Nathalie K Zgheib

American University of Beirut, Beyrouth, Beyrouth, Lebanon

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Publications (41)118.31 Total impact

  • Jumana Antoun · Rihab Nasr · Nathalie K. Zgheib
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    ABSTRACT: This qualitative study aimed at comparing and contrasting the feasibility, efficiency, and students’ attitudes toward the use of paper, automated response system (ARS) and computer based testing (CBT) in the readiness assurance process (RAP) of team based learning (TBL). It also aimed at assessing whether the use of technology enhances cooperative learning when compared to paper. The first module of the clinical pharmacology course was conducted in the traditional way using paper. In the second and third modules, the paper-based TBL RAP component was replaced by ARS and CBT respectively. Forty-five third year medical students attended each of the three sessions. Both ARS and CBT based RAP were feasible and efficient, though with some technical constraints. The class during ARS was very interactive, but the test features had some disadvantages. The main problem with CBT was the suboptimal physical set up. When asked to rank their preferences for each method, most students (73%) ranked ARS as first, while paper and CBT almost equally ranked 2. Each method is characterized by peculiar strengths and weaknesses. Technology should be used in parallel to educational theories that support learning.
    Computers in Human Behavior 05/2015; 46. DOI:10.1016/j.chb.2015.01.003 · 2.69 Impact Factor
  • Cancer Research 05/2015; 75(9 Supplement):P1-03-06-P1-03-06. DOI:10.1158/1538-7445.SABCS14-P1-03-06 · 9.28 Impact Factor
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    ABSTRACT: Breast cancer is the most common malignancy among women in Lebanon and in Arab countries, with 50% of cases presenting before age 50 years. Between 2009 and 2012, 250 Lebanese women with breast cancer who were considered to be at high risk of carrying BRCA1 or BRCA2 mutations because of presentation at young age and/or positive family history (FH) of breast or ovarian cancer were recruited. Clinical data were analyzed statistically. Coding exons and intron-exon boundaries of BRCA1 and BRCA2 were sequenced from peripheral blood DNA. All patients were tested for BRCA1 rearrangements using multiplex ligation-dependent probe amplification (MLPA). BRCA2 MLPA was done in selected cases. Overall, 14 of 250 patients (5.6%) carried a deleterious BRCA mutation (7 BRCA1, 7 BRCA2) and 31 (12.4%) carried a variant of uncertain significance. Eight of 74 patients (10.8%) aged ≤40 years with positive FH and only 1 of 74 patients (1.4%) aged ≤40 years without FH had a mutated BRCA. Four of 75 patients (5.3%) aged 41-50 years with FH had a deleterious mutation. Only 1 of 27 patients aged >50 years at diagnosis had a BRCA mutation. All seven patients with BRCA1 mutations had grade 3 infiltrating ductal carcinoma and triple-negative breast cancer. Nine BRCA1 and 17 BRCA2 common haplotypes were observed. Prevalence of deleterious BRCA mutations is lower than expected and does not support the hypothesis that BRCA mutations alone cause the observed high percentage of breast cancer in young women of Lebanese and Arab descent. Studies to search for other genetic mutations are recommended. ©AlphaMed Press.
