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Qian Liu, Junjie Deng, Xundong Wei, Wei Yuan, Jie Ma
Colorectal cancer (CRC) is a common malignant tumor with high morbidity and mortality around the world. The aim of this study was to determine the genes significantly associated with the overall survival (OS) of CRC patients and predict their function in the competing endogenous RNA (ceRNA) regulation networks. We constructed the lncRNA-miRNA-mRNA networks according to the differentially expressed RNAs from the The Cancer Genome Atlas data sets of 561 CRC patients. Twelve differentially expressed messenger RNAs from the ceRNA networks were selected through a univariate Cox proportional hazards regression...
February 12, 2019: Journal of Cellular Biochemistry
Qiuyan Xia, Yan Zhou, Hongmei Yong, Xudong Wang, Wei Zhao, Guipeng Ding, Jin Zhu, Xiaohua Li, Zhenqing Feng, Bing Wang
Epiregulin (EREG) is a novel family member of EGF-like ligands and have elevated expression in a variety of human cancers. EREG expression promotes tumor progression and metastasis and reduces patient survival. However, the expression of EREG and its prognostic value are not clear in gastric cancer (GC). We assessed EREG mRNA and protein expression in GC tissues from Chinese patients using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical staining of tissue microarray, and analyzed the correlation between the level of EREG expression and patient clinical characteristics and prognosis...
January 28, 2019: Pathology, Research and Practice
Li Fang, Peng-Fei Zhang, Kang-Kai Wang, Zhi-Lin Xiao, Mei Yang, Zai-Xin Yu
The current study aimed to clarify the role of nucleolin in the phenotypic transformation of vascular smooth muscle cells (VSMCs) and to preliminarily explore its underlying mechanism. The spatial and temporal expression patterns of nucleolin, and the effects of angiotensin II (Ang II) on the expression of VSMC phenotypic transformation markers, α‑smooth muscle‑actin, calponin, smooth muscle protein 22α and osteopontin were investigated. The effects of nucleolin on VSMC phenotypic transformation and the expression of phenotypic transformation‑associated genes, tropoelastin, epiregulin and fibroblast growth factor 2 (b‑FGF), were determined...
February 4, 2019: International Journal of Molecular Medicine
Wen Cao, Liu-Lin Luo, Wei-Wei Chen, Li Liang, Ran-Ran Zhang, Yan-Lin Zhao, Jin Chen, Jun Yue
BACKGROUND: Host genetic factors affect the immune response to Mycobacterium tuberculosis (Mtb) infection as well as the progression of the disease. Epiregulin (EREG) belongs to the epidermal growth factor (EGF) family, which binds to the epidermal growth factor receptor (EGFR) to regulate the immune response of the host during infections. Our study aimed to compare EREG levels in tuberculosis (TB) patients and healthy controls and assess whether polymorphisms in EREG increase the risk of TB...
January 11, 2019: BMC Medical Genetics
Zhen Wang, Huaping Zheng, Hong Zhou, Nongyu Huang, Xiaoqiong Wei, Xiao Liu, Xiu Teng, Zhonglan Hu, Jun Zhang, Xikun Zhou, Wei Li, Jiong Li
Psoriasis is a chronic inflammatory skin disease. Keratinocytes (KCs), as skin‑specific cells, serve an important role in the immunopathogenesis of psoriasis. In the present study, transcriptome data derived from psoriasis‑like KCs were used together with the reported transcriptome data from the skin/epidermis of patient with psoriasis, excluding known psoriasis‑associated genes that have been well described in the previous studies according to GeneCards database, to screen for novel psoriasis‑associated genes...
December 20, 2018: Molecular Medicine Reports
Yi-Jen Chen, Wei-An Chang, Ling-Yu Wu, Ya-Ling Hsu, Chia-Hsin Chen, Po-Lin Kuo
The phenotypic change of chondrocytes and the interplay between cartilage and subchondral bone in osteoarthritis (OA) has received much attention. Structural changes with nerve ingrowth and vascular penetration within OA cartilage may contribute to arthritic joint pain. The aim of this study was to identify differentially expressed genes and potential miRNA regulations in OA knee chondrocytes through next-generation sequencing and bioinformatics analysis. Results suggested the involvement of SMAD family member 3 ( SMAD3 ) and Wnt family member 5A ( WNT5A ) in the growth of blood vessels and cell aggregation, representing features of cartilage damage in OA...
