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María Paula Ceballos, Giulia Decándido, Ariel Darío Quiroga, Carla Gabriela Comanzo, Verónica Inés Livore, Florencia Lorenzetti, Flavia Lambertucci, Lorena Chazarreta-Cifre, Claudia Banchio, María de Luján Alvarez, Aldo Domingo Mottino, María Cristina Carrillo
Sirtuins (SIRTs) 1 and 2 deacetylases are overexpressed in hepatocellular carcinoma (HCC) and are associated with tumoral progression and multidrug resistance (MDR). In this study we analyzed whether SIRTs 1 and 2 activities blockage was able to affect cellular survival and migration and to modulate p53 and FoxO1 acetylation in HepG2 and Huh7 cells. Moreover, we analyzed ABC transporters P-glycoprotein (P-gp) and multidrug resistance-associated protein 3 (MRP3) expression. We used cambinol and EX-527 as SIRTs inhibitors...
March 12, 2018: Toxicology Letters
Jennifer Gill, Andrei Baiceanu, Paul J Clark, Andrew Langford, Julianah Latiff, Pei-Ming Yang, Eric M Yoshida, Panos Kanavos
AIM: To better understand the hepatocellular carcinoma (HCC) patient journey, we conducted a patient survey across 13 countries. METHODS: The survey included closed- and open-ended questions developed using an iterative process to gather information on demographics, diagnosis and treatment. Patients self-selected or were directed to the online survey by their doctor. RESULTS: A total of 256 patients completed the survey. More than two-thirds (68%) felt they did not receive enough information about HCC at diagnosis...
March 15, 2018: Future Oncology
Shuyi Wang, Cong Wang, Subat Turdi, Kacy L Richmond, Yingmei Zhang, Jun Ren
BACKGROUND AND AIMS: Uncorrected obesity contributes to cardiac remodeling and contractile dysfunction although the underlying mechanism remains poorly understood. Mitochondrial aldehyde dehydrogenase (ALDH2) is a mitochondrial enzyme with some promises in a number of cardiovascular diseases. This study was designed to evaluate the impact of ALDH2 on cardiac remodeling and contractile property in high fat diet-induced obesity. METHODS: Wild-type (WT) and ALDH2 transgenic mice were fed low (10% calorie from fat) or high (45% calorie from fat) fat diet for 5 months prior to the assessment of cardiac geometry and function using echocardiography, IonOptix system, Lectin, and Masson Trichrome staining...
March 13, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Lucia Altucci, Vincenzo Carafa, Angela Nebbioso, Francesca Cuomo, Dante Rotili, Gilda Cobellis, Paola Bontempo, Alfonso Baldi, Enrico P Spugnini, Gennaro Citro, Angela Chambery, Rosita Russo, Menotti Ruvo, Paolo Ciana, Luca Maravigna, Jani Shaik, Enrico Radaelli, Pasqualino De Antonellis, Domenico Tarantino, Adele Pirolli, Rino Ragno, Massimo Zollo, Hendrik G Stunnenberg, Antonello Mai
PURPOSE: Alteration in cell death is a hallmark of cancer. A functional role regulating survival, apoptosis and necroptosis has been attributed to RIP1/3 complexes. EXPERIMENTAL DESIGN: We have investigated the role of RIP1 and the effects of MC2494 in cell death induction, using different methods as flow cytometry, transcriptome analysis, immunoprecipitation, enzymatic assays, transfections, mutagenesis and in vivo studies with different mice models. RESULTS: Here, we show that RIP1 is highly expressed in cancer and we define a novel RIP1/3-SIRT1/2-HAT1/4 complex...
March 13, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Yan Li, Ying Ma, Liqiang Song, Lu Yu, Le Zhang, Yingmei Zhang, Yuan Xing, Yue Yin, Heng Ma
Mitochondrial dynamics have critical roles in aging, and their impairment represents a prominent risk factor for myocardial dysfunction. Mitochondrial deacetylase sirtuin (SIRT)3 contributes greatly to the prevention of redox stress and cell aging. The present study explored the role of SIRT3 on myocardium aging. Western blot analysis demonstrated that SIRT3 expression levels were significantly lower in the myocardia of aged mice compared with young mice. Immunoprecipitation and western blot assays indicated that the activity of mitochondrial manganese superoxide dismutase (MnSOD) and peroxisome proliferator‑activated receptor γ coactivator (PGC)‑1α was reduced in the aged heart...
