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https://www.readbyqxmd.com/read/29345968/mature-gastric-chief-cells-are-not-required-for-the-development-of-metaplasia
#1
Hiroto Kinoshita, Yoku Hayakawa, Zhengchuan Niu, Mitsuru Konishi, Masahiro Hata, Mayo Tsuboi, Yuki Hayata, Yohko Hikiba, Sozaburo Ihara, Hayato Nakagawa, Yoshihiro Hirata, Timothy C Wang, K Koike
During human gastric carcinogenesis, intestinal metaplasia (IM) is frequently seen in the atrophic stomach. In mice, a distinct type of metaplasia known as spasmolytic polypeptide-expressing metaplasia (SPEM) is found in several inflammatory and genetically engineered models. Given the diversity of long- and short-term models of mouse SPEM, it remains unclear whether all models have a shared or distinct molecular mechanism. The origin of SPEM in mice is currently under debate. It is postulated that stem or progenitor cells acquire genetic alterations that then supply metaplastic cell clones, while the possibility of transdifferentiation or dedifferentiation from mature gastric chief cells has also been suggested...
January 18, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29343849/mutant-p53-gain-of-function-underlies-high-expression-levels-of-colorectal-cancer-stem-cells-markers
#2
Hilla Solomon, Nathan Dinowitz, Ioannis S Pateras, Tomer Cooks, Yoav Shetzer, Alina Molchadsky, Meital Charni, Stav Rabani, Gabriela Koifman, Ohad Tarcic, Ziv Porat, Ira Kogan-Sakin, Naomi Goldfinger, Moshe Oren, Curtis C Harris, Vassilis G Gorgoulis, Varda Rotter
Emerging notion in carcinogenesis ascribes tumor initiation and aggressiveness to cancer stem cells (CSCs). Specifically, colorectal cancer (CRC) development was shown to be compatible with CSCs hypothesis. Mutations in p53 are highly frequent in CRC, and are known to facilitate tumor development and aggressiveness. Yet, the link between mutant p53 and colorectal CSCs is not well-established. In the present study, we set to examine whether oncogenic mutant p53 proteins may augment colorectal CSCs phenotype...
January 18, 2018: Oncogene
https://www.readbyqxmd.com/read/29340033/cxcr4-expressing-mist1-progenitors-in-the-gastric-antrum-contribute-to-gastric-cancer-development
#3
Kosuke Sakitani, Yoku Hayakawa, Huan Deng, Hiroshi Ariyama, Hiroto Kinoshita, Mitsuru Konishi, Satoshi Ono, Nobumi Suzuki, Sozaburo Ihara, Zhengchuan Niu, Woosook Kim, Takayuki Tanaka, Haibo Liu, Xiaowei Chen, Yagnesh Tailor, James G Fox, Stephen F Konieczny, Hiroshi Onodera, Antonia R Sepulveda, Samuel Asfaha, Yoshihiro Hirata, Daniel L Worthley, Kazuhiko Koike, Timothy C Wang
Mist1 was recently shown to identify a discrete population of stem cells within the isthmus of the oxyntic gland within the gastric corpus. Chief cells at the base of the gastric corpus also express Mist1. The relevance of Mist1 expression as a marker of specific cell populations within the antral glands of the distal stomach, however, is unknown. Using Mist1-CreERT mice, we revealed that Mist1+ antral cells, distinct from the Mist1+ population in the corpus, comprise long-lived progenitors that reside within the antral isthmus above Lgr5+ or CCK2R+ cells...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29329541/a-role-for-endothelial-nitric-oxide-synthase-in-intestinal-stem-cell-proliferation-and-mesenchymal-colorectal-cancer
#4
Jon Peñarando, Laura M López-Sánchez, Rafael Mena, Silvia Guil-Luna, Francisco Conde, Vanessa Hernández, Marta Toledano, Victoria Gudiño, Michela Raponi, Caroline Billard, Carlos Villar, César Díaz, José Gómez-Barbadillo, Juan De la Haba-Rodríguez, Kevin Myant, Enrique Aranda, Antonio Rodríguez-Ariza
BACKGROUND: Nitric oxide (NO) has been highlighted as an important agent in cancer-related events. Although the inducible nitric oxide synthase (iNOS) isoform has received most attention, recent studies in the literature indicate that the endothelial isoenzyme (eNOS) can also modulate different tumor processes including resistance, angiogenesis, invasion, and metastasis. However, the role of eNOS in cancer stem cell (CSC) biology and mesenchymal tumors is unknown. RESULTS: Here, we show that eNOS was significantly upregulated in VilCre ERT2 Apc fl/+ and VilCre ERT2 Apc fl/fl mouse intestinal tissue, with intense immunostaining in hyperproliferative crypts...
