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Jun Sang Bae, See-Hyoung Park, Urangoo Jamiyandorj, Kyoung Min Kim, Sang Jae Noh, Jung Ryul Kim, Hye Jeong Park, Keun Sang Kwon, Sung Hoo Jung, Ho Sung Park, Byung-Hyun Park, Ho Lee, Woo Sung Moon, Karl G Sylvester, Kyu Yun Jang
Recently, the roles of sirtuins (SIRTs) in tumorigenesis have been of interest to oncologists, and casein kinase 2 α1 (CSNK2A1) has been shown to be involved in tumorigenesis by phosphorylating various proteins, including SIRT1. Therefore, we evaluated the roles of CSNK2A1, SIRT6, and phosphorylated SIRT6 and their relationships in breast carcinoma. Nuclear expression of CSNK2A1 and SIRT6 predicted shorter overall survival and relapse-free survival by multivariate analysis. Inhibition of CSNK2A1 decreased the proliferative and invasive activity of cancer cells...
October 13, 2016: American Journal of Pathology
Wynand Paul Roos, Andrea Krumm
Histone/protein deacetylases play multiple roles in regulating gene expression and protein activation and stability. Their deregulation during cancer initiation and progression cause resistance to therapy. Here, we review the role of histone deacetylases (HDACs) and the NAD(+) dependent sirtuins (SIRTs) in the DNA damage response (DDR). These lysine deacetylases contribute to DNA repair by base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), non-homologous end joining (NHEJ), homologous recombination (HR) and interstrand crosslink (ICL) repair...
October 13, 2016: Nucleic Acids Research
Kishor Pant, Ajay K Yadav, Parul Gupta, Abhishek Singh Rathore, Baibaswata Nayak, Senthil K Venugopal
Hepatitis B Virus (HBV) utilizes several mechanisms to survive in the host cells and one of the main pathways being autophagosome formation. Humic acid (HA), one of the major components of Mineral pitch, is an Ayurvedic medicinal food, commonly used by the people of the Himalayan regions of Nepal and India for various body ailments. We hypothesized that HA could induce cell death and inhibit HBV-induced autophagy in hepatic cells. Incubation of Hep G2.2.1.5 cells (HepG2 cells stably expressing HBV) with HA (100 μM) inhibited both cell proliferation and autophagosome formation significantly, while apoptosis induction was enhanced...
October 6, 2016: Scientific Reports
Lincy Edatt, K Haritha, T V Sruthi, P Aswini, V B Sameer Kumar
MMP9 is a member of the family of zinc-containing endopeptidases which degrade various components of the extracellular matrix, thereby regulating matrix remodeling. Since matrix remodeling plays an important role during growth and progression of cancer and considering the fact that, tumor cells switch to aerobic glycolysis as its major energy source, this study was designed to analyze if partial inhibition of glycolysis (the major energy pathway during hypoxia) can be used as a means to control matrix remodeling in terms of MMP9 activity and expression...
October 4, 2016: Molecular and Cellular Biochemistry
Ashok Mandala, Nabanita Das, Sudarshan Bhattacharjee, Bidisha Mukherjee, Satinath Mukhopadhyay, Sib Sankar Roy
Insulin resistance (IR) is an important determinant of type-2 diabetes mellitus (T2DM). Free fatty acids (FFAs) induce IR by various mechanisms. A surfeit of circulating FFA leads to intra-myocellular lipid accumulation that induces mitochondrial ROS generation and worsens IR. However, the molecular mechanisms behind are unclear. We identified thioredoxin interacting protein (TxNIP), which is overexpressed in T2DM, to be a promoter of ROS-induced IR. We observed upregulation of TxNIP upon palmitate treatment in skeletal muscle cells that led to ROS generation and Glut-4 downregulation resulting in impaired glucose-uptake...
October 28, 2016: Biochemical and Biophysical Research Communications
Sara Giovanna Romeo, Alfredo Conti, Francesca Polito, Chiara Tomasello, Valeria Barresi, Domenico La La Torre, Maria Cucinotta, Flavio Filippo Angileri, Marcello Bartolotta, Rosa Maria Di Giorgio, M'Hammed Aguennouz
Sirtuins are a family of 7 histone deacetylases largely involved in the regulation of cell proliferation, survival and death. The role of sirtuins in tumorigenesis and cancer progression has been previously studied in certain cancer types. Few studies have investigated sirtuin expression in gliomas, with controversial results. The aim of the present study was to investigate the expression of sirtuin-1 (Sirt-1) in diffuse astrocytoma [low grade astrocytoma (LGA)], anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM) and in primary glioma cell lines: PLGAC (primary LGA cells); PAAC (primary AA cells); and PGBMC (primary GBM cells)...
