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Current evidence for histone deacetylase inhibitors in pancreatic cancer 被引量:9
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作者 ioannis koutsounas Constantinos Giaginis +1 位作者 Efstratios Patsouris Stamatios Theocharis 《World Journal of Gastroenterology》 SCIE CAS 2013年第6期813-828,共16页
Pancreatic cancer is one of the most aggressive human cancers,with more than 200 000 deaths worldwide every year.Despite recent efforts,conventional treatment approaches,such as surgery and classic chemotherapy,have o... Pancreatic cancer is one of the most aggressive human cancers,with more than 200 000 deaths worldwide every year.Despite recent efforts,conventional treatment approaches,such as surgery and classic chemotherapy,have only slightly improved patient outcomes.More effective and well-tolerated therapies are required to reverse the current poor prognosis of this type of neoplasm.Among new agents,histone deacetylase inhibitors (HDACIs) are now being tested.HDACIs have multiple biological effects related to acetylation of histones and many non-histone proteins that are involved in regulation of gene expression,apoptosis,cell cycle progression and angiogenesis.HDACIs induce cell cycle arrest and can activate the extrinsic and intrinsic pathways of apoptosis in different cancer cell lines.In the present review,the main mechanisms by which HDACIs act in pancreatic cancer cells in vitro,as well as their antiproliferative effects in animal models are presented.HDACIs constitute a promising treatment for pancreatic cancer with encouraging anti-tumor ef-fects,at well-tolerated doses. 展开更多
关键词 PANCREATIC cancer HISTONE DEACETYLASES HISTONE DEACETYLASE INHIBITORS Experimental studies
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Histone deacetylase inhibitors and pancreatic cancer:Are there any promising clinical trials? 被引量:3
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作者 ioannis koutsounas Constantinos Giaginis Stamatios Theocharis 《World Journal of Gastroenterology》 SCIE CAS 2013年第8期1173-1181,共9页
Pancreatic cancer,although not very frequent,has an exceptionally high mortality rate,making it one of the most common causes of cancer mortality in developed countries.Pancreatic cancer is difficult to diagnose,allow... Pancreatic cancer,although not very frequent,has an exceptionally high mortality rate,making it one of the most common causes of cancer mortality in developed countries.Pancreatic cancer is difficult to diagnose,allowing few patients to have the necessary treatment at a relatively early stage.Despite a marginal benefit in survival,the overall response of pancreatic cancer to current systemic therapy continues to be poor,and new therapies are desperately needed.Histone deacetylase(HDAC) enzymes play an important role in the development and progression of cancer and HDAC inhibitors(HDACIs) have been shown to induce differentiation and cell cycle arrest,activate the extrinsic or intrinsic pathways of apoptosis,and inhibit invasion,migration and angiogenesis in different cancer cell lines.As a result of promising preclinical data,various HDACIs are being tested as either monotherapeutic agents or in combination regimens for both solid and hematological malignancies.Vorinostat was the first HDACI approved by the Food and Drug Administration for patients with cutaneous T-cell lymphoma.The use of HDACIs in clinical trials,in pretreated and relapsed patients suffering from advanced pancreatic cancer is discussed.Unfortunately,clinical data for HDACIs in patients with pancreatic cancer are inadequate,because only a few studies have included patients suffering from this type of neoplasm and the number of pancreatic cancer patients that entered HDACIs phase Ⅱ/Ⅲ trials,among others with advanced solid tumors,is very limited.More studies recruiting patients with pancreatic cancer remain to determine the efficiency of these therapies. 展开更多
关键词 PANCREATIC cancer HISTONE DEACETYLASES HISTONE DEACETYLASE inhibitors Clinical trials
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Markers of bacterial translocation in end-stage liver disease 被引量:3
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作者 ioannis koutsounas Garyfallia Kaltsa +1 位作者 Spyros I Siakavellas Giorgos Bamias 《World Journal of Hepatology》 CAS 2015年第20期2264-2273,共10页
Bacterial translocation(BT) refers to the passage of viable bacteria or bacterial products from the intestinal lumen, through the intestinal epithelium, into the systemic circulation and extraintestinal locations. The... Bacterial translocation(BT) refers to the passage of viable bacteria or bacterial products from the intestinal lumen, through the intestinal epithelium, into the systemic circulation and extraintestinal locations. The three principal mechanisms that are thought to be involved in BT include bacterial overgrowth, disruption of the gut mucosal barrier and an impaired host defence.BT is commonly observed in liver cirrhosis and has been shown to play an important role in the pathogenesis of the complications of end stage liver disease, including infections as well as hepatic encephalopathy and hepatorenal syndrome. Due to the importance of BT in the natural history of cirrhosis, there is intense interest for the discovery of biomarkers of BT. To date, several such candidates have been proposed, which include bacterial DNA, soluble CD14, lipopolysaccharides endotoxin, lipopolysaccharide-binding protein, calprotectin and procalcitonin. Studies on the association of these markers with BT have demonstrated not only promising data but, oftentimes, contradictory results. As a consequence, currently, there is no optimal marker that may be used in clinical practice as a surrogate for the presence of BT. 展开更多
关键词 END stage liver disease CIRRHOSIS SOLUBLE CD14 BAC
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