    The Oncologist 03/2015; 20(4). DOI:10.1634/theoncologist.2014-0364 · 4.54 Impact Factor
  • The Breast 03/2015; 24:S76. DOI:10.1016/S0960-9776(15)70191-8 · 2.58 Impact Factor
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    ABSTRACT: The purpose of this study was to measure the frequency of three CYP2B6 [CYP2B6*4 (rs2279343), CYP2B6*5 (rs3211371) and CYP2B6*9 (rs3745274)] alleles in patients with breast cancer receiving cyclophosphamide (CP) therapy and test whether these variants are predictors of CP-associated toxicity and efficacy. A total of 145 female breast cancer patients admitted to the American University of Beirut Medical Center for breast cancer-related therapy were included. Chart review was performed for collection of toxicity data. A time-to-event analysis was performed with a subset of 38 patients. The minor allele frequencies of CYP2B6*9, CYP2B6*4 and CYP2B6*5 were 0.27, 0.29 and 0.07, respectively. CYP2B6 *5/*6, *6/*9 or *6/*6 haplotypes were associated with a significantly shorter time to recurrence of the disease. There were no significant associations with myelo-toxicity. This is the first report on the pharmacogenetic profile of patients with breast cancer and the therapeutic and myelo-toxic behavior of CP in women from an Arab Middle Eastern country. Our results show that genotyping for these CYP2B6 alleles does not help in personalizing therapy from a toxicity perspective, and the association of shorter survival in these subjects with homozygous variants is interesting yet insufficient to justify routine genotyping prior to therapy, or to consider using a higher CP dose. Larger future studies or meta-analyses will be needed to further clarify the potential implication of these genetic polymorphisms.
    Cancer Chemotherapy and Pharmacology 11/2014; DOI:10.1007/s00280-014-2632-4 · 2.57 Impact Factor
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    ABSTRACT: Relative to western populations, the percentage of women diagnosed with breast cancer at a young age in Lebanon is high. While the younger age of the Lebanese population compared to the West certainly contributes to this difference, potential genetic, reproductive and/or biological factors likely play an important role. The objective of this study is to investigate the contribution of miRNAs in this setting through the analysis of the expression of five reported dysregulated miRNAs, miR-148b, miR-10b, miR-21, miR-221, and miR-155 in 20 normal and 57 cancerous breast tissues from Lebanese breast cancer patients. After finding their relative expression by quantitative reverse transcription real time PCR, the results were analyzed with respect to the patients' clinical and histopathology presentations. Compared to normal breast tissues, significant upregulation of miR-155, miR-21 and miR-148b, notable downregulation of miR-10b and non-significant expression of miR-221 were observed in tumor tissues. Moreover, miR-10b was significantly underexpressed in estrogen/progesterone receptor (ER/PR) negative tumors relative to ER/PR positive tumor tissues. miR-155 was also significantly overexpressed in postmenopausal patients and in those of age at diagnosis greater than 40 years old as well as in PR negative or in human epidermal growth factor 2 (Her2) positive tissues. This study is the first one to report miRNA expression patterns in Lebanese breast cancer patients. We found that differential miRNA expression in breast cancer could be variable between Lebanese and Western populations. miR-10b was positively correlated with the ER and PR status and miR-155 could be a noteworthy biomarker for the menopausal state, age at diagnosis, PR and Her2 status. Hence, miRNA can be used as biomarkers for early breast cancer detection.
    PLoS ONE 09/2014; 9(9):e107566. DOI:10.1371/journal.pone.0107566 · 3.23 Impact Factor
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    ABSTRACT: Tamoxifen is the standard-of-care treatment for estrogen receptor-positive premenopausal breast cancer. We examined tamoxifen metabolism via blood metabolite concentrations and germline variations of CYP3A5, CYP2C9, CYP2C19 and CYP2D6 in 587 premenopausal patients (Asians, Middle Eastern Arabs, Caucasian-UK; median age 39 years) and clinical outcome in 306 patients. N-desmethyltamoxifen (DM-Tam)/(Z)-endoxifen and CYP2D6 phenotype significantly correlated across ethnicities (R(2): 53%, P<10(-77)). CYP2C19 and CYP2C9 correlated with norendoxifen and (Z)-4-hydroxytamoxifen concentrations, respectively (P<0.001). DM-Tam was influenced by body mass index (P<0.001). Improved distant relapse-free survival (DRFS) was associated with decreasing DM-Tam/(Z)-endoxifen (P=0.036) and increasing CYP2D6 activity score (hazard ratio (HR)=0.62; 95% confidence interval (CI), 0.43-0.91; P=0.013). Low (<14 nM) compared with high (>35 nM) endoxifen concentrations were associated with shorter DRFS (univariate P=0.03; multivariate HR=1.94; 95% CI, 1.04-4.14; P=0.064). Our data indicate that endoxifen formation in premenopausal women depends on CYP2D6 irrespective of ethnicity. Low endoxifen concentration/formation and decreased CYP2D6 activity predict shorter DRFS.The Pharmacogenomics Journal advance online publication, 5 August 2014; doi:10.1038/tpj.2014.34.
