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https://www.readbyqxmd.com/read/28430648/radioimmunotherapy-for-cd133-colonic-cancer-stem-cells-inhibits-tumor-development-in-nude-mice
#1
Dinghu Weng, Xueyan Jin, Saimei Qin, Xiaoli Lan, Chong Chen, Xun Sun, Xianliang She, Changling Dong, Rui An
Accumulating evidence indicates that cancer stem cells (CSCs) are the cause of tumor drug/radio-resistance or distant metastasis; therefore, it is essential to eliminate CSCs to cure cancer completely. The purpose of this study was to utilize radioimmunotherapy (RIT) to target CD133(+) colonic CSCs and observe whether this prevented tumor development, by assessing the maximum tolerated dose (MTD) of HCT116 tumor-bearing nude mice with escalating doses of 131I-AC133.1 monoclonal antibody (mAb), and determining the therapeutic efficacy of RIT with 131I-AC133...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429766/beyond-growth-signaling-paneth-cells-metabolically-suppport-iscs
#2
Talya L Dayton, Hans Clevers
Single Lgr5 intestinal stem cells (ISCs) can be expanded in vitro into epithelial organoids or "mini-guts", self-organizing cellular structures that recreate the intestinal differentiation program; Paneth cells, which constitute the intestinal stem cell niche, secrete stem cell growth signals, and are thus essential for this process. In a recent paper published in Nature, Rodríguez-Colman et al. describe how Paneth cells may be supporting the metabolic state of ISCs.
April 21, 2017: Cell Research
https://www.readbyqxmd.com/read/28411208/lgr5-cancer-stem-cells-drive-primary-and-metastatic-colorectal-cancer
#3
(no author information available yet)
LGR5(+) colorectal cancer CSCs are dispensable for primary tumor growth due to plasticity.
April 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28404940/rnai-mediated-inhibition-of-lgr5-leads-to-decreased-angiogenesis-in-gastric-cancer
#4
Hong-Qing Xi, Ke-Cheng Zhang, Ji-Yang Li, Jian-Xin Cui, Yun-He Gao, Bo Wei, Dongsheng Huang, Lin Chen
Leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) is a novel gastric cancer marker. However, it is unclear whether it can play roles in tumor angiogenesis. In this study, we aim to investigate the role of Lgr5 on gastric cancer angiogenesis. Lgr5, VEGF expression levels and microvessel density (MVD) were detected in tumor tissue. Then, Lgr5 mRNA was downregulated by small interference RNA technique. Western blotting and real-time quantitative PCR (qRT-PCR) were performed to detect the expression of Lgr5 and VEGF protein and mRNA in Lgr5 siRNA-transfected gastric cancer cells...
February 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404917/expression-and-functional-regulation-of-stemness-gene-lgr5-in-esophageal-squamous-cell-carcinoma
#5
Zhuan Lv, Yu Jane J, Wei-Jie Zhang, Li Xiong, Feng Wang, Li-Feng Li, Xue-Liang Zhou, Xin-Ya Gao, Xian-Fei Ding, Li Han, Ya-Fei Cai, Wang Ma, Liu-Xing Wang
Cancer stem cells (CSCs) are defined as a rare subpopulation of undifferentiated cells with biological characteristics that include the capacity for self-renewal, differentiation into various lineages, and tumor initiation. To explore the mechanism of CSCs in esophageal squamous cell carcinoma (ESCC), we focused on Leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5), a target gene of the Wnt signaling pathway, which has been identified as a marker of intestinal stem cells and shown to be overexpressed in several human malignancies...
February 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28394276/targeting-colorectal-cancer-proliferation-stemness-and-metastatic-potential-using-brassicaceae-extracts-enriched-in-isothiocyanates-a-3d-cell-model-based-study
#6
Lucília P Pereira, Patrícia Silva, Marlene Duarte, Liliana Rodrigues, Catarina M M Duarte, Cristina Albuquerque, Ana Teresa Serra
Colorectal cancer (CRC) recurrence is often attributable to circulating tumor cells and/or cancer stem cells (CSCs) that resist to conventional therapies and foster tumor progression. Isothiocyanates (ITCs) derived from Brassicaceae vegetables have demonstrated anticancer effects in CRC, however little is known about their effect in CSCs and tumor initiation properties. Here we examined the effect of ITCs-enriched Brassicaceae extracts derived from watercress and broccoli in cell proliferation, CSC phenotype and metastasis using a previously developed three-dimensional HT29 cell model with CSC-like traits...
