{"title":"CYP2D6 EXPRESSION IS CUMULATIVELY UP REGULATED IN MULTIDRUG TREATED HEPATOMA CELLS: A PREDECTIVE PHARMACOGENETICS IN VITRO MODEL","authors":"Sherine Khedr, Thoria Donia, E. Salim, M. Hessien","doi":"10.21608/EJB.2020.136526","DOIUrl":"https://doi.org/10.21608/EJB.2020.136526","url":null,"abstract":"Cancer and many other diseases require concomitant treatments with combinations of many drugs.Debrisoquine 4-Hydroxylayase (CYP2D6) is microsomal enzyme involved in phase I metabolism of a long list of drugs. Also, it is a marker of inter-individual variability in drug responsiveness. This study was designated to explore the regulation of CYP2D6 in hepatoma cells exposed to combinations of anticancer and epigenetic modifying drugs. HepG2 cell were treated with combinations of anticancer drug (Taxol), glucocorticoid (dexamethasone, DEX) and epigenetic modifiers: Trichostatin A (TSA) and 5 aza-deoxycytidine (5 aza-dC). The expression of CYP2D6 was determined by quantitative RT-PCR and compared to other CYPs and the corresponding cumulative apoptotic effect was determined by flow cytometry. The obtained results revealed thatUnder non-induced conditions, CYP2D6 was stably expressed and sub micromolar concentration of DEX mildly increased its expression. Individual treatments as DEX, Taxol, TSA and 5-azadC induced 2-6-fold increase in the transcript level, where the TSA was the most potent inducer. Combinations of 2 drugs as (Taxol+DEX), (Taxol+TSA), (Taxol+5-aza-dC) and (TSA+5-aza-dC). led to 3-10-fold increase (average 6.2), whereas cocktails of 3 drugs as (Taxol+DEX+5-aza-dC), (Taxol+DEX+TSA) and (Taxol+TSA+5-aza-dC) led to further up regulatory effect (11-27-fold). The highest increment (28-fold) was observed when cells were treated with 4 drugs as (Taxol+TSA+5-aza-dC+DEX). The progressive induction of CYP2D6 was correlated with the cumulative apoptotic effect (r=0.79). Conclusively, the data suggest, for the first time, that anticancer, epigenetic regulatory factors and dexamethasone cumulatively enhanced the baseline expression of CYP2D6","PeriodicalId":269335,"journal":{"name":"The Egyptian Journal of Biochemistry and Molecular Biology","volume":"42 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116314290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amany A. Saleh, W. Shehata, Mohammed Elhelbawy, N. Elhelbawy
{"title":"ASSOCIATION BETWEEN GENETIC VARIANTS OF SINGLE NUCLEOTIDE POLYMORPHISMS OF THE DISCOIDIN DOMAIN RECEPTOR TYROSINE KINASE 1 (DDR1) A/C (RS 2267641) AND GRANZYME B (GZMB) C/T (RS8192917) GENES IN VITILIGO","authors":"Amany A. Saleh, W. Shehata, Mohammed Elhelbawy, N. Elhelbawy","doi":"10.21608/EJB.2020.136524","DOIUrl":"https://doi.org/10.21608/EJB.2020.136524","url":null,"abstract":"","PeriodicalId":269335,"journal":{"name":"The Egyptian Journal of Biochemistry and Molecular Biology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126932396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
F. Mohammed, R. A. E. Shazly, S. Gohar, S. Soliman
{"title":"THE STUDY OFLONG NON-CODING RNAs(NAALADL2 AND XIST) GENEEXPRESSION IN DIFFUSE LARGE B CELL LYMPHOMA","authors":"F. Mohammed, R. A. E. Shazly, S. Gohar, S. Soliman","doi":"10.21608/EJB.2020.136525","DOIUrl":"https://doi.org/10.21608/EJB.2020.136525","url":null,"abstract":"Diffuse large B cell lymphoma (DLBCL) is the most predominant type of Non Hodgkin- Lymphomas, representing more than one third of all recently diagnosed cases. Long non-coding RNAs (lncRNAs) are a class of RNA not coding for protein having more than 200 nucleotides and have significant roles in tumor formation and they have been investigated in different types of solid and hematologic tumors, including DLBCL.This work aims to study the level of lncRNAs(NAALADL2 and XIST)gene expression in DLBCL.NAALADL2 and XIST gene expression levels in blood were performed by real time qPCR technique. Forty five DLBCL patients and forty five age and gender matched healthy controls were included in this study.There was significant statistical increase in the expression of NAALADL2 and decrease of XIST expression in patients compared to control group (p value 10.3 and<1.57 for NAALADL2 and XISTrespectively.There was significant positive correlation between NAALADL2 and advanced stage and a significant negative correlation is found between XIST and advanced stage. It may be concluded that NAALADL2 and XISTexpression levels were obviously associated with DLBCL and might determine the disease progression.","PeriodicalId":269335,"journal":{"name":"The Egyptian Journal of Biochemistry and Molecular Biology","volume":"43 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129059521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marwa A. Gaber, N. Idriss, G. Seifeldein, Reem M. Elkady, Rania M. Makboul, H. Imam, Lobna Wahid
