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lipid hcc

Yukimasa Makita, Mika Teratani, Shumpei Murata, Yasutaka Hoashi, Satoru Matsumoto, Yuji Kawamata
It has been widely reported that patient-derived tumor xenografts (PDXs) are more similar to tumor tissues than conventional cancer cell lines. Kinetochore-associated protein 2 (KNTC2) is known to be upregulated specifically in tumor tissues of cancer patients and is recognized as a potential target for cancer therapy. Previously, in vivo antitumor activities of KNTC2 short interfering RNA encapsulated into a lipid nanoparticle (KNTC2-LNP) were reported in orthotopic hepatocellular carcinoma mouse models. However, it remains unclear whether KNTC2-LNP exhibits antitumor activities against lung cancer PDXs...
April 2018: Oncology Letters
Vladimir Alexei Morozov, Sylvie Lagaye
Hepatitis C virus (HCV) is a major cause of liver diseases including liver cirrhosis and hepatocellular carcinoma. Approximately 3% of the world population is infected with HCV. Thus, HCV infection is considered a public healthy challenge. It is worth mentioning, that the HCV prevalence is dependent on the countries with infection rates around 20% in high endemic countries. The review summarizes recent data on HCV molecular biology, the physiopathology of infection (immune-mediated liver damage, liver fibrosis and lipid metabolism), virus diagnostic and treatment...
February 27, 2018: World Journal of Hepatology
Silvano Fasolato, Elisabetta Trevellin, Mariagrazia Ruvoletto, Marnie Granzotto, Giacomo Zanus, Elisa Boscaro, Enrico Babetto, Liliana Terrin, Maria Alberta Battocchio, Francesco Ciscato, Cristian Turato, Santina Quarta, Umberto Cillo, Patrizia Pontisso, Roberto Vettor
AIMS: In hepatocellular carcinoma (HCC), the regulatory protease Dipeptidyl-peptidase IV (DPPIV/CD26), that possesses pro-apoptotic properties, has been found abnormally regulated. The protease inhibitor SerpinB3, exerting anti-apoptotic activity, has also been described to be upregulated, especially in HCCs with poor prognosis. The aim of this study was to investigate the possible relationship between these two molecules in HCC patients and in experimental models. MATERIALS AND METHODS: DPPIV/CD26 and SerpinB3 expression was measured in liver specimens of 67 patients with HCC...
March 7, 2018: Life Sciences
Nataliya Rohr-Udilova, Eva Bauer, Gerald Timelthaler, Robert Eferl, Klaus Stolze, Matthias Pinter, Martha Seif, Hubert Hayden, Thomas Reiberger, Rolf Schulte-Hermann, Markus Peck-Radosavljevic, Dagmar Stoiber, Michael Trauner
Insufficient supplementation with the micronutrient selenium and persistent hepatic inflammation predispose to hepatocellular carcinoma (HCC). Inflammation-associated reactive oxygen species attack membrane lipids and form lipid hydroperoxides able to propagate oxidative hepatic damage. Selenium-containing enzyme glutathione peroxidase 4 (GPx4) antagonizes this damage by reducing lipid hydroperoxides to respective hydroxides. However, the role of GPx4 in HCC remains elusive. We generated two human HCC cell lines with stable overexpression of GPx4, performed xenotransplantation into NOD...
February 9, 2018: Oncotarget
Xiaoping Zhao, Li Zhao, Hao Yang, Jiajin Li, Xuejie Min, Fajun Yang, Jianjun Liu, Gang Huang
Dysregulation of lipid metabolism is common in cancer cells, but the underlying mechanisms are poorly understood. Sterol regulatory element-binding proteins (SREBPs) stimulate lipid biosynthesis through transcriptional activation of lipogenic enzymes. However, SREBPs' roles and potential interacting partners in cancer cells are not fully defined. Using a biochemical approach, we found here that pyruvate kinase M2 (PKM2) physically interacts with the nuclear form of SREBP-1a (nBP1a), by binding to amino acids 43-56 in nBP1a...
