Phase I/II study of temsirolimus for patients with unresectable Hepatocellular Carcinoma (HCC)- a correlative study to explore potential biomarkers for response

Park, Yeon Hee; Chan, Stephen L.; Mo, Frankie; Chu, Cheuk Man; Hui, J.Y.; Tong, Jianping; Chan, Anthony W.H.; Koh, Jane; Hui, Edwin P.; Loong, Herbert H.; Lee, Kirsty; Li, Leung; B.Y., Brigette; To, Ka Fai; Yu, Simon C.H.

doi:10.1186/s12885-015-1334-6

Cited by 110 publications

(81 citation statements)

References 49 publications

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“…An H-score evaluation was performed. The histochemistry score (H-score) was evaluated according to previous studies (26,27). The process was performed as follows: The number of cells in each slice with positive staining and its staining intensity were converted into the corresponding values in order to semi-quantify the staining of the tissues.…”

Section: Study Populationmentioning

confidence: 99%

High expression of microRNA‑31 and its host gene LOC554202 predict favorable outcomes in patients with colorectal cancer treated with oxaliplatin

Xin

et al. 2018

Oncol Rep

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The expression levels of microRNA‑31 (miR‑31) and LOC554202 have been previously investigated in colorectal cancer (CRC) and their oncogenic and/or tumor suppressive roles have been described. The aim of the present study was to examine the role of miR‑31 and its host gene LOC554202 in the prognosis of patients with CRC. Patients with CRC treated with oxaliplatin‑based chemotherapy between June 2005 and March 2010 were recruited to the First Affiliated Hospital of China Medical University. Tumor and adjacent mucosal tissues were collected. The detection of miR‑31 and/or LOC554202 was performed with probe hybridization targeting. Correlation analysis was performed among the expression levels of miR‑31, LOC554202, and their association with clinicopathological parameters and/or survival rates. miR‑31 and LOC554202 were expressed at high levels in CRC (P<0.01) compared with adjacent intestinal mucosa. A linear correlation was noted for the two markers in CRC tissues (P<0.01). The expression of miR‑31 was significantly higher in adenocarcinoma than in the adjacent intestinal mucosa (P<0.01), whereas the expression of LOC554202 was significantly higher in the adenocarcinoma and the rectal cancer tissue regions (P<0.01). The high expression levels of miR‑31 and LOC554202 were associated with high disease‑free survival (DFS) and overall survival (OS) rates (P<0.05). Associations between the increase in DFS and OS and the elevated expression levels of miR‑31 and LOC554202 were present in patients with colon cancer but not in patients with rectal cancer (P<0.05). These data indicated that miR‑31 and LOC554202 may be potential markers for evaluation of the prognosis of patients treated with oxaliplatin‑based chemotherapy.

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Section: Study Populationmentioning

confidence: 99%

High expression of microRNA‑31 and its host gene LOC554202 predict favorable outcomes in patients with colorectal cancer treated with oxaliplatin

Xin

et al. 2018

Oncol Rep

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“…Everolimus has been reported to delay tumor progression in patients with sorafenib-refractory HCC (9); however, a recent investigation did not demonstrate improved patient survival in a second-line setting or in sorafenib-intolerant patients (10). Yeo et al (11) and Cho et al (12) hypothesized that only selected patients, depending on the expression of relevant target proteins, may benefit from an mTOR-based treatment regimen. The benefit of an everolimus-sorafenib combination is controversial, since although a dose-finding study on patients with advanced HCC yielded encouraging results (13), a randomized multicenter, multinational phase II trial did not indicate a synergistic effect (14).…”

Section: Discussionmentioning

confidence: 99%

mTOR inhibition reduces growth and adhesion of hepatocellular carcinoma cells in vitro

