Jovanny Zabaleta

Louisiana State University Health Sciences Center New Orleans, New Orleans, Louisiana, United States

Are you Jovanny Zabaleta?

Claim your profile

Publications (53)207.65 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Obesity has reached epidemic proportions worldwide with disproportionate prevalence in different communities and ethnic groups. Recently, the American Medical Association recognized obesity as a disease, which is a significant milestone that opens the possibilities of treating obesity under standardized health plans. Obesity is an inflammatory disease characterized by elevated levels of biomarkers associated with abnormal lipid profiles, glucose levels, and blood pressure that lead to the onset of metabolic syndrome. Interestingly, inflammatory biomarkers, in particular, have been implicated in the risk of developing several types of cancer. Likewise, obesity has been linked to esophageal, breast, gallbladder, kidney, pancreatic, and colorectal cancers. Thus, there exists a link between obesity status and tumor appearance, which may be associated to the differential levels and the circulating profiles of several inflammatory molecules. For example, mediators of the inflammatory responses in both obesity and gastric cancer risk are the same: pro-inflammatory molecules produced by the activated cells infiltrating the inflamed tissues. These molecules trigger pathways of activation shared by obesity and cancer. Therefore, understanding how these different pathways are modulated would help reduce the impact that both diseases, and their concomitant existence, have on society.
    Methods in molecular biology (Clifton, N.J.) 01/2015; 1238:689-707. · 1.29 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Adolescent African-American females in Louisiana post high obesity prevalence. Body mass index (BMI), is commonly employed in nutrition and behavioral interventions to estimate body composition, despite its inability to discern excess fat versus lean muscle mass. This study aims to demonstrate that significant reductions in adiposity may only be possible with intensive, culturally-relevant interventions, and detected by sensitive, direct clinical measures, like those obtained by dual-energy x-ray absorptiometry (DXA). Methods Obese (BMI >95th percentile) African-American female participants (n=13; 13-19 years) were enrolled into a clinic-based 10-week nutrition and behavioral intervention, and prescribed a hypocaloric, non-ketogenic, high protein-modified fast supplemented with daily multi-vitamins, calcium plus vitamin D, and potassium. Lessons were instructed by Master of Public Health (MPH)-level staff (registered dietician (RD) and health educator). Fat mass, lean muscle mass and bone mineral content (BMC) were measured at pre-and-post-intervention directly by DXA; BMI(kg/m2)_for-gender-age-z-score was estimated based on the Centers for Disease Control (CDC) 2010 growth charts; waist circumference (cm) was measured using standard procedures. Results Significantly decreased fat mass (ȳ=-2469.8, se=671.88, p=0.0015) and increased BMC (ȳ=110.2, se=0.0134, p=0.0134) were observed from pre-to-post-intervention. Total weight was also reduced significantly (ȳ=-2.2, se=1.0, p=0.0425). No significant differences were detected in lean muscle mass, BMI_z-score, height, or waist circumference. Conclusions DXA detected significant fat loss and improved BMC, post-intervention. However, BMI_z-score and waist circumference revealed no significant changes. When replicating intensive, culturally-relevant, clinic-based nutrition and behavioral interventions in community settings, it may be important to avoid BMI_z-score to detect treatment effect in obese adolescent African-American females.
