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Feng Hao, Fuqiang Zhang, Daniel Dongwei Wu, Dong An, Jing Shi, Guohong Li, Xuemin Xu, Mei-Zhen Cui
Vascular smooth muscle cell (SMC) migration is an essential step involved in neointimal formation in restenosis and atherosclerosis. Lysophosphatidic acid (LPA) is a bioactive component of oxidized low density lipoprotein and is produced by activated platelets, implying that LPA influences vascular remodeling. Our previous study revealed that matricellular protein CCN1, a prominent extracellular matrix (ECM) protein, mediates LPA-induced SMC migration in vitro. Here we examined the role of CCN1 in LPA-induced neointimal formation...
October 19, 2016: American Journal of Physiology. Cell Physiology
Osama Mosa, Milan Skitek, Ales Jerin
CONTEXT AND OBJECTIVE: Acute kidney injury (AKI) is still a headache for clinicians and scientists as a possible reason for increased death among intensive care unit (ICU) patients after invasive cardiac surgery. Furthermore, the diagnostic process for AKI using conventional biomarkers is not sufficient to ensure early warning of this condition because of the morbid influence of non-renal factors that definitively delay the time for the prognosis. These imposed limitations have led to significant amounts of research targeted towards identifying novel biomarkers for AKI with a sustained degree of sensitivity and specificity...
October 13, 2016: São Paulo Medical Journal, Revista Paulista de Medicina
Y F Song, Z B Xu, X J Zhu, X Tao, J L Liu, F L Gao, C L Wu, B Song, Q Lin
PURPOSE: To determine the sensitivity and specificity of serum Cyr61 as a potential biomarker for the diagnosis of colorectal cancer (CRC) and to assess the association between serum Cyr61 level and CRC clinicopathological status. METHODS: We used an enzyme-linked immunosorbent assay to measure serum Cyr61 in patients with CRC, patients with colorectal adenomas, and healthy controls. We also analyzed the relationship between serum Cyr61 and clinicopathological features of CRC patients...
October 14, 2016: Clinical & Translational Oncology
Takayuki Furumatsu, Toshifumi Ozaki
The multifunctional growth factor CYR61/CTGF/NOV (CCN) 2, also known as connective tissue growth factor, regulates cellular proliferation, differentiation, and tissue regeneration. Recent literatures have described important roles of CCN2 in the meniscus metabolism. However, the mechanical stress-mediated transcriptional regulation of CCN2 in the meniscus remains unclear. The meniscus is a fibrocartilaginous tissue that controls complex biomechanics of the knee joint. Therefore, the injured unstable meniscus has a poor healing potential especially in the avascular inner region...
2017: Methods in Molecular Biology
Ricardo I Monzon, Ki-Hyun Kim, Lester F Lau
The embryonic lethality of mice with conventional global knockout of Ccn1 (Cyr61) precludes analysis of Ccn1 functions in late embryonic development or in adulthood. To circumvent this limitation, we have generated conditional knockout mice that allow cell type-specific deletion of Ccn1, and constructed an allelic series of Ccn1 knockin mice that express CCN1 defective for binding specific integrins in lieu of the wild type protein. Here we describe the construction of these mice and discuss how analysis of these animals can provide unique insights into Ccn1 functions mediated through specific integrin receptors...
2017: Methods in Molecular Biology
Bora Lee, Lindsay L Kroener, Ning Xu, Erica T Wang, Alexandra Banks, John Williams, Mark O Goodarzi, Yii-der I Chen, Jie Tang, Yizhou Wang, Vineela Gangalapudi, Margareta D Pisarska
Pregnancies resulting from fresh in-vitro fertilization (IVF) cycles exposed to supra-physiologic estrogen levels have been associated with higher rates of low birth weight and small for gestational age babies. We identified GATA3, a transcription factor selectively expressed in the trophectoderm during the blastocyst stage of embryo development, in an upstream analysis of genes that were differentially methylated in chorionic villus samples between IVF and non-IVF infertility treatment (NIFT) pregnancies. In this study, we investigate the hypothesis that GATA3 is hormonally regulated and plays an important functional role in trophoblast migration, invasion and placentation...
October 12, 2016: Biology of Reproduction
Xianjin Zhu, Yanfang Song, Conglian Wu, Chuxi Pan, Pingxia Lu, Meihua Wang, Peizheng Zheng, Rongfen Huo, Chenqing Zhang, Wanting Li, Yulin Lin, Yingping Cao, Ningli Li
Cyr61 (CCN1) is the product of a growth factor-inducible immediate early gene and is involved in cell adhesion, survival, proliferation, and differentiation. Cyr61 is overexpressed in human tumors and is involved in the development of tumors. However, the role that Cyr61 plays in acute lymphoblastic leukemia (ALL) cells remains undetermined. The aim of this study was to identify the role of Cyr61 in regulating ALL cell survival. Here, we found that the level of Cyr61 was increased in the plasma and bone marrow (BM) from ALL patients compared with samples from normal control patients...