March 7, 2018: Journal of Biological Chemistry
Sha Li, Hor Yue Tan, Ning Wang, Fan Cheung, Ming Hong, Yibin Feng
Liver disease, involving a wide range of liver pathologies from fatty liver, hepatitis, and fibrosis to cirrhosis and hepatocellular carcinoma, is a serious health problem worldwide. In recent years, many natural foods and herbs with abundant phytochemicals have been proposed as health supplementation for patients with hepatic disorders. As an important category of phytochemicals, natural polyphenols have attracted increasing attention as potential agents for the prevention and treatment of liver diseases. The striking capacities in remitting oxidative stress, lipid metabolism, insulin resistance, and inflammation put polyphenols in the spotlight for the therapies of liver diseases...
2018: Oxidative Medicine and Cellular Longevity
Bappa Maiti, Mohini Kamra, Anjali A Karande, Santanu Bhattacharya
Herein, five new α-tocopheryl cationic gemini lipids with hydroxyethyl bearing headgroups (THnS, n = 4, 5, 6, 8, 12) have been synthesized for efficient plasmid DNA (pDNA) delivery into cancer cells. Among these gemini lipid formulations, the lipid with an octamethylene [-(CH2 )8 ] spacer (TH8S) showed the highest transfection efficiency (TE) that was comparable to that of the commercial standard lipofectamine 2000 (L2K) in terms of luciferase expression in HepG2 (liver hepatocellular carcinoma) cells. The addition of the helper lipid DOPE (1,2-dioleoyl phosphatidyl ethanolamine) with cationic lipids in mixed liposomes further enhanced the TE and the optimized molar ratio was 2 : 1 (DOPE : cationic lipid)...
March 2, 2018: Organic & Biomolecular Chemistry
Laura Berliocchi, Carlotta Chiappini, Annagrazia Adornetto, Debora Gentile, Silvia Cerri, Rossella Russo, Giacinto Bagetta, Maria Tiziana Corasaniti
BACKGROUND: d-Limonene is a natural monoterpene abundant in Citrus essential oils. It is endowed with several biological activities, including inhibition of carcinogenesis and promotion of tumour regression. Recently, d-limonene has been shown to modulate autophagic markers in vitro at concentrations found in vivo, in clinical pharmacokinetic studies. Autophagy is an intracellular catabolic process serving as both an adaptive metabolic response and a quality control mechanism. Because autophagy defects have been linked to a wide range of human pathologies, including neurodegeneration and cancer, there is a need for new pharmacological tools to control deregulated autophagy...
February 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Srinivasan Perumal, Kulanthaivel Langeshwaran, Jayaraman Selvaraj, Rajagopal Ponnulakshmi, B Shyamaladevi, M P Balasubramanian
The aim of the present study was to evaluate the antioxidant and chemopreventive efficiency of diosmin against N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis in adult male rats. Rats were classified into four groups as follows: Group I: Control, Group II: NDEA-induced hepatocellular carcinogenic rats, Group III: Cancer-bearing animals treated with diosmin (200 mg/kg/body weight/day) orally for 28 days, Group IV: Control animals treated with diosmin (200 mg/kg/body weight/day) alone for 28 days...
February 26, 2018: Molecular and Cellular Biochemistry
Xiaoling Li, Liansheng Liu, Ran Li, Ailing Wu, Jinqiu Lu, Qingzhe Wu, Junling Jia, Mujun Zhao, Hai Song
The liver is a major organ in lipid metabolism and its malfunction leads to various diseases. Nonalcoholic fatty liver disease, the most common chronic liver disorder in developed countries is characterized by the abnormal retention of excess lipid within hepatocytes and predisposes individuals to liver cancer. We previously reported that the levels of Lissencephaly 1 (LIS1, also known as Pafah1b1) are down-regulated in human hepatocellular carcinoma. Following up on this observation, we found that genetic deletion of Lis1 in the mouse liver increases lipid accumulation and inflammation in this organ...
February 23, 2018: Journal of Biological Chemistry
Qiang Li, Qiang Zhao, Chuanzhao Zhang, Peng Zhang, Anbin Hu, Longjuan Zhang, Paul M Schroder, Yi Ma, Zhiyong Guo, Xiaofeng Zhu, Xiaoshun He
Fibroblast growth factor (FGF) has been considered to modulate liver regeneration (LR) after partial hepatectomy (PH) at the tissue level. Previous studies have demonstrated that FGF15 and FGF19 induce the activation of its receptor, FGF receptor 4 (FGFR4), which can promote hepatocellular carcinoma progression and regulate liver lipid metabolism. In this study, we aimed to explore the role of the ileal FGF15/19- hepatic FGFR4 axis in the LR after PH. Male C57BL/6 mice aged 8-12 weeks were partially hepatectomized and assessed for expression of ileal FGF15/19 to hepatic FGFR4 signaling...