    142nd APHA Annual Meeting and Exposition 2014; 11/2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Chronic binge alcohol (CBA) administration exacerbates skeletal muscle (SKM) wasting at the terminal stage of simian immunodeficiency virus (SIV) infection in rhesus macaques. This is associated with a pro-inflammatory and oxidative milieu which we have previously shown to be associated with a disrupted balance between anabolic and catabolic mechanisms. In this study, we attempted to characterize the SKM gene expression signature in CBA-administered SIV-infected macaques, using the same animals from the previous study.Methods Administration of intragastric alcohol or sucrose to male rhesus macaques began 3 months prior to SIV infection and continued throughout the duration of study. Gene transcriptomes of SKM excised at necropsy (~10 months post-SIV) from healthy na\xEFve control (Control), sucrose-administered, SIV-infected (SUC-SIV), and CBA-administered, SIV-infected (CBA-SIV) macaques were evaluated in microarray data sets. The Protein Analysis Through Evolutionary Relationships classification tool was used to filter differentially regulated genes based on their predicted function into select biological processes relevant to SKM wasting which were inflammation, extracellular matrix (ECM) remodeling, and metabolism.ResultsIn total, 1,124 genes were differentially regulated between SUC-SIV and Controls, 2,022 genes were differentially expressed between the CBA-SIV and Controls, and 836 genes were differentially expressed between CBA-SIV and SUC-SIV animals. The relevance of altered gene expression was reflected in the up-regulation of pro-inflammatory CCL-2, CCL-8, CX3CL1, SELE, HP, and TNFRS10A mRNA expression. In addition, ECM remodeling was reflected in the up-regulation of TIMP-1, MMP 2, and MMP 9 mRNA expression and transforming growth factor-beta 1 protein expression. In addition, hydroxyproline content and picrosirius staining reflected increased collagen deposition in the CBA-SIV muscle tissue.Conclusions The results of the study demonstrate SKM inflammation as an important underlying mechanism for muscle wasting. In addition, the study provides evidence of SKM fibrotic transformation as a factor in CBA-induced accentuation of SIV-associated muscle wasting.
    Alcoholism Clinical and Experimental Research 11/2014; 38(11). · 3.42 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The speckle-type POZ protein (SPOP) is a tumor suppressor in prostate cancer (PCa). SPOP somatic mutations have been reported in up to 15% of PCa of those of European descent. However, the genetic roles of SPOP in African American (AA)-PCa are currently unknown. We sequenced the SPOP gene to identify somatic mutations in 49 AA prostate tumors and identified three missense mutations (p.Y87C, p.F102S, and p.G111E) in five AA prostate tumors (10%) and one synonymous variant (p.I106I) in one tumor. Intriguingly, all of mutations and variants clustered in exon six, and all of the mutations altered conserved amino acids. Moreover, two mutations (p.F102S and p.G111E) have only been identified in AA-PCa to date. Quantitative real-time polymerase chain reaction analysis showed a lower level of SPOP expression in tumors carrying SPOP mutations than their matched normal prostate tissues. In addition, SPOP mutations and novel variants were detected in 5 of 27 aggressive PCa and one of 22 less aggressive PCa (P < 0.05). Further studies with increased sample size are needed to validate the clinicopathological significance of these SPOP mutations in AA-PCa.
    Asian Journal of Andrology 06/2014; · 2.14 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Our studies have demonstrated that chronic Δ9-tetrahydrocannabinol (THC) administration results in a generalized attenuation of viral load and tissue inflammation in simian immunodeficiency virus (SIV)-infected male rhesus macaques. Gut-associated lymphoid tissue is an important site for HIV replication and inflammation that can impact disease progression. We used a systems approach to examine the duodenal immune environment in 4-6 yr-old male rhesus monkeys inoculated intravenously with SIVMAC251 after 17 mo of chronic THC administration (0.18-0.32 mg/kg, intramuscularly, twice daily). Duodenal tissue samples excised from chronic THC- (N=4) and vehicle (VEH)-treated (N=4) subjects at ~5 mo post-inoculation showed lower viral load, increased duodenal integrin beta 7+ (β7) CD4+ and CD8+ central memory T cells, and a significant preferential increase in Th2 cytokine expression. Gene array analysis identified 6 genes to be differentially expressed in intestinal samples of the THC/SIV animals when compared to those differentially expressed between VEH/SIV and uninfected controls. These genes were identified to have significant participation in 1) apoptosis; 2) cell survival, proliferation, and morphogenesis; and 3) energy and substrate metabolic processes. Additional analysis comparing the duodenal gene expression in THC/SIV vs. VEH/SIV animals identified 93 differentially expressed genes that participate in processes involved in muscle contraction, protein folding, cytoskeleton remodeling, cell adhesion and cell signaling. Immunohistochemical staining showed attenuated apoptosis in epithelial crypt cells of THC/SIV subjects. Our results indicate that chronic THC treatment modulated duodenal T cell populations, favored a pro-Th2 cytokine balance, and decreased intestinal apoptosis. These findings reveal novel mechanisms that may potentially contribute to cannabinoid-mediated disease modulation.
