Publications by authors named "Vikash Sewram"

32 Publications

Baseline audiological profiling of South African females with cervical cancer: an important attribute for assessing cisplatin-associated ototoxicity.

BMC Womens Health 2021 Apr 20;21(1):164. Epub 2021 Apr 20.

Department of Global Health, African Cancer Institute, Faculty of Medicine and Health Sciences, Stellenbosch University, P.O. Box 241, Cape Town, 8000, South Africa.

Background: Cisplatin is a popular antineoplastic agent used to treat cervical cancer in women from low and middle-income countries. Cisplatin treatment is associated with ototoxicity, often resulting in hearing loss. In light of this, it is crucial to conduct baseline audiological assessments prior to treatment initiation in order to evaluate the extent of cisplatin-associated-ototoxicity. Additionally, the identification of inherent risk factors and hearing patterns in specific patient cohorts is needed, especially in South Africa, a middle-income country characterized by the quadruple burden of disease (Human Immunodeficiency Virus (HIV), Tuberculosis (TB), Diabetes and Hypertension).

Methods: This study aimed to describe a profile of risk factors and hearing in a cohort of females with cervical cancer before cisplatin treatment commenced. A descriptive study design that included 82 cervical cancer patients, who underwent audiological evaluation prescribed for ototoxicity monitoring was conducted.

Results: All participants (n = 82) presented with risk factors (diabetes, hypertension, HIV, and antiretroviral therapy) for cisplatin ototoxicity and/or pre-existing sensorineural hearing loss. High-frequency tinnitus was the most common otological symptom experienced by 25 (31%) participants. Fifty-nine (72%) participants presented with normal hearing, twenty-two (27%) with a sensorineural hearing loss, and 36% were diagnosed with mild hearing loss. Abnormal Distortion Product Otoacoustic Emissions (DPOAE) findings were obtained bilaterally in two participants (2.4%), in the right ear only of another two (2.4%) participants and the left ear of three participants (3.7%). Most participants (94%) had excellent word recognition scores, demonstrating an excellent ability to recognize words within normal conversational levels under optimal listening conditions. Age was significantly associated with hearing loss at all thresholds. Among the co-morbidities, an HIV positive status significantly triggered hearing loss, especially at higher frequencies.

Conclusion: This study demonstrated that South African females with cervical cancer present with various co-morbidities, which may predispose them to develop cisplatin-associated -ototoxic hearing loss. Identification of these co-morbidities and hearing loss is essential for the accurate monitoring of cisplatin toxicities. Appropriate management of these patients is pivotal to reduce the adverse effects that hearing impairment can have on an individual's quality of life and to facilitate informed decision-making regarding the commencement of cisplatin chemotherapy.
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http://dx.doi.org/10.1186/s12905-021-01313-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056627PMC
April 2021

Neighborhood greenness and burden of non-communicable diseases in Sub-Saharan Africa: A multi-country cross-sectional study.

Environ Res 2020 Oct 31:110397. Epub 2020 Oct 31.

Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, USA; Channing Division of Network Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, USA.

Population growth, demographic transitions and urbanization in sub-Saharan Africa (SSA) will increase non-communicable disease (NCD) burden. We studied the association between neighborhood greenness and NCDs in a multi-country cross-sectional study. Among 1178 participants, in adjusted models, a 0.11 unit NDVI increase was associated with lower BMI (β: -1.01, 95% CI: -1.35, -0.67), and lower odds of overweight/obesity (aOR: 0.73, 95% CI: 0.62, 0.85), diabetes (aOR: 0.77, 95% CI: 0.62, 0.96), and having ≥3 allostatic load components compared to none (aOR: 0.66, 95% CI: 0.52, 0.85). Except for diabetes, these remained statistically significant after Bonferroni correction. We observed no association between NDVI and hypertension or cholesterol. Our findings are consistent with health benefits of neighborhood greenness reported in other countries, suggesting greening strategies could be considered as part of broader public health interventions for NCDs.
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http://dx.doi.org/10.1016/j.envres.2020.110397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085185PMC
October 2020

Clinical Trials for Treatment and Prevention of HIV-Associated Malignancies in Sub-Saharan Africa: Building Capacity and Overcoming Barriers.

