Browsing by Author "Abdul-Rasool, Sahar"

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    Autosomal recessive congenital cataract in captive-bred vervet monkeys (Chlorocebus aethiops)
    (Wiley, 2018) Magwebu, Zandisiwe E.; Abdul-Rasool, Sahar; Seier, Jurgen V.; Chauke, Chesa G.
    BACKGROUND: The aim of the study was to evaluate the genetic predisposition of congenital cataract in a colony of captive-bred vervet monkeys. METHODS: Four congenital cataract genes: glucosaminyl (N-acetyl) transferase 2 (GCNT2), heat shock transcription factor 4 (HSF4), crystallin alpha A (CRYAA) and lens intrinsic membrane protein-2 (LIM2) were screened, sequenced and analysed for possible genetic variants in 36 monkeys. Gene expression was also evaluated in these genes. RESULTS: Fifteen sequence variants were identified in the coding regions of three genes (GCNT2, HSF4 and CRYAA). Of these variations, only three were missense mutations (M258V, V16I and S24N) and identified in the GCNT2 transcripts A, B and C, respectively, which resulted in a downregulated gene expression. CONCLUSION: Although the three missense mutations in GCNT2 have a benign effect, a possibility exists that the candidate genes (GCNT2, HSF4 and CRYAA) might harbour mutations that are responsible for total congenital cataract.
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    The effects of various combinations of different classes of anticancer drugs and tyrosine kinase inhibitors on the human MCF-7 breast carcinoma cell line
    (University of the Western Cape, 2014) Abrahams, Beynon; Hiss, D.C.; Abdul-Rasool, Sahar
    This study investigated the effects of TKIs on the growth and proliferation of MCF-7 breast carcinoma cells in culture. MCF-7 cells were exposed to different concentrations of TKIs alone and in combination with each other. Inhibition of cell growth by TKIs used individually occurred in a dose- and time-dependent manner. When EGFR Inhibitor I, EGFR Inhibitor II/BIBX1382 and the multi-specific EGFR/ErbB-2/ErB-4 Inhibitor were used in combination with each other at equimolar log dose concentrations, the combined effects on cell growth was significantly different to inhibitors used individually as reflected in a decreased EC50 (IC50) during combination treatments. Generally, for the combinations with DOX, CPL and the TKIs, synergistic as well as antagonistic effects were observed at isoeffective concentrations with resultant decreases in dose reduction indices (DRIs) implying greater efficacies with the respective combinations. In this study, conventional PCR was used to detect and illustrate the presence of the EGFR gene in the samples, while RT-qPCR was used to determine the mRNA expression levels of this gene in MCF-7 breast carcinoma cells
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    Genomic instability in South African breast cancer patients
    (2013) Langa, Bridget Cebisile; Abdul-Rasool, Sahar; Hiss, Donavon
    Breast cancer (BC) is one of the most common malignancies in women. Death results from treatment failure and metastatic disease. Thousands of lives might be saved if it was possible to detect and eliminate occult metastatic cells before they become clinically evident. Therefore, there is a critical need to identify new markers to improve treatment options for these patients. Genomic instability is the earliest indication of breast cancer and the use of genomic methodologies is a progress towards early detection and treatment, through the identification of biomarkers that can be translated into novel therapy targets. The interferon regulatory factor-1(IRF-1) gene, localized on chromosome 5q31.1, is believed to act as a tumor suppressor gene in breast cancer. The IRF-1 was found to be inactivated by single nucleotide polymorphism (SNP) in breast cancer suggesting that the loss of its function might be critical to the development of the disease. The phosphatidylinositol 3-kinase (PIK3) signaling pathway mediates key cellular functions and alterations of genes in this pathway, including PIK3CA, serine-threonine protein kinases (AKT1and AKT2), phosphatase and tensin homolog (PTEN), fibroblast growth factor receptor 2 (FGFR2) and ERBB2, whose expression have been demonstrated to be altered in breast cancer patients. In addition, these genes are linked to treatment resistance. vi In this study, we have investigated allelic loss of IRF-1 gene in primary tumors obtained from patients undergoing mastectomy at Groote Schuur hospital (Cape Town, South Africa). These samples were then further analyzed for the DNA copy number changes of specific genes involved in the PIK3/AKT signaling pathway. Statistical analysis has been performed in order to correlate genomic findings with clinical-histopathological and follow up information from the patients and to establish whether these genes can predict prognosis. Our data analysis has indicated that 46 cases (45.5%) out of 101 cases were informative for the IRF-1 dinucleotide marker used for LOH analysis (Figure 3.1). LOH was detected in 23 of these informative cases (23/46; 50%). No statistical significance was found between LOH at the IRF-1 locus and age (≤50 years or >50 years) (P value = 1.0000) and earlier stage (Stages I and II) (P value= 0.4982) based on Fisher’s exact test. Patients presented a high level of DNA copy number changes in genes involved in the PIK3/AKT pathway. The most frequent changes were observed in the PIK3CA and PTEN genes. PIK3CA presented high copy number in 36.8% of the cases. PTEN was observed with low copy number in 47.5% of the cases. This dissertation shows the effectiveness of genomic methodologies as means for the detection of early breast cancer progression in South African women. The PIK 3/AKT genes can validate the usefulness of breast cancer therapies.
