Index: Karolinska Institutet: KI North: Department of Women's and Children's Health


Neuroblastoma therapy response and resistance - In vitro studies of cell cycle regulation and cell death.


Supervisor: Shahrzad Shirazi Fard, PhD
Department: Department of Women's and Children's Health at Karolinska Institutet, Stockholm. Sweden
Postal Address: 171 76
Telephone: 08-517 72 764

E-mail: shahrzad.shirazifard@ki.se
Homepage: http://ki.se/en/kbh/neuroblastoma-micro-colonisation-and-chemotherapy-responseresistance


Neuroectodermal tumours include some of the most common and deadly malignancies of children. Relapse is the main cause of death and the outmost challenge in treatment is to inhibit spread and relapse. Neuroblastoma (NB) comprises a spectrum of embryonic tumours of the peripheral sympathetic nervous system. The group of NB tumours generally show a high degree of inter- and intratumoural heterogeneity on the genetic as well as phenotypic levels, and unique abilities to spontaneously regress/differentiate, or develop aggressive metastatic phenotypes.

We investigate cellular selection based on intra tumour heterogeneity in young children. Chemotherapy is central for high-risk neuroblastoma therapy and response has been associated with outcome. The project involves testing neuroblastoma cell-lines to visualise and quantitatively measure early outcome parameters following chemotherapy, such as analysis of markers of apoptosis, cell death, proliferation and cell cycle. Using a microscope scanning system, single cells will be identified, excluding overlaying cells and background noise. This is followed by Metafer analysis for automated quantitative high through-put measurements of DNA index enabling single cell subG1 measurements, used as a quantitative indicator of cell death. Thereafter parameters for therapy response, including single cell analysis of markers for proliferation and cell death will be investigated.

Main techniques used: Cell culturing, immunohistochemistry, EdU staining, TUNEL, microscope scanning and Metafer analysis.

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