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hcc pathophysiology

Jennie Ka Ching Lau, Xiang Zhang, Jun Yu
Non-alcoholic fatty liver disease (NAFLD) is a continuous spectrum of diseases characterized by excessive lipid accumulation in hepatocytes. NAFLD progresses from simple liver steatosis to non-alcoholic steatohepatitis (NASH) and in more severe cases to liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Due to its growing worldwide prevalence, various animal models that mirror both the histopathology and pathophysiology of each stage of human NAFLD have been developed. The selection of appropriate animal models continues to be one of the key questions faced in this field...
October 18, 2016: Journal of Pathology
Carrie R Wong, Mindie H Nguyen, Joseph K Lim
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States and represents an increasingly important etiology of hepatocellular carcinoma (HCC) with annual cumulative incidence rates ranging from 2% to 12% in cohorts of NAFLD cirrhosis. While the risk of progression of NAFLD to HCC remains higher among patients with fibrosis or cirrhosis, an increasing amount of literature describes NAFLD-HCC as a disease that can occur in the absence of cirrhosis. Efforts to characterize the pathogenesis of NAFLD-HCC have suggested mechanisms that strongly associate with states of hyperinsulinemia and chronic inflammation, cellular mechanisms including adaptive immune responses and hepatic progenitor cell populations, and genetic polymorphisms including mutations of PNPLA3...
October 7, 2016: World Journal of Gastroenterology: WJG
Mamatha Bhat, Bianca M Arendt, Venkat Bhat, Eberhard L Renner, Atul Humar, Johane P Allard
The intestinal microbiome (IM) is altered in patients with cirrhosis, and emerging literature suggests that this impacts on the development of complications. The PubMed database was searched from January 2000 to May 2015 for studies and review articles on the composition, pathophysiologic effects and therapeutic modulation of the IM in cirrhosis. The following combination of relevant text words and MeSH terms were used, namely intestinal microbiome, microbiota, or dysbiosis, and cirrhosis, encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome, variceal bleeding, hepatopulmonary syndrome, portopulmonary hypertension and hepatocellular carcinoma...
September 28, 2016: World Journal of Hepatology
Marta Spodzieja, Katarzyna Kalejta, Aleksandra S Kołodziejczyk, Martyna Maszota-Zieleniak, Sylwia Rodziewicz-Motowidło, Wioletta Żmudzińska, Paulina Czaplewska
Cystatin C originally identified as a cysteine proteases inhibitor has a broad spectrum of biological roles ranging from inhibition of extracellular cysteine protease activities, bone resorption, and modulation of inflammatory responses to stimulation of fibroblasts proliferation. There is an increasing number of evidence to suggest that human cystatin C (hCC) might play a protective role in the pathophysiology of sporadic Alzheimer's disease. In vivo and in vitro results well documented the association of hCC with Aβ and the hCC-induced inhibition of Aβ fibril formation...
October 7, 2016: Journal of Molecular Recognition: JMR
Xiaorui Liu, Jingjing Li, Zujiang Yu, Juan Li, Ranran Sun, Quancheng Kan
Hepatocellular carcinoma (HCC) is the most common cancer in the world. MicroRNAs (miRNAs) are a type of small noncoding RNA that can regulate the expression of target genes under physiological and pathophysiological conditions. Aberrant expression of MicroRNA-935 (MiR-935) has been reported in cancer studies. However, its expression and mechanism in hepatocellular carcinoma remain unclear. In our study, we found that miR-935 was upregulated in liver cancer tissues and cells. Overexpression of miR-935 in liver cells promoted cell proliferation, tumorigenesis, and cell cycle progression, whereas inhibition of miR-935 reduced cell proliferation, tumorigenicity, and cell cycle progression...
September 30, 2016: Oncology Research
Elizabeth Hernández-Pérez, Plácido Enrique León García, Norma Edith López-Díazguerrero, Fernando Rivera-Cabrera, Elizabeth Del Ángel Benítez
Non-alcoholic fatty liver disease refers to a disease spectrum that ranges from steatosis to non-alcoholic steatohepatitis, which leads to fibrosis, cirrhosis and hepatocellular carcinoma. Given the increasing prevalence of obesity worldwide, the incidence of non-alcoholic fatty liver disease has become a world health problem. Non-alcoholic fatty liver disease is considered to be the hepatic manifestation of metabolic syndrome associated with insulin resistance, central obesity, and type 2 diabetes mellitus...
September 13, 2016: Medwave
Shi-Yan Yan, Jian-Gao Fan, Liang Qiao
Liver cancer is a common disease and the third leading cause of cancer-related deaths worldwide [1]. Hepatocellular carcinoma (HCC) is the most deadly form of liver cancer. Chronic hepatitis and subsequent liver fibrosis and cirrhosis are the major causes of HCC [2]. Chronic hepatitis B (CHB) is one of the most common infections worldwide. It is estimated that two billion people have been infected with hepatitis B virus (HBV), and up to 400,000 people worldwide are believed to have chronic HBV infection [3]...
