Genotype-Tailored ERK/MAPK Pathway and HDAC Inhibition Rewires the Apoptotic Rheostat to Trigger Colorectal Cancer Cell Death.

The EGFR/RAS/MEK/ERK signaling pathway (ERK/MAPK) is hyperactivated in most colorectal cancers. A current limitation of inhibitors of this pathway is that they primarily induce cytostatic effects in colorectal cancer cells. Nevertheless, these drugs do induce expression of proapoptotic factors, suggesting they may prime colorectal cancer cells to undergo apoptosis. As histone deacetylase inhibitors (HDACis) induce expression of multiple proapoptotic proteins, we examined whether they could synergize with ERK/MAPK inhibitors to trigger colorectal cancer cell apoptosis. Combined MEK/ERK and HDAC inhibition synergistically induced apoptosis in colorectal cancer cell lines and patient-derived tumor organoids in vitro, and attenuated Apc-initiated adenoma formation in vivo. Mechanistically, combined MAPK/HDAC inhibition enhanced expression of the BH3-only proapoptotic proteins BIM and BMF, and their knockdown significantly attenuated MAPK/HDAC inhibitor-induced apoptosis. Importantly, we demonstrate that the paradigm of combined MAPK/HDAC inhibitor treatment to induce apoptosis can be tailored to specific MAPK genotypes in colorectal cancers, by combining an HDAC inhibitor with either an EGFR, KRASG12C or BRAFV600 inhibitor in KRAS/BRAFWT; KRASG12C, BRAFV600E colorectal cancer cell lines, respectively. These findings identify a series of ERK/MAPK genotype-tailored treatment strategies that can readily undergo clinical testing for the treatment of colorectal cancer.

Mass media exposure and childhood diarrhea: a secondary analysis of the 2011 Bangladesh Demographic and Health Survey.

In order to reduce child mortality, recommendations for diarrhea management practices have been widely promoted by various methods, including mass media. This study examined whether mother's exposure to mass media was associated with child's diarrhea, and with the diarrhea management practiced by their mothers. Data on 7,068 women, whose youngest child was under five years old, were extracted from the Bangladesh Demographic and Health Survey, 2011, together with information on the child. The outcome variables were an episode of diarrhea in the two weeks prior to the survey and diarrhea management practices; exposure to mass media was used as the major explanatory variable. They were descriptively summarized, and logistic regression analyses were performed. Television was found to be the most common form of media. Among 346 children who had experienced an episode of diarrhea in the previous 2 weeks, less than 42.5% were given zinc and only 26.3% of the mothers provided sufficient fluids. No significant associations between mother's mass media exposure and child's diarrhea were observed. Women who read newspapers/magazines were more likely to provide sufficient fluids and food, and those exposed to the radio were more likely to provide zinc supplementation. Since mother's exposure to newspaper/magazines and radio showed associations with some recommended practices for the treatment of childhood diarrhea, mass media clearly has the potential to improve diarrhea management practices. More effective use of mass media is anticipated; in particular, promotion of zinc supplementation and increasing fluid intake during diarrhea, neither of which were currently well practiced.

Perception and attitude of medical doctors in Dhaka, Bangladesh, with regard to Ayurvedic medicine.

The World Health Organization (WHO) Traditional Medicine Strategy (2014-2023) aimed to help member states promote the safe and effective use of traditional medicine. While economic conditions have markedly improved in Bangladesh, the country is experiencing significant public health problems. Because of limited medical resources, there is a strong incentive to enhance complementary and alternative medicine usage in Bangladesh. Therefore, this study aimed to confirm the perceptions and attitudes of medical doctors (MDs) in Dhaka, Bangladesh, with regard to Ayurvedic medicine (AM). A total number of 159 MDs in Dhaka were interviewed by face-to-face between February and June 2015. The study revealed that 62.0% of MDs had treated patients with AM and 55.3% believed that AM should be regarded as its own specialty, whereas 39.7% of MDs believed that AM should be part of the conventional medical curriculum and 32.7% thought that AM did not seem scientific. In terms of gender, 45.3% of male MDs agreed or strongly agreed that AM only had a placebo effect. On the other hand, 65.8% of female MDs disagreed or strongly disagreed it. In terms of age, 77.0% of MDs aged 36 or elder (elder MDs) believed they were more likely to recommend AM use and 80.3% of elder MDs believed that the government should encourage more initiatives to promote AM. To enhance AM use, scientifically robust information on the efficacy, safety and scientific basis of AM should be more effectively conveyed to male MDs.