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https://www.readbyqxmd.com/read/29163782/bmi1-reduces-atr-activation-and-signalling-caused-by-hydroxyurea
#1
Xiaozeng Lin, Fengxiang Wei, Peter Whyte, Damu Tang
BMI1 facilitates DNA damage response (DDR) induced by double strand DNA breaks; however, it remains unknown whether BMI1 functions in single strand DNA (ssDNA) lesions-initiated DDR. We report here that BMI1 reduces hydroxyurea-elicited ATR activation, thereby reducing the S-phase checkpoints. Hydroxyurea induces ssDNA lesions, which activate ATR through binding TOPBP1 as evidenced by phosphorylation of ATR at threonine 1989 (ATRpT1989). ATR subsequently phosphorylates H2AX at serine 139 (γH2AX) and CHK1 at serine 345 (CHK1pS345), leading to phosphorylation of CDK1 at tyrosine 15 (CDK1pY15) and S-phase arrest...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29162051/in-vitro-characterization-of-cd133-lo-cancer-stem-cells-in-retinoblastoma-y79-cell-line
#2
Rohini M Nair, Murali Ms Balla, Imran Khan, Ravi Kiran Reddy Kalathur, Paturu Kondaiah, Geeta K Vemuganti
BACKGROUND: Retinoblastoma (Rb), the most common childhood intraocular malignant tumor, is reported to have cancer stem cells (CSCs) similar to other tumors. Our previous investigation in primary tumors identified the small sized cells with low CD133 (Prominin-1) and high CD44 (Hyaluronic acid receptor) expression to be putative Rb CSCs using flow cytometry (FSC(lo)/SSC(lo)/CD133(lo)/CD44(hi)). With this preliminary data, we have now utilized a comprehensive approach of in vitro characterization of Y79 Rb cell line following CSC enrichment using CD133 surface marker and subsequent validation to confirm the functional properties of CSCs...
November 21, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29158468/evaluating-the-mechanism-and-therapeutic-potential-of-ptc-028-a-novel-inhibitor-of-bmi-1-function-in-ovarian-cancer
#3
Anindya Dey, Xunhao Xiong, Aleia Crim, Shailendra Kumar Dhar Dwivedi, Soumyajit Banerjee Mustafi, Priyabrata Mukherjee, Liangxian Cao, Nadiya Sydorenko, Ramil Baiazitov, Young-Choon Moon, Melissa Dumble, Thomas Davis, Resham Bhattacharya
BMI-1, also known as a stem cell factor, is frequently upregulated in several malignancies. Elevated expression of BMI-1 correlates with poor prognosis and is therefore considered a viable therapeutic target in a number of malignancies including ovarian cancer. Realizing the immense pathological significance of BMI-1, small molecule inhibitors against BMI1 are recently being developed. In the current study, we functionally characterize PTC-028, an orally bioavailable compound that decreases BMI-1 levels by post-translational modification We report that PTC-028 treatment selectively inhibits cancer cells in clonal growth and viability assays whereas normal cells remain unaffected...
November 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29156724/lncrna-pvt1-and-its-splicing-variant-function-as-competing-endogenous-rna-to-regulate-clear-cell-renal-cell-carcinoma-progression
#4
Tao Yang, Hui Zhou, Peijun Liu, Libin Yan, Weimin Yao, Ke Chen, Jin Zeng, Heng Li, Junhui Hu, Hua Xu, Zhangqun Ye
Long non-coding RNAs (lncRNAs) exert critical regulatory roles in the development and progression of several cancers. Plasmacytoma variant translocation 1 (PVT1), an lncRNA, was shown to be upregulated in clear cell renal cell carcinoma (ccRCC) in our study, while Kaplan-Meier curve and Cox regression analysis showed that high expression of PVT1 was associated with poor overall survival (OS) and disease free survival (DFS) in ccRCC patients. In vitro experiments revealed that PVT1 promoted renal cancer cell proliferation, migration, and invasion, while in vivo studies confirmed its oncogenic roles in ccRCC...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29149196/easy-xeno-free-and-feeder-free-method-for-isolating-and-growing-limbal-stromal-and-epithelial-stem-cells-of-the-human-cornea
#5
Djida Ghoubay-Benallaoua, Céline de Sousa, Raphaël Martos, Gaël Latour, Marie-Claire Schanne-Klein, Elisabeth Dupin, Vincent Borderie
Epithelial and stromal stem cells are required to maintain corneal transparency. The aim of the study was to develop a new method to isolate and grow both corneal stromal (SSC) and epithelial limbal (LSC) stem cells from small human limbal biopsies under culture conditions in accordance with safety requirements mandatory for clinical use in humans. Superficial limbal explants were retrieved from human donor corneo-scleral rims. Human limbal cells were dissociated by digestion with collagenase A, either after epithelial scraping or with no scraping...
