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Olugbenga Awolaran, Susan A Brooks, Verna Lavender
Metastasis accounts for most of the deaths from breast cancer and the preference of invasive breast cancer metastasising to bone has been widely reported. However, the biological basis of breast cancer osteotropism is not fully understood. This paper provides, for the first time, an integrative, systematic review of evidence of molecular factors that have functional roles in the homing of metastatic breast cancer to the bone. Pubmed, Web of Science and EBSCOhost were searched using keywords and synonyms for molecular, metastasis, breast cancer and bone to identify articles published between January 2004 and August 2016...
October 14, 2016: Breast: Official Journal of the European Society of Mastology
Dongmei Su, Jun-Xian Song, Qianqian Gao, Lina Guan, Qian Li, Cuige Shi, Xu Ma
Gestational diabetes mellitus is a risk factor for abnormal heart development, but the molecular basis remains obscure. To further analyze this, the hyperglycemia rat and cell model were established in this study. The results showed that hyperglycemic rats gained significantly less weight during gestation than controls. The number of embryos per litter was significantly reduced in diabetic mothers compared to controls. Ventricular wall thickness was often decreased in the diabetic offspring and cardiomyocyte apoptosis participated in ventricular wall thinness...
October 28, 2016: Biochemical and Biophysical Research Communications
Daoyin Dong, Yuji Zhang, E Albert Reece, Lei Wang, Christopher R Harman, Peixin Yang
Maternal pregestational diabetes mellitus (PGDM) induces congenital heart defects (CHDs). The molecular mechanism underlying PGDM-induced CHDs is unknown. microRNAs (miRNAs), small non-coding RNAs, repress gene expression at the posttranscriptional level and play important roles in heart development. We performed a global miRNA profiling study to assist in revealing potential miRNAs modulated by PGDM and possible developmental pathways regulated by miRNAs during heart development. A total of 149 mapped miRNAs in the developing heart were significantly altered by PGDM...
October 2016: Reproductive Toxicology
Hiroyuki Minemura, Kiyoshi Takagi, Ai Sato, Hikaru Takahashi, Yasuhiro Miki, Yukiko Shibahara, Mika Watanabe, Takanori Ishida, Hironobu Sasano, Takashi Suzuki
CITED2 (Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 2) is a member of CITED family and involved in various cellular functions during development and differentiation. Mounting evidence suggests importance of CITEDs in the progression of human malignancies, but significance of CITED2 protein has not yet been examined in breast carcinoma. Therefore, in this study, we examined clinical significance and biological functions of CITED2 in breast carcinoma by immunohistochemistry and in vitro studies...
September 14, 2016: Cancer Science
Xuanchun Wang, Samuel M Lockhart, Thomas Rathjen, Hassan Albadawi, Ditte Sørensen, Brian T O'Neill, Nishant Dwivedi, Simone R Preil, Hans Christian Beck, Sally L Dunwoodie, Michael T Watkins, Lars Melholt Rasmussen, Christian Rask-Madsen
In patients with atherosclerotic complications of diabetes, impaired neovascularization of ischemic tissue in the myocardium and lower limb limits the ability of these tissues to compensate for poor perfusion. We identified 10 novel insulin-regulated genes, among them Adm, Cited2 and Ctgf, which were downregulated in endothelial cells by insulin through FoxO1. CITED2, which was downregulated by insulin by up to 54%, is an important negative regulator of hypoxia-inducible factor (HIF) and impaired HIF signaling is a key mechanism underlying the impairment of angiogenesis in diabetes...
August 25, 2016: Diabetes
Christopher W Pugh
Hypoxia stimulates a variety of adaptive responses, many mediated via the hypoxia inducible factors (HIF) family of transcriptional complexes. The balance of HIF-1, -2 and -3 controls a variety of genes, directly up-regulating transcription of genes involved in erythropoiesis, angiogenesis, vasomotor tone, metabolic pathways and processes related to cell multiplication and survival, and indirectly reducing the transcription of genes with other effects. HIF transcription factors are heterodimers consisting of an oxygen-regulated alpha chain bound to the constitutive aryl hydrocarbon receptor nuclear translocator...
2016: Advances in Experimental Medicine and Biology
Ryann M Fame, Jessica L MacDonald, Sally L Dunwoodie, Emi Takahashi, Jeffrey D Macklis
UNLABELLED: The neocortex contains hundreds to thousands of distinct subtypes of precisely connected neurons, allowing it to perform remarkably complex tasks of high-level cognition. Callosal projection neurons (CPN) connect the cerebral hemispheres via the corpus callosum, integrating cortical information and playing key roles in associative cognition. CPN are a strikingly diverse set of neuronal subpopulations, and development of this diversity requires precise control by a complex, interactive set of molecular effectors...
