Increases in NMR-visible lipid and glycerophosphocholine during phenylbutyrate-induced apoptosis in human prostate cancer cells.

DU145 human prostatic carcinoma cells were treated with the differentiating agents phenylacetate (PA) and phenylbutyrate (PB) and examined in perfused cultures by diffusion-weighted 1H and 31P nuclear magnetic resonance spectroscopy (NMR). PA and PB (10 mM) induced significant (>3-fold) time-dependent increases in the level of NMR-visible lipids and total choline in 1H spectra, and glycerophosphocholine levels in the 31P spectra, with the increases being greater for PB. These effects were accompanied by significant increases in cytoplasmic lipid droplets and intracellular lipid volume fraction as observed by morphometric analysis of Oil Red O-stained cells.

Capecitabine plus paclitaxel as front-line combination therapy for metastatic breast cancer: a multicenter phase II study.

Purpose: The goal of this multicenter, open-label phase II study was the clinical evaluation of combination therapy with the oral fluoropyrimidine capecitabine and the taxane paclitaxel in patients with metastatic breast cancer (MBC).

Patients And Methods: Forty-seven patients with MBC received oral capecitabine at 1650 mg/m(2)/d (825 mg/m(2) twice daily) on days 1 through 14, and intravenous infusion of paclitaxel at 175 mg/m(2) on day 1 of each 21-day treatment cycle. Treatment continued until disease progression, intolerable toxicity, or patient' s decision to discontinue.

Phase II study of capecitabine in patients with fluorouracil-resistant metastatic colorectal carcinoma.

Purpose: Capecitabine is an oral fluoropyrimidine converted to fluourouracil (FU) preferentially in tumor tissue. It has proven clinical activity against colorectal cancer when used as first-line therapy. The objectives of this study were to assess the safety and efficacy of capecitabine in patients with metastatic colorectal carcinoma who progressed despite previous FU therapy.

Inhibition of estrogen-dependent breast cell responses with phenylacetate.

The aromatic fatty acid phenylacetate (PA) and its analogs have come under intense investigation due to their ability to cause the growth arrest of a variety of neoplasia, including human breast cancer. We have determined that PA and its halide derivative 4-chlorophenylacetate (4-CPA) showed marked antiproliferative activity on 3 of 6 human breast cancer cell lines tested. Interestingly, the 3 cell lines that were growth inhibited by PA and 4-CPA were estrogen receptor (ER) positive (T47-D, MCF-7 and ZR-75-1) whereas those that were little affected by these compounds were ER-negative (MDA-MB-157, MDA-MB-231 and SK-Br-3).

Peroxisome proliferator-activated receptor gamma as a novel target in cancer therapy: binding and activation by an aromatic fatty acid with clinical antitumor activity.

Aromatic fatty acids, of which phenylacetate is a prototype, constitute a class of low toxicity drugs with demonstrated antitumor activity in experimental models and in humans. Using in vitro models, we show here a tight correlation between tumor growth arrest by phenylacetate and activation of peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the nuclear receptor superfamily. In support are the following observations: (a) the efficacy of phenylacetate as a cytostatic agent was correlated with pre-treatment levels of PPARgamma, as documented using established tumor lines and forced expression models; (b) in responsive tumor cells, PPARgamma expression was up-regulated within 2-9 h of treatment preceding increases in p21waf1, a marker of cell cycle arrest; (c) inhibition of mitogen-activated protein kinase, a negative regulator of PPARgamma, enhanced drug activity; and (d) phenylacetate interacted directly with the ligand-binding site of PPARgamma and activated its transcriptional function.