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https://www.readbyqxmd.com/read/28195397/alcohol-injury-damages-intestinal-stem-cells
#1
Rong Lu, Robin M Voigt, Yongguo Zhang, Ikuko Kato, Yinglin Xia, Christopher B Forsyth, Ali Keshavarzian, Jun Sun
BACKGROUND: Alcohol consumption is associated with intestinal injury including intestinal leakiness and the risk of developing progressive gastrointestinal cancer. Alcoholics have disruption of intestinal barrier dysfunction that persists weeks after stopping alcohol intake and this occurs in spite of the fact that intestinal epithelial cells turn over every 3-5 days. The renewal and functional regulation of the intestinal epithelium largely relies on intestinal stem cells (ISCs). Chronic inflammation and tissue damage in the intestine can injure stem cells including accumulation of mutations that may result in ISC dysfunction and transformation...
February 14, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28179359/vegfa-activates-an-epigenetic-pathway-upregulating-ovarian-cancer-initiating-cells
#2
Kibeom Jang, Minsoon Kim, Candace A Gilbert, Fiona Simpkins, Tan A Ince, Joyce M Slingerland
The angiogenic factor, VEGFA, is a therapeutic target in ovarian cancer (OVCA). VEGFA can also stimulate stem-like cells in certain cancers, but mechanisms thereof are poorly understood. Here, we show that VEGFA mediates stem cell actions in primary human OVCA culture and OVCA lines via VEGFR2-dependent Src activation to upregulate Bmi1, tumor spheres, and ALDH1 activity. The VEGFA-mediated increase in spheres was abrogated by Src inhibition or SRC knockdown. VEGFA stimulated sphere formation only in the ALDH1(+) subpopulation and increased OVCA-initiating cells and tumor formation in vivo through Bmi1...
February 8, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28176811/intestinal-cancer-stem-cells-marked-by-bmi1-or-lgr5-expression-contribute-to-tumor-propagation-via-clonal-expansion
#3
Hirotsugu Yanai, Naho Atsumi, Toshihiro Tanaka, Naohiro Nakamura, Yoshihiro Komai, Taichi Omachi, Kiyomichi Tanaka, Kazuhiko Ishigaki, Kazuho Saiga, Haruyuki Ohsugi, Yoko Tokuyama, Yuki Imahashi, Shuichi Ohe, Hiroko Hisha, Naoko Yoshida, Keiki Kumano, Masanori Kon, Hiroo Ueno
Although the existence of cancer stem cells in intestine tumors has been suggested, direct evidence has not been yet provided. Here, we showed, using the multicolor lineage-tracing method and mouse models of intestinal adenocarcinoma and adenoma that Bmi1- or Lgr5- positive tumorigenic cells clonally expanded in proliferating tumors. At tumor initiation and during tumor propagation in the colon, the descendants of Lgr5-positive cells clonally proliferated to form clusters. Clonal analysis using ubiquitous multicolor lineage tracing revealed that colon tumors derived from Lgr5-positive cells were monoclonal in origin but eventually merged with neighboring tumors, producing polyclonal tumors at the later stage...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28148261/dclk1-a-tumor-stem-cell-marker-regulates-pro-survival-signaling-and-self-renewal-of-intestinal-tumor-cells
#4
Parthasarathy Chandrakesan, Jiannan Yao, Dongfeng Qu, Randal May, Nathaniel Weygant, Yang Ge, Naushad Ali, Sripathi M Sureban, Modhi Gude, Kenneth Vega, Eddie Bannerman-Menson, Lijun Xia, Michael Bronze, Guangyu An, Courtney W Houchen
BACKGROUND: More than 80% of intestinal neoplasia is associated with the adenomatous polyposis coli (APC) mutation. Doublecortin-like kinase 1 (Dclk1), a kinase protein, is overexpressed in colorectal cancer and specifically marks tumor stem cells (TSCs) that self-renew and increased the tumor progeny in Apc (Min/+) mice. However, the role of Dclk1 expression and its contribution to regulating pro-survival signaling for tumor progression in Apc mutant cancer is poorly understood. METHODS: We analyzed DCLK1 and pro-survival signaling gene expression datasets of 329 specimens from TCGA Colon Adenocarcinoma Cancer Data...