{"title":"THE IMPACT OF CYCLOOXYGENASE-2 GENE POLYMORPHISM 899G/C AND CERTAIN INDICES ON HEPATITIS C RELATED LIVER FIBROSIS","authors":"Marwa A. Gaber, N. Idriss, G. Seifeldein, Reem M. Elkady, Rania M. Makboul, H. Imam, Lobna Wahid","doi":"10.21608/ejb.2019.63580","DOIUrl":"https://doi.org/10.21608/ejb.2019.63580","url":null,"abstract":"The link between cyclooxygenase-2 (COX-2) gene polymorphisms and liver diseases has been widely reported. Early and precise estimation and staging of hepatic fibrosis are crucial for prognosis and treatment decisions in those patients. We aimed in this study to clarify role of -899G/C polymorphism of COX-2 gene, alteration of CA 19-9 and CA 125 levels, and plasma protein pattern in staging of liver fibrosis comparing them to METAVIR stages of liver fibrosis. We recruited 103 patients with post-hepatitis C liver fibrosis and 42 healthy controls. COX-2 gene polymorphism was detected by PCR- TaqMan probes, while CA19-9, CA125 levels were estimated using quantitative ELISA. Plasma proteins were detected by the capillary electrophoresis method. The results revealed that the frequency of COX-2 -899G/C genotypes GG, GC, and CC were 68.0%, 28.2% and 3.9% in the fibrotic group; 97.06%, 2.4%, and 0.0% in healthy control group respectively. The percent of COX-2 expression for the fibrotic group and the healthy group were 32% and 2.3% respectively. COX-2 expression scores on mild- vs. sever-fibrosis stages (METAVIR stages 1, 2 vs. stages 3,4) were 18.2 %and 81.8% respectively (OR=48.00, 95%CI). The serum level of tested tumor markers were significantly higher in fibrotic patients than in control group (69.40 ±51.82, 13.41 ± 6.49 respectively for CA 19.9 and 59.16 ± 47.23, 10.90 ± 8.36 for CA 125) and in GC/CC genotypes than GG one (116.96 ± 55.00, 33.64 ± 28.39 respectively for CA 19.9 and 101.62 ± 51.29, 27.89 ± 25.51 respectively for CA 125). In conclusion, COX-2 -899 C allele carriers are more vulnerable to develop hepatitis C- related hepatic fibrosis. The combined estimation of CA 19-9 and CA 125 levels are useful for identifying and staging patients with liver fibrosis. Keywords: COX-2 gene polymorphisms, CA 19-9, CA 125, protein electrophoresis, liver fibrosis","PeriodicalId":269335,"journal":{"name":"The Egyptian Journal of Biochemistry and Molecular Biology","volume":"97 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121764850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. S. Alkafaas, Thoria Diab, Thanaa Shalaby, M. Hessien
{"title":"DEXAMETHASONE IMPROVES THE RESPONSIVENESS OF HEPATOMA CELLS FOR BOTH FREE AND SOLVENT CONTAINING PACLITAXEL IN VITRO","authors":"S. S. Alkafaas, Thoria Diab, Thanaa Shalaby, M. Hessien","doi":"10.21608/ejb.2019.63581","DOIUrl":"https://doi.org/10.21608/ejb.2019.63581","url":null,"abstract":"This work was designated to explore the effect of glucocorticoid (dexamethasone) on the responsiveness of hepatoma cells to Paclitaxel (PTX) and the expression of Taxol resistance gene (Txr1) and the paclitaxel metabolizing genes. Hepatocellular carcinoma cells (HepG2) were treated with standard paclitaxel (PTX) or solvent containing paclitaxel (Taxol) in the presence or absence of dexamethasone (DEX). Cell viability and apoptosis were determined by MTT assay and flow cytometry, respectively. Also, total RNA was isolated, reverse transcribed and used to determine the expression levels of Txr1, CYP 3A4, and CYP2C8 genes. Initially, HepG2 cells were more resistant to PTX than Taxol. Also, cells became more responsive to the standard PTX and Taxol in the presence of DEX, where the IC50 values decreased from 