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Impact of the new class of clinically relevant drugs: Imipridones on the migration of mantle cell Lymphoma cells
University of Skövde, School of Bioscience.
2018 (English)Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

Mantle cell lymphoma (MCL)is a subtype of B-cell lymphoma characterized by chromosomal translocation t(11;14)(q13;q32), enhancing the expression of cyclin D1, resulting in alteration in cell cycle progression. The translocation is the key event for initiation of mantle cell lymphoma however is not sufficient for the development of the disease. Changes in the expression of the G-protein coupled receptors in different cancer types due to mutations and other regulating mechanisms can lead to changes in expression of proteins, resulting in defects in signalling pathways,favouring tumor dissemination. Growing evidences suggests that the disease progression in various B cell malignancies is due to the interactions between neoplastic B cells and stromal cells in tissue microenvironment. ONC201 is an imipridone, which is an antagonist to a type of G-protein coupled receptor: dopamine receptor D2. ONC201 has the property for inhibiting proliferation and inducing apoptosis. The objective of the project was to investigate the migration of MCL cells towards fetal bovine serum and by this, study the impact of ONC201 on the migration of mantle cell lymphoma cells using chemotaxis assay. Theapoptotic effect of the drug was examined by detection of activecaspase-3 and cleaved PARP proteins using western blotting. The chemotaxis assay and western blot demonstrated that ONC201 inhibited migration of the mantle cell lymphoma cell lines at the concentration-dependent manner without inducing apoptosis in the cells at the investigated time point. The expression of cyclin D1 in the cells treated with ONC201 was also investigated after incubation period of 24 hours and it was observed that ONC201 plays a role in reducing cyclin D1 expression in mantle cell lymphoma cells.

Place, publisher, year, edition, pages
2018. , p. 30
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:his:diva-16296OAI: oai:DiVA.org:his-16296DiVA, id: diva2:1255760
Subject / course
Molecular Biology
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Available from: 2018-10-16 Created: 2018-10-15 Last updated: 2019-01-09Bibliographically approved

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