October 2016: Oncology Letters
Seong-Hui Eo, Soo Young Choi, Song Ja Kim
Matrix metalloproteinases (MMPs) are critical for the degradation of the extracellular matrix (ECM), which includes cartilage-specific collagen types I, II and XI. We previously found that PEP-1-sirtuin (SIRT)2 could induce dedifferentiation of articular chondrocytes; however, the underlying mechanisms remains unclear. We addressed this in the present study by examining the association between PEP-1-SIRT2 and the expression of MMP-1 and MMP-13 and type II collagen in rabbit articular chondrocytes. We found that PEP-1-SIRT2 increased MMP-1 and -13 expression in a dose- and time-dependent manner, as determined by western blotting...
September 30, 2016: Experimental Cell Research
Amanda R Townsend, Li Chia Chong, Christos Karapetis, Timothy J Price
Liver metastases are often the dominant site of metastatic disease in colorectal cancer. Selective internal radiation therapy (SIRT) involves embolising radiolabeled spheres (SIR-Spheres) into the arterial supply of the liver. This review assesses the effectiveness and toxicity of SIRT in the treatment of metastatic colorectal cancer liver metastasis when given alone or with systemic or regional hepatic artery chemotherapy. We reviewed only randomised controlled trials comparing SIRT and chemotherapy (systemic and/or regional) with chemotherapy alone, or comparing SIRT alone with best supportive care...
September 10, 2016: Cancer Treatment Reviews
Lisa M Rowley, Kevin M Bradley, Philip Boardman, Aida Hallam, Daniel R McGowan
: Imaging on a gamma camera with Yttrium-90 ((90)Y) following selective internal radiotherapy (SIRT) may allow for verification of treatment delivery but suffers relatively poor spatial resolution and imprecise dosimetry calculation. (90)Y Positron Emission Tomography (PET) / Computed Tomography (CT) imaging is possible on 3D, time-of-flight machines however images are usually poor due to low count statistics and noise. A new PET reconstruction software using a Bayesian penalized likelihood (BPL) reconstruction algorithm (termed Q...
September 29, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Z Li, B Bridges, J Olson, S A Weinman
The multispecific transcription factor and tumor suppressor FOXO3 is an important mediator of apoptosis, but the mechanisms that control its proapoptotic function are poorly understood. There has long been evidence that acetylation promotes FOXO3-driven apoptosis and recently a specific JNK (c-Jun N-terminal kinase)-dependent S574 phosphorylated form (p-FOXO3) has been shown to be specifically apoptotic. This study examined whether acetylation and S574 phosphorylation act independently or in concert to regulate the apoptotic function of FOXO3...
September 26, 2016: Oncogene
Stephanie K Nygard, Anthony Klambatsen, Bailey Balouch, Vanya Quinones-Jenab, Shirzad Jenab
The aim of this study was to investigate the intracellular responses associated with the acquisition and expression of cocaine-context associations. ERK (extracellular regulated kinase), CREB (cAMP responsive element binding protein), FosB and ΔFosB proteins were of particular interest due to their involvement in cocaine reward and in synaptic plasticity underlying learning and memory. We used the conditioned place preference (CPP) paradigm, which employs a Pavlovian conditioning procedure to establish an association between a drug-paired environment and the drug's rewarding effects, to study the role of these signaling pathways in cocaine-context associations...
September 21, 2016: Behavioural Brain Research
Rong Shuang, Xu Rui, Li Wenfang
As the aging of the world's population is becoming increasingly serious, dementia-related diseases have become a hot topic in public health research. In recent years, human epidemiological studies have focused on lipid metabolism disorders and dementia. The efficacy of phytosterol intake as a cholesterol-lowering agent has been demonstrated. Phytosterols directly serve as ligands of the nuclear receptors, peroxisome proliferator-activated receptors (PPARs), activating Sirtuin 1 (SIRT-1), which are involved in the regulation of lipid metabolism and the pathogenesis of dementia...
September 23, 2016: Plant Foods for Human Nutrition
Mareike Sandvoß, Arne Björn Potthast, Frauke von Versen-Höynck, Anibh Martin Das
The hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome is frequently observed in mothers whose offspring have long-chain fatty acid oxidation defects. We previously found that fatty acid oxidation is compromised not only in these inborn errors of metabolism but also in human umbilical vein endothelial cells (HUVECs) from all pregnancies complicated by the HELLP syndrome. Sirtuins are oxidized nicotinamide adenine dinucleotide (NAD(+))dependent deacetylases linked to the metabolic status of the cell...