JCO Glob Oncol 2020 07;6:1134-1146

Center for Global Health, National Cancer Institute, Rockville, MD.

Purpose: The aim of this study was to review the current status of clinical trials for HIV-associated malignancies in people living with HIV in sub-Saharan Africa (SSA) and efforts made by the AIDS Malignancy Consortium (AMC) to build capacity in SSA for HIV malignancy research.

Methods: All malignancy-related clinical trials in 49 SSA countries on ClinicalTrials.gov were reviewed and evaluated for inclusion and exclusion criteria pertaining to HIV status. Additional studies by AMC in SSA were compiled from Web-based resources, and narrative summaries were prepared to highlight AMC capacity building and training initiatives.

Results: Of 96 cancer trials identified in SSA, only 11 focused specifically on people living with HIV, including studies in Kaposi sarcoma, cervical dysplasia and cancer, non-Hodgkin lymphoma, and ocular surface squamous neoplasia. Recognizing the increasing cancer burden in the region, AMC expanded its clinical trial activities to SSA in 2010, with 4 trials completed to date and 6 others in progress or development, and has made ongoing investments in developing research infrastructure in the region.

Conclusion: As the HIV-associated malignancy burden in SSA evolves, research into this domain has been limited. AMC, the only global HIV malignancy-focused research consortium, not only conducts vital HIV-associated malignancies research in SSA, but also develops pathology, personnel, and community-based infrastructure to meet these challenges in SSA. Nonetheless, there is an ongoing need to build on these efforts to improve HIV-associated malignancies outcomes in SSA.
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http://dx.doi.org/10.1200/GO.20.00153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392698PMC
July 2020

Perspectives and practices of ototoxicity monitoring.

S Afr J Commun Disord 2020 May 19;67(1):e1-e10. Epub 2020 May 19.

Discipline of Audiology, School of Health Sciences, University of KwaZulu-Natal, Durban.

Background: Treatment of cancer with cisplatin can result in hearing loss. Given the increasing burden of cancer in Africa, appropriate and timely identification, intervention and management of hearing loss in affected patients is of paramount importance.

Objectives: This study describes the perspectives and practices of healthcare professionals in relation to cisplatin-associated ototoxicity at an institution treating patients diagnosed with cancer.

Method: A concurrent triangulation study design was used to collect quantitative data from seven oncologists, nine nurses and 13 pharmacists using self-administered questionnaires, and qualitative data from four audiologists through semi-structured interviews for this hospital-based study, conducted in South Africa.

Results: Levels of awareness of cisplatin-associated ototoxicity varied with only 33% of the nursing personnel being aware in comparison to the oncologists and pharmacists. Oncologists were identified as the main custodians for providing information to patients. Whilst 82% of the participants considered the audiologist to be part of the oncology team, there was no provision for ototoxicity monitoring in the chemotherapy protocols, nor any ototoxicity-monitoring programme in place. There was no evidence that knowledge of cisplatin-associated ototoxicity translated into an appropriate management strategy for such patients.

Conclusion: Healthcare personnel overseeing the care and management of cancer patients need to improve their awareness of ototoxicity and refer timeously for audiological evaluation. Audiologists require greater awareness of monitoring programmes to appropriately implement and manage such programmes within a cancer platform and be part of a multidisciplinary team.
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http://dx.doi.org/10.4102/sajcd.v67i1.685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276482PMC
May 2020

Systematic Review of Genetic Factors in the Etiology of Esophageal Squamous Cell Carcinoma in African Populations.

Front Genet 2019 2;10:642. Epub 2019 Aug 2.

African Cancer Institute, Division of Health Systems and Public Health, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.

