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Hepatocellular carcinoma mtor

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https://www.readbyqxmd.com/read/28794477/up-regulation-of-brca1-associated-ring-domain-1-promotes-hepatocellular-carcinoma-progression-by-targeting-akt-signaling
#1
Yan Liao, Shengguang Yuan, Xinhuang Chen, Pengpeng Zhu, Jun Li, Liling Qin, Weijia Liao
The present study was designed to investigate the potential clinical, pathological, prognostic value, role and mechanism of BRCA1-associated RING Domain 1 (BARD1) in Hepatocellular carcinoma (HCC). Quantitative real-time PCR and immunohistochemistry were performed to evaluate the expression of BARD1 mRNA and protein. The expression of BARD1 in the HCC tissue samples was markedly higher than that in the adjacent noncancerous liver tissues. Elevated BARD1 expression was positively correlated with tumor-node-metastasis stage, Barcelona-Clinic Liver Cancer stage, hepatitis B surface antigen, large tumor size, serum alpha-fetoprotein levels, and serum aspartate aminotransferase levels...
August 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28766170/aegle-marmelos-differentially-affects-hepatic-markers-of-glycolysis-insulin-signalling-pathway-hypoxia-and-inflammation-in-hepg2-cells-grown-in-fructose-versus-glucose-rich-environment
#2
H Aggarwal, J Nair, P Sharma, R Sehgal, U Naeem, P Rajora, R Mathur
Fructose consumption is responsible for the onset of insulin resistance (IR), and metabolic syndrome. It possesses no functional utility in body and its detrimental effects on hepatic metabolic milieu are beyond those produced by glucose. The need of the hour is to identify fructose-induced IR as an unique pathological state to be managed differentially. The effect of aqueous leaf extract of Aegle marmelos (AM) on hepatic markers of insulin resistance using HepG2 cells cultured in either fructose or glucose-rich environment is investigated...
August 1, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28743539/recommendations-of-everolimus-use-in-liver-transplant
#3
Angel Rubín Suárez, Itxarone Bilbao Aguirre, Javier Fernández-Castroagudin, José Antonio Pons Miñano, Magdalena Salcedo Plaza, Evaristo Varo Pérez, Martín Prieto Castillo
Mammalian target of rapamycin (mTOR) inhibitors, everolimus (EVL) and sirolimus are immunosuppressive agents with a minor nephrotoxic effect, limited to the development of proteinuria in some cases. The combination of EVL and low-dose tacrolimus has proven to be as safe and effective as standard therapy with tacrolimus for the prevention of acute cellular rejection. Early initiation of EVL-based immunosuppressive regimens with reduced exposure to calcineurin inhibitors has been shown to significantly improve renal function of LT recipients during induction and maintenance phases, with comparable efficacy and safety profiles...
July 22, 2017: Gastroenterología y Hepatología
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
#4
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/28731193/promotion-of-glycolysis-by-hotair-through-glut1-upregulation-via-mtor-signaling
#5
Shibo Wei, Qing Fan, Liang Yang, Xiaodong Zhang, Yingbo Ma, Zhihong Zong, Xiangdong Hua, Dongming Su, Hongzhi Sun, Hangyu Li, Zhen Liu
The long non-coding RNA HOX transcript antisense RNA (HOTAIR) plays a key role in the progression of various carcinomas. However, whether or not HOTAIR influences glucose metabolism and the specific underlying mechanism in hepatocellular carcinoma (HCC) cells remain unclear. In the present study, we found markedly increased HOTAIR expression in 84 HCC tissues and demonstrated that HOTAIR overexpression promoted cell proliferation using Cell Counting Kit-8. The effect on glucose metabolism regulated by HOTAIR in HCC cells was determined by detecting lactate and glucose levels: HOTAIR promoted glycolysis by upregulating glucose transporter isoform 1 (GLUT1) and activating mammalian target of rapamycin (mTOR) signaling, whereas knockdown of HOTAIR suppressed this effect...
July 20, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28715695/new-liver-cancer-biomarkers-pi3k-akt-mtor-pathway-members-and-eukaryotic-translation-initiation-factors
#6
Nicole Golob-Schwarzl, Stefanie Krassnig, Anna M Toeglhofer, Young Nyun Park, Margit Gogg-Kamerer, Klemens Vierlinger, Fabian Schröder, Hyungjn Rhee, Rudolf Schicho, Peter Fickert, Johannes Haybaeck
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. The initiation of protein translation is an important rate-limiting step in eukaryotes and is crucial in many viral infections. Eukaryotic translation initiation factors (eIFs) are involved in the initiation step of protein translation and are linked to the phosphatidylinositol-3-kinases PI3K/AKT/mTOR pathway. Therefore we aimed to investigate a potential role of eIFs in HCC. We herein report on the immunohistochemical expression of the various eIF subunits in 235 cases of virus-related human HCC...
