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https://www.readbyqxmd.com/read/29149105/lgr5-expression-is-regulated-by-egf-in-early-colorectal-adenomas-and-governs-egfr-inhibitor-sensitivity
#1
R G Morgan, E Mortensson, D N Legge, B Gupta, T J Collard, A Greenhough, A C Williams
BACKGROUND: LGR5 serves as a co-receptor for Wnt/β-catenin signalling and marks normal intestinal stem cells; however, its role in colorectal cancer (CRC) remains controversial. LGR5(+) cells are known to exist outside the stem cell niche during CRC progression, and the requirement for epidermal growth factor (EGF) signalling within early adenomas remains to be fully elucidated. METHODS: Epidermal growth factor and gefitinib treatments were performed in EGF-responsive LGR5(+) early adenoma RG/C2 cells...
November 16, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29120819/towards-a-defined-ecm-and-small-molecule-based-monolayer-culture-system-for-the-expansion-of-mouse-and-human-intestinal-stem-cells
#2
Zhixiang Tong, Keir Martyn, Andy Yang, Xiaolei Yin, Benjamin E Mead, Nitin Joshi, Nicholas E Sherman, Robert S Langer, Jeffrey M Karp
Current ISC culture systems face significant challenges such as animal-derived or undefined matrix compositions, batch-to-batch variability (e.g. Matrigel-based organoid culture), and complexity of assaying cell aggregates such as organoids which renders the research and clinical translation of ISCs challenging. Here, through screening for suitable ECM components, we report a defined, collagen based monolayer culture system that supports the growth of mouse and human intestinal epithelial cells (IECs) enriched for an Lgr5(+) population comparable or higher to the levels found in a standard Matrigel-based organoid culture...
October 26, 2017: Biomaterials
https://www.readbyqxmd.com/read/29102042/the-prognostic-value-of-cancer-stem-like-cell-markers-sox2-and-cd133-in-stage-iii-colon-cancer-is-modified-by-expression-of-the-immune-related-markers-foxp3-pd-l1-and-cd3
#3
T J Miller, M J McCoy, C Hemmings, M K Bulsara, B Iacopetta, C F Platell
Cancer stem-like cells are highly tumourigenic cells that can repopulate entire tumours after apparent successful treatment. Recent evidence suggests they interact with other cells in the tumour microenvironment, including immune cell subsets, to enhance their survival. The aim of this study was to determine whether the expression of immune cell markers in primary colon cancer impacts the prognostic significance of cancer stem-like cell marker expression. Immunohistochemistry was used to assess the expression of putative stem cell markers (ALDH1, CD44v6, CD133, Lgr5, SOX2) and immune cell related markers (CD3, CD8, FoxP3, PD-L1) in 104 patients with stage III colon cancer...
October 25, 2017: Pathology
https://www.readbyqxmd.com/read/29084052/personalizing-gastric-cancer-screening-with-predictive-modeling-of-disease-progression-biomarkers
#4
Rachel Walker, Jaime Mejia, Jae K Lee, Jose M Pimiento, Mokenge Malafa, Anna R Giuliano, Domenico Coppola, Heiko Enderling
Gastric cancer (GC) remains the third most common cause of cancer-related death worldwide. Infection with Helicobacter pylori is responsible for over 70% of GC incidence; colonization induces chronic inflammation, which can facilitate progression to intestinal metaplasia, dysplasia, and GC (Correa pathway). Although H. pylori eradication is a necessary first step in GC prevention, some patients continue to progress to advanced stage disease if substantial tissue damage has occurred or inflammation persists...
October 27, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29079780/hgf-r-spondin1-rescues-liver-dysfunction-through-the-induction-of-lgr5-liver-stem-cells
#5
Yuan Lin, Zhe-Ping Fang, Hong-Juan Liu, Li-Jing Wang, Zhiqiang Cheng, Na Tang, Tingting Li, Tengfei Liu, Hai-Xiong Han, Guangwen Cao, Li Liang, Yan-Qing Ding, Wei-Jie Zhou
Induction of endogenous adult stem cells by administering soluble molecules provides an advantageous approach for tissue damage repair, which could be a clinically applicable and cost-effective alternative to transplantation of embryonic or pluripotent stem cell-derived tissues for the treatment of acute organ failures. Here, we show that HGF/Rspo1 induce liver stem cells and rescue liver dysfunction. Carbon tetrachloride treatment promotes both fibrosis and Lgr5(+) liver stem cell proliferation, whereas Lgr5 knockdown worsens fibrosis...