December 10, 2018: Journal of Clinical Medicine
Yingxin Zhang, Jie Ding, Cong Xu, Hongli Yang, Peng Xia, Shengjun Ma, Haiying Chen
Background and Objectives: Previous studies have shown that integrins alpha5beta1 (ITGA5B1) gene-modified rat bone marrow mesenchymal stem cells (rBMSCs) could prevent cell anoikis and increase the nitric oxide (NO) production. Here we examined the capability of rBMSCs/ITGA5B1 on the phenotype modulation of Human Pulmonary Artery Smooth Muscle Cell (HPASMC) in vitro. Methods and Results: The synthetic (dedifferentiated) phenotype of HPASMC was induced by monocrotaline (MCT, 1 μ M) for 24 h and then co-cultured with rBMSCs/ITGA5B1 in a transwell culture system...
November 30, 2018: International Journal of Stem Cells
Sebastian Stintzing, Boryana Ivanova, Ingrid Ricard, Andreas Jung, Thomas Kirchner, Andrea Tannapfel, Hendrik Juette, Susanna Hegewisch-Becker, Dirk Arnold, Anke Reinacher-Schick
Background: The EGFR (epithelial growth factor receptor) ligands amphiregulin (AREG) and epiregulin (EREG) have been considered as predictors for EGFR-antibody efficacy. The effect of AREG and EREG expression levels in primary tumor samples on the outcome of bevacizumab-treated patients is unknown. Patients and Methods: Formalin-fixed paraffin-embedded (FFPE) tumor samples from surgically removed primaries of the AIO KRK-0207 trial have been tested for AREG and EREG expression. The AIO KRK-0207 trial was a randomized phase-3 study to investigate the best maintenance strategy after oxaliplatin/fluoropyrimidine plus bevacizumab induction treatment in patients with mCRC...
2018: Frontiers in Oncology
Hao Han, Shu Yang, Yu Liang, Peng Zeng, Lipei Liu, Xiaoxiao Yang, Yajun Duan, Jihong Han, Yuanli Chen
The switch of vascular smooth muscle cells (SMCs) from the contractile phenotype to proliferative one can make contributions to atherosclerosis and neointima formation. MiR-21 can prevent the rupture of advanced lesion plaques. We previously reported the protection of DNA topoisomerase II (Topo II) inhibitors against atherosclerosis and vascular calcification. However, it remains unknown if Topo II inhibitors can change SMC phenotypes. Herein, we show that teniposide protected SMC phenotype switching during atherosclerosis by enhancing expression of smooth muscle α-actin (SMA) while reducing osteopontin (OPN) expression in aortic lesion plaques...
November 5, 2018: Biochemical and Biophysical Research Communications
Rumana Yasmeen, Qiwen Shen, Aejin Lee, Jacob H Leung, Devan Kowdley, David J DiSilvestro, Lu Xu, Kefeng Yang, Andrei Maiseyeu, Naresh C Bal, Muthu Periasamy, Paolo Fadda, Ouliana Ziouzenkova
Adipokine leptin regulates neuroendocrine circuits that control energy expenditure, thermogenesis and weight loss. However, canonic regulators of leptin secretion, such as insulin and malonyl CoA, do not support these processes. We hypothesize that epiregulin (EREG), a growth factor that is secreted from fibroblasts under thermogenic and cachexia conditions, induces leptin secretion associated with energy dissipation. The effects of EREG on leptin secretion were studied ex vivo, in the intra-abdominal white adipose tissue (iAb WAT) explants, as well as in vivo, in WT mice with diet-induced obesity (DIO) and in ob/ob mice...
