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العنوان
Molecular Analysis of Induced Leukemia in Mice Treated with a Novel Bithiophene Derivative \
المؤلف
Al-gharib, Ali Mohamed Samy.
هيئة الاعداد
باحث / على محمد سامي الغريب
مشرف / جميلة محمد لبيب شنب
مشرف / عبدالرحمن بدرالدين عبدالغفار
مشرف / رانيا حسن محمد
تاريخ النشر
2022.
عدد الصفحات
198 p. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
Biochemistry
تاريخ الإجازة
1/1/2022
مكان الإجازة
جامعة عين شمس - كلية العلوم - الكيمياء الحيوية
الفهرس
Only 14 pages are availabe for public view

from 198

from 198

Abstract

Leukemia is a group of malignant disorders affecting the blood and blood-forming tissues in the bone marrow, lymphatic system, and spleen. Leukemias are classified as myeloid or lymphoid, according to the affected stem cell type, and also can be classified as either chronic or acute. The behavior of leukemia is different from that of other cancers, which usually begin in major organs and ultimately spread to the bone marrow. The risk for cancer is multifactorial and often seems to have confusing causes with no easy cures. A substantial portion of cancer incidence rates is believed to be due to environmental factors (e.g. diet and exposure to certain chemicals). In the light of the resistance developed to many of the current chemotherapeutic drugs, the main aim in cancer chemoprevention remains the discovery of new medicines that are safe and effective. The current research was undertaken to investigate the anti-cancer efficacy of a novel bithiophene derivative bithienyl fluorobenzamidine (BFB) on induced leukemia. Male Swiss albino mice were divided randomly into 6 groups: normal healthy control, leukemic positive control group treated with 7,12-dimethyl benz[a] anthracene (DMBA) in order to induce leukemia (DMBA-treated), control mice treated with either 1\10 and 1/5 LD50 (controls), leukemic mice treated with either 1\10 and 1/5 LD50 (treated). Histological examination of liver and spleen tissues was performed via the light microscope. Hematological examination of peripheral blood and bone marrow were also assayed. Induction of acute myeloid leukemia (AML) in mice treated with DMBA was diagnosed as a significant increase in bone marrow hematological parameters. Treatment with BFB ameliorates leukemic mice significantly as shown by histological and hematological examination. To assess the molecular effect of BFB, the expression of p53, cdk1, p21, p-AKT, PTEN and caspase-3 was evaluated by qPCR, ELISA and/or Western blotting. The improvement in the leukemic group after treatment was through modulation of cell cycle and apoptosis, as manifested by the significant up-regulation of p53 and CDKN1a and downregulation of CDK1 gene expression, as well as up-regulation of caspase-3 level. In conclusion, the novel bithiophene derivative may have a potential as a prospective drug for the treatment of AML by either induction of apoptosis or by cell cycle arrest.