𝔖 Bobbio Scriptorium
✦   LIBER   ✦

Epigenetic combination therapy as a tumor-selective treatment approach for hepatocellular carcinoma

✍ Scribed by Sascha Venturelli; Sorin Armeanu; Anita Pathil; Chih-Jen Hsieh; Thomas S. Weiss; Reinhard Vonthein; Manfred Wehrmann; Michael Gregor; Ulrich M. Lauer; Michael Bitzer

Publisher
John Wiley and Sons
Year
2007
Tongue
English
Weight
259 KB
Volume
109
Category
Article
ISSN
0008-543X

No coin nor oath required. For personal study only.

✦ Synopsis

Abstract

BACKGROUND.

Innovative epigenetic therapeutics comprise histone deacetylase inhibitors (HDAC‐I) and demethylating agents (DA). It was recently found that HDAC‐I compounds exhibit profound therapeutic activities against hepatocellular carcinoma (HCC). A comprehensive preclinical investigation was performed on the potential of a combined HDAC‐I/DA epigenetic regimen for the highly chemotherapy‐resistant HCC entity.

METHODS.

Human HCC‐derived cell lines or primary human hepatocytes (PHH) were treated with HDAC‐I compound suberoylanilide hydroxamic acid (SAHA) or DA compound 5‐aza‐2′‐deoxycytidine (5‐aza‐dC) or both and examined for cellular damage, proliferation, histone acetylation pattern, and DNA methylation. In vivo activities were investigated in a xenograft hepatoma model.

RESULTS.

Monotherapeutic application of SAHA or 5‐aza‐dC was found to induce substantial antiproliferative effects in HCC‐derived cells, strongly enhanced by combined SAHA and 5‐aza‐dC treatment. PHH from different human donors did not exhibit any relevant cellular damage even when applying high doses of the combination regimen, whereas HCC‐derived cell lines showed a dose‐dependent damage. In vivo testing demonstrated a statistical significant inhibition of hepatoma cell growth for the combined treatment regime.

CONCLUSIONS.

Because the combined HDAC‐I/DA epigenetic approach was found to produce significant antitumor effects in HCC model systems and did not impair cellular integrity of untransformed hepatocytes, this combination therapy is now considered for further investigation in clinical trials. Cancer 2007;109:2132–41. © 2007 American Cancer Society.

📜 SIMILAR VOLUMES

Selective targeting by preS1 domain of h
Selective targeting by preS1 domain of hepatitis B surface antigen conjugated with phosphorylcholine-based amphiphilic block copolymer micelles as a biocompatible, drug delivery carrier for treatment of human hepatocellular carcinoma with paclitaxel
✍ Ryohei Miyata; Masakazu Ueda; Hiromitsu Jinno; Tomohiro Konno; Kazuhiko Ishihara 📂 Article 📅 2009 🏛 John Wiley and Sons 🌐 French ⚖ 474 KB

## Abstract Using dithioester‐capped 2‐methacryloyloxyethyl phosphorylcholine (MPC) as a macro chain transfer agent, a diblock copolymer was synthesized with __n__‐butyl methacrylate (BMA) as hydrophobic core‐forming blocks. The MPC–BMA unit was copolymerized with an immobilizable unit, __p__‐nitro

Sakon M, Nagano H, Dono K, Nakamori S, U
Sakon M, Nagano H, Dono K, Nakamori S, Umeshita K, Yamada A, Kawata S, Imai Y, Iijima S, Monden M. Combined intraarterial 5-fluorouracil and subcutaneous interferon-α therapy for advanced hepatocellular carcinoma with tumor thrombi in the major portal branches. Cancer. 2002;94(2):435–42.
📂 Article 📅 2002 🏛 John Wiley and Sons 🌐 English ⚖ 35 KB

## Abstract The original article to which this Erratum refers was published in Cancer (2002) 94(2):435–42