Factors Associated with Cancer Prevention/Risk Reduction Behaviors among Latinos.

Improving understanding of behaviors that increase or reduce cancer risk for different Hispanic groups is a public health priority; such knowledge is sparse in new gateway immigration locations such as Indiana. The aims of this study were to: 1) describe cancer beliefs and cancer preventive/risk reduction behaviors (physical activity, tobacco, and alcohol use) among Hispanic adults; 2) examine differences in cancer beliefs and preventive behaviors by country/territory of birth, socioeconomic status, and area of residence (urban vs. rural); and 3) determine predictors of engagement in cancer prevention and risk reduction behaviors in this population.

Novel differential calcium regulation of hematopoietic stem and progenitor cells under physiological low oxygen conditions.

Low oxygen bone marrow (BM) niches (~1%-4% low O ) provide critical signals for hematopoietic stem/progenitor cells (HSC/HSPCs). Our presented data are the first to investigate live, sorted HSC/HSPCs in their native low O conditions. Transcriptional and proteomic analysis uncovered differential Ca regulation that correlated with overlapping phenotypic populations consisting of robust increases of cytosolic and mitochondrial Ca , ABC transporter (ABCG2) expression and sodium/hydrogen exchanger (NHE1) expression in live, HSC/HSPCs remaining in constant low O We identified a novel Ca high population in HSPCs predominantly detected in low O that displayed enhanced frequency of phenotypic LSK/LSKCD150 in low O replating assays compared to Ca low populations.

Cancer-related knowledge, beliefs, and behaviors among Hispanic/Latino residents of Indiana.

Background: Cancer is the leading cause of death for Hispanics in the USA. Screening and prevention reduce cancer morbidity and mortality.

Methods: This study administered a cross-sectional web-based survey to self-identified Hispanic residents in the state of Indiana to assess their cancer-related knowledge, beliefs, and behaviors, as well as to identify what factors might be associated with cancer screening and prevention.

High-dose sitagliptin for systemic inhibition of dipeptidylpeptidase-4 to enhance engraftment of single cord umbilical cord blood transplantation.

Delayed engraftment remains a limitation of umbilical cord blood (UCB) transplantation. We previously showed that inhibition of dipeptidylpeptidase (DPP)-4 using sitagliptin 600 mg daily was safe with encouraging results on engraftment, but inhibition was not sustained. We evaluated the efficacy and feasibility of higher doses of sitagliptin to enhance engraftment of UCB in patients with hematological cancers.

Utility of CRISPR/Cas9 systems in hematology research.

Since the end of the 20th century, novel approaches have emerged to manipulate experimental models of hematological disorders so that they more accurately mirror what is observed in the clinical setting. Despite these technological advances, the characterization of crucial genes for benign or malignant hematological disorders remains challenging, given the dynamic nature of the hematopoietic system and the genetic heterogeneity of these disorders. To overcome this limitation, genome-editing technologies have been developed to manipulate the genome specifically via deletion, insertion, or modification of targeted loci.

Enhancing Hematopoietic Stem Cell Transplantation Efficacy by Mitigating Oxygen Shock.

Hematopoietic stem cells (HSCs) reside in hypoxic niches within bone marrow and cord blood. Yet, essentially all HSC studies have been performed with cells isolated and processed in non-physiologic ambient air. By collecting and manipulating bone marrow and cord blood in native conditions of hypoxia, we demonstrate that brief exposure to ambient oxygen decreases recovery of long-term repopulating HSCs and increases progenitor cells, a phenomenon we term extraphysiologic oxygen shock/stress (EPHOSS).

The importance of hypoxia and extra physiologic oxygen shock/stress for collection and processing of stem and progenitor cells to understand true physiology/pathology of these cells ex vivo.

Purpose Of Review: Hematopoietic stem (HSCs) and progenitor (HPCs) cells reside in a hypoxic (lowered oxygen tension) environment, in vivo. We review literature on growth of HSCs and HPCs under hypoxic and normoxic (ambient air) conditions with a focus on our recent work demonstrating the detrimental effects of collecting and processing cells in ambient air through a phenomenon termed extra physiologic oxygen shock/stress (EPHOSS), and we describe means to counteract EPHOSS for enhanced collection of HSCs.

Recent Findings: Collection and processing of bone marrow and cord blood cells in ambient air cause rapid differentiation and loss of HSCs, with increases in HPCs.

Contribution of electromechanical coupling between Kv and Ca v1.2 channels to coronary dysfunction in obesity.

Previous investigations indicate that diminished functional expression of voltage-dependent K(+) (KV) channels impairs control of coronary blood flow in obesity/metabolic syndrome. The goal of this investigation was to test the hypothesis that KV channels are electromechanically coupled to CaV1.2 channels and that coronary microvascular dysfunction in obesity is related to subsequent increases in CaV1.

Implications of DPP4 modification of proteins that regulate stem/progenitor and more mature cell types.

Dipeptidylpeptidase (DPP) 4 has the potential to truncate proteins with a penultimate alanine, proline, or other selective amino acids at the N-terminus. DPP4 truncation of certain chemokines, colony-stimulating factors, and interleukins have recently been linked to regulation of hematopoietic stem/progenitor cells, more mature blood cells, and other cell types. We believe that the potential role of DPP4 in modification of many regulatory proteins, and their subsequent effects on numerous stem/progenitor and other cell-type functions has not been adequately appreciated.

Dipeptidylpeptidase 4 negatively regulates colony-stimulating factor activity and stress hematopoiesis.

Enhancement of hematopoietic recovery after radiation, chemotherapy, or hematopoietic stem cell (HSC) transplantation is clinically relevant. Dipeptidylpeptidase (DPP4) cleaves a wide variety of substrates, including the chemokine stromal cell-derived factor-1 (SDF-1). In the course of experiments showing that inhibition of DPP4 enhances SDF-1-mediated progenitor cell survival, ex vivo cytokine expansion and replating frequency, we unexpectedly found that DPP4 has a more general role in regulating colony-stimulating factor (CSF) activity.

VE-cadherin and PECAM-1 enhance ALL migration across brain microvascular endothelial cell monolayers.

Objective: Infiltration of the central nervous system (CNS) by leukemia is a problematic disease manifestation of acute lymphoblastic leukemia (ALL). The mechanisms by which leukocytes interact with human brain-derived microvasculature endothelial cells (HBMEC) and enter the CNS are largely derived from models of inflammation. However, our data indicate that ALL cells do not elicit an inflammatory phenotype by HBMEC.

Neurotrophins regulate bone marrow stromal cell IL-6 expression through the MAPK pathway.

Background: The host's response to infection is characterized by altered levels of neurotrophins and an influx of inflammatory cells to sites of injured tissue. Progenitor cells that give rise to the differentiated cellular mediators of inflammation are derived from bone marrow progenitor cells where their development is regulated, in part, by cues from bone marrow stromal cells (BMSC). As such, alteration of BMSC function in response to elevated systemic mediators has the potential to alter their function in biologically relevant ways, including downstream alteration of cytokine production that influences hematopoietic development.