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Detection of ABCB1 Polymorphisms in Breast Cancer By High-Resolution Melting Curve Analysis And Its Association with Clinical, Radiological Outcome and Drug Resistance (Assuit University)
Egypt (IFMSA-Egypt) - Assiut University, Assiut
South Egypt Oncology Institute, City Street, Assiut city, Assiut, Egypt.
Prof. Dr. Mustafa El-Sharkawi
Dr. Dina Ismail Abd El Razik
Type of Research Project
- Clinical Project with Laboratory work
What is the background of the project?
Breast carcinoma is the most common cancer in women. Cytotoxic, hormonal and targeted drugs play an important role in the treatment of patients with breast carcinoma. Anthracycline-based regimens are preferred and the addition of taxanes increases the survival rate. Primary or acquired overexpression of ABCB1 is the major cause of resistance to chemotherapy and is associated with reduced patient survival, also negatively correlated with disease prognosis and quality of life, a multidrug resistance phenotype often correlates with high expression of P-glycoprotein, the most common ABC transporter in the ABCB1 gene region. A highly sensitive method to identify a single nucleotide change in a specific DNA sequence was described, which determines DNA changes based on the fine melting temperature properties of an amplicon of the sequence of interest, this method is called high-resolution melting (HRM).
What is the aim of the project?
1) To develop and validate HRM-based methods for assessment of the most frequently studied SNPs in ABCB1 (rs2214102, rs2035282 ) 2) Study the Associations of ABCB1 SNPs with radiological and/or pathological complete response of breast carcinoma patients treated by poly chemotherapy containing either anthracycline or taxane chemotherapy in order to show potential importance of ABCB1 genetic variability for drugs resistance and outcome of patients.
What techniques and methods are used?
1-Peripheral blood samples will undergo DNA extraction 2- ABC1 gene amplification using PCR and analsis of ABC1 polymorphysim using high resolution melting curve analysis.
What is the role of the student?
- The student will observe the practical experiments but will be highly involved in the analysis of the results
- The tasks will be done under supervision
- If the project includes “lab work”
- the student will take active part in the practical aspect of the project
- If the project is clinical
- the student will take active part in the clinical examination
- If the project is clinical
- the student will be allowed to work with patients
- The tasks of the student will be performed on his/her own
What are the tasks expected to be accomplished by the student?
1-Help in the collection of samples from 50 breast cancer patients. 2- participate in the process of DNA extraction and the amplification of ABC1 gene using PCR and its analysis using high resolution melting curve analysis. 3-data analysis and results comprehension are expected to be done under supervision of the professor first, then done on the student’s own, and the professor will review and discuss the results with them at the end.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Lectures conecring the topic & presentation of the clinical skills used.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a scientific report - The student will prepare a poster - The student will prepare a presentation - The student will prepare an abstract
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
it's prefered if the student have studied Oncology.
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students
- Ferlay J; Shin HR; Bray F; Forman D; Mathers C; Parkln DM. GLOBOCAN 2008 v1.2; Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 (Internet). Lyon; France: international Agency for Reseach on Cancer; 2010. Avariable from URI;: http://globooan.iarc.fr Accessed 19 September; 2011'
- Aigner J; Schneeweiss A; Sohn C;Marm E F The role of neoadjuvant chemotherapy in the management of primay breast cancer Minerva Gineco 2011;63:261-74..
- Wise JG (2012). Catalytic transitions in the human MDRI P-glycoprotein drug binding sites Biochemistry 51 5125-5141
- Baker EK; johnstone RW; Zalcberg JR and El-Osta A (2005) Epigenetic changes to the MDR1 locus in response to chemotherapeutic drugs Oncogcne 24 8061-8075
- Sakaeda T; Nakamura T; Okumura K. Pharmacognetics of drug transporters and its impact on the ;pharmacotherapy Curr TopMed Chem 2004:4:1395- 98.
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