4-Aminobiphenyl suppresses homologous recombination repair by a reactive oxygen species-dependent p53/miR-513a-5p/p53 loop.

4-Aminobiphenyl (4-ABP), a well-known human carcinogen, can cause oxidative DNA damage and induce miR-513a-5p. However, the interplay between miR-513a-5p and DNA damage remains unclear. In our result of ChIP assay, we speculated that p53 as transcription factor could regulate miR-513a-5p expression. In addition, we found that miR-513a-5p-induced by 4-ABP could suppress p53 expression and HR repair activity. On the other hand, the levels of p53, miR-513a-5p, and γH2AX were attenuated by 5 mM N-acetyl-l-cysteine (NAC) pretreatment, indicating that the reactive oxygen species (ROS)-dependent p53-miR-513a-5p was involved in DSB repair in 4-ABP-treated cells. These findings indicated that the ROS/p53/miR-513a-5p/p53 loop axis plays a relevant role in regulating HR repair which may facilitate our understanding of molecular mechanisms regarding how miR-513a-5p impacts DSB repair in 4-ABP-treated cells.

Toxicity of diuron in HepG2 cells and zebrafish embryos.

Diuron is an herbicide, which is used to control a wide variety of annual and perennial broadleaf, grassy weeds, and mosses. However, the toxicity of diuron in HepG2 cells and zebrafish embryos was unclear. In this study, HpeG2 cells and zebrafish embryos were exposed to different concentrations of diuron for 24 h and 48 h, respectively. Results reveal the diuron caused cytotoxicity and the generation of reactive oxygen species (ROS) in the treated HepG2 cells. The effects of diuron on the expression of catalase and superoxide dismutase (SOD1 and SOD2), an antioxidant enzyme, were investigated. Results showed that only SOD1 was significantly induced after treated diuron 48 h, but the expression of catalase and SOD2 was unaffected. Additionally, the cytotoxicity of diuron was not attenuated in cells pretreated with of N-acetyl-cysteine (NAC), a well-known antioxidant, indicating that oxidative stress could not contribute to cellular death in the treated HepG2 cells. In zebrafish embryos, results from proteomic analysis show that 332 differentially upregulated proteins and 199 down-regulated proteins were detected in the treated embryos (P < 0.05). In addition to the up-regulated antioxidant proteins (prdx3, cat, prdx4, txnrd1, prdx1, sod1, prdx2, and sod2), some decreased proteins were related to cytoskeleton formation, tight junction, and gap junction, which could be related to the malformation of the treated zebrafish embryos. In summary, diuron caused cytotoxicity in HepG2 cells, and the mechanisms of toxicity in zebrafish were addressed using the proteomic analysis.

Effect of eribulin on patients with metastatic breast cancer: multicenter retrospective observational study in Taiwan.

PURPOSE: The aim of this study was to confirm the therapeutic role of eribulin on Taiwanese women with metastatic breast cancer. METHODS: This retrospective study examined 449 females who received eribulin between March 2014 and June 2017 at 14 hospitals in Taiwan for treatment of locally advanced or metastatic breast cancer. RESULTS: The survival rate at 24 months was 57.2% (95% CI 51.0-62.9%) and the median time to treatment failure (TTF) was 3.91 months (95% CI 3.45-3.94). A total of 175 patients (40.1%) received eribulin for fewer than 90 days and the others received it for 90 days or more. Eight patients (1.83%) had complete remission, 82 (18.8%) had partial remission, 202 (46.3%) had stable disease, and 144 (33.0%) had progressive disease (PD). Patients' tumors with the luminal A subtype had a significantly better objective response rate. Kaplan-Meier analysis indicated that hormone receptor positivity, luminal A subtype, receipt of eribulin as the 1st to 3rd line therapy, and metastasis to fewer than 4 organs were significantly associated with longer TTF. Stepwise multivariate analysis showed that only receipt of eribulin as the 1st to 3rd line therapy was significantly associated with TTF (HR 1.49, p < 0.001). All toxicities were manageable and only 18 patients (4.1%) discontinued treatment due to adverse events. CONCLUSIONS: Eribulin appears to have better efficacy and cause fewer adverse events, especially neutropenia, in Taiwanese women than Western women.

Perceived Stress, Parent-Adolescent/Young Adult Communication, and Family Resilience Among Adolescents/Young Adults Who Have a Parent With Cancer in Taiwan: A Longitudinal Study.

BACKGROUND: Family resilience helps family members successfully overcome adversity, for example, chronic disease or unpleasant situations. However, few studies have identified correlates of family resilience among adolescents/young adults having a parent with cancer. OBJECTIVE: This longitudinal study explored (1) relationships among family resilience, adolescents' perceived stress, and parent-adolescent/young adult communication; (2) trends in family resilience with data collection time; and (3) differences in parent-adolescent/young adult communication by parent gender (ie, father or mother). METHODS: Participants were teenagers and young adults (12-25 years) with a parent who had cancer. Data were collected using structured questionnaires at 3 times for 4 to 5 months, with 2 months between each collection. RESULTS: Of 96 adolescent/young adult participants enrolled at T1, only 32 completed all measurements at T3. We found that (1) family resilience was negatively associated with adolescents' perceived stress (B = -0.35) and positively associated with adolescent/young adult communication with both the father (B = 0.58) and the mother (B = 0.36), (2) the degree of family resilience at T3 was significantly lower than at T1 (B = -4.79), and (3) at all 3 data collection times, the degree of adolescent/young adult communication was higher with mothers than with fathers, whether the mother had cancer or did not have cancer. CONCLUSIONS: Family resilience was positively associated with parent-adolescent/young adult communication and negatively related to perceived stress. Family resilience tended to decline with longer parental survival since cancer diagnosis. IMPLICATIONS FOR PRACTICE: We suggest nursing interventions to reduce adolescent/young adult stress and develop optimal parent-adolescent/young adult communication to enhance family resilience.