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https://www.readbyqxmd.com/read/27935476/assessing-the-mechanism-and-therapeutic-potential-of-modulators-of-the-human-mediator-complex-associated-protein-kinases
#1
Paul Andrew Clarke, Maria-Jesus Ortiz-Ruiz, Robert TePoele, Olajumoke Adeniji-Popoola, Gary Box, Will Court, Stefanie Czasch, Samer El Bawab, Christina Esdar, Ken Ewan, Sharon Gowan, Alexis De Haven Brandon, Phllip Hewitt, Stephen M Hobbs, Wolfgang Kaufmann, Aurélie Mallinger, Florence Raynaud, Toby Roe, Felix Rohdich, Kai Schiemann, Stephanie Simon, Richard Schneider, Melanie Valenti, Stefan Weigt, Julian Blagg, Andree Blaukat, Trevor C Dale, Suzanne A Eccles, Stefan Hecht, Klaus Urbahns, Paul Workman, Dirk Wienke
Mediator-associated kinases CDK8/19 are context-dependent drivers or suppressors of tumorigenesis. Their inhibition is predicted to have pleiotropic effects, but it is unclear whether this will impact on the clinical utility of CDK8/19 inhibitors. We discovered two series of potent chemical probes with high selectivity for CDK8/19. Despite pharmacodynamic evidence for robust on-target activity, the compounds exhibited modest, though significant, efficacy against human tumor lines and patient-derived xenografts...
December 9, 2016: ELife
https://www.readbyqxmd.com/read/27932500/notch1-and-notch2-regulate-epithelial-cell-proliferation-in-mouse-and-human-gastric-corpus
#2
Elise S Demitrack, Gail B Gifford, Theresa M Keeley, Nobukatsu Horita, Andrea Todisco, D Kim Turgeon, Christian W Siebel, Linda C Samuelson
The Notch signaling pathway is known to regulate stem cells and epithelial cell homeostasis in gastrointestinal tissues; however, Notch function in the corpus region of the stomach is poorly understood. In this study we examined the consequences of Notch inhibition and activation on cellular proliferation and differentiation and defined the specific Notch receptors functioning in the mouse and human corpus. Notch pathway activity was observed in the mouse corpus epithelium, and gene expression analysis revealed NOTCH1 and NOTCH2 to be the predominant Notch receptors in both mouse and human...
December 8, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27930406/stress-response-protein-rbm3-promotes-the-development-of-colitis-associated-cancer
#3
Toshiharu Sakurai, Hiroshi Kashida, Yoriaki Komeda, Tomoyuki Nagai, Satoru Hagiwara, Tomohiro Watanabe, Masayuki Kitano, Naoshi Nishida, Jun Fujita, Masatoshi Kudo
BACKGROUND: Colitis-associated cancer (CAC) is caused by chronic intestinal inflammation and often results from refractory inflammatory bowel disease (IBD). Stress response proteins Cirp and HSPA4 are involved in the refractory clinical course and development of CAC. RNA-binding motif protein 3 (RBM3) is induced in response to various stresses and is upregulated in several cancers. However, the role of RBM3 in CAC is unclear. METHODS: We assessed RBM3 expression and function in 263 human intestinal mucosa samples from patients with IBD and in Rbm3-deficient (Rbm3) mice...
December 7, 2016: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/27927684/in-vitro-patterning-of-pluripotent-stem-cell-derived-intestine-recapitulates-in-vivo-human-development
#4
Yu-Hwai Tsai, Roy Nattiv, Priya H Dedhia, Melinda S Nagy, Alana M Chin, Matthew Thomson, Ophir Klein, Jason Spence
The intestine plays a central role in digestion, nutrient absorption and metabolism, with individual regions of the intestine having distinct functional roles. For example, the most proximal region of the small intestine, the duodenum, is associated with absorption of micronutrients such as iron and folate, whereas the more distal ileum is responsible for recycling bile salts. Many examples of region-specific gene expression in the adult intestine are known, but how intestinal regional identity is established during development is a largely open question...
