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Article
THE INFLUENCE OF N-RAS GENE MUTATIONS ON THE RESPONSE TO INDUCTION THERAPY IN AML IRAQI PATIENTS

Authors: Nahidh K. Alwan ناهض كامل علوان --- Raad J. Musa رعد جابر موسى --- Ban A. Abdul-Majeed بان عباس عبد المجيد
Journal: IRAQI JOURNAL OF MEDICAL SCIENCES المجلة العراقية للعلوم الطبية ISSN: P16816579,E22244719 Year: 2013 Volume: 11 Issue: 3 Pages: 230-237
Publisher: Al-Nahrain University جامعة النهرين

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Abstract

Background:N-RAS mutations are the most commonly detected molecular abnormalities in hematologic malignancies, especially in those of myeloid origin.Objective:Current study aimed to determine the frequency of N-RAS mutation; and its influence on response to induction therapy in patients with acute myelogenous leukemia (AML) in Iraq.Methods:Peripheral blood and bone marrow samples were taken from 58 newly diagnosed AML patients and 30 individuals with reactive bone marrow were selected as a control group. Samples screened for N-RAS gene mutations using nested PCR were followed by mutation sensitive digestion analysis (MSDA).Results:N-RAS mutations at the time of diagnosis were found in 10/58 (17.24%) patients with AML and no mutation in control individuals. Patients with mutant N-RAS showed lower complete remission (CR) than wild type, the difference was not significant (60% vs. 72.92%, P = 0.414).Conclusion:The current results provide clues for activation of RAS-signaling cascade in AML patients, supporting their role in molecular pathogenesis of leukemia. N-RAS mutations show no influence on CR rate in AML patients. Further studies on larger scale to define the prognostic significance of N-RAS mutations are recommended.Keyword:AML, N-RAS mutation, MSDA, complete remission.

Keywords

AML --- N-RAS mutation --- MSDA --- complete remission


Article
DETECTION OF NUCLEOPHOSMIN (NPM-1) AND FLT3-ITD MUTATIONS IN 30 IRAQI PEDIATRIC ACUTE MYELOID LEUKEMIA PATIENTS

Author: Subh S AL-Mudallal صبح سالم المدلل
Journal: IRAQI JOURNAL OF MEDICAL SCIENCES المجلة العراقية للعلوم الطبية ISSN: P16816579,E22244719 Year: 2013 Volume: 11 Issue: 1 Pages: 40-49
Publisher: Al-Nahrain University جامعة النهرين

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Abstract

Background:Mutation within the FLT 3 and NPM 1 genes ranked within the most frequent recurrent known genetic markers in acute myeloid leukemia (AML) and show apparently opposite prognostic significance.Objective:To detect the frequency of FLT3-ITD and NPM-1 mutations in Iraqi pediatric AML patients using conventional polymerized chain reaction (PCR), and to relate their prevalence with the clinical presentation and the response to induction therapy.Methods:A prospective study of 30 children presented with AML and 16 children who were age and gender matched served as negative control for the mutation. AML cases were classified according to FAB classification. WBC count, platelet count and hematocrit were measured at diagnosis and after 30 days. Molecular analysis was done on peripheral blood or bone marrow aspirate samples by conventional PCR technology.Results:FLT 3-ITD mutation was detected in 3/30 (10%) patients, whereas NPM1 mutation was detected in 4/30 (13.33%) patients. Both mutations were detected in older age patients and predominantly in male. No significant correlation between each mutation and various hematological parameters, however WBC count was significantly higher in FLT-ITD unmutated patients. FLT3-ITD mutation was detected in M3 and M3 variant whereas NPM-1 mutation was detected in M2 and M3v. The three patients having FLT-3-ITD mutation (100%) did not achieved complete hematological remission, whereas 3/24 (12.5%) patients without the mutation did not achieve remission. On the other hand 2 out of 4 (50%) patients with NPM-1 mutation had not achieved complete hematological remission and 4/22 (18.18%) patients without mutation did not achieve remission. Finally regarding the interrelation between the two mutations, the two children who had NPM1 mutation and no FLT3-ITD mutation had achieved complete remission on induction therapy whereas the three children who had FLT3-ITD mutation with or without NPM1 mutation did not achieved complete remission.Conclusion:Prevalence of FLT3-ITD and NPM-1 mutations in Iraqi pediatric AML patients is comparable to that recorded worldwide and both mutations were observed in older age children and mainly in male. FLT3-ITD mutation unlike NPM-1 mutation associate with poor response to induction therapy and the adverse effect of FLT3-ITD mutation overcome the favorable effect of NPM-1 mutation when they exist together.Keywords:Pediatric AML, Flt3-ITD mutation, NPM1 mutation, PCR


