Fusion Genes in Prostate Cancer: A Comparison in Men of African and European Descent.

Prostate cancer is one of the most prevalent cancers worldwide, particularly affecting men living a western lifestyle and of African descent, suggesting risk factors that are genetic, environmental, and socioeconomic in nature. In the USA, African American (AA) men are disproportionately affected, on average suffering from a higher grade of the disease and at a younger age compared to men of European descent (EA). Fusion genes are chimeric products formed by the merging of two separate genes occurring as a result of chromosomal structural changes, for example, inversion or trans/cis-splicing of neighboring genes.

A Systems Approach to Interrogate Gene Expression Patterns in African American Men Presenting with Clinically Localized Prostate Cancer.

An emerging theory about racial differences in cancer risk and outcomes is that psychological and social stressors influence cellular stress responses; however, limited empirical data are available on racial differences in cellular stress responses among men who are at risk for adverse prostate cancer outcomes. In this study, we undertook a systems approach to examine molecular profiles and cellular stress responses in an important segment of African American (AA) and European American (EA) men: men undergoing prostate biopsy. We assessed the prostate transcriptome with a single biopsy core via high throughput RNA sequencing (RNA-Seq).

Vitamin D binding protein polymorphisms significantly impact vitamin D status in children.

Background: Polymorphic alleles of the vitamin D (vitD)-binding protein (VDBP) gene are associated with discriminatory differences in circulating concentrations of 25-hydroxyvitamin D (25-D), the indicator of vitD status (sufficiency defined by the Endocrine Society as ≥75 nmol/L). Within a diverse group of children, we hypothesized that reaching recommended daily allowance (RDA) of vitD intake would have differential impact on vitD status depending on VDBP variability.

Methods: VDBP alleles (Gc1S, Gc1F, Gc2) in 123 children (1-4 annual visits/child; ages 1-8 years) were compared for relationships with serum 25-D concentrations and daily vitD intake.

Discordance in perceived risk and epidemiological outcomes of prostate cancer among African American men.

As guidelines for prostate cancer screening have changed from an annual screening recommendation starting at age 50 to discussing the benefits and harms of screening with health care providers, it is necessary to examine other types of factors that are important to prostate cancer screening decisions among African American men. Perceived risk of developing cancer has been shown to predict cancer control behaviors and is lower among African Americans. We characterized perceived risk of developing prostate cancer among African American men from November 2009 to 2011 and evaluated the relationship between prostate cancer risk perceptions and sociodemographic characteristics, health care experiences, and knowledge and exposure to health information about cancer.

Restoration of Immune Responsiveness to Glioma by Vaccination of Mice with Established Brain Gliomas with a Semi-Allogeneic Vaccine.

Prior studies had shown the clinical efficacy of a semi-allogeneic glioma vaccine in mice with lethal GL261 gliomas. This was confirmed in the present study. As subcutaneous vaccination resulted in protection against tumor in the brain, the present study assessed the impact of this vaccination of mice bearing established GL261 brain gliomas on their cytokine production upon in vitro exposure to tumor-derived products.

Systems analysis of the prostate transcriptome in African-American men compared with European-American men.

Aim: African-Americans (AA) have increased prostate cancer risk and a greater mortality rate than European-Americans (EA). AA exhibit a high prevalence of vitamin D deficiency. We examined the global prostate transcriptome in AA and EA, and the effect of vitamin D supplementation.

A therapeutic cancer vaccine against GL261 murine glioma.

Background: Glioblastoma (GBM) is the deadliest of brain tumors. Standard treatment for GBM is surgery, followed by combined radiation therapy and chemotherapy. Current therapy prolongs survival but does not offer a cure.

Ever and Annual Use of Prostate Cancer Screening in African American Men.

Since prostate cancer continues to disproportionately affect African American men in terms of incidence, morbidity, and mortality, prostate-specific antigen (PSA) screening plays an important role in early detection, especially when men engage in informed decision making to accept or decline this test. The authors evaluated utilization of PSA testing among African American men based on factors that are important components of making informed decisions. Utilization of PSA testing was evaluated based on whether men had ever had PSA testing and PSA testing during the past year in a community-based sample of African American men ages 50 to 75 ( n = 132).