42.5 μg/ml to 13.07 μg/ml and from 6.5 μg/ml to 3.6 μg/ml, respectively. Apoptosis was the main mechanism of cytotoxicity in cells treated with PTX or Taxol. The involvement of DEX, however, decreased the percent of apoptotic cells. Moreover, the expression of Txr1 decreased by 18% and 35% in cells cotreated with PTX+DEX or Taxol+DEX. In parallel, the expression of paclitaxel metabolizing genes (CYP3A4 and CYP2C8) was increased compared to DEX free cells. This in vitro study reports the associations between the enhanced responsiveness of hepatoma cells to paclitaxel or Taxol in presence of dexamethasone, Samar S. Alkafaas et all ـــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ ـــــــــــــــــ ـــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ ـــــــــ 96 associated with a decrease in drug resistance and upregulation of the paclitaxel metabolizing genes.","PeriodicalId":269335,"journal":{"name":"The Egyptian Journal of Biochemistry and Molecular Biology","volume":"11 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126219924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amany A. Saleh, S. Tayel, -. NESREENG.EL, Helbawy, K. M. Elzorkany
{"title":"ASSESSMENT OF PROVOCATIVE INFLAMMATORY ROLE OF TRISTETRAPROLIN AND TUMOR NECROSIS FACTOR ALPHA GENES EXPRESSION IN CHRONIC KIDNEY DISEASE","authors":"Amany A. Saleh, S. Tayel, -. NESREENG.EL, Helbawy, K. M. Elzorkany","doi":"10.21608/ejb.2019.63547","DOIUrl":"https://doi.org/10.21608/ejb.2019.63547","url":null,"abstract":"","PeriodicalId":269335,"journal":{"name":"The Egyptian Journal of Biochemistry and Molecular Biology","volume":"12 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124317944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Ayoub, O. Shaker, E. Hassan, Tarek I. Ahmed, N. A. Ahmed, M. Abdelwahed
{"title":"MIR 129 5-P AS A NONINVASIVE PROGNOSTIC BIOMARKER OF LIVER FIBROSIS IN HCV EGYPTIAN POPULATION","authors":"S. Ayoub, O. Shaker, E. Hassan, Tarek I. Ahmed, N. A. Ahmed, M. Abdelwahed","doi":"10.21608/ejb.2019.63546","DOIUrl":"https://doi.org/10.21608/ejb.2019.63546","url":null,"abstract":"Background: Hepatic fibrosis is the inevitable pathological process of chronic hepatitis C (CHC), Accurate assessment of liver fibrosis has an important role in determining prognosis and to follow-up disease progression. Current aim was to evaluate MiR 129 5-p as a noninvasive serum marker for assessment of liver fibrosis in chronic hepatitis C Egyptian populations. Subject and Methods: Eighty HCV patients complicated by liver fibrosis and 80 subjects were enrolled as controls. MiRNA expression level was tested using miScript SYBR Green PCR Kit (Qiagen, USA). Results: Results showed significant differences between the HCV patients and controls as regard the mean± SD of expression level of MiR-129-5p with down- regulation in HCV patients (0.10±0.02) (P<0.0001) . The results also showed that MiR 129-5p relative expression level was significantly down-regulated in sever fibrosis (F3-F4) compared with mild fibrosis (F1-F2). ROC curve analysis showed the prognostic value of MiR 129-5p to differentiate between severe fibrosis (F3 and F4) from mild (F1, F2) (sensitivity=70% and specificity =90%). Conclusion: miR-129- 5p might be a potential prognostic biomarker for liver fibrosis. Keywords: Liver fibrosis, CHC, MiR129-5p","PeriodicalId":269335,"journal":{"name":"The Egyptian Journal of Biochemistry and Molecular Biology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130654757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Soliman, M. Habib, M. El-Dien, S. Gohar, S. Alhassanin