April 10, 2017: Nutrients
https://www.readbyqxmd.com/read/28390865/spdef-induces-quiescence-of-colorectal-cancer-cells-by-changing-the-transcriptional-targets-of-%C3%AE-catenin
#7
Yuan-Hung Lo, Taeko K Noah, Min-Shan Chen, Winnie Zou, Ester Borras, Eduardo Vilar, Noah F Shroyer
BACKGROUND & AIMS: The canonical Wnt signaling pathway activates the transcriptional activity of β-catenin. This pathway is often activated in colorectal cancer cells, but strategies to block it in tumors have not been effective. The SAM pointed domain containing ETS transcription factor (SPDEF) suppresses formation of colon tumors by unclear mechanisms. We investigated these mechanisms and the effects of SPDEF on β-catenin activity in mouse models of colorectal cancer (CRC), CRC cell lines, and mouse and human normal and cancer colonoids...
April 5, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28386338/pigment-epithelium-derived-factor-pedf-peptide-promotes-the-expansion-of-hepatic-stem-progenitor-cells-via-erk-and-stat3-dependent-signaling
#8
Shou-Chuan Shih, Tsung-Chuan Ho, Show-Li Chen, Yeou-Ping Tsao
Hepatic stem/progenitor cells (HPC) have been considered as a potential cell source of an alternative to liver transplantation. Production of large numbers of autologous HPC from small pieces of live tissue is crucial for the application of HPC-based liver therapy. In this study, we demonstrated that a synthetic 44-amino acid peptide (44-mer) derived from pigment epithelium-derived factor (PEDF) can facilitate the production of a large number of actively dividing HPC from normal adult rat livers in a 35-day culture period...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28383763/upregulated-mir-132-in-lgr5-gastric-cancer-stem-cell-like-cells-contributes-to-cisplatin-resistance-via-sirt1-creb-abcg2-signaling-pathway
#9
Lanfang Zhang, Xiaohe Guo, Dezhong Zhang, Yingying Fan, Lei Qin, Shuping Dong, Lanfang Zhang
Cisplatin resistance has long been a major problem that restricts its use. A novel paradigm in tumor biology suggests that gastric tumor chemo-resistance is driven by gastric cancer stem cell-like (GCSCs). Growing evidence has indicated that microRNAs (miRNAs) contributes to chemo-resistance in gastric cancer (GC). Here, Lgr5(+) cells derived from gastric cancer cell lines displayed stem cell-like features. Flow cytometry demonstrated the presence of a variable fraction of Lgr5 in 19 out of 20 GC specimens...
April 6, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28368388/methylation-of-wnt-target-genes-axin2-and-dkk1-as-robust-biomarkers-for-recurrence-prediction-in-stage-ii-colon-cancer
#10
R Kandimalla, J F Linnekamp, S van Hooff, A Castells, X Llor, M Andreu, R Jover, A Goel, J P Medema
Stage II colon cancer (CC) still remains a clinical challenge with patient stratification for adjuvant therapy (AT) largely relying on clinical parameters. Prognostic biomarkers are urgently needed for better stratification. Previously, we have shown that WNT target genes AXIN2, DKK1, APCDD1, ASCL2 and LGR5 are silenced by DNA methylation and could serve as prognostic markers in stage II CC patients using methylation-specific PCR. Here, we have extended our discovery cohort AMC90-AJCC-II (N=65) and methylation was analyzed by quantitative pyrosequencing...
April 3, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28362133/intestinal-epithelial-stem-cells-distinct-behavior-after-surgical-injury-and-teduglutide-administration
#11
Beatriz P Costa, Ana C Gonçalves, Ana M Abrantes, Raquel Alves, Paulo Matafome, Raquel Seiça, Ana B Sarmento-Ribeiro, M Filomena Botelho, Francisco Castro-Sousa
BACKGROUND: Previous studies suggest that intestinal epithelial stem cells (IESC), critical drivers of homeostasis and regeneration, include two subpopulations: crypt-based columnar and "position +4" stem cells, identified by Lgr5 and Bmi1 biomarkers, respectively. Teduglutide is an enterotrophic counterpart of glucagon-like peptide 2. This study aimed to investigate the response of putative IESC to surgical injury and teduglutide administration on an animal model of intestinal resection and anastomosis...
