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The role of polymorphic cytochrome P450 gene(CYP2B6)in B-chronic lymphocytic leukemia(B-CLL)incidence and outcome among Egyptian patients

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Oncology Research 2024年第4期32卷 785-797页

作者： MENNA AL-ADL magdy MYOUSSEF AHMED EL-SEBAIE sherif REFAAT AFAF EL-SAID Division of Biochemistry Department of ChemistryFaculty of ScienceMansoura UniversityMansoura35511Egypt Hematology Unit Department of Clinical PathologyFaculty of MedicineMansoura UniversityMansoura35511Egypt Medical Oncology Unit Oncology Center Mansoura UniversityMansoura35511Egypt Department of Genetics Mansoura University Children’s HospitalMansoura35511Egypt

Cytochromes P450(CYPs)play a prominent role in catalyzing phase I xenobiotic biotransformation and account for about 75%of the total metabolism of commercially available drugs,including *** gene expression and enzyme activity of CYPs are variable between individuals,which subsequently leads to different patterns of susceptibility to carcinogenesis by genotoxic xenobiotics,as well as differences in the efficacy and toxicity of clinically used *** research aimed to examine the presence of the CYP2B6*9 polymorphism and its possible association with the incidence of B-CLL in Egyptian patients,as well as the clinical outcome after receiving cyclophosphamide *** was isolated from whole blood samples of 100 de novo B-CLL cases and also from 100 sex-and age-matched healthy *** presence of the CYP2B6*9(G516T)polymorphism was examined by PCR-based allele specific amplification(ASA).Patients were further indicated for receiving chemotherapy,and then they were followed *** CYP2B6*9 variant indicated a statistically significant higher risk of B-CLL under different genetic models,comprising allelic(T-allele vs.G-allele,OR=4.8,p<0.001)and dominant(GT+TT ***,OR=5.4,p<0.001)*** cyclophosphamide chemotherapy,we found that the patients with variant genotypes(GT+TT)were less likely to achieve remission compared to those with the wild-type genotype(GG),with a response percentage of(37.5%vs.83%,respectively).In conclusion,our findings showed that the CYP2B6*9(G516T)polymorphism is associated with B-CLL susceptibility among Egyptian *** variant greatly affected the clinical outcome and can serve as a good therapeutic marker in predicting response to cyclophosphamide treatment.

关键词： B-CLL Xenobiotics Cytochromes P450 CYP2B6

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Postoperative Radiotherapy in Bladder Cancer Patients: 5-Year Institutional Experience of National Cancer Institute, Cairo University

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Journal of Cancer Therapy 2015年第7期6卷 579-593页

作者： Azza M. Nasr Magda El Mongi Mamdouh Hagag Manar M. Moneer Hisham El Hossieny Azza Taher sherif magdy Radiation Oncology Department National Cancer Institute Cairo University Giza Egypt Clinical Oncology Department Faculty of Medicine Cairo University Giza Egypt Cancer Epidemiology and Biostatistics Department National Cancer Institute Cairo University Giza Egypt

Purpose: Adjuvant radiation therapy could reduce loco regional failure, but currently has no defined role because of previously reported morbidity. NCI-Cairo routine work is to give adjuvant PORT for locally advanced bladder carcinoma patients. The aim of this work is to re-evaluate this protocol regarding its effect on prognosis and complications. Patients and Method: A retrospective study included 208 patients with pathologically proven bladder cancer who presented to the NCI, Cairo University from 2007-2011. All of them underwent RC with bilateral PLND followed by conventional post-operative radiotherapy in 2 - 6 weeks after surgery for 5000 cGy in 25 fractions, over 5 weeks using 2D technique. Analysis of data from their files was done for the treatment results, prognostic factors and complications. Results: Three years overall survival (OS) and disease free survival (DFS) for the whole group was ~60%, and 54% respectively in favour of the female gender, non-smokers, Squamous cell carcinoma patients, low grade tumours (grade 1 and 2) negative margins, N0, pT2b and early stage group showed the best prognoses. The 3 years metastases free survival (MFS) was ~71%. Only four factors showed a significant relation with the MFS which were the grade, LN status, T-stage and group staging. The local recurrence rate (LRC) at 2 years for the whole group was ~95% and 94% at 3 years. Only surgical margin status and extent of LN dissection had a significant impact on the LRC. Conclusions: Adjuvant radiotherapy shows sustained improvement in the loco regional control, and should be recommended for patients with locally advanced disease especially those with less than 10 dissected lymph nodes and those with positive margins.

