Prostate tumor-initiating cells: A new target for telomerase inhibition therapy?

Conventional therapies for prostate cancer, especially in its androgen-independent form, may result in the survival of small populations of resistant cells with tumor-initiating potential. These “cancer stem cells” are believed to be responsible for cancer relapse, and therapeutic strategies targeting these cells are of great importance. Telomerase is a ribonucleoprotein enzyme responsible for telomere elongation and is activated in the majority of malignancies, including prostate cancer, but is absent in most normal cells. Putative tumor-initiating cells have significant levels of telomerase, indicating that they are an excellent target for telomerase inhibition therapy. In this review, we present some evidence for the hypothesis that conventional therapies (standard chemotherapy and/or radiation therapy) in combination with telomerase inhibitors may result in effective and more durable responses.     

Incorporation of biological information in cancer risk assessment: Example — Vinyl chloride

Vinyl chloride (VC) is used as an example to demonstrate how biological information can be incorporated into quantitative risk assessment. The information included is the pharmacokinetics of VC in animals and humans and the data-generated hypothesis that VC primarily affects the initiation stage of the multistage carcinogenesis. The emphasis in this paper is on the improvement of risk assessment methodology rather than the risk assessment of VC per se.Sufficient data are available to construct physiologically-based pharmacokinetic models for both animals and humans. These models are used to calculate the metabolized dose corresponding to exposure scenarios in animals and in humans.On the basis of the data on liver angiosarcomas and carcinomas in rats, the cancer risk per unit of metabolized dose is comparable, irrespective of routes (oral or inhalation) of exposure. The tumor response from an intermittent/partial lifetime exposure is shown to be consistent with that from a lifetime exposure when VC is assumed to affect the first (initiation) stage of the multistage carcinogenic process. Furthermore, the risk estimates calculated on the basis of animal data are shown to be consistent with the human experience.     

Phytochrome control of oscillating levels of phenylalanine ammonia lyase in Hordeum vulgare shoots

Five-day-old etiolated barley shoots respond to brief illumination with red light by increasing their level of PAL ca 50% within 5 hr. When assayed s