March 31, 2017: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
https://www.readbyqxmd.com/read/28359679/activation-of-wnt-signaling-increases-numbers-of-enteric-neurons-derived-from-neonatal-mouse-and-human-progenitors-cells
#12
Ying Zhang, Karin Seid, Florian Obermayr, Lothar Just, Peter H Neckel
BACKGROUND & AIMS: Neural stem and progenitor cells from the enteric nervous system (ENS) might serve as a source of cells for treatment of neurogastrointestinal disorders. Before we can use these cells, we must increase our understanding of the signaling mechanisms that regulate proliferation and differentiation. We systematically evaluated the effects of canonical Wnt signaling on proliferation and differentiation of cultured ENS progenitor cells from neonatal mice and humans. METHODS: We isolated ENS progenitors from tunica muscularis of the small intestine of new-born (P0) wild-type C57BL/6 mice as well as from Wnt1-Cre2 reporter mice...
March 27, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28358093/a-distinct-role-for-lgr5-stem-cells-in-primary-and-metastatic-colon-cancer
#13
Felipe de Sousa E Melo, Antonina V Kurtova, Jonathan M Harnoss, Noelyn Kljavin, Joerg D Hoeck, Jeffrey Hung, Jeffrey Eastham Anderson, Elaine E Storm, Zora Modrusan, Hartmut Koeppen, Gerrit J P Dijkgraaf, Robert Piskol, Frederic J de Sauvage
Cancer stem cells (CSCs) have been hypothesized to represent the driving force behind tumour progression and metastasis, making them attractive cancer targets. However, conclusive experimental evidence for their functional relevance is still lacking for most malignancies. Here we show that the leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) identifies intestinal CSCs in mouse tumours engineered to recapitulate the clinical progression of human colorectal cancer. We demonstrate that selective Lgr5(+) cell ablation restricts primary tumour growth, but does not result in tumour regression...
March 29, 2017: Nature
https://www.readbyqxmd.com/read/28355176/visualization-and-targeting-of-lgr5-human-colon-cancer-stem-cells
#14
Mariko Shimokawa, Yuki Ohta, Shingo Nishikori, Mami Matano, Ai Takano, Masayuki Fujii, Shoichi Date, Shinya Sugimoto, Takanori Kanai, Toshiro Sato
The cancer stem cell (CSC) theory highlights a self-renewing subpopulation of cancer cells that fuels tumour growth. The existence of human CSCs is mainly supported by xeno-transplantation of prospectively isolated cells, but their clonal dynamics and plasticity remain elusive. Here, we demonstrate that human LGR5(+) colorectal cancer cells serve as CSCs in growing cancer tissues. Lineage-tracing experiments with a CRISPR-Cas9-mediated LGR5-CreER knock-in allele reveal self-renewal and differentiation capacity of LGR5(+) tumour cells...
March 29, 2017: Nature
https://www.readbyqxmd.com/read/28351943/apc-but-not-obesity-synergizes-with-pten-to-drive-intestinal-stem-cell-tumors
#15
Tahmineh Tabrizian, Donghai Wang, Fangxia Guan, Zunju Hu, Amanda Beck, Fabien Delahaye, Derek M Huffman
Obesity is a major risk factor for colorectal cancer and can accelerate Lgr5+ intestinal stem cell (ISC)-derived tumorigenesis following inactivation of Apc. However, whether non-canonical pathways involving PI3K-Akt signaling in ISCs can lead to tumor formation, and if this can be further exacerbated by obesity is unknown. Despite the synergy between Pten and Apc inactivation in epithelial cells on intestinal tumor formation, their combined role in Lgr5+-ISCs, which are the most rapidly dividing ISC population in the intestine, is unknown...