{"title":"EVALUATION OF RECEPTOR FOR ADVANCED GLYCATION END PRODUCT /HIGH-MOBILITY GROUP BOX 1 (RAGE/HMGB1) EXPRESSION STATUS AND ITS PROGNOSTIC VALUE IN BREAST CANCER","authors":"S. Soliman, M. Habib, M. El-Dien, S. Gohar, S. Alhassanin","doi":"10.21608/ejb.2019.63545","DOIUrl":"https://doi.org/10.21608/ejb.2019.63545","url":null,"abstract":"Sucess in breast cancer treatment is not built only on diversity but on clinical relevance to tumor pathogenesis. So, gathering of many prognositic biomarkers involved in cancer progression could yield new treatment modalities in order to maitain good quality of life for patients .The receptor for advanced glycation end product (RAGE) and its ligand the high-mobility group box 1 (HMGB1) protein seem to play a role in many cancers , their cross-talk affects breast cancer behaviour. The aim of this study was to investigate the tissue RAGE and HMGB1 expression levels and their association with clinico-pathological features and overall survival in breast cancer patients.Tissue RAGE and HMGB1 mRNA levels were measured by real time-polymerase chain reaction (RT-PCR). Results showed tissue RAGE and HMGB1 displayed significant higher expression levels compared to benign group. RAGE and HMGB1 expression levels in breast cancer tissues were significantly associated with high tumour grade , lymph node metastasis ,stage III wih no significant relation to the molecular type of tumor nor overall survival. RAGE-HMGB1 system seems to be linked to breast cancer which may represent a prognostic biomarker of clinical and theraputic significance. Keywords: Breast cancer, RAGE, HMGB1, RT-PCR","PeriodicalId":269335,"journal":{"name":"The Egyptian Journal of Biochemistry and Molecular Biology","volume":"2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115182963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
El-Sayed, A. Emam, M. Neamat-Allah, Moustafa Abo Zeid, Raymonde H. Assaf, A. Baiomy
{"title":"STUDY OF THE ROLE OF LEUCINE-RICH REPEAT-CONTAINING G-PROTEIN COUPLED RECEPTOR 5 (LGR5) AND WNT PATHWAY IN COLON CANCER","authors":"El-Sayed, A. Emam, M. Neamat-Allah, Moustafa Abo Zeid, Raymonde H. Assaf, A. Baiomy","doi":"10.21608/ejb.2019.63544","DOIUrl":"https://doi.org/10.21608/ejb.2019.63544","url":null,"abstract":"","PeriodicalId":269335,"journal":{"name":"The Egyptian Journal of Biochemistry and Molecular Biology","volume":"37 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116277611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohammed A. Hajar, Nagwan A. Sabek, Amany Y. Elkazaz, F. M. Hassan, Abdelraouf Eldeib
{"title":"Insulin-like Growth Factor 2 Binding Protein 2 Gene Polymorphism in Egyptian Patients with Type 2 Diabetes","authors":"Mohammed A. Hajar, Nagwan A. Sabek, Amany Y. Elkazaz, F. M. Hassan, Abdelraouf Eldeib","doi":"10.21608/EJB.2018.19873","DOIUrl":"https://doi.org/10.21608/EJB.2018.19873","url":null,"abstract":"Genome-wide association studies (GWAS) identified novel genes associated with type 2 diabetes mellitus (T2DM) which have been replicated in different ethnic populations and yielded inconsistent results. The insulin-like growth factor mRNA-2 binding protein 2 (IGF2BP2) is highly expressed in pancreatic islets, which play roles in normal embryonic growth and development. Our study aimed to replicate the association between insulin growth factor 2 mRNA binding protein 2 (IGF2BP2) gene (rs4402960) variant and T2DM in Egyptian diabetic patients resident in Ismailia city. The study included 152 subjects (76 unrelated T2DM patients and 76 control subjects) who were genotyped by polymerase chain reaction-restriction fragment length polymorphism technique (PCR- RFLP). Age, sex, blood pressure, BMI and Waist Circumference were recorded, and blood glucose, serum triglyceride, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and homeostatic model assessment (HOMA) indices were determined. Fasting serum insulin and IGF2BP2 protein levels were analyzed by ELISA. For rs440960 variant of IGF2BP2 gene, risk allele T frequency was associated with T2DM [OR (95% CI)=1.82 (1.14- 2.93), P= 0.012]. The frequency of T/T genotype versus (GG+G/T) genotypes was significantly higher in T2DM patients compared to controls (22.4% vs. 77.6% and 5.3% vs. 94.7%, respectively), (P=0.002). This association remained significant under additive (P=0.003) and co-dominant (P=0.009) genetic models. From this study, it could be concluded that IGF2BP2 rs4402960 polymorphism was found to be significantly associated with the increased risk of T2DM.Keywords: Type 2 diabetes mellitus, Single nucleotide polymorphism, IGF2BP2.","PeriodicalId":269335,"journal":{"name":"The Egyptian Journal of Biochemistry and Molecular Biology","volume":"95 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122046229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}