    The Pharmacogenomics Journal 08/2014; 15(1). DOI:10.1038/tpj.2014.34 · 5.51 Impact Factor
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    ABSTRACT: The aim of this study is to analyze polymorphisms in genes involved in 6-mercaptopurine detoxification (TPMT); methotrexate (MTX) metabolism including ABCB1 (or MDR1), ABCC2, SLC19A1 (or RFC1), and SLCO1B1; and the MTX effect mainly MTHFR and TYMS, and to assess whether these polymorphisms are predictors of treatment toxicity and/or MTX clearance.
    Pharmacogenetics and Genomics 08/2014; 24(8):387-396. DOI:10.1097/FPC.0000000000000069 · 3.45 Impact Factor
  • Zeinab Awada · Nathalie Khoueiry Zgheib
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    ABSTRACT: In this report, we review the importance of pharmacovigilance in detecting postmarketing adverse drug events and the potential for developing pharmacogenovigilance programs by integrating pharmacogenomics with pharmacovigilance. We propose to start developing such a program in primary healthcare systems that use basic features of electronic medical records and have access to large numbers of patients commonly prescribed drugs. Such programs, if carefully designed, may grow over time and hopefully enhance the collection and interpretation of useful data for the clinical applications of pharmacogenomics testing.
    Pharmacogenomics 04/2014; 15(6):845-856. DOI:10.2217/pgs.14.44 · 3.43 Impact Factor
  • Safaa Ossaily · Nathalie K Zgheib
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    ABSTRACT: Abstract Drug metabolizing enzymes (DMEs) play a major role in the metabolism and final elimination of most drugs and xenobiotics from the body. Both phase I and phase II enzymes are highly polymorphic. Most studies on the pharmacogenetics (PGx) of DMEs and its influence on interindividual variability have been conducted in Western countries. Middle Easterners, however, may have a different genetic makeup and may be exposed to different environmental factors when compared with their Western counterparts. Thus, results obtained in Western populations cannot be extrapolated to the population of the Middle East, and it is important to examine and document PGx differences and influences within the Middle Eastern population as there have been very little published data from this region. Herein, we provide an update on the genetic polymorphisms of DMEs that were studied in Lebanon and their impact on drug toxicity and efficacy. It is hoped that with more time, additional funds, and perseverance, the PGx of DMEs in Lebanon picks up and becomes closer in quantity and quality to that in the West.
    01/2014; 29(2):1-10. DOI:10.1515/dmdi-2013-0058
  • Zainab Awada · Safaa Ossaily · Nathalie K. Zgheib
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    ABSTRACT: In this manuscript, we review the literature on the nutrigenetics and pharmacogenetics of vitamin D pathways, with a focus on genes involved in the pharmacokinetic and pharmacodynamic pathways of vitamin D as they have been major research targets. These include: VDR, CYP2R1, CYP27B1, DHCR7/NADSYN1, GC and CYP24A1. So far only 2 genome wide associations studies evaluated the potential role of genetic polymorphisms in the variability in 25 hydroxy vitamin D (25(OH)D) levels. Most of the evidence is based on the candidate gene approach with some conflicting results when it comes to effect size and associating disease outcome with 25(OH)D levels and genetic polymorphisms. Moreover, very little has been done to look at the effect of significant polymorphisms on the response to vitamin D supplementation. Further research is needed on larger population samples of different ethnicities to resolve some of the controversies. In addition, emerging technologies such as next generation sequencing may be a better genotyping alternative in order to detect rare but potentially important genetic variants. Functional studies are also needed to better understand the association results. This includes coupling genotyping data with gene expression studies as well as epigenetic evaluations.
