satoshi Inagawa, Kazunori Kikuchi
RATIONALE: Gastric adenocarcinoma of fundic gland type (GA-FG) is a new histological type of gastric cancer manifesting with differentiation into a fundic gland. Furthermore, gastric adenocarcinoma of fundic gland mucosa type (GA-FGM) is a tumor that shows differentiation into not only a fundic gland but also foveolar epithelium and a mucous gland. These tumors tend to invade the submucosal layer. However, no cases of these tumors being localized only in the submucosa have been reported...
September 2018: Medicine (Baltimore)
Haiqin Wu, Lulu Ye, Xiaoxi Lu, Shuang Xie, Qian Yang, Qinghua Yu
SCOPE: The intestinal mucosal barrier, including the mucus layer, protects against invasion of enteropathogens, thereby inhibiting infection. In this study, the protective effect of Lactobacillus on the intestinal barrier against Salmonella infection is investigated. The underlying mechanism of its effect, specifically on the regulation of goblet cells through the Notch pathway, is also elucidated. METHODS AND RESULTS: Here, the protective effect of Lactobacillus on alleviating changes in the intestinal barrier caused by Salmonella infection is explored...
September 10, 2018: Molecular Nutrition & Food Research
Osmel Companioni, Catalina Bonet, Nadia García, María José Ramírez-Lázaro, Sergio Lario, Jorge Mendoza, Mª Magdalena Adrados, Elvira Poves, Laura Espinosa, José Juan Pozo-Kreilinger, Luís Ortega, Luis Bujanda, Angel Cosme, Angel Ferrández, Guillermo Muñoz, Miriam Cuatrecasas, Ignasi Elizalde, Victoria Andreu, Mª José Paules, Beatriz Madrigal, Jesús Barrio, María Berdasco, Xavier Calvet, José Miguel Sanz-Anquela, Javier P Gisbert, Carlos A González, Núria Sala
Gastric carcinogenesis proceeds through a series of gastric cancer precursor lesions (GCPLs) leading to gastric cancer (GC) development. Although Helicobacter pylori infection initiates this process, genetic factors also play a role. We previously reported that genetic variability in MUC2 is associated with the evolution of GCPLs. In order to replicate previous results in an independent sample series and to explore whether genetic variability in other candidate genes plays a role in the evolution of GCPL, genomic DNA from 559 patients with GCPLs, recruited from 9 Spanish hospitals and followed for a mean of 12 years, was genotyped for 141 SNPs in 29 genes...
August 31, 2018: International Journal of Cancer. Journal International du Cancer
Svend Kirkeby, Anne Marie Lynge Pedersen
Binding of cholera toxin subunit B (CTB) to its receptor and toxin transport into the intestinal epithelial cells are the causative events for the potentially lethal disease cholera. The five sugar mono-sialo ganglioside GM1 is the cell surface receptor for cholera toxin B-subunit. CTB binding was determined by use of immobilized GM1 to microtiter plates and by immunohistochemistry. Sections from the human colon and the human soft palate were incubated with FITC-conjugated CTB and with anti-MUC2. Both the luminal surface of the intestine and the secretory goblet cells exhibited strong binding...
August 24, 2018: Microbial Pathogenesis
N A Zolotova, A V Polikarpova, D N Khochanskii, O V Makarova, L P Mikhailova
We studied changes in the expression of mRNA for mucins and claudins in the medial part of the colon in male C57Bl/6 mice on the model of acute and chronic colitis induced by substitution of drinking water with 1% solution of dextran sodium sulphate for 5 days. In acute colitis, the expression of the main structural component of glycocalyx, mucin Muc3, decreased and expression of pore-forming claudin Cldn2 increased, which reflected enhanced permeability of tight junctions. In the chronic colitis group, in comparison with the normal group, we observed an increase in expression of mRNA of main structural mucus component Muc2, enhanced of expression of Muc1 associated with carcinogenesis, and reduced expression of Muc13, which led to a more severe course of colitis; the expression of pore-forming claudin Cldn2 was elevated...
August 2018: Bulletin of Experimental Biology and Medicine
Keiko Igaki, Yoshiki Nakamura, Yusaku Komoike, Keiko Uga, Akira Shibata, Yoshimasa Ishimura, Masashi Yamasaki, Yasuhiro Tsukimi, Noboru Tsuchimori
IL-17-producing Th17 cells and IFN-γ and IL-17 double-producing Th1/17 cells have been identified as the pathogenic cells in inflammatory bowel disease (IBD). Retinoic acid-related orphan receptor γt (RORγt) is a master regulator for the differentiation and activation of Th17 and Th1/17 cells. We discovered a novel orally available TAK-828F, a strong and selective RORγt inverse agonist. To assess the potential of RORγt blockade in the therapy for IBD, the efficacy of TAK-828F in activated T cell transfer mouse colitis model was investigated...
August 18, 2018: Inflammation
Kiyoshi Saeki, Yoshihiro Miyasaka, Yoshihiro Ohishi, Takeo Yamamoto, Ryota Matsuda, Naoki Mochidome, Yasuhisa Mori, Kohei Nakata, Takao Ohtsuka, Kousei Ishigami, Yosuke Minoda, Yutaka Koga, Yoshinao Oda, Masafumi Nakamura
BACKGROUND: Intraductal tubulopapillary neoplasm (ITPN) is a rare pancreatic intraductal neoplasm. It is characterized by a tubulopapillary growth pattern, entirely high-grade atypical cells, minimal cytoplasmic mucin, and no obvious luminal mucin secretion. Most of its biological nature remains unclear. CASE PRESENTATION: We herein report a case of intrapancreatic recurrence of ITPN in the remnant pancreas of a patient who underwent pancreatoduodenectomy 16 years previously for a noninvasive intraductal pancreatic head tumor...
August 16, 2018: Surgical Case Reports
Eiji Noda, Kenji Kuroda, Tomohisa Sera, Takuya Mori, Haruhito Kinoshita, Tsuyoshi Hasegawa, Hitoshi Teraoka, Takaaki Chikugo
We report a case of intraductal papillary mucinous neoplasm arising within the heterotopic pancreatic tissue which was found incidentally in the jejunum during surgery for bowel obstruction. A 54-year-old female patient was admitted to our hospital due to sudden abdominal pain. In preoperative findings, we diagnosed bowel obstruction and performed surgery. Intra-operative findings showed adhesive intestinal obstruction, we performed synechiotomy for adhesion release. During surgery, when searching the small intestine, we coincidentally found a tumor in the jejunum and partial resected the jejunum...
August 2018: Journal of Surgical Case Reports
Lilli Saarinen, Pirjo Nummela, Hannele Leinonen, Annamari Heiskanen, Alexandra Thiel, Caj Haglund, Anna Lepistö, Tero Satomaa, Sampsa Hautaniemi, Ari Ristimäki
Pseudomyxoma peritonei (PMP) is a subtype of mucinous adenocarcinoma that most often originates from the appendix, and grows in the peritoneal cavity filling it with mucinous ascites. KRAS and GNAS mutations are frequently found in PMP, but other common driver mutations are infrequent. As altered glycosylation can promote carcinogenesis, we compared N-linked glycan profiles of PMP tissues to those of normal appendix. Glycan profiles of eight normal appendix samples and eight low-grade and eight high-grade PMP specimens were analyzed by mass spectrometry...
August 2, 2018: Molecular & Cellular Proteomics: MCP
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