Masters Degrees (Nuclear Medicine)

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Browsing Masters Degrees (Nuclear Medicine) by browse.metadata.advisor "Akudugu, John M."

Now showing 1 - 3 of 3
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    Evaluation of BCL-2 and PARP-1 as potential therapeutic targets to radiosensitise lung cancer
    (Stellenbosch : Stellenbosch University, 2021-12) Guillaume, Muteba Mpolesha; Akudugu, John M.; Serafin, Antonio M.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Nuclear Medicine.
    ENGLISH SUMMARY : Lung cancer remains the most incident malignancy worldwide, representing 13% of all cancers. It is also the leading cause of death in the world, accounting for 18 18.2% of global cancer-related deaths. The burden of lung cancer in Africa is increasing due to ag ageing an and population growth, increased prevalence of risks factors such as smoking, occupational exposure, infections, lifestyle changes, and environmental pollutants. The efficacy of many therapeutic strategies has been hindered by normal tissue toxicity and treatment resistance. For many cancer patients, radiotherapy has been the chosen therapeutic option to minimise cancer cell spread by shrinking the tumour while ensuring protection of normal tissue. There is evidence that small molecule inhibitor s can effectively target cell survival signa signalling pathways, but cancer cell cells manage to find molecular escape routes to either repair the damage or evade cell death. Combination therapy appears to be an appropriate approach to address these challenges. Therefore, targeting more than one component of the cell survival signa signalling pathways could potentially sensitise cancer cells to irradiation and improve the outcome of radiotherapy. The purpose of this study was to evaluate the role of targeting the anti-apoptotic (B-cell lymphoma 2 (Bcl -2)) pathway and the DNA repair (poly (ADP ADP-ribose) polymerase 1 (PARPPARP-1)) pathway with specific inhibitors in modulating the radiosensitivity of a lung cancer cell line ( and an apparently normal lung cell line ( For this, Bcl -2 and PARP PARP-1 were inhibited using ABT ABT-737 and ABT ABT-888, respectively. At a dose of 2 Gy, the typical fractional dose in conventional radiotherapy, combined inhibition of Bcl-2 and PARP-1 or inhibition of Bcl-2 alone resulted in significant radio-sensitisation in only the A549 cells. However, at a larger radiation dose of 6 Gy (a potentially useful fractional dose in hypo-fractionated radiotherapy), inhibition of Bcl-2 and PARP-1 markedly radio-sensitised the apparently normal (L132) and malignant (A549) cell lines, respectively. These findings suggest that use of Bcl-2 and PARP-1 inhibitors might be beneficial when combined with conventional radiotherapy, but not with hypo-fractionated radiotherapy when large fractional radiation doses are employed. However, validation of these results with a larger panel of cell lines is warranted.
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    Evaluation of the effect of low and intermediate frequency electromagnetic waves on radiosensitivity
    (Stellenbosch : Stellenbosch University, 2016-12) Chinhengo, Angela; Akudugu, John M.; Serafin, Antonio M.; Stellenbosch University. Faculty of Medicine and Health Science. Dept. of Medical Imaging and Clinical Oncology. Nuclear Medicine.
    ENGLISH SUMMARY : The incidence of epidemic Kaposi’s sarcoma in HIV/AIDS patients is high due to their compromised immune system. HIV-positive individuals presenting with cancer tend to be more sensitive to ionizing radiation and are at a higher risk of developing severe side effects during radiotherapy, and there is a need to develop non-invasive methods to preferentially sensitize cancer cells and reduce therapeutic doses. Here, the effects of 100 and 1000 Hz electromagnetic fields (EMF) broadcast via an argon plasma ray tube at 50 W on the radio sensitivity of apparently normal Chinese hamster lung fibroblasts (V79) and human malignant melanoma cells (MeWo) were evaluated using the colony forming assay. Pre-exposure of the fibroblasts to both fields had no effect on their radio sensitivity, if X-ray irradiation followed within 2 h or at 6 h. Significant radio sensitization was observed when X-rays were administered 4 h after EMF exposure. For the MeWo cells, pre-exposure to 100 Hz resulted in a significant radioprotection when irradiation followed within 6 h. However, treatment of these cells with a 1000 Hz field significantly potentiated the effect of X-rays. When cells were irradiated prior to EMF exposure, the V79 cells were marginally protected by the 100 Hz field and sensitized by the 1000 Hz field. In contrast, the melanoma cells were slightly protected by the 1000 Hz field and sensitized by the 100 Hz field. The survival rate of the normal fibroblasts when treated with 2 Gy, in two fractions of 1 Gy 6 h apart, was similar to those obtained when cells received an acute dose of 2 Gy 6 h prior to or after exposure to both EMF frequencies. On the other hand, the melanoma cells were significantly sensitized when they were either treated with a combination of X-rays and then 100 Hz EMF 6 h later or with a combination of either of the EMF frequencies and then X-rays 6 h later. These data suggest that use of electromagnetic fields may sensitize tumours to radiation therapy and reduce normal tissue toxicity. Informed and well-designed combinations of low-medium frequency electromagnetic fields and radiation therapy might be beneficial in the management of cancers, especially epidemic Kaposi’s sarcoma.
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    Radiosensitisation of low HER-2 expressing human breast cancer cell lines
    (Stellenbosch : Stellenbosch University, 2015-04) Hamid, Mogammad Baahith; Akudugu, John M.; Serafin, Antonio M.; Stellenbosch University. Faculty of Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Nuclear Medicine.
    ENGLISH ABSTRACT: Breast Cancer remains one of the world’s leading causes of cancer related deaths amongst women. Its treatment has evolved from invasive, highly toxic therapies to treatments that possess a higher specificity and a lower toxicity. Despite improvements in overall survival, many patients do not benefit from these agents because of acquired and/or inherent tumour resistance, which could hinder treatment efficacy. Novel treatment strategies are, therefore, warranted to address these challenges and to significantly improve patient responses. Inhibiting components of the HER-2 signalling pathway can significantly sensitise breast cancer cells to low doses of ionising radiation. The objective of this study was to inhibit key molecular targets of the human epidermal growth factor receptor 2 (HER-2) signalling pathway and expose breast cancer cell lines to doses of radiation, so as to establish potential therapeutic targets that may be amenable to combined modality therapy, and formulate a cocktail of inhibitors to evaluate its radiosensitising capability. This study found that pre-treatment of two breast cancer cell lines (MDA-MB-231 and MCF-7) with a HER-2 inhibitor (TAK-165) had little or no effect on radiosensitivity. However, a radiation enhancement was observed when these cells were pre-treated either with BEZ235, a dual inhibitor of phosphoinositide 3-kinase (PI3K) and mammalian target for rapamycin (mTOR), or a cocktail of TAK-165 and BEZ235. These findings suggest that concurrent inhibition of HER-2, PI3K and mTOR during radiotherapy might improve treatment response of breast cancer patients.