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https://www.readbyqxmd.com/read/28732118/pd-1-checkpoint-blockade-in-combination-with-an-mtor-inhibitor-restrains-hepatocellular-carcinoma-growth-induced-by-hepatoma-cell-intrinsic-pd-1
#1
Hui Li, Xiaoqiang Li, Shuang Liu, Lei Guo, Bo Zhang, Jubo Zhang, Qinghai Ye
Inhibitors of PD-1 administered as single agents have resulted in durable tumor regression in advanced cancer patients. However, only a minority of cancer patients respond to anti PD-1 immunotherapy. Here, we show that PD-1 expression in hepatocellular carcinoma (HCC) promotes tumor growth independently of adaptive immunity. Knockdown of PD-1 suppress tumor growth, whereas PD-1 overexpression enhances tumorigenesis in immunodeficient xenografted mice. Mechanistically, PD-1 binds the downstream mTOR effectors eukaryotic initiation factor 4E (eIF4E) and ribosomal protein S6 (S6), thus promoting their phosphorylation...
July 21, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28726775/oroxylin-a-activates-pkm1-hnf4-alpha-to-induce-hepatoma-differentiation-and-block-cancer-progression
#2
Libin Wei, Yuanyuan Dai, Yuxin Zhou, Zihao He, Jingyue Yao, Li Zhao, Qinglong Guo, Lin Yang
Liver cancer is the second cause of death from cancer worldwide, without effective treatment. Traditional chemotherapy for liver cancer has big side effects for patients, whereas targeted drugs, such as sorafenib, commonly have drug resistance. Oroxylin A (OA) is the main bioactive flavonoids of Scutellariae radix, which has strong anti-hepatoma effect but low toxicity to normal tissue. To date, no differentiation-inducing agents have been reported to exert a curative effect on solid tumors. Here our results demonstrated that OA restrained the proliferation and induced differentiation of hepatoma both in vitro and in vivo, via inducing a high PKM1 (pyruvate kinase M1)/PKM2 (pyruvate kinase M2) ratio...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28723638/se2mo10v3-a-heteropoly-compound-containing-selenium-inhibits-tumor-growth
#3
Hong-Ning Zhang, Wei-Li Feng, Chun-Na An, Wen-Guang Li
Selenium compounds have strong anti-tumor effects and are well-tolerated. We examined the anti-tumor effects of (NH4)2H15Se2VIMo10V3O52·2H2O (Se2Mo10V3), a heteropoly compound containing selenium. Se2Mo10V3 inhibited proliferation in K562 cells with a half-maximal inhibitory concentration of 78.72±2.82 mg/L after 48 h and 24.94±0.88 mg/L after 72 h. Typical apoptotic morphologies were also observed in K562 cells treated with Se2Mo10V3, as were increased intracellular levels of Ca2+, Mg2+, H+, and reactive oxygen species, and decreased mitochondrial membrane potential...
July 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722813/knockdown-of-long-non-coding-rna-malat1-inhibits-growth-and-motility-of-human-hepatoma-cells-via-modulation-of-mir-195
#4
Dingli Liu, Yun Zhu, Jinke Pang, Xie Weng, Xiaorong Feng, Yabing Guo
The metastasis-associated lung adenocarcinoma transcription 1 (Malat1) is a long non-coding RNA (lncRNA), exerts oncogenic role in multiple cancers, including hepatocellular carcinoma (HCC). This study was aimed to investigate its posttranscriptional regulation in HCC cells. RT-PCR was performed to monitor the expression levels of Malat1 in normal liver and HCC cell lines. The expression of Malat1, microRNA (miR)-195 and epidermal growth factor receptor (EGFR) in HepG2 and MHCC97 cells was respectively or synchronously altered by transfection...
July 19, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28721844/cd81-large-extracellular-loop-containing-fusion-proteins-with-a-dominant-negative-effect-on-hcv-cell-spread-and-replication
#5
Boyan Grigorov, Jennifer Molle, Eric Rubinstein, Fabien Zoulim, Birke Bartosch
The roles of CD81 in the hepatitis C virus (HCV) life cycle are multiple but remain ill characterized. CD81 is known to interact with the HCV glycoproteins as an attachment factor. It also has an important role in the post-attachment entry process. Its interaction with claudin-1, for example, is vital for viral uptake and trafficking. Furthermore, CD81 and its role in membrane organization and trafficking are thought to play a pivotal role in HCV replication. Some of these functions are particularly limited to human CD81; others can be substituted with CD81 molecules from other species...