July 14, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28676953/regulation-of-sirt1-ampk-axis-is-critically-involved-in-gallotannin-induced-senescence-and-impaired-autophagy-leading-to-cell-death-in-hepatocellular-carcinoma-cells
#7
Hee Young Kwon, Ju-Ha Kim, Bonglee Kim, Sanjay K Srivastava, Sung-Hoon Kim
Hepatocellular carcinoma (HCC) is one of the most fatal malignancies with high mortality worldwide. Here the underlying antitumor mechanism of gallotannin was elucidated in HCC cells. Gallotannin suppressed viability and colony formation, increased subG1 portion and also induced senescence via upregulation of p21, G0/G1 arrest and higher SA-β-gal activity in HepG2 and SK-Hep1 cells. However, pan-caspase inhibitor Z-VAD-FMK reversed the ability of gallotannin to activate caspase 3 at 48 h after treatment in two HCC cells...
July 4, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28675698/the-mtor-inhibition-in-concurrence-with-erk1-2-activation-is-involved-in-excessive-autophagy-induced-by-glycyrrhizin-in-hepatocellular-carcinoma
#8
Xuan Zhang, Hua Yang, Shuqiang Yue, Guangbin He, Shibin Qu, Zhuochao Zhang, Ben Ma, Rui Ding, Wei Peng, Hongtao Zhang, Zhaoxu Yang, Kefeng Dou, Kaishan Tao, Xiao Li
Autophagy is a life phenomenon in which autophagosomes remove damaged or aging organelles and long-lived circulating proteins to maintain the cell's stability. However, disorders of excessive autophagy are a response of cancer cells to a variety of anticancer treatments which lead to cancer cell death. The Akt/mammalian target of rapamycin (mTOR) and the extracellular signal-regulated kinase 1/2 (ERK1/2) pathways are both involved in nutrient-induced autophagic phenomenon and exhibit vital relevance to oncogenesis in various cancer cell types, including hepatocellular carcinoma (HCC)...
August 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28668827/a-novel-mtor-inhibitor-anthracimycin-for-the-treatment-of-human-hepatocellular-carcinoma
#9
Tomoyuki Hayashi, Taro Yamashita, Hikari Okada, Naoki Oishi, Hajime Sunagozaka, Kouki Nio, Takehiro Hayashi, Yasumasa Hara, Yoshiro Asahina, Mariko Yoshida, Tomomi Hashiba, Tsuyoshi Suda, Takayoshi Shirasaki, Yasuhiro Igarashi, Koji Miyanouchi, Tatsuya Yamashita, Masao Honda, Shuichi Kaneko
BACKGROUND/AIM: Anthracimycin, a secondary metabolite of Streptomyces, has been shown to inhibit the invasion of certain cancer cell lines. MATERIALS AND METHODS: In this study we evaluated the effect of anthracimycin on cell growth and signaling pathways in hepatocellular carcinoma (HCC). RESULTS: Anthracimycin suppressed cell proliferation and motility and induced apoptosis in human HCC cell lines. Furthermore, anthracimycin had no effect on the enrichment of EpCAM-high liver cancer stem cells (CSCs), while fluorouracil dramatically enriched the CSCs with activation of the stemness-related genes EPCAM and SOX9 in HuH7 cells...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28659990/antihepatocarcinoma-effect-of-portulaca-oleracea-l-in-mice-by-pi3k-akt-mtor-and-nrf2-ho-1-nf-%C3%AE%C2%BAb-pathway
#10
Zheng Guoyin, Peng Hao, Li Min, Gu Wei, Chen Zhe, Ling Changquan
The purpose of the present study was to evaluate the pharmacological effects of Portulaca oleracea L. (Purslane) (PL) on N-nitrosodiethylamine- (NDEA-) induced hepatocellular carcinomas (HCC) and explore its potential mechanism. Mice were randomly assigned to four groups: control group, NDEA group, NDEA + Purslane (100 mg/kg) group, and NDEA + Purslane (200 mg/kg) group. The animal of each group was given NDEA (100 ppm) in drinking water. 1 h later, Purslane dissolved in PBS was intragastrically administered for continuous seven days...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28638267/synergistic-antitumor-effect-of-sorafenib-in-combination-with-atm-inhibitor-in-hepatocellular-carcinoma-cells
#11
Jianhua Liu, Yahui Liu, Lingyu Meng, Bai Ji, Daqing Yang
