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العنوان
Investigation of Genetic and Gene Expression changes Driving Poor Outcome Pediatric Hodgkin’s Lymphoma /
المؤلف
Ahmed, Ghada Mohamed Abdel-Salam.
هيئة الاعداد
باحث / غاده محمد عبد السلام احمد
مشرف / ماجده مراد السيد حسن
مشرف / بول موراي
مشرف / ايمان عطيه علي
الموضوع
Lymphoma.
تاريخ النشر
2015.
عدد الصفحات
171 p. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
علم الأورام
تاريخ الإجازة
1/1/2015
مكان الإجازة
جامعة القاهرة - معهد الأورام القومى - Oncologic Pathology
الفهرس
Only 14 pages are availabe for public view

from 202

from 202

Abstract

A subset of children with Hodgkin’s lymphoma has disease that is either refractory to treatment or which relapses early; outcome for these groups is particularly poor. Moreover, patients receiving combined treatment including chemotherapy and radiotherapy are at higher risk for second malignancies and show a higher morbidity and mortality than other people of the same age because of long-term therapy-related events. For these reasons, there is a need for better treatment strategies, through reduction of chemotherapy dose, the use of less toxic chemotherapeutic agents as well as developing a mutation-directed therapy. In our study we generated a list for the top 30 up-regulated genes in HL and we showed that ”Thioredoxin, TRX-1, TXN” is up-regulated in the malignant Hodgkin Reed-Sternberg (HRS) cells of Classic Hodgkin lymphoma (cHL). However its role and clinical impact haven’t been studied in HL. We have confirmed by western blot and qPCR analysis that HL cells are characterized by higher basal level of TRX-1 expression than that in B -germinal center cells (the proposed site of HL origin). Our immunohistochemical results also proved that TRX-1 protein is weak or nega􀆟ve in GCs of reactive lymphoid tissues. We have shown for the first time that TRX-1 knock-down had a significant reduction effect on cHL cell lines proliferation. Moreover, we showed that cHL cells are sensitive to one of TRX-1 inhibitor, PX-12 which significantly reduced HL cells prolifera􀆟on in a dose-dependent manner. Furthermore in our study, by investigating TRX-1 expression in cHL pa􀆟ents (185 cases), we showed that TRX-1 protein is always expressed in the cases (both in H/RS cells and microenviroment macrophages) but with variable intensities. We suggested that TRX-1 has a role in HL through both intrinsic and extrinsic ways (by its high expression in both HL tumor cells and microenviroment cells). Importantly, we found a significant correlation between TRX-1 expression and pediatric cHL (52 cases) stage as well as with the initial presentation with numbers of the affected lymph nodal sites, which usually used as risk stratification in HL patients. Overall, our results highlighted for the first time the importance of TRX-1 in HL pathobiology and prognosis.