    Current Pharmacogenomics and Personalized Medicine (Formerly Current Pharmacogenomics) 01/2014; 12(2).
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    ABSTRACT: The unpredictability of acenocoumarol dose needed to achieve target blood thinning level remains a challenge. We aimed to apply and compare a pharmacogenetic least-squares model (LSM) and artificial neural network (ANN) models for predictions of acenocoumarol dosing. LSM and ANN models were used to analyze previously collected data on 174 participants (mean age: 67.45 SD 13.49 years) on acenocoumarol maintenance therapy. The models were based on demographics, lifestyle habits, concomitant diseases, medication intake, target INR, and genotyping results for CYP2C9 and VKORC1. LSM versus ANN performance comparisons were done by two methods: by randomly splitting the data as 50 % derivation and 50 % validation cohort followed by a bootstrap of 200 iterations, and by a 10-fold leave-one-out cross-validation technique. The ANN-based pharmacogenetic model provided higher accuracy and larger R value than all other LSM-based models. The accuracy percentage improvement ranged between 5 % and 24 % for the derivation cohort and between 12 % and 25 % for the validation cohort. The increase in R value ranged between 6 % and 31 % for the derivation cohort and between 2 % and 31 % for the validation cohort. ANN increased the percentage of accurately dosed subjects (mean absolute error ≤1 mg/week) by 14.1 %, reduced the percentage of mis-dosed subjects (mean absolute error 2-3 mg/week) by 7.04 %, and reduced the percentage of grossly mis-dosed subjects (mean absolute error ≥4 mg/week) by 24 %. ANN-based pharmacogenetic guidance of acenocoumarol dosing reduces the error in dosing to achieve target INR. These results need to be ascertained in a prospective study.
    European Journal of Clinical Pharmacology 12/2013; 70(3). DOI:10.1007/s00228-013-1617-2 · 2.70 Impact Factor
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    ABSTRACT: Abstract We investigated the association of genetic polymorphisms in drug metabolizing enzymes (DMEs) and transporters in patients with docetaxel-induced febrile neutropenia, by a new high-throughput DMEs and transporters (DMETPlus) microarray platform, characterizing 1936 single nucleotide polymorphisms (SNPs) in 225 genes. We recruited 100 Lebanese breast cancer patients from a consecutive cohort of 277 patients who received docetaxel either alone, or in combination with trastuzumab. Out of 100 patients, 18 had developed febrile neutropenia (cases). They were age- and treatment- matched with 18 patients who did not develop febrile neutropenia on docetaxel (controls). We found that 12 SNPs in seven genes (ABCC6, ABCG1, ABCG2, CYP1A2, CYP2D6, FMO2, and FMO3) were significantly associated with febrile neutropenia after docetaxel treatment. Many of these SNPs have not been previously reported to be associated with toxicity due to docetaxel treatment. Interestingly, one SNP in the FMO3 gene (rs909530) was significantly associated with three clinical endpoints: febrile neutropenia, reduced absolute neutrophil count, and hemoglobin reduction. To the best of our knowledge, this is the first study that evaluated the effect of a large array of nearly 2000 polymorphisms in DMEs and transporters on docetaxel toxicity in breast cancer patients, and in a previously understudied population. Additionally, it attests to the feasibility of genomics research in low- and middle-income countries (LMICs). In light of the current global epidemic of noncommunicable diseases (NCDs) such as breast cancer impacting LMICs, we suggest pharmacogenomics is considered as an integral part of the global health research agenda for NCDs and personalized therapeutics.
