Browsing by Author "Jaca, Anelisa"

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    Open Access
    Investigating the relationship between miRNA expression and epithelial mesenchymal transition in colorectal cancer
    (2016) Jaca, Anelisa; Naidoo, Richard; Locketz, Michael L
    Introduction: Epithelial-mesenchymal transition (EMT) is characterized by the loss of an epithelial phenotype and gain of a mesenchymal phenotype, i.e., migratory and metastatic properties. The EMT process is therefore characterized by a low expression of E-cadherin and high expression of mesenchymal markers (e.g., N-cadherin, snail and vimentin). It is stated that cells which have undergone EMT also gain stem cell features. Therefore, both EMT and stem cell phenotypes have been implicated in carcinogenesis and metastasis of tumour cells. Furthermore, EMT is regulated by small non-coding molecules (miRNAs) that either function as tumour suppressors or oncogenes (oncomirs). Tumour suppressor miRNAs reverse EMT while oncomirs activate it. Therefore, investigating the relationship between miRNAs and EMT is important in addressing metastasis of colorectal cancers (CRC). Aims and Objectives: The aim of the study was to determine the association between miRNA (miRNA-21 and miRNA-34a) expression levels and EMT in CRC. In addition, this investigation aimed to correlate miRNA and EMT data with clinicopathologic features of the study cohort. Methodology: A total of 100 CRC (including 8 known HNPCC cases) Formalin Fixed Paraffin Embedded (FFPE) tissue blocks and their corresponding H&E slides were collected from the archives of the Division of Anatomical Pathology at the University of Cape Town. Subsequently, the FFPE tissue blocks were sectioned at 3ÎĽm and IHC analysis of 4 EMT markers (E-cadherin, N-cadherin, snail-1 and vimentin) and 1 stem cell marker (CD44V6) was performed. The stains were then evaluated and scored by a pathologist. The IHC data were then correlated with clinicopathologic features. Furthermore, 59 cases (FFPE tissues and corresponding H&E slides) which included the 8 HNPCCs were randomly selected for miRNA analysis. The H&Es were examined by a pathologist to demarcate normal and tumour regions. RNA was then extracted from 59 tumours and 12 normal tissues using a High Pure FFPET Isolation Kit (Roche). Subsequently, cDNA was synthesized and qRT-PCR was performed to determine the expression levels of miRNA-21 and miRNA-34a. MiRNA-21 and miRNA-34a expression levels were ascertained using the relative quantification method. Moreover, the clinical significance of the two miRNAs was evaluated in relation to MSI status. Therefore, IHC analysis of MLH1, MSH2 and MSH6 mismatch repair proteins was performed on the Ventana platform. Statistical analysis was performed using Fisher's and Pearson's Chi Square tests in Stata 12 to correlate EMT and clinicopathologic data. Additionally, the Mann-Whitney non-parametric test in GraphPad prism 6 was used to determine miRNA-21 and miRNA-34a expression in relation to EMT and MSI data. Results: Our results showed low expression of E-cadherin in 77% of cases. In addition, there was decreased expression of N-cadherin and vimentin in 98% whilst snail-1 expression was decreased in 65% of the cases. Low expression of CD44v6 was also seen in 78% of the cases. There was no correlation between EMT/stem cell markers and clinicopathologic data. Furthermore, increased miRNA-21 expression was significantly associated with grade, lymph node metastasis and age of patients. There was a significant correlation between high miRNA- 21 expression and down-regulated snail-1 and N-cadherin expression. MiRNA-34a expression was not associated with any of the clinicopathologic features. In addition, high miRNA-34a expression was linked with low expression of snail-1 and CD44v6. Increased miRNA-21 expression was related with MSS tumours, whereas there was no relationship between miRNA- 34a and MSI status. Conclusion: Our investigation shows that there is an inverse association between miRNA (miRNA-21 and miRNA-34a) expression and two EMT (N-cadherin and snail-1) markers in our colorectal cancer cohort. Our data also show that both miRNA-21 and miRNA-34a cannot be used as biomarkers to determine progression of the cancer. Contrary to previous studies, our findings indicate that miRNA-21 does not activate EMT in this CRC cohort. However, similar to other studies our results confirm that miRNA-34a may be repressing snail-1 expression, thereby inhibiting EMT in the cancer.
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    Pandemic influenza preparedness in the WHO African region: are we ready yet?
    (BioMed Central, 2018-11-14) Sambala, Evanson Z; Kanyenda, Tiwonge; Iwu, Chinwe J; Iwu, Chidozie D; Jaca, Anelisa; Wiysonge, Charles S
    Background Prior to the 2009 pandemic H1N1, and the unprecedented outbreak of Highly Pathogenic Avian Influenza (HPAI) caused by the H5N1 virus, the World Health Organization (WHO) called upon its Member States to develop preparedness plans in response to a new pandemic in humans. The WHO Member States responded to this call by developing national pandemic plans in accordance with the International Health Regulations (IHR) to strengthen the capabilities of Member States to respond to different pandemic scenarios. In this study, we aim to evaluate the quality of the preparedness plans in the WHO African region since their inception in 2005. Methods A standard checklist with 61 binary indicators (“yes” or “no”) was used to assess the quality of the preparedness plans. The checklist was categorised across seven thematic areas of preparedness: preparation (16 indicators); coordination and partnership (5 indicators); risk communication (8 indicators); surveillance and monitoring (7 indicators); prevention and containment (10 indicators); case investigation and treatment (10 indicators) and ethical consideration (5 indicators). Four assessors independently scored the plans against the checklist. Results Of the 47 countries in the WHO African region, a total of 35 national pandemic plans were evaluated. The composite score for the completeness of the pandemic plans across the 35 countries was 36%. Country-specific scores on each of the thematic indicators for pandemic plan completeness varied, ranging from 5% in Côte d’Ivoire to 79% in South Africa. On average, preparation and risk communication scored 48%, respectively, while coordination and partnership scored the highest with an aggregate score of 49%. Surveillance and monitoring scored 34%, while prevention and containment scored 35%. Case investigation and treatment scored 25%, and ethical consideration scored the lowest of 14% across 35 countries. Overall, our assessment shows that pandemic preparedness plans across the WHO African region are inadequate. Conclusions Moving forward, these plans must address the gaps identified in this study and demonstrate clarity in their goals that are achievable through drills, simulations and tabletop exercises.