Background: Currently, sorafenib is the only systemic chemotherapy drug for advanced stage Hepatocellular carcinoma (HCC). However, emerging data from some clinical HCC patients indicate that sorafenib alone has only moderate antitumor efficacy, and could not inhibit disease metastasis and progression. KU-55933 is a specific ATM inhibitor, which has pro-apoptotic effect on tumor cells. In this study, we analyzed the synergistic effect of sorafenib and KU-55933 on the proliferation of HCC cell lines. Methods: Three HCC cell lines were treated with sorafenib and KU-55933 alone or combination in vitro to investigate inhibitory effect by MTT and wound healing assay...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28631359/management-of-pediatric-hepatocellular-carcinoma-a-multimodal-approach
#12
Mira A Kohorst, Deepti M Warad, Jane M Matsumoto, Julie K Heimbach, Mounif El-Youssef, Carola A S Arndt, Vilmarie Rodriguez, Amulya A Nageswara Rao
HCC is rare in the pediatric population, but is the second most common liver malignancy in children. Survival rates for primary unresectable HCC have been dismal. The objective of this study was to describe our experience with a multimodal approach for the management of unresectable HCC in two adolescent patients and to review the literature. Both patients are currently alive with no recurrence at 51 and 29 months post-transplant. Multimodality treatment involving chemotherapy with doxorubicin, cisplatin, and sorafenib; TACE; timely liver transplantation; and post-transplant therapy with sorafenib and mTOR inhibitors may help improve outcomes and prolong survival in pediatric patients with unresectable HCC...
June 20, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28624790/co-targeting-of-igf1r-mtor-pathway-by-mir-497-and-mir-99a-impairs-hepatocellular-carcinoma-development
#13
Henghui Cheng, Jin Xue, Shouhua Yang, Yaobin Chen, Yu Wang, Yuanli Zhu, Xiaoyan Wang, Dong Kuang, Qiurong Ruan, Yaqi Duan, Guoping Wang
Persistent activation of IGF1R/mTOR signaling pathway plays crucial role in the development of hepatocellular carcinoma (HCC). Therefore, our goal was to elucidate microRNAs (miRNAs) targeting IGF1R/mTOR and the therapeutic potential of single or dual miRNA on HCC development. In this study, we found that miR-497 and miR-99a that target the 3'-UTR of both IGF1R and mTOR were down-regulated in HCC human tissues and cell lines. Functional assay revealed that ectopic expression of miR-497 or miR-99a in HCC cells resulted in a significant inhibition on tumor growth and invasiveness in vitro and tumor development in vivo via repressing the expression of IGF1R and mTOR...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28604762/tip30-regulates-lipid-metabolism-in-hepatocellular-carcinoma-by-regulating-srebp1-through-the-akt-mtor-signaling-pathway
#14
F Yin, G Sharen, F Yuan, Y Peng, R Chen, X Zhou, H Wei, B Li, W Jing, J Zhao
Lipid reprogramming has been considered as a crucial characteristic in hepatocellular carcinoma (HCC) initiation and progression. However, detailed molecular mechanisms have yet to be clearly defined. Here, we examined the effects of tumor suppressor TIP30 on the regulation of HCC lipid metabolism. We found that decreased TIP30 expression leads to elevated fatty acid synthesis and enhanced levels of lipogenic enzymes SCD and FASN in HCC cells. Moreover, SREBP1 is one of the key transcription factors regulating liver lipid metabolism, and TIP30 deficiency significantly increased SREBP1 expression and nuclear accumulation...
June 12, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28600122/oxidative-stress-plays-a-key-role-in-butyrate-mediated-autophagy-via-akt-mtor-pathway-in-hepatoma-cells
#15
Kishor Pant, Anoop Saraya, Senthil K Venugopal
Hepatocellular Carcinoma (HCC) is one of the most aggressive forms of cancer, responsible for a number of deaths in humans. Butyrate, one of the short chain fatty acids produced by the gut microbiota during anaerobic fermentation, was shown to be beneficial for inhibiting cancer growth. In this study, we showed that sodium butyrate induced autophagy via reactive oxygen species (ROS) in hepatoma cells. Butyrate (0-6 mM) incubation significantly increased intracellular ROS levels (45.2% compared to control), which in turn inhibited phosphorylation of akt and mTOR, leading to the upregulation of autophagic proteins, such as beclin 1, ATG 5, LC3-II, followed by the increased autophagosome formation (34...
