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Hongfang Zhang, Conghua Xie, Jing Yue, Zhenzhen Jiang, Rongjing Zhou, Ruifei Xie, Yan Wang, Shixiu Wu
Previous studies on the mechanisms underlying ESCC (esophageal squamous cell carcinoma) chemoresistance only focused on tumor cells while tumor microenvironment has been completely ignored. Our study aimed to clarify the effect of CAFs (cancer-associated fibroblasts), one major component of tumor microenvironment, on the chemoresistance of ESCC. By primary culture, two pairs of CAFs and matched NFs (normal fibroblasts) were isolated from tumor tissues of ESCC patients and matched normal esophageal epithelial tissues, respectively...
October 21, 2016: Molecular Carcinogenesis
Lorenza Brocca, Luana Toniolo, Carlo Reggiani, Roberto Bottinelli, Marco Sandri, Maria Antonietta Pellegrino
Muscle atrophy is a complex process that is in common with many different catabolic diseases including disuse/inactivity and ageing. The signalling pathways that control the atrophy program in the different disuse/inactivity conditions have not yet been completely dissected. It has been recently reported that inhibition of FoxO only partially spared muscle mass after denervation. The purposes of this study were: (i) to determine the involvement of FoxOs in hindlimb suspension disuse model, (ii) to define whether the molecular events of protein breakdown are shared among different unloaded muscles and finally (iii) to compare the data obtained in this model with another model of inactivity such as denervation...
October 21, 2016: Journal of Physiology
Maria Böhm, Marco Wachtel, Joana G Marques, Natalie Streiff, Dominik Laubscher, Paolo Nanni, Kamel Mamchaoui, Raffaella Santoro, Beat W Schäfer
A vast number of cancer genes are transcription factors that drive tumorigenesis as oncogenic fusion proteins. Although the direct targeting of transcription factors remains challenging, therapies aimed at oncogenic fusion proteins are attractive as potential treatments for cancer. There is particular interest in targeting the oncogenic PAX3-FOXO1 fusion transcription factor, which induces alveolar rhabdomyosarcoma (aRMS), an aggressive cancer of skeletal muscle cells for which patient outcomes remain dismal...
October 17, 2016: Journal of Clinical Investigation
Gang Chen, Dongsheng Yu, Xue Nian, Junyi Liu, Ronald J Koenig, Bin Xu, Liang Sheng
Nonalcoholic fatty liver disease (NAFLD), the most common form of chronic liver disease, manifests as an over-accumulation of hepatic fat. We have recently shown that mice with genetic knockout of a long non-coding RNA (lncRNA) steroid receptor RNA activator (SRA) (SRAKO) are resistant to high fat diet-induced obesity with a phenotype that includes improved glucose tolerance and attenuated hepatic steatosis. The underlying mechanism was investigated in the present study. We found that hepatic levels of SRA and adipose triglyceride lipase (ATGL), a major hepatic triacylglycerol (TAG) hydrolase, were inversely regulated by fasting in mice, and the expression of liver ATGL was induced by SRAKO under normal and high fat diet (HFD) feeding...
October 19, 2016: Scientific Reports
Petra Balogh, Rita Bánusz, Monika Csóka, Zsófia Váradi, Edit Varga, Zoltán Sápi
BACKGROUND: Rhabdomyosarcoma (RMS) is a malignant tumor of mesenchymal origin and comprises the largest category of soft-tissue sarcomas both in children and adolescents. From a pediatric oncology point of view, RMS has traditionally been classified into alveolar (ARMS) and embryonal (ERMS) subtypes. The anatomical localization of the tumor may vary, but commonly involve the head/neck regions, male and female urogenital tract or the trunk and extremities. CASE PRESENTATION: Here, we report two challenging cases involving 17- and 9-years-olds males where diffuse and multiplex bone lesions suggested either a hematological disease or a primary bone tumor (mesenchymal chondrosarcoma)...
October 18, 2016: Diagnostic Pathology
Rong Lian, Baocai Lu, Lei Jiao, Shaomei Li, Huimin Wang, Wenjie Miao, Wenfa Yu
Increasing evidence indicates that the dysregulation of microRNAs is involved in tumor progression and development. The purpose of the present study was to explore the expression of microRNA-132 (miR-132) and its function in laryngeal squamous cell carcinoma (LSCC). The results showed that miR-132 expression was markedly upregulated in LSCC tissues and cell lines. Functional analyses indicated that overexpression of miR-132 enhanced cell proliferation and tumor growth, which resulted in the downregulation of p27 and p21 and the upregulation of cyclin D1...
October 14, 2016: European Journal of Pharmacology
Hongyu Shen, Dandan Wang, Liangpeng Li, Sujin Yang, Xiu Chen, Siying Zhou, Shanliang Zhong, Jianhua Zhao, Jinhai Tang
BACKGROUND AND PURPOSE: Acquisition of resistance to adriamycin (ADR) is one of the most important clinical obstacles in the treatment of breast cancer, but the molecular mechanisms underlying sensitivity to ADR remain elusive. In our previous study, through miRNA microarray and experiments, we have emphasized that miR-222 could promote the ADR-resistance in breast cancer cells. The aim of this study was to explore the possible mechanism by which miR-222 affects sensitivity to ADR. METHODS: Through pathway enrichment analyses for miR-222, we found that PTEN/Akt/FOXO1 signaling pathway may be of importance...