March 28, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28347989/wrn-conditioned-media-is-sufficient-for-in-vitro-propagation-of-intestinal-organoids-from-large-farm-and-small-companion-animals
#16
Robin H Powell, Michael S Behnke
Recent years have seen significant developments in the ability to continuously propagate organoids derived from intestinal crypts. These advancements have been applied to mouse and human samples providing models for gastrointestinal tissue development and disease. We adapt these methods for the propagation of intestinal organoids (enteroids) from various large farm and small companion (LF/SC) animals, including cat, dog, cow, horse, pig, sheep, and chicken. We show that LF/SC enteroids propagate and expand in L-WRN conditioned media containing signaling factors Wnt3a, R-spondin-3, and Noggin (WRN)...
March 27, 2017: Biology Open
https://www.readbyqxmd.com/read/28345588/macrophages-induce-akt-%C3%AE-catenin-dependent-lgr5-stem-cell-activation-and-hair-follicle-regeneration-through-tnf
#17
Xusheng Wang, Haiyan Chen, Ruiyun Tian, Yiling Zhang, Marina S Drutskaya, Chengmei Wang, Jianfeng Ge, Zhimeng Fan, Deqiang Kong, Xiaoxiao Wang, Ting Cai, Ying Zhou, Jingwen Wang, Jinmei Wang, Shan Wang, Zhihai Qin, Huanhuan Jia, Yue Wu, Jia Liu, Sergei A Nedospasov, Edward E Tredget, Mei Lin, Jianjun Liu, Yuyang Jiang, Yaojiong Wu
Skin stem cells can regenerate epidermal appendages; however, hair follicles (HF) lost as a result of injury are barely regenerated. Here we show that macrophages in wounds activate HF stem cells, leading to telogen-anagen transition (TAT) around the wound and de novo HF regeneration, mostly through TNF signalling. Both TNF knockout and overexpression attenuate HF neogenesis in wounds, suggesting dose-dependent induction of HF neogenesis by TNF, which is consistent with TNF-induced AKT signalling in epidermal stem cells in vitro...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28337708/intestinal-crypt-organoid-isolation-of-intestinal-stem-cells-in-vitro-culture-and-optical-observation
#18
Yun Chen, Chuan Li, Ya-Hui Tsai, Sheng-Hong Tseng
The isolation and culture of intestinal stem cells (ISCs) was first demonstrated in the very recent decade with the identification of ISC marker Lgr5. The growth of ISCs into crypt organoids provides an in vitro model for studying the mucosal physiology, intestinal cancer tumorigenesis, and intestinal regeneration. Here, we describe two different isolation protocols and demonstrate a fixation method that aids in the confocal observation of the organoids.
March 24, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28323899/lawsonia-intracellularis-exploits-%C3%AE-catenin-wnt-and-notch-signalling-pathways-during-infection-of-intestinal-crypt-to-alter-cell-homeostasis-and-promote-cell-proliferation
#19
Yang W Huan, Rebecca J Bengtsson, Neil MacIntyre, Jack Guthrie, Heather Finlayson, Sionagh H Smith, Alan L Archibald, Tahar Ait-Ali
Lawsonia intracellularis is an obligate intracellular bacterial pathogen that causes proliferative enteropathy (PE) in pigs. L. intracellularis infection causes extensive intestinal crypt cell proliferation and inhibits secretory and absorptive cell differentiation. However, the affected host upstream cellular pathways leading to PE are still unknown. β-catenin/Wnt signalling is essential in maintaining intestinal stem cell (ISC) proliferation and self-renewal capacity, while Notch signalling governs differentiation of secretory and absorptive lineage specification...
2017: PloS One
https://www.readbyqxmd.com/read/28304405/the-erbb3-receptor-tyrosine-kinase-negatively-regulates-paneth-cells-by-pi3k-dependent-suppression-of-atoh1
#20
Dana Almohazey, Yuan-Hung Lo, Claire V Vossler, Alan J Simmons, Jonathan J Hsieh, Edie B Bucar, Michael A Schumacher, Kathryn E Hamilton, Ken S Lau, Noah F Shroyer, Mark R Frey
Paneth cells (PCs), a secretory population located at the base of the intestinal crypt, support the intestinal stem cells (ISC) with growth factors and participate in innate immunity by releasing antimicrobial peptides, including lysozyme and defensins. PC dysfunction is associated with disorders such as Crohn's disease and necrotizing enterocolitis, but the specific pathways regulating PC development and function are not fully understood. Here we tested the role of the neuregulin receptor ErbB3 in control of PC differentiation and the ISC niche...
March 17, 2017: Cell Death and Differentiation
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