Cancer cell CCL5 mediates bone marrow independent angiogenesis in breast cancer.

It has recently been suggested that the chemokine receptor (CCR5) is required for bone marrow (BM) derived endothelial progenitor cell (EPC) mediated angiogenesis. Here we show that suppression of either cancer cell produced CCL5, or host CCR5 leads to distinctive vascular and tumor growth defects in breast cancer. Surprisingly, CCR5 restoration in the BM alone was not sufficient to rescue the wild type phenotype, suggesting that impaired tumor growth associated with inhibiting CCL5/CCR5 is not due to defects in EPC biology.

Synthesis and NMDA-receptor affinity of 4-oxo-dexoxadrol derivatives.

A synthesis of novel dexoxadrol analogues is described, which allows modifications of the piperidine substructure. The key step of the synthesis is a hetero Diels-Alder reaction of the imine 12 with Danishefsky's diene 6. After separation of the diastereomeric piperidones 14a and 14b, the relative configuration of the unlike configured piperidone 15b was determined by X-ray crystal structure analysis.

Relationships between the structure of dexoxadrol and etoxadrol analogues and their NMDA receptor affinity.

In the mid 1960s the (dioxolan-4-yl)piperidine derivatives dexoxadrol ((S,S)-1a) and etoxadrol ((S,S,S)-2a) were synthesized. Their pharmacological potential as analgesics, anesthetics and local anesthetics was evaluated in animal models and later on in clinical trials with patients. However, severe side effects including psychotomimetic effects, unpleasant dreams and aberrations stopped the clinical evaluation of dexoxadrol and etoxadrol.

Essential steps and practical applications for database studies.

As the information that is collected from health care encounters becomes more available, managed care pharmacy will have greater insights on the impact of pharmaceutical policy on patient outcomes. Database studies provide valuable information that depicts actual health care consumption and provides a tool to help manage the health care benefit. As compared with clinical trials, one of the strengths of database studies is that they are nonintrusive to patients and providers.