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Histone deacetylase inhibitors as a novel therapeutic approach for pheochromocytomas and paragangliomas

Oncology Research 2022年第5期30卷 211-219页

作者： ASPASIA MANTA SPYRIDON KAZANAS STEFANOS KARAMAROUDIS HELEN GOGAS dimitrios c.ziogas Endocrine Unit Second Department of Internal Medicine Propaedeutic&Research InstituteMedical SchoolNational and Kapodistrian University of AthensAttikon University HospitalAthens12461Greece First Department of Internal Medicine Medical SchoolNational and Kapodistrian University of AthensLaikon General HospitalAthens11527Greece Department of Obstetrics&Gynecology General Hospital of Elefsina ThriassioElefsina19600Greece

Epigenetic mechanisms,such as DNA methylation and histone modiﬁcations(e.g.,acetylation and deacetylation),are strongly implicated in the carcinogenesis of various *** transcription,the expression and functionality of coding gene products are altered following the histone acetylation and *** processes are regulated by histone acetyltransferases(HATs)and histone deacetylases(HDAcs),*** inhibitors(HDAcis)have been developed as promising therapeutic agents,to limit exposure to traditional and toxic chemotherapies and offer more alternatives for some speciﬁc malignant diseases with limited ***,these agents affect many intracellular pathways,including cell cycle arrest,apoptosis and differentiation,and their mechanism of action mainly depends on the type of ***,ﬁve HDAcis have been approved for the treatment of several hematological malignancies(e.g.,T-cell lymphoma subtypes and multiple myeloma);while,many of them are tested for further therapeutic indications in solid tumors(e.g.,colorectal,thyroid,breast,lung and pancreatic cancer).Herein,we review the literature and gather all available evidence,from in vitro and in vivo data to clinical trial results,that recognizes the antitumor activity of HDAcis on pheochromocytomas and paragangliomas;and supports their clinical implementation in the treatment of these rare neuroendocrine tumors at metastatic setting.

关键词： HDAcis HDAc inhibitors Neuroendocrine tumors Epigenetics Histone deacetylation cancer

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circulating autoantibodies to endogenous erythropoietin are associated with chronic hepatitis c virus infection-related anemia

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Hepatobiliary & Pancreatic Diseases International 2017年第3期16卷 289-295页

作者： Aristotelis Tsiakalos Theoharis Voumvas Alexandros Psarris christina K Oikonomou dimitrios c.ziogas Ioannis Ketikoglou Grigorios Hatzis Nikolaos V Sipsas Department of Pathophysiology Laikon General Hospital Medical School National and Kapodistrian University of Athens Athens Greece hird Department of Internal Medicine Laikon General Hospital Medical School National and Kapodistrian University of Athens Athens Greece Microbiology Department Red Cross General Hospital Athens Greece Department of Internal Medicine Hippocration General Hospital Athens Greece

BAcKGROUND： chronic hepatitis c virus （HcV） infection is associated with autoimmune phenomena and is often complicated by anemia. circulating autoantibodies to endogenous erythropoietin （anti-EPO） have been detected in patients with chronic viral infections and were correlated to anemia. The present study aimed to determine anti-EPO prevalence in pa- tients with chronic HcV infection and investigate its possible association with anemia. METHODS： Ninety-three consecutive patients （62 males and 31 females） with chronic HcV infection, who had never re- ceived antiviral therapy or recombinant EPO, were enrolled in the study. circulating anti-EPO were detected in the serum by using an ELISA assay. Quantitative determination of serum EPO levels was done by radioimmunoassay. HcV RNA viral load t and genotype sequencing were also performed. RESULTS： circulating anti-EPO were detected in 10.8% of HcV-infected patients and the prevalence of anti-EPO was significantly higher in patients with anemia （19.4% vs 5.3%, P=0.040） compared to that in those without anemia. compared to anti-EPO negative cases, anti-EPO positive patients had higher frequency of anemia （70.0% vs 34.9%, P=0.030）, lower EPO concentrations （median 16.35 vs 30.65 mU/mL, P=0.005）, and higher HcV RNA viral load （median 891.5x103 vs 367.5x 103 IU/mL, P=0.016）. In multivariate regression anal- ysis the presence of anti-EPO remained an independent predictor of anemia （adjusted OR： 14.303, 95% cI： 1.417-36.580, P=0.024）. EPO response to anemia was less prominent among anti-EPO positive patients （P=0.001）. cONcLUSIONS： circulating anti-EPO are detected in a significant proportion of treatment-naive HcV-infected patients and are independently associated with anemia, suggesting a further implication of autoimmunity in the pathophysiology of HcV-related anemia.

关键词： hepatitis c virus erythropoietin anemia autoantibodies

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