February 22, 2018: Journal of Physiology and Biochemistry
Renumathy Dhanasekaran, Meital Gabay-Ryan, Virginie Baylot, Ian Lai, Adriane Mosley, Xinqiang Huang, Sonya Zabludoff, Jian Li, Vivek Kaimal, Priya Karmali, Dean W Felsher
Hepatocellular carcinoma (HCC) remains a significant clinical challenge with few therapeutic options. Genomic amplification and/or overexpression of the MYC oncogene is a common molecular event in HCC, thus making it an attractive target for drug therapy. Unfortunately, currently there are no direct drug therapies against MYC. As an alternative strategy, microRNAs regulated by MYC may be downstream targets for therapeutic blockade. MiR-17 family is a microRNA family transcriptionally regulated by MYC and it is commonly overexpressed in human HCCs...
January 19, 2018: Oncotarget
Naoto Fujiwara, Hayato Nakagawa, Kenichiro Enooku, Yotaro Kudo, Yuki Hayata, Takuma Nakatsuka, Yasuo Tanaka, Ryosuke Tateishi, Yohko Hikiba, Kento Misumi, Mariko Tanaka, Akimasa Hayashi, Junji Shibahara, Masashi Fukayama, Junichi Arita, Kiyoshi Hasegawa, Hadassa Hirschfield, Yujin Hoshida, Yoshihiro Hirata, Motoyuki Otsuka, Keisuke Tateishi, Kazuhiko Koike
OBJECTIVE: Metabolic reprogramming of tumour cells that allows for adaptation to their local environment is a hallmark of cancer. Interestingly, obesity-driven and non-alcoholic steatohepatitis (NASH)-driven hepatocellular carcinoma (HCC) mouse models commonly exhibit strong steatosis in tumour cells as seen in human steatohepatitic HCC (SH-HCC), which may reflect a characteristic metabolic alteration. DESIGN: Non-tumour and HCC tissues obtained from diethylnitrosamine-injected mice fed either a normal or a high-fat diet (HFD) were subjected to comprehensive metabolome analysis, and the significance of obesity-mediated metabolic alteration in hepatocarcinogenesis was evaluated...
February 6, 2018: Gut
Yonghai Lu, Juanjuan Chen, Chong Huang, Ning Li, Li Zou, Sin Eng Chia, Shengsen Chen, Kangkang Yu, Qingxia Ling, Qi Cheng, Mengqi Zhu, Weidong Zhang, Mingquan Chen, Choon Nam Ong
We compared hepatic and serum lipid changes in hepatocellular carcinoma (HCC) patients to have a better understanding of the molecular pathogenesis of this disease and discovery novel lipid biomarkers. Hepatic and serum lipid profiling was conducted in paired liver and serum samples from 50 HCC patients and 24 healthy controls. A total of 20 hepatic and 40 serum lipid signatures were identified, yet there was hardly any significant correlation between them. The results indicated that triglycerides and phosphatidylcholines contributed significantly to altered hepatic lipids, whereas triglycerides and phosphatidylethanolamine-based plasmalogens (PEp) contributed most to altered serum lipids...
January 12, 2018: Oncotarget
Blake R Rushing, Mustafa I Selim
Aflatoxin B1 (AFB1), a class 1 carcinogen and prominent food contaminant, is highly linked to the development of hepatocellular carcinoma (HCC) and plays a causative role in a large portion of global HCC cases. We have demonstrated that a mixture of common organic acids (citric and phosphoric acid) along with arginine can eliminate >99% of AFB1 in solution as well as on corn kernels and convert it to the AFB2a-Arg adduct, acting as a potential detoxification process for contaminated foods. Evaluation of toxicokinetic changes after AFB2a-Arg formation show that the product is highly stable in biological fluids, is not metabolized by P450 enzymes, is highly plasma protein bound, has low lipid solubility, and has poor intestinal permeability/high intestinal efflux compared to AFB1...
