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Hepatocellular carcinoma mtor

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https://www.readbyqxmd.com/read/29331106/kbtbd2-inhibits-the-cytotoxic-activity-of-immortalized-nk-cells-through-down-regulating-mtor-signaling-in-a-mouse-hepatocellular-carcinoma-model
#1
Kai Dai, Yabing Huang, Zubing Chen, Xiaomei Sun, Lihua Yang, Yingan Jiang
Natural killer cell (NK cell)-based immunotherapy is a promising therapeutic strategy for hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying the regulation of NK cell function in the tumor sites are not completely elucidated. In this study, we identified the enhanced expression of kelch repeat and BTB (POZ) domain containing 2 (Kbtbd2) in intratumoral NK cells in a mouse HCC implantation model as a negative regulator of NK cells. To investigate this interaction,, we used a Tet-on inducible expression system to control Kbtbd2 expression in an immortalized mouse NK cell line KIL C...
January 13, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29328424/vitexin-induces-g2-m%C3%A2-phase-arrest-and-apoptosis-via-akt-mtor-signaling-pathway-in-human-glioblastoma-cells
#2
Guangning Zhang, Dongyuan Li, Hao Chen, Junchen Zhang, Xingyi Jin
Glioblastoma is a common primary brain tumor with aggressive malignancy, which results in poor outcomes, short survival time and high mortality. Vitexin, an active ingredient from natural products, has been reported to inhibit cell growth and induce cell apoptosis in various cancer cell lines including hepatocellular carcinoma, oral and esophageal cancer. To the best of the authors knowledge, the present study was the first to investigate anticancer effects of vitexin on human glioblastoma cells and potential underlying mechanisms...
January 8, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29312601/inhibition-of-hepatocellular-carcinoma-growth-by-blockade-of-glycosphingolipid-synthesis
#3
Richard Jennemann, Giuseppina Federico, Daniel Mathow, Mariona Rabionet, Francesca Rampoldi, Zoran V Popovic, Martina Volz, Thomas Hielscher, Roger Sandhoff, Hermann-Josef Gröne
Hepatocellular carcinoma (HCC) is one of the most frequent cancers. In vitro studies suggest that growth and response to therapy of human carcinomas may depend on glycosphingolipid (GSL) expression. Glucosylceramide synthase (GCS), encoded by the gene Ugcg, is the basic enzyme required for the synthesis of GSLs. Gene array analysis implied that Ugcg is significantly overexpressed in human HCC as compared to non-tumorous liver tissue. Therefore we have investigated whether tumor - genesis and - growth is altered in the absence of GSLs...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29305580/the-epigenetically-regulated-mir-494-associates-with-stem-cell-phenotype-and-induces-sorafenib-resistance-in-hepatocellular-carcinoma
#4
Daniela Pollutri, Clarissa Patrizi, Sara Marinelli, Catia Giovannini, Elena Trombetta, Ferdinando A Giannone, Maurizio Baldassarre, Santina Quarta, Y P Vandewynckel, A Vandierendonck, H Van Vlierberghe, Laura Porretti, Massimo Negrini, Luigi Bolondi, Laura Gramantieri, Francesca Fornari
Hepatocellular carcinoma (HCC) represents the second cause of cancer-related mortality worldwide and is associated with poor prognosis, especially in patients not amenable for curative treatments. The multi-kinase inhibitor sorafenib represents the first-line treatment option for advanced HCC; nevertheless, its effectiveness is limited due to tumor heterogeneity as well as innate or acquired drug resistance, raising the need for new therapeutic strategies. MicroRNAs (miRNAs) involvement in treatment response as well as their safety and efficacy in preclinical models and clinical trials have been widely documented in the oncologic field, including HCC...
January 5, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29303510/loss-of-pten-synergizes-with-c-met-to-promote-hepatocellular-carcinoma-development-via-mtorc2-pathway
#5
Zhong Xu, Junjie Hu, Hui Cao, Maria G Pilo, Antonio Cigliano, Zixuan Shao, Meng Xu, Silvia Ribback, Frank Dombrowski, Diego F Calvisi, Xin Chen
Hepatocellular carcinoma (HCC) is a deadly malignancy with limited treatment options. Activation of the AKT/mTOR cascade is one of the most frequent events along hepatocarcinogenesis. mTOR is a serine/threonine kinase and presents in two distinct complexes: mTORC1 and mTORC2. While mTORC1 has been extensively studied in HCC, the functional contribution of mTORC2 during hepatocarcinogenesis has not been well characterized, especially in vivo. Pten expression is one of the major mechanisms leading to the aberrant activation of the AKT/mTOR signaling...