2017: PloS One
https://www.readbyqxmd.com/read/29110049/diagnostic-accuracy-of-low-dose-versus-ultra-low-dose-ct-for-lumbar-disc-disease-and-facet-joint-osteoarthritis-in-patients-with-low-back-pain-with-mri-correlation
#6
Sun Hwa Lee, Seong Jong Yun, Hyeon Hwan Jo, Dong Hyeon Kim, Jae Gwang Song, Yong Sung Park
OBJECTIVE: To compare the image quality, radiation dose, and diagnostic performance between low-dose (LD) and ultra-low-dose (ULD) lumbar-spine (L-spine) CT with iterative reconstruction (IR) for patients with chronic low back pain (LBP). METHODS: In total, 260 patients with chronic LBP who underwent L-spine CT between November 2015 and September 2016 were prospectively enrolled. Of these, 143 underwent LD-CT with IR and 117 underwent ULD-CT with IR. The patients were divided according to their body mass index (BMI) into BMI1 (<22...
November 6, 2017: Skeletal Radiology
https://www.readbyqxmd.com/read/29100291/hinokitiol-up-regulates-mir-494-3p-to-suppress-bmi1-expression-and-inhibits-self-renewal-of-breast-cancer-stem-progenitor-cells
#7
Shih-Ming Chen, Bing-Yen Wang, Che-Hsin Lee, Hsueh-Te Lee, Jung-Jung Li, Guan-Ci Hong, Yu-Chieh Hung, Peng-Ju Chien, Che-Ying Chang, Li-Sung Hsu, Wen-Wei Chang
Hinokitiol (β-thujaplicin) is a tropolone-related compound that has anti-microbe, anti-inflammation, and anti-tumor effects. Cancer stem/progenitor cells (CSCs) are a subpopulation of cancer cells with tumor initiation, chemoresistant, and metastatic properties and have been considered the important therapeutic target in future cancer therapy. Previous studies reported that hinokitiol exhibits an anti-cancer activity against murine tumor cells through the induction of autophagy. The current research revealed that hinokitiol suppressed the self-renewal capabilities of human breast CSCs (BCSCs) and inhibited the expression of BMI1 at protein level without suppressing its mRNA...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29081167/-effect-of-bmi1-gene-overexpression-on-hematopoietic-differentiation-colony-forming-assay-of-human-embryonic-stem-cells
#8
Y Zhao, R W Huang, Q Chen, J J Liu
Objective: To study the effect of Bmi1 gene overexpression on hematopoietic differentiation colony-forming assay of human embryonic stem cells. Method: Human embryonic stem cell H1 was co-cultured with mouse bone marrow mesenchymal stem cells OP9 to simulate hematopoietic differentiation in vitro. On the eighth day of co-culture, CD34(+) hematopoietic progenitor cells were selected for colony- forming assay to induce hematopoietic colonies. The expression of Bmi1 gene and BMI1 protein in the process of H1 in vitro hematopoietic differentiation to CD34(+) precursor cells was respectively detected by real-time PCR and Western Blot...
October 31, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/29061784/bmi1-inhibitors-down-regulate-notch-signaling-and-suppress-proliferation-of-acute-leukemia-cells
#9
Mika Ohtaka, Mai Itoh, Shuji Tohda
BACKGROUND/AIM: B cell-specific Moloney murine leukemia virus integration site 1 (BMI1) is up-regulated in several cancers; therefore, we investigated the effects of BMI1 inhibitors on leukemia cells. MATERIALS AND METHODS: Four acute myeloid leukemia and two T-lymphoblastic leukemia cell lines were treated with BMI1 inhibitors artemisinin, PRT4165, and PTC-209 and analyzed for cell proliferation and gene expression by microarray and immunoblotting. RESULTS: PTC-209 and PRT4165 suppressed the growth of all cell lines through apoptosis...
