An arsenic trioxide nanoparticle prodrug (ATONP) potentiates a therapeutic effect on an aggressive hepatocellular carcinoma model via enhancement of intratumoral arsenic accumulation and disturbance of the tumor microenvironment

2019 ◽  
Vol 7 (19) ◽  
pp. 3088-3099 ◽  
Author(s):  
Xin Fu ◽  
Qing-rong Liang ◽  
Rong-guang Luo ◽  
Yan-shu Li ◽  
Xiao-ping Xiao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Microenvironment ◽  
Liver Cancer ◽  
Arsenic Trioxide ◽  
Therapeutic Effect ◽  
Cancer Model ◽  
Arsenic Accumulation ◽  
Delivery Efficiency

An arsenic trioxide nanoparticle prodrug has a therapeutic effect on a transgenic liver cancer model by disturbing the tumor micro-environment and increasing the delivery efficiency.

scholarly journals Glucose-6-Phosphate Dehydrogenase is a Prognostic Biomarker and Correlated with Immune Infiltrates in Hepatocellular Carcinoma

2022 ◽  
Author(s):  
Yang Bu ◽  
Kejun Liu ◽  
Yiming Niu ◽  
Ji Hao ◽  
Lei Cui ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Microenvironment ◽  
Liver Cancer ◽  
Immune Cell ◽  
Cox Regression ◽  
Functional Enrichment ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Potential Biomarker ◽  
Glucose 6 Phosphate Dehydrogenase

Abstract Background: Glucose-6-phosphate dehydrogenase (G6PD) plays an important role in the metabolic and immunological aspects of tumors. In hepatocellular carcinoma (HCC), the alteration of tumor microenvironment influences recurrence and metastasis. We extracted G6PD-related data from public databases of HCC tissues and used a bioinformatics approach to explore the correlation between G6PD expression and clinicopathological features and prognosis of immune cell infiltration in HCC.Methods: We extract G6PD expression information from TCGA and GEO databases in liver cancer tissues and normal tissues, validated by immunohistochemistry, and the correlation between G6PD expression and clinical features is analyzed, and the clinical significance of G6PD in liver cancer is assessed by Kaplan-Meier, Cox regression and prognostic line graph models. Functional enrichment analysis is performed by protein-protein interaction (PPI) network, GO/KEGG, GSEA and G6PD-associated differentially expressed genes (DEGs). TIMER and ssGSEA packages are used to assess the correlation between expression and the level of immune cell infiltration.Results: Our results show that G6PD expression is significantly upregulated in hepatocellular carcinoma tissues (P < 0.001). G6PD expression is associated with histological grade, pathological stage, T-stage, vascular infiltration and AFP level (P < 0.05); HCC patients in the low G6PD expression group had longer overall survival and better prognosis compared with the high G6PD expression group (P < 0.05). The level of G6PD expression also affects the levels of macrophages, unactivated dendritic cells, B cells, and follicular helper T cells in the tumor microenvironment.Conclusion: High expression of G6PD is a potential biomarker for poor prognosis of hepatocellular carcinoma, and G6PD may be a target for immunotherapy of HCC.

scholarly journals A Novel Immune and Inflammatory Related Gene Signature in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Yunji Xu ◽  
Guo Huang ◽  
Wen bing Li
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Microenvironment ◽  
Liver Cancer ◽  
Cell Line ◽  
Cell Function ◽  
Immune Cell ◽  
Gene Signature ◽  
Treg Cells ◽  
Clinical Staging ◽  
Response Analysis

Abstract Background: The prognosis of hepatocellular carcinoma (HCC) is closely related to immunity and inflammation, but the value of using immune and inflammation-related genes as predicting the prognosis of HCC requires further research.Methods: The Hepatocellular Carcinomar mRNA data was downloaded in the TCGA and ICGC database. The R package "limma" was used to analyze the differential expression of genes (DEGs) irelated to immune and inflammatory .Univariate Cox analysis screen for immune and inflammation related genes with prognostic value, then construction and verification of the prognostic model in Hepatocellular Carcinomar. The correlation between risk score with tumor immune immersion and immune cell function was assessed through tumor microensure and immune response analysis. NCI-60 cell line to explore the relationship between prognostic gene expression and drug sensitivity.Results: We evaluated 8 immune and inflammatory-related genes to build a prognostic risk prediction model, riskscore is an independent risk factor affecting prognosis, closely related to histological grading and clinical staging. The immune of adCs, macrophages, Tfh cells, Treg cells and Th1 cells higher in the tumor microenvironment leads to poor prognosis of liver cancer. Using data from the NCI-60 cell line, DNASE1L3 high expression may increased resistance of liver cancer cells to bovine platinum, solafinil and bovine platinum. The expression of SLC7A11 can increase the sensitivity of liver cancer to arsenic trioxide (ATO). Simultaneously constructing models and tumor microenvironment and drug resistance may provide effective and safe strategies for HCC chemotherapy and immunotherapy.Conclusion:Our study screened eight immune and inflammation-related genes play an important role in HCC tumor immunity and can be used to predict the prognosis of HCC.

scholarly journals CTL–doxorubicin (DOX)–gold complex nanoparticles (DOX–AuGCs): from synthesis to enhancement of therapeutic effect on liver cancer model