February 1, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28104398/down-regulation-of-boris-ctcfl-efficiently-regulates-cancer-stemness-and-metastasis-in-mycn-amplified-neuroblastoma-cell-line-by-modulating-wnt-%C3%AE-catenin-signaling-pathway
#5
Koteswara Rao Garikapati, Nibedita Patel, Venkata Krishna Kanth Makani, Priyanka Cilamkoti, Utpal Bhadra, Manika Pal Bhadra
BORIS/CTCFL is a vital nucleotide binding protein expressed during embryogenesis and gametogenesis. BORIS/CTCFL is the paralogue of transcriptional repressor protein CTCF, which is aberrantly expressed in various malignancies and primarily re-expressed in cancer stem cells (CSCs). The mechanism behind regulation of BORIS in various cancer conditions and tumor metastases is so far not explored in detail. The aim of the study was to understand the influence of BORIS/CTCFL on stemness and metastasis by regulating well-known oncogenes and related signaling pathways...
January 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28098896/microrna-194-represses-glioma-cell-epithelial%C3%A2-to%C3%A2-mesenchymal-transition-by-targeting-bmi1
#6
Xi Zhang, Chunyan Wei, Jin Li, Jiali Liu, Jianqiang Qu
MicroRNA-194 (miR-194) is frequently dysregulated in many types of cancer. However, the function of miR-194 in glioma remains unknown. In the present study, we aimed to investigate the biological functions of miR-194 in glioma and the potential molecular mechanism of miR-194 involved in glioma progression. We found that miR-194 expression was significantly reduced in glioma specimens and cell lines, as detected by real-time quantitative polymerase chain reaction (RT-qPCR) analysis. The overexpression of miR-194 inhibited while the suppression of miR-194 promoted cell migration, invasion and epithelial mesenchymal transition (EMT) in glioma cells...
January 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28079973/a-regulatory-bmi1-let-7i-erk3-pathway-controls-the-motility-of-head-and-neck-cancer-cells
#7
Lobna Elkhadragy, Minyi Chen, Kennon Miller, Muh-Hwa Yang, Weiwen Long
Extracellular signal-regulated kinase 3 (ERK3) is an atypical mitogen-activated protein kinase (MAPK), whose biological activity is tightly regulated by its cellular abundance. Recent studies have revealed that ERK3 is upregulated in multiple cancers and promotes cancer cell migration/invasion and drug resistance. Little is known, however, about how ERK3 expression level is upregulated in cancers. Here, we have identified the oncogenic polycomb group protein BMI1 as a positive regulator of ERK3 level in head and neck cancer cells...
February 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28041973/prognostic-significance-of-stromal-grem1-expression-in-colorectal-cancer
#8
Bo Gun Jang, Hye Sung Kim, Weon Young Chang, Jeong Mo Bae, Hyeon Jeong Oh, Xianyu Wen, Seorin Jeong, Nam Yun Cho, Woo Ho Kim, Gyeong Hoon Kang
Cancer associated fibroblasts (CAFs) are the dominant cell population in the cancer stroma. Gremlin 1 (GREM1), an antagonist of the bone morphogenetic protein pathway, is expressed by CAFs in a variety of human cancers. However, its biological significance for cancer patients is largely unknown. We applied RNA in situ hybridization (ISH) to evaluate the prognostic value of stromal GREM1 expression in a large cohort of 670 colorectal cancers (CRCs). Overall GREM1 expression in CRCs was lower than that of the matched normal mucosa, and GREM1 expression had a strong positive correlation with BMI1 and inverse correlations with EPHB2 and OLFM4...
December 29, 2016: Human Pathology
https://www.readbyqxmd.com/read/28004815/bmi1-positive-cells-in-the-lingual-epithelium-could-serve-as-cancer-stem-cells-in-tongue-cancer
#9
Toshihiro Tanaka, Naho Atsumi, Naohiro Nakamura, Hirotsugu Yanai, Yoshihiro Komai, Taichi Omachi, Kiyomichi Tanaka, Kazuhiko Ishigaki, Kazuho Saiga, Haruyuki Ohsugi, Yoko Tokuyama, Yuki Imahashi, Hiroko Hisha, Naoko Yoshida, Keiki Kumano, Kazuichi Okazaki, Hiroo Ueno
We recently reported that the polycomb complex protein Bmi1 is a marker for lingual epithelial stem cells (LESCs), which are involved in the long-term maintenance of lingual epithelial tissue in the physiological state. However, the precise role of LESCs in generating tongue tumors and Bmi1-positive cell lineage dynamics in tongue cancers are unclear. Here, using a mouse model of chemically (4-nitroquinoline-1-oxide: 4-NQO) induced tongue cancer and the multicolor lineage tracing method, we found that each unit of the tumor was generated by a single cell and that the assembly of such cells formed a polyclonal tumor...
