(C) 2009 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.”
“Thromboxane A(2) (TXA(2)) is known to stimulate colonic cancer cell proliferation, although the mechanism

has not been clarified. In this study, we compared the expression levels of Kv7.1 K+ channels between human colorectal cancer tissue and the accompanying non-tumor mucosa. Kv7.1 proteins were found to be consistently up-regulated in the cancer tissues from different patients. Kv7.1 was also expressed in human colonic cancer cell lines. Treatment of colonic cancer cells with 9,11-epithio-11,12-methano-thromboxane A(2) (STA(2)), a stable analogue of TXA(2), GSI-IX significantly increased whole-cell K+ currents sensitive to chromanol 293B, an inhibitor of Kv7.1 channels, in parallel with an increased

expression of Kv7.1 proteins. In contrast, TXB2, an inactive metabolite of TXA(2), had no effects on expression level and function of Kv7.1. A TXA(2) receptor antagonist (SQ29548) and an inhibitor of cAMP-dependent protein kinase (Rp-8-Br-MB-cAMPS) inhibited STA(2)-induced increases in both Kv7.1 expression and chromanol 293B-sensitive K+ currents. Interestingly, STA(2)-stimulated proliferation of colonic cancer cells was inhibited by chromanol 293B. These results suggest that Kv7.1 channels are involved in the TXA(2)-induced cancer cell proliferation and that they are up-regulated by the TXA(2) receptor-mediated cAMP pathway.”
“Mental retardation/intellectual disability is a devastating GW2580 neurodevelopmental disorder with serious impact oil affected individuals and their families, as well as on health and social services. It occurs with a prevalence of similar to 2%, is an etiologically heterogeneous condition, and is frequently the result of genetic aberrations. Autosomal-recessive forms of nonsyndromic MR (NS-ARMR) CYT387 in vivo are believed to be

common, yet only five genes have been identified. We have used homozygosity mapping to search for the gene responsible for NS-ARMR in a large Pakistani pedigree. Using Affymetrix 5.0 single nucleotide polymorphism (SNP) microarrays, we identified a 3.2 Mb region on 8q24 with a continuous run of 606 homozygous SNPs shared among all affected members of the family. Additional genotype data from microsatellite markers verified this, allowing Lis to calculate a two-point LOD score of 5.18. Within this region, we identified a truncating homozygous mutation, R47SX, in exon 7 of the gene TRAPPC9. In a second large NS-ARMR/ID family, previously linked to 8q24 in a study of Iranian families, we identified a 4 bp deletion within exon 14 of TRAPPC9, also segregating with the phenotype and truncating the protein.