January 10, 2018: BMC Biology
https://www.readbyqxmd.com/read/29328371/cd133-expression-predicts-post-operative-recurrence-in-patients-with-colon-cancer-with-peritoneal-metastasis
#5
Hiroshi Nagata, Soichiro Ishihara, Junko Kishikawa, Hirofumi Sonoda, Koji Murono, Shigenobu Emoto, Manabu Kaneko, Kazuhito Sasaki, Kensuke Otani, Takeshi Nishikawa, Toshiaki Tanaka, Tomomichi Kiyomatsu, Keisuke Hata, Kazushige Kawai, Hiroaki Nozawa
Despite extensive research on cancer stem cells in colorectal cancer, the impact of stem cell markers on patient survival remains unclear, particularly in those with distant metastasis. In this study, we focused on colon cancer with peritoneal metastasis and investigated the association between the expression of CD133, aldehyde dehydrogenase-1 (ALDH1) and leucine-rich repeating G-protein coupled receptor-5 (Lgr5), and disease prognosis. Putative stem cell marker expression was immunohistochemically evaluated in samples from 142 primary tumours and 75 peritoneal nodules...
January 8, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29316982/the-tankyrase-inhibitor-g007-lk-inhibits-small-intestine-lgr5-stem-cell-proliferation-without-altering-tissue-morphology
#6
Jens Henrik Norum, Ellen Skarpen, Andreas Brech, Raoul Kuiper, Jo Waaler, Stefan Krauss, Therese Sørlie
BACKGROUND: The WNT pathway regulates intestinal stem cells and is frequently disrupted in intestinal adenomas. The pathway contains several potential biotargets for interference, including the poly-ADP ribosyltransferase enzymes tankyrase1 and 2. LGR5 is a known WNT pathway target gene and marker of intestinal stem cells. The LGR5+ stem cells are located in the crypt base and capable of regenerating all intestinal epithelial cell lineages. RESULTS: We treated Lgr5-EGFP-Ires-CreERT2;R26R-Confetti mice with the tankyrase inhibitor G007-LK for up to 3 weeks to assess the effect on duodenal stem cell homeostasis and on the integrity of intestinal epithelium...
January 9, 2018: Biological Research
https://www.readbyqxmd.com/read/29290616/reconstruction-of-the-human-colon-epithelium-in%C3%A2-vivo
#7
Shinya Sugimoto, Yuki Ohta, Masayuki Fujii, Mami Matano, Mariko Shimokawa, Kosaku Nanki, Shoichi Date, Shingo Nishikori, Yoshihiro Nakazato, Tetsuya Nakamura, Takanori Kanai, Toshiro Sato
Genetic lineage tracing has revealed that Lgr5+ murine colon stem cells (CoSCs) rapidly proliferate at the crypt bottom. However, the spatiotemporal dynamics of human CoSCs in vivo have remained experimentally intractable. Here we established an orthotopic xenograft system for normal human colon organoids, enabling stable reconstruction of the human colon epithelium in vivo. Xenografted organoids were prone to displacement by the remaining murine crypts, and this could be overcome by complete removal of the mouse epithelium...