October 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/29078734/ovarian-cancer-stem-cells-unravelling-a-germline-connection
#6
Seema Chandrakant Parte, Andrei S Smolenkov, Surinder K Batra, Mariusz Z Ratajczak, Sham Sunder Kakar
Ovarian cancer is most lethal among gynaecological cancers with often fatal consequences due to lack of effective bio-markers and relapse which propels ovarian cancer research into unique directions to establish solid targeted therapeutics. 'Ovarian stem cells' expressing germline, pluripotent markers serve as novel paradigm with potential to address infertility, menopause and probably influence tumor initiation. Cancer stem cells (CSCs) pose vital role in tumor recurrence and hence it is extremely important to study them with respect to ovarian stem cells across various cancer stages and normal ovaries...
October 27, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/29070673/il-17a-induced-plet1-expression-contributes-to-tissue-repair-and-colon-tumorigenesis
#7
Jarod A Zepp, Junjie Zhao, Caini Liu, Katazyna Bulek, Ling Wu, Xing Chen, Yujun Hao, Zhenghe Wang, Xinxin Wang, Wenjun Ouyang, Matthew F Kalady, Julie Carman, Wen-Pin Yang, Jun Zhu, Clare Blackburn, Yina H Huang, Thomas A Hamilton, Bing Su, Xiaoxia Li
This study identifies a novel mechanism linking IL-17A with colon tissue repair and tumor development. Abrogation of IL-17A signaling in mice attenuated tissue repair of dextran sulfate sodium (DSS)-induced damage in colon epithelium and markedly reduced tumor development in an azoxymethane/DSS model of colitis-associated cancer. A novel IL-17A target gene, PLET1 (a progenitor cell marker involved in wound healing), was highly induced in DSS-treated colon tissues and tumors in an IL-17RC-dependent manner. PLET1 expression was induced in LGR5(+) colon epithelial cells after DSS treatment...
October 25, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29065140/novel-insights-into-the-pathways-regulating-the-canine-hair-cycle-and-their-deregulation-in-alopecia-x
#8
Magdalena A T Brunner, Vidhya Jagannathan, Dominik P Waluk, Petra Roosje, Monika Linek, Lucia Panakova, Tosso Leeb, Dominique J Wiener, Monika M Welle
Alopecia X is a hair cycle arrest disorder in Pomeranians. Histologically, kenogen and telogen hair follicles predominate, whereas anagen follicles are sparse. The induction of anagen relies on the activation of hair follicle stem cells and their subsequent proliferation and differentiation. Stem cell function depends on finely tuned interactions of signaling molecules and transcription factors, which are not well defined in dogs. We performed transcriptome profiling on skin biopsies to analyze altered molecular pathways in alopecia X...
2017: PloS One
https://www.readbyqxmd.com/read/29064439/roles-of-micrornas-and-rna-binding-proteins-in-the-regulation-of-colorectal-cancer-stem-cells
#9
REVIEW
Junko Mukohyama, Yohei Shimono, Hironobu Minami, Yoshihiro Kakeji, Akira Suzuki
Colorectal cancer stem cells (CSCs) are responsible for the initiation, progression and metastasis of human colorectal cancers, and have been characterized by the expression of cell surface markers, such as CD44, CD133, CD166 and LGR5. MicroRNAs (miRNAs) are differentially expressed between CSCs and non-tumorigenic cancer cells, and play important roles in the maintenance and regulation of stem cell properties of CSCs. RNA binding proteins (RBPs) are emerging epigenetic regulators of various RNA processing events, such as splicing, localization, stabilization and translation, and can regulate various types of stem cells...
October 24, 2017: Cancers
https://www.readbyqxmd.com/read/29048660/canonical-and-non-canonical-wnt-signaling-in-cancer-stem-cells-and-their-niches-cellular-heterogeneity-omics-reprogramming-targeted-therapy-and-tumor-plasticity-review
#10
Masaru Katoh
Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal replacement and reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49)...
