Basal-like breast cancers form a distinct subtype of breast cancer characterized by the expression of markers expressed in normal basal/myoepithelial cells. Breast cancers arising in carriers of germline BRCA1 mutations are predominately of basal-like type, suggesting that BRCA1 dysfunction may play a role in the pathogenesis of sporadic basal-like cancers. We analysed 37 sporadic breast cancers expressing the basal marker cytokeratin 5/6, and age-and grade-matched controls, for downregulation of BRCA1. Although BRCA1 promoter methylation was no more common in basal-like cancers (basal 14% vs controls 11%, P ¼ 0.72), BRCA1 messenger RNA expression was twofold lower in basal-like breast cancers compared to matched controls (P ¼ 0.008). ID4, a negative regulator of BRCA1, was expressed at 9.1-fold higher levels in basal-like breast cancer (Po0.0001), suggesting a potential mechanism of BRCA1 downregulation. BRCA1 downregulation correlated with the presence of multiple basal markers, revealing heterogeneity in the basal-like phenotype. Finally, we found that 63% of metaplastic breast cancers, a rare type of basal-like cancers, had BRCA1 methylation, in comparison to 12% of controls (Po0.0001). The high prevalence of BRCA1 dysfunction identified in this study could be exploited in the development of novel approaches to targeted treatment of basal-like breast cancer.
During 1977 a survey was undertaken by practising veterinary surgeons of the incidence of different lesions causing lameness in dairy cattle. Forty-eight veterinary practices participated and they treated 7526 cases of lameness in 1821 herds. The average incidence of lameness among all cows was 5.5 per cent and the annual incidence among practices ranged from 1.8 to 11.8 per cent. Most lesions (88.3 per cent) occurred in the feet; the commonest were foul of the foot (16.7 per cent), white line abscess (15.6 per cent), sole ulcer (13.6 per cent), punctured sole and pus (10.4 per cent) and underrun heel (8.7 per cent). These proportions varied in different parts of the country. Eighty-four per cent of foot lesions occurred in the hind feet and of these lesions 85 per cent occurred in the outer claw; 42 per cent of foot lesions occurred in abnormally shaped claws. The remaining 11.7 per cent of lesions occurred in the legs and trunk, 76 per cent of which occurred in the hindlimb. Trauma was the main cause of leg lesions, which occurred most frequently in the joints and ligaments.
One thousand, four hundred and ninety-one lactations in 770 Friesian, Holstein and Ayrshire crossbred cows have been used to study the associations between lameness and fertility. Lameness was associated with a longer interval between calving and first service and a longer interval between calving and conception. The largest increases in these intervals, of 17 and 30 days, respectively, occurred in cows with either sole or white line lesions occurring between 36 and 70 days after calving. The conception rate during the 63 days before a diagnosis of lameness was made was lower (31 per cent) than at other times (40 per cent).
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.