Abstract:
:BACKGROUND Although 5-Flourouracil(5-FU) is used as the first-choice treatment for advanced hepatocellular carcinoma (HCC), it is associated with acquired and intrinsic resistance. Hyperactivation of mTOR signaling has been linked to tumorigenesis and chemoresistance in HCC. The aim of this study was to evaluate and compare the antitumor effects of mTORC1 inhibitor everolimus and mTORC1/2 inhibitor AZD8055 and to examine the interaction between 5-FU and mTORC1/2 inhibitor in HCC. MATERIAL AND METHODS Using cultured HCC cells and mouse xenograft, the antitumor effects of everolimus and AZD8055 were analyzed as mono- and combination therapy with 5-Flourouracil. RESULTS TSC2-deficient HCC cell lines were more sensitive to everolimus and AZD8055. AZD8055, but not everolimus, potently prevented cells from transitioning from G1 phase to S phase in TSC2-high-expressing HCC cells. AZD8055 reduced phosphorylation of both mTORC1 and mTORC2 substrates. In contrast, everolimus reduced the phosphorylation of mTORC1 substrates, but increased the phosphorylation of AKT. Notably, AZD8055, but not everolimus, synergistically enhanced the efficacy of 5-FU via reversing 5-FU-induced upregulation of P-glycoprotein (P-gp). The synergistic antitumor effect of AZD8055 and 5-FU was also observed in a HCC xenograft mouse model. CONCLUSIONS TSC2 in HCC is a promising efficacy-predicting biomarker for the treatment of mTORC1/2 inhibitor. AZD8055 showed stronger antitumor activity than everolimus in TSC2-high-expressing HCC cells. Moreover, the combination of mTORC1/2 inhibitor with 5-FU appears to be a promising option for HCC patients refractory to chemotherapy.
journal_name
Med Sci Monitjournal_title
Medical science monitor : international medical journal of experimental and clinical researchauthors
Zhang Y,Jia QA,Kadel D,Zhang XF,Zhang QBdoi
10.12659/MSM.907514subject
Has Abstractpub_date
2018-05-03 00:00:00pages
2735-2743eissn
1234-1010issn
1643-3750pii
907514journal_volume
24pub_type
杂志文章abstract:BACKGROUND:Current biological investigations tend to operate with genomes, instead of genes as during the last century. It is possible to compare entire genomes, transcriptomes or proteomes, using alphanumeric data corresponding to the differential expression levels of thousands of genes. What remains difficult is to l...
journal_title:Medical science monitor : international medical journal of experimental and clinical research
pub_type: 杂志文章
doi:
更新日期:2003-08-01 00:00:00
abstract::BACKGROUND This study aimed to identify hub genes and pathways in a rat model of renal ischemia-reperfusion injury (IRI) using bioinformatics analysis of the Gene Expression Omnibus (GEO) microarray dataset and integration of gene expression profiles. MATERIAL AND METHODS GEO software and the GEO2R calculation method ...
journal_title:Medical science monitor : international medical journal of experimental and clinical research
pub_type: 杂志文章
doi:10.12659/MSM.920364
更新日期:2019-11-08 00:00:00
abstract:BACKGROUND:Success in treating hepatitis B virus (HBV) infection with nucleoside analogues drugs is limited by the emergence of drug-resistant viral strains upon prolonged therapy. In addition to mutation patterns in the viral polymerase gene, host factors are assumed to contribute to failure of treatment in chronic HB...
journal_title:Medical science monitor : international medical journal of experimental and clinical research
pub_type: 杂志文章
doi:10.12659/MSM.889788
更新日期:2014-02-26 00:00:00
abstract::DNA repair is an important defense mechanism against DNA damage and includes four distinct pathways: direct, excision, mismatch, and double-strand break repair systems. Recent evidence suggests that alterations in proteins participating in the DNA repair systems may result in cellular senescence, cell death, and neopl...
journal_title:Medical science monitor : international medical journal of experimental and clinical research
pub_type: 杂志文章,评审
doi:
更新日期:2008-01-01 00:00:00
abstract::BACKGROUND Post-traumatic syringomyelia (PTS) is a common disease after spinal cord injury (SCI). The present study was performed to evaluate the advantages of diffusion tensor imaging (DTI) in estimating SCI and prognosing PTS in SCI rats. MATERIAL AND METHODS Forty rats were divided into 3 groups based on the extent...