September 19, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29037931/distinct-populations-of-embryonic-epithelial-progenitors-generate-lgr5-intestinal-stem-cells
#11
Margarita M Dzama, Lira Nigmatullina, Sergi Sayols, Nastasja Kreim, Natalia Soshnikova
The adult intestinal stem cells (ISCs) are transcriptionally heterogeneous. As the mechanisms governing their developmental specification are still poorly understood, whether this heterogeneity reflects an early determination of distinct cellular sub-types with potentially distinct physiological functions remains an open question. We investigate the cellular heterogeneity within the mouse embryonic midgut epithelium at the molecular and functional levels. Cell fate mapping analysis revealed that multiple early embryonic epithelial progenitors give rise to Lgr5(+) ISCs...
October 13, 2017: Developmental Biology
https://www.readbyqxmd.com/read/29029005/biopsy-derived-intestinal-epithelial-cell-cultures-for-pathway-based-stratification-of-patients-with-inflammatory-bowel-disease
#12
Wiebe Vanhove, Kris Nys, Ingrid Arijs, Isabelle Cleynen, Manuel Noben, Sebastiaan De Schepper, Gert Van Assche, Marc Ferrante, Séverine Vermeire
Background: Endoplasmic reticulum stress was shown to be pivotal in the pathogenesis of inflammatory bowel disease. Despite progress in IBD drug development, not more than one third of patients achieve steroid-free remission and mucosal healing with current therapies. Furthermore, patient stratification tools for therapy selection are lacking. We aimed to identify and quantify epithelial ER stress in a patient-specific manner in an attempt towards personalized therapy. Methods: A biopsy-derived intestinal epithelial cell culture system was developed and characterized...
September 23, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/29018960/influence-of-stress-factors-on-intestinal-epithelial-injury-and-regeneration
#13
Carol Lee, Adam Minich, Bo Li, Hiromu Miyake, Shogo Seo, Agostino Pierro
PURPOSE: Lgr5+ intestinal epithelial stem cells (ISCs) crucial for intestinal epithelial regeneration are impaired during necrotizing enterocolitis. This study aims to investigate the influence of different stressors on intestinal epithelial injury and regeneration in vitro. METHODS: Intestinal epithelial cells (IEC-18) were exposed to stressors such as lipopolysaccharide, hydrogen peroxide, and serum. Cell viability was assessed using MTT assay at 18 and 24 h...
October 10, 2017: Pediatric Surgery International
https://www.readbyqxmd.com/read/28992396/alcohol-feeding-in-mice-promotes-colonic-hyperpermeability-and-changes-in-colonic-organoid-stem-cell-fate
#14
Christopher B Forsyth, Maliha Shaikh, Faraz Bishehsari, Garth Swanson, Robin M Voigt, Hemraj Dodiya, Peter Wilkinson, Beata Samelco, Shiwen Song, Ali Keshavarzian
BACKGROUND: Alcohol increases intestinal permeability to pro-inflammatory microbial products that promote liver disease, even after a period of sobriety. We sought to test the hypothesis that alcohol affects intestinal stem cells using an in vivo model and ex vivo organoids generated from jejunum and colon from mice fed chronic alcohol. METHODS: Mice were fed a control or an alcohol diet. Intestinal permeability, liver steatosis/inflammation, and stool short chain fatty acids (SCFA) were measured...
October 9, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28986650/expression-of-stem-cell-factors-in-the-adult-sea-cucumber-digestive-tube
#15
Vladimir Mashanov, Olga Zueva, Daria Mashanova, José E García-Arrarás
Homeostatic cell turnover has been extensively characterized in mammals. In their adult tissues, lost or aging differentiated cells are replenished by a self-renewing cohort of stem cells. The stem cells have been particularly well studied in the intestine and are clearly identified by the expression of marker genes including Lgr5 and Bmi1. It is, however, unknown if the established principles of tissue renewal learned from mammals would be operating in non-mammalian systems. Here, we study homeostatic cell turnover in the sea cucumber digestive tube, the organ with high tissue plasticity even in adult animals...
