Anti-Claudin-2 Antibody-Drug Conjugates for the Treatment of Colorectal Cancer Liver Metastasis.

We have previously demonstrated that Claudin-2 is required for colorectal cancer (CRC) liver metastasis. The expression of Claudin-2 in primary CRC is associated with poor survival and highly expressed in liver metastases. Claudin-2 also promotes breast cancer liver metastasis by enabling seeding and cancer cell survival.

Functional genomics of the rat neuromedin U receptor 1 reveals a naturally occurring deleterious allele.

Neuromedin U (NMU) plays an important role in a number of physiological processes, but the relative contribution of its two known receptors, NMUR1 and NMUR2, is still poorly understood. Here we report the existence of a SNP T(1022)→A (Val(341)→Glu) in the third exon of the rat Nmur1 gene that leads to an inactive receptor. This SNP is present within the coding region of the highly conserved NPXXY motif found within all class A type G protein-coupled receptors and translates to an NMUR1 receptor that is not expressed on the cell surface.

Biochemical characterization and in vitro activity of AZ513, a noncovalent, reversible, and noncompetitive inhibitor of fatty acid amide hydrolase.

Fatty acid amide hydrolase (FAAH) hydrolyzes several bioactive lipids including the endocannabinoid anandamide. Synthetic FAAH inhibitors are being generated to help define the biological role(s) of this enzyme, the lipids it degrades in vivo, and the disease states that might benefit from its pharmacological modulation. AZ513 inhibits human FAAH (IC(50)=551 nM), is 20-fold more potent against rat FAAH (IC(50)=27 nM), and is inactive at 10 μM against the serine hydrolases acetylcholinesterase, thrombin, and trypsin.

Distribution of the voltage-gated sodium channel Na(v)1.7 in the rat: expression in the autonomic and endocrine systems.

It is generally accepted that the voltage-gated, tetrodotoxin-sensitive sodium channel, Na(V)1.7, is selectively expressed in peripheral ganglia. However, global deletion in mice of Na(V)1.

A stop codon mutation in SCN9A causes lack of pain sensation.

The general lack of pain experience is a rare occurrence in humans, and the molecular causes for this phenotype are not well understood. Here we have studied a Canadian family from Newfoundland with members who exhibit a congenital inability to experience pain. We have mapped the locus to a 13.