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Identifier

000419774

Title

Study of p53 dependent signaling pathways involved in human lymphoma pathogenesis using MS-based proteomics combined with Transmission Electron Microscopy and High Content Imaging

Alternative Title

Μελέτη p53 εξαρτώμενων σηματοδοτικών μονοπατιών σχετιζόμενα με την παθολογία του λεμφώματος μέσω MS-προτεωμικής ανάλυσης σε συνδυασμό με TEM και HCI

Author

Καρκαβίτσα, Άννα-Ασπασία Ν.

Thesis advisor

Αϊβαλιώτης, Μιχαήλ

Reviewer

Παπαματθαιάκης Ιωσήφ
Ποντικόγλου, Χ.

Abstract

The heterogeneity of lymphomas is the major issue that leads to different responses to treatments. Even though the survival rate has increased over the last decades, many patients and particularly elderly people, do not respond to treatments, and in fact the chemotherapy regimens used are not well-tolerated by them. Thus, it is of great need to find new ways for developing new more tolerable and efficient treatments. Nutlin-3a (N3a) is a recently developed small molecule which antagonizes MDM2 and disrupts the interaction between p53 and MDM2. Lymphomas show high percentage of wild type p53 at diagnosis and as a result they are strong candidates for treatment with N3a.The apoptotic effect of N3a was assessed in three lymphoma types (Hodgkin lymphoma, Mantle Cell Lymphoma and Anaplastic Large Cell Lymphoma) using High Content Imaging. High Content Imaging was also used for the study of the mitochondria and their membrane potential deregulation after treatment with N3a. Bionformatics analysis of data from MS-based proteomics revealed that N3a treatment influenced the autophagic pathway. Verification of the proteomics data was achieved using Transmission Electron Microscopy and Western Blots. In addition, an effort was made to study the effect of N3a on NFκΒ signaling. Finally, our results showed the apoptotic effect of N3a in the three lymphoma types of our study and also indicated a deregulation of the mitochondrion’s’ membrane potential. They also indicated an increase in the autophagic pathway after treatment with different concentrations of N3a.

Language

English

Subject

Lymphoma

Nutlin-3a

Λέμφωμα

Issue date

2018-11-23

Collection

School/Department--School of Sciences and Engineering--Department of Biology--Post-graduate theses

Type of Work--Post-graduate theses

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