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1.
Biochem Biophys Res Commun ; 515(1): 241-247, 2019 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-31146910

RESUMO

Phosphatases play an important role in cellular signaling and are often found dysregulated in cancers including glioblastoma (GBM). A comprehensive bioinformatics analysis of phosphatases (n = 403) in multiple datasets revealed their deregulation in GBM. Among the differentially regulated phosphatases (n = 186; 46.1%), majority of them were found to be regulated by microRNA (n = 94; 50.5%) followed by DNA methylation (n = 22; 11.8%) and altered copy number variation (n = 10; 5.37%). STYXL1 (Serine/threonine/tyrosine-interacting-like protein 1) was found to be the second most amplified gene in GBM, upregulated, and correlated to poor prognosis. The expression of STYXL1 was also found to be higher in IDH1 mutant gliomas and G-CIMP- gliomas which are reported to be more aggressive than their corresponding counterparts. Silencing STYXL1 inhibited glioma cell growth, soft agar colony formation, migration, invasion, proliferation, and xenograft tumor growth. Further, ectopic expression of STYXL1 was found to promote glioma cell growth, soft agar colony formation, migration, and RasV12 induced in-vitro transformation of immortalized human astrocytes, thus confirming its oncogenic potential in GBM. In this report, we provide a comprehensive overview of deregulation of phosphatases in GBM and demonstrate for the first time, the oncogenic nature of STYXL1 in GBM. This study might be useful for treatment of GBM patients with deregulated STYXL1.


Assuntos
Proteínas Reguladoras de Apoptose/genética , Neoplasias Encefálicas/genética , Carcinogênese/genética , Glioma/genética , Monoéster Fosfórico Hidrolases/genética , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/terapia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Glioma/metabolismo , Glioma/terapia , Humanos , Camundongos , Monoéster Fosfórico Hidrolases/metabolismo , Terapêutica com RNAi/métodos , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
2.
J Mol Med (Berl) ; 96(11): 1177-1187, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30155768

RESUMO

Endothelial cells respond to mechanical stimuli such as stretch. This property can be exploited with caution to induce angiogenesis which will have immense potential to treat pathological conditions associated with insufficient angiogenesis. The primary aim of this study is to test if low-pressure shock waves can be used to induce angiogenesis. Using a simple diaphragm-based shock tube, we demonstrate that a single pulse of low pressure (0.4 bar) shock wave is enough to induce proliferation in bovine aortic endothelial cells and human pulmonary microvascular endothelial cells. We show that this is associated with enhanced Ca++ influx and phosphorylation of phosphatidylinositol-3-kinase (PI3K) which is normally observed when endothelial cells are exposed to stretch. We also demonstrate the pro-angiogenic effect of shock waves of single pulse (per dose) using murine back punch wound model. Shock wave treated mice showed enhanced wound-induced angiogenesis as reflected by increased vascular area and vessel length. They also showed accelerated wound closure compared to control mice. Overall, our study shows that just a single pulse/shot (per dose) of shock waves can be used to induce angiogenesis. Importantly, we demonstrate this effect using a pulse of low-pressure shock waves (0.4 bar, in vitro and 0.15 bar, in vivo). KEY MESSAGES: Low-pressure single-pulse shock waves can induce endothelial cell migration and proliferation. This effect is endothelial cell specific. These shock waves enhance wound-induced angiogenesis in vivo. These shock waves can also accelerate wound healing in vivo.


Assuntos
Tratamento por Ondas de Choque Extracorpóreas , Neovascularização Fisiológica , Animais , Bovinos , Movimento Celular , Proliferação de Células , Células Endoteliais/fisiologia , Feminino , Humanos , Camundongos Endogâmicos BALB C
3.
PLoS One ; 10(7): e0131706, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26158453

RESUMO

Health monitoring is an integral part of laboratory animal quality standards. However, current or past prevalence data as well as regulatory requirements dictate the frequency, type and the expanse of health monitoring. In an effort to understand the prevalence of rodent pathogens in India, a preliminary study was carried out by sero-epidemiology. Sera samples obtained from 26 public and private animal facilities were analyzed for the presence of antibodies against minute virus of mice (MVM), ectromelia virus (ECTV), lymphocytic choriomeningitis virus (LCMV), mouse hepatitis virus (MHV), Sendai virus (SeV), and Mycoplasma pulmonis in mice, and SeV, rat parvo virus (RPV), Kilham's rat virus (KRV) and sialodacryoadenitis virus (SDAV) in rats, by sandwich ELISA. It was observed that MHV was the most prevalent agent followed by Mycoplasma pulmonis and MVM in mice, and SDAV followed by RPV were prevalent in rats. On the other hand, none of the samples were positive for ECTV in mice, or SeV or KRV in rats. Multiple infections were common in both mice and rats. The incidence of MHV and Mycoplasma pulmonis was higher in facilities maintained by public organizations than in vivaria of private organizations, although the difference was not statistically different. On the other hand the prevalence of rodent pathogens was significantly higher in the northern part of India than in the South. These studies form the groundwork for detailed sero-prevalence studies which should further lay the foundations for country-specific guidelines for health monitoring of laboratory animals.


Assuntos
Infecções por Mycoplasma/epidemiologia , Doenças dos Roedores/epidemiologia , Viroses/epidemiologia , Animais , Animais de Laboratório , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Ensaio de Imunoadsorção Enzimática , Geografia , Incidência , Índia/epidemiologia , Camundongos , Infecções por Mycoplasma/microbiologia , Mycoplasma pulmonis/imunologia , Mycoplasma pulmonis/fisiologia , Prevalência , Ratos , Doenças dos Roedores/microbiologia , Doenças dos Roedores/virologia , Estudos Soroepidemiológicos , Viroses/virologia , Vírus/imunologia
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