October 11, 2016: Scientific Reports
Peng Wang, Li Li, Ting Li
OBJECTIVES: To analyze the relationship between cysteine-rich 61 (Cyr61) and target genes of Wnt/β-catenin pathway (CCND1 and MYC) in 40 esophageal squamous cell carcinoma (ESCC) tissue specimens. Another aim of this study was to verify whether Cyr61 could be regulated by Wnt/β-catenin signaling. MATERIALS AND METHODS: Forty ESCC tissue specimens with paired adjacent normal epithelial tissues were obtained. The expression of Cyr61, CCND1, and MYC was examined by quantitative real-time polymerase chain reaction...
October 2016: Journal of Cancer Research and Therapeutics
Javier A Menendez, Luciano Vellon, Ingrid Espinoza, Ruth Lupu
The angiogenic inducer CCN1 (Cysteine-rich 61, CYR61) is differentially activated in metastatic breast carcinomas. However, little is known about the precise mechanisms that underlie the pro-metastatic actions of CCN1. Here, we investigated the impact of CCN1 expression on fatty acid synthase (FASN), a metabolic oncogene thought to provide cancer cells with proliferative and survival advantages. Forced expression of CCN1 in MCF-7 cells robustly up-regulated FASN protein expression and also significantly increased FASN gene promoter activity 2- to 3-fold, whereas deletion of the sterol response element-binding protein (SREBP) binding site in the FASN promoter completely abrogated CCN1-driven transcriptional activation...
2016: Oncoscience
Weidong Shi, Chenyue Zhang, Zhen Chen, Hao Chen, Luming Liu, Zhiqiang Meng
Efficient inhibition of tumor metastasis after resection of primary tumors is critical for cancer therapy. We have recently shown that Cyr61 promotes growth of pancreatic ductal adenocarcinoma (PDAC) through PI3k/Akt signaling-enhanced nuclear exclusion of p27. Here, we report that administration of adeno-associated viral vectors carrying a short-hairpin interfering RNA (shRNA) for Cyr61 via pancreatic duct significantly decreased the distal tumor metastases after resection of primary pancreatic tumor in mice...
September 26, 2016: Oncotarget
Nicholas V Skladnev, Varshika Ganeshan, Ji Yeon Kim, Thomas J Burton, John Mitrofanis, Jonathan Stone, Daniel M Johnstone
Dietary saffron has shown promise as a neuroprotective intervention in clinical trials of retinal degeneration and dementia and in animal models of multiple CNS disorders, including Parkinson's disease. This therapeutic potential makes it important to define the relationship between dose and protection and the mechanisms involved. To explore these two issues, mice were pre-conditioned by providing an aqueous extract of saffron (0.01% w/v) as their drinking water for 2, 5 or 10 days before administration of the parkinsonian neurotoxin MPTP (50 mg/kg)...
October 1, 2016: Journal of Neurochemistry
Kuei-Chun Wang, Yi-Ting Yeh, Phu Nguyen, Elaine Limqueco, Jocelyn Lopez, Satenick Thorossian, Kun-Liang Guan, Yi-Shuan J Li, Shu Chien
The focal nature of atherosclerotic lesions suggests an important role of local hemodynamic environment. Recent studies have demonstrated significant roles of Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) in mediating mechanotransduction and vascular homeostasis. The objective of this study is to investigate the functional role of YAP/TAZ in the flow regulation of atheroprone endothelial phenotypes and the consequential development of atherosclerotic lesions. We found that exposure of cultured endothelial cells (ECs) to the atheroprone disturbed flow resulted in YAP/TAZ activation and translocation into EC nucleus to up-regulate the target genes, including cysteine-rich angiogenic inducer 61 (CYR61), connective tissue growth factor (CTGF), and ankyrin repeat domain 1 (ANKRD1)...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
Jun Chen, Yang Liu, Qilin Sun, Beiqing Wang, Ningli Li, Xiangdong Chen
Cysteine-rich protein 61 (CCN1/CYR61) is an important marker of proliferation and metastasis in malignant melanoma, making it a potential target for melanoma treatment. In this study, we compared the expression of CRY61 in Chinese patients with malignant melanoma with its expression in patients with other skin tumors or with no skin pathological conditions. We examined the effects of anti-human CYR61 monoclonal antibody on proliferation and evaluated the changes in CYR61 expression and cell proliferation in response to treatment with either epirubicin or interferon (IFN)-α...
September 23, 2016: Oncology Reports
Duo Zhang, Wei Xia, Tong Tong, Cheng Li, Wei Shi, Ming-Xing Yan, Rui-Hong Xue, Xiao-Ming Guan, Jian Zhang
Adenomyosis, a benign invasion of endometrium, is closely related to endometriosis. Cysteine-rich 61 (Cyr61), a protein present in all endometrial tissues and menstrual effluents, is known to be associated with endometriosis. However, its relation to adenomyosis has not been determined thus far. Therefore, here, we aimed to investigate the expression of Cyr61 protein in adenomyosis and determine the correlation between Cyr61 expression and clinicopathologic parameters in patients with adenomyosis. One hundred and twenty patients with histologically diagnosed adenomyosis, who underwent hysterectomy for non-endometrial disease were enrolled in this study...