January 5, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29299170/c21-steroid-enriched-fraction-refined-from-marsdenia-tenacissima-inhibits-hepatocellular-carcinoma-through-the-coordination-of-hippo-yap-and-pten-pi3k-akt-signaling-pathways
#6
Yu Zhang, Kaiqiang Li, Youmin Ying, Bingyu Chen, Ke Hao, Boxu Chen, Yu Zheng, Jianxin Lyu, Xiangming Tong, Xiaopan Chen, Ying Wang, Zhajun Zhan, Wei Zhang, Zhen Wang
Marsdenia tenacissimae extraction (MTE), a traditional herbal medicine, has exhibited anti-tumor effects on a variety of cancers. However, its effectiveness and the mechanism of action in Hepatocellular carcinoma (HCC) has not been fully understood. In the present study, we demonstrate that C21 steroid-enriched fraction from MTE, which contains five main C21 steroids (FR5) exhibits obvious pharmacological activities on HCC cells in vitro and in vivo. FR5 induces apoptosis and inhibits proliferation and migration of HepG2 and Bel7402 cells in a dose and time dependent manner...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29251327/survival-pathway-of-cholangiocarcinoma-via-akt-mtor-signaling-to-escape-raf-mek-erk-pathway-inhibition-by-sorafenib
#7
Kenta Yokoi, Akira Kobayashi, Hiroaki Motoyama, Masato Kitazawa, Akira Shimizu, Tsuyoshi Notake, Takahide Yokoyama, Tomio Matsumura, Michiko Takeoka, Shin-Ichi Miyagawa
Cholangiocarcinoma (CCC) is a strongly aggressive malignancy for which surgical resection is the only potential curative therapy. Sorafenib, a multikinase inhibitor of the RAF/MEK/ERK pathway, is a molecular-targeted drug that is approved for hepatocellular carcinoma (HCC) but not for CCC. The differences in signaling pathway characteristics under sorafenib treatment between HCC (HLF, Huh7, PLC/PRF/5) and CCC (RBE, YSCCC, Huh28) cell lines were therefore investigated using cell proliferation, western blotting, and apoptosis analyses...
February 2018: Oncology Reports
https://www.readbyqxmd.com/read/29249451/mir-199-3p-replacement-affects-e-cadherin-expression-through-notch1-targeting-in-hepatocellular-carcinoma
#8
Catia Giovannini, Francesca Fornari, Rossella Dallo, Martina Gagliardi, Elisa Nipoti, Francesco Vasuri, Camelia Alexandra Coadă, Matteo Ravaioli, Luigi Bolondi, Laura Gramantieri
Hepatocellular carcinoma (HCC) represents the second cause of cancer-related mortality worldwide and is associated with poor prognosis, due to a high recurrence rate after curative treatments and a drug resistance phenotype. In this scenario, the identification of innovative and effective therapeutic strategies is an unmet clinical need. The safety and efficacy of microRNA (miRNA) mediated approaches in preclinical models and clinical trials have been widely described in cancer. MicroRNA-199a downregulation is a common feature of HCC where its reduced expression contributes to mTOR and c-Met pathways activation...
December 14, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/29246230/bifunctional-enzyme-atic-promotes-propagation-of-hepatocellular-carcinoma-by-regulating-ampk-mtor-s6%C3%A2-k1-signaling
#9
Minjing Li, Changzhu Jin, Maolei Xu, Ling Zhou, Defang Li, Yancun Yin
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the cancer types with poor prognosis. To effectively treat HCC, new molecular targets and therapeutic approaches must be identified. 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate (IMP) cyclohydrolase (ATIC), a bifunctional protein enzyme, catalyzes the last two steps of the de novo purine biosynthetic pathway. Whether ATIC contributes to cancer development remains unclear. METHODS: ATIC mRNA levels in different types of human HCC samples or normal tissues were determined from Gene Expression across Normal and Tumor tissue (GENT) database...
December 16, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29232555/mtorc2-promotes-tumorigenesis-via-lipid-synthesis
#10
Yakir Guri, Marco Colombi, Eva Dazert, Sravanth K Hindupur, Jason Roszik, Suzette Moes, Paul Jenoe, Markus H Heim, Isabelle Riezman, Howard Riezman, Michael N Hall
Dysregulated mammalian target of rapamycin (mTOR) promotes cancer, but underlying mechanisms are poorly understood. We describe an mTOR-driven mouse model that displays hepatosteatosis progressing to hepatocellular carcinoma (HCC). Longitudinal proteomic, lipidomics, and metabolomic analyses revealed that hepatic mTORC2 promotes de novo fatty acid and lipid synthesis, leading to steatosis and tumor development. In particular, mTORC2 stimulated sphingolipid (glucosylceramide) and glycerophospholipid (cardiolipin) synthesis...