October 13, 2016: Gene
E D Rosen
Insulin resistance is one of the defining features of type 2 diabetes and the metabolic syndrome and accompanies many other clinical conditions, ranging from obesity to lipodystrophy to glucocorticoid excess. Extraordinary efforts have gone into defining the mechanisms that underlie insulin resistance, with most attention focused on altered signalling as well as mitochondrial and endoplasmic reticulum stress. Here, nuclear mechanisms of insulin resistance, including transcriptional and epigenomic effects, will be discussed...
October 14, 2016: Journal of Internal Medicine
Natalia Papeta, Ami Patel, Vivette D D'Agati, Ali G Gharavi
HIV-1 transgenic mice on the FVB/NJ background (TgFVB) represent a validated model of HIV-associated nephropathy (HIVAN). A major susceptibility locus, HIVAN1, was previously mapped to chromosome 3A1-A3 in a cross between TgFVB and CAST/EiJ (CAST) strains, and introgression of a 51.9 Mb segment encompassing HIVAN1 from CAST into TgFVB resulted in accelerated development of nephropathy. We generated three sub-congenic strains carrying CAST alleles in the proximal or distal regions of the HIVAN1 locus (Sub-II, 3...
2016: PloS One
Bo Wu, Bomin Guo, Jie Kang, Xianzhao Deng, Youben Fan, Xiaoping Zhang, Kaixing Ai
Smad ubiquitin regulatory factor 2 (Smurf2) is an E3 ubiquitin ligase that regulates transforming growth factor β (TGF-β)/Smad signaling and is implicated in a wide range of cellular responses. However, the exact mechanism whereby Smurf2 controls TGF-β-induced signaling pathways remains unknown. Here, we identified the relationship between the alternate TGF-β signaling pathways: TGF-β/PI3K/Akt/β-catenin and TGF-β/Smad2/3/FoxO1/PUMA and Smurf2. The results showed that TGF-β promoted proliferation, invasion, and migration of human pancreatic carcinoma (PANC-1) cells through the PI3K/Akt/β-catenin pathway...
October 11, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Sukanta Jash, Vishwajeet Puri
No abstract text is available yet for this article.
August 12, 2016: Cell Cycle
Alba Chacon-Cabrera, Joaquim Gea, Esther Barreiro
Skeletal muscle dysfunction and atrophy are characteristic features accompanying chronic conditions. Epigenetic events regulate muscle mass and function maintenance. We hypothesized that the pattern of epigenetic events (muscle-enriched microRNAs and histone acetylation) and acetylation of transcription factors known to signal muscle wasting may differ between early- and late-time points in skeletal muscles of mice exposed to hindlimb immobilization (I) and recovery following I. Body and muscle weights, grip strength, muscle-enriched microRNAs, histone deacetylases (HDACs), acetylation of proteins, histones, and transcription factors (TF), myogenic TF factors, and muscle phenotype were assessed in gastrocnemius of mice exposed to periods (1, 2, 3, 7, 15 and 30 days, I groups) of hindlimb immobilization, and in those exposed to reloading for different periods of time (1, 3, 7, 15, and 30 days, R groups) following 7-day immobilization...
October 7, 2016: Journal of Cellular Physiology
Juan Han, Runming Jin, Meiling Zhang, Qing Guo, Fen Zhou
Ikaros isoform 6 (Ik6) is associated with a poor prognosis for children with acute lymphoblastic leukemia (ALL). Our previous study demonstrated that overexpression of Ik6 enhances proliferation and chemoresistance of leukemia cells, with a possible underlying mechanism that involves antiapoptosis. In the present study, we investigated whether Ik6 protects against apoptosis by regulating the Akt-FoxO1 pathway. Bone marrow samples from children with ALL were collected and evaluated. In Ik6(+) patients, the Akt-FoxO1 pathway was activated such that expression of phosphorylated Akt and FoxO1 was significantly increased, but that of Bim and p27 decreased...
October 5, 2016: Journal of Leukocyte Biology
M Balakumar, L Raji, D Prabhu, C Sathishkumar, P Prabu, V Mohan, M Balasubramanyam
In the context of high human consumption of fructose diets, there is an imperative need to understand how dietary fructose intake influence cellular and molecular mechanisms and thereby affect β-cell dysfunction and insulin resistance. While evidence exists for a relationship between high-fat-induced insulin resistance and metabolic disorders, there is lack of studies in relation to high-fructose diet. Therefore, we attempted to study the effect of different diets viz., high-fat diet (HFD), high-fructose diet (HFS), and a combination (HFS + HFD) diet on glucose homeostasis and insulin sensitivity in male Wistar rats compared to control animals fed with normal pellet diet...