journal_title:Medical science monitor : international medical journal of experimental and clinical research
pub_type: 杂志文章
doi:10.12659/msm.907955
更新日期:2018-01-09 00:00:00
abstract:BACKGROUND:Studies have assessed the association between Interleukin-10 (IL-10) -1082A/G polymorphism and diabetic nephropathy (DN) risk, but the results were inconclusive and contradictory. Therefore, we performed a meta-analysis to investigate the association between IL10-1082A/G polymorphism and DN risk. MATERIAL A...
journal_title:Medical science monitor : international medical journal of experimental and clinical research
pub_type: 杂志文章,meta分析
doi:10.12659/MSM.892972
更新日期:2015-03-25 00:00:00
abstract:BACKGROUND:Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system with possible involvement of vascular dysregulation secondary to endothelial dysfunction caused by destruction of the vessel wall. Vascular dysregulation leads to excessive vasoconstriction or insufficient vasodilatat...
journal_title:Medical science monitor : international medical journal of experimental and clinical research
pub_type: 杂志文章
doi:10.12659/MSM.890899
更新日期:2015-04-13 00:00:00
abstract::BACKGROUND Piperine has been reported to inhibit proliferation and induce apoptosis in various cancer cells. This study aimed to explore the efficacy and underlying mechanism of piperine in human gastric cancer. MATERIAL AND METHODS MTT assay was performed to examine the effect of piperine (concentrations of 0-300 μM)...
journal_title:Medical science monitor : international medical journal of experimental and clinical research
pub_type: 杂志文章
doi:10.12659/MSM.928403
更新日期:2020-12-31 00:00:00
abstract:BACKGROUND:Concomitant incisional and parastomal hernias is a challenging condition. We used a hybrid technique of sublay and onlay to treat patients with this condition. MATERIAL AND METHODS:The clinical data of 32 consecutive patients treated from February 2008 to April 2014 for concomitant incisional and parastomal...
journal_title:Medical science monitor : international medical journal of experimental and clinical research
pub_type: 杂志文章
doi:10.12659/MSM.893838
更新日期:2015-07-17 00:00:00
abstract:BACKGROUND:The causal relation of high sensitivity C-reactive protein (hsCRP) to ischemic cerebrovascular disease remains unclear, though an inflammatory effect has been suggested in many studies. The aim of our study was to evaluate serum hsCRP levels in ischemic stroke patients and in a control group, and to correlat...
journal_title:Medical science monitor : international medical journal of experimental and clinical research
pub_type: 杂志文章
doi:
更新日期:2005-11-01 00:00:00
abstract::BACKGROUND Septin9 is a member of GTP-binding protein family, and is used as a predictive diagnostic index. However, it has not been widely adopted due to inconsistent results reported in the literature. The present study was performed to determine the diagnostic accuracy of methylated Septin9 (mSEPT9) for colorectal ...
journal_title:Medical science monitor : international medical journal of experimental and clinical research
pub_type: 杂志文章
doi:10.12659/msm.900590
更新日期:2016-09-25 00:00:00
abstract:BACKGROUND:Considering the high prevalence of dementia, it would be of great value to develop effective tools to improve cognitive function. We examined the effects of a human-type communication robot on cognitive function in elderly women living alone. MATERIAL/METHODS:In this study, 34 healthy elderly female volunte...
journal_title:Medical science monitor : international medical journal of experimental and clinical research
pub_type: 杂志文章,随机对照试验
doi:10.12659/msm.883350
更新日期:2012-09-01 00:00:00
abstract::BACKGROUND The aim of this study was to evaluate the association of maternal serum 25-hydroxyvitamin D, paraoxonase 1, and neutrophil-to-lymphocyte ratio in women having early spontaneous preterm birth without clinical chorioamnionitis. MATERIAL AND METHODS This study was prospectively administered in women referred t...