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    The potential therapeutic role of palm oil on prostate cancer
    (University of the Western Cape, 2020) Hasan, Ghanaim; Abdul-Rasool, Sahar
    Prostate cancer is one of the heterogeneous groups of neoplastic diseases originating from the reproductive system of the male naming, the prostate gland. In the west, prostate cancer is the most common cancer affecting African men in older age (over the age of 55) and usually with a family history of the disease. The initiation and progression of this disease is thought to result from the genetic alterations of gene expression in the prostate epithelial cells. Prostate cancer has a very slow progression. This observation provides the advantage of early detection and the notion for using diet to prevent the cellular and molecular processes of carcinogenesis. Epidemiological research has documented a positive health role for red palm oil on atherosclerosis, arterial thrombosis and several types of cancers. This thesis focuses on investigating the effect of different concentrations of the red palm oil (0.1, 1, 10, 100, 500, 1 000 μg/ml) on malignant (LNCaP) prostate cells and benign (PWR-1E) prostate cells over 24 and 72- hours. The following parameters were investigated: cell morphology and viability (using MTT assay), the expression of androgen receptors and prostate-specific antigen (PSA) via RT-PCR and/or PSA ELISA kit. The results of this study demonstrate that red palm oil has significant cytotoxic effects on malignant (LNCaP) prostate cells but caused only a slight decrease in cell viability of benign (PWR- 1E) prostate cells. Morphologically, we noted a clear increase in detachment and cell death in malignant (LNCaP) cells as the concentrations of red palm oil increased. Moreover, the viability decreased significantly in both 24 and 72-hour treatment of red palm oil. Further to this, red palm oil significantly promoted the reduction of total PSA concentration in malignant (LNCaP) prostate cells whereas in benign (PWR-1E) prostate cells the Red Palm Oil maintained the total serum PSA at its basal physiological level. In conclusion, red palm oil is significantly cytotoxic to malignant (LNCaP) prostate cells whereas weakly cytotoxic effect toward benign (PWR-1E) prostate cells. The potent inhibition to mitochondrial dehydrogenase activity is responsible for the aforementioned effects respectively. The decrease in total serum PSA demonstrate the strong therapeutic effects that red palm oil has on malignant (LNCaP) prostate cells
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    The synergistic and neuroprotective effects of alcohol–antioxidant treatment on blood–brain barrier endothelial cells
    (Wiley-Blackwell, 2020) Fisher, David W.; Thomas, Kelly Angelique; Abdul-Rasool, Sahar
    Background: Alcohol (EtOH) is reported to adversely affect one of the most crucial roles of the blood–brain barrier (BBB), the regulation of its permeability, thereby compromising the stability of the homeostatic environment of the brain. The central component of the BBB, endothelial cells (ECs), regulates BBB transcellular transport, while their paracellular pathways are made virtually impermeable by molecular structures called tight junctions (TJs). These TJs are composed of proteins, such as claudin-5, a protein involved in the regulation of paracellular permeability and of key interest in this study. Methods and Results: The working hypothesis of this study postulated that the high levels of antioxidants (AOs) in the fermented Aspalathus linearis (Rooibos; Rf) tincture may protect the ECs of the BBB against oxidative stress induced by EtOH exposure. Cells were exposed for 24 hours to selected concentrations of EtOH (25 and 100 mM), Rf (containing an antioxidant equivalence of 1.9 nM Aspalathin), and cotreatments of EtOH and Rf. Cell viability, live cell number, and toxicity were analyzed using the trypan blue exclusion assay. RT-qPCR was implemented to quantify claudin-5 transcription. In addition, permeability (Transepithelial Electrical Resistance) of bEnd5 monolayers was measured. The experimental timeline for the above-mentioned parameters was 24 and 48 hours. Conclusions: Our study showed that simultaneous exposure of Rf and EtOH was able to negate the effects of EtOH on cell viability and cell proliferation, but was not able to reverse or reduce the effects of EtOH on claudin-5 transcription and paracellular permeability. Furthermore, a novel finding in this study suggests that very low concentrations of AOs in tinctures such as Rooibos tea could profoundly alter the redox status of brain ECs.
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    Understanding human coronavirus HCoV-NL63
    (Bentham Science, 2010) Abdul-Rasool, Sahar; Fielding, Burtram C.
    Even though coronavirus infection of humans is not normally associated with severe diseases, the identification of the coronavirus responsible for the outbreak of severe acute respiratory syndrome showed that highly pathogenic coronaviruses can enter the human population. Shortly thereafter, in Holland in 2004, another novel human coronavirus (HCoV-NL63) was isolated from a seven-month old infant suffering from respiratory symptoms. This virus has subsequently been identified in various countries, indicating a worldwide distribution. HCoV-NL63 has been shown to infect mainly children and the immunocommpromised, who presented with either mild upper respiratory symptoms (cough, fever and rhinorrhoea) or more serious lower respiratory tract involvement such as bronchiolitis and croup, which was observed mainly in younger children. In fact, HCoV-NL63 is the aetiological agent for up to 10% of all respiratory diseases. This review summarizes recent findings of human coronavirus HCoV-NL63 infections, including isolation and identification, phylogeny and taxonomy, genome structure and transcriptional regulation, transmission and pathogenesis, and detection and diagnosis.