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    Predictors of COVID-19 Vaccine Hesitancy in South African Local Communities: The VaxScenes Study
    (Multidisciplinary Digital Publishing Institute, 2022-02-25) Katoto, Patrick D M C; Parker, Saahier; Coulson, Nancy; Pillay, Nirvana; Cooper, Sara; Jaca, Anelisa; Mavundza, Edison; Houston, Gregory; Groenewald, Candice; Essack, Zaynab; Simmonds, Jane; Shandu, Londiwe Deborah; Couch, Marilyn; Khuzwayo, Nonkululeko; Ncube, Nobukhosi; Bhengu, Phelele; Rooyen, Heidi van; Wiysonge, Charles Shey
    South Africa launched a mass COVID-19 vaccination campaign in May 2021, targeting 40 million adults. Understanding predictors of COVID-19 vaccine intentions was required to achieve this goal. We conducted a population-based survey in June–July 2021 using the WHO Behavioral and Social Drivers (BeSD) of COVID-19 Vaccination tool to determine predictors of vaccine hesitancy, defined as intention to refuse or uncertainty whether to accept COVID-19 vaccination. There were 1193 participants, mean age 39 (standard deviation 15) years, and 53% women, of whom 58% trusted information provided by healthcare workers and 32% were vaccine hesitant. Independent predictors of vaccine hesitancy included concerns about side effects (odds ratio (OR) 11.41; 95% confidence interval (CI) 3.5–50.80), lack of access to the online vaccine registration platform (OR 4.75; CI 2.15–10.37), distrust of government (OR 3.0; CI 1.33–6.77), belief in conspiracy theories (OR 3.01; CI 1.32–6.77), having no monthly income (OR 1.84; CI 1.12–3.07), and depending on someone else to make vaccination decision (OR 2.47; CI 1.06–5.77). We identified modifiable predictors of vaccine hesitancy at the start of South Africa’s COVID-19 vaccination rollout. These factors should be addressed by different stakeholders involved in the national immunization program through tailored communication and other effective strategies that increase vaccine literacy, reach low-income households, and engender confidence in government.
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    Protocol for a systematic review of the effects of interventions for vaccine stock management
    (2019-01-08) Iwu, Chinwe J; Jaca, Anelisa; Abdullahi, Leila H; Ngcobo, Ntombenhle J; Wiysonge, Charles S
    Abstract Background Inadequate vaccine stock management in health facilities leads to vaccine stock-outs. The latter threatens the success of immunisation programmes. Countries have used various approaches to reduce stock-outs and improve vaccine availability, but we are not aware of a systematic review of these interventions. This protocol describes the methods we will use to assess the effects of existing approaches for improving vaccine stock management. Methods We include randomised and non-randomised studies identified through a compehensive search of peer-reviewed and grey literature databases. We will search PubMed, Cochrane Central Register of Controlled Trials, Embase, Web of Science, PDQ-Evidence and Scopus. We will also search websites of the World Health Organisation (WHO), Global Alliance for Vaccine and Immunisation, PATH Vaccine Resources Library and United Nations Children’s Fund. In addition, we will search the WHO International Clinical Trials Registry Platform and reference lists of included studies and relevant reviews. Finally, we plan to do a citation search for included studies. We will use Cochrane recommended methods to screen search outputs, assess study eligibility and risk of bias, extract and analyse study results. We will use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool to assess the certainty of the evidence on the effects of the interventions. Discussion We believe that the findings of this review will serve as valuable information for policy makers on ways to improve vaccine stock management and vaccine availability. When vaccine availability is improved, those who need them, especially children, will be adequately protected from vaccine-preventable diseases. Systematic review registration PROSPERO CRD42018092215
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    Sequence analysis of the E-cadherin (CDH1) gene in a cohort of gastric cancers seen in the Western Cape
    (2013) Jaca, Anelisa; Naidoo, Richard
    Gastric cancer is commonly seen in the Western Cape. There are numerous factors that contribute to the development of this cancer and these include both environmental and genetic factors. Amongst the genetic factors, the E-cadherin (CDH1) gene is said to play a major role in the development of gastric cancer. Both germline and somatic mutations have been identified in the CDH1 gene. The germline mutations span the entire exon of this gene and are seen in approximately 29% to 56% of familial gastric cancers. On the other hand, CDH1 somatic mutations are seen in approximately 31% of sporadic cancers. These mutations have been identified in exons 7 to 10, with exons 8 and 9 being the commonly mutated regions. The primary objective of this study was to determine the prevalence of CDH1 genetic mutations in gastric cancer in the Western Cape and to correlate these findings with the demographic/clinicopathologic data.