    Omics: a journal of integrative biology 06/2013; 17. DOI:10.1089/omi.2013.0019 · 2.73 Impact Factor
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    ABSTRACT: Changes in the activity of drug metabolizing enzymes (DMEs) are potentially associated with cancer risk. This relationship is attributed to their involvement in the bioactivation of multiple procarcinogens or the metabolism of multiple substrates including an array of xenobiotics and environmental carcinogens. 326 Lebanese women of whom 99 were cancer free (controls) and 227 were diagnosed with breast cancer (cases) were included. Blood for DNA was collected and medical charts were reviewed. Three genotyping methods were employed including: (1) restriction fragment length polymorphism (RFLP) for CYP2E1*5B, CYP2E1*6, NAT2*5 and NAT2*6; (2) gel electrophoresis for GSTM1 and GSTT1; and (3) real-time PCR for GSTP1 Ile/Val polymorphism. We analyzed the relationship between genetic susceptibilities in selected xenobiotic metabolizing genes and breast cancer risk. Allele frequencies were fairly similar to previously reported values from neighboring populations with relevant migration routes. There were no statistically significant differences in the distribution of variant carcinogen metabolizing genes between cases and controls even after adjusting for age at diagnosis, menopausal status, smoking, and alcohol intake. Despite its limitations, this is the first study that assesses the role of genetic polymorphisms in DMEs with breast cancer in a sample of Lebanese women. Further studies are needed to determine the genetic predisposition and gene-environment interactions of breast cancer in this population.
    Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 04/2013; DOI:10.1016/j.mrfmmm.2013.04.004 · 4.44 Impact Factor
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    ABSTRACT: Abstract Biomedical science in the 21(st) century is embedded in, and draws from, a digital commons and "Big Data" created by high-throughput Omics technologies such as genomics. Classic Edisonian metaphors of science and scientists (i.e., "the lone genius" or other narrow definitions of expertise) are ill equipped to harness the vast promises of the 21(st) century digital commons. Moreover, in medicine and life sciences, experts often under-appreciate the important contributions made by citizen scholars and lead users of innovations to design innovative products and co-create new knowledge. We believe there are a large number of users waiting to be mobilized so as to engage with Big Data as citizen scientists-only if some funding were available. Yet many of these scholars may not meet the meta-criteria used to judge expertise, such as a track record in obtaining large research grants or a traditional academic curriculum vitae. This innovation research article describes a novel idea and action framework: micro-grants, each worth $1000, for genomics and Big Data. Though a relatively small amount at first glance, this far exceeds the annual income of the "bottom one billion"-the 1.4 billion people living below the extreme poverty level defined by the World Bank ($1.25/day). We describe two types of micro-grants. Type 1 micro-grants can be awarded through established funding agencies and philanthropies that create micro-granting programs to fund a broad and highly diverse array of small artisan labs and citizen scholars to connect genomics and Big Data with new models of discovery such as open user innovation. Type 2 micro-grants can be funded by existing or new science observatories and citizen think tanks through crowd-funding mechanisms described herein. Type 2 micro-grants would also facilitate global health diplomacy by co-creating crowd-funded micro-granting programs across nation-states in regions facing political and financial instability, while sharing similar disease burdens, therapeutics, and diagnostic needs. We report the creation of ten Type 2 micro-grants for citizen science and artisan labs to be administered by the nonprofit Data-Enabled Life Sciences Alliance International (DELSA Global, Seattle). Our hope is that these micro-grants will spur novel forms of disruptive innovation and genomics translation by artisan scientists and citizen scholars alike. We conclude with a neglected voice from the global health frontlines, the American University of Iraq in Sulaimani, and suggest that many similar global regions are now poised for micro-grant enabled collective innovation to harness the 21(st) century digital commons.