March 9, 2018: International Journal of Molecular Medicine
Han Jiang, Shijie Xin, Yumeng Yan, Yu Lun, Xiao Yang, Jian Zhang
BACKGROUND AND AIMS: Acetylation levels of FOXP3 could influence its expression level and SIRT1 is a deacetylase, which could regulate the acetylation level of FOXP3. We aimed to investigate the mechanism of Treg dysfunction, which might be caused by abnormal acetylation of FOXP3 regulated by SIRT1 in abdominal aortic aneurysm (AAA) patients. METHODS: Peripheral CD4+ T cells from AAA patients, abdominal aortic atherosclerotic occlusive disease (AOD) patients, and healthy donors (HC) were analyzed by flow cytometry to determine the percentage of CD4+ CD25+ Tregs and CD4+ CD25+ FOXP3+ T cells in CD4+ T cells...
February 14, 2018: Atherosclerosis
Vindya Abeysinghe, Siva Sundararajan, Luc Delriviere, Jonathan Tibballs
Unresectableintrahepaticcholangiocarcinoma has a very poor prognosis despite various treatment options. The case presented describes the diagnostic challenges of a young pregnant woman with unresectable cholangiocarcinoma. The current treatment options for cholangiocarcinoma have limited evidence and high recurrence rate. Given the young age of this patient, selective internal radiotherapy was trialled with traditional chemotherapy with a clinically significant result. This case highlights the delays when diagnosing cholangiocarcinoma in younger patients and the possibility of selective internal radiation therapy in combination with chemotherapy as a potential first-line treatment for a complete response in unresectable disease...
March 9, 2018: BMJ Case Reports
Bong-Geum Jang, Boyoung Choi, Suyeon Kim, Jae-Yong Lee, Min-Ju Kim
Neuroblastoma cell differentiation is a valuable model for studying therapeutic methods in neuroblastoma and the mechanisms of neuronal differentiation. Here, we used trichostatin A (TSA) and sirtinol, which are inhibitors of cHDACs and sirtuins, respectively, to show that classical histone deacetylases (cHDACs) and sirtuins (silent mating type information regulation 2 homolog; SIRTs) affect all-trans retinoic acid (ATRA)-induced differentiation of neuroblastoma cells. After first determining neurite elongation and expression levels of tyrosine hydroxylase and high size neurofilament as useful differentiation markers, we observed that TSA increased neuroblastoma cell differentiation, while sirtinol had the antagonistic effect of decreasing it...
March 7, 2018: Journal of Molecular Neuroscience: MN
Hanlin Yao, Zhen Yao, Shaocheng Zhang, Wenjun Zhang, Wen Zhou
Osteoporosis is a disease that significantly influences life expectancy and quality in humans. Oxidative stress may stimulate bone marrow osteoclast differentiation and inhibit osteoblast (OB) differentiation. OB proliferation and differentiation are affected by the forkhead box O (FoxO)1/β‑catenin signaling pathway. The osteogenic differentiation of mesenchymal stem cells (MSCs) may be promoted by silent information regulator type‑1 [sirtuin (SIRT)1]. However, the molecular mechanism of SIRT1 regulation of osteogenic differentiation of MSCs remains unclear, and further elucidation is needed...
March 1, 2018: Molecular Medicine Reports
Xiaojuan Wang, Jun Li, Wei Tang, Yiqiao Zhao, Xing Li
Background The development of an effective treatment for type 2 diabetes mellitus is urgently needed. This study aimed to investigate the role of micro RNA (miR)-323-3p in regulating the expression of adiponectin receptor 1 (AdipoR1), as well as the insulin secretion and cell function of pancreatic MIN6 β-cells. Methods MIN6 cells were treated with miR-323-3p mimics or inhibitors, and the effects on cell growth, proliferation, mitosis, and insulin secretion were studied. The expression levels of sirtuin-1 (SIRT-1) and AMP-activated protein kinase (AMPK) genes were also assessed...
