RESUMEN
BACKGROUND: Acute myeloid leukemia (AML) is the malignant proliferation of immature myeloid cells characterized by a block in differentiation. As such, novel therapeutic strategies to promote the differentiation of immature myeloid cells have been successful in AML, although these agents are targeted to a specific mutation that is only present in a subset of AML patients. In the current study, we show that targeting the epigenetic modifier enhancer of zeste homolog 2 (EZH2) can induce the differentiation of immature blast cells into a more mature myeloid phenotype and promote survival in AML murine models. METHODS: The EZH2 inhibitor EPZ011989 (EPZ) was studied in AML cell lines, primary in AML cells and normal CD34+ stem cells. A pharmacodynamic assessment of H3K27me3; studies of differentiation, cell growth, and colony formation; and in vivo therapeutic studies including the influence on primary AML cell engraftment were also conducted. RESULTS: EPZ inhibited H3K27me3 in AML cell lines and primary AML samples in vitro. EZH2 inhibition reduced colony formation in multiple AML cell lines and primary AML samples, while exhibiting no effect on colony formation in normal CD34+ stem cells. In AML cells, EPZ promoted phenotypic evidence of differentiation. Finally, the pretreatment of primary AML cells with EPZ significantly delayed engraftment and prolonged the overall survival when engrafted into immunodeficient mice. CONCLUSIONS: Despite evidence that EZH2 silencing in MDS/MPN can promote AML pathogenesis, our data demonstrate that the therapeutic inhibition of EZH2 in established AML has the potential to improve survival.
RESUMEN
BACKGROUND: Menstrual hygiene management plays a significant role in the achievement of sustainable development goals, including good health and well-being, quality education, gender equality, women's empowerment, and sanitation. Even though the United Nations emphasizes menstrual hygiene management as a global public health and human rights issue, studies from different parts of the world have shown there is a lack of policies in this area that affects adolescent girls. OBJECTIVE: The study aimed to assess the menstrual-related knowledge and practices of adolescent girls (10-18 years) attending urban and rural public schools of district Khairpur of province Sindh of Pakistan. DESIGN: This research is an analytical cross-sectional study design. METHODS: Adolescent girls (n = 310), 159 girls from urban and 159 girls from rural schools, were enrolled. Data were collected through self-administered questionnaires. Knowledge was considered satisfactory if the participant scored ⩾12/20, and <12/20 was considered unsatisfactory knowledge. Practice scores were considered good for >10 and poor for <10. Statistical Package for the Social Science (SPSS) version 20.0 was used for data analysis. Descriptive statistics such as mean and standard deviation were calculated. The chi-square test was used to assess and compare the differences between practices and knowledge of menstrual hygiene management between urban and rural adolescent school girls. RESULTS: We found significant differences in menstrual hygiene management among adolescent girls between urban and rural areas. Approximately two-thirds of the total school girls thought that school management had inadequate resources and toilet facilities (rural: 76% versus urban: 62%). The major source of knowledge in adolescent rural and urban girls for menstrual-related matters was mothers. More girls from the urban school (81%) were aware of using sanitary pads during menstruation. The majority of the girls from urban areas showed satisfactory knowledge whereas only 38% of rural girls were shown to have satisfactory results. Nearly 71% of urban girls were found to have good practices when compared with rural girls (12%). CONCLUSION: With further importance by the United Nations on female education in less developed regions, where the health of women is usually given less importance, policies are required on the inclusion of reproductive health of female adolescents in the curriculum.