December 21, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29286377/the-organoid-reconstitution-assay-ora-for-the-functional-analysis-of-intestinal-stem-and-niche-cells
#8
Matthias Schewe, Andrea Sacchetti, Mark Schmitt, Riccardo Fodde
The intestinal epithelium is characterized by an extremely rapid turnover rate. In mammals, the entire epithelial lining is renewed within 4 - 5 days. Adult intestinal stem cells reside at the bottom of the crypts of Lieberkühn, are earmarked by expression of the Lgr5 gene, and preserve homeostasis through their characteristic high proliferative rate1. Throughout the small intestine, Lgr5+ stem cells are intermingled with specialized secretory cells called Paneth cells. Paneth cells secrete antibacterial compounds (i...
November 20, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29282803/hair-follicle-stem-cell-faith-is-dependent-on-chromatin-remodeling-capacity-following-low-dose-radiation
#9
Nadine Schuler, Sara Timm, Claudia E Rübe
The main function of the skin, to protect against the environment, is supported by the activity of different stem cell populations. The main focus of this study was elucidating the coping mechanisms of stem cells against the stimulation of constant exposure to genotoxic stresses, both endogenous and exogenous, to ensure long-term function. Investigation of various mouse strains, differing in their DNA repair capacity, enables us to clarify fractionated low-dose irradiation (LDR)-induced consequences for different stem cell populations of the murine hair follicle in their physiological stem cell niche...
December 28, 2017: Stem Cells
https://www.readbyqxmd.com/read/29281035/cellular-responses-and-gene-expression-profiles-of-colonic-lgr5-stem-cells-after-low-dose-low-dose-rate-radiation-exposure
#10
Kensuke Otsuka, Keiji Suzuki, Yuki Fujimichi, Masanori Tomita, Toshiyasu Iwasaki
We previously found that high-dose-rate radiation induced a replenishment of the colonic Lgr5+ stem cell pool, whereas low-dose-rate radiation did not. To identify key molecules that determine the dose-rate effects on this stem cell pool, we harvested colonic Lgr5+ stem cells by cell sorting at 2 weeks after exposure to 1 Gy of high-dose-rate (30 Gy/h) or low-dose-rate (0.003 Gy/h) radiation and analyzed their gene expression profiles using RNA-Seq. We found that pathways related to DNA damage response, cell growth, cell differentiation and cell death were upregulated in Lgr5+ stem cells irradiated with high dose rates, whereas pathways related to apical junctions and extracellular signaling were upregulated in low-dose-rate-irradiated colonic Lgr5+ stem cells...
December 21, 2017: Journal of Radiation Research
https://www.readbyqxmd.com/read/29251085/radioprotective-and-radiomitigative-effects-of-bp-c2-a-novel-lignin-derived-polyphenolic-composition-with-ammonium-molybdate-in-two-mouse-strains-exposed-to-total-body-irradiation
#11
Vladimir N Bykov, Igor S Drachev, Sergey Yu Kraev, Mikhail A Maydin, Ekaterina A Gubareva, Sergey E Pigarev, Vladimir N Anisimov, Irina A Baldueva, Elena I Fedoros, Andrey V Panchenko
PURPOSE: There remains an unmet medical need for radioprotective and mitigative agents. BP-C2 is a novel lignin-derived polyphenolic composition with ammonium molybdate, developed as radioprotector/radiomitigator. OBJECTIVES: The present study evaluated BP-C2 for mitigation of acute radiation syndrome (ARS). METHODS: A total-body irradiation mouse model (TBI, 4.0 - 8.0 Gy) was used in the study. RESULTS: In a 30-day survival study, performed in CBA mice, BP-C2, at a dosage of 81...