July 18, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28721743/responses-of-human-hepatoma-hepg2-cells-to-silver-nanoparticles-and-polycyclic-aromatic-hydrocarbons
#6
Francisco Filipak Neto, Ludiana Cardoso da Silva, Samuel Liebel, Carmen Lúcia Voigt, Ciro Alberto de Oliveira Ribeiro
The nanotechnology has revolutionized the global market with silver nanoparticles (AgNP) occupying a prominent position due to their remarkable anti-bacterial properties. However, there is no data about the adverse and toxic effects of associations of AgNP and ubiquitous compounds, such as polycyclic aromatic hydrocarbons (PAH). In the current study, we investigated the responses of HepG2 cells to realistic concentrations of AgNP (0.09, 0.9 and 9 ng ml(-1)) and mixture of PAH (30 and 300 ng ml(-1)), separately and in association...
July 19, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28720813/a-new-prenylated-flavonoid-induces-g0-g1-arrest-and-apoptosis-through-p38-jnk-mapk-pathways-in-human-hepatocellular-carcinoma-cells
#7
Di Wang, Qian Sun, Jie Wu, Wei Wang, Guodong Yao, Tianyang Li, Xue Li, Lingzhi Li, Yan Zhang, Wei Cui, Shaojiang Song
Prenylated flavonoids have been demonstrated to possess diverse bioactivities including antitumor effects. One new, daphnegiravone D (1), and four known (2-5) prenylated flavonoids were isolated from Daphne giraldii. Their cytotoxic activities revealed that daphnegiravone D markedly inhibited the proliferation of cancer cells, but had no apparent cytotoxicity on human normal cells. Mechanistically, daphnegiravone D induced G0/G1 arrest and apoptosis, reduced the expression of cyclin E1, CDK2 and CDK4, and promoted the cleavage of caspase 3 and PARP in Hep3B and HepG2 cells...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28717196/trib1-is-a-positive-regulator-of-hepatocyte-nuclear-factor-4-alpha
#8
Sébastien Soubeyrand, Amy Martinuk, Ruth McPherson
The TRIB1 locus has been linked to both cardiovascular disease and hepatic steatosis. Recent efforts have revealed TRIB1 to be a major regulator of liver function, largely, but not exclusively, via CEBPA degradation. We recently uncovered a functional interaction between TRIB1 and HNF4A, another key regulator of hepatic function, whose molecular underpinnings remained to be clarified. Here we have extended these findings. In hepatoma models, HNF4A levels were found to depend on TRIB1, independently of its impact on CEBPA...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28717041/activation-of-sting-in-hepatocytes-suppresses-the-replication-of-hepatitis-b-virus
#9
Fang Guo, Liudi Tang, Sainan Shu, Mohit Sehgal, Muhammad Sheraz, Bowei Liu, Qiong Zhao, Junjun Cheng, Xuesen Zhao, Tianlun Zhou, Jinhong Chang, Ju-Tao Guo
Induction of interferon and proinflammatory cytokines is a hallmark of the infection of many different viruses. However, hepatitis B virus (HBV) does not elicit a detectable cytokine response in infected hepatocytes. In order to investigate the molecular mechanism underlying the innate immune evasion, a functional cGAS-STING pathway was reconstituted in a human hepatoma cell line supporting tetracycline-inducible HBV replication. It was demonstrated that induction of HBV replication neither activated nor inhibited this cytosolic DNA sensing pathway...
July 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28713954/microrna%C3%A2-139-suppressed-tumor-cell-proliferation-migration-and-invasion-by-directly-targeting-hdgf-in-epithelial-ovarian-cancer
#10
Junli Liu, Shuangling Jin, Rui Wang
The current study investigated the expression and functional roles of microRNA‑139 (miR‑139) on human epithelial ovarian cancer (EOC). Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was performed to measure miR‑139 expression in EOC tissues and cell lines. The effects of miR‑139 on EOC cell proliferation, migration and invasion were assessed using MTT, cell migration and invasion assays, respectively. Subsequently, the molecular mechanism underlying the tumor suppressive roles of miR‑139 on EOC was determined by bioinformatics analysis, RT‑qPCR, western blotting and the luciferase reporter assay...