    Omics: a journal of integrative biology 04/2013; 17(4):161-72. DOI:10.1089/omi.2013.0034 · 2.73 Impact Factor
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    ABSTRACT: The aim of this study is to investigate the effect of CYP2C19 polymorphism and co-therapy with rabeprazole or esomeprazole on the anti-platelet effect of clopidogrel. Patients receiving clopidogrel 75 mg ± rabeprazole or esomeprazole underwent genotyping for CYP2C19*2 and *3, and vasodilator stimulated phosphoprotein (VASP) testing to measure platelet reactivity index (PRI). 239 consecutive patients were enrolled: 92 clopidogrel (C group), 94 clopidogrel + rabeprazole (CR), and 53 clopidogrel + esomeprazole (CE). 45 patients had loss of function polymorphism (LOF) (43 heterozygous; 2 homozygous mutant for CYP2C19*2). The mean platelet reactivity index (PRI) was 20.7±21.9% in the C group, 19.1±20.9% in the CR group, and 24.5±22.9% in the CE group (p= NS). High-on-treatment Platelet Reactivity (HPR), defined as PRI>50%, was observed in 12 (13.0%), 13 (13.8%), and 10 (18.9%) patients on C, CR, and CE respectively (p=NS). HPR was similar in rapid metabolizers between groups. On multivariate logistic regression, neither CYP2C19 LOF alleles nor PPI co-therapy were associated with HPR. The use of PPIs was indicated in 30.6% of recipients. As a conclusion, CYP2C19*2 LOF allele and the use of esomeprazole or rabeprazole have no effect on the action of clopidogrel.
    Journal of cardiovascular pharmacology 03/2013; 62(1). DOI:10.1097/FJC.0b013e31828ecf44 · 2.11 Impact Factor
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    Gillian Bartlett · Jumana Antoun · Nathalie K Zgheib
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    ABSTRACT: Theranostics represents a broadening in the scope of personalized medicine to include companion diagnostics for health interventions ranging from drugs to vaccines, as well as individual susceptibility to disease. Surprisingly, in the course of this broadening of personalized medicine discourse, relatively little attention has been paid to primary care (as compared with tertiary healthcare settings) despite its vast patient population and being a crucial entry point to health services. Recent advances in pharmacogenomics (PGx), a classical theranostics application whereby genotyping and/or gene expression-based tests are used for targeted or optimal therapy, revealed new opportunities to characterize more precisely human genomic variation and the ways in which it contributes to person-to-person and population variations in drug response. In the immediate foreseeable future, the primary-care physicians are expected to play an ever increasing crucial role in PGx-based prescribing in order to reduce the rates of adverse drug events and improve drug efficacy, yet PGx testing in primary care remains limited. In this article, the authors review the advances in PGx applications, the barriers for their adoption in the clinic from a primary care point of view and the efforts that are being undertaken to move PGx forward in this hitherto neglected application context of theranostic medicine. Finally, the authors propose several salient recommendations, including a 5-year forecast, to accelerate the current convergence between PGx and primary care.
    Expert Review of Molecular Diagnostics 11/2012; 12(8):841-55. DOI:10.1586/erm.12.115 · 4.27 Impact Factor
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    05/2012; 10(2):101-105. DOI:10.2174/187569212800626430
  • Cancer Research 02/2012; 71(24 Supplement):P4-01-16-P4-01-16. DOI:10.1158/0008-5472.SABCS11-P4-01-16 · 9.28 Impact Factor
  • Nathalie Zgheib · Jumana Antoun · Ali Taher

Publication Stats

331 Citations
118.31 Total Impact Points

Institutions

  • 2010–2015
    • American University of Beirut
      • • Department of Pediatrics and Adolescent Medicine
      • • Department of Pharmacology and Toxicology
      • • Faculty of Medicine
      Beyrouth, Beyrouth, Lebanon
    • Beirut Arab University
      Beyrouth, Beyrouth, Lebanon
  • 2012
    • McGill University
      • Department of Family Medicine
      Montréal, Quebec, Canada
  • 2007–2009
    • University of Pittsburgh
      • Pharmacy and Therapeutics
      Pittsburgh, Pennsylvania, United States
  • 2006
    • University of Florida
      • College of Pharmacy
      Gainesville, FL, United States