September 20, 2016: Reproductive Sciences
Sabine Sellner, Ricardo Paricio-Montesinos, Alena Spieß, Annette Masuch, Daniel Erny, Laura A Harsan, Dominik V Elverfeldt, Marius Schwabenland, Knut Biber, Ori Staszewski, Sergio Lira, Steffen Jung, Marco Prinz, Thomas Blank
Homo and heterozygote cx3cr1 mutant mice, which harbor a green fluorescent protein (EGFP) in their cx3cr1 loci, represent a widely used animal model to study microglia and peripheral myeloid cells. Here we report that microglia in the dentate gyrus (DG) of cx3cr1 (-/-) mice displayed elevated microglial sirtuin 1 (SIRT1) expression levels and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) p65 activation, despite unaltered morphology when compared to cx3cr1 (+/-) or cx3cr1 (+/+) controls...
2016: Acta Neuropathologica Communications
Nan Hu, Jun Ren, Yingmei Zhang
Insulin resistance contributes to the high prevalence of type 2 diabetes mellitus, leading to cardiac anomalies. Emerging evidence depicts a pivotal role for mitochondrial injury in oxidative metabolism and insulin resistance. Mitochondrial aldehyde dehydrogenase (ALDH2) is one of metabolic enzymes detoxifying aldehydes although its role in insulin resistance remains elusive. This study was designed to evaluate the impact of ALDH2 overexpression on insulin resistance-induced myocardial damage and mechanisms involved with a focus on autophagy...
September 12, 2016: Oncotarget
A Bauschke, A Altendorf-Hofmann, C Malessa, S Schüle, J Zanow, U Settmacher
AIM: In the 7th edition of the TNM classification, not only HCC with distant metastases but also those with regional lymph node metastases are classified as stage IV. MATERIALS AND METHODS, RESULTS: From our prospectively recorded tumor registry, 138 patients (17 %) with HCC were in stage IV. Among those were 68 and 70, respectively, in stage IVA (regional lymph node metastases) and IVB (distant metastases). The tumors were less frequently treated with resection or local ablative treatment (chemoembolization, RFA, SIRT, percutaneous radiation) than patients in stage I-III...
September 15, 2016: Journal of Cancer Research and Clinical Oncology
Ratana Lim, Gillian Barker, Ramkumar Menon, Martha Lappas
Preterm birth remains the major cause of neonatal mortality and morbidity, mediated largely by an inflammatory process. The sirtuin (SIRT) family of cellular regulators have been implicated as key inhibitors of inflammation. We have previously reported a role for SIRT1, SIRT2 and SIRT6 in regulating inflammation-induced pro-labor mediators. In this study, we determined the effect of term labor and pro-inflammatory cytokines on SIRT3, SIRT4, SIRT5 and SIRT7 expression in human myometrium. Functional studies were also employed to investigate the effect of siRNA knockdown of SIRTs in regulating inflammation-induced pro-labor mediators...
September 14, 2016: Biology of Reproduction
Justin K Mikell, Armeen Mahvash, Wendy Siman, Veera Baladandayuthapani, Firas Mourtada, S Cheenu Kappadath
PURPOSE: To quantify differences that exist between dosimetry models used for (90)Y selective internal radiation therapy (SIRT). METHODS AND MATERIALS: Retrospectively, 37 tumors were delineated on 19 post-therapy quantitative (90)Y single photon emission computed tomography/computed tomography scans. Using matched volumes of interest (VOIs), absorbed doses were reported using 3 dosimetry models: glass microsphere package insert standard model (SM), partition model (PM), and Monte Carlo (MC)...
July 27, 2016: International Journal of Radiation Oncology, Biology, Physics
Jana Kudová, Ondřej Vašíček, Milan Číž, Lukáš Kubala
Melatonin, a molecule involved in the regulation of circadian rhythms, has protective effects against myocardial injuries. However, its capability to regulate the maturation of cardiac progenitor cells is unclear. Recently, several studies have shown that melatonin inhibits the stabilization of hypoxia-inducible factors (HIFs), important signaling molecules with cardioprotective effects. In this study, by employing differentiating mouse embryonic stem cells, we report that melatonin significantly upregulated the expression of cardiac cell-specific markers (myosin heavy chains six and seven) as well as the percentage of myosin heavy chain-positive cells...
September 7, 2016: Journal of Pineal Research
Michael J Magnetta, Anish Ghodadra, Steven J Lahti, Minzhi Xing, Di Zhang, Hyun S Kim
PURPOSE: To determine whether pathologic colorectal tumor KRAS mutation status is correlated with progression-free survival (PFS) by imaging after selective internal radiation therapy with Yttrium-90 (SIRT Y90) for metastatic colorectal cancer in the liver (mCRC). MATERIALS AND METHODS: This was an IRB approved, HIPAA compliant retrospective cohort study. Consecutive patients with unresectable mCRC with documented KRAS mutation status treated at a single center from 2002 to 2013 with SIRT Y90 were investigated...
September 6, 2016: Abdominal Radiology
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