September 26, 2016: Current Cancer Drug Targets
Arijit Mondal, Tanmoy Guria, Tapan Kumar Maity, Anupam Bishayee
Amaranthus spinosus Linn. (Family: Amaranthaceae) has been shown to be useful in preventing and mitigating adverse pathophysiological conditions and complex diseases. However, only limited information is available on the anticancer potential of this plant. In this study, we examined the antiproliferative and pro-apoptotic effects of a novel fatty acid isolated from A. spinosus-(14E,18E,22E,26E)-methyl nonacosa-14,18,22,26 tetraenoate-against HepG2 human liver cancer cells. We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to determine cell viability, flow cytometry assay for cell cycle analysis, and Western blot analysis to measure protein expression of Cdc2), cyclin B1, Bcl-2-associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2)...
2016: International Journal of Molecular Sciences
Nghiem Xuan Hoan, Nguyen Khuyen, Mai Thanh Binh, Dao Phuong Giang, Hoang Van Tong, Phan Quoc Hoan, Ngo Tat Trung, Do Tuan Anh, Nguyen Linh Toan, Christian G Meyer, Peter G Kremsner, Thirumalaisamy P Velavan, Le Huu Song
BACKGROUND: As an immune modulator, vitamin D is involved in various pathophysiological mechanisms in a plethora of diseases. This study aims to correlate the vitamin D deficiency status and clinical progression of liver diseases associated with hepatitis B virus (HBV) infection in patients in Vietnam and to compare it to healthy controls. METHODS: We quantified the levels of total vitamin D [25-(OH) D2 and D3] in serum samples from 400 HBV patients (chronic hepatitis B infection [CHB], n = 165; HBV-associated liver cirrhosis [LC], n = 127; HBV-associated hepatocellular carcinoma [HCC], n = 108) and 122 unrelated healthy controls (HC)...
2016: BMC Infectious Diseases
Alexandra M Hetherington, Cynthia G Sawyez, Emma Zilberman, Alexandra M Stoianov, Debra L Robson, Nica M Borradaile
BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) progression to fibrosis, cirrhosis and hepatocellular carcinoma, alters the cellular composition of this organ. During late-stage NAFLD, fibrotic and possibly cancerous cells can proliferate and, like normal hepatocytes, are exposed to high concentrations of fatty acids from both surrounding tissue and circulating lipid sources. We hypothesized that primary human activated hepatic stellate cells and epithelial hepatoma (HepG2) cells respond differently to lipotoxic conditions, and investigated the mechanisms involved...
2016: Cellular Physiology and Biochemistry
Shinya Imada, Tsuyoshi Kobayashi, Azusa Kitao, Osamu Matsui, Masakazu Hashimoto, Kentaro Ide, Kohei Ishiyama, Koji Arihiro, Hirotaka Tashiro, Hideki Ohdan
BACKGROUND: Indocyanine green (ICG) excretory defect is a dye excretory disorder, and it is characterized by the selective impairment of plasma ICG clearance with normal liver histology. The pathophysiology involves selective loss of active transporters for ICG in the hepatic cell membrane. Several cases of hepatectomy in patients with ICG excretory defect have been reported, but the expression of hepatic transporters involved in ICG excretory defect has not been examined in these cases...
December 2016: Surgical Case Reports
Xiao-Ting Zhu, Ji-Hang Yuan, Teng-Teng Zhu, Yang-Yang Li, Xiao-Yang Cheng
Long noncoding RNAs (lncRNAs) have critical roles in various pathophysiological processes, and are frequently dysregulated in many diseases, particular in cancer. LncRNA GPC3 antisense transcript 1 (GPC3-AS1) has been reported to be a potential biomarker for hepatocellular carcinoma (HCC) screening. However, the exact biological functions of GPC3-AS1 in HCC, and its roles and regulation mechanisms on GPC3 are still unknown. In this study, we observed significant upregulation of GPC3-AS1 in HCC. Increased expression of GPC3-AS1 is associated with α-fetoprotein, tumour size, microvascular invasion, encapsulation, BCLC stage, and worse prognosis of HCC patients...
August 30, 2016: FEBS Journal
Yankai Wen, Seogsong Jeong, Qiang Xia, Xiaoni Kong
Osteopontin (OPN), a multifunctional protein, is involved in numerous pathological conditions including inflammation, immunity, angiogenesis, fibrogenesis and carcinogenesis in various tissues. Extensive studies have elucidated the critical role of OPN in cell signaling such as regulation of cell proliferation, migration, inflammation, fibrosis and tumor progression. In the liver, OPN interacts with integrins, CD44, vimentin and MyD88 signaling, thereby induces infiltration, migration, invasion and metastasis of cells...