December 7, 2016: Development
https://www.readbyqxmd.com/read/27927191/somatostatin-signaling-via-sstr1-contributes-to-the-quiescence-of-colon-cancer-stem-cells
#5
Shirin R Modarai, Lynn M Opdenaker, Vignesh Viswanathan, Jeremy Z Fields, Bruce M Boman
BACKGROUND: Neuroendocrine cells (NECs) reside adjacent to colonic stem cells (SCs) in the crypt stem cell (SC) niche, but how NECs are involved in regulation of SCs is unclear. We investigated NECs expressing somatostatin (SST) and somatostatin receptor type 1 (SSTR1) because SST inhibits intestinal proliferation. HYPOTHESIS: SSTR1 cells maintain SCs in a quiescent state, and aberrant SST signaling contributes to SC overpopulation in colorectal cancer (CRC). METHODS: The proportion of SCs to NECs cells was quantified, by flow cytometry, in CRC cell lines and primary normal/tumor tissues based on cellular ALDH and SSTR1 levels, respectively...
December 7, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27927062/the-possible-role-of-gastrointestinal-endocrine-cells-in-the-pathophysiology-of-irritable-bowel-syndrome
#6
Magdy El-Salhy, Trygve Hausken, Odd Helge Gilja, Jan Gunnar Hatlebakk
The etiology of irritable bowel syndrome (IBS) is unknown, but several factors appear to play a role in its pathophysiology, including abnormalities of the gastrointestinal endocrine cells. The present review illuminates the possible role of gastrointestinal hormones in the pathophysiology of IBS and the possibility of utilizing the current knowledge in treating the disease. Areas covered: Research into the intestinal endocrine cells and their possible role in the pathophysiology of IBS is discussed. Furthermore, the mechanisms underlying the abnormalities in the gastrointestinal endocrine cells in IBS patients are revealed...
December 7, 2016: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/27923325/a-gingiva-derived-mesenchymal-stem-cell-laden-porcine-small-intestinal-submucosa-extracellular-matrix-construct-promotes-myomucosal-regeneration-of-the-tongue
#7
Qilin Xu, Rabie M Shanti, Qunzhou Zhang, Steven B Cannady, Bert W O'Malley, Anh D Le
In the oral cavity, the tongue is the anatomic subsite most commonly involved by invasive squamous cell carcinoma. Current treatment protocols often require significant tissue resection to achieve adequate negative margins and optimal local tumor control. Reconstruction of the tongue while preserving and/or restoring its critical vocal, chewing, and swallowing functions remains one of the major challenges in head and neck oncologic surgery. We investigated the in vitro feasibility of fabricating a novel combinatorial construct using porcine small intestinal submucosa extracellular matrix (SIS-ECM) and human gingival mesenchymal stem cells (GMSCs) as a GMSC/SIS-ECM tissue graft for the tongue reconstruction...
December 6, 2016: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/27923223/intestinal-pneumatosis-associated-with-tuberculosis-after-allogeneic-hematopoietic-stem-cell-transplantation
#8
Vivek Venkataramani, Ali Seif Amir Hosseini, Marco H Schulze, Lorenz Trümper, Gerald Wulf, Ulrike Bacher, Wolfram Jung
Pneumatosis intestinalis (PI), defined as intestinal intra- and extramural gas accumulation, is a rare radiographic finding in conditions of intestinal wall damage of varied etiology. Here, we report on a 56-year-old female with multiple myeloma who presented with undulating fever, fluctuating abdominal symptoms, and a distended abdomen 5 months after allogeneic hematopoietic stem cell transplantation (HSCT). Abdominal X-ray and CT scan documented PI with gas accumulation both in the intestinal and colonic bowel walls...
December 7, 2016: Acta Haematologica
https://www.readbyqxmd.com/read/27919339/the-role-of-gene-mutations-and-gene-products-in-intestinal-tissue-reactions-from-ionising-radiation
#9
Jolyon H Hendry, Kensuke Otsuka
The response of the intestine to (low linear-energy-transfer) ionising radiation is reviewed regarding the cellular basis to the reactions, the regenerative processes which restore the tissue, and external agents which aid its recovery. In the steady-state, it is generally considered that the crypt cell lineages in both small and large intestine are maintained by a small number of stem cells, but there are differences for example in the composition of their niche residence and in the numbers of transit cell generations...
