Purpose: Little is known about the definitive course of the tendinous intersections from anterior to posterior through the rectus abdominis (RA) muscle. The implications of a full thickness intersection may have effects on the ability to neurotize the RA. We hypothesized that these tendinous inscriptions would be fully adherent to the anterior rectus sheath, but there would be an incomplete penetrance into the posterior surface, thereby allowing for muscle fibers and neurovascular structures to run the entire course of the RA muscle.
View Article and Find Full Text PDFHigh-affinity, functionally potent, urea-based antagonists of CCR1 have been discovered. Modulation of PXR transactivation has revealed the selective and orally bioavailable CCR1 antagonist BMS-817399 (29), which entered clinical trials for the treatment of rheumatoid arthritis.
View Article and Find Full Text PDFA series of compounds which exhibited good human CCR1 binding and functional potency was modified resulting in the discovery of a novel series of high affinity, functionally potent antagonists of the CCR1 receptor. Issues of PXR activity, ion-channel potency, and poor metabolic stability were addressed by the addition of a hydroxyl group to an otherwise lipophilic area in the molecule resulting in the discovery of preclinical candidate BMS-457 for the treatment of rheumatoid arthritis.
View Article and Find Full Text PDFBioorg Med Chem Lett
February 2007
We have identified and synthesized a series of diaryl substituted pyrazoles as potent antagonists of the chemokine receptor subtype 2. Structure-activity relationship studies directed toward improving the potency led to the discovery of 23 (IC50 = 6 nM).
View Article and Find Full Text PDFObjective: Antibodies to CA 125 have been used to predict relapse of ovarian cancer, but have performed poorly as therapeutic agents. One rationale for this is antibody binding to circulating shed antigen. Our aim in this study was to develop antibodies to human CA 125 that have enhanced selectivity for the cell-associated form of the antigen.
View Article and Find Full Text PDFThere is considerable interest in developing immunotherapeutic approaches to elicit tumor-specific CTL responses in cancer patients. Epitope-based approaches aim to deliver the antigenic peptides or epitopes recognized by CTLs rather than the intact tumor antigen. Many tumor-associated proteins are nonmutated self proteins for which the dominant peptide epitopes are usually poorly immunogenic.
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