December 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29221196/identification-of-cellular-genes-and-pathways-important-for-tumorigenicity-of-hepatocellular-carcinoma-cell-lines-by-proteomic-profiling
#11
Ali Zamani, Huahao Fan, Guangxiang Luo
Hepatocellular carcinoma (HCC) is the most commonly diagnosed malignancy of the liver. A more thorough understanding of HCC pathogenesis will provide novel targets for development of cancer drugs to effectively treat HCC. To further this goal, we carried out a proteomic profiling of HCC cell lines Huh-7.4 and Huh-7.5. These two cell lines were derived from subgenomic HCV RNA-replicating Huh-7 cells upon clearance of HCV RNA by antiviral drug treatment. Initially, the tumorigenicity of each cell line was determined and compared in parallel in the same immunedeficient mice...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29220539/significance-and-mechanism-of-androgen-receptor-ar-overexpression-and-ar-mtor-crosstalk-in-hepatocellular-carcinoma
#12
Hong Zhang, Xiaoxing Li, Yang Yang, Yanjie Zhang, Hui-Yun Wang, X F Steven Zheng
Hepatocellular carcinoma (HCC) is a male-dominant cancer and androgen receptor (AR) has been linked to the pathogenesis of HCC. However, AR expression and its precise role in HCC remain controversial. Moreover, previous anti-androgen and -AR clinical trials in HCC failed to demonstrate clinical benefits. In this study, we found that AR is overexpressed in the nucleus of approximately 37% HCC tumors, which is significantly associated with advanced disease stage and poor survival. AR overexpression in HCC cells markedly alters AR-dependent transcriptome, stimulates oncogenic growth and determines therapeutic response to enzalutamide, a second generation of AR antagonist...
December 8, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29190940/elevation-of-map17-enhances-the-malignant-behavior-of-cells-via-the-akt-mtor-pathway-in-hepatocellular-carcinoma
#13
Xinhuang Chen, Yan Liao, Yaqun Yu, Pengpeng Zhu, Jun Li, Liling Qin, Weijia Liao, Zhaoquan Huang
MAP17, a small non-glycosylated membrane protein, was significantly up-regulated in hepatocellular carcinoma (HCC) tissues in our previous genome-wide microarray analysis. In this study, quantitative real-time RT-PCR and immunohistochemistry were applied to examine MAP17 mRNA and protein expression in primary HCC and matched peritumoral tissues. The disease-free survival (DFS) and overall survival (OS) was estimated using the Kaplan-Meier analysis. The expression of MAP17 was significantly higher in HCC tissues compared to the paired peritumoral tissues at both mRNA and protein levels...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29187559/reprograming-of-glucose-metabolism-by-zerumbone-suppresses-hepatocarcinogenesis
#14
Nissar Wani, Bo Zhang, Kun-Yu Teng, Juan Barajas, Tasneem Motiwala, Peng Hu, Lianbo Yu, Rafael Brüschweiler, Kalpana Ghoshal, Samson T Jacob
Hepatocellular carcinoma (HCC) is the most prevalent and a highly aggressive liver malignancy with limited therapeutic options. Here, the therapeutic potential of zerumbone, a sesquiterpene derived from the ginger plant Zingiber zerumbet, against HCC was explored. Zerumbone inhibited proliferation and clonogenic survival of HCC cells in a dose-dependent manner by arresting cell at the G2/M phase, and inducing apoptosis. To elucidate the underlying molecular mechanism, a phosphokinase array was performed that showed significant inhibition of the PI3K/AKT/mTOR and STAT3 signaling pathways in zerumbone treated HCC cells...
November 29, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29179453/microrna-deregulation-in-nonalcoholic-steatohepatitis-associated-liver-carcinogenesis
#15
Aline de Conti, Juliana Festa Ortega, Volodymyr Tryndyak, Kostiantyn Dreval, Fernando Salvador Moreno, Ivan Rusyn, Frederick A Beland, Igor P Pogribny
Hepatocellular carcinoma (HCC) is the fastest-rising cause of cancer-related death in the United States. Recent epidemiological studies have identified nonalcoholic steatohepatitis (NASH), a progressive form of nonalcoholic fatty liver disease (NAFLD), as a major risk factor for HCC. Elucidating the underlying mechanisms associated with the development of NASH-derived HCC is critical for identifying early biomarkers for the progression of the disease and for treatment and prevention. In the present study, using liver samples from C57BL/6J mice submitted to the Stelic Animal Model (STAM) of NASH-associated liver carcinogenesis, we investigated the role of microRNA (miRNA) alterations in the pathogenesis of NASH-derived HCC...
