Panobinostat Synergizes with Chemotherapeutic Agents and Improves Efficacy of Standard-of-Care Chemotherapy Combinations in Ewing Sarcoma Cells.

The survival rate of patients with Ewing sarcoma (EWS) has seen very little improvement over the past several decades and remains dismal for those with recurrent or metastatic disease. HDAC2, ALK, JAK1, and CDK4 were identified as potential targets using RNA sequencing performed on EWS patient tumors with the bioinformatic analysis of gene expression. The pan-HDAC inhibitor Panobinostat was cytotoxic to all the Ewing sarcoma cell lines tested.

DFMO inhibition of neuroblastoma tumorigenesis.

Background: Most high-risk neuroblastoma patients who relapse succumb to disease despite the existing therapy. We recently reported increased event-free and overall survival in neuroblastoma patients receiving difluoromethylornithine (DFMO) during maintenance therapy. The effect of DFMO on cellular processes associated with neuroblastoma tumorigenesis needs further elucidation.

Assessment of knowledge of malaria and its control practices in mining and sugarcane growing regions of Western Kenya highlands.

Background: Despite upscaled control efforts, deaths and hospitalization due to malaria remained high in counties of western Kenya highlands.

Objectives: This study assessed the knowledge of malaria in two rural communities, the control strategies they use, and their capacity to integrate the available control programs.

Methods: A cross-sectional survey was carried out in two rural villages in November - December 2018.

The burden and types of anaemia among HIV infected, ART-naive injection substance users in Kenya.

Introduction: Illicit substance use and HIV infection cause haematological derangements. Anaemia characterized by a reduction in the quality and quantity erythrocytes is the most common disorder in both HIV-positive persons and illicit substance users.

Objective: To describe anaemia burden, types, and its association with HIV in injectable substance users in Mombasa, Kenya.

Resistance of sensu lato to Pirimiphos-methyl Insecticide in Kakamega County, Highlands of Western Kenya.

Background: Insecticide treated bed nets and Indoor residual spraying remains the principal interventional malaria control strategies. To achieve malaria disease eradication, vector control programmes that monitor insecticide resistance profiles are necessary.

Objective: The study evaluated pirimiphos-methyl susceptibility of sensu lato in Kakamega County, western Kenya.

Interplay between IL-10, IFN-γ, IL-17A and PD-1 Expressing EBNA1-Specific CD4 and CD8 T Cell Responses in the Etiologic Pathway to Endemic Burkitt Lymphoma.

Children diagnosed with endemic Burkitt lymphoma (eBL) are deficient in interferon-γ (IFN-γ) responses to Epstein-Barr Nuclear Antigen1 (EBNA1), the viral protein that defines the latency I pattern in this B cell tumor. However, the contributions of immune-regulatory cytokines and phenotypes of the EBNA1-specific T cells have not been characterized for eBL. Using a bespoke flow cytometry assay we measured intracellular IFN-γ, IL-10, IL-17A expression and phenotyped CD4 and CD8 T cell effector memory subsets specific to EBNA1 for eBL patients compared to two groups of healthy children with divergent malaria exposures.

Correlation of HIV-1 drug resistant mutations and virologic failure.

Introduction: mutations are important by ensuring that the HIV-1 agent remains fit in the environment and evades drugs that are developed purposely to kill them. In Kenya, mutations conferring resistance to available ARVs have been reported in previous studies. However, there is a paucity of information on whether these previous studies have reported all mutations conclusively that confer resistance to available drugs leading to virologic failure.

Abundance and Distribution of Malaria Vectors in Various Aquatic Habitats and Land Use Types in Kakamega County, Highlands of Western Kenya.

Background: Management of malaria transmission relies heavily on vector control. Implementation and sustenance of effective control measures require regular monitoring of malaria vector occurrences, species abundance and distribution. The study assessed mosquito larval species composition, distribution and productivity in Kakamega County, western Kenya.

Human immunodeficiency virus (HIV) type 1 genetic diversity in HIV positive individuals on antiretroviral therapy in a cross-sectional study conducted in Teso, Western Kenya.

Introduction: high HIV-1 infection rates and genetic diversity especially in African population pose significant challenges in HIV-1 clinical management and drug design and development. HIV-1 is a major health challenge in Kenya and causes mortality and morbidity in the country as well as straining the healthcare system and the economy. This study sought to identify HIV-1 genetic subtypes circulating in Teso, Western Kenya which borders the Republic of Uganda.

Clinical laboratory hematology reference values among infants aged 1month to 17 months in Kombewa Sub-County, Kisumu: A cross sectional study of rural population in Western Kenya.

There is an urgent need for reliable region-specific hematological reference values for clinical monitoring. Laboratory reference ranges are important for assessing study participant eligibility, toxicity grading and management of adverse events in clinical trials and clinical diagnosis. Most clinical laboratories in Kenya rely on hematological reference values provided by instrument manufacturers and/or textbooks, which are based on population from Europe or North America.

Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya.

Introduction: in Kenya, about 1.5 million people are living with the Human Immunodeficiency Virus (HIV). Antiretroviral therapy aids in viral suppression.

A Pentavalent Epstein-Barr Virus-Like Particle Vaccine Elicits High Titers of Neutralizing Antibodies against Epstein-Barr Virus Infection in Immunized Rabbits.

Primary infection with Epstein-Barr virus (EBV) is associated with acute infectious mononucleosis, whereas persistent infection is associated with chronic diseases such as autoimmune diseases and various types of cancer. Indeed, approximately 2% of all new cancer cases occurring annually worldwide are EBV-associated. Currently, there is no licensed EBV prophylactic vaccine.

Identification of multiple potent neutralizing and non-neutralizing antibodies against Epstein-Barr virus gp350 protein with potential for clinical application and as reagents for mapping immunodominant epitopes.

Prevention of Epstein-Barr virus (EBV) infection has focused on generating neutralizing antibodies (nAbs) targeting the major envelope glycoprotein gp350/220 (gp350). In this study, we generated 23 hybridomas producing gp350-specific antibodies. We compared the candidate gp350-specific antibodies to the well-characterized nAb 72A1 by: (1) testing their ability to detect gp350 using enzyme-linked immunosorbent assay, flow cytometry, and immunoblot; (2) sequencing their heavy and light chain complementarity-determining regions (CDRs); (3) measuring the ability of each monoclonal antibody (mAb) to neutralize EBV infection in vitro; and (4) mapping the gp350 amino acids bound by the mAbs using competitive cell and linear peptide binding assays.

A multivalent Kaposi sarcoma-associated herpesvirus-like particle vaccine capable of eliciting high titers of neutralizing antibodies in immunized rabbits.

Kaposi sarcoma-associated herpesvirus (KSHV) is an emerging pathogen and the causative agent of multiple cancers in immunocompromised patients. To date, there is no licensed prophylactic KSHV vaccine. In this study, we generated a novel subunit vaccine that incorporates four key KSHV envelope glycoproteins required for viral entry in diverse cell types (gpK8.

Kaposi Sarcoma-Associated Herpesvirus Glycoprotein H Is Indispensable for Infection of Epithelial, Endothelial, and Fibroblast Cell Types.

Kaposi sarcoma-associated herpesvirus (KSHV) is an emerging pathogen and is the causative infectious agent of Kaposi sarcoma and two malignancies of B cell origin. To date, there is no licensed KSHV vaccine. Development of an effective vaccine against KSHV continues to be limited by a poor understanding of how the virus initiates acute primary infection in diverse human cell types.

Malaria and Geohelminthiasis Coinfections in Expectant Women: Effect on Maternal Health and Birth Outcomes in a Malaria Endemic Region in Kenya.

Geohelminthiasis and malaria coinfections in pregnancy are common in sub-Saharan Africa. The consequences of the disease combination on maternal health and birth outcomes are poorly understood. For a better understanding of this coinfection in expectant mothers, a cross-sectional study was carried out to evaluate the effect of the coinfection on maternal health and birth outcomes in expectant mothers in Bungoma County, Kenya.

Interleukin-6 and interleukin-10 gene promoter polymorphisms and risk of endemic Burkitt lymphoma.

Overexpression of interleukin-6 (IL-6) and IL-10 in endemic Burkitt lymphoma (eBL) may facilitate tumorigenesis by providing a permissive cytokine milieu. Promoter polymorphisms influence interindividual differences in cytokine production. We hypothesized that children genetically predisposed for elevated cytokine levels may be more susceptible to eBL.

Sickle cell trait is not associated with endemic Burkitt lymphoma: an ethnicity and malaria endemicity-matched case-control study suggests factors controlling EBV may serve as a predictive biomarker for this pediatric cancer.

Endemic Burkitt lymphoma (eBL) is associated with Epstein-Barr virus (EBV) and Plasmodium falciparum coinfections. Malaria appears to dysregulate immunity that would otherwise control EBV, thereby contributing to eBL etiology. Juxtaposed to human genetic variants associated with protection from malaria, it has been hypothesized that such variants could decrease eBL susceptibility, historically referred to as "the protective hypothesis.

Holoendemic malaria exposure is associated with altered Epstein-Barr virus-specific CD8(+) T-cell differentiation.

Coinfection with Plasmodium falciparum malaria and Epstein-Barr virus (EBV) is a major risk factor for endemic Burkitt lymphoma (eBL), still one of the most prevalent pediatric cancers in equatorial Africa. Although malaria infection has been associated with immunosuppression, the precise mechanisms that contribute to EBV-associated lymphomagenesis remain unclear. In this study, we used polychromatic flow cytometry to characterize CD8(+) T-cell subsets specific for EBV-derived lytic (BMFL1 and BRLF1) and latent (LMP1, LMP2, and EBNA3C) antigens in individuals with divergent malaria exposure.