Jovanny Zabaleta

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

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Publications (44)179.46 Total impact

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    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;
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    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
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    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.
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    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.
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    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
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    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. · 3.10 Impact Factor
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    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
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    Jovanny Zabaleta
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    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
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    Jovanny Zabaleta
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    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.
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    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
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    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
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    ABSTRACT: Adult patients with acute lymphoblastic T cell leukemia (T-ALL) have a very poor prognosis and few effective therapeutic options. Therefore, novel therapies that increase the efficacy of the treatments and that prolong T-ALL patient survival are needed. Malignant T cells require high concentrations of nutrients to sustain their increased rate of proliferation. In this study, we determined whether L-Arginine depletion by the pegylated form of the L-Arginine-metabolizing enzyme arginase I (peg-Arg I) impairs the proliferation of malignant T cells. Our results show that peg-Arg I depleted L-Arginine levels in vitro and in vivo. In addition, treatment of malignant T-cell lines with peg-Arg I significantly impaired their proliferation, which correlated with a decreased progression into the cell cycle, followed by the induction of apoptosis. Furthermore, peg-Arg I impaired the expression of cyclin D3, a fundamental protein in T-ALL proliferation, through a global arrest in protein synthesis. Injection of peg-Arg I plus chemotherapy agent Cytarabine prolonged survival in mice bearing T-ALL tumors. This antitumoral effect correlated with an inhibition of T-ALL proliferation in vivo, a decreased expression of cyclin D3, and T-ALL apoptosis. The results suggest the potential benefit of L-Arginine depletion by peg-Arg I in the treatment of T-cell malignancies.
    Blood 06/2010; 115(25):5214-21. · 9.06 Impact Factor
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    ABSTRACT: Prostate cancer (PCa) is one of the most common cancers in the world. Inflammation has been described as a risk factor for PCa and depends on the production of cytokines in response to tissue damage or the presence of stimuli that induces cellular stress. Interindividual variation in cytokine production is partially controlled by single-nucleotide polymorphisms (SNPs) that have been associated with differential production of cytokines. We have recently showed that SNP-SNP interactions of cytokine genes are associated with PCa risk. However, little is known about the association of cytokine SNPs and PCa aggressiveness. In this study, we evaluated the association of 15 SNPs in five cytokine genes and aggressiveness of PCa in African- and Caucasian-American individuals. Caucasian Americans with the genotypes IL10-1082GG or IL1B+3954TT had 2.31-fold [95% confidence interval (CI) = 1.13-4.72] and 3.11 (95% CI = 1.20-8.06)-fold risk, respectively, of developing aggressive PCa, as compared with individuals without those genotypes. We did not find any associations in the African-American group. Using Multivariate Adaptive Regression Splines modeling for exploratory SNP-SNP interactions, our results showed that more aggressive PCa in Caucasians Americans is associated with the CT genotype at IL8-47 [odds ratios (OR) = 3.50; 95% CI = 1.13-10.88] or combined genotypes of IL1B-511CC and IL10-1082GG (OR = 3.38; 95% CI = 1.70-6.71). Unfortunately, the same analysis could not be performed in the African-Americans due to limited number of individuals. With limited sample size, the results from this study suggest that SNPs in cytokine genes may be associated with PCa aggressiveness. More extensive studies are warranted to validate our findings.