December 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27965321/suppressing-p16ink4a-and-p14arf-pathways-overcomes-apoptosis-in-individualized-human-embryonic-stem-cells
#10
Wenqian Wang, Yanling Zhu, Ke Huang, Yongli Shan, Juan Du, Xiaoya Dong, Ping Ma, Penafei Wu, Jian Zhang, Wenhao Huang, Tian Zhang, Baojian Liao, Deyang Yao, Guangjin Pan, Jiajun Liu
Dissociation-induced apoptosis is a striking phenomenon in human embryonic stem cells (hESCs), but not in naïve mouse ESCs. Rho-associated kinase-dependent actin-myosin hyperactivation is an underlying mechanism that triggers apoptosis in dissociated hESCs; however, in this study, we show that the Ink4A-ARF-mediated senescence pathway is another mechanism to cause apoptosis in individualized hESCs. We show that P16(INK4A) and P14(ARF) are immediately induced in hESCs upon dissociation, but not in mouse ESCs...
December 13, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27926533/andrographolide-impedes-cancer-stemness-and-enhances-radio-sensitivity-in-oral-carcinomas-via-mir-218-activation
#11
Po-Yu Yang, Pei-Ling Hsieh, Tong Hong Wang, Cheng-Chia Yu, Ming-Yi Lu, Yi-Wen Liao, Tzu-Hsin Lee, Chih-Yu Peng
Current evidence suggests that oral cancer stem cells (OCSCs) possess high tumorigenic and metastatic properties as well as chemo- and radioresistance. In this study, we demonstrated that andrographolide, the main bioactive component in the medicinal plant Andrographis, significantly reduced oncogenicity and restored radio-sensitivity of ALDH1+CD44+ OCSCs. Mechanistic studies showed that andrographolide treatment increased the expression of microRNA-218 (miR-218), leading to the downregulation of Bmi1. We showed that knockdown of miR-218 in ALDH1-CD44- non-OCSCs enhanced cancer stemness, while silencing of Bmi1 significantly counteracted it...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27920552/the-relationship-between-the-expression-of-usp22-bmi1-and-ezh2-in-hepatocellular-carcinoma-and-their-impacts-on-prognosis
#12
Run Zhai, Fang Tang, Jianhua Gong, Jing Zhang, Biao Lei, Bo Li, Yangchao Wei, Xingsi Liang, Bo Tang, Songqing He
Recent studies have shown that deubiquitination plays a key role in tumor progression, metastasis, resistance to chemotherapy drugs, and prognosis. In this study, we investigated the effects of the deubiquitinating enzyme USP22 on the expression of the drug-resistance genes BMI1 and EZH2 in hepatocellular carcinoma (HCC) and on prognosis. Downregulation of USP22 expression with interference ribonucleic acid in resistant HCC cell lines with high USP22 expression resulted in decreased BMI1 expression, but had no effect on EZH2 expression...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27904674/bmi1-plays-an-important-role-in-dentin-and-mandible-homeostasis-by-maintaining-redox-balance
#13
Ying Yin, Xian Xue, Qian Wang, Ning Chen, Dengshun Miao
To explore whether polycomb repressor Bmi1 plays an important role in dentin and mandible development homeostasis by maintaining redox balance, 3-week-old Bmi1 gene knockout (Bmi1(-/-)) mice were treated with the antioxidant N-acetylcysteine (NAC) for 2 weeks in their drinking water and phenotypes of the tooth and mandibles were compared with vehicle-treated Bmi1(-/-) mice and wild-type mice by radiograph, histochemistry and immunohistochemistry. Alterations of oxidative stress, DNA damage, cell proliferation and cell cycle-related parameters were also examined in mandibles...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27901496/cancer-initiating-cells-are-enriched-in-the-ca9-positive-fraction-of-primary-cervix-cancer-xenografts
#14
Delphine Tamara Marie-Egyptienne, Naz Chaudary, Tuula Kalliomäki, David William Hedley, Richard Peter Hill
Numerous studies have suggested that Cancer Initiating Cells (CIC) can be identified/enriched in cell populations obtained from solid tumors based on the expression of cell surface marker proteins. We used early passage primary cervix cancer xenografts to sort cells based on the expression of the intrinsic hypoxia marker Carbonic Anhydrase 9 (CA9) and tested their cancer initiation potential by limiting dilution assay. We demonstrated that CICs are significantly enriched in the CA9+ fraction in 5/6 models studied...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/27900059/expression-and-survival-significance-of-b-cell-specific-moloney-murine-leukemia-virus-integration-site-1-and-matrix-metalloproteinase-9-in-non-small-cell-lung-cancer
#15
Mingkui Mu, Yang Song, Bin Zhang
