Pegylated Interferon-α2a Inhibits Proliferation of Human Liver Cancer Cells In Vitro and In Vivo

Kusano, Hironori; Akiba, Jun; Ogasawara, Satoshi; Sanada, Sakiko; Yasumoto, Makiko; Nakayama, Masamichi; Ueda, Kenichi; Ueda, Kosuke; Kurita, Takashi; Todoroki, Keita; Umeno, Yumi; Nakashima, Osamu; Yano, Hirohisa

doi:10.1371/journal.pone.0083195

Cited by 21 publications

(12 citation statements)

References 28 publications

(31 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pegylation of IFN has been shown to efficiently resolve the half-life and bioavailability issues ( 47 ) by providing longer half-life and a persistent steady state of drug activity. Indeed, pegylated type I IFNs showed therapeutic efficacy in different preclinical models of cancer ( 48 , 49 ). More recently, pegylated IFN-β was shown to significantly inhibit the vascular permeability of the peritoneal membrane in animal models of ovarian cancer and gastric cancer cell xenograft mice ( 50 ).…”

Section: Common Cancer Therapies and Type I Ifn Signalingmentioning

confidence: 99%

Plasticity of Type I Interferon-Mediated Responses in Cancer Therapy: From Anti-tumor Immunity to Resistance

2018

View full text Add to dashboard Cite

The efficacy of several therapeutic strategies against cancer, including cytotoxic drugs, radiotherapy, targeted immunotherapies and oncolytic viruses, depend on intact type I interferon (IFN) signaling for the promotion of both direct (tumor cell inhibition) and indirect (anti-tumor immune responses) effects. Malfunctions of this pathway in tumor cells or in immune cells may be responsible for the lack of response or resistance. Although type I IFN signaling is required to trigger anti-tumor immunity, emerging evidence indicates that chronic activation of type I IFN pathway may be involved in mediating resistance to different cancer treatments. The plastic and dynamic features of type I IFN responses should be carefully considered to fully exploit the therapeutic potential of strategies targeting IFN signaling. Here, we review available evidence supporting the involvement of type I IFN signaling in mediating resistance to various cancer therapies and highlight the most promising modalities that are being tested to overcome resistance.

show abstract

Section: Common Cancer Therapies and Type I Ifn Signalingmentioning

confidence: 99%

Plasticity of Type I Interferon-Mediated Responses in Cancer Therapy: From Anti-tumor Immunity to Resistance

2018

View full text Add to dashboard Cite

show abstract

“…While IFNs have been reported to exert diverse antiviral effects, type I IFNs, including IFN-α, have been used for the treatment of numerous human cancer types, and the type I IFN status is associated with the outcome of anti-cancer therapy ( 45 ). Indeed, IFN is known to suppress liver cancer growth via the induction of apoptosis in vitro and in vivo ( 46 , 47 ). Therefore, the attenuation of IFN-signaling by ECM may contribute to the frequent development of liver cancer from the fibrotic liver.…”

Section: Discussionmentioning

confidence: 99%

Regulation of interferon signaling and HCV‑RNA replication by extracellular matrix

et al. 2018

View full text Add to dashboard Cite

Although interferon (IFN)-based treatment of patients with chronic hepatitis C virus (HCV) infection is widely applied, treatment resistance is often observed in patients with advanced liver fibrosis. Given that the molecular mechanisms of IFN resistance in liver fibrosis remain elusive, the present study investigated the effects of extracellular matrix (ECM) on IFN signaling in hepatic cells. The native HuH-7 human hepatoma cell line and HuH-7 cells were stably transfected with full-length HCV-RNA fused with Renilla luciferase (OR6 cells) were cultured on ECM-coated dishes or non-coated plastic dishes (NDs), and treated with human IFN-α. In Huh-7 cells cultured on coated dishes, the IFN-stimulated response element (ISRE) luciferase activity was measured following ISRE plasmid transfection and the expression of IFN-stimulated genes (ISG) were significantly lower than those in cells cultured on NDs. In addition, after IFN-α treatment, the amount of HCV-RNA and viral protein produced by OR6 cells cultured on coated dishes was higher than that produced by cells cultured on NDs. When cells were treated with β1-integrin-blocking antibody to disrupt the cell-matrix interaction, the ISRE luciferase activity was restored, and the protein expression of ISG was increased, while that of HCV proteins was suppressed. Treatment of cells with integrin-linked kinase (ILK) inhibitor or focal adhesion kinase (FAK) inhibitor restored the ISRE luciferase activity and expression of ISG proteins. These results suggested that β1-integrin-mediated signals affected the IFN signaling and promoted HCV replication. Therefore, the accumulation of ECM in liver fibrosis may impair IFN signaling through β1-integrin-mediated signaling involving ILK and FAK.