Engl

Rutz

Maxeiner

et al. 2017

Molecular Medicine Reports

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Mechanistic target of rapamycin (mTOR) signaling is typically increased in hepatocellular carcinoma (HCC). A panel of HCC cell lines (HepG2, Hep3B and HuH6) was exposed to various concentrations of the mTOR inhibitors, everolimus and temsirolimus, in order to investigate their effects on cell growth, clonal formation, cell cycle progression, and adhesion and chemotactic migration using MTT and clonal cell growth assays, fluorometric detection of cell cycle phases and a Boyden chamber assay. In addition, integrin α and β adhesion receptors were analyzed by flow cytometry and blocking studies using function blocking monoclonal antibodies were conducted to explore functional relevance. The results demonstrated that everolimus and temsirolimus significantly suppressed HCC cell growth and clonal formation, at 0.1 or 1 nM (depending on the cell line). In addition, the number of cells in G0/G1 phase was increased in response to drug treatment, whereas the number of G2/M phase cells was decreased. Drug treatment also considerably suppressed HCC cell adhesion to immobilized collagen. Integrin profiling revealed strong expression of integrin α1, α2, α6 and β1 subtypes; and integrin α1 was upregulated in response to mTOR inhibition. Suppression of integrin α1 did not affect cell growth; however, it did significantly decrease adhesion and chemotaxis, with the influence on adhesion being greater than that on motility. Due to a positive association between integrin α1 expression and the extent of adhesion, whereby reduced receptor expression was correlated to decreased cell adhesion, it may be hypothesized that the adhesion‑blocking effects of mTOR inhibitors are not associated with mechanical contact inhibition of the α1 receptor but with integrin α1‑dependent suppression of oncogenic signaling, thus preventing tumor cell‑matrix interaction.

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“…Scanning of the TMA slides was performed using the Pannoramic MIDI scanner (3D Histech; Hungary). Quant center, an analysis software supporting the Pannoramic viewer, was used to measure the intensity of ASPN staining (brown color) as described previously [23,24]. Identi cation of DCM-related DEGs Similar to ICM, the DEGs of DCM compared with the normal control in each dataset were screened out.…”

Section: Immunohistochemistrymentioning

confidence: 99%

ASPN is a Potential Promising Biomarker for Common Heart Failure

Zhang

Zhou

et al. 2020

Preprint

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Background: Heart failure (HF), the leading cause of adult mortality and morbidity worldwide, is the end-stage of various diseases, especially ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM). This study aimed to investigate the common molecular mechanism of ICM and DCM.Methods: Four gene expression datasets, GSE1869, GSE5406, GSE57338, and GSE79962, were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) of ICM or DCM samples compared with those of nonfailing samples were identified. Gene ontology (GO) annotation, Kyoto encyclopedia of gene and genome (KEGG) pathway analysis, and the protein-protein network (PPI) of the coregulated DEGs in at least three datasets were performed using the online tools of DAVID, the KOBAS database, and the STRING database, respectively. Hub genes of HF were analyzed for their correlation with left ventricular ejection fraction (LVEF) in dataset GSE19303. The expression levels of notable DEGs were further validated in our tissue microarray (TMA).Results: Fifty-nine coregulated ICM and sixty-eight coregulated DCM relevant DEGs were identified (in at least three datasets). Moreover, 38 common DEGs between ICM and DCM relevant DEGs were obtained that were mainly involved in inflammatory/stress processes, proliferation, and some lipid metabolism pathways. Among the ten hub genes with top degrees, four genes showed a correlation with LVEF, and ASPN had the most significant correlation. Finally, the expression of ASPN protein was validated in our TMA and was significantly increased in ICM and DCM left ventricular samples.Conclusion: The present study revealed some common molecular mechanisms of HF with different causes. Furthermore, ASPN may be a potential promising biomarker for HF.

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Phase I/II study of temsirolimus for patients with unresectable Hepatocellular Carcinoma (HCC)- a correlative study to explore potential biomarkers for response

Cited by 110 publications

References 49 publications

High expression of microRNA‑31 and its host gene LOC554202 predict favorable outcomes in patients with colorectal cancer treated with oxaliplatin

High expression of microRNA‑31 and its host gene LOC554202 predict favorable outcomes in patients with colorectal cancer treated with oxaliplatin

mTOR inhibition reduces growth and adhesion of hepatocellular carcinoma cells in vitro

ASPN is a Potential Promising Biomarker for Common Heart Failure

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