December 1, 2018: Journal of Endocrinology
Yasunao Kogashiwa, Hitoshi Inoue, Kiyomi Kuba, Ryuichiro Araki, Masanori Yasuda, Mitsuhiko Nakahira, Masashi Sugasawa
BACKGROUND: Cetuximab combined with chemoradiotherapy is the standard therapy for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). However, survival benefit is limited. The purpose of this study was to investigate the expression of epiregulin (EREG) and amphiregulin (AREG), as predictive prognostic markers for the efficacy of cetuximab combined with chemotherapy in R/M HNSCC. METHODS: We conducted a retrospective analysis of 37 patients diagnosed with R/M HNSCC...
October 10, 2018: Head & Neck
Georgia E Fouli, Luigi Gnudi
Diabetic nephropathy is the commonest cause of end-stage renal disease and affects between 30 and 45% of patients with diabetes mellitus. There is no cure for diabetic nephropathy and the current management of this condition includes glycaemic control, blockade of the renin-angiotensin aldosterone system and lifestyle changes. However, many patients eventually progress to end-stage renal disease. The exact pathogenesis of diabetic nephropathy is still being researched, and recent advances have led to the development of several novel potential therapeutic targets...
September 26, 2018: Nephron
Felix Bormann, Sebastian Stinzing, Sascha Tierling, Markus Morkel, Maria Rivera Markelova, Jörn Walter, Wilko Weichert, Florian Roßner, Natalia Kuhn, Juliane Perner, Johanna Dietz, Sylvia Ispasanie, Manfred Dietel, Reinhold Schäfer, Volker Heinemann, Christine Sers
Expression of the epidermal growth factor ligands amphiregulin (AREG) and epiregulin (EREG) is positively correlated with a response to EGFR-targeted therapies in colorectal cancer. Gene-body methylation sites, which show a strong inverse correlation with AREG and EREG gene expression, were identified in cell lines using targeted 454 FLX-bisulfite sequencing and SIRPH analyses for AREG/EREG promoters and intragenic CpGs. Upon treatment of colorectal cancer cells with 5-aza-2´-desoxycytidine, methylation decreases at specific intragenic CpGs accompanied by upregulation of AREG and EREG gene expression...
September 25, 2018: International Journal of Cancer. Journal International du Cancer
Yangyang Cao, Liping Wang, Haoqing Yang, Xiao Lin, Guoqing Li, Nannan Han, Juan Du, Zhipeng Fan
To investigate the function of epiregulin (EREG) in the migration and chemotaxis ability of mesenchymal stem cells. Adipose-derived stem cells (ADSCs) were used in this investigation. Lentiviral EREG short hairpin RNA was applied to silence EREG expression in ADSCs. Human recombinant EREG protein (rhEREG) was used to perform a gain-of-function study. Scratch-simulated wound migration and transwell chemotaxis assays were used to examine the migration and chemotaxis capacity of ADSCs in vitro. Using a Western blot assay, the expressions of p38 mitogen-activated protein kinase (p38 MAPK), c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinases 1 and 2 (Erk1/2), and protein kinase B were detected...
July 16, 2018: Journal of Cellular Biochemistry
Joabel T Dos Santos, Matheus P De Cesaro, Juliana G Ferst, Andressa M Pereira Dau, Paulo R A da Rosa, Bruno M Pasqual, Alfredo Q Antoniazzi, Bernardo G Gasperin, Vilceu Bordignon, Paulo B D Gonçalves
During folliculogenesis, the luteinizing hormone (LH) surge triggers dynamic events in granulosa cells that culminate with ovulation. The aim of this study was to evaluate if the epidermal growth factor receptor (EGFR) is required for ovulation in cattle, and if it regulates the expression of the natriuretic peptide (NP) system in granulosa cells after gonadotropin-releasing hormone (GnRH)/LH stimulation. It was observed that GnRH induces amphiregulin (AREG) and epiregulin (EREG) mRNA at 3 and 6 h after in vivo treatment, but the expression of these genes was not regulated by atrial (ANP) and C-type (CNP) NPs in granulosa cells cultured in vitro...
