The Potential for Targeting AVIL and Other Actin-Binding Proteins in Rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue cancer with a survival rate below 27% for high-risk children despite aggressive multi-modal therapeutic interventions. After decades of research, no targeted therapies are currently available. Therapeutically targeting actin-binding proteins, although promising, has historically been challenging. Recent advances have made this possibility more salient, including our lab's identification of advillin (AVIL), a novel oncogenic actin-binding protein that plays a role in many cytoskeletal functions. AVIL is overexpressed in many RMS cell lines, patient-derived xenograft models, and a cohort of 30 clinical samples of both the alveolar (ARMS) and embryonal (ERMS) subtypes. Overexpression of AVIL in mesenchymal stem cells induces neoplastic transformation both in vitro and in vivo, and reversing overexpression through genetic modulation reverses the transformation. This suggests a critical role of AVIL in RMS tumorigenesis and maintenance. As an actin-binding protein, AVIL would not traditionally be considered a druggable target. This perspective will address the feasibility of targeting differentially expressed actin-binding proteins such as AVIL therapeutically, and how critical cell infrastructure can be damaged in a cancer-specific manner.

The Role of Epstein-Barr Virus in Modulating Key Tumor Suppressor Genes in Associated Malignancies: Epigenetics, Transcriptional, and Post-Translational Modifications.

Epstein-Barr virus (EBV) is ubiquitous and carried by approximately 90% of the world's adult population. Several mechanisms and pathways have been proposed as to how EBV facilitates the pathogenesis and progression of malignancies, such as Hodgkin's lymphoma, Burkitt's lymphoma, nasopharyngeal carcinoma, and gastric cancers, the majority of which have been linked to viral proteins that are expressed upon infection including latent membrane proteins (LMPs) and Epstein-Barr virus nuclear antigens (EBNAs). EBV expresses microRNAs that facilitate the progression of some cancers. Mostly, EBV induces epigenetic silencing of tumor suppressor genes, degradation of tumor suppressor mRNA transcripts, post-translational modification, and inactivation of tumor suppressor proteins. This review summarizes the mechanisms by which EBV modulates different tumor suppressors at the molecular and cellular levels in associated cancers. Briefly, EBV gene products upregulate DNA methylases to induce epigenetic silencing of tumor suppressor genes via hypermethylation. MicroRNAs expressed by EBV are also involved in the direct targeting of tumor suppressor genes for degradation, and other EBV gene products directly bind to tumor suppressor proteins to inactivate them. All these processes result in downregulation and impaired function of tumor suppressors, ultimately promoting malignances.

Knowledge of preeclampsia and its associated factors among pregnant women: a possible link to reduce related adverse outcomes.

BACKGROUND: Pre-eclampsia (PE) is one of the leading causes of maternal morbidity and mortality globally. Adequate knowledge about a disorder contributes greatly to its prevention, control and management. This study assessed the level of knowledge of PE and evaluated the factors associated with knowledge adequacy among pregnant women attending antenatal care at a University Hospital in Kumasi-Ghana. METHODS: This cross-sectional study was conducted at the University Hospital in Kumasi, Ghana. A validated closed-ended questionnaire was used to collect socio-demographic information and history of PE. Knowledge of PE was assessed based on a series of questions regarding the awareness, signs/symptoms, risk factors and complications of PE. Responses were scored percentage-wise and grouped into low (< 60%), moderate (60-80%) and high (80-100%). Knowledge score was then re-stratified into adequate (% score of ≥60%) and inadequate knowledge of PE (% score of < 60%). RESULTS: The prevalence of inadequate and adequate knowledge of PE was 88.6% (mean score = 55.5 ± 4.3%) and 11.4% (mean score = 76.3 ± 5.9%), respectively. For participants with adequate knowledge of PE, 9.1% (mean score = 67.4 ± 6.9%) and 2.3% (mean score = 85.2 ± 5.1%) had moderate and high knowledge, respectively. Using univariate logistic regression models, being older (> 35 years old) [cOR = 3.09, 95%CI (0.88-10.88), p = 0.049] and having a higher level of education (> SHS education) [cOR = 4.45, 95%CI (2.18-9.10), p < 0.0001] were significantly associated with greater odds of having adequate knowledge of PE. After controlling for potential confounders in multivariate logistic regression analysis, we found higher level of education to be independently associated with adequate knowledge of PE [aOR = 2.87, 95%CI (1.31-6.30), p = 0.008]. CONCLUSION: The knowledge of PE among pregnant women in Ghana is low. The prominent factor that facilitates adequacy of knowledge of PE is higher level of education.