One of the main challenges in lung cancer research is identifying patients at high risk of progression and metastasis following surgical resection. In the present study, the prognostic significance of B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1) and matrix metalloproteinase-9 (MMP9) in non-small-cell lung cancer (NSCLC) was evaluated. BMI1 and MMP9 expression in tumors from 132 surgical NSCLC patients [squamous cell carcinoma (SCC), n=79; and adenocarcinoma (AD), n=53] was evaluated by immunohistochemistry...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27893710/muc1-c-activates-bmi1-in-human-cancer-cells
#16
M Hiraki, T Maeda, A Bouillez, M Alam, A Tagde, K Hinohara, Y Suzuki, T Markert, M Miyo, K Komura, R Ahmad, H Rajabi, D Kufe
B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1) is a component of the polycomb repressive complex 1 (PRC1) complex that is overexpressed in breast and other cancers, and promotes self-renewal of cancer stem-like cells. The oncogenic mucin 1 (MUC1) C-terminal (MUC1-C) subunit is similarly overexpressed in human carcinoma cells and has been linked to their self-renewal. There is no known relationship between MUC1-C and BMI1 in cancer. The present studies demonstrate that MUC1-C drives BMI1 transcription by a MYC-dependent mechanism in breast and other cancer cells...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27876791/an-amino-acid-based-oral-rehydration-solution-aa-ors-enhanced-intestinal-epithelial-proliferation-in-mice-exposed-to-radiation
#17
Liangjie Yin, Reshu Gupta, Lauren Vaught, Astrid Grosche, Paul Okunieff, Sadasivan Vidyasagar
Destruction of clonogenic cells in the crypt following irradiation are thought to cause altered gastrointestinal function. Previously, we found that an amino acid-based oral rehydration solution (AA-ORS) improved gastrointestinal function in irradiated mice. However, the exact mechanisms were unknown. Electrophysiology, immunohistochemistry, qPCR, and Western blot analysis were used to determine that AA-ORS increased proliferation, maturation, and differentiation and improved electrolyte and nutrient absorption in irradiated mice...
November 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27869129/reprogramming-mouse-fibroblasts-into-engraftable-myeloerythroid-and-lymphoid-progenitors
#18
Hui Cheng, Heather Yin-Kuan Ang, Chadi A El Farran, Pin Li, Hai Tong Fang, Tong Ming Liu, Say Li Kong, Michael Lingzi Chin, Wei Yin Ling, Edwin Kok Hao Lim, Hu Li, Tara Huber, Kyle M Loh, Yuin-Han Loh, Bing Lim
Recent efforts have attempted to convert non-blood cells into hematopoietic stem cells (HSCs) with the goal of generating blood lineages de novo. Here we show that hematopoietic transcription factors Scl, Lmo2, Runx1 and Bmi1 can convert a developmentally distant lineage (fibroblasts) into 'induced hematopoietic progenitors' (iHPs). Functionally, iHPs generate acetylcholinesterase(+) megakaryocytes and phagocytic myeloid cells in vitro and can also engraft immunodeficient mice, generating myeloerythoid and B-lymphoid cells for up to 4 months in vivo...
November 21, 2016: Nature Communications
https://www.readbyqxmd.com/read/27865367/circulating-tumor-stem-like-cells-in-oral-squamous-cell-carcinoma-an-unresolved-paradox
#19
Shanaya Patel, Kavan Shah, Sheefa Mirza, Kanisha Shah, Rakesh Rawal
OBJECTIVE: Circulating tumor cells (CTCs) are increasingly gaining importance due to their immense potential in enhancing diagnosis, prognosis and response to therapy in solid malignancies. Therefore, we aimed to comprehend the molecular diversity and critical role of this disseminated tumor population in OSCC. METHODOLOGY: CD44+ subpopulation was isolated using immuno-magnetic cell separation and their purity was validated using flow cytometry. Characterisation of self renewal potential and resistance to chemotherapy was assessed using tumor sphere forming and cytotoxicity assay...
November 2016: Oral Oncology
https://www.readbyqxmd.com/read/27863490/suberoylanilide-hydroxamic-acid-represses-glioma-stem-like-cells
#20
Che-Chia Hsu, Wen-Chang Chang, Tsung-I Hsu, Jr-Jiun Liu, Shiu-Hwa Yeh, Jia-Yi Wang, Jing-Ping Liou, Chiung-Yuan Ko, Kwang-Yu Chang, Jian-Ying Chuang
BACKGROUND: Glioma stem-like cells (GSCs) are proposed to be responsible for high resistance in glioblastoma multiforme (GBM) treatment. In order to find new strategies aimed at reducing GSC stemness and improving GBM patient survival, we investigated the effects and mechanism of a histone deacetylases (HDACs) inhibitor, suberoylanilide hydroxamic acid (SAHA), since HDAC activity has been linked to cancer stem-like cell (CSC) abundance and properties. METHODS: Human GBM cell lines were plated in serum-free suspension cultures allowed for sphere forming and CSC enrichment...
November 18, 2016: Journal of Biomedical Science
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