    Carcinogenesis 06/2009; 30(8):1358-62. · 5.64 Impact Factor
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    ABSTRACT: Dendritic cells (DC) have a critical effect on the outcome of adaptive immune responses against growing tumors. Whereas it is generally assumed that the presence of phenotypically mature DCs should promote protective antitumor immunity, evidence to the contrary does exist. We describe here a novel mechanism by which tumor-infiltrating dendritic cells (TIDC) actively contribute to the suppression of protective CD8(+) T-cell-based antitumor immunity. Using the BALB/NeuT model of spontaneously arising mammary carcinoma, we found that canonical MHC II(+)/CD11b(+)/CD11c(high) TIDCs act as regulatory DCs to suppress CD8(+) T-cell function, resulting in diminished T-cell-based antitumor immunity in vivo. Stimulation of naive T cells with regulatory TIDCs resulted in an altered cell fate program characterized by minimal T-cell expansion, impaired IFNgamma production, and anergy. Suppression by regulatory TIDCs overcame stimulatory signals provided by standard DCs, occurred in the absence of cognate interactions with T cells, and was mediated primarily by arginase metabolism of l-arginine. Immunosuppressive TIDCs were found in every murine tumor type examined and were phenotypically distinct from tumor-infiltrating CD11c(int-low)/CD11b(+)/Gr-1(+) myeloid-derived suppressor cells. Thus, within the tumor microenvironment, MHC II(+) TIDCs can function as potent suppressors of CD8(+) T-cell immunity.
    Cancer Research 05/2009; 69(7):3086-94. · 8.65 Impact Factor
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    ABSTRACT: Myeloid-derived suppressor cells (MDSC) producing arginase I are increased in the peripheral blood of patients with renal cell carcinoma (RCC). MDSC inhibit T-cell function by reducing the availability of L-arginine and are therefore considered an important tumor escape mechanism. We aimed to determine the origin of arginase I-producing MDSC in RCC patients and to identify the mechanisms used to deplete extracellular L-arginine. The results show that human MDSC are a subpopulation of activated polymorphonuclear (PMN) cells expressing high levels of CD66b, CD11b, and VEGFR1 and low levels of CD62L and CD16. In contrast to murine MDSC, human MDSC do not deplete L-arginine by increasing its uptake but instead release arginase I into the circulation. Activation of normal PMN induces phenotypic and functional changes similar to MDSC and also promotes the release of arginase I from intracellular granules. Interestingly, although activation of normal PMN usually ends with apoptosis, MDSC showed no increase in apoptosis compared with autologous PMN or PMN obtained from normal controls. High levels of VEGF have been shown to increase suppressor immature myeloid dendritic cells in cancer patients. Treatment of RCC patients with anti-VEGF antibody bevacizumab, however, did not reduce the accumulation of MDSC in peripheral blood. In contrast, the addition of interleukin-2 to the treatment increased the number of MDSC in peripheral blood and the plasma levels of arginase I. These results may provide new insights on the mechanisms of tumor-induced anergy/tolerance and may help explain why some immunotherapies fail to induce an antitumor response.
    Cancer Research 03/2009; 69(4):1553-60. · 8.65 Impact Factor
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    ABSTRACT: Prostate cancer (CaP) is the second leading cause of cancer death in American men. Chronic inflammation has been one of several factors associated with the development of CaP. Single-nucleotide polymorphisms (SNPs) in cytokine genes have been associated with increased inflammation, increased cytokine production and possibly increased CaP risk. However, the effects of cytokine SNPs on CaP susceptibility have not been consistent. Using the genomic DNA collected in a CaP case-control study (557 cases and 547 controls), we pilot tested the interactions of nine functionally characterized SNPs of three cytokine genes in CaP risk using the multivariate adaptive regression splines (MARS)-logit models. African-Americans with the IL10-819TT genotype had a lower CaP risk [odds ratio (OR) = 0.27, 95% confidence interval (CI) = 0.07-1.01], but subjects with the genotype combination of IL1B-511CT/TT and IL10-592CC had a higher CaP risk (OR = 2.56, 95% CI = 1.09-6.02). In Caucasians, higher CaP risk was associated with the IL10-1082AG/GG genotype (OR = 3.62, 95% CI = 1.42-9.28), the genotype combination of IL10-1082AA plus IL1B-31TT/TC (OR = 2.92, 95% CI = 1.13-7.55) and the genotype combination of TNF-238GG plus IL10-592AA (OR = 2.14, 95% CI = 1.05-4.38). Our results highlight the importance of cytokine SNPs and their interactions in CaP risk.
    Carcinogenesis 04/2008; 29(3):573-8. · 5.64 Impact Factor