journal_title:Medical science monitor : international medical journal of experimental and clinical research
pub_type: 杂志文章
doi:10.12659/msm.897983
更新日期:2016-04-13 00:00:00
abstract::BACKGROUND The aim of this study was to study the effects of 1-alpha,25-dihydroxy-cholecalcifero (1,25(OH)2D3) on liver fibrosis and the generation of Th17 cells in vivo and in vitro. MATERIAL AND METHODS Thirty C57 mice were randomly divided into control, model, and treatment groups. Hepatic fibrosis was induced by s...
journal_title:Medical science monitor : international medical journal of experimental and clinical research
pub_type: 杂志文章
doi:10.12659/msm.904271
更新日期:2017-04-29 00:00:00
abstract::BACKGROUND Long non-coding RNAs (lncRNAs) have been implicated in various human cancer types. However, the underlying mechanisms involved in hepatocellular carcinoma (HCC) progression remain poorly understood. MATERIAL AND METHODS In this study, lncRNA array was used to identify HCC related lncRNAs. RNA immunoprecipit...
journal_title:Medical science monitor : international medical journal of experimental and clinical research
pub_type: 杂志文章
doi:10.12659/MSM.911179
更新日期:2018-11-25 00:00:00
abstract::BACKGROUND Predictive values of admission blood glucose for early hematoma expansion in patients with intracranial hemorrhage (ICH) remain controversial. Blend sign is a novel image predictor for early hematoma growth that suggests presence of active bleeding. We investigated the association between hyperglycemia and ...
journal_title:Medical science monitor : international medical journal of experimental and clinical research
pub_type: 杂志文章
doi:10.12659/MSM.910024
更新日期:2018-09-07 00:00:00
abstract:BACKGROUND:Suicide gene therapy, particularly that utilizing the cytosine deaminase/5-fluorocytosine (CD/5-FC) system, represents a novel and attractive methodology of cancer research. Mechanistically, the CD enzyme can convert the antifungal agent 5-FC into the antimetabolite agent 5-fluorouracil (5-FU), thereby killi...
journal_title:Medical science monitor : international medical journal of experimental and clinical research
pub_type: 杂志文章
doi:
更新日期:2009-01-01 00:00:00
abstract::BACKGROUND The ADRB2 gene encodes the ß2-adrenergic receptor (ß2-AR). This study aimed to determine the association between the C79G polymorphism of the ADRB2 gene and its association with pediatric asthma using a meta-analysis of the published data. MATERIAL AND METHODS Review of publications up to May 2018 was from ...
journal_title:Medical science monitor : international medical journal of experimental and clinical research
pub_type: 杂志文章,meta分析,评审
doi:10.12659/MSM.913780
更新日期:2019-05-30 00:00:00
abstract::BACKGROUND Pancreatic cancer is a major cause of mortality worldwide. Inefficient drugs, their adverse effects, and the development of drug resistance make it difficult to curb the growing incidence of pancreatic cancer. Against this backdrop, the development new drug regimens with no or negligible adverse effects is ...
journal_title:Medical science monitor : international medical journal of experimental and clinical research
pub_type: 杂志文章
doi:10.12659/MSM.914244
更新日期:2019-04-21 00:00:00
abstract:BACKGROUND:Sex differences in epidemiological, clinical and pathological characteristics of colorectal cancer have been under intensive investigation for the last three decades. Given that most of the sex-related differences reported were also age-related, this study sought to determine the potential effect of a sex-ag...
journal_title:Medical science monitor : international medical journal of experimental and clinical research
pub_type: 杂志文章
doi:10.12659/MSM.883842
更新日期:2013-03-20 00:00:00
abstract::BACKGROUND Let-7 microRNAs (miRNAs) have the effects of inhibiting tumor growth and metastasis, however, the research in nasopharyngeal carcinoma (NPC) is limited. This study focused on the effects of Let-7 on NPC migration and invasion and the mechanism of action. MATERIAL AND METHODS Plasmid transfection was used to...