November 2017: Anticancer Research
https://www.readbyqxmd.com/read/29050200/targeting-muc1-c-suppresses-polycomb-repressive-complex-1-in-multiple-myeloma
#10
Ashujit Tagde, Tahireh Markert, Hasan Rajabi, Masayuki Hiraki, Maroof Alam, Audrey Bouillez, David Avigan, Kenneth Anderson, Donald Kufe
The polycomb repressive complex 1 (PRC1) includes the BMI1, RING1 and RING2 proteins. BMI1 is required for survival of multiple myeloma (MM) cells. The MUC1-C oncoprotein is aberrantly expressed by MM cells, activates MYC and is also necessary for MM cell survival. The present studies show that targeting MUC1-C with (i) stable and inducible silencing and CRISPR/Cas9 editing and (ii) the pharmacologic inhibitor GO-203, which blocks MUC1-C function, downregulates BMI1, RING1 and RING2 expression. The results demonstrate that MUC1-C drives BMI1 transcription by a MYC-dependent mechanism...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29042984/bmi1-and-brg1-drive-myocardial-repair-by-regulating-cardiac-stem-cell-function-in-acute-rheumatic-heart-disease
#11
Pingxi Xiao, Kai Zhang, Zhiwen Tao, Niannian Liu, Bangshun Ge, Min Xu, Xinzheng Lu
Rheumatic heart disease (RHD) occurs due to the accumulation of complications associated with rheumatic fever, and it results in high morbidity and mortality. The majority of cases of RHD are diagnosed in the chronic stages, when treatment options are limited. A small reservoir of cardiac stem cells is responsible for maintaining cardiac homeostasis and repairing tissue damage. Understanding the role of cardiac stem cells and the various proteins responsible for their functions in different pathological stages of RHD is an important area of investigation...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29039452/molecular-analysis-of-keratocystic-odontogenic-tumor-cell-lines-derived-from-sporadic-and-basal-cell-nevus-syndrome-patients
#12
Kazuma Noguchi, Keiko Wakai, Tohru Kiyono, Mutsuki Kawabe, Kyohei Yoshikawa, Tomoko Hashimoto-Tamaoki, Hiromitsu Kishimoto, Yoshiro Nakano
Keratocystic odontogenic tumor (KCOT) is a benign tumor often associated with basal cell nevus syndrome (BCNS). Mutations in Patched 1 (PTCH1), the Hedgehog (Hh) receptor, are responsible for BCNS. BCNS is distinguished by morphological anomalies and predisposition to benign and malignant tumors, including medulloblastoma, basal cell carcinoma, KCOT and ovarian fibromas. Among these tumors, KCOT is the least well studied because a suitable model system is not available for its investigation. To enable KCOT to be studied, we established two KCOT cell lines, one from a BCNS case (designated as iKCOT1) and one from a sporadic KCOT case (designated as sKCOT1)...
October 9, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29035367/targeting-glioma-stem-cells-through-combined-bmi1-and-ezh2-inhibition
#13
Xun Jin, Leo J Y Kim, Qiulian Wu, Lisa C Wallace, Briana C Prager, Tanwarat Sanvoranart, Ryan C Gimple, Xiuxing Wang, Stephen C Mack, Tyler E Miller, Ping Huang, Claudia L Valentim, Qi-Gang Zhou, Jill S Barnholtz-Sloan, Shideng Bao, Andrew E Sloan, Jeremy N Rich
Glioblastomas are lethal cancers defined by angiogenesis and pseudopalisading necrosis. Here, we demonstrate that these histological features are associated with distinct transcriptional programs, with vascular regions showing a proneural profile, and hypoxic regions showing a mesenchymal pattern. As these regions harbor glioma stem cells (GSCs), we investigated the epigenetic regulation of these two niches. Proneural, perivascular GSCs activated EZH2, whereas mesenchymal GSCs in hypoxic regions expressed BMI1 protein, which promoted cellular survival under stress due to downregulation of the E3 ligase RNF144A...
November 2017: Nature Medicine
https://www.readbyqxmd.com/read/29026462/murine-hepatocellular-carcinoma-derived-stem-cells-reveal-epithelial-to-mesenchymal-plasticity
#14
Aparna Jayachandran, Ritu Shrestha, Bijay Dhungel, I-Tao Huang, Marianna Yumi Kawashima Vasconcelos, Brian J Morrison, Charmaine A Ramlogan-Steel, Jason C Steel
AIM: To establish a model to enrich and characterize stem-like cells from murine normal liver and hepatocellular carcinoma (HCC) cell lines and to further investigate stem-like cell association with epithelial-to-mesenchymal transition (EMT). METHODS: In this study, we utilized a stem cell conditioned serum-free medium to enrich stem-like cells from mouse HCC and normal liver cell lines, Hepa 1-6 and AML12, respectively. We isolated the 3-dimensional spheres and assessed their stemness characteristics by evaluating the RNA levels of stemness genes and a cell surface stem cell marker by quantitative reverse transcriptase-PCR (qRT-PCR)...