    AIDS research and human retroviruses 01/2014; · 2.18 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Embryonic development of articular cartilage has not been well understood and the role of doublecortin (DCX) in determination of chondrocyte phenotype is unknown. Here, we use a DCX promoter-driven eGFP reporter mouse model to study the dynamic gene expression profiles in mouse embryonic handplates at E12.5 to E13.5 when the condensed mesenchymal cells differentiate into either endochondral chondrocytes or joint interzone cells. Illumina microarray analysis identified a variety of genes that were expressed differentially in the different regions of mouse handplate. The unique expression patterns of many genes were revealed. Cytl1 and 3110032G18RIK were highly expressed in the proximal region of E12.5 handplate and the carpal region of E13.5 handplate, whereas Olfr538, Kctd15, and Cited1 were highly expressed in the distal region of E12.5 and the metacarpal region of E13.5 handplates. There was an increasing gradient of Hrc expression in the proximal to distal direction in E13.5 handplate. Furthermore, when human DCX protein was expressed in human adipose stem cells, collagen II was decreased while aggrecan, matrilin 2, and GDF5 were increased during the 14-day pellet culture. These findings suggest that DCX may play a role in defining chondrocyte phenotype.
    International Journal of Molecular Sciences 01/2014; 15(4):6941-60. · 2.46 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The Androgen receptor (AR) plays a central role in the normal development of the prostate gland, in prostate carcinogenesis, and in the progression of prostate cancer (PCa) to advanced metastatic disease. African American (AA) men with PCa present with higher tumor volume, more advanced tumor stage, and higher Gleason score. This could be in part related to the AR expression or activity in the prostate tissue of AA men, or to unique mutations or polymorphisms of the AR. In Caucasian Americans (CAs), AR mutations are rare or infrequent in organ-confined tumors, but occur at a higher rate in advanced, metastatic, or castrate-recurrent disease. In AAs, the prevalence, clinical, and biological significance of AR mutations in PCa are unknown. In this study, we investigated the occurrence of somatic and germline AR mutations in patients with primary PCa in AAs compared with CAs. Due to very limited data available on allelic distribution of E213 (G/A) single nucleotide polymorphism (SNP), we also assessed this in patients with sporadic PCa and in unrelated healthy individuals from both ethnic populations. Somatic missense AR mutations were detected at a higher rate in AAs (17 out of 200 cases) than in CAs (2 out of 100 cases). In AAs, the majority of these mutations (41.1%) were from Gleason 7 tumors, a small portion (23.5%) from Gleason 8 tumors, and the rest (35.2%) from Gleason 6 tumors. Analysis of genomic DNAs extracted from white blood cells of patients with sporadic PCa revealed that the rate of germline AR mutations were also higher (~4 times) in AAs than in CAs. With respect to E213 (G/A) SNP, the E213 A-allele expression was 5.85 times higher in healthy unrelated AA men than in CA men. However, in AAs with somatic AR mutation, the E213 G-allele distribution was almost equal to the A-allele. Silencing of one of the somatic AR mutations (i.e., 597 Ser>Gly) in a primary AA-PCa cell line (e.g., E006AA) revealed that similar AR mutation can be associated simultaneously with both "gain-of-function" phenotype (cell migration and invasion) and a "loss-of-function" phenotype (proliferation). Our data demonstrated a higher susceptibility for genetic alterations in the AR in the form of somatic mutations in sporadic PCa or in the form of germline mutations in AAs as compared with CAs. These data may support the idea that AR-specific hypermutator phenotype in combination with other genes, might serve as a contributing factor to ethnic differences in PCa and potentially different clinical outcome in AAs as a high-risk population.