关键词： Bladder Cancer Radiotherapy Pelvic Irradiation

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Behavior of circulating epithelial tumor cells(CETC)and FISH(fluorescence in situ hybridisation)of epidermal growth factor receptor(EGFR)-gene amplification in lung cancer patients during the course of therapy

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Advances in Lung Cancer 2013年第1期2卷 1-8页

作者： May El sherif Claus Peter Schneider Carola Rabenstein Amina Hessein Hassab magdy Mamdouh El Bordiny Mona Wagdy Ayad Katharina Pachmann Departement of Experimental Heamatology and Oncology Clinic for Internal Medicine II Friedrich-Schiller-Universität JenaJenaGermany Oncology Departement Bad Berka Central Clinic Bad BerkaGermany Transfusion Center Bayreuth BayreuthGermany Clinical Pathology Department Faculty of MedicineAlexandria UniversityAlexandriaEgypt

Introduction: Monitoring the response of CETC to therapy in lung cancer allows early detection of patients at risk of progression. Analysis of the EGFR-gene amplification in these cells may help to characterize patients who might benefit from tyrosine kinase inhibitors. Methods: CETCs were quantified at least twice during treatment from blood of 52 patients with advanced non small cell lung cancer (NSCLC) using fluorescence labelled anti-EpCAM. EGFR-gene amplification was analysed in these cells with double probe (EGFR/CEP7) using FISH analysis. Results: Progression of the tumor was observed in 30 of the 52 patients (58%). With respect to changes in CETCs during therapy and progression free survival 31 patients showed a decrease in CETCs, 2 developing a single brain metastasis and 12 progressive disease;20 patients showed an increase in CETC more than twofold 16 of which developed progressive disease. The difference was highly significant (p=0.007 Fisher’s exact test) irrespective of age, sex, tumor size, pathological type and therapy. Kaplan-Meier progression free survival was significantly different between patients with decreasing and increaseing CETC (p=0.038). 5/20 patients tested were positive for EGFR amplification with 85-100% of EpCAM positive cells showing this chromosomal abnormality. One patient could be followed during therapy with increasing CETC during therapy with bevacizumab followed by relapse. He subsequently received erlotinib resulting in a decrease in CETC and is still free of progress after 516 days. Conclusions: These results show that peripherally circulating tumor cells in patients with advanced NSCLC are influenced by systemic chemotherapy and an increase in spite of therapy is a marker of aggressiveness of the tumor cells. Determination of the EGFR amplification might help to better treat part of these patients.

关键词： Circulating Epithelial Tumor Cells Lung Cancer EGFR-Gene Mutation Amplification FISH

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Role of endoscopic ultrasound and cyst fluid tumor markers in diagnosis of pancreatic cystic lesions

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World Journal of Gastrointestinal Endoscopy 2022年第6期14卷 402-415页

