Growth inhibitory effects of pegylated IFN α‐2b on human liver cancer cells <i>in vitro</i> and <i>in vivo</i>

Yano, Hirohisa; Ogasawara, Satoshi; Momosaki, Seiya; Akiba, Jun; Kojiro, Sakiko; Fukahori, Suguru; Ishizaki, Hironori; Kuratomi, Keitaro; Basaki, Yuji; Oie, Shinji; Kuwano, Michihiko; Kojiro, Masamichi

doi:10.1111/j.1478-3231.2006.01321.x

Cited by 44 publications

(37 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several reports showed that PEG- IFN exhibited a strong anti-tumor effect, and that the combination of PEG-IFN and chemoreagents was effective for the treatment of several cancer types (10,21,22). It was also reported that PEG-IFN had an anti-tumor effect against HCC (11), and our results supported this. In our study, the anti-tumor effect of PEG-IFN was almost the same as that of conventional IFN.…”

Section: Discussionsupporting

confidence: 81%

Anti-tumor effect of pegylated interferon in the rat hepatocarcinogenesis model

Miki

Yano²,

Kato³

et al. 2008

Int J Oncol

View full text Add to dashboard Cite

Abstract. Interferon (IFN) is a multifunctional cytokine which works as a suppressor of hepatocarcinogenesis. Pegylated interferon (PEG-IFN) is a modified form of IFN with different pharmacokinetics. We evaluated the antitumor effect of PEG-IFN using a rat hepatocarcinogenesis model. Male Fisher Rats were treated using the Solt and Faber model to induce liver cancer. IFN and PEG-IFN were administered from chemical initiation, and pre-neoplastic foci and neoplastic hepatocellular carcinoma (HCC) were examined at 4 and 40 weeks after chemical initiation, respectively. Apoptosis-related molecules such as p53 and Fas-L, proliferating cell nuclear antigen (PCNA), and oxidative stress-related molecules such as 8-hydroxydeoxyguanosine (8-OHdG) and thioredoxin (TRX) were assessed by immunohistochemical analysis and reverse transcriptase-polymerase chain reaction (RT-PCR). The expression of Notch-1, a molecule related to the regenerative and oncogenic processes was also examined. The generation of foci and HCC were significantly suppressed in IFN and PEG-IFN groups compared with the control group. Whereas PCNA and Notch-1 were strongly expressed in the foci and HCC, Fas-L was mainly detected in the surrounding hepatocytes. 8-OHdG and TRX were also detected in the foci. Although PCNA and Notch-1 were down-regulated in IFN-and PEG-IFN-treated groups, Fas-L was up-regulated in those groups. The activation of Notch-1 signaling and the accumulation of oxidative stress in the pre-neoplastic foci might be associated with the progression of HCC in the DEN-induced hepatocarcinogenesis model. The inhibitory effect of the PEG-IFN and IFN on hepatocarcinogenesis was almost the same, and this might be induced by the Fas-related apoptosis in the surrounding tissues.

show abstract

Section: Discussionsupporting

confidence: 81%

Anti-tumor effect of pegylated interferon in the rat hepatocarcinogenesis model

Miki

Yano²,

Kato³

et al. 2008

Int J Oncol

View full text Add to dashboard Cite

show abstract

“…INFs induce apoptosis in hepatoma cells, activate pro-apoptotic PKR [10] and upregulate death receptor ligands. However, antiapoptotic effects have also been described [7,[31][32][33] .…”

Section: Enhanced Hepatocyte Apoptosis In Hcv Infection In Vivomentioning

confidence: 99%

Hepatitis C virus infection and apoptosis

Fischer

Baumert²,

Blum³

2007

WJG

117

View full text Add to dashboard Cite

“…Liver diseases, such as viral hepatitis, liver cancer, and alcohol-related and drug-related liver injury, are great challenges for health. Worldwide, there are over 350 million hepatitis virus carriers, and over a million deaths per year (about 10% of all deaths in the adult age range) can be attributed to viral hepatitis, and over a million deaths per year are due to hepatocellular carcinoma [44][45][46][47]. The Human Liver Proteome Project (HLPP) is one of the initiatives launched by the HUPO, and is the first initiative of the human proteome project for human organs/tissues [45].…”

Section: Introductionmentioning

confidence: 99%

Large‐scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography

et al. 2008

View full text Add to dashboard Cite

The mixture of phosphopeptides enriched from proteome samples are very complex. To reduce the complexity it is necessary to fractionate the phosphopeptides. However, conventional enrichment methods typically only enrich phosphopeptides but not fractionate phosphopeptides. In this study, the application of strong anion exchange (SAX) chromatography for enrichment and fractionation of phosphopeptides was presented. It was found that phosphopeptides were highly enriched by SAX and majority of unmodified peptides did not bind onto SAX. Compared with Fe 31 immobilized metal affinity chromatography (Fe 31 -IMAC), almost double phosphopeptides were identified from the same sample when only one fraction was generated by SAX. SAX and Fe 31-IMAC showed the complementarity in enrichment and identification of phosphopeptides. It was also demonstrated that SAX have the ability to fractionate phosphopeptides under gradient elution based on their different interaction with SAX adsorbent. SAX was further applied to enrich and fractionate phosphopeptides in tryptic digest of proteins extracted from human liver tissue adjacent to tumorous region for phosphoproteome profiling. This resulted in the highly confident identification of 274 phosphorylation sites from 305 unique phosphopeptides corresponding to 168 proteins at false discovery rate (FDR) of 0.96%.

show abstract

Growth inhibitory effects of pegylated IFN α‐2b on human liver cancer cells in vitro and in vivo

Abstract: Continuous contact with PEG-IFN-alpha2b induces strong antitumor effects and the down-regulation of IFNAR-2 in HCC cells. The data suggest potential clinical application of PEG-IFN-alpha2b for the prevention and treatment of HCC.

Cited by 44 publications

References 44 publications

Anti-tumor effect of pegylated interferon in the rat hepatocarcinogenesis model

Anti-tumor effect of pegylated interferon in the rat hepatocarcinogenesis model

Hepatitis C virus infection and apoptosis

Large‐scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography

Contact Info

Product

Resources

About