Oncolytic Adenovirus-Mediated E1A Gene Therapy Induces Tumor-Cell Apoptosis and Reduces Tumor Angiogenesis Leading to Inhibition of Hepatocellular Carcinoma Growth in Animal Model

Ye, Zhenmin; Wang, Xiaohua; Hao, Siguo; Zhong, Jun; Xiang, Jim; Yang, Jicheng

doi:10.1089/cbr.2006.21.225

Cited by 16 publications

(9 citation statements)

References 47 publications

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“…The adenovirus vector is one of the most widely used vectors in gene therapy applications for the treatment of diverse human diseases including cancer (23). Ye et al (24) reported that adenovirus-mediated gene therapy demonstrated beneficial preclinical outcomes by inducing apoptosis of tumor cells and inhibiting tumor angiogenesis, which led to HCC regression in a HCC tumor model. Hu et al (25) revealed that adenovirus-mediated expression of melanoma differentiation-associated-7 efficiently inhibited HCC growth.…”

Section: Discussionmentioning

confidence: 99%

Genetically engineered recombinant adenovirus expressing interleukin‑2 for hepatocellular carcinoma therapy

Sun

Chen

et al. 2017

Mol Med Report

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Regulatory and effector T cells possess immunological cytotoxicity for tumor cells in the tumor microenvironment during tumor progression and are the primary suppressors inhuman cancer therapy. Interleukin‑2 (IL‑2) is an anticancer cytokine, which triggers human innate and adaptive immunity by stimulating T cell propagation and lymphocyte infiltration into tumor sites. IL‑2 has been used successfully for cancer therapy. Recombinant adenovirus expressing IL‑2 (rAd‑IL‑2) injection is a gene therapy agent that may improve prognosis of hepatocellular carcinoma (HCC) patients. In the present study, the ability of IL‑2 to stimulate an immune response and the ability of recombinant adenovirus to inhibit tumor cell growth in HCC was investigated in a HCC tumor model. It was demonstrated that the regulatory and effector cell‑mediated tumor suppression by antitumor cluster of differentiation (CD)4+ and CD8+ T cells stimulated by rAd‑IL‑2 is tumor‑specific. Furthermore, rAd‑IL‑2 significantly stimulated tumor‑specific cytotoxic T lymphocyte responses, increased interferon‑γ release and enhanced antitumor immunity by inducing CD4+ and CD8+ T cell recruitment into the tumor, and additionally induced memory to protect tumor‑bearing mice against tumor challenge. Treatment with rAd‑IL‑2 led to tumor regression and long‑term survival of mice in the 120‑day treatment period. Tumor challenge experiments demonstrated that rAd‑IL‑2 induced memory, protecting against reinfection. In conclusion, rAd‑IL‑2 may promote tumor‑associated effector and regulatory T cell expansion and may be a potential therapeutic agent for clinical immunotherapy application in the treatment of cancer.

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Section: Discussionmentioning

confidence: 99%

Genetically engineered recombinant adenovirus expressing interleukin‑2 for hepatocellular carcinoma therapy

Sun

Chen

et al. 2017

Mol Med Report

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“…In the treatment of HCC, p53 products are injected into liver tissue by a variety of routes [55,72,82,[88][89][90][91][92] . When p53 products are injected intratumorally [55,88,89] , introduction of exogenous wt-p53 can inhibit cell growth, the expression of both p53 and p21 proteins is up-regulated in tumor cells. Intraarterial gene delivery into animal hepatic tumors can lead to selective gene expression in tumor cells [72] .…”

Section: Empirical Studies Of P53 Therapy For Hccmentioning

confidence: 99%

“…This gene transfer technique may have potential in clinical gene therapy for HCC. Oncolytic adenovirusmediated gene therapy induces tumor-cell apoptosis and reduces tumor angiogenesis, leading to inhibition of HCC growth in animal model [88] . Because CNHK200-mE is capable of selectively replicating in HCC cells, thus suppressing tumor growth and antiangiogenic activity in nude mice [85] , it can be used as a potential agent in the treatment of HCC.…”

Section: Empirical Studies Of P53 Therapy For Hccmentioning

confidence: 99%

p53 gene in treatment of hepatic carcinoma:Status quo

Guan

La²,

Yang³

et al. 2007

WJG

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Hepatocellular carcinoma (HCC) is one of the 10 most common cancers worldwide. There is no ideal treatment for HCC yet and many researchers are trying to improve the effects of treatment by changing therapeutic strategies. As the majority of human cancers seem to exhibit either abnormal p53 gene or disrupted p53 gene activation pathways, intervention to restore wild-type p53 (wt-p53) activities is an attractive anti-cancer therapy including HCC. Abnormalities of p53 are also considered a predisposition factor for hepatocarcinogenesis. p53 is frequently mutated in HCC. Most HCCs have defects in the p53-mediated apoptotic pathway although they

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“…E1A was also shown to stabilize c-Myc protein, the key regulator of cellular proliferation, by binding to p400, and this stabilization is critical for the ability of E1A to sensitize tumor cells to chemotherapy [27]. Moreover, it was demonstrated that E1A induced apoptosis in HCC cells by a p53-dependent pathway, in which E1A upregulated pro-apoptotic factors Bax, caspase-3, and Fas, and down-regulated anti-apoptosis factors survivin and Bcl-2 [28].…”

Section: Introductionmentioning

confidence: 99%

Polyethylenimine (PEI)-Mediated E1A Increases the Sensitivity of Hepatocellular Carcinoma Cells to Chemotherapy

Li¹,

Yao

Zhang

et al. 2019

Med Sci Monit Basic Res

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Background The aim of this study was to assess the ability of polyethylenimine (PEI) as an E1A plasmid vector to transfect hepatocellular carcinoma SMMC-7721 cells and to analyze the sensitization effect of E1A on various anti-tumor drugs. Material/Methods PEI-mediated recombinant plasmid psv-E1A with high expression of the E1A gene was introduced into hepatocellular carcinoma SMMC-7721 cells, and the effective transfection of E1A gene was determined by RT-PCR and Western blot analysis. The CCK8 method was used to detect the proliferation inhibition of docetaxel, epirubicin, gemcitabine, and 5-fluorouracil on SMMC-7721 cells before and after the transfection of the E1A gene. Results RT-PCR and Western blot analysis showed that PEI could transfect plasmid psv-E1A with stable expression. After the transfection of E1A gene, the sensitivity of SMMC-7721 cells to docetaxel, epirubicin, gemcitabine, and 5-fluorouracil was increased (P <0.05), and the sensitivity to docetaxel was significantly improved ( P <0.01). Conclusions PEI can transfect plasmid psv-E1A. The E1A gene can increase the sensitivity of hepatocellular carcinoma cells to chemotherapeutic drugs. The mechanism may be related to the increased ability of the E1A gene to inhibit proliferation of hepatocellular carcinoma cells and altering the cell cycle of hepatocellular carcinoma cells.

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Oncolytic Adenovirus-Mediated E1A Gene Therapy Induces Tumor-Cell Apoptosis and Reduces Tumor Angiogenesis Leading to Inhibition of Hepatocellular Carcinoma Growth in Animal Model

Cited by 16 publications

References 47 publications

Genetically engineered recombinant adenovirus expressing interleukin‑2 for hepatocellular carcinoma therapy

Genetically engineered recombinant adenovirus expressing interleukin‑2 for hepatocellular carcinoma therapy

p53 gene in treatment of hepatic carcinoma:Status quo

Polyethylenimine (PEI)-Mediated E1A Increases the Sensitivity of Hepatocellular Carcinoma Cells to Chemotherapy

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