Masteruppsatser / Medicinsk strålningsvetenskap

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Browsing Masteruppsatser / Medicinsk strålningsvetenskap by Subject "apoptosis"

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    Apoptosis induction in breast cancer cells after radiotherapy and potential radiosensitizers
    (2023-06-27) Simonsson, Klara; University of Gothenburg/Institute of Clinical Sciences; Göteborgs universitet/Institutionen för kliniska vetenskaper
    Background. Today breast cancer is the foremost cancer death type amongst women around the world. At present some of the toughest challenges in the clinic is recurrent, radioresistant breast cancer, and metastatic breast cancer where low cure rates are observed after surgery and radiotherapy. One way to possibly increase survival rates, is combining radiotherapy and systemic therapy that doubles as a radiosensitizer. The aim of this thesis was to identify pathways that increase radiosensitivity in breast cancer cells after combination treatment with external irradiation and anti-cancer drugs, specifically through increased apoptosis. Method. Three different human breast cancer cell lines were cultured: MCF-7, MDA-MB-453 and HCC-1806. A dose-response study with irradiation was performed on the cells to determine a radiation absorbed dose and time-point after irradiation for the following combination treatment. Lastly, cells were treated with anti-cancer drugs +/– irradiation, and then stained with the fluorescent dyes Annexin V-DyLight 650 (apoptosis marker) and Hoechst 33342 (cell viability marker) whereafter flow cytometry was performed. Results. A dose and time dependency was observed in the dose-response study. In total, 29 of 31 anti-cancer drugs exhibited a synergistic effect with radiation on any cell line at any concentration. The drugs birinapant (with target IAP) and ganetespib (with target HSP90) showed statistically significant radiosensitizing effects on all three cell lines. Conclusions. Possible radiosensitizing targets for all three cell types included in this study are HSP90 and IAP. In addition, BH3 mimetics are potential radiosensitizing targets for cell lines MDA-MB-453 and HCC-1806, and the DNA repair machinery was a radiosensitizing target for cell line HCC-1806.
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    APOPTOTIC EFFECTS IN RENAL CORTEX AFTER TREATMENT WITH 177LU-OCTREOTATE
    (2021-05-10) Andersson, Michelle; University of Gothenburg/Institute of Clinical Sciences; Göteborgs universitet/Institutionen för kliniska vetenskaper
    Purpose: The purpose of this project was to investigate gene regulation of a predetermined panel of apoptotic genes in murine renal cortex after treatment with 177Lu-octreotate after one day and seven days. Theory: The kidneys and bone marrow are the risk organs in 177Lu-octreotate treatment, but by fractioning the treatment the bone marrow recovers. This leads to the kidneys being the dose-limiting risk organ. Apoptosis is a known effect after irradiation of cells and can result in nephrotoxicity after treatment. Whether apoptosis is initiated or inhibited after irradiation depends on a balance of pro-apoptotic and anti-apoptotic signals in the cells and is controlled by many genes divided into gene families. By analysing the expression of apoptotic genes, information about the induction or inhibition of apoptosis can be obtained. The absorbed dose is calculated in order to relate the responses in the tissue to irradiation by 177Lu. The renal cortex receives a higher absorbed dose after treatment with 177Lu-octreotate and is therefore of high interest when studying apoptosis. Method: RNA from the kidney cortex of 12 different mice was used for the analysis. The mice were divided into two irradiated and two control groups and killed at one or seven days after administration of 150 MBq 177Lu-octreotate or physiological saline, respectively. A panel of both pro-apoptotic and anti-apoptotic genes was investigated with a quantitative real-time polymerase chain reaction (QPCR) array. Prior to this, the RNA-concentration was determined with the Qubit ® assay in order to use the same amount of RNA in the QPCR assay. The absorbed dose in the kidney cortex was calculated for each mouse in the irradiated groups and the transcriptional response was related to the absorbed dose and time of irradiation. Result: The group that received a lower absorbed dose and was killed after one day (group 1) showed a higher increase in transcriptional response to irradiation than the group killed after seven days (group 2). The regulation in group 1 indicated pro-apoptotic responses in the renal cortex, wheras in group 2, a shift to anti-apoptotic responses was observed.