June 22, 2018: Theriogenology
Wenjing Zhao, Liping Yang, Xudong Chen, Hongyan Qian, Suqing Zhang, Yali Chen, Runhua Luo, Jingjing Shao, Huanliang Liu, Jianguo Chen
AIMS: Tumor endothelial cells (TECs) have been investigated using human tumor xenografts in mice models. In order to provide pure human TECs for the updating of clinical anti-angiogenic cancer therapy, in the present study we established a protocol of purification of TECs derived from clinical hepatocellular carcinoma (HCC) and revealed the TEC features by in vitro and in vivo assays. METHODS: We isolated TECs from fresh surgical resections of HCC by magnetic-activated cell sorting and purified by flow cytometry sorting upon CD31 expression, referred to as ECDHCCs...
June 28, 2018: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Thiagarajan Venkatesan, Ali Alaseem, Aiyavu Chinnaiyan, Sivanesan Dhandayuthapani, Thanigaivelan Kanagasabai, Khalid Alhazzani, Priya Dondapati, Saad Alobid, Umamaheswari Natarajan, Ruben Schwartz, Appu Rathinavelu
The Murine Double Minute 2 (MDM2) amplification or overexpression has been found in many tumors with high metastatic and angiogenic ability. Our experiments were designed to explore the impact of MDM2 overexpression, specifically on the levels of angiogenesis-related genes, which can also play a major role in tumor propagation and increase its metastatic potential. In the present study, we have used the human angiogenesis RT² profiler PCR array to compare the gene expression profile between LNCaP and LNCaP-MST (MDM2 transfected) prostate cancer cells, along with LNCaP-MST cells treated with Nutlin-3, an MDM2 specific inhibitor...
May 10, 2018: Cells
Yoji Kyotani, Asako Itaya-Hironaka, Akiyo Yamauchi, Sumiyo Sakuramoto-Tsuchida, Mai Makino, Shin Takasawa, Masanori Yoshizumi
Patients with obstructive sleep apnea (OSA) experience repetitive episodes of desaturation and resaturation of blood oxygen (known as intermittent hypoxia or IH), during sleep. We showed previously that IH induced excessive proliferation of rat vascular smooth muscle cells through upregulation of members of the epidermal growth factor family, especially epiregulin (EREG), and the erbB2 receptor. In this study, we exposed human coronary artery smooth muscle cells to IH and found that IH significantly increased the expression of EREG...
May 2018: FEBS Open Bio
Marian Acevedo-Alvarez, Judy Yeh, Lery Alvarez-Lugo, Ming Lu, Nitin Sukumar, Warren G Hill, Toby C Chai
AIMS: Symptoms from overactive bladder (OAB) and cystitis secondary to urinary tract infection (UTI) can be similar in post-menopausal women. Effects of ovariectomy (OVX) on voiding behavior after lipopolysaccharide (LPS) intravesical exposure (surrogate for cystitis) in mice were measured. Urothelial genes associated with micturition changes were identified. METHODS: Female C57BL6/J mice underwent OVX or sham surgeries (n = 10 for each). Voiding spot assays (VSA) were performed prior to surgery, 4 weeks post-surgery, and each time after 3 consecutive days of transurethral instillation of LPS...
November 2018: Neurourology and Urodynamics
Joanne Sloan-Lancaster, Eyas Raddad, Mark A Deeg, Michelle Eli, Amy Flynt, James Tumlin
Two phase 1 studies (TGAA and TGAB) evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of LY3016859 (LY), a monoclonal antibody that binds epiregulin and transforming growth factor α (TGF-α), administered intravenously or subcutaneously. In TGAA, 56 healthy subjects received a single dose of LY (0.1-750 mg intravenously, 50 mg subcutaneously) or placebo. In TGAB part A, 15 patients with diabetic nephropathy (DN) received 2 doses of LY (10-750 mg intravenously) or placebo, and in TGAB part B, 45 patients with DN received 5 doses of LY (50-750 mg intravenously) or placebo...
September 2018: Clinical Pharmacology in Drug Development
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