Nanoformulation of Talazoparib Increases Maximum Tolerated Doses in Combination With Temozolomide for Treatment of Ewing Sarcoma.

The Pediatric Preclinical Testing Program previously identified the PARP inhibitor talazoparib (TLZ) as a means to potentiate temozolomide (TMZ) activity for the treatment of Ewing sarcoma. However, the combination of TLZ and TMZ has been toxic in both preclinical and clinical testing, necessitating TMZ dose reduction to ~15% of the single agent maximum tolerated dose. We have synthesized a nanoparticle formulation of talazoparib (NanoTLZ) to be administered intravenously in an effort to modulate the toxicity profile of this combination treatment.

Environment, endocrinology, and biochemistry influence expression of stress proteins in bottlenose dolphins.

Natural and anthropogenic stressors have been reported to impact the health of marine mammals. Therefore, investigation of quantifiable biomarkers in response to stressors is required. We hypothesized that stress protein expression would be associated with biological and health variables in wild and managed-care bottlenose dolphins (Tursiops truncatus).

Development and application of an antibody-based protein microarray to assess physiological stress in grizzly bears (Ursus arctos).

A novel antibody-based protein microarray was developed that simultaneously determines expression of 31 stress-associated proteins in skin samples collected from free-ranging grizzly bears (Ursus arctos) in Alberta, Canada. The microarray determines proteins belonging to four broad functional categories associated with stress physiology: hypothalamic-pituitary-adrenal axis proteins, apoptosis/cell cycle proteins, cellular stress/proteotoxicity proteins and oxidative stress/inflammation proteins. Small skin samples (50-100 mg) were collected from captured bears using biopsy punches.

Ecotoxicological risks associated with land treatment of petrochemical wastes. III. Immune function and hematology of cotton rats.

Landfarming is a widely used method of treating petrochemical waste through microbial bio-degradation. The effects of residual petrochemical contamination on wildlife, especially terrestrial mammals, are poorly understood. The effects of contaminants on the immune system and hematology of cotton rats (Sigmodon hispidus) living on five abandoned petrochemical landfarms (units 1-5) in Oklahoma were studied.

Ecotoxicological risks associated with land treatment of petrochemical wastes. II. Effects on hepatic phase I and phase II detoxification enzymes in cotton rats.

The purpose of this study was to evaluate possible exposure and resultant hepatic effects of petrochemical waste on cotton rats (Sigmodon hispidus) living on landfarmed sites. Male and female cotton rats were collected in summer, fall, and winter from four landfarm sites and four ecologically similar reference sites. Hepatic methoxyresorufin O-deethylase (MROD) activity was significantly induced in male and female rats collected from landfarms compared to rats collected from reference sites.

Ecotoxicological risks associated with land treatment of petrochemical wastes. I. Residual soil contamination and bioaccumulation by cotton rats (Sigmodon hispidus).

Petrochemical waste contains both organic and inorganic contaminants that can pollute soil and may pose significant ecological risks to wildlife. Petrochemical waste typically is disposed of in land treatment units, which are widespread throughout Oklahoma and the United States. Few studies have been conducted evaluating possible toxicity risks to terrestrial organisms residing on these units.