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Prevention of Occurrence and Recurrence of Human Hepatocarcinogenesis Guest Editors: Soo Ryang Kim, Kobe; Okio Hino, Tokyo; Masatoshi Kudo, Osaka
Paper
Prevention of Second Primary Tumors by an Acyclic Retinoid in Patients with Hepatocellular Carcinoma
Updated Analysis of the Long-Term Follow-Up Data
Koji Takai, Masataka Okuno, Ichiro Yasuda, Rie Matsushima-Nishiwaki, Takahiro Uematsu, Hisashi Tsurumi, Yoshimune Shiratori, Yasutoshi Muto, Hisataka Moriwaki
Department of Gastroenterology, Gifu University School of Medicine, Gifu, Japan
Address of Corresponding Author
Intervirology 2005;48:39-45 (DOI: 10.1159/000082093)
Key Words
- Lectin-reactive alpha-fetoprotein
- Chemoprevention
- Clonal deletion
- Protein induced by vitamin K absence or antagonist-II
- Retinoid
Abstract
Oral administration with acyclic retinoid, a synthetic vitamin A analog, for a limited period of 12 months (48 weeks) prevented the development of second primary hepatocellular carcinoma (HCC) and also improved the survival of patients who underwent curative treatments of the initial tumor. Following that randomized controlled study reported in 1996 and 1999, we have continued to follow up the patients by medical imaging and blood chemical analyses, and found that the preventive effect of acyclic retinoid lasted up to 199 weeks after randomization (or 151 weeks after completion of retinoid administration). The retinoid's effect was not mediated by reduction in hepatic necro-inflammation since no significant decrease in serum aminotransferase activity was seen in the retinoid group. Such observation seems quite distinct from the cancer-preventive mechanism of interferon, a potent immunopreventive agent for HCC. We have also shown here the reduction by the retinoid in serum levels of lectin-reactive -fetoprotein (AFP-L3) and protein induced by vitamin K absence or antagonist-II (PIVKA-II), both of which indicate the presence of latent HCC cells. These results suggest that acyclic retinoid may delete such malignant clones before they expand to clinically detectable tumors and thereby inhibited second primary HCC. Once such latent clones are eradicated, it may well take at least several years for the next cancer clone to arise clinically. This may possibly explain a reason for the long-term effect of the retinoid even after the limited period of administration. Copyright © 2005 S. Karger AG, Basel
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Author Contacts
Hisataka Moriwaki, MD Department of Gastroenterology Gifu University School of Medicine Gifu 501-1194 (Japan) Tel./Fax +81 58 230 6313, E-Mail hmori@cc.gifu-u.ac.jp
Article Information
Number of Print Pages : 7
Number of Figures : 4, Number of Tables : 2, Number of References : 21
Publication Details
Intervirology (International Journal of Basic and Medical Virology)
Vol. 48, No. 1, Year 2005 (Cover Date: 2005)
Journal Editor: U.G. Liebert, Leipzig
ISSN: 0300-5526 (print), 1423-0100 (Online) For additional information: http://www.karger.com/int
Drug Dosage / Copyright
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center. |
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