September 26, 2017: World Journal of Stem Cells
https://www.readbyqxmd.com/read/29018209/erratum-mir-15a-mir-16-down-regulates-bmi1-impacting-ub-h2a-mediated-dna-repair-and-breast-cancer-cell-sensitivity-to-doxorubicin
#15
Nibedita Patel, Koteswara Rao Garikapati, Raj K Pandita, Dharmendra Kumar Singh, Tej K Pandita, Utpal Bhadra, Manika Pal Bhadra
A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.
October 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28994199/inhibition-of-mek-erk-signalling-pathway-promotes-erythroid-differentiation-and-reduces-hscs-engraftment-in-ex%C3%A2-vivo-expanded-haematopoietic-stem-cells
#16
Morteza Zarrabi, Elaheh Afzal, Mohammad Hossein Asghari, Monireh Mohammad, Hamidreza Aboulkheyr Es, Marzieh Ebrahimi
The MEK/ERK pathway is found to be important in regulating different biological processes such as proliferation, differentiation and survival in a wide variety of cells. However, its role in self-renewal of haematopoietic stem cells is controversial and remains to be clarified. The aim of this study was to understand the role of MEK/ERK pathway in ex vivo expansion of mononuclear cells (MNCs) and purified CD34(+) cells, both derived from human umbilical cord blood (hUCB). Based on our results, culturing the cells in the presence of an inhibitor of MEK/ERK pathway-PD0325901 (PD)-significantly reduces the expansion of CD34(+) and CD34(+)  CD38(-) cells, while there is no change in the expression of stemness-related genes (HOXB4, BMI1)...
October 10, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28986650/expression-of-stem-cell-factors-in-the-adult-sea-cucumber-digestive-tube
#17
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/28976514/role-of-epigenetic-regulation-on-the-induction-of-apoptosis-in-jurkat-leukemia-cells-by-white-grape-pomace-rich-in-phenolic-compounds
#18
Antonio J León-González, M José Jara-Palacios, Malak Abbas, Francisco J Heredia, Valérie B Schini-Kerth
Grape pomace is a rich source of phenolic compounds commonly employed for elaboration of dietary supplements. The aim of the present study was to investigate the anticancer effect of a purified white grape pomace extract (PWGPE) in acute lymphoblastic leukemia Jurkat cells and to characterize the underlying mechanism. Apoptosis, mitochondrial membrane potential and reactive oxygen species (ROS) levels were assessed by flow cytometry and protein expression levels were analysed by Western blotting. PWGPE induced apoptosis in Jurkat cells in a time- and concentration-dependent manner...
October 4, 2017: Food & Function
https://www.readbyqxmd.com/read/28966728/deregulated-expression-of-microrna-200b-c-and-suz12-a-polycomb-repressive-complex-2-subunit-in-chemoresistant-colorectal-cancer-cells
#19
KayKay San, Megan Horita, Aravinda Ganapathy, G Chinnadurai, Uthayashanker R Ezekiel
In colorectal cancer, chemotherapy and/or radiotherapy can lead to the formation of resistant cells that become metastatic through Epithelial-Mesenchymal Transition (EMT). Invasive and metastatic characteristics of carcinoma cells in primary tumors are mediated by EMT. During EMT, the primary tumor cells lose cell-cell adhesion, have increased intercellular separation, and gain an elongated shape with pseudopodia. There is also dysregulation of Polycomb group proteins (such as BMI1, SUZ12, and EZH2), and changes in the expression of microRNA-200 (miR-200) family...
July 2017: Genes & Cancer
https://www.readbyqxmd.com/read/28950927/mir-29a-inhibits-growth-and-metastasis-of-melanoma-a375-cells-by-directly-targeting-bmi1
#20
Ying Xiong, Liqian Liu, Ying Qiu, Lili Liu
Melanoma is one of the most aggressive malignant tumors, with increasing incidence, poor prognosis, and lack of any effective targeted therapy. Abnormal expression of miR-29a has been found in several types of cancers, including melanoma. However, the role of miR-29a in melanoma, and the molecular mechanism by which miR-29a represses melanoma are rarely reported. Cell transfection efficiency was determined by Quantitative real-time PCR or Western blot. The cell viability, apoptosis, migration, and invasion were respectively determined by Cell Counting Kit-8 assay, PI/FITC-Annexin V staining assay, wound healing assay and Transwell assay...
September 26, 2017: Oncology Research
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