The effect Akt2 deletion on tumor development in Pten+/− mice

The serine/threonine kinase Akt is frequently activated in human cancers and is considered an attractive therapeutic target. However, the relative contributions of the different Akt isoforms to tumorigenesis, and the effect of their deficiencies on cancer development are not well understood. We had previously shown that Akt1 deficiency is sufficient to markedly reduce the incidence of tumors in Pten+/− mice. Particularly, Akt1 deficiency inhibits endometrial carcinoma and prostate neoplasia in Pten+/− mice. Here, we analyzed the effect of Akt2 deficiency on the incidence of tumors in Pten+/− mice. Relative to Akt1, Akt2 deficiency had little-to-no effect on the incidence of prostate neoplasia, endometrial carcinoma, intestinal polyps and adrenal lesions in Pten+/− mice. However, Akt2 deficiency significantly decreased the incidence of thyroid tumors in Pten+/−, which correlates with the relatively high level of Akt2 expression in the thyroid. Thus, unlike Akt1 deletion, Akt2 deletion is not sufficient to markedly inhibit tumorigenesis in Pten+/− mice in most tested tissues. The relatively small effect of Akt2 deletion on the inhibition of tumorigenesis in Pten+/− mice could be explained, in part, by an insufficient decrease in total Akt activity, due to the relatively lower Akt2 versus Akt1 expression, and relatively high blood insulin levels in Pten+/−Akt2−/− mice. The relatively high blood insulin levels in Pten+/−Akt2−/− mice may elevate the activity of Akt1, and possibly Akt3, thus, limiting the reduction of total Akt activity and preventing this activity from dropping to a threshold level required to inhibit tumorigenesis

Primary caregivers, healthcare workers, teachers and community leaders' perceptions and experiences of their involvement, practice and challenges of disclosure of HIV status to children living with HIV in Malawi: A qualitative study

Background: The World Health Organisation has recommended that healthcare workers, teachers and community leaders work with parents to support children living with HIV. The aim of this study was to assess the perceptions and experiences of primary caregivers and other care providers such as healthcare workers, teachers, and community leaders regarding their involvement, practice and challenges of HIV disclosure to children aged between 6 and 12 years living with HIV in Malawi. Methods: Twelve focus group discussions and 19 one-on-one interviews involving a total of 106 participants were conducted in all three administrative regions of Malawi. The interviews and focus group discussions explored perceptions and experiences regarding involvement, practice and challenges of disclosure of HIV status to children. Data were analysed using thematic analysis. Results: Primary caregivers, healthcare workers, teachers, and community leaders all reported that the disclosure of HIV status to children was not well coordinated because each of the groups of participants was working in isolation instead of working as a team. A "working together" model emerged from the data analysis where participants expressed the need for them to work as a team in order to promote safe and effective HIV status disclosure through talking about HIV, sharing responsibility and open communication. Participants reported that by working together, the team members would ensure that the prevalence of HIV disclosure to young children increases and that there would be a reduction in any negative impact of disclosure. Conclusion: Global resources are required to better support children living with HIV and their families. Healthcare workers and teachers would benefit greatly from training in working together with families living with HIV and, specifically, training in the disclosure process. Resources, in the form of books and other educational materials, would help them explain HIV and its effective management to children and families