16 research outputs found
A Novel Homozygous Mutation Affecting Integrin α6 in a Case of Junctional Epidermolysis Bullosa with Pyloric Atresia Detected In Utero by Ultrasound Examination
Naturally occurring mutations in the canine CFTR gene
Naturally occurring cystic fibrosis (CF)-causing mutations in the CFTR gene have not been identified in any nonhuman animal species. Since domestic dogs are known to develop medical conditions associated with atypical CF in humans (e.g., bronchiectasis and pancreatitis), we hypothesized that dogs with these disorders likely have a higher expression rate of CFTR mutations than the at-large population. Temporal temperature-gradient gel electrophoresis (TTGE) was used to screen canine CFTR in 400 animals: 203 dogs diagnosed with pancreatitis, 23 dogs diagnosed with bronchiectasis, and 174 dogs admitted to clinics for any illness (at-large dogs). Twenty-eight dogs were identified with one of four CFTR missense mutations. P1281T and P1464H mutations occur in relatively unconserved residues. R1456W is analogous to the human R1453W mutation, which has âŒ20% of normal CFTR function and is associated with pancreatitis and panbronchiolitis. R812W disrupts a highly conserved protein kinase A recognition site within the regulatory domain. We conclude that naturally occurring CFTR mutations are relatively common in domestic dogs and can be detected with TTGE. No substantive differences in mutation frequency were observed between the at-large, pancreatitis, and bronchiectasis dogs
Gene dosage effect of <i>WEE1</i> on growth and morphogenesis from arabidopsis hypocotyl explants
Background and Aims How plant cell-cycle genes interface with development is unclear. Preliminary evidence from our laboratory suggested that over-expression of the cell cycle checkpoint gene, WEE1, repressed growth and development. Here the hypothesis is tested that the level of WEE1 has a dosage effect on growth and development in Arabidospis thaliana. To do this, a comparison was made of the development of gain- and loss-of-function WEE1 arabidopsis lines both in vivo and in vitro.
Methods Hypocotyl explants from an over-expressing Arath;WEE1 line (WEE1oe), two T-DNA insertion lines (wee1-1 and wee1-4) and wild type (WT) were cultured on two-way combinations of kinetin and naphthyl acetic acid. Root growth and meristematic cell size were also examined.
Key Results Quantitative data indicated a repressive effect in WEE1oe and a significant increase in morphogenetic capacity in the two T-DNA insertion lines compared with WT. Compared with WT, WEE1oe seedlings exhibited a slower cell-doubling time in the root apical meristem and a shortened primary root, with fewer laterals, whereas there were no consistent differences in the insertion lines compared with WT. However, significantly fewer adventitious roots were recorded for WEE1oe and significantly more for the insertion mutant wee1-1. Compared with WT there was a significant increase in meristem cell size in WEE1oe for all three ground tissues but for wee1-1 only cortical cell size was reduced.
Conclusions There is a gene dosage effect of WEE1 on morphogenesis from hypocotyls both in vitro and in vivo.</br
Reasons for delay in time to initiation of adjuvant chemotherapy for colon cancer: A multi-institution study.
Inherited Junctional Epidermolysis Bullosa in the German Pointer: Establishment of a Large Animal Model
Reasons for delay in time to initiation of adjuvant chemotherapy (TTAC) for colon cancer (CC): Analysis from six academic centers in Ontario, Canada.
Exemestane Versus Anastrozole in Postmenopausal Women With Early Breast Cancer: NCIC CTG MA.27âA Randomized Controlled Phase III Trial
PURPOSE
In patients with hormone-dependent postmenopausal breast cancer, standard adjuvant therapy involves 5 years of the nonsteroidal aromatase inhibitors anastrozole and letrozole. The steroidal inhibitor exemestane is partially non-cross-resistant with nonsteroidal aromatase inhibitors and is a mild androgen and could prove superior to anastrozole regarding efficacy and toxicity, specifically with less bone loss.
PATIENTS AND METHODS
We designed an open-label, randomized, phase III trial of 5 years of exemestane versus anastrozole with a two-sided test of superiority to detect a 2.4% improvement with exemestane in 5-year event-free survival (EFS). Secondary objectives included assessment of overall survival, distant disease-free survival, incidence of contralateral new primary breast cancer, and safety.
RESULTS
In the study, 7,576 women (median age, 64.1 years) were enrolled. At median follow-up of 4.1 years, 4-year EFS was 91% for exemestane and 91.2% for anastrozole (stratified hazard ratio, 1.02; 95% CI, 0.87 to 1.18; P = .85). Overall, distant disease-free survival and disease-specific survival were also similar. In all, 31.6% of patients discontinued treatment as a result of adverse effects, concomitant disease, or study refusal. Osteoporosis/osteopenia, hypertriglyceridemia, vaginal bleeding, and hypercholesterolemia were less frequent on exemestane, whereas mild liver function abnormalities and rare episodes of atrial fibrillation were less frequent on anastrozole. Vasomotor and musculoskeletal symptoms were similar between arms.
CONCLUSION
This first comparison of steroidal and nonsteroidal classes of aromatase inhibitors showed neither to be superior in terms of breast cancer outcomes as 5-year initial adjuvant therapy for postmenopausal breast cancer by two-way test. Less toxicity on bone is compatible with one hypothesis behind MA.27 but requires confirmation. Exemestane should be considered another option as up-front adjuvant therapy for postmenopausal hormone receptor-positive breast cancer