| InChI | InChI=1S/C20H30O2/c1-16(2)9-6-10-17(3)11-7-12-18(4)13-8-14-19(5)15-20(21)22/h8-9,11,13-15H,6-7,10,12H2,1-5H3,(H,21,22)/b14-8+,17-11+,18-13+,19-15+ |
| Reference | 1. Expert Rev Gastroenterol Hepatol. 2016 Nov;10(11):1201-1210. Epub 2016 Sep 27.
<br>
Peretinoin as an adjuvant therapy for hepatocellular carcinoma.
<br>
Tan CK(1)(2).
<br>
Author information: <br>
(1)a Department of Gastroenterology and Hepatology , Singapore General Hospital ,
Singapore , Singapore.
(2)b Duke-NUS Medical School , National University of Singapore , Singapore ,
Singapore.
<br>
INTRODUCTION: The current curative treatment modalities for hepatocellular
carcinoma (HCC) are unfortunately fraught with high rates of HCC recurrence.
Hence there is a need to prevent or reduce HCC recurrence after initial curative
therapy. Peretinoin is a synthetic oral retinoid showing significant reduction in
the incidence of recurrent or new HCC in patients who had received curative HCC
therapy. Areas covered: Peretinoin is analysed against the background of
molecular pathogenesis of the different causes of HCC. Publications related to
peretinoin since 1996 are reviewed, covering clinical characteristics, safety and
tolerance profile as well as the current status of clinical development. Expert
commentary: Early phase studies are promising but we need to await the results of
the ongoing phase III study of peretinoin in hepatitis C related HCC. Long term
impact of peretinoin may be diminished by the foreseeable near eradication of
hepatitis C by the direct acting antivirals.
<br>
2. BMC Cancer. 2013 Apr 15;13:191. doi: 10.1186/1471-2407-13-191.
<br>
Peretinoin, an acyclic retinoid, improves the hepatic gene signature of chronic
hepatitis C following curative therapy of hepatocellular carcinoma.
<br>
Honda M(1), Yamashita T, Yamashita T, Arai K, Sakai Y, Sakai A, Nakamura M,
Mizukoshi E, Kaneko S.
<br>
Author information: <br>
(1)Department of Gastroenterology, Graduate School of Medicine, Kanazawa
University, 13-1Takara-machi, Kanazawa 920-0934, Japan. [email protected]
<br>
BACKGROUND: The acyclic retinoid, peretinoin, has been shown to be effective for
suppressing hepatocellular carcinoma (HCC) recurrence after definitive treatment
in a small-scale randomized clinical trial. However, little has been documented
about the mechanism by which peretinoin exerts its inhibitory effects against
recurrent HCC in humans in vivo.<br>
METHODS: Twelve hepatitis C virus-positive patients whose HCC had been eradicated
through curative resection or ablation underwent liver biopsy at baseline and
week 8 of treatment with either a daily dose of 300 or 600 mg peretinoin. RNA
isolated from biopsy samples was subjected to gene expression profile analysis.
RESULTS: Peretinoin treatment elevated the expression levels of IGFBP6, RBP1,
PRB4, CEBPA, G0S2, TGM2, GPRC5A, CYP26B1, and many other retinoid target genes.
Elevated expression was also observed for interferon-, Wnt-, and tumor
suppressor-related genes. By contrast, decreased expression levels were found for
mTOR- and tumor progression-related genes. Interestingly, gene expression
profiles for week 8 of peretinoin treatment could be classified into two groups
of recurrence and non-recurrence with a prediction accuracy rate of 79.6%
(P<0.05). In the liver of patients with non-recurrence, expression of PDGFC and
other angiogenesis genes, cancer stem cell marker genes, and genes related to
tumor progression was down-regulated, while expression of genes related to
hepatocyte differentiation, tumor suppression genes, and other genes related to
apoptosis induction was up-regulated.<br>
CONCLUSIONS: Gene expression profiling at week 8 of peretinoin treatment could
successfully predict HCC recurrence within 2 years. This study is the first to
show the effect of peretinoin in suppressing HCC recurrence in vivo based on gene
expression profiles and provides a molecular basis for understanding the efficacy
of peretinoin.
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