October 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/29167516/nanoparticle-core-stability-and-surface-functionalization-drive-the-mtor-signaling-pathway-in-hepatocellular-cell-lines
#16
Mariia Lunova, Andrey Prokhorov, Milan Jirsa, Martin Hof, Agnieszka Olżyńska, Piotr Jurkiewicz, Šárka Kubinová, Oleg Lunov, Alexandr Dejneka
Specifically designed and functionalized nanoparticles hold great promise for biomedical applications. Yet, the applicability of nanoparticles is critically predetermined by their surface functionalization and biodegradability. Here we demonstrate that amino-functionalized polystyrene nanoparticles (PS-NH2), but not amino- or hydroxyl-functionalized silica particles, trigger cell death in hepatocellular carcinoma Huh7 cells. Importantly, biodegradability of nanoparticles plays a crucial role in regulation of essential cellular processes...
November 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29156790/kaempferol-induces-autophagic-cell-death-of-hepatocellular-carcinoma-cells-via-activating-ampk-signaling
#17
Bing Han, Yi-Qun Yu, Qi-Lian Yang, Chun-Ying Shen, Xiao-Juan Wang
In the present study, we demonstrate that Kaempferol inhibited survival and proliferation of established human hepatocellular carcinoma (HCC) cell lines (HepG2, Huh-7, BEL7402, and SMMC) and primary human HCC cells. Kaempferol treatment in HCC cells induced profound AMP-activated protein kinase (AMPK) activation, which led to Ulk1 phosphorylation, mTOR complex 1 inhibition and cell autophagy. Autophagy induction was reflected by Beclin-1/autophagy gene 5 upregulation and p62 degradation as well as light chain 3B (LC3B)-I to LC3B-II conversion and LC3B puncta formation...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29133128/bca3-contributes-to-the-malignant-progression-of-hepatocellular-carcinoma-through-akt-activation-and-nf-%C3%AE%C2%BAb-translocation
#18
Dong Ma, Mengquan Li, Jing Su, Shuijun Zhang
Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide with elusive molecular mechanisms. The aim of this study is to investigate the clinical significance and biological roles of breast cancer-associated protein 3 (BCA3) in HCC. Our investigation demonstrated that BCA3 expression was up-regulated in primary HCC tissues, and BCA3 levels were positively correlated with tumor size, TNM stage, microvascular invasion and poor prognosis. BCA3 promoted tumor growth, metastasis and angiogenesis of HCC in vitro and in vivo...
November 10, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29112301/ribavirin-augments-doxorubicin-s-efficacy-in-human-hepatocellular-carcinoma-through-inhibiting-doxorubicin-induced-eif4e-activation
#19
Jun Tan, Jingfen Ye, Meijun Song, Mi Zhou, Yaoren Hu
Activation of eukaryotic translation initiation factor 4E (eIF4E) is a cellular survival mechanism in response to chemotherapy in cancers. In this work, we demonstrate that targeting eIF4E by ribavirin sensitizes hepatocellular carcinoma (HCC) cell response to doxorubicin. Ribavirin inhibits growth and survival of HCC cells, and to a greater extent than in normal liver cells. Its combination with doxorubicin achieves greater efficacy than single drug in vitro and in vivo. Ribavirin suppresses phosphorylation of molecules involved in Akt/mTOR/eIF4E pathway...
November 7, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/29108133/targeted-delivery-of-mir-199a-3p-using-self-assembled-dipeptide-nanoparticles-efficiently-reduces-hepatocellular-carcinoma
#20
Aditi Varshney, Jiban J Panda, Avishek K Singh, Nitin Yadav, Chhagan Bihari, Subhrajit Biswas, Shiv K Sarin, Virander S Chauhan
Hepatocellular carcinoma (HCC) is an aggressive tumor with limited systemic and locoregional modalities of treatment. Although microRNA (miRNA) based therapies have significant potential, their targeted delivery remains a major challenge. miR-199a-3p functions as an important tumor suppressor in HCC, which regulates various cellular processes. Recently, peptide-based nanoparticles (NPs) have been developed to deliver oligonucleotides including miRNA. Here, we describe the synthesis and characterization of arginine α,β-dehydrophenylalanine (RΔF) nanoparticles for the selective delivery of miR-199a-3p to restore dysregulated gene expression in HCC...
November 6, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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