Expression of DNA Damage Response Proteins and Associations with Clinicopathologic Characteristics in Chinese Familial Breast Cancer Patients with BRCA1/2 Mutations / 한국유방암학회지

PURPOSE: The characteristic expression of DNA damage response proteins in familial breast cancers with BRCA1, BRCA2, or non-BRCA1/2 mutations has not been analyzed in Chinese patients. Our study aimed to assess the differential expression of microcephalin 1 (BRIT1), ATM serine/threonine kinase (ATM), checkpoint kinase 2 (CHEK2), BRCA1, RAD51 recombinase (RAD51), and poly (ADP-ribose) polymerase 1 (PARP-1) and establish the profile of Chinese familial breast cancers with different mutation status. METHODS: We constructed five tissue microarrays from 183 familial breast cancer patients (31 with BRCA1 mutations; 14 with BRCA2 mutations, and 138 with non-BRCA1/2 mutations). The DNA response and repair markers used for immunohistochemistry analysis included BRIT1, ATM, CHEK2, BRCA1, RAD51, and PARP-1. The expressions of these proteins were analyzed in BRCA1/2 mutated tumors. The association between pathologic characteristics with BRCA1/2 mutation status was also analyzed. RESULTS: In familial breast cancer patients, BRCA1 mutated tumors were more frequent with high nuclear grade, estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2 negative, low Ki-67, and positive CK5/6. BRCA1 mutated tumors had lower CHEK2 and higher cytoplasmic BRIT1 expression than BRCA2 and non-BRCA1/2 mutation tumors. BRCA2-associated tumors showed higher CHEK2 and cytoplasmic RAD51 expression than those in other groups. Nuclear PARP-1 expression in BRCA1/2-associated tumors was significantly higher than in non-BRCA1/2 mutation tumors. Moreover, we found quite a few of negative PARP-1 expression cases in BRCA1/2 mutated groups. CONCLUSION: The clinicopathologic findings of BRCA1-associated Chinese familial breast cancers were similar to the results of other studies. Chinese familial breast cancer patients with BRCA1/2 mutations might have distinctive expression of different DNA damage response proteins. The reduced expression of PARP-1 in Chinese BRCA1/2 mutated breast cancer patients could influence the therapeutic outcome of PARP-1 inhibitors.

Effects of 20-minute warm ischemia on coronary endothelial function of pig donor hearts after cardiac death / 中国组织工程研究

BACKGROUND:Myocardial and coronary endothelial injury occurs in donor hearts due to warm ischemia during cardiac transplantation. Coronary endothelial structure and function play a critical role in long-term outcomes for patients after cardiac transplantation. OBJECTIVE:To study the effect of hypoxia-induced warm ischemia (20 minutes) on coronary endothelial function of porcine donor hearts after cardiac death (DCD). METHODS:Sixteen healthy Swedish domestic pigs were randomized into control (n=6), DCD (n=5), and DCD plus cold storage (n=5) groups, respectively. A DCD model in pigs was established using the method of hypoxia-induced 20-minute warm ischemia in the DCD and DCD plus cold storage groups. Isolation of the heart left anterior descending coronary artery or combined with heart preservation pretreatment for 4 hours was performed in the DCD and DCD plus cold storage groups. The maximum coronary endothelium-dependent relaxation was determined in the three groups. RESULTS AND CONCLUSION:There were no significant differences in the maximum coronary endothelium-dependent relaxation and the minus logarithmic of substance concentration induced 50%maximal relaxation among three groups (P>0.05). These results indicate that 20-minute warm ischemia cannot lead to obvious coronary endothelial dysfunction. In addition, DCD combined with 4-hour cold storage does not affect coronary endothelial function.