    International journal of biological sciences. 01/2014; 10(6):643-51.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Serum arginase levels have been shown to be elevated in conditions, such as trauma, cancer, chronic wounds, pregnancy, and diabetes. This also has been found to be true in atopic diseases, such as asthma and allergic rhinitis. Objective To study arginase activity in patients with atopic dermatitis (AD). Methods In this pilot study, arginase activity levels in 15 pediatric patients with AD were compared with those in controls to determine whether arginase levels in AD are altered as in patients with other atopic diseases. Results In contrast to the other diseases studied, arginase activity was found to be decreased in granulocytes and in the plasma of patients with AD compared with controls. This finding was coupled with a trend toward higher L-arginine plasma levels. Conclusion In AD, a different mechanism of arginine metabolism seems to be stimulated, leading to the formation of nitric oxide pathway components causing suppression of the arginase pathway and impairment in skin hydration, collagen synthesis, and wound healing.
    Annals of Allergy, Asthma & Immunology. 01/2014;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Several variations in the nicotinic receptor genes have been identified to be associated with both lung cancer risk and smoking in the genome-wide association (GWA) studies. However, the relationships among these three factors (genetic variants, nicotine dependence, and lung cancer) remain unclear. In an attempt to elucidate these relationships, we applied mediation analysis to quantify the impact of nicotine dependence on the association between the nicotinic receptor genetic variants and lung adenocarcinoma risk. We evaluated 23 single nucleotide polymorphisms (SNPs) in the five nicotinic receptor related genes (CHRNB3, CHRNA6, and CHRNA5/A3/B4) previously reported to be associated with lung cancer risk and smoking behavior and 14 SNPs in the four 'control' genes (TERT, CLPTM1L, CYP1A1, and TP53), which were not reported in the smoking GWA studies. A total of 661 lung adenocarcinoma cases and 1,347 controls with a smoking history, obtained from the Environment and Genetics in Lung Cancer Etiology case-control study, were included in the study. Results show that nicotine dependence is a mediator of the association between lung adenocarcinoma and gene variations in the regions of CHRNA5/A3/B4 and accounts for approximately 15% of this relationship. The top two CHRNA3 SNPs associated with the risk for lung adenocarcinoma were rs1051730 and rs12914385 (p-value = 1.9×10-10 and 1.1×10-10, respectively). Also, these two SNPs had significant indirect effects on lung adenocarcinoma risk through nicotine dependence (p = 0.003 and 0.007). Gene variations rs2736100 and rs2853676 in TERT and rs401681 and rs31489 in CLPTM1L had significant direct associations on lung adenocarcinoma without indirect effects through nicotine dependence. Our findings suggest that nicotine dependence plays an important role between genetic variants in the CHRNA5/A3/B4 region, especially CHRNA3, and lung adenocarcinoma. This may provide valuable information for understanding the pathogenesis of lung adenocarcinoma and for conducting personalized smoking cessation interventions.
    PLoS ONE 01/2014; 9(9):e107268. · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective:To examine for the first time the associations between pro-inflammatory cytokines and obesity-related metabolic biomarkers in, exclusively pre-pubertal, otherwise healthy obese and non-obese Black and White children, 7-9 years of age.Design & Methods:Body Mass Index (BMI), insulin resistance (HOMA-IR), visceral and subcutaneous adipose tissues (VAT and SAT [MRI]); total body fat (DXA), ectopic, intrahepatic (IHL) and intramyocellular (IMCL) fat ((1)H-MRS) and serum levels of Interleukin (IL)-1, IL-6, IL-8, Tumor Necrosis Factor alpha (TNF-α), and monocyte chemoattractant protein 1 (MCP-1) were measured in 40 obese and non-obese children. Relationships between inflammatory cytokines and obesity were assessed by ANOVA and Spearman's Rank correlation.Results:Significant inverse correlations were found between z_BMI, SAT, total body fat and IHL and levels of TNF-α (Spearman's rho=-0.36, -0.39, -0.43, and -0.39, respectively; P<0.05). Levels of IL-8 were significantly and inversely correlated with IMCL (-0.39; P=0.03) and remained significant after adjusting for race. IMCL was inversely associated with TNF-α only after adjusting for race (-0.37; P=0.04).Conclusions:Relationships between pro-inflammatory and metabolic markers commonly observed in adults are reversed in healthy, Black and White children prior to puberty. Prospective studies are warranted to determine how these inverse relationships modify chronic disease risk later in life.International Journal of Obesity accepted article preview online, 26 November 2013. doi:10.1038/ijo.2013.220.