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    ABSTRACT: More than 20 years after the identification of Helicobacter pylori as a human pathogen, gastric cancer continues to be a leading cause of cancer deaths worldwide. Genetic association studies have the potential for helping to identify those at greatest risk for developing gastric cancer subsequent to infection by H. pylori. IL1B promoter polymorphisms have been supported by several meta-analyses as being associated with gastric cancer risk. In this review, we discuss challenges in experimental design of gene association studies in gastric cancer, with attention to gene-environment interactions that may lead to inconsistency in findings across populations.
    Cancer biology & therapy 03/2008; 7(2):157-62. · 3.29 Impact Factor
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    ABSTRACT: Differences in incidence and outcome of cancer among ethnic groups may be explained by biological and/or socio-economic factors. Genetic variations that affect chronic inflammation, a potentially important risk factor for carcinogenesis, may differ across ethnic groups. Such differences may help explain cancer disparities among these groups. Single nucleotide polymorphisms (SNPs) within cytokine genes can affect cytokine levels and the degree of inflammation. Associations between cancer and some cytokine SNPs have been suggested. However, these have not been consistently replicated among populations, suggesting that SNP function may differ according to ethnicity, or that SNPs alone do not completely account for regulation of inflammation. We examined seven polymorphisms in African-American (n = 294) and Caucasian (n = 299) newborns in Louisiana: IL1B-511C > T, IL1B-31T > C, IL1B + 3954C > T, IL1RN*2, IL10-1082G > A, IL10-592C > A, and TNF-308G > A. African-American newborns had significantly higher frequencies of IL1B-511T, IL1B-31C, IL10-1082A and IL10-592A alleles and complete linkage equilibrium between IL1B + 3954 and IL1B-31. In contrast, IL1B + 3954T, IL1RN*2, and TNF-308A were more frequent in Caucasian newborns and exhibited strong linkage disequilibrium between IL1B + 3954 and IL1B-31. All allelic frequencies were significantly different between groups. We hypothesize that these dissimilarities may contribute to differences in the inflammatory response and cancer incidence and mortality between African-Americans and Caucasians in Louisiana.
    Cancer Immunology and Immunotherapy 02/2008; 57(1):107-14. · 3.64 Impact Factor
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    Cancer Epidemiology Biomarkers &amp Prevention 04/2007; 16(3):635; author reply 635-6. · 4.56 Impact Factor
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    ABSTRACT: The protective immune response against Mycobacterium tuberculosis relies both on antigen-presenting cells and on T lymphocytes. In patients with different forms of tuberculosis, varying degrees of T cell function--ranging from positive delayed-type hypersensitivity, in asymptomatic infected healthy individuals, to the absence of the response, in patients with miliary or pulmonary tuberculosis (PTB)--have been reported. The decreased expression of CD3zeta reported in T cells from patients with either cancer or leprosy has provided possible explanations for the altered immune response observed in these diseases. The present study aimed to compare the expression of CD3zeta , nuclear transcription factor- kappa B (NF- kappa B), arginase activity, and cytokine production in 20 patients with PTB, in 20 tuberculin-positive asymptomatic subjects, and in 14 tuberculin-negative control subjects. Compared with those in tuberculin (purified protein derivative)-negative control subjects, peripheral-blood T lymphocytes from patients with active PTB had significantly (P < .001) decreased expression of CD3zeta and absence of the p65/p50 heterodimer of NF- kappa B. These alterations were reversed only in patients who responded to treatment. Also reported here for the first time is that the presence of arginase activity in peripheral-blood mononuclear-cell lysates of patients with PTB parallels high production of interleukin-10. The presence of arginase could, in part, explain the decreased expression of CD3zeta . These findings provide a novel mechanism that may explain the T cell dysfunction observed in patients with PTB.
    The Journal of Infectious Diseases 12/2006; 194(10):1385-93. · 5.85 Impact Factor

Publication Stats

2k Citations
179.46 Total Impact Points

Institutions

  • 2004–2014
    • Louisiana State University Health Sciences Center New Orleans
      • • Department of Pediatrics
      • • Stanley S. Scott Cancer Center
      • • 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
  • 1997–2001
    • University of Antioquia
      • Facultad de Medicina
      Antioquia, Departamento de Antioquia, Colombia