Alteration of dihydropyrimidine dehydrogenase expression by IFN-alpha affects the antiproliferative effects of 5-fluorouracil in human hepatocellular carcinoma cells.

Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the catabolism of 5-fluorouracil (5-FU) and its activity is closely associated with cellular sensitivity to 5-FU. This study examines the role of DPD in the antiproliferative effects of 5-FU combined with IFN-alpha on hepatocellular carcinoma (HCC) cells in culture and asks whether IFN-alpha could affect DPD expression. The combined action of IFN-alpha and 5-FU on three HCC lines was quantified by a combination index method.

The up-regulation of type I interferon receptor gene plays a key role in hepatocellular carcinoma cells in the synergistic antiproliferative effect by 5-fluorouracil and interferon-alpha.

Combination therapy with interferon (IFN)-alpha and 5-fluorouracil (5-FU) has been reported to show an improved therapeutic efficacy in patients with advanced hepatocellular carcinoma (HCC) but the mechanism behind this has not been completely elucidated. We examined the molecular events underlying the antiproliferative effects of IFN-alpha and 5-FU in combination using six human HCC cell lines. When the antiproliferative effects of administering IFN-alpha and 5-FU together were analyzed using isobolograms, we found that the cell lines could be divided into two groups: the S-group containing three cell lines, which showed synergistic effects, and the A-group, containing the remaining three cell lines, which showed additive effects.

A novel cinnamic acid derivative that inhibits Cdc25 dual-specificity phosphatase activity.

The Cdc25 dual-specificity phosphatases are key regulators of cell cycle progression through activation of cyclin-dependent kinases (Cdk). Three homologs exist in humans: Cdc25A, Cdc25B, and Cdc25C. Cdc25A and Cdc25B have oncogenic properties and are overexpressed in some types of tumors.

Napthalimidobenzamide DB-51630: a novel DNA binding agent inducing p300 gene expression and exerting a potent anti-cancer activity.

Control of gene expression by small molecule compounds is a novel therapeutic strategy for cancer and usually it requires the presence of specific molecular recognition. The development of the compounds preferentially binding to the specific DNA sequence is one of the potential but very difficult approaches in this strategy. We designed and synthesized novel napthalimidobenzamide derivatives and analyzed their binding preferences to oligonucleotides by EtBr-displacement assay with DNA sequences, being essential fragments of the genes.

TAS-108, a novel oral steroidal antiestrogenic agent, is a pure antagonist on estrogen receptor alpha and a partial agonist on estrogen receptor beta with low uterotrophic effect.

Purpose: Investigators are currently conducting phase II trials on TAS-108, a novel oral steroidal antiestrogenic agent. The purpose of this study is to investigate the molecular and pharmacologic properties of TAS-108 compared with other antiestrogenic agents such as tamoxifen,raloxifene, and fulvestrant.

Experimental Design: The antagonistic or agonistic activities of these agents against both estrogen receptors (ER) alpha and beta were compared in the reporter assay systems.