    International journal of obesity (2005) 11/2013; · 5.22 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The link between obesity and self-esteem among minority youth has received minimal empirical evaluation. This study aims to describe the magnitude of risk that body mass index, household income, and transitional age have on global self-esteem levels among African-American adolescents. These analyses were conducted on cross-sectional data obtained from 264 urban-dwelling African-American females between 14 and 18 years of age. Survey data on global self-esteem levels, transitory age, and socioeconomic levels were collected using self-administered questionnaires. Measured height and weight values were used to calculate and categorize weight status according to body mass index. Logistic regression models examined the probability of reporting less than average levels of global self-esteem. Adolescent African-American females residing in low-income households were 10 times more likely to report lower global self-esteem scores than those individuals from more affluent households (95% CI: 1.94, 60.19, p < .001). Neither weight status (95% CI: 0.81, 2.55; p = .26) nor age (95% CI: 0.05, 1.87; p = .82) were significant risk indicators for lower than average levels of global self-esteem among participants in this study. Household income appears to be the greatest predictor of global self-esteem levels. Further research in this area is needed to fully elucidate precursors for psychological health vulnerability and facilitate intervention development.
    Journal of National Black Nurses' Association: JNBNA 07/2013; 24(1):1-8.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Glioblastoma multiforme is characterized by rapid proliferation, aggressive metastatic potential, and resistance to radio- and chemotherapy. The matricellular protein CYR61 regulates cellular proliferation and migration and is highly expressed in Glioblastomas. MicroRNAs are 22-nucleotides long RNAs that regulate gene expression post-transcriptionally. Here, we utilized the LN229 glioblastoma cell line and found that CYR61 is a target of miR-136, miR-155, and miR-634. Over-expression of miR-136 and miR-634 miRNAs negatively affected proliferation, but not migration, while expression of miR-155 reduced migration but did not affect the proliferation of LN229 cells. Investigation of the molecular mechanisms affected by expression of miR-634 revealed an increased phosphorylation of p70S6 kinase, suggesting an induction of the mammalian target of rapamycin (mTOR) complex 1 pathway. Additionally, in miR-634 overexpressing cells, TSC2, a negative regulator of mTOR signaling, was found to be decreased. Altogether, our study provides insights on the differential roles of miRs-136, -155, and -634 in regulating glioblastoma cell growth and migration, and how microRNAs could be manipulated to decrease the aggressiveness and metastatic potential of tumor cells.
    Genes. 01/2013; 4(1):46-64.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: MicroRNAs are short non-coding RNAs that modulate gene expression by translational repression. Because of their high stability in intracellular as well as extracellular environments, miRNAs have recently emerged as important biomarkers in several human diseases. However, they have not been tested in the cerebrospinal fluid (CSF) of HIV-1 positive individuals. Here, we present results of a study aimed at determining the feasibility of detecting miRNAs in the CSF of HIV-infected individuals with and without encephalitis (HIVE). We also evaluated similarities and differences between CSF and brain tissue miRNAs in the same clinical setting. We utilized a high throughput approach of miRNA detection arrays and identified differentially expressed miRNAs in the frontal cortex of three cases each of HIV+, HIVE, and HIV- controls, and CSF of ten HIV-positive and ten HIV-negative individuals. For the CSF samples, the group of HIV+ individuals contained nine cases of HIV-Associated Neurological Disorders (HAND) and, among those, four had HIVE. All the HIV-negative samples had non-viral acute disseminate encephalomyelitis. A total of 66 miRNAs were found differentially regulated in HIV+ compared to HIV- groups. The greatest difference in miRNA expression was observed when four cases of HIVE were compared to five non-HIVE cases, previously normalized with the HIV-negative group. After statistical analyses, eleven miRNAs were fund significantly up-regulated in HIVE. Although more clinical samples should be examined, this work represents the first report of CSF miRNAs in HIV-infection and offers the basis for future investigation. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc.