July 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713155/hypoxia-induces-universal-but-differential-drug-resistance-and-impairs-anticancer-mechanisms-of-5-fluorouracil-in-hepatoma-cells
#11
Jing-Qiu Li, Xian Wu, Lu Gan, Xiang-Liang Yang, Ze-Hong Miao
Hepatocellular carcinoma (HCC) is one of the most refractory cancers. The mechanisms by which hypoxia further aggravates therapeutic responses of advanced HCC to anticancer drugs remain to be clarified. Here, we report that hypoxia (1% O2) caused 2.55-489.7-fold resistance to 6 anticancer drugs (sorafenib, 5-fluorouracil [5-FU], gemcitabine, cisplatin, adriamycin and 6-thioguanine) in 3 HCC cell lines (BEL-7402, HepG2 and SMMC-7721). Among the 6 drugs, sorafenib, the sole one approved for HCC therapy, inhibited proliferation with little influence from hypoxia and displayed the smallest variation among the 3 HCC cell lines tested...
July 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28712391/-hepatic-stellate-cells-inhibit-the-proliferation-and-invasion-of-hepg2-hepatocellular-carcinoma-via-activating-%C3%AE-%C3%AE-t-cells
#12
Kai Fan, Rui Liao, Yuxiao Xie, Cong Peng, Chengyou Du
Objective To investigate the effects of γδ T cells co-cultured with human hepatic stellate cells (HSCs) on the proliferation and invasion of hepatocellular carcinoma (HCC) cells. Methods Peripheral γδ T cells of healthy volunteers and HCC patients were separated and collected by density gradient centrifugation and flow cytometry. Transwell(TM) chambers were used to co-culture LX-2 cells and γδ T cells. The concentration of IFN-γ in γδ T cell supernatant was detected by ELISA. The proliferation of HepG2 cells was analyzed by CCK-8 assay, and the invasion ability of HepG2 cells was evaluated by Transwell(TM) chamber assay...
July 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28708602/development-of-hepatoma-derived-bidirectional-oval-like-cells-as-a-model-to-study-host-interactions-with-hepatitis-c-virus-during-differentiation
#13
Masahiko Ito, Suofeng Sun, Takasuke Fukuhara, Ryosuke Suzuki, Miho Tamai, Toyohiko Yamauchi, Kenji Nakashima, Yoh-Ichi Tagawa, Shigetoshi Okazaki, Yoshiharu Matsuura, Takaji Wakita, Tetsuro Suzuki
Directed differentiation of human stem cells including induced pluripotent stem cells into hepatic cells potentially leads to acquired susceptibility to hepatitis C virus (HCV) infection. However, cellular determinants that change their expression during cell reprogramming or hepatic differentiation and are pivotal for supporting the HCV life cycle remain unclear. In this study, by introducing a set of reprogramming factors, we established HuH-7-derived oval-like cell lines, Hdo-17 and -23, which possess features of bipotential liver precursors...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28708106/evodiamine-exerts-an-anti-hepatocellular-carcinoma-activity-through-a-wwox-dependent-pathway
#14
Che-Yuan Hu, Hung-Tsung Wu, Yu-Chu Su, Ching-Han Lin, Chih-Jen Chang, Chao-Liang Wu
Evodiamine is one of the main components isolated from Evodia rutaecarpa, and it has been reported to exert inhibitory effects on cancers by anti-proliferative and apoptosis-inducing activities. Although the anti-cancer activity of evodiamine has been identified, the precise mechanisms of this action remain obscure. While previous studies indicated that evodiamine exerts anti-tumor effects through inhibiting β-catenin activity, and WW domain-containing oxidoreductase (WWOX) regulates β-catenin accumulation in cytoplasm, the effects of evodiamine on the expression of WWOX are still unknown...
July 14, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28707223/inhibition-of-exendin-4-induced-steatosis-by-protein-kinase-a-in-cultured-hepg2-human-hepatoma-cells
#15
Alice Y Chen-Liaw, Gabrielle Hammel, George Gomez
Nonalcoholic fatty liver is characterized by the abnormal accumulation of triglycerides within hepatocytes, resulting in a steatotic liver. Glucagon-like peptide 1 and its analog exendin-4 can ameliorate certain aspects of this syndrome by inducing weight loss and reducing hepatic triglyceride accumulation, but it is unclear whether these effects result from the effects of glucagon-like peptide 1 on the pancreas, or from direct action on the liver. This study investigated the direct action and putative cellular mechanism of exendin-4 on steatotic hepatocytes in culture...