January 12, 2018: Oncotarget
Esther Nuñez-Durán, Mariam Aghajan, Manoj Amrutkar, Silva Sütt, Emmelie Cansby, Sheri L Booten, Andrew Watt, Marcus Ståhlman, Norbert Stefan, Hans-Ulrich Häring, Harald Staiger, Jan Borén, Hanns-Ulrich Marschall, Margit Mahlapuu
Nonalcoholic fatty liver disease (NAFLD) contributes to the pathogenesis of type 2 diabetes and cardiovascular disease, and patients with nonalcoholic steatohepatitis (NASH) are also at risk of developing cirrhosis, liver failure, and hepatocellular carcinoma. To date, no specific therapy exists for NAFLD/NASH, which has been recognized as one of the major unmet medical needs of the twenty-first century. We recently identified serine/threonine protein kinase (STK)25 as a critical regulator of energy homeostasis and NAFLD progression...
January 2018: Hepatology Communications
Fumika Shigiyama, Naoki Kumashiro, Yasuhiko Furukawa, Takashi Funayama, Kageumi Takeno, Noritaka Wakui, Takashi Ikehara, Hidenari Nagai, Hikari Taka, Tsutomu Fujimura, Hiroshi Uchino, Yoshifumi Tamura, Hirotaka Watada, Tetsuo Nemoto, Nobuyuki Shiraga, Yasukiyo Sumino, Takahisa Hirose
Nonalcoholic fatty liver disease (NAFLD) plays a crucial role in type 2 diabetes and hepatocellular carcinoma. The major underlying pathogenesis is hepatic insulin resistance. The aim of the present study was to characterize patients with NAFLD with paradoxically normal hepatic insulin sensitivity relative to patients with NAFLD with hepatic insulin resistance. We recruited 26 patients with NAFLD and divided them into three groups ranked by the level of hepatic insulin sensitivity (HIS; high-HIS, mid-HIS, low-HIS), as assessed by the hyperinsulinemic-euglycemic clamp studies using stable isotope...
September 2017: Hepatology communications
Mei Zhou, R Marc Learned, Stephen J Rossi, Alex M DePaoli, Hui Tian, Lei Ling
Nonalcoholic fatty liver disease (NAFLD) is an increasingly prevalent chronic liver disease for which no approved therapies are available. Despite intensive research, the cellular mechanisms that mediate NAFLD pathogenesis and progression are poorly understood. Although obesity, diabetes, insulin resistance, and related metabolic syndrome, all consequences of a Western diet lifestyle, are well-recognized risk factors for NAFLD development, dysregulated bile acid metabolism is emerging as a novel mechanism contributing to NAFLD pathogenesis...
December 2017: Hepatology Communications
Antonietta Stellavato, Anna Virginia Adriana Pirozzi, Francesca de Novellis, Ilaria Scognamiglio, Valentina Vassallo, Andrea Maria Giori, Mario De Rosa, Chiara Schiraldi
BACKGROUND: Steatosis is a chronic liver disease that depends on the accumulation of intracellular fatty acids. Currently, no drug treatment has been licensed for steatosis; thus, only nutritional guidelines are indicated to reduce its progression. The aim of this study is to combine different nutraceutical compounds in order to evaluate their synergistic effects on a steatosis in vitro model compared to their separate use. In particular, three different formulations based on silymarin, curcumin, vitamin E, docosahexaenoic acid (DHA), choline, and phosphatidylcholine were assayed...
February 5, 2018: Lipids in Health and Disease
Chih-Hung Chuang, Pao-Chu Wu, Teng-Huang Tsai, Yi-Ping Fang, Yi-Hung Tsai, Ta-Chun Cheng, Chien-Chaio Huang, Ming-Yii Huang, Fang-Ming Chen, Yuan-Chin Hsieh, Wen-Wei Lin, Ming-Jun Tsai, Tian-Lu Cheng
Solid lipid nanoparticles (SLNs) are suitable candidates for the delivery of various anti-cancer drugs. However, currently insufficient tumor-permeability and non-specific uptake by the reticuloendothelial system limits the application of SLNs. Here, we developed novel pH-sensitive cationic polyoxyethylene (PEGylated) SLNs (PEG-SLNs+) that could accumulate long-term at various tumor sites to enhance the therapeutic efficiency of camptothecin (CPT). These CPT-loaded PEG-SLNs+ (CPT-PEG-SLNs+) were spherical nanoparticles, with small size (∼52...
February 2017: Journal of Biomedical Nanotechnology
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