October 2016: Mutation Research
https://www.readbyqxmd.com/read/27915968/peripheral-t-cell-lymphoma-a-posttransplant-lymphoproliferative-disorder-presenting-as-a-jejunal-mass-in-a-renal-transplant-recipient
#10
Aanchal Kakkar, Immanuel Pradeep, Geetika Singh, Amit Dinda, Sanjay K Agarwal
Posttransplant lymphoproliferative disorders are a spectrum of lymphoproliferative disorders seen in recipients of solid-organ, bone marrow, and stem cell allografts. They include polyclonal early lesions mimicking infectious mononucleosis and monoclonal proliferations of B and T cells, indistinguishable from lymphomas occurring in immunocompetent individuals. Although most posttransplant lymphoproliferative disorders are B-cell neoplasms, T-cell posttransplant lymphoproliferative disorders are very rare. Among solid-organ transplants, renal allografts have low risk for development of posttransplant lymphoproliferative disorders...
December 2, 2016: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/27913222/human-liver-regeneration-in-advanced-cirrhosis-is-organized-by-the-portal-tree
#11
Katalin Dezső, András Rókusz, Edina Bugyik, Armanda Szücs, András Szuák, Bence Dorogi, Mátyás Kiss, Ágnes Nemeskéri, Péter Nagy, Sándor Paku
BACKGROUND&AIMS: In advanced cirrhosis new hepatocytic nodules are generated by budding of ductules in areas of parenchymal extinction. However, the vascular alterations in the areas of parenchymal extinction, the blood supply and the structure of the new hepatocytic nodules have not been analyzed in detail. METHODS: Explanted human cirrhotic livers of three different etiologies and two experimental models of cirrhosis in rats were examined thoroughly. 3D reconstruction of the immunohistochemically stained serial sections and casting of human and experimental cirrhotic livers have been used to reveal the structural organization of the regenerative buds...
November 29, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27912759/intestinal-dysbiosis-and-allogeneic-hematopoietic-progenitor-cell-transplantation
#12
REVIEW
Vikram M Raghunathan, Iris Sheng, Seah H Lim
The intestinal microbiota is a diverse and dynamic ecosystem that is increasingly understood to play a vital role in human health. Hematopoietic stem cell transplant recipients undergo prolonged exposure to antimicrobials, chemotherapeutic agents, and immunosuppressants, resulting in profound shifts in the gut microbiome. A growing body of research has revealed the ways in which these microbiologic shifts shape immune modulation, affecting susceptibility to infections and graft-versus-host disease, the two major post-transplant complications in this population...
December 3, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27910783/recent-advances-and-challenges-in-studies-of-control-of-cancer-stem-cells-and-the-gut-microbiome-by-the-trametes-derived-polysaccharopeptide-psp-review
#13
Joseph M Wu, Barbara B Doonan, Tze-Chen Hsieh, Qingyao Yang, Xiao-Tong Yang, Ming-Tat Ling
The medicinal mushroom Trametes versicolor has been well recognized for its activity in maintaining the general health of the population and in managing and treating human diseases in various cultures. Its use has been recently gaining acceptance and popularity in Western countries. The reported health benefits of T. versicolor led to a search for the identity of its bioactive ingredients. These efforts have resulted in the isolation of the polysaccharopeptide PSP from cultured mycelia of strain Cov-1, which expresses large amounts of PSP...
2016: International Journal of Medicinal Mushrooms
https://www.readbyqxmd.com/read/27909715/a-new-scaffold-containing-small-intestinal-submucosa-and-mesenchymal-stem-cells-improves-pancreatic-islet-function-and-survival-in%C3%A2-vitro-and-in%C3%A2-vivo
#14
Dan Wang, Xiaoming Ding, Wujun Xue, Jin Zheng, Xiaohui Tian, Yang Li, Xiaohong Wang, Huanjin Song, Hua Liu, Xiaohui Luo
It is unknown whether a scaffold containing both small intestinal submucosa (SIS) and mesenchymal stem cells (MSCs) for transplantation may improve pancreatic islet function and survival. In this study, we examined the effects of a SIS-MSC scaffold on islet function and survival in vitro and in vivo. MSCs and pancreatic islets were isolated from Sprague-Dawley rats, and SIS was isolated from Bamei pigs. The islets were apportioned among 3 experimental groups as follows: SIS-islets, SIS-MSC-islets and control-islets...