October 7, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28983091/therapeutic-potential-of-human-minor-salivary-gland-epithelial-progenitor-cells-in-liver-regeneration
#16
Chen Zhang, Yan Li, Xiang-Yu Zhang, Lei Liu, Hai-Zhou Tong, Ting-Lu Han, Wan-di Li, Xiao-Lei Jin, Ning-Bei Yin, Tao Song, Hai-Dong Li, Juan Zhi, Zhen-Min Zhao, Lin Lu
Liver disease is a serious problem affecting millions of people with continually increasing prevalence. Stem cell therapy has become a promising treatment for liver dysfunction. We previously reported on human minor salivary gland mesenchymal stem cells (hMSGMSCs), which are highly self-renewable with multi-potent differentiation capability. In this study, keratinocyte-like cells with self-regeneration and hepatic differentiation potential were isolated and characterized, and named human minor salivary gland epithelial progenitor cells (hMSG-EpiPCs)...
October 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28979689/interleukin-25-primed-mesenchymal-stem-cells-achieve-better-therapeutic-effects-on-dextran-sulfate-sodium-induced-colitis-via-inhibiting-th17-immune-response-and-inducing-t-regulatory-cell-phenotype
#17
Weizi Cheng, Jingling Su, Yiqun Hu, Qingwen Huang, Huaxiu Shi, Lin Wang, Jianlin Ren
AIM: This study aimed to investigate the anti-inflammatory mechanism of IL-25 mediated mesenchymal stem cells (MSC) treatment for inflammatory bowel disease (IBD) in a DSS-induced rat colitis model. METHODS: Rats with DSS-induced colitis were divided into control and treatment groups: normal control group (rats fed with water), DSS group (rats fed with DSS solution), MSC group (DSS-treated rats injected intravenously with GFP-MSCs), IL-25-MSC group (DSS-treated rats injected intravenously with IL-25 primed GFP-MSCs), and mesalazine group (DSS-treated rats fed with mesalazine)...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28970066/foxo1-reduces-tumorsphere-formation-capacity-and-has-crosstalk-with-lgr5-signaling-in-gastric-cancer-cells
#18
Yiseul Choi, Jinju Park, Young San Ko, Younghoon Kim, Jung-Soo Pyo, Bo Gun Jang, Min A Kim, Jae-Seon Lee, Mee Soo Chang, Byung Lan Lee
Gastric cancer (GC) is a major of cause of cancer-related death and is characterized by its heterogeneity and molecular complexity. FOXO1 is a transcription factor that plays a key role in GC growth and metastasis. However, the implication of FOXO1 in GC cell stemness has been elusive. This study, for the first time, demonstrates that FOXO1 regulates GC cell stemness in association with LGR5. FOXO1 expression was significantly lower in GC tumorsphere cells than in adherent GC cells. FOXO1 silencing and overexpression promoted and inhibited the tumorsphere formation capacity of GC cells, respectively...
November 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28968998/identification-of-aqp3-and-cd24-as-biomarkers-for-carcinogenesis-of-gastric-intestinal-metaplasia
#19
Haijian Zhao, Jianfei Wen, Xuqiang Dong, Ruji He, Cheng Gao, Weiming Zhang, Zhihong Zhang, Lizong Shen
Gastric intestinal metaplasia (GIM) is a precancerous gastric carcinoma (GC) lesion with pivotal roles in carcinogenesis. CD24, LGR5 and Ki67 are expressed in GIM; we previously demonstrated that aquaporin 3 (AQP3) is expressed in goblet cells and is positively correlated with GIM severity. However, the relationships of AQP3 with GIM classification and with other proteins, and their roles in the transition from GIM to gastric carcinoma (GC) remain unknown. Sixteen patients with intestinal-type GC were enrolled in this study...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28963394/casein-kinase-1-epsilon-or-1-delta-required-for-wnt-mediated-intestinal-stem-cell-maintenance
#20
Yael Morgenstern, Upasana Das Adhikari, Muneef Ayyash, Ela Elyada, Beáta Tóth, Andreas Moor, Shalev Itzkovitz, Yinon Ben-Neriah
The intestinal epithelium holds an immense regenerative capacity mobilized by intestinal stem cells (ISCs), much of it supported by Wnt pathway activation. Several unique regulatory mechanisms ensuring optimal levels of Wnt signaling have been recognized in ISCs. Here, we identify another Wnt signaling amplifier, CKIε, which is specifically upregulated in ISCs and is essential for ISC maintenance, especially in the absence of its close isoform CKIδ. Co-ablation of CKIδ/ε in the mouse gut epithelium results in rapid ISC elimination, with subsequent growth arrest, crypt-villous shrinking, and rapid mouse death...
October 16, 2017: EMBO Journal
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