December 18, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/29250176/leucine-rich-repeat-containing-g-protein-coupled-receptor-5-and-cd133-expression-is-associated-with-tumor-progression-and-resistance-to-preoperative-chemoradiotherapy-in-low-rectal-cancer
#12
Yuzo Harada, Shinsuke Kazama, Teppei Morikawa, Koji Murono, Koji Yasuda, Kensuke Otani, Takeshi Nishikawa, Toshiaki Tanaka, Tomomichi Kiyomatsu, Kazushige Kawai, Keisuke Hata, Hiroaki Nozawa, Hironori Yamaguchi, Soichiro Ishihara, Toshiaki Watanabe
Preoperative chemoradiotherapy has been performed as a standard therapy for advanced low rectal cancer. Cancer stem cells (CSCs) have been reported to contribute to resistance to treatment and patient prognosis. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) and cluster of differentiation (CD133) are putative markers for CSCs. However, their prognostic ability remains unknown, and evaluation of a single marker can be insufficient due to the heterogeneity of cancer. LGR5 and CD133 expression was immunohistochemically evaluated in surgical specimens of 56 patients who received curative resection following chemoradiotherapy for advanced low rectal cancer...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29235493/small-molecules-related-to-adrenomedullin-reduce-tumor-burden-in-a-mouse-model-of-colitis-associated-colon-cancer
#13
Laura Ochoa-Callejero, Josune García-Sanmartín, Sonia Martínez-Herrero, Susana Rubio-Mediavilla, Judit Narro-Íñiguez, Alfredo Martínez
To investigate the contribution of adrenomedullin (AM) and its gene-related peptide, proadrenomedullin N-terminal 20 peptide (PAMP), to the progression and potential treatment of colon cancer we studied the effects of four small molecules (SM) related to AM and PAMP on a mouse model of colon cancer. For each SM, four experimental groups of male mice were used: (i) Control group; (ii) SM group; (iii) DSS group (injected with azoxymethane [AOM] and drank dextran sulfate sodium [DSS]); and (iv) DSS + SM group (treated with AOM, DSS, and the SM)...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29233928/integrated-molecular-characterization-of-the-lethal-pediatric-cancer-pancreatoblastoma
#14
Tomoya Isobe, Masafumi Seki, Kenichi Yoshida, Masahiro Sekiguchi, Yusuke Shiozawa, Yuichi Shiraishi, Shunsuke Kimura, Misa Yoshida, Yoshikage Inoue, Akira Yokoyama, Nobuyuki Kakiuchi, Hiromichi Suzuki, Keisuke Kataoka, Yusuke Sato, Tomoko Kawai, Kenichi Chiba, Hiroko Tanaka, Teppei Shimamura, Motohiro Kato, Akihiro Iguchi, Asahito Hama, Tomoaki Taguchi, Masaharu Akiyama, Junya Fujimura, Akiko Inoue, Tsuyoshi Ito, Takao Deguchi, Chikako Kiyotani, Tomoko Iehara, Hajime Hosoi, Akira Oka, Masashi Sanada, Yukichi Tanaka, Kenichiro Hata, Satoru Miyano, Seishi Ogawa, Junko Takita
Pancreatoblastoma (PBL) is a rare pediatric pancreatic malignancy for which the molecular pathogenesis is not understood. In this study, we report the findings of an integrated multi-omics study of whole exome and RNA sequencing as well as genome-wide copy number and methylation analyses of 10 PBL cases. The PBL genome was characterized by a high frequency of aberrant activation of the Wnt signaling pathway, either via somatic mutations of CTNNB1 (90%) and copy-neutral loss of heterozygosity (CN-LOH) of APC (10%)...
December 12, 2017: Cancer Research
https://www.readbyqxmd.com/read/29190952/verrucarin-j-inhibits-ovarian-cancer-and-targets-cancer-stem-cells
#15
Kelsey Carter, Pranela Rameshwar, Mariusz Z Ratajczak, Sham S Kakar
Ovarian Cancer is the fifth leading cause of death among women from cancer. Cancer stem cells are a small population of cells present in cancer and the cause of chemoresistance and recurrence of cancer. We tested a new compound "Verrucarin J (VJ)", a metabolite of the Myrothecium fungus family, and showed that VJ significantly inhibits cell proliferation of both cisplatin-sensitive (A2780 and OVCAR5) and cisplatin-resistant (A2780/CP70) cell lines in a dose- and time-dependent manner with IC50 value of approximately 10 nM after 48 h of treatment...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29180573/plasticity-within-the-niche-ensures-the-maintenance-of-a-sox2-stem-cell-population-in-the-mouse-incisor
#16
Maria Sanz-Navarro, Kerstin Seidel, Zhao Sun, Ludivine Bertonnier-Brouty, Brad A Amendt, Ophir D Klein, Frederic Michon
In mice, the incisors grow throughout the animal's life, and this continuous renewal is driven by dental epithelial and mesenchymal stem cells. Sox2 is a principal marker of the epithelial stem cells that reside in the mouse incisor stem cell niche, called the labial cervical loop, but relatively little is known about the role of the Sox2+ stem cell population. In this study, we show that conditional deletion of Sox2 in the embryonic incisor epithelium leads to growth defects and impairment of ameloblast lineage commitment...