January 1, 2018: Journal of International Medical Research
Cathal O'Leary, Megan Greally, John McCaffrey, Peter Hughes, Leo L P Lawler, Martin O'Connell, Tony Geoghegan, Cormac Farrelly
BACKGROUND: Liver metastases are the commonest cause of death for patients with colorectal cancer. Growing evidence supports the use of selective internal radiation therapy (SIRT) in combination with conventional chemotherapy regimens for liver-only or liver-dominant unresectable metastatic colorectal cancer. AIMS: To measure and evaluate outcomes of the first 20 consecutive patients with unresectable colorectal liver metastasis selected for SIRT in addition to their chemotherapy at a single Irish institution...
March 6, 2018: Irish Journal of Medical Science
Yung-Tsung Chen, Yu-Chun Lin, Jin-Seng Lin, Ning-Sun Yang, Ming-Ju Chen
SCOPE: Non-alcoholic fatty liver disease (NAFLD) is a common disease that is concomitant with obesity, resulting in increased mortality. To date, the efficiency of NAFLD treatment still needs to be improved. Therefore, we aimed to evaluate the effect of Lactobacillus mali APS1, which was isolated from sugary kefir, on hepatic steatosis in rats fed a high-fat diet (HFD). METHODS AND RESULTS: Sprague Dawley rats were fed a control diet, a high-fat diet with saline and a high-fat diet with APS1 intervention by gavage daily for 12 weeks...
March 5, 2018: Molecular Nutrition & Food Research
Aglaia Domouchtsidou, Vahé Barsegian, Stefan P Mueller, Jan Best, Judith Ertle, Sotiria Bedreli, Peter A Horn, Andreas Bockisch, Monika Lindemann
The purpose of our study was to assess the immune function of patients with inoperable hepatic malignancies after treatment with selective internal radiotherapy (SIRT) and to identify possible correlations with clinical parameters. In 25 patients receiving SIRT lymphocyte proliferation and the production of pro- and anti-inflammatory cytokines (interferon-γ and interleukin-10) after stimulation with mitogens and microbial antigens were tested prior to therapy, directly after therapy (day 1) and at day 2, 7 and 28 post therapy using the lymphocyte transformation test and enzyme-linked immunospot assays...
March 2, 2018: Cancer Immunology, Immunotherapy: CII
Mégane Lemaire, Valerio Lucidi, Fikri Bouazza, Georgios Katsanos, Bruno Vanderlinden, Hugo Levillain, Philippe Delatte, Camilo A Garcia, Michael Vouche, Maria Gomez Galdon, Pieter Demetter, Amélie Deleporte, Alain Hendlisz, Patrick Flamen, Vincent Donckier
BACKGROUND/PURPOSE: Preoperative selective internal radiation therapy (SIRT) may improve the results of partial hepatectomy (PH) or radiofrequency destruction (RF) for hepatocellular carcinoma (HCC) in patients with cirrhosis. The aim of this study was to evaluate the feasibility and safety of this combined approach. METHODS: Patients with cirrhosis and HCC selected for PH or RF were prospectively included and systematically proposed for preoperative SIRT. Feasibility and safety of SIRT and post-SIRT PH or RF were assessed...