July 13, 2017: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/28698067/glycyrrhetinic-acid-modified-tpgs-polymeric-micelles-for-hepatocellular-carcinoma-targeted-therapy
#16
Xiumei Zhu, Altansukh Tsend-Ayush, Zhongyue Yuan, Jing Wen, Jiaxin Cai, Shifu Luo, Jianxu Yao, Junxing Bian, Linfang Yin, Jianping Zhou, Jing Yao
In this study, glycyrrhetinic acid (GA)-modified D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) polymeric micelles (TGA PMs) were developed for the delivery of etoposide (ETO) to hepatoma cells. GA was incorporated as a ligand because of its high affinity to the hepatocytes, while TPGS functioned as a P-gp inhibitor to reverse multidrug resistance. ETO-loaded TGA PMs (ETO-TGA PMs) displayed a mean particle size of 133.6±1.2nm with a low poly-dispersity index (0.224±0.013) and negative zeta potential (-16...
July 8, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28696570/effects-of-combined-lysosomal-and-mitochondrial-photodamage-in-a-non-small-cell-lung-cancer-cell-line-the-role-of-paraptosis
#17
David Kessel, John J Reiners
We previously reported that a low-level of lysosomal photodamage potentiated the phototoxic effect of subsequent mitochondrial photodamage mediated by the benzoporphyrin derivative BPD in murine hepatoma 1c1c7 cells. This was attributed to release of Ca(2+) from damaged lysosomes and a calpain-mediated conversion of the autophagy-related protein ATG5 to a pro-apoptotic fragment. We now report a comparison of these results with those obtained with the human non small-cell lung cancer A549 cell line. A549 cells contained lower levels of ATG5 and were less responsive than 1c1c7 cultures to the PDT combination...
July 11, 2017: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/28694689/synthesis-and-cytotoxic-activities-of-novel-4-methoxy-substituted-and-5-methyl-substituted-3-s-4-s-cis-khellactone-derivatives-that-induce-apoptosis-via-the-intrinsic-pathway
#18
Jingrun Chen, Junjie Liu, Dongxiao Cui, Chaoqun Yan, Liqiang Meng, Liqian Sun, Shurong Ban, Rui Ge, Taigang Liang, Qingshan Li
This study deals with the design and synthesis of a series of novel 4-methoxy-substituted and 5-methyl-substituted (3'S,4'S)-(-)-cis-khellactones. The newly synthesized compounds were characterized by (1)H nuclear magnetic resonance (NMR), (13)C-NMR, mass spectrometry, and elemental analysis. All the derivatives were subjected to in vitro cytotoxicity screening against HEPG-2 (human liver carcinoma), SGC-7901 (human gastric carcinoma), and LS174T (human colon carcinoma), by using the MTT assay. The results revealed that several of the 4-methoxy-substituted compounds exhibited potent cytotoxicity...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28694219/hepatic-abca1-deficiency-is-associated-with-delayed-apolipoprotein-b-secretory-trafficking-and-augmented-vldl-triglyceride-secretion
#19
Mingxia Liu, Soonkyu Chung, Gregory S Shelness, John S Parks
ATP binding cassette transporter A1 (ABCA1) is a membrane transporter that facilitates nascent HDL formation. Tangier disease subjects with complete ABCA1 deficiency have <5% of normal levels of plasma HDL, elevated triglycerides (TGs), and defective vesicular trafficking in fibroblasts and macrophages. Hepatocyte-specific ABCA1 knockout mice (HSKO) have a similar lipid phenotype with 20% of normal plasma HDL levels and a two-fold elevation of plasma TGs due to hepatic overproduction of large, triglyceride-enriched VLDL...
July 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28693232/microrna-195-inhibits-the-behavior-of-cervical-cancer-tumors-by-directly-targeting-hdgf
#20
Rongrong Song, Lin Cong, Guantai Ni, Min Chen, Honmei Sun, Yunxia Sun, Meiling Chen
MicroRNAs (miRNAs/miRs) are a class of conserved non-coding endogenous small regulatory RNAs that regulate target gene expression by binding to the 3'-untranslated region of target mRNAs in a base-pairing manner, resulting in repression of transcription or degradation of target mRNAs. It has been demonstrated previously that the abnormal expression of miRNAs is involved in the carcinogenesis and progression of cervical cancer. The aim of the present study was to investigate the expression, biological functions and underlying molecular mechanisms of miR-195 in cervical cancer...
July 2017: Oncology Letters
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