journal_title:Medical science monitor : international medical journal of experimental and clinical research
pub_type: 杂志文章
doi:10.12659/MSM.914555
更新日期:2019-08-02 00:00:00
abstract:PURPOSE:It is difficult to obtain reliable figures on incidence of anorectal malformations (ARM) from literature. The aim of the present study was to reveal the real incidence of these defects in a given area. MATERIAL AND METHODS:Between 1992 and 1997, 86 children with ARM were treated at the departments of paediatri...
journal_title:Medical science monitor : international medical journal of experimental and clinical research
pub_type: 杂志文章
doi:
更新日期:2000-01-01 00:00:00
abstract::BACKGROUND Clogging of the suction tip frequently occurs during orthopedic surgery. We developed a novel anti-clog suction tip using 3D printing technology to improve orthopedic surgery efficiency. MATERIAL AND METHODS We studied the root causes of obstructions in suction tips currently employed in orthopedic surgery ...
journal_title:Medical science monitor : international medical journal of experimental and clinical research
pub_type: 杂志文章
doi:10.12659/MSM.909900
更新日期:2018-09-25 00:00:00
abstract:BACKGROUND:A rare case of Mirizzi syndrome with atypical presentation is reported. CASE REPORT:An 81-year-old woman with a known history of cholelithiasis presented with epigastric discomfort and indigestion. Imaging investigations revealed Mirizzi syndrome, while a cholecystobiliary fistula at the junction of the hep...
journal_title:Medical science monitor : international medical journal of experimental and clinical research
pub_type: 杂志文章
doi:
更新日期:2009-03-01 00:00:00
abstract::BACKGROUND We aimed to investigate the functions of long non-coding RNA (lncRNA) non-coding RNA activated by DNA damage (NORAD) in glioma and identify the potential mechanisms. MATERIAL AND METHODS The expression of NORAD and AKR1B1 in human glioma cell lines were examined using reverse transcription-quantitative poly...
journal_title:Medical science monitor : international medical journal of experimental and clinical research
pub_type: 杂志文章
doi:10.12659/MSM.922659
更新日期:2020-07-21 00:00:00
abstract::Antithrombin is a potent inhibitor of the coagulant effect of thrombin. In the latter half of 20th century, many families have been described in which an autosomaly dominant inherited antithrombin deficiency has caused severe venous thromboembolic disease in successive generations. The important complication is severe...
journal_title:Medical science monitor : international medical journal of experimental and clinical research
pub_type: 杂志文章,评审
doi:
更新日期:2005-11-01 00:00:00
abstract::BACKGROUND The aim of this study was to explore the emotional resilience of middle school students learning at home in February and March 2020 during the COVID-19 pandemic, and the impact of this resilience on students' learning management skills. The results could provide a basis for psychological health education of...
journal_title:Medical science monitor : international medical journal of experimental and clinical research
pub_type: 杂志文章
doi:10.12659/MSM.924994
更新日期:2020-09-01 00:00:00
abstract:UNLABELLED:Thirty two children (8 girls and 32 boys), aged 4-14, with chronic hepatitis C were treated with interferon alpha at a dose of 3 MU or 5 MU, given times weekly for 6 months. Five children (16%) were complete responders (defined as disappearance of viremia), none of them relapsed, 6 (19%) were partial respond...
journal_title:Medical science monitor : international medical journal of experimental and clinical research
pub_type: 临床试验,杂志文章
doi:
更新日期:2000-11-01 00:00:00
abstract:BACKGROUND:Previous studies have shown that administration of ghrelin exhibits protective and therapeutic effects in the gut. The aim of the present investigation was to examine the influence of ghrelin administration on the course of cysteamine-induced duodenal ulcers, as well as effects on mucosal production of oxyge...
journal_title:Medical science monitor : international medical journal of experimental and clinical research
pub_type: 杂志文章
doi:10.12659/msm.882727
更新日期:2012-05-01 00:00:00
abstract:BACKGROUND:Benzodiazepine binding sites distinct from the GABA-receptor-chloride-complex in the central nervous system have been recognized in many peripheral tissues, but their physiological role remains unexplained. Our study was undertaken to examine the effects of diazepam, clonazepam, and PK 11195, a peripheral be...
journal_title:Medical science monitor : international medical journal of experimental and clinical research
pub_type: 杂志文章
doi:
更新日期:2002-04-01 00:00:00