Cisapride-induced torsades de pointes.

Two cases of torsades de pointes associated with cisapride are presented, both in association with concomitant drug therapy that inhibits cisapride biotransformation. In one case, plasma cisapride was elevated days after the event, strongly supporting a role for accumulation of the drug in causing the arrhythmia. It is emphasized that these adverse drug reactions are not idiosyncratic, but rather are predictable based on an understanding of the underlying mechanisms.

Anti-angiogenic treatment with linomide as adjuvant to surgical castration in experimental prostate cancer.

Purpose: Escape from "castration inhibition," be it surgical or chemically induced, is still the major problem in prostate cancer treatment. New agents that can be given as adjuvant therapy are needed. Linomide has demonstrated both anti-tumor and anti-angiogenic activity with little toxicity in the Dunning R-3327 rat prostate tumor system.

Antiangiogenic treatment with linomide as chemoprevention for prostate, seminal vesicle, and breast carcinogenesis in rodents.

There are two distinct phases during prostatic carcinogenesis with regard to tumor blood vessel development. During the first or prevascular phase, which may persist for years, cells that have undergone some but not all of the transformation steps undergo a limited amount of net growth, producing premalignant prostatic intraepithelial neoplastic (PIN) lesions. Most of these PIN lesions do not continue net growth and do not progress to produce histologically detectable cancer.

Human prostatic cancer cells are sensitive to programmed (apoptotic) death induced by the antiangiogenic agent linomide.

Human prostatic cancer cells have a remarkably low rate of proliferation even when they have metastasized to the bone and have become androgen independent (Berges et al., Clin. Cancer Res.

KAI1, a metastasis suppressor gene for prostate cancer on human chromosome 11p11.2.

A gene from human chromosome 11p11.2 was isolated and was shown to suppress metastasis when introduced into rat AT6.1 prostate cancer cells.