October 3, 2016: Molecular and Cellular Biochemistry
So Young Lee, Yun Young Lee, Joong Sub Choi, Mee-Sup Yoon, Joong-Soo Han
Decidualization of human endometrial stromal cells (hESCs) is crucial for successful uterine implantation and maintaining pregnancy. We previously reported that phospholipase D1 (PLD1) is required for cAMP-induced decidualization of hESCs. However, the mechanism by which phosphatidic acid (PA), the product of PLD1 action, might regulate decidualization is not known. We confirmed that PA induced decidualization of hESCs by observing morphological changes and measuring increased levels of decidualization markers such as IGFBP1 and prolactin transcripts (P < 0...
October 3, 2016: FEBS Journal
Mark F McCarty
In type 1 diabetics, hepatic exposure to insulin is chronically subnormal even in the context of insulin therapy; as a result, expression of glycolytic enzymes is decreased, and that of gluconeogenic enzymes is enhanced, resulting in a physiologically inappropriate elevation of hepatic glucose output. Subnormal expression of glucokinase (GK) is of particular importance in this regard. Possible strategies for correcting this perturbation of hepatic enzyme expression include administration of small molecule allosteric activators of GK, as well as a procedure known as chronic intermittent intravenous insulin therapy (CIIIT); however, side effects accompany the use of GK activators, and CIIIT is time and labor intensive...
October 2016: Medical Hypotheses
Luisa Montanini, Arianna Smerieri, Mariolina Gullì, Francesca Cirillo, Giovanna Pisi, Chiara Sartori, Sergio Amarri, Sergio Bernasconi, Nelson Marmiroli, Maria E Street
CONTEXT: Cystic Fibrosis Related Diabetes (CFRD) is the most frequent and severe co-morbidity in CF. Presentation and severity are quite variable. OBJECTIVE: To investigate changes in miRNAs due to CFTR malfunctioning in vitro and to study the circulating levels of selected miRNAs in serum samples from patients, and assess their relationships in different age-groups with genotype, glucose tolerance state and at onset of CFRD. Design/Setting/Patients/Interventions: Transcriptional profiling of all known miRNAs in CFBE41o- cells, in their normal counterparts (16HBE14o- cells), and in IB3 cells was performed...
September 30, 2016: Journal of Clinical Endocrinology and Metabolism
Adepitan A Owosho, Shih-Chiang Huang, Sonja Chen, Shruti Kashikar, Cherry L Estilo, Suzanne L Wolden, Leonard H Wexler, Joseph M Huryn, Cristina R Antonescu
BACKGROUND: Based on their distinctive histologic and genetic features, the latest WHO classification of soft tissue tumors includes four pathologic variants of rhabdomyosarcoma (RMS): embryonal (ERMS), alveolar (ARMS), spindle cell-sclerosing (SRMS-ScRMS) and pleomorphic RMS. The aim of this study focused on a detailed clinicopathologic and survival analysis of head and neck RMS (HNRMS) using the latest pathologic and molecular criteria reflecting this new subclassification in a large cohort...
October 2016: Oral Oncology
Khanh V Doan, Ann W Kinyua, Dong Joo Yang, Chang Mann Ko, Sang Hyun Moh, Ko Eun Shong, Hail Kim, Sang-Kyu Park, Dong-Hoon Kim, Inki Kim, Ji-Hye Paik, Ronald A DePinho, Seul Gi Yoon, Il Yong Kim, Je Kyung Seong, Yun-Hee Choi, Ki Woo Kim
Dopaminergic (DA) neurons are involved in the integration of neuronal and hormonal signals to regulate food consumption and energy balance. Forkhead transcriptional factor O1 (FoxO1) in the hypothalamus plays a crucial role in mediation of leptin and insulin function. However, the homoeostatic role of FoxO1 in DA system has not been investigated. Here we report that FoxO1 is highly expressed in DA neurons and mice lacking FoxO1 specifically in the DA neurons (FoxO1 KO(DAT)) show markedly increased energy expenditure and interscapular brown adipose tissue (iBAT) thermogenesis accompanied by reduced fat mass and improved glucose/insulin homoeostasis...
2016: Nature Communications
Cong Wan, Chang-Yun Ping, Xiao-Yu Shang, Jiang-Tian Tian, Si-Han Zhao, Lei Li, Shao-Hong Fang, Wei Sun, Yan-Feng Zhao, Zhao-Ying Li, Yan-Wen Xu, Li-Li Mu, Jing-Hua Wang, Qing-Fei Kong, Guang-You Wang, Hu-Lun Li, Bo Sun
MicroRNA 182 has been found to have a distinct contribution in the clonal expansion of activated- and functioning of specialized-helper T cells. In this study we knocked down microRNA 182 in vivo and induced experimental autoimmune encephalomyelitis (EAE) to determine the influences of microRNA 182 in the Treg cells functional specialization through Foxo1 dependent pathway in the peripheral lymphoid organs. Down-regulation of microRNA 182 significantly increased the proportions of Foxp3(+) T cells in the peripheral lymph nodes and spleen...
September 21, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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