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Darryl R Peterson

Publications and source records attributed to Darryl R Peterson.

4 recordsLinked to original sources
PubMed2004

Bone marrow chemoprotection without compromise of chemotherapy efficacy in a rat brain tumor model.

Thiol chemoprotective agents can reduce chemotherapy side effects, but clinical use is limited due to concerns of impaired chemotherapeutic efficacy. We evaluated whether an optimized bone marrow chemoprotection regimen impaired the efficacy of enhanced chemotherapy against rat brain tumors. Nude rats with intracerebral human lung carcinoma xenografts were treated with carboplatin, melphalan, and etoposide phosphate delivered intra-arterially with osmotic blood-brain barrier disruption (n = 8/group). Thiol chemoprotection was N-acetyl-L-cysteine (1000 mg/kg) 60 min before chemotherapy and/or sodium thiosulfate (8 g/m(2)) 4 and 8 h after chemotherapy, when the blood-brain barrier is reestablished. Blood counts were obtained before treatment on day 3 and at sacrifice on day 9. N-acetylcysteine serum clearance half-life was 9 to 11 min. Pretreatment with N-acetylcysteine combined with delayed administration of sodium thiosulfate protected against toxicity toward total white cells, granulocytes, and platelets (P = 0.0016). Enhanced chemotherapy reduced intracerebral tumor volume to 4.3 +/- 1.0 mm(3) compared with 29.1 +/- 4.1 mm(3) in untreated animals (P < 0.0001). Tumor volume was 3.7 +/- 0.6 mm(3) in rats that received N-acetylcysteine before and sodium thiosulfate after chemotherapy. The data indicate the efficacy of enhanced chemotherapy for rat brain tumors was not affected by thiol chemoprotection that provided excellent protection for hematological toxicity. Negative interactions of thiols with antitumor efficacy were avoided by temporal and spatial separation of chemoprotectants and chemotherapy.

Acetylcysteine↗
PubMed2002

The complementary membranes forming the blood-brain barrier.

Brain capillary endothelial cells form the blood-brain barrier. They are connected by extensive tight junctions, and are polarized into luminal (blood-facing) and abluminal (brain-facing) plasma membrane domains. The polar distribution of transport proteins allows for active regulation of brain extracellular fluid. Experiments on isolated membrane vesicles from capillary endothelial cells of bovine brain demonstrated the polar arrangement of amino acid and glucose transporters, and the utility of such arrangements have been proposed. For instance, passive carriers for glutamine and glutamate have been found only in the luminal membrane of blood-brain barrier cells, while Na-dependent secondary active transporters are at the abluminal membrane. This organization could promote the net removal of nitrogen-rich amino acids from brain, and account for the low level of glutamate penetration into the central nervous system. Furthermore, the presence of a gamma-glutamyl cycle at the luminal membrane and Na-dependent amino acid transporters at the abluminal membrane may serve to modulate movement of amino acids from blood-to-brain. Passive carriers facilitate amino acid transport into brain. However, activation of the gamma-glutamyl cycle by increased plasma amino acids is expected to generate oxoproline within the blood-brain barrier. Oxoproline stimulates secondary active amino acid transporters (Systems A and B(o)+) at the abluminal membrane, thereby reducing net influx of amino acids to brain. Finally, passive glucose transporters are present in both the luminal and abluminal membranes of the blood-brain barrier. Interestingly, a high affinity Na-dependent glucose carrier has been described only in the abluminal membrane. This raises the question whether glucose entry may be regulated to some extent. Immunoblotting studies suggest more than one type of passive glucose transporter exist in the blood-brain barrier, each with an asymmetrical distribution. In conclusion, it is now clear that the blood-brain barrier participates in the active regulation of brain extracellular fluid, and that the diverse functions of each plasma membrane domain contributes to these regulatory functions.

Ammonia↗
PubMed2002

Targeted delivery in primary and metastatic brain tumors: summary report of the seventh annual meeting of the Blood-Brain Barrier Disruption Consortium.

The November 2000 NIH report of the Brain Tumor Progress Review Group identified delivering and targeting therapeutic agents as a priority in the treatment of malignant brain tumors. For this reason, the seventh annual Blood-Brain Barrier Disruption Consortium meeting, partially funded by an NIH R13 Grant, focused on recent advances in targeted delivery to the central nervous system, clinical trials for primary and metastatic brain tumors using enhanced chemotherapy delivery, and strategies to lessen the toxicities associated with dose intensive treatments, using thiols.

Antineoplastic Agents↗