    Journal of Cellular Physiology 10/2012; · 4.22 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Helicobacter pylori causes acute and chronic gastric inflammation induced by proinflammatory cytokines and chemokines secreted by cells of the gastric mucosa, including gastric epithelial cells. Previous studies have demonstrated that the bacterial arginase, RocF, is involved in inhibiting T cell proliferation and CD3ζ expression, suggesting that arginase could be involved in a more general dampening of the immune response, perhaps by down-regulation of certain pro-inflammatory mediators. Global transcriptome analysis was performed on AGS gastric epithelial cells infected for 16 hours with a wild type Helicobacter pylori strain 26695, an arginase mutant (rocF-) or a rocF+ complemented strain. H. pylori infection triggered altered host gene expression in genes involved in cell movement, death/growth/proliferation, and cellular function and maintenance. While the wild type strain stimulates host inflammatory pathways, the rocF- mutant induced significantly more expression of IL-8. The results of the microarray were verified using real-time PCR, and the differential levels of protein expression were confirmed by ELISA and Bioplex analysis. MIP-1B was also significantly secreted by AGS cells after H. pylori rocF- mutant infection, as determined by Bioplex. Even though not explored in this manuscript, the impact that the results presented here may have on the development of gastritis, warrant further research to understand the underlying mechanisms of the relationship between H. pylori RocF and IL-8 induction. We conclude that H. pylori arginase modulates multiple host signaling and metabolic pathways of infected gastric epithelial cells. Arginase may play a critical role in anti-inflammatory host responses that could contribute to the ability of H. pylori to establish chronic infections.
    BMC Microbiology 08/2012; 12:175. · 2.98 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Estrogens may influence gastric cancer risk, but published studies are inconclusive. We therefore carried out a meta-analysis addressing the associations of gastric cancer in women with menstrual and reproductive factors and with use of estrogen- and antiestrogen-related therapies. Searches of PubMed up to June, 2011 and review of citations yielded a total of 28 independent studies, including at least one exposure of interest. Random effects pooled estimates of relative risk (RR) and corresponding 95% CIs were calculated for eight exposures reported in at least five studies, including: age at menarche, age at menopause, years of fertility, parity, age at first birth, oral contraceptive use, hormone replacement therapy (HRT), and tamoxifen treatment. Longer years of fertility (RR = 0.74, 95% CI: 0.63-0.86) and HRT (RR = 0.77; 95% CI: 0.64-0.92) were each associated with decreased gastric cancer risk. Conversely, tamoxifen treatment was associated with increased risk (RR = 1.82; 95% CI: 1.39-2.38). The other five exposures were not significantly associated. Our analysis supports the hypothesis that longer exposure to estrogen effects of either ovarian or exogenous origin may decrease risk of gastric cancer. Additional studies are warranted to extend this finding and to identify the underlying mechanisms.