February 24, 2018: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
Weifeng Wan, Yan Ding, Zongyi Xie, Qian Li, Feng Yan, Enkhjargal Budbazar, William J Pearce, Richard Hartman, Andre Obenaus, John H Zhang, Yong Jiang, Jiping Tang
Platelet-derived growth factor receptor-β (PDGFR-β) has been reported to promote phenotypic transformation of vascular smooth muscle cells (VSMCs). The purpose of this study was to investigate the role of the PDGFR-β/IRF9/SIRT-1/NF-κB pathway in VSMC phenotypic transformation after subarachnoid hemorrhage (SAH). SAH was induced using the endovascular perforation model in Sprague-Dawley rats. PDGFR-β small interfering RNA (siRNA) and IRF9 siRNA were injected intracerebroventricularly 48 h before SAH. SIRT1 activator (resveratrol) and inhibitor (EX527) were administered intraperitoneally 1 h after SAH induction...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
Sebastian Mafeld, Jeremy French, Dina Tiniakos, Beate Haugk, Derek Manas, Peter Littler
We describe a 52-year-old female patient who presented with a 9.5-cm fibrolamellar hepatocellular carcinoma (FL-HCC). The patient was initially unsuitable for surgical resection and therefore underwent transarterial chemoembolization followed by selective internal radiation therapy (SIRT) with Yttrium-90 to downsize the tumour. Following SIRT, the tumour decreased in volume from 350 to 20 cm3 allowing curative (R0) resection with an extended left hepatectomy and reconstruction of IVC. This is the first reported case of FL-HCC treated with SIRT in which, due to the good SIRT response, the patient was downsized to allow curative resection...
February 21, 2018: Cardiovascular and Interventional Radiology
Mina S Makary, Lawrence S Krishner, Evan J Wuthrick, Mark P Bloomston, Joshua D Dowell
Adrenocortical carcinoma (ACC) is a rare malignancy with generally poor outcomes and limited treatment options. While surgical resection can be curative for early local disease, most patients present with advanced ACC owing to nonspecific symptoms. For those patients, treatment options include systemic chemotherapy and locoregional therapies including radiofrequency ablation and transarterial chemoembolization. We present the first reported case of utilizing yttrium-90 microsphere selective internal radiation therapy (SIRT) in combination with first line EDP-M (Etoposide, Doxorubicin, Cisplatin, Mitotane) chemotherapy and debulking surgical primary tumor resection for treatment of metastatic ACC...
February 10, 2018: World Journal of Clinical Oncology
Hui-Rong Jing, Fu-Wen Luo, Xing-Ming Liu, Xiao-Feng Tian, Yun Zhou
AIM: To evaluate whether fish oil (FO) can protect liver injury induced by intestinal ischemia/reperfusion (I/R) via the AMPK/SIRT-1/autophagy pathway. METHODS: Ischemia in Wistar rats was induced by superior mesenteric artery occlusion for 60 min and reperfusion for 240 min. One milliliter per day of FO emulsion or normal saline was administered by intraperitoneal injection for 5 consecutive days to each animal. Animals were sacrificed at the end of reperfusion...
February 21, 2018: World Journal of Gastroenterology: WJG
Misa Hayashida, Shinichi Ogawa, Marek Malac
We evaluate the suitability of simultaneous iterative reconstruction technique (SIRT), filtered back projection, and simultaneous algebraic reconstruction technique methods for buried interface roughness measurements. We also investigate the effect of total electron dose distributed over the entire tilt series on measured roughness values. We investigate the applicability of the dose fractionation theorem by evaluating the effect of an increasing number of images, i.e., decreasing tilt increment size at fixed total electron irradiation dose on the quantitative measurement of buried interface roughness...
February 21, 2018: Microscopy Research and Technique
Hyun S Kim, Walid L Shaib, Chao Zhang, Ganji Purnachandra Nagaraju, Christina Wu, Olatunji B Alese, Zhengjia Chen, Edith Brutcher, Meredith Renfroe, Bassel F El-Rayes
BACKGROUND: Neuroendocrine tumors (NETs) metastasize to the liver. Everolimus and selective internal radioembolization (SIRT) are approved treatments. Pasireotide is a somatostatin analogue with an affinity for somatostatin receptors 1, 2, 3, and 5. Everolimus and pasireotide may potentiate SIRT radiosensitization and inhibit rebound angiogenesis. This study evaluated the safety of pasireotide, everolimus, and SIRT. METHODS: This 3 + 3 phase 1 trial evaluated 3 dose levels of everolimus (2...
February 16, 2018: Cancer
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