June 11, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28594907/gastrointestinal-cancer-cells-treatment-with-bevacizumab-activates-a-vegf-autoregulatory-mechanism-involving-telomerase-catalytic-subunit-htert-via-pi3k-akt-hif-1%C3%AE-and-vegf-receptors
#16
Nadine Mahfouz, Roula Tahtouh, Nada Alaaeddine, Joelle El Hajj, Riad Sarkis, Ray Hachem, Issam Raad, George Hilal
BACKGROUND: Targeting angiogenesis has been considered a promising treatment of choice for a large number of malignancies, including gastrointestinal cancers. Bevacizumab is an anti-vascular endothelial growth factor (anti-VEGF) being used for this purpose. However, treatment efficacy is largely questioned. Telomerase activity, responsible for cancer cell immortality, is detected in 85-95% of human cancers and is considered a potential regulator of VEGF. The aim of our study was to investigate the interrelationship between VEGF and hTERT in gastrointestinal cancers and to explore cell response to a combined inhibition of telomerase and VEGF...
2017: PloS One
https://www.readbyqxmd.com/read/28593618/rig-i-a-multifunctional-protein-beyond-a-pattern-recognition-receptor
#17
REVIEW
Xiao-Xiao Xu, Han Wan, Li Nie, Tong Shao, Li-Xin Xiang, Jian-Zhong Shao
It was widely known that retinoic acid inducible gene I (RIG-I) functions as a cytosolic pattern recognition receptor that initiates innate antiviral immunity by detecting exogenous viral RNAs. However, recent studies showed that RIG-I participates in other various cellular activities by sensing endogenous RNAs under different circumstances. For example, RIG-I facilitates the therapy resistance and expansion of breast cancer cells and promotes T cell-independent B cell activation through interferon signaling activation by recognizing non-coding RNAs and endogenous retroviruses in certain situations...
June 8, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28586051/overexpression-of-microrna-133b-is-associated-with-the-increased-survival-of-patients-with-hepatocellular-carcinoma-after-curative-hepatectomy-involvement-of-the-egfr-pi3k-akt-mtor-signaling-pathway
#18
Xuedong Wang, Jianping Zeng, Liang Wang, Xinjing Zhang, Zhiqian Liu, Hongyi Zhang, Jiahong Dong
The aim of the present study was carried out to investigate the association of microRNA-133b (miRNA-133b) expression with the prognosis of patients with hepatocellular carcinoma (HCC) after curative hepatectomy. In the present study, the expression of miRNA-133b in HCC tissues was determined to be lower than that noted in the adjacent normal tissues. Overall and disease-free survival of the HCC patients with high miRNA-133b expression was observably extended, compared with the HCC patients with low miRNA‑133b expression...
June 6, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28560380/sorafenib-induces-variations-of-the-dna-methylome-in-ha22t-vgh-human-hepatocellular-carcinoma-derived-cells
#19
Edoardo Abeni, Alessandro Salvi, Eleonora Marchina, Michele Traversa, Bruna Arici, Giuseppina De Petro
Sorafenib is currently used to treat advanced and/or unresectable hepatocellular carcinoma (HCC), but the increase of the median survival was only 3 months. Moreover, sorafenib has severe side effects and patients develop resistance quickly. Epigenetic alterations such as DNA methylation play a decisive role in the development and progression of HCC. To our knowledge, there are no studies that analysed the global DNA methylation changes in HCC cells treated with sorafenib. Using MeDip-chip technologies, we found 1230 differentially methylated genes in HA22T/VGH cells treated with sorafenib compared to untreated cells...
July 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28549345/a-novel-synthetic-derivative-of-quercetin-8-trifluoromethyl-3-5-7-3-4-o-pentamethyl-quercetin-inhibits-bladder-cancer-growth-by-targeting-the-ampk-mtor-signaling-pathway
#20
Ting Tao, Caimei He, Jun Deng, Yanjun Huang, Qiongli Su, Mei Peng, Meiling Yi, Kwame Oteng Darko, Hui Zou, Xiaoping Yang
Quercetin is a naturally existing compound and shows attractive anticancer properties for a variety of solid tumors including glioma, bladder cancer, hepatocellular carcinoma, breast cancer, hematological malignancies and prostate carcinoma. However, these anticancer properties have not been clinically approved due to unclear mechanistic information and its low bioactivity. In our previous study, we elucidated that quercetin activates AMPK pathway which is the major mechanism for its unique anticancer effect in bladder cancer...
May 11, 2017: Oncotarget
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