June 15, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Zhuo Zhang, Daniel J Leong, Lin Xu, Zhiyong He, Angela Wang, Mahantesh Navati, Sun J Kim, David M Hirsh, John A Hardin, Neil J Cobelli, Joel M Friedman, Hui B Sun
BACKGROUND: Curcumin has been shown to have chondroprotective potential in vitro. However, its effect on disease and symptom modification in osteoarthritis (OA) is largely unknown. This study aimed to determine whether curcumin could slow progression of OA and relieve OA-related pain in a mouse model of destabilization of the medial meniscus (DMM). METHODS: Expression of selected cartilage degradative-associated genes was evaluated in human primary chondrocytes treated with curcumin and curcumin nanoparticles and assayed by real-time PCR...
2016: Arthritis Research & Therapy
Swaathi Jayaraman, Michele Doucet, Wen Min Lau, Scott L Kominsky
UNLABELLED: Previously, we identified the transcriptional coactivator CITED2 as a potential facilitator of bone metastasis using a murine mammary cancer model. Extending these studies to human breast cancer, it was observed that CITED2 mRNA expression was significantly elevated in patient specimens of metastatic breast cancer relative to primary tumors, with highest levels in metastasis to bone relative to non-bone sites. To further evaluate CITED2 functions in breast cancer metastasis, CITED2 expression was stably reduced in the human breast cancer cell lines MDA-MB-231 and MDA-MB-468, which are metastatic in animal models...
August 2016: Molecular Cancer Research: MCR
Kazuhiko Imakawa, Pramod Dhakal, Kaiyu Kubota, Kazuya Kusama, Damayanti Chakraborty, M A Karim Rumi, Michael J Soares
Trophoblast stem (TS) cells possess the capacity to differentiate along a multi-lineage pathway yielding several specialized cell types. The regulatory network controlling trophoblast cell differentiation is poorly understood. Cbp/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain, 2 (CITED2) has been implicated in the regulation of placentation; however, we know little about how CITED2 acts to influence trophoblast cells. Rat Rcho-1 TS cells can be manipulated to proliferate or differentiate into specialized trophoblast lineages and are an excellent model for investigating trophoblast differentiation...
May 2016: Reproduction: the Official Journal of the Society for the Study of Fertility
Ryann M Fame, Colette Dehay, Henry Kennedy, Jeffrey D Macklis
Callosal projection neurons (CPN) interconnect the neocortical hemispheres via the corpus callosum and are implicated in associative integration of multimodal information. CPN have undergone differential evolutionary elaboration, leading to increased diversity of cortical neurons-and more extensive and varied connections in neocortical gray and white matter-in primates compared with rodents. In mouse, distinct sets of genes are enriched in discrete subpopulations of CPN, indicating the molecular diversity of rodent CPN...
February 13, 2016: Cerebral Cortex
Yuan Fang, Wei Shang, De-Li Wei, Shen-Ming Zeng
OBJECTIVE: To determine whether the levels of CBP/p300 interacting transactivator with ED-rich tail 2 (Cited2) protein in cumulus cells (CCs) derived from patients undergoing IVF related to infertility factors, embryo quality, and clinical outcomes in one IVF cycle. DESIGN: Retrospective analysis of human CCs. SETTING: Public hospital and university. PATIENT(S): A total of 103 (conventional) IVF patients and 32 intracytoplasmic sperm injection patients...
May 2016: Fertility and Sterility
Tara L Teppen, Harish R Krishnan, Huaibo Zhang, Amul J Sakharkar, Subhash C Pandey
BACKGROUND: The antianxiety effects of ethanol appear to be a crucial factor in promoting alcohol intake. Regulation of gene expression by microRNA (miRNA) is an important epigenetic mechanism that affects neuronal pathways and behaviors. We investigated the role of miRNAs underlying the mechanisms of ethanol-induced anxiolysis. METHODS: Acute ethanol-induced anxiolysis was measured in adult rats, and amygdaloid tissues were used for miRNA profiling by microarray analysis...
November 26, 2015: Biological Psychiatry
X Zhao, H Cai, X Wang, L Ma
Gene expression profiles of gastric cancer (GC) were analyzed with bioinformatics tools to identify signature genes associated with prognosis. Four gene expression data sets (accession number: GSE2685, GSE30727, GSE38932 and GSE26253) were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) were screened out using significance analysis of microarrays (SAM) algorithm. P-value 1 were set as the threshold. A co-expression network was constructed for the GC-related genes with package WGCNA of R...
2016: Neoplasma
Z He, D J Leong, Z Zhuo, R J Majeska, L Cardoso, D C Spray, M B Goldring, N J Cobelli, H B Sun
OBJECTIVE: To determine the strain-induced signaling pathways involved in regulating the transactivation of the transcription regulator Cbp/p300 Interacting Transactivator with ED-rich tail 2 (CITED2) and downstream targets in chondrocytes. METHODS: Primary human chondrocytes or C28/I2 chondrocytic cells were subjected to various strain regimes. C57BL/6 mice were subjected to treadmill running. Loss-of-function was carried out using siRNA or inhibitors specific for targeted molecules...