2016: International Journal of Biological Sciences
Nidhi Jariwala, Devanand Sarkar
Hepatocellular carcinoma (HCC) accounts for the second largest number of cancer related deaths globally with limited management options for the advanced disease. Although substantial research has identified molecular targets, with strong validation in pre-clinical in vivo studies, translation of therapeutics to clinics has shown modest success. In a recent manuscript in Hepatology, Zhou and Yang et al. unravel a novel p53 associated long non-coding RNA (PRAL) as a potential prognostic marker and molecular target in HCC...
August 2016: Annals of Translational Medicine
Jill S Gluskin, Fabrizio Chegai, Serena Monti, Ettore Squillaci, Lorenzo Mannelli
Differentiating between cancerous tissue and healthy liver parenchyma could represent a challenge with the only conventional Magnetic Resonance (MR) imaging. Diffusion weighted imaging (DWI) exploits different tissue characteristics to conventional Magnetic Resonance Imaging (MRI) sequences that enhance hepatocellular carcinoma (HCC) detection, characterization, and post-treatment evaluation. Detection of HCC is improved by DWI, infact this technology increases conspicuity of lesions that might otherwise not be identified due to obscuration by adjacent vessels or due to low contrast between the lesion and background liver...
2016: Journal of Cancer
M Ilamathi, P C Prabu, K Ashok Ayyappa, V Sivaramakrishnan
Activation of the IL-6 mediated JAK-STAT (Janus associated kinase-signal transducer and activator of transcription) oncogenic signalling plays a major role in hepatocellular carcinoma pathogenesis. The aim of this study is to assess the anti-tumour, anti-proliferative and apoptotic potential of artesunate and its capacity to modulate JAK-STAT pathway in a nitrosodiethylamine mediated experimental hepatocellular carcinoma model. Administration of nitrosodiethylamine (200mg/kg body weight by i.p. Injections) to rats resulted in alterations of liver pathophysiological parameters such as increased relative liver weight, and increased tumour nodule occurrence...
August 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Bo Chen, Yan Liang, Zheng He, Yunhe An, Weihong Zhao, Jianqing Wu
Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin superfamily, which has been implicated in the pathophysiology of the nervous system. Recently, several studies have suggested that BDNF and/or its receptor, tropomyosin related kinase B (TrkB), are involved in tumor growth and metastasis in several cancers, including prostate cancer, neuroblastoma, pancreatic ductal carcinoma, hepatocellular carcinoma, and lung cancer. Despite the increasing emphasis on BDNF/TrkB signaling in human tumors, how it participates in primary tumors has not yet been determined...
2016: Scientific Reports
Wenbo Meng, Bing Bai, Zhongtian Bai, Yan Li, Ping Yue, Xun Li, Liang Qiao
Human hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. Alpha-fetoprotein (AFP) is perhaps the best-defined tumor marker for HCC, and as such, it is widely used in clinical settings as an adjuvant diagnostic and prognostic tool. Up to 70% of HCC cases exhibit elevated serum level of AFP, but its pathophysiological functions in HCC are poorly defined. It is now known that AFP is not just a fetal form of carrier protein and a tumor marker, it is also critically involved in the regulation of several important cellular functions, such as cell growth, differentiation, apoptosis, angiogenesis, and immune regulation...
June 2016: Discovery Medicine
Koji Taniguchi, Shinichiro Yamachika, Feng He, Michael Karin
p62/SQSTM1 is a multifunctional signaling hub and autophagy adaptor with many binding partners, which allow it to activate mTORC1-dependent nutrient sensing, NF-κB-mediated inflammatory responses, and the NRF2-activated antioxidant defense. p62 recognizes polyubiquitin chains via its C-terminal domain and binds to LC3 via its LIR motif, thereby promoting the autophagic degradation of ubiquitinated cargos. p62 accumulates in many human liver diseases, including nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC), where it is a component of Mallory-Denk bodies and intracellular hyaline bodies...
August 2016: FEBS Letters
Winston Dunn, Vijay H Shah
Alcoholic liver disease includes a broad clinical-histological spectrum from simple steatosis, cirrhosis, acute alcoholic hepatitis with or without cirrhosis to hepatocellular carcinoma as a complication of cirrhosis. The pathogenesis of alcoholic liver disease can be conceptually divided into (1) ethanol-mediated liver injury, (2) inflammatory immune response to injury, (3) intestinal permeability and microbiome changes. Corticosteroids may improve outcomes, but this is controversial and probably only impacts short-term survival...
August 2016: Clinics in Liver Disease
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