November 29, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27904037/analysis-of-cyp2r1-and-cyp26a1-expression-patterns-in-regeneration-in-mice-with-liver-injury
#15
Akiyo Hirose, Wataru Ochiai, Yuka Yamamoto, Masashi Fukaya, Hiroshi Iwasaki, Nozomi Wakui, Ayumi Takahashi, Yusuke Takahashi, Satoshi Kitaoka, Jo Hatogai, Nobutomo Ikarashi, Kiyoshi Sugiyama
Cytochrome P450 enzymes (CYPs) are involved in the metabolism of various substances in the liver and small intestine and show markedly higher expression levels in the liver compared to other organs. The liver exhibits a remarkable capacity to regenerate. After excision of 70% of the liver, the organ can regenerate to its original size in approximately 1 week. Unlike the normal liver, in the injured liver, hepatic stem cells known as oval cells are considered to play an important role in regeneration. However, the role of CYPs in liver regeneration remains unclear...
2016: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27900603/enteropathy-associated-t-cell-lymphoma
#16
REVIEW
Sarah Ondrejka, Deepa Jagadeesh
Enteropathy-associated T-cell lymphoma is a rare neoplasm with uniformly aggressive features that arises from intestinal T-cells. There is strong evidence supporting its association as a dire complication of celiac disease. The clinical presentation can vary from malabsorption and abdominal pain to an acute abdominal emergency. Originally, it was divided into types I and II in World Health Organization (WHO) classification schemes, reflective of epidemiology and differences in clinicopathologic features. The debate over the degree of separation of the two types is ongoing as new data emerges regarding the pathogenetics...
November 29, 2016: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/27888356/intestinal-stem-cell-transplantation
#17
REVIEW
Tetsuya Nakamura, Mamoru Watanabe
Organoid technologies to expand intestinal epithelial cells are gaining increasing attention as a useful tool to investigate many aspects of intestinal epithelial biology and pathology. One important application of organoid systems would be to use intestinal epithelial cells expanded in culture for following transplantation experiments. In this article, we present a brief overview of the studies that have succeeded in generating new epithelial tissues in the surface of native intestines in mice by organoid transplantation...
November 25, 2016: Journal of Gastroenterology
https://www.readbyqxmd.com/read/27888216/drosophila-sulf1-is-required-for-the-termination-of-intestinal-stem-cell-division-during-regeneration
#18
Masahiko Takemura, Hiroshi Nakato
Stem cell division is activated to trigger regeneration in response to tissue damage. The molecular mechanisms by which this stem cell mitotic activity is properly repressed at the end of regeneration are poorly understood. Here we show that a specific modification of heparan sulfate (HS) is critical in regulating Drosophila intestinal stem cell (ISC) division during normal midgut homeostasis and regeneration. Loss of the extracellular HS endosulfatase Sulf1 results in increased ISC division during normal homeostasis, which is caused by upregulation of mitogenic signaling including the JAK/STAT, EGFR, and Hedgehog pathways...
November 25, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27879260/antibiotics-impair-murine-hematopoiesis-by-depleting-intestinal-microbiota
#19
Kamilla S Josefsdottir, Megan T Baldridge, Claudine S Kadmon, Katherine Y King
Bone marrow suppression is an adverse effect associated with many antibiotics, especially when administered for prolonged treatment courses. Recent advances in our understanding of steady-state hematopoiesis have allowed us to explore the effects of antibiotics on hematopoietic progenitors in detail using a murine model. Antibiotic-treated mice exhibited anemia, thrombocytosis, and leukopenia, with pronounced pan-lymphopenia as demonstrated by flow cytometric analysis of peripheral blood. Bone marrow progenitor analysis revealed depletion of hematopoietic stem cells and multipotent progenitors across all subtypes...
November 22, 2016: Blood
https://www.readbyqxmd.com/read/27878827/review-article-mesenchymal-stromal-cell-therapy-for-inflammatory-bowel-diseases
#20
REVIEW
C Grégoire, C Lechanteur, A Briquet, É Baudoux, F Baron, E Louis, Y Beguin
BACKGROUND: Inflammatory bowel diseases (IBD) are chronic relapsing diseases in which pro-inflammatory immune cells and cytokines induce intestinal tissue damage and disability. Mesenchymal stromal cells (MSCs) exert powerful immunomodulatory effects and stimulate tissue repair. AIM: To review the current data on mesenchymal stromal cell therapy in IBD. METHOD: We searched PubMed and 'ClinicalTrials.gov' databases using the terms 'mesenchymal stromal cells', 'mesenchymal stem cell transplantation', 'inflammatory bowel diseases', 'Crohn disease' and 'colitis, ulcerative'...
January 2017: Alimentary Pharmacology & Therapeutics
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