Browsing by Author "Chinhengo, Angela"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    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.
  • Thumbnail Image
    Item
    Evaluation of the effect of radiofrequency electromagnetic waves on radiosensitivity
    (Stellenbosch : Stellenbosch University, 2019-12) Chinhengo, Angela; Akudugu, J. M.; Serafin, A. M.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Radiobiology.
    ENGLISH SUMMARY : Cancer is a major cause of human death worldwide, and one of the very real challenges is how to control treatment resistance. An additional challenge is the co-morbidity of cancer, with certain infections complicating its management. Radiotherapy (RT) is considered the first line of treatment for most superficial cancers, as these malignancies tend to respond well to radiation. The use of hypofractionated treatment may be beneficial for certain tumours, but hypofractionation may result in severe side-effects from normal tissue toxicity from which the patient may not recover. To circumvent this, radiation modifying agents that potentiate the tumour inactivating effects of ionising radiation and thereby lead to a reduction in radiation dose and prevent normal tissue toxicity, can be utilised. Magnetic fields have long been suggested as potential enhancers of radiation effects. Studies on the combined biological effects of radiofrequency fields (RFF) and ionising radiation are virtually non-existent. The use of RFF adjuvant to radiotherapy may be beneficial, as they have been shown to exhibit in vitro radiosensitising and radioprotective effects in malignant and normal cells, respectively, with the possibility of a significant dose reduction. There is, however, a need to understand the mechanisms by which these RFF influence radiosensitivity so that they can be employed efficiently as radiotherapy modulators. The main goal of radiotherapy is to kill tumour cells and spare normal tissue, and a good modifying agent would be one that sensitises the tumour whilst protecting normal tissue. This study assessed the effect of radiofrequency fields (RFF), modulated at 100, 1000, 2000 and 4000 Hz, on the radiosensitivity of four cell lines: a p53 mutant melanoma cell line, MeWo; a p53 wild-type melanoma cell line, Be11; a p53 mutant prostate cancer cell line, DU145; and a p53 wild-type normal lung fibroblast cell line, L132. The radiomodulatory effect of radiofrequency fields was evaluated using the colony assay. The 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), superoxide dismutase (SOD) and micronucleus assays were used to assess the possible mechanisms by which radiofrequency fields influence the radiosensitivity of cells. The data demonstrate that radiofrequency fields are more efficient in modulating large fractional doses of X-rays and could find application in hypofractionated radiotherapy as adjuvants, especially for tumours with low alpha/beta ratios. This can have a positive impact on the management of patients with superficial tumours that may be resistant to low fractional doses of radiation. Radiofrequency fields modulate cellular radiosensitivity in a frequency- and cell type-dependent manner and their effects appear to be linked to p53 status. Cellular responses such as metabolism, DNA damage processing (based on micronuclei formation), and abnormal proliferation (based on binucleation) seem to be underlying factors mediating the radiomodulatory effects of radiofrequency fields. Mechanisms by which radiofrequency fields can possibly modulate radiosensitivity are: amplification of radiation-induced genotoxicity, cell cycle arrest, and disturbance of other cellular biochemical processes that lead to alteration of homeostasis. Alternative ways by which RFF affect radiosensitivity are: interfering with the synthesis and function of charged proteins in the cell leading to programmed cell death or premature cell ageing, perturbation of intracellular calcium ions which can trigger apoptotic or necrotic cell death, and/or modulating the expression of Bcl-2 family proteins. Given this complexity, a potential use of radiofrequency fields as a non-invasive therapeutic modality would require standardisation to establish reproducibility. A more detailed understanding of how radiofrequency fields interact with ionising radiation would also prove beneficial in the broader field of radiation protection.
  • Thumbnail Image
    Item
    A multi-parameter approach for predicting prostate cancer
    (Cogent OA, 2017) Serafin, Antonio; Chinhengo, Angela; Fernandez, Pedro; Akudugu, John
    Urokinase plasminogen activator (uPA) and its inhibitor (PAI-1) have shown to be of merit as biomarkers for a variety of cancers. The objective of this project was to assay for uPA and PAI-1 in prostate needle biopsy tissue from 217 patients using the FEMTELLE enzyme linked immunosorbent (ELISA) assay, and to examine the robustness of PAI-1 as a candidate marker in benign prostatic hyperplasia (BPH) and prostate cancer (PCa), as previously identified in a different cohort of 111 patients. These results validate the assertion that PAI-1 levels of >4.5 ng mg−1 protein in prostate biopsies are indicative of prostate malignancy in elderly men, but further show that tissue from BPH patients in the 70–80 year age interval express significantly high levels of this marker. To address this anomaly, a malignancy index, derived from the concentrations of prostate-specific antigen (PSA), uPA, and PAI-1, and patient age is proposed. This simple index discriminates prostate tissue from BPH and PCa patients with concordance indices of 0.59 and 0.69 when tissues are taken as biopsy or transurethral resection of the prostate (TURP), respectively. Corresponding indices for PSA as a predictor of prostate disease were 0.67 and 0.73. Further evaluation of the proposed malignancy index using specimens, such as venous blood, could prove valuable in the search for non-invasive predictive assays.