    Cancer Epidemiology Biomarkers &amp Prevention 01/2012; 21(1):20-38. · 4.56 Impact Factor
  • Source
    Jovanny Zabaleta
    [Show abstract] [Hide abstract]
    ABSTRACT: The prevalence of gastric cancer is associated with several factors including geographical location, diet, and genetic background of the host. However, it is evident that infection with Helicobacter pylori (H. pylori) is crucial for the development of the disease. Virulence of the bacteria is also important in modulating the risk of the disease. After infection, H. pylori gains access to the gastric mucosa and triggers the production of cytokines that promote recruitment of inflammatory cells, probably involved in tissue damage. Once the infection is established, a cascade of inflammatory steps associated with changes in the gastric epithelia that may lead to cancer is triggered. H. pylori-induced gastritis and H. pylori-associated gastric cancer have been the focus of extensive research aiming to discover the underlying mechanisms of gastric tissue damage. This research has led to the association of host genetic components with the risk of the disease. Among these is the presence of single nucleotide polymorphisms (SNPs) in several genes, including cytokine genes, which are able to differentially modulate the production of inflammatory cytokines and then modulate the risk of gastric cancer. Interestingly, the frequency of some of these SNPs is different among populations and may serve as a predictive factor for gastric cancer risk within that specific population. However, the role played by other genetic modifications should not be minimized. Methylation of gene promoters has been recognized as a major mechanism of gene expression regulation without changing the primary structure of the DNA. Most DNA methylation occurs in cytosine residues in CpG dinucleotide, but it can also be found in other DNA bases. DNA methyltransferases add methyl groups to the CpG dinucleotide, and when this methylation level is too high, the gene expression is turned off. In H. pylori infection as well as in gastric cancer, hypermethylation of promoters of genes involved in cell cycle control, metabolism of essential nutrients, and production of inflammatory mediators, among others, has been described. Interestingly, DNA changes like SNPs or mutations can create CpG sites in sequences where transcription factors normally sit, affecting transcription.In this chapter, we review the literature about the role of SNPs and methylation on H. pylori infection and gastric cancer, with big emphasis to the H. pylori role in the development of the disease due to the strong association between both.
    Methods in molecular biology (Clifton, N.J.) 01/2012; 863:411-35. · 1.29 Impact Factor
  • Source
    Jovanny Zabaleta
    [Show abstract] [Hide abstract]
    ABSTRACT: Helicobacter pylori (H. pylori) infection is a recognized risk factor for gastric cancer. The disease is one of the most common in the world and explains for a significant number of cancer cases and cancer-associated deaths worldwide. H. pylori infection induces huge array of responses at the gastric epithelial cells and the immune system, inducing both pro- and anti-inflammatory molecules that are intended to either perpetuate or control the infection. Despite the strong immune response, the infection is not cleared and can persist mostly without causing major significant discomfort in the human host. Among the mediators induced in response to the infection, microRNA (miRNA) have the potential to play a major impact on the outcome of the bacteria-host interaction. These miRNA are small 18-24 nucleotide long nucleotide molecules that can interact with mRNA molecules and block their translation into proteins or induce their degradation. Many efforts have been put into the generation of miRNA profiles and their role in gastric cancer. This has led to the identification of miRNA associated with promoting the inflammatory response initiated by the H. pylori infection, increasing the malignant progression of the gastric epithelium, and enhancing the invasiveness and migratory capacity of cancer cells. However, at the same time, several miRNA have been associated with events that are totally opposite, leading to reduced inflammation, inhibition of malignancy and increased apoptosis of transformed cells. In summary, as it is in many other examples, the role played by miRNA in gastric cancer is the results of a delicate balance between pro- and anti-cancer miRNA, and this balance is modified by the interaction of many players, many of which are still waiting to be discovered.
    Frontiers in Genetics 01/2012; 3:294.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Marijuana is one of the most commonly used and abused drugs. Δ-9-tetrahydrocannabinol (Δ-9-THC), the primary psychoactive component in marijuana, is FDA-approved to ameliorate AIDS-associated wasting. Because cannabinoid receptors are expressed on cells of the immune system, it is possible that chronic Δ-9-THC use may impact HIV disease progression. Until recently, longitudinal, controlled, systems-approach studies on the effects of cannabinoids on disease progression were lacking. Data from our controlled studies in non-human primates show chronic Δ-9-THC administration prior to and during simian immunodeficiency virus (SIV) infection ameliorates disease progression, attenuates viral load and tissue inflammation, significantly reducing morbidity and mortality of SIV-infected macaques. Identification of possible mechanisms responsible for this modulation of disease progression is complicated due to the multiplicity of cannabinoid-mediated effects, tissue-specific responses to the viral infection, multiple cellular mechanisms involved in inflammatory responses, coordinated neuroendocrine and localized responses to infection, and kinetics of viral replication. Emerging results from our studies reveal that the overall mechanisms mediating the protective effects of cannabinoids involve novel epigenomic regulatory mechanisms in need of systematic investigation. Here, we review the evidence supporting an immunomodulatory role for cannabinoids and its impact on disease progression with focus on HIV/SIV infection.