作者： Hussein Hassan Okasha Abeer Abdellatef Shaimaa Elkholy Mohamad-sherif Mogawer Ayman Yosry magdy Elserafy Eman Medhat Hanaa Khalaf magdy Fouad Tamer Elbaz Ahmed Ramadan Mervat E Behiry Kerolis Y William Ghada Habib Mona Kaddah Haitham Abdel-Hamid Amr Abou-Elmagd Ahmed Galal Wael A Abbas Ahmed Youssef Altonbary Mahmoud El-Ansary Aml E Abdou Hani Haggag Tarek Ali Abdellah Mohamed A Elfeki Heba Ahmed Faheem Hani M Khattab Mervat El-Ansary Safia Beshir Mohamed El-Nady Department of Internal Medicine and Hepatogastroenterology Kasr Al-Aini HospitalsCairo UniversityKasr Al-Aini HospitalsCairo UniversityCairo 11451Egypt Department of Endemic Diseases Cairo UniversityCairo 11451Egypt Department of Tropical Medicine and Gastroenterology Minia UniversityMinia 61511Egypt Department of Internal Medicine Kasr Al-Aini HospitalsCairo UniversityCairo 11562Egypt Department of Gastroenterology Armed forces College of MedicineCairo 11451Egypt Endoscopy and Internal Medicine Consultant at Dr/Ahmed Galal Endoscopy Center Alexandria 35516Egypt Department of Internal Medicine Faculty of MedicineAssuit UniversityAssuit 71111Egypt Department of Gastroenterology and Hepatology Mansoura UniversityMansoura 35511Egypt Department of Gastroenterology and Hepatology Theodor Bilharz Research InstituteCairo 11451Egypt Department of Microbiology and Immunology Faculty of Medicine for girls Al-Azhar UniversityCairo 11451Egypt Department of Internal Medicine Faculty of MedicineAin shams UniversityCairo 11451Egypt Department of Internal Medicine Bani-suef UniversityBani-suefBani-suef 62511Egypt Department of Pathology Faculty of MedicineCairo UniversityCairo 11451Egypt Department of Clinical Pathology Faculty of MedicineCairo UniversityCairo 11451Egypt Department of Environmental Medicine&Clinical Pathology National Research CentreCairo 11451Egypt

BACKGROUND Pancreatic cystic lesions(PCLs) are common in clinical practice. The accurate classification and diagnosis of these lesions are crucial to avoid unnecessary treatment of benign lesions and missed opportunities for early treatment of potentially malignant *** To evaluate the role of cyst fluid analysis of different tumor markers such as cancer antigens [e.g., cancer antigen(CA)19-9, CA72-4], carcinoembryonic antigen(CEA), serine protease inhibitor Kazal-type 1(SPINK1), interleukin 1 beta(IL1-β), vascular endothelial growth factor A(VEGF-A), and prostaglandin E2(PGE2)], amylase, and mucin stain in diagnosing pancreatic cysts and differentiating malignant from benign *** This study included 76 patients diagnosed with PCLs using different imaging modalities. All patients underwent endoscopic ultrasound(EUS) and EUS-fine needle aspiration(EUS-FNA) for characterization and sampling of different *** The mean age of studied patients was 47.4 ± 11.4 years, with a slight female predominance(59.2%). Mucin stain showed high statistical significance in predicting malignancy with a sensitivity of 87.1% and specificity of 95.56%. It also showed a positive predictive value and negative predictive value of 93.1% and 91.49%, respectively(P < 0.001). We found that positive mucin stain, cyst fluid glucose, SPINK1, amylase, and CEA levels had high statistical significance(P < 0.0001). In contrast, IL-1β, CA 72-4, VEGF-A, VEGFR2, and PGE2 did not show any statistical significance. Univariate regression analysis for prediction of malignancy in PCLs showed a statistically significant positive correlation with mural nodules, lymph nodes, cyst diameter, mucin stain, and cyst fluid CEA. Meanwhile, logistic multivariable regression analysis proved that mural nodules, mucin stain, and SPINK1 were independent predictors of malignancy in cystic pancreatic *** EUS examination of cyst morphology with cytopathological analysis and cyst fluid ana

关键词： Pancreatic cystic neoplasm Mucinous cystic neoplasm Intraductal papillary mucinous neoplasm Mucin stain Amylase

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