2020 ◽  
Vol 2 (11) ◽  
pp. 5231-5241
Author(s):  
Qiqian Liu ◽  
Hui Liu ◽  
Pasquale Sacco ◽  
Nadia Djaker ◽  
Marc Lamy de la Chapelle ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Therapeutic Effect ◽  
Hybrid Nanoparticles ◽  
Gold Complex ◽  
Cancer Model ◽  
Modified Chitosan

In this work, we bring a rapid way to conceive a fast methodology, in which DOX and Au(iii) ions were complexed with a hydrochloride-lactose-modified chitosan (CTL) and polymer (PEG), leading to hybrid nanoparticles (DOX–AuGSs).

scholarly journals Targeting mTOR and Src restricts hepatocellular carcinoma growth in a novel murine liver cancer model

PLoS ONE ◽  
2019 ◽  
Vol 14 (2) ◽  
pp. e0212860 ◽  
Author(s):  
Sarah Walker ◽  
Miriam Wankell ◽  
Vikki Ho ◽  
Rose White ◽  
Nikita Deo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Cancer Model ◽  
Murine Liver

scholarly journals A single-cell atlas of hepatocellular carcinoma.

2019 ◽  
Vol 5 (suppl) ◽  
pp. 46-46
Author(s):  
Ankur Sharma
Keyword(s):  
Hepatocellular Carcinoma ◽  
Endothelial Cells ◽  
Tumor Microenvironment ◽  
Liver Cancer ◽  
Single Cell ◽  
Stromal Cells ◽  
Tumor Heterogeneity ◽  
Rna Seq ◽  
Therapeutic Targeting ◽  
Complex Ecosystem

46 Background: Tumors reside and evolve in a complex ecosystem of immune and non-immune stromal cells. Methods: We employed multi-sectoral single-cell RNA-seq to catalogue intra-tumor heterogeneity in human hepatocellular carcinoma (HCC). Results: We generated single-cell atlas of ~76,000 cells from fourteen HCC patients, each consisting of 2-5 tumor and matched adjacent normal sectors. In total, we profiled 57 individual tumor and normal sectors consisting of HBV+ and HBV- HCC. By analysing matched normal and malignant sectors we observed intriguing remodelling of the tumor microenvironment (TME).We identify >70 distinct cells-states in HCC including novel, previously uncharacterized subpopulations. Specifically, we demonstrate remarkable heterogeneity in hepatocytes, fibroblast and endothelial cells. Most importantly, we consistently observed a marked remodellingof stromal cells suggesting a role in dynamic tumor-TME interactions. Conclusions: We present the first comprehensive single-cell atlas of HCC. This resource provides unprecedented insights into liver cancer, which will pave the way for early detection and therapeutic targeting.

scholarly journals A Novel Immune and Inflammatory Related Gene Signature in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Yunji Xu ◽  
Guo Huang ◽  
Wenbing Li
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Microenvironment ◽  
Liver Cancer ◽  
Cell Line ◽  
Cell Function ◽  
Immune Cell ◽  
Gene Signature ◽  
Treg Cells ◽  
Clinical Staging ◽  
Response Analysis

Abstract Background: The prognosis of hepatocellular carcinoma (HCC) is closely related to immunity and inflammation, but the value of using immune and inflammation-related genes as predicting the prognosis of HCC requires further research.Methods: The Hepatocellular Carcinomar mRNA data was downloaded in the TCGA and ICGC database. The R package "limma" was used to analyze the differential expression of genes (DEGs) irelated to immune and inflammatory .Univariate Cox analysis screen for immune and inflammation related genes with prognostic value, then construction and verification of the prognostic model in Hepatocellular Carcinomar. The correlation between risk score with tumor immune immersion and immune cell function was assessed through tumor microensure and immune response analysis. NCI-60 cell line to explore the relationship between prognostic gene expression and drug sensitivity.Results: We evaluated 8 immune and inflammatory-related genes to build a prognostic risk prediction model, riskscore is an independent risk factor affecting prognosis, closely related to histological grading and clinical staging. The immune of adCs, macrophages, Tfh cells, Treg cells and Th1 cells higher in the tumor microenvironment leads to poor prognosis of liver cancer. Using data from the NCI-60 cell line, DNASE1L3 high expression may increased resistance of liver cancer cells to bovine platinum, solafinil and bovine platinum. The expression of SLC7A11 can increase the sensitivity of liver cancer to arsenic trioxide (ATO). Simultaneously constructing models and tumor microenvironment and drug resistance may provide effective and safe strategies for HCC chemotherapy and immunotherapy.Conclusion:Our study screened eight immune and inflammation-related genes play an important role in HCC tumor immunity and can be used to predict the prognosis of HCC.

scholarly journals Development of a PD-L1-Expressing Orthotopic Liver Cancer Model: Implications for Immunotherapy for Hepatocellular Carcinoma

Liver Cancer ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 155-171 ◽  
Author(s):  
Da-Liang Ou ◽  
Yu-Yang Lin ◽  
Chia-Lang Hsu ◽  
Yin-Yao Lin ◽  
Chia-Wei Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Cancer Model
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