Article
ANALYSIS OF N-RAS GENE MUTATIONS AND P21N-RAS PROTEIN EXPRESSION IN IRAQI PATIENTS WITH IN AML

Authors: Nahidh K. Alwan ناهض كامل علوان --- Raad J. Musa رعد جابر موسى --- Ban A. Abdul-Majeed بان عباس عبد المجيد
Journal: IRAQI JOURNAL OF MEDICAL SCIENCES المجلة العراقية للعلوم الطبية ISSN: P16816579,E22244719 Year: 2013 Volume: 11 Issue: 4 Pages: 329-339
Publisher: Al-Nahrain University جامعة النهرين

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Abstract

Background:N-RAS mutations are the most commonly detected molecular abnormalities in hematologic malignancies, especially in those of myeloid origin.Objective:Current study aimed to determine the frequency of N-RAS mutation and its correlation with P21N-RAS protein expression in patients with acute myelogenous leukemia (AML) in Iraq.Methods:Peripheral blood, bone marrow aspirate and biopsy samples were taken from 58 newly diagnosed AML patients (57 de novo and 1 therapy related AML) and 30 individuals with reactive bone marrow conditions were selected as a control group. Samples screened for N-RAS gene mutations using nested PCR followed by mutation sensitive digestion analysis (MSDA), and immunohistochemical analysis of P21N-RAS protein expression by using anti N-RAS monoclonal antibody.Results:N-RAS mutations at the time of diagnosis were found in 10/58 (17.24%) and P21N-RAS expression found in 5/58 (8.62%) patients with AML. There was a significant difference (P = 0.001) in P21N-RAS expression between mutant and wild type N-RAS patients with AML. No N-RAS mutations or P21N-RAS expression detected in the control group individuals.Conclusion:It can be suggested that there is activation of RAS-signaling cascade in AML patients, this is may support their role in molecular pathogenesis of acute leukemia. Also, there was a significant difference between N-RAS gene status and P21N-RAS protein expression in patients with AML.Keyword:AML, N-RAS Mutation, MSDA, P21N-RAS expression, Digital analysis.


Article
Experience with treatment of fifty eight Iraqi patients with Acute Myeloid Leukemia
الخبرة في معالجة ثمانية وخمسون مريضا عراقيا بالغاً مصابين بسرطان الدم النقياني الحاد

Author: Khudhair A. AL-Khalissi خضير عباس الخالصي
Journal: Journal of the Faculty of Medicine مجلة كلية الطب ISSN: PISSN: 00419419 / EISSN: 24108057 Year: 2013 Volume: 55 Issue: 4 Pages: 290-295
Publisher: Baghdad University جامعة بغداد

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Abstract

Background: Adults with Acute Myelogenous Leukemia (AML) have the lowest survival rate of all leukemias. Complete remission (CR) rate after induction therapy is about 55-85%, however 30% of patients fail to achieve remission and they remain alive only for about a year. Consolidation chemotherapy results in 5-year overall survival (OS) of about 30%.Objectives: To study characteristics of adult patients with AML who attended Baghdad Teaching Hospital, their response to induction therapy and then to consolidation therapy, and their 5-year (OS) and disease free survival (DFS).Patients and methods: Sixty seven patients with AML (excluding M3) were admitted to the haematology ward /seventh floor/Medical city teaching hospital during 2008 with follow up till the end of 2012. Fifty eight patients included in the study, 47 patients (≤ 60-year) received 3+7 induction regimen. Nine (> 60 year) received attenuated courses of subcutaneous cytosar, or 2+5 regimen (according to presence or absence of co-morbidities). Those who attained CR were consolidated mainly with Modified MiDAC.Results: Eleven patients who received attenuated induction therapy had a median survival of 6-8 months and none of them achieved CR. Twenty six (55.5%) out of 47 patients who received 3+7 induction regimen had CR with treatment related mortality( TRM) of 34%, while OS and DFS were 30% and 34% respectively.Conclusion and recommendation: Early referral to the hospital is essential to avoid high early mortality. OS and DFS in our study is comparable to other studies in spite of shortage of antibiotics and cytotoxic therapy.Key words: AML, induction, consolidation, OS, DFS.