November 27, 2017: Development
https://www.readbyqxmd.com/read/29180181/marked-stem-progenitor-cell-expansion-occurs-early-after-murine-ileostomy-a-new-model
#17
Kathryn L Fowler, Minna M Wieck, Ashley E Hilton, Xiaogang Hou, Christopher R Schlieve, Tracy C Grikscheit
BACKGROUND: Improving treatment for short bowel syndrome requires a better understanding of how intestinal adaptation is affected by factors like mechanoluminal stimulation. We hypothesized that in mice, luminal diversion via an ileostomy would drive adaptive changes similar to those seen in human intestine after diversion while offering the opportunity to study the immediate events after resection that precede intestinal adaptation. MATERIALS AND METHODS: With Institutional Animal Care and Use Committee approval, a distal ileostomy with a long distal Hartman's was created in 9- to 14-week-old C57/B6 mice (n = 8)...
December 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/29177131/recent-advances-in-intestinal-stem-cells
#18
Laura R McCabe, Narayanan Parameswaran
Purpose of review: The intestine is a dynamic organ with rapid stem cell division generating epithelial cells that mature and apoptose in 3-5 days. Rapid turnover maintains the epithelial barrier and homeostasis. Current insights on intestinal stem cells (ISCs) and their regulation are discussed here. Recent findings: The Lgr5+ ISCs maintain intestinal homeostasis by dividing asymmetrically, but also divide symmetrically to extinguish or replace ISCs. Following radiation or mucosal injury, reserve BMI1+ ISCs as well as other crypt cells can de-differentiate into Lgr5+ ISCs...
September 2017: Current Molecular Biology Reports
https://www.readbyqxmd.com/read/29167573/metformin-transiently-inhibits-colorectal-cancer-cell-proliferation-as-a-result-of-either-ampk-activation-or-increased-ros-production
#19
Angela Mogavero, Maria Valeria Maiorana, Susanna Zanutto, Luca Varinelli, Fabio Bozzi, Antonino Belfiore, Chiara C Volpi, Annunziata Gloghini, Marco A Pierotti, Manuela Gariboldi
Metformin is a widely used and well-tolerated anti-diabetic drug that can reduce cancer risk and improve the prognosis of certain malignancies. However, the mechanism underlying its anti-cancer effect is still unclear. We studied the anti-cancer activity of metformin on colorectal cancer (CRC) by using the drug to treat HT29, HCT116 and HCT116 p53-/- CRC cells. Metformin reduced cell proliferation and migration by inducing cell cycle arrest in the G0/G1 phase. This was accompanied by a sharp decrease in the expression of c-Myc and down-regulation of IGF1R...
November 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29155957/identification-of-cells-expressing-olfm4-and-lgr5-mrna-by-in-situ-hybridization-in-the-yolk-sac-and-small-intestine-of-embryonic-and-early-post-hatch-chicks
#20
H Zhang, E A Wong
The chicken yolk sac (YS) and small intestine are essential for nutrient absorption during the pre-hatch and post-hatch periods, respectively. Absorptive enterocytes and secretory cells line the intestinal villi and originate from stem cells located in the intestinal crypts. Similarly, in the YS, there are absorptive and secretory cells that presumably originate from a stem cell population. Leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5) and olfactomedin 4 (Olfm4) are 2 widely used markers for intestinal stem cells...
November 15, 2017: Poultry Science
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