bioRxiv Science⌕ Search

Biology subjects

Awah, C.

Publications and source records attributed to Awah, C..

2 recordsLinked to original sources

Destabilized 3UTR ARE therapeutically degrades ERBB2 in drug-resistant ERBB2+ cancer models

Breast, lung, and colorectal cancer resistance to molecular targeted therapy is a major challenge and unfavorably impacts clinical outcomes, leading to hundreds of thousands of deaths yearly. In ERBB2+ cancers regardless of the tissue of origin, ERBB2 is the driver oncogene of resistance. We discovered that the ERBB2+ cancers are enriched with poly U sequences on their 3UTR AU rich elements which are mRNA stabilizing sequences. We developed a novel technology, in which we engineered these ERBB2 mRNA stabilizing sequences to unstable forms and specifically controlled and degraded ERBB2 transcript and protein across multiple cancer types both in the wildtype and drug resistance settings in vitro and in vivo, offering a unique novel modality to control ERBB2 and other pervasive oncogenic signals where other therapies fail. One-Sentence SummaryEngineered destabilized 3UTR ARE of ERBB2 degrades ERBB2 in many cancer types and controlled resistance. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=163 SRC="FIGDIR/small/503914v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@139d8dborg.highwire.dtl.DTLVardef@cc1fd3org.highwire.dtl.DTLVardef@13d9086org.highwire.dtl.DTLVardef@db69bf_HPS_FORMAT_FIGEXP M_FIG A. Depiction represents multiple ERBB2 expressing cancer cells with stable 3UTR ARE and the signaling cascade known to cause chemo resistance. B. Depiction of the engineered destabilized 3UTR ARE of ERBB2 and the destabilization and degradation of the ERBB2 transcript, protein and kinases involved in mediation of drug resistance C_FIG

cancer biology↗

An integrated approach to assess Knowledge, Attitude and Practices (KAP) regarding major Neglected Tropical Diseases endemic in the Mbengwi health district (North West Region, Cameroon)

BackgroundPreventive chemotherapy (PCT) is the main strategy currently used to control and/or eliminate onchocerciasis (Oncho), lymphatic filariasis (LF) and Soil Transmitted Helminthiasis (STH), and community participation (through implementation of MDA or adherence to PCT) is critical to achieve this goal. However, these Neglected Tropical Diseases (NTDs) are still persisting in most endemic areas as a consequence of sub-optimal treatment coverage, the presence of systematic non-compliers in communities ... This study aimed at investigating whether the knowledge, attitudes and practices of populations about these NTDs can explain the poor trends towards elimination.\n\nMethodologyA cross-sectional survey was carried out in the Mbengwi Health District (North West Region, Cameroon) using the cluster sampling technique. Clusters were selected using the Probability Proportionate to Estimate Size strategy. In each cluster, the random walk technique was used for the selection of households, and a structure questionnaire was administered to 2-3 of its members.\n\nPrincipal FindingsA total of 254 households from 26 clusters were visited, and 514 individuals were interviewed. The sex ratio of interviewees (1.08) was unbiased, and their ages ranged between 10 and 99 years old. Though most of the respondents declared having already heard of these NTDs (41.2%, 73.7% and 89.9% for Oncho, LF and STH respectively), only a minority of them were aware of correct response of how they are acquired/transmitted (3.7%, 6.8% and 12.5% for Oncho, LF and STH respectively), and prevented (23.1%, 18.9% and 47.2% for Oncho, LF and STH respectively). Even when respondents were aware that medicines were useful to prevent and/or treat these NTDs, almost none of them knew the drug used or the treatment frequency.\n\nConclusion/SignificanceThis study reveals that interviewees exhibit poor knowledge, attitudes and practices as regards to these NTDs, although they are endemic in the study area and PCTs given yearly since a while. These misconceptions can seriously affect the adherence and contribution of populations to the success of PCTs, and it appears compulsory to improve individual knowledge, with a focus on the importance and rationale behind MDA, to optimize their attitudes and practices, especially community participation to PCTs.\n\nAuthor summaryThe control and/or elimination of Neglected Tropical Diseases (NTDs) are currently on top of the agenda of endemic countries control programs and stakeholders. Ivermectin- and Albendazole/Mebendazole-based mass distribution is currently the main strategy to control/interrupt transmission of onchocerciasis, lymphatic filariasis and soil-transmitted helminthiasis, and adherence of communities is compulsory for the success of this approach. Despite the success registered in the fight against these diseases, the trend towards elimination remains unsatisfactory in many endemic areas. This study was carried out to assess whether the perceptions, attitudes, and practices of the Mbengwi health district (North West Region, Cameroon) populations regarding these three parasitic diseases can explain the poor trend towards elimination. A cross-sectional study revealed important misconceptions about these NTDs amongst most of the respondents, which can clearly affect their adherence and contribution to the success of preventive chemotherapies, and seriously slower the momentum towards elimination.

epidemiology↗