show abstract

“…[ 30 , 31 ] Moreover, IFN have been proven to have various effects on different types of cells, such as antiproliferation, induction of apoptosis, and immunomodulation. [ 32 – 34 ] All these potential mechanisms may explain the positive effects of Peg-IFN on the survival outcomes of patients with hepatitis-related HCC after curative treatment.…”

Section: Discussionmentioning

confidence: 99%

Adjuvant pegylated interferon therapy improves the survival outcomes in patients with hepatitis-related hepatocellular carcinoma after curative treatment

Yin

Cao

et al. 2018

Medicine

View full text Add to dashboard Cite

Background:Hepatocellular carcinoma (HCC) is one of the most common cancers and the second leading cause of cancer-related deaths in men worldwide. Surgical resection of HCC remains the mainstay treatment procedure. As a result of hepatitis viral infection, the postoperative survival outcome in patients with HCC is not satisfactory. Recently, studies have reported that due to its treatment effect on hepatitis infection, pegylated interferon (Peg-IFN)-based therapy could improve the survival outcome after the treatment of hepatitis-related HCC. However, the postoperative effect of this regimen on the survival outcomes in patients with hepatitis-related HCC remains debatable. The present study conducted a meta-analysis to evaluate the effects of adjuvant Peg-IFN-based therapy on the survival outcomes in patients with hepatitis-related HCC after the curative treatment.Methods:A systematic search was conducted to identify studies on the survival outcomes in patients with hepatitis-related HCC after a curative treatment with adjuvant Peg-IFN. PubMed, EmBase, and Cochrane Library databases were searched until September 20, 2017. The retrieved studies were independently assessed by 2 reviewers, to identify the potentially eligible studies and extract data of interest. STATA software (Version 10.0, STATA Corporation, College Station, Texas) software was used for all statistical analyses.Results:The pooled results showed that adjuvant Peg-IFN-based therapy improved the 3- and 5-year recurrence-free survival (RFS) rates of patients with hepatitis-related HCC (3-year RFS, HR = 0.80; 95% CI: 0.64–0.99, P = .04; P = .81 for heterogeneity; 5-year RFS, HR = 0.82; 95% CI: 0.67–0.99, P = .04; P = .84 for heterogeneity). For the 5-year overall survival (OS) outcomes of Peg-IFN therapy for hepatitis-related HCC after the curative treatment, the pooled results showed a significant difference between the 2 groups (HR = 0.67; 95% CI: 0.47–0.97, P = .03; P = .99 for heterogeneity).Conclusions:Adjuvant Peg-IFN-based therapy could improve the RFS and OS outcomes in patients after curative treatment of hepatitis-related HCC, with no severe adverse effects.

show abstract

Pegylated Interferon-α2a Inhibits Proliferation of Human Liver Cancer Cells In Vitro and In Vivo

Cited by 21 publications

References 28 publications

Plasticity of Type I Interferon-Mediated Responses in Cancer Therapy: From Anti-tumor Immunity to Resistance

Plasticity of Type I Interferon-Mediated Responses in Cancer Therapy: From Anti-tumor Immunity to Resistance

Regulation of interferon signaling and HCV‑RNA replication by extracellular matrix

Adjuvant pegylated interferon therapy improves the survival outcomes in patients with hepatitis-related hepatocellular carcinoma after curative treatment

Contact Info

Product

Resources

About