Faculty Of Pharmacy Graduation Project 2017 - 2018

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Browsing Faculty Of Pharmacy Graduation Project 2017 - 2018 by Subject "Clinical Pharmacy"

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    Pharmacokinetics and pharmacogenomics of cyclophosphamide in Rhabdomyosarcoma patients
    (October University for Modern Sciences and Arts, 2018) Hamdy Ibrahim, Nyera; Mustafa Ibrahim, Loubna; Ashraf Milad, Merna
    This study is done on Caucasians Rhabdomyosarcoma patients, under 18 years old, and treated with cyclophosphamide 50mg/ml in 57357 Children Hospital. We choose a set of SNPs (rs4793665), (rs733392) and (rs4148412), in order to determine their interindividual genetic variation effect on the ABCC3 transporters action, the SNPs were chosen based on their minor allele frequency in the Caucasian population and their expected phenotypes in different drugs which was shown in previous studies. Allele's frequencies in Caucasians were obtained from The 1000 Genome project and The HapMap project. The extraction of DNA from the patients' blood samples was done using GeneJET Whole Blood Genomic DNA Purification Mini Kit and the concentration of the extracted DNA was detected by the NanoQuant Spectrophotometer. The genotyping was done using TaqManTM SNP Genotyping Assay for a total of 40 DNA samples for each SNP, and we used for the Real Time PCR the QuantStudio 6 Flex Real-Time PCR Device, all the PCR conditions including the setting of the thermal cycling settings were step up based on the protocol that was suggested in TaqMan® SNP Genotyping Assays User Guide. The 44 genotyped samples showed the following, At SNP rs733392, variant Allele A frequency is 0.1375 and nearly 75% of the samples are Homozygous G/G. SNP rs4148412, Variant Allele C frequency is 0.475and the majority of the samples are Heterozygous C/ T by 40%. At the third SNP rs4793665, which is located in the promoter region, the majority of the samples were Homozygous T/T by nearly 52.5%, and frequency of Variant Allele T is 0.675. The aim of this research is to find the association between the cyclophosphamide pharmacokinetics and the genetic variation in the enzymes and try to determine if it has an effect on the drug’s efficacy.