    Journal of Neuroimmune Pharmacology 08/2011; 6(4):516-27. · 3.80 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Identification of biomarkers is needed for development of screening programs to prevent gastric cancer. Because racial differences exist in cancer rates, we aimed to evaluate the association between polymorphisms in inflammation-related genes and gastric preneoplastic lesions in African Americans and Caucasians from Louisiana, USA. Gastric biopsies from 569 adults (361 African Americans and 208 Caucasians) undergoing diagnostic endoscopy were used for histological diagnosis and genomic DNA extraction. Polymorphisms within eight genes (IL1B, IL8, IL6, TNF, PTGS2, ARG1, IL10 and TGFB1) were investigated by TaqMan. The cagA status of Helicobacter pylori infection was assessed by PCR. Haplotype logistic regression models were used to identify variables associated with intestinal metaplasia or dysplasia. African Americans carrying the haplotype IL1B-511T/-31C/+3954T, which includes the three risk-associated alleles at the IL1B locus, were more likely to being diagnosed with intestinal metaplasia or dysplasia than those carrying the most common haplotype T-C-C (adjusted OR: 2.51, 95% CI: 1.1-5.5). None of the polymorphisms were associated with intestinal metaplasia and dysplasia in Caucasians. Age and cagA-positive status were independent factors associated with these lesions. Haplotypes at the IL1B locus may participate in mediating the susceptibility to gastric carcinogenesis and might be useful as markers of advanced premalignant lesions in African Americans. Interestingly, carriage of IL1B+3954T allele seems to be the key factor, even though the role played by other polymorphisms cannot be excluded.
    International Journal of Cancer 02/2011; 128(3):668-75. · 6.20 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Myeloid-derived suppressor cells are a major mechanism of tumor-induced immune suppression in cancer. Arginase I-producing myeloid-derived suppressor cells deplete l-arginine (L-Arg) from the microenvironment, which arrests T cells in the G(0)-G(1) phase of the cell cycle. This cell cycle arrest correlated with an inability to increase cyclin D3 expression resulting from a decreased mRNA stability and an impaired translation. We sought to determine the mechanisms leading to a decreased cyclin D3 mRNA stability in activated T cells cultured in medium deprived of L-Arg. Results show that cyclin D3 mRNA instability induced by L-Arg deprivation is dependent on response elements found in its 3'-untranslated region (UTR). RNA-binding protein HuR was found to be increased in T cells cultured in medium with L-Arg and bound to the 3'-untranslated region of cyclin D3 mRNA in vitro and endogenously in activated T cells. Silencing of HuR expression significantly impaired cyclin D3 mRNA stability. L-Arg deprivation inhibited the expression of HuR through a global arrest in de novo protein synthesis, but it did not affect its mRNA expression. This alteration is dependent on the expression of the amino acid starvation sensor general control nonderepressible 2 kinase. These data contribute to an understanding of a central mechanism by which diseases characterized by increased arginase I production may cause T cell dysfunction.
    The Journal of Immunology 10/2010; 185(9):5198-204. · 5.52 Impact Factor

Publication Stats

2k Citations
207.65 Total Impact Points

Institutions

  • 2004–2014
    • Louisiana State University Health Sciences Center New Orleans
      • • Stanley S. Scott Cancer Center
      • • Department of Pediatrics
      • • Department of Genetics
      • • Microbiology, Immunology & Parasitology
      New Orleans, Louisiana, United States
  • 2004–2012
    • Louisiana State University Health Sciences Center Shreveport
      • Department of Microbiology & Immunology
      Shreveport, LA, United States
  • 2002–2012
    • Louisiana State University
      Baton Rouge, Louisiana, United States
  • 1997–1998
    • University of Antioquia
      • Facultad de Medicina
      Antioquia, Departamento de Antioquia, Colombia