Dietary supplementation of GrandFusion(®) mitigates cerebral ischemia-induced neuronal damage and attenuates inflammation.

Objectives: Dietary supplementation of fruits and vegetables has been the main stay for nutritional benefit and overall well-being. GrandFusion(®) is a nutritional supplement that contains the natural nutrients from whole fruits and vegetables that include complex nutrients and phytonutrients that contain anti-oxidant, anti-inflammatory, and neuroprotective properties.

Methods: In this study, C57BL/6 mice were fed a diet supplemented with GrandFusion(®) for 2 months prior to 1 hour of ischemia induced by occlusion of the middle cerebral artery (MCAo) followed by various times of reperfusion.

Vitamin D3 supplementation, low-risk prostate cancer, and health disparities.

Vitamin D promotes the differentiation of prostate cancer cells, raising the possibility that vitamin D deficiency over time may contribute to the progression from subclinical prostate cancer to clinical disease. Since low-risk prostate cancers are monitored over time in an effort to determine which progress into clinically important, more aggressive cancers, they provide an excellent model in which to study, over an extended period of time, the effects of enhancing vitamin D status and related changes in tumor progression. This is particularly relevant to African-American men, who exhibit a high prevalence of vitamin D deficiency as well as higher incidence of prostate cancer and higher mortality rates from prostate cancer than Caucasians.

Vitamin D3 supplementation (4000 IU/d for 1 y) eliminates differences in circulating 25-hydroxyvitamin D between African American and white men.

Background: African Americans suffer disproportionately from diabetes and cardiovascular disease and are significantly more likely to have suboptimal concentrations of circulating 25-hydroxyvitamin D [25(OH)D]. The results of epidemiologic and observational studies suggest that there is a link between vitamin D deficiency and the risk of cardiometabolic disorders, which underscores the importance of maintaining healthy concentrations of 25(OH)D.

Objective: The objective was to investigate whether daily supplementation with 4000 IU vitamin D(3) for 1 y would eliminate any disparities in circulating concentrations of 25(OH)D between African American and white men.

Vitamin D3 supplementation at 4000 international units per day for one year results in a decrease of positive cores at repeat biopsy in subjects with low-risk prostate cancer under active surveillance.

Context: We wanted to investigate vitamin D in low-risk prostate cancer.

Objectives: The objective of the study was to determine whether vitamin D(3) supplementation at 4000 IU/d for 1 yr is safe and would result in a decrease in serum levels of prostate-specific antigen (PSA) or in the rate of progression.

Design: In this open-label clinical trial (Investigational New Drug 77,839), subjects were followed up until repeat biopsy.

Protective effects of incensole acetate on cerebral ischemic injury.

The resin of Boswellia species is a major anti-inflammatory agent that has been used for centuries to treat various conditions including injuries and inflammatory conditions. Incensole acetate (IA), a major constituent of this resin, has been shown to inhibit NF-κB activation and concomitant inflammation, as well as the neurological deficit following head trauma. Here, we show that IA protects against ischemic neuronal damage and reperfusion injury in mice, attenuating the inflammatory nature of ischemic damage.

Vitamin D3-enriched diet correlates with a decrease of amyloid plaques in the brain of AβPP transgenic mice.

In addition to its function in calcium and bone metabolism, vitamin D is neuroprotective and important for mitigating inflammation. Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the central nervous system, characterized by neuronal loss in many areas of the brain, and the formation of senile (neuritic) plaques, which increase in number and size over time. The goal of this project was to investigate whether vitamin D3 supplementation would affect amyloid plaque formation in amyloid-β protein precursor (AβPP) transgenic mice that spontaneously develop amyloid plaques within 3-4 months of birth.

Transcranial laser therapy attenuates amyloid-β peptide neuropathology in amyloid-β protein precursor transgenic mice.

Transcranial laser therapy (TLT) was tested for efficacy in a mouse model of Alzheimer's disease (AD) using a near-infrared energy laser system. TLT is thought to stimulate ATP production, increase mitochondrial activity, and help maintain neuronal function. Studies were performed to determine the effect of TLT in an amyloid-β protein precursor (AβPP) transgenic mouse model.