May 2016: Osteoarthritis and Cartilage
Rita Alaggio, Lei Zhang, Yun-Shao Sung, Shih-Chiang Huang, Chun-Liang Chen, Gianni Bisogno, Angelica Zin, Narasimhan P Agaram, Michael P LaQuaglia, Leonard H Wexler, Cristina R Antonescu
Sclerosing rhabdomyosarcoma (ScRMS) and spindle cell rhabdomyosarcoma (SRMS) have been recently reclassified as a stand-alone pathologic entity, separate from embryonal RMS. Genetically, a subset of the congenital cases display NCOA2 gene rearrangements, whereas tumors occurring in older children or adults harbor MYOD1 gene mutations with or without coexisting PIK3CA mutations. Despite these recent advances, a significant number of tumors lack known genetic alterations. In this study we sought to investigate a large group of pediatric SRMS/ScRMS, spanning a diverse clinical and pathologic spectrum, by using a combined fluorescence in situ hybridization, targeted DNA, and whole-transcriptome sequencing methodology for a more definitive molecular classification...
February 2016: American Journal of Surgical Pathology
Hui Gu, Jingwen Yu, Daoyin Dong, Qun Zhou, Jian-Ying Wang, Shengyun Fang, Peixin Yang
High glucose in vivo and in vitro induces neural tube defects (NTDs). CITED2 (CBP/p300-interacting transactivator with ED-rich tail 2) is essential for neural tube closure. We explored the regulatory mechanism underlying CITED2 expression and its relationship with miRNA and endoplasmic reticulum (ER) stress. miR-200b levels were increased by maternal diabetes or high glucose in vitro, and this increase was abrogated by transgenic overexpression of superoxide dismutase 1 (SOD1) or an SOD1 mimetic. CITED2 was the target of miR-200b and was downregulated by high glucose...
January 2016: Diabetes
Yu-Chin Liu, Pu-Yuan Chang, Chuck C-K Chao
In this study, we show that silencing of CITED2 using small-hairpin RNA (shCITED2) induced DNA damage and reduction of ERCC1 gene expression in HEK293, HeLa and H1299 cells, even in the absence of cisplatin. In contrast, ectopic expression of ERCC1 significantly reduced intrinsic and induced DNA damage levels, and rescued the effects of CITED2 silencing on cell viability. The effects of CITED2 silencing on DNA repair and cell death were associated with p53 activity. Furthermore, CITED2 silencing caused severe elimination of the p300 protein and markers of relaxed chromatin (acetylated H3 and H4, i...
December 15, 2015: Nucleic Acids Research
Zhengqi Wang, Magdalena Medrzycki, Silvia T Bunting, Kevin D Bunting
Despite being an attractive molecular target for both lymphoid and myeloid leukemias characterized by activated tyrosine kinases, the molecular and physiological consequences of reduced signal transducer and activator of transcription-5 (Stat5) during leukemogenesis are not well known. Stat5 is a critical regulator of mouse hematopoietic stem cell (HSC) self-renewal and is essential for normal lymphocyte development. We report that pan-hematopoietic deletion in viable adult Vav1-Cre conditional knockout mice as well as Stat5ab(null/null) fetal liver transplant chimeras generated HSCs with reduced expression of quiescence regulating genes (Tie2, Mpl, Slamf1, Spi1, Cited2) and increased expression of B-cell development genes (Satb1, Dntt, Btla, Flk2)...
October 6, 2015: Oncotarget
Stéphane Prost, Francis Relouzat, Marc Spentchian, Yasmine Ouzegdouh, Joseph Saliba, Gérald Massonnet, Jean-Paul Beressi, Els Verhoeyen, Victoria Raggueneau, Benjamin Maneglier, Sylvie Castaigne, Christine Chomienne, Stany Chrétien, Philippe Rousselot, Philippe Leboulch
Whether cancer is maintained by a small number of stem cells or is composed of proliferating cells with approximate phenotypic equivalency is a central question in cancer biology. In the stem cell hypothesis, relapse after treatment may occur by failure to eradicate cancer stem cells. Chronic myeloid leukaemia (CML) is quintessential to this hypothesis. CML is a myeloproliferative disorder that results from dysregulated tyrosine kinase activity of the fusion oncoprotein BCR-ABL. During the chronic phase, this sole genetic abnormality (chromosomal translocation Ph(+): t(9;22)(q34;q11)) at the stem cell level causes increased proliferation of myeloid cells without loss of their capacity to differentiate...
September 17, 2015: Nature
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