الخلفية : سرطان الدم النقياني الحاد عند البالغين يعتبر من الأمراض التي لا يعمر فيها المريض طويلا وان نسبة الشفاء لمدة خمس سنوات هي حوالي 30%.الغرض من البحث : دراسة خصائص المرضى المصابين المراجعين الى مستشفى بغداد التعليمي واستجابتهم للعلاج ونسبة المرضى الذي يتعافون لمدة خمس سنوات.طريقة اجراء البحث : تم ادخال 67 مريضاً الى الطابق السابع في مستشفى بغداد التعليمي خلال سنة 2008 وبعد استلامهم للعلاج تمت متابعتهم لغاية نهاية 2012. تم استبعاد 9 مرضى من الدراسة بسبب وفاتهم خلال اسبوعين وكان عدد المرضى المشمولين بالبحث هو 58 من ضمنهم 47 مريضا بعمر 60 سنة أو أقل واستلموا العلاج (7+3). أما المرضى الذين كانت أعمارهم فوق الستين سنة فتمت معالجتهم بـ(5+2) أو دواء السايتوسار تحت الجلد ثم اعطي العلاج (المايداك المحور)لمن اكتسبوا حالة الهدوء لغرض تثبيت الشفاءالنتائج : كان معدل بقاء المرضى الذين كانت أعمارهم أكثر من ستين سنة هي 6 – 8 شهور ولم يكتسب أيا منهم الشفاء أما نسبة البقاء لمدة 5 سنوات بالنسبة للمرضى الذين كانت أعمارهم 60 سنة أو أقل فقد كانت 30%.الاستنتاج والتوصيات : الاحالة السريعة الى المستشفى عند التشخيص أو الاشتباه بالمرض ضرورية جدا لتلافي الوفاة المبكرة وقد كانت نسبة الشفاء لمدة 5 سنوات مقاربة للدراسات المنشورة الاخرى.مفتاح الكلمات : سرطان الدم النقياني الحاد، العلاج، تثبيت العلاج، نسبة الشفاء لمدة خمس سنوات


Article
Role of Interleukin-1α and Interleukin-8 in Myocardial Infarction
دور (IL_8) و (αIL- 1) في احتشاء العضلة القلبية

Author: Mosadak.I. Shakib مصدق ابراهيم شكيب
Journal: IRAQI JOURNALOF COMMUNITY MEDICINE المجلة العراقية لطب المجتمع ISSN: 16845382 Year: 2013 Volume: 26 Issue: 1 Pages: 75-77
Publisher: Al-Mustansyriah University الجامعة المستنصرية

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Abstract

AbstractObjective: To study the effect of interleukin-1α and interleukin-8 in tissue injury during ischaemia and reperfusion in acute myocardial infarction patients.Methods: Concentrations of (IL-1α) and (IL-8) for 25 patients with Acute Myocardial Infarction measured by enzyme linked immunosorbent assay (ELISA). Results: All 25 patients with acute Myocardial Infarction had a significant rise in serum (IL-1α) and ( IL-8) concentrations (33.62333±12.82255) (117.46±109.75) compared to normal subjects (14.032467±1.798464) (8.951± 5.7) respectively.Conclusion: It is clear that (IL-1α) and (IL-8) results have a role in the development of tissue injury in acute myocardial infarction.Key Words: Acute Myocardial Infarction (AML), Interleukin-1α (IL-1α) and Interleukin-8 (IL-8).

الخلاصة:الهدف: لتحديد هل ان (IL-8) و (αIL- 1) (كلاهما منشط قوي للكريات الدموية البيضاء المتعادلة) لهما دور في تلف الانسجة خلال Ischaemia وعوده الحياة في تلك الانسجة في المرضى المصابين باحتشاء العضلة القلبية الحاد (AMI).طريقة العمل: تم قياس التراكيز (IL-8) و (αIL- 1) لـ 25 مريض مصاب باحتشاء العضلة القلبية الحاد بطريقة (ELISA).النتائج: اظهرت النتائج زيادة احصائية ملحوظه لتراكيز (IL-8) و (αIL- 1) في مصول مرضى احتشاء العضلة القلبية الحاد مقارنة بالاشخاص الطبيعيين.الاستنتاج: هذه النتائج تشير الى ان (IL-8) و (αIL- 1) مهمة في تطور تقدم مراحل احتشاء العضلة القلبية في مرضى احتشاء العضلة القلبية الحاد.الكلمات المفتاحية: احتشاء العضلة القلبية الحاد (AMI)، (αInterleukin-1) (αIL-1) و (Interleukin-8) (IL-8) Mobile: 07703921469

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