The impact of methylmercury on 1,25-dihydroxyvitamin D3-induced transcriptomic responses in dolphin skin cells.

The Atlantic bottlenose dolphin has been the focus of much attention owing to the considerable impact of environmental stress on its health and the associated implications for human health. Here, we used skin cells from the dolphin to investigate the protective role of the vitamin D pathway against environmental stressors. We previously reported that dolphin skin cells respond to 1,25-dihydroxyvitamin D3 (1,25D3), the bioactive metabolite of vitamin D3, by upregulation of the vitamin D receptor (VDR) and expression of several genes.

The vitamin D3 transcriptomic response in skin cells derived from the Atlantic bottlenose dolphin.

The Atlantic bottlenose dolphin has attracted attention due to the evident impact that environmental stressors have taken on its health. In order to better understand the mechanisms linking environmental health with dolphin health, we have established cell cultures from dolphin skin as in vitro tools for molecular evaluations. The vitamin D3 pathway is one mechanism of interest because of its well established chemopreventative and immunomodulatory properties in terrestrial mammals.

Semi-allogeneic vaccines and tumor-induced immune tolerance.

Experimental results from studies with inbred mice and their syngeneic tumors indicated that the inoculation of semi-allogeneic cell hybrids (derived from the fusion between syngeneic tumor cells and an allogeneic cell line) protects the animal host from a subsequent lethal challenge with unmodified syngeneic tumor cells. Semi-allogeneic somatic cell hybrids were generated by the fusion of EL-4 T lymphoma cells (H-2b) and BALB/c-derived renal adenocarcinoma RAG cells (H-2d). Cell hybrids were injected intra-peritoneally (i.

Semi-allogeneic vaccine for T-cell lymphoma.

Background: Experimental results from studies with inbred mice and their syngeneic tumors indicated that the inoculation of semi-allogeneic cell hybrids (derived from the fusion between syngeneic tumor cells and an allogeneic cell line) protects the animal host from a subsequent lethal challenge with unmodified syngeneic tumor cells.

Methods: Semi-allogeneic somatic cell hybrids were generated by the fusion of EL-4 T lymphoma cells (H-2b) and BALB/c-derived renal adenocarcinoma RAG cells (H-2d). Cell hybrids were injected intra-peritoneally (i.

A dolphin peripheral blood leukocyte cDNA microarray for studies of immune function and stress reactions.

A microarray focused on stress response and immune function genes of the bottlenosed dolphin has been developed. Random expressed sequence tags (ESTs) were isolated and sequenced from two dolphin peripheral blood leukocyte (PBL) cDNA libraries biased towards T- and B-cell gene expression by stimulation with IL-2 and LPS, respectively. A total of 2784 clones were sequenced and contig analysis yielded 1343 unigenes (archived and annotated at ).

Establishment of epidermal cell lines derived from the skin of the Atlantic bottlenose dolphin (Tursiops truncatus).

The Atlantic bottlenose dolphin (Tursiops truncatus), a marine mammal found off the Atlantic coast, has become the focus of considerable attention because of an increasing number of mortality events witnessed in this species over the last several years along the southeastern United States. Assessment of the impact of environmental stressors on bottlenose dolphins (BND) has been difficult because of the protected status of these marine mammals. The studies presented herein focused on establishing epidermal cell cultures and cell lines as tools for the in vitro evaluation of environmental stressors on BND skin.

Cross-reactivity between HLA-A2-restricted FLU-M1:58-66 and HIV p17 GAG:77-85 epitopes in HIV-infected and uninfected individuals.

BACKGROUND: The matrix protein of the influenza A virus and the matrix and capsid proteins of the human immunodeficiency virus (HIV) share striking structural similarities which may have evolutionary and biological significance. These similarities led us to hypothesize the existence of cross-reactivity between HLA-A2-restricted FLU-M1:58-66 and HIV-1 p17 GAG:77-85 epitopes. METHODS: The hypothesis that these two epitopes are cross-reactive was tested by determining the presence and extent of FLU/GAG immune cross-reactivity in lymphocytes from HIV-seropositive and seronegative HLA-A2+ donors by cytotoxicity assays and tetramer analyses.