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PurposeRadiotherapy (RT) constitutes an important part of breast cancer treatment. However, triple negative breast cancers (TNBC) exhibit remarkable resistance to most therapies, including RT. Developing new ways to radiosensitize TNBC cells could result in improved patient outcomes. The M2 isoform of pyruvate kinase (PK-M2) is believed to be responsible for the re-wiring of cancer cell metabolism after oxidative stress. The aim of the study was to determine the effect of ionizing radiation (IR) on PK-M2-mediated metabolic changes in TNBC cells, and their survival. In addition, we determine the effect of PK-M2 activators on breast cancer stem cells, a radioresistant subpopulation of breast cancer stem cells.MethodsGlucose uptake, lactate production, and glutamine consumption were assessed. The cellular localization of PK-M2 was evaluated by western blot and confocal microscopy. The small molecule activator of PK-M2, TEPP46, was used to promote its pyruvate kinase function. Finally, effects on cancer stem cell were evaluated via sphere forming capacity.ResultsExposure of TNBC cells to IR increased their glucose uptake and lactate production. As expected, PK-M2 expression levels also increased, especially in the nucleus, although overall pyruvate kinase activity was decreased. PK-M2 nuclear localization was shown to be associated with breast cancer stem cells, and activation of PK-M2 by TEPP46 depleted this population.ConclusionsRadiotherapy can induce metabolic changes in TNBC cells, and these changes seem to be mediated, at least in part by PK-M2. Importantly, our results show that activators of PK-M2 can deplete breast cancer stem cells in vitro. This study supports the idea of combining PK-M2 activators with radiation to enhance the effect of radiotherapy in resistant cancers, such as TNBC.

Unintentional injury prevention research focuses on parental supervision as critical to reducing toddler injury. We examine how the promotion of childproofing-as a mode of supervision-sells mothers "peace of mind" while also increasing "intensive mothering" and the "privatization of risk." Drawing on the childproofing literature and meaning centered interviews with mothers of toddlers and childproofing business owners, we argue that the connection made by these groups between childproofing and "good parenting" ultimately obscures how this form of harm reduction economically and socially individualizes responsibility for child care.

PurposeThe lack of a molecular target in triple-negative breast cancer (TNBC) makes it one of the most challenging breast cancers to treat. Radiation therapy (RT) is an important treatment modality for managing breast cancer; however, we previously showed that RT can also reprogram a fraction of the surviving breast cancer cells into breast cancer-initiating cells (BCICs), which are thought to contribute to disease recurrence. In this study, we characterize mebendazole (MBZ) as a drug with potential to prevent the occurrence of radiation-induced reprogramming and improve the effect of RT in patients with TNBC.Methods and materialsA high-throughput screen was used to identify drugs that prevented radiation-induced conversion of TNBC cells into cells with a cancer-initiating phenotype and exhibited significant toxicity toward TNBC cells. MBZ was one of the drug hits that fulfilled these criteria. In additional studies, we used BCIC markers and mammosphere-forming assays to investigate the effect of MBZ on the BCIC population. Staining with propidium iodide, annexin-V, and γ-H2AX was used to determine the effect of MBZ on cell cycle, apoptosis, and double-strand breaks. Finally, the potential for MBZ to enhance the effect of RT in TNBC was evaluated in vitro and in vivo.ResultsMBZ efficiently depletes the BCIC pool and prevents the ionizing radiation-induced conversion of breast cancer cells into therapy-resistant BCICs. In addition, MBZ arrests cells in the G2/M phase of the cell cycle and causes double-strand breaks and apoptosis. MBZ sensitizes TNBC cells to ionizing radiation in vitro and in vivo, resulting in improved tumor control in a human xenograft model of TNBC.ConclusionsThe data presented in this study support the repurposing of MBZ as a combination treatment with RT in patients with TNBC.

As unintentional injuries continue to be the leading cause of hospitalization and death for toddlers between the ages of 1 and 4, the Centers for Disease Control has argued that child supervision is a key factor in reducing these injuries and fatalities. This article focuses on the affective relationships in the concept of supervision and practice of watching as an injury prevention method. Three parts frame our argument. First, we describe how watching is an ordinary affect. Second, as part of the ethos of caring, watching is embedded in a temporal frame of anticipation and gives rise to an affectsphere of watching and to a parents' subjectivity as 'good' or 'bad' supervisors. Third, these affective relationships generate seemingly contradictory outcomes wherein children are expected to gain independence and experience injury. The affective qualities of watching provide a critique of the individualizing forces of supervision and an analysis of subjectivities generated by gender and class.

Background: The catastrophic health expenditure and impoverishment indices offer guidance for developing appropriate health policies and intervention programs to decrease financial inequity. This study assesses socioeconomic inequalities in catastrophic health expenditure and impoverishment in relation to self-reported non-communicable diseases (NCD) in urban Hanoi, Vietnam. Methods: A cross-sectional survey was conducted from February to March 2013 in Hanoi, the capital city of Vietnam. We estimated catastrophic health expenditure and impoverishment using information from 492 slum household and 528 non-slum households. We calculated concentration indexes to assess socioeconomic inequalities in catastrophic health expenditure and impoverishment. Factors associated with catastrophic health expenditure and impoverishment were modelled using logistic regression analysis. Results: The poor households in both slum and non-slum areas were at higher risk of experiencing catastrophic health expenditure, while only the poor households in slum areas were at higher risk of impoverishment because of healthcare spending. Households with at least one member reporting an NCD were significantly more likely to face catastrophic health expenditure (odds ratio [OR] = 2.4; 95 % confidence interval [CI], 1.8-4.0) and impoverishment (OR = 2.3; 95 % CI, 1.1-6.3) compared to households without NCDs. In addition, households in slum areas, with people age 60 years and above, and belonging to the poorest socioeconomic group were significantly associated with increased catastrophic health expenditure, while only households that lived in slum areas, and belonging to the poor or poorest socioeconomic groups were significantly associated with increased impoverishment because of healthcare spending. Conclusion: Financial interventions to prevent catastrophic health expenditure and impoverishment should target poor households, especially those with family members suffering from NCDs, with older members and those located in slum areas in Hanoi Vietnam. Potential interventions derived from this study include targeting and monitoring of health insurance enrolment, and developing a specialized NCD service package for Vietnam's social health insurance program. [ABSTRACT FROM AUTHOR]

This study measures and decomposes socioeconomic inequalities in the prevalence of self-reported chronic non-communicable diseases (NCDs) in urban Hanoi, Vietnam. A cross-sectional survey of 1211 selected households was carried out in four urban districts in both slum and non-slum areas of Hanoi city in 2013. The respondents were asked if a doctor or health worker had diagnosed any household members with an NCD, such as cardiovascular diseases, chronic respiratory, diabetes or cancer, during last 12 months. Information from 3736 individuals, aged 15 years and over, was used for the analysis. The concentration index (CI) was used to measure inequalities in self-reported NCD prevalence, and it was also decomposed into contributing factors. The prevalence of chronic NCDs in the slum and non-slum areas was 7.9% and 11.6%, respectively. The CIs show gradients disadvantageous to both the slum (CI = -0.103) and non-slum (CI = -0.165) areas. Lower socioeconomic status and aging significantly contributed to inequalities in the self-reported NCDs, particularly for those living in the slum areas. The findings confirm the existence of substantial socioeconomic inequalities linked to NCDs in urban Vietnam. Future policies should target these vulnerable areas.