August 17, 2016: Journal of Reproductive Immunology
Kati Kemppainen, Nina Wentus, Taru Lassila, Asta Laiho, Kid Törnquist
Sphingosylphosphorylcholine (SPC) is a bioactive sphingolipid which regulates many cancer-related processes, including cellular proliferation. The Hippo signaling pathway consists of a cascade of tumor suppressive kinases Mst1/2 and Lats1/2 and their downstream targets YAP and TAZ which are generally pro-proliferative transcriptional regulators. Direct phosphorylation by Lats1/2 causes inhibition or degradation of YAP/TAZ and down-regulation of their target genes. We found SPC treatment of MDA-MB-435S breast cancer cells to strongly inhibit their proliferation and to induce a sustained Lats2 protein expression (6-24h)...
December 2016: Cellular Signalling
Jun Li, Xiangyu Gao, Ke Ji, Andrew J Sanders, Zhongtao Zhang, Wen G Jiang, Jiafu Ji, Lin Ye
CCN is an acronym for cysteine-rich protein 61 (CYR61), connective tissue growth factor (CTGF) and nephroblastoma overexpressed (NOV). Aberrations of certain CCN members including CYR61, CTGF, Wnt1-inducible signalling pathway protein (WISP)-1 and -3 have been reported in gastric cancer. The present study aimed to examine the clinical relevance of NOV along with CYR61 and CTGF in gastric cancer by analysing their transcript levels. CYR61, CTGF and NOV transcript expression in 324 gastric cancer samples with paired adjacent normal gastric tissues were determined using real-time quantitative PCR and the results were statistically analysed against patient clinicopathological data using SPSS software...
September 8, 2016: Oncology Reports
Michael J LaQuaglia, James L Grijalva, Kaly A Mueller, Antonio R Perez-Atayde, Heung Bae Kim, Ghazaleh Sadri-Vakili, Khashayar Vakili
Pediatric hepatocellular carcinoma (HCC) is a rare tumor which is associated with an extremely high mortality rate due to lack of effective chemotherapy. Recently, the Hippo pathway and its transcriptional co-activator Yes-associated protein (YAP) have been shown to play a role in hepatocyte proliferation and development of HCC in animal models. Therefore, we sought to examine the activity of YAP and the expression of Hippo pathway components in tumor and non-neoplastic liver tissue from 7 pediatric patients with moderately differentiated HCC...
2016: Scientific Reports
Rachel A Hesler, Jennifer J Huang, Mark D Starr, Victoria M Treboschi, Alyssa G Bernanke, Andrew B Nixon, Shannon J McCall, Rebekah R White, Gerard C Blobe
Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer in part due to inherent resistance to chemotherapy, including the first-line drug gemcitabine. While low expression of the nucleoside transporters hENT1 and hCNT3 that mediate cellular uptake of gemcitabine has been linked to gemcitabine resistance, the mechanisms regulating their expression in the PDAC tumor microenvironment are largely unknown. Here, we report that the matricellular protein cysteine-rich angiogenic inducer 61 (CYR61) negatively regulates the nucleoside transporters hENT1 and hCNT3...
September 7, 2016: Carcinogenesis
Tianhang Zhai, Chenxin Gao, Rongfen Huo, Huiming Sheng, Songtao Sun, Jun Xie, Yong He, Huali Gao, Huidan Li, Jie Zhang, Haichuan Li, Yue Sun, Jinpiao Lin, Baihua Shen, Lianbo Xiao, Ningli Li
OBJECTIVES: The aim of this study was to investigate the effect and potential mechanism of Cysteine-rich 61 (Cyr61) on stimulating MMP-3 expression by fibroblast-like synoviocytes (FLS) from rheumatoid arthritis (RA) patients. METHODS: Primarily cultured RA FLS were treated with exogenous Cyr61 protein or Cyr61-siRNA, then, MMP-3 expression was analyzed by real-time PCR, western blotting and ELISA. Signal transduction pathways in Cyr61-induced MMP-3 production were examined by real-time PCR, western blotting, confocal microscopy, luciferase reporter assay...
September 1, 2016: Modern Rheumatology
Joana Cardoso, Marta Mesquita, António Dias Pereira, Mónica Bettencourt-Dias, Paula Chaves, José B Pereira-Leal
Barrett's esophagus is the major risk factor for esophageal adenocarcinoma. It has a low but non-neglectable risk, high surveillance costs and no reliable risk stratification markers. We sought to identify early biomarkers, predictive of Barrett's malignant progression, using a meta-analysis approach on gene expression data. This in silico strategy was followed by experimental validation in a cohort of patients with extended follow up from the Instituto Português de Oncologia de Lisboa de Francisco Gentil EPE (Portugal)...
2016: PloS One
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