Esophageal squamous cell carcinoma (ESCC), one of the most aggressive cancers, is endemic in Sub-Saharan Africa, constituting a major health burden. It has the most divergence in cancer incidence globally, with high prevalence reported in East Asia, Southern Europe, and in East and Southern Africa. Its etiology is multifactorial, with lifestyle, environmental, and genetic risk factors. Very little is known about the role of genetic factors in ESCC development and progression among African populations. The study aimed to systematically assess the evidence on genetic variants associated with ESCC in African populations. We carried out a comprehensive search of all African published studies up to April 2019, using PubMed, Embase, Scopus, and African Index Medicus databases. Quality assessment and data extraction were carried out by two investigators. The strength of the associations was measured by odds ratios and 95% confidence intervals. Twenty-three genetic studies on ESCC in African populations were included in the systematic review. They were carried out on Black and admixed South African populations, as well as on Malawian, Sudanese, and Kenyan populations. Most studies were candidate gene studies and included DNA sequence variants in 58 different genes. Only one study carried out whole-exome sequencing of 59 ESCC patients. Sample sizes varied from 18 to 880 cases and 88 to 939 controls. Altogether, over 100 variants in 37 genes were part of 17 case-control genetic association studies to identify susceptibility loci for ESCC. In these studies, 25 variants in 20 genes were reported to have a statistically significant association. In addition, eight studies investigated changes in cancer tissues and identified somatic alterations in 17 genes and evidence of loss of heterozygosity, copy number variation, and microsatellite instability. Two genes were assessed for both genetic association and somatic mutation. Comprehensive large-scale studies on the genetic basis of ESCC are still lacking in Africa. Sample sizes in existing studies are too small to draw definitive conclusions about ESCC etiology. Only a small number of African populations have been analyzed, and replication and validation studies are missing. The genetic etiology of ESCC in Africa is, therefore, still poorly defined.
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http://dx.doi.org/10.3389/fgene.2019.00642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687768PMC
August 2019

A Review of Cisplatin-Associated Ototoxicity.

Semin Hear 2019 May 26;40(2):108-121. Epub 2019 Apr 26.

African Cancer Institute.

Cisplatin, an effective antineoplastic drug used in the treatment of many cancers, has ototoxic potential, thus placing cancer patients, receiving this treatment, at risk of hearing loss. It is therefore important for health care professionals managing these patients to be aware of cisplatin's ototoxic properties and its clinical signs to identify patients at risk of developing a hearing impairment. Eighty-five English peer-reviewed articles and two books, from January 1975 to July 2015, were identified from PubMed, ScienceDirect, and EBSCOhost. An overview of cisplatin-associated ototoxicity, namely its clinical features, incidence rates, molecular and cellular mechanisms, and risk factors, is presented in this article. This review further highlights the importance of a team-based approach to complement an audiological monitoring program in reducing any further loss in the quality of life of affected patients, as there is currently no otoprotective agent routinely recommended for the prevention of cisplatin-associated ototoxicity.
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http://dx.doi.org/10.1055/s-0039-1684041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486385PMC
May 2019

Withania somnifera modulates cancer cachexia associated inflammatory cytokines and cell death in leukaemic THP-1 cells and peripheral blood mononuclear cells (PBMC's).

BMC Complement Altern Med 2018 Apr 10;18(1):126. Epub 2018 Apr 10.

African Cancer Institute, Stellenbosch University, P.O. Box 241, Cape Town, 8000, South Africa.

Background: Cancer and inflammation are associated with cachexia. Withania somnifera (W. somnifera) possesses antioxidant and anti-inflammatory potential. We investigated the potential of an aqueous extract of the root of W. somnifera (W) to modulate cytokines, antioxidants and apoptosis in leukaemic THP-1 cells and peripheral blood mononuclear cells (PBMC's).

Methods: Cytotoxcity of W was determined at 24 and 72 h (h). Oxidant scavenging activity of W was evaluated (2, 2-diphenyl-1 picrylhydrazyl assay). Glutathione (GSH) levels, caspase (- 8, - 9, - 3/7) activities and adenosine triphosphate (ATP) levels (Luminometry) were thereafter assayed. Tumour necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β and IL-10 levels were also assessed using enzyme-linked immunosorbant assay.

Results: At 24 h, W (0.2-0.4 mg/ml) decreased PBMC viability between 20 and 25%, whereas it increased THP-1 viability between 15 and 23% (p < 0.001). At 72 h, W increased PBMC viability by 27-39% (0.05, 0.4 mg/ml W) whereas decreased THP-1 viability between 9 and 16% (0.05-0.4 mg/ml W) (p < 0.001). Oxidant scavenging activity was increased by W (0.05-0.4 mg/ml, p < 0.0001). PBMC TNF-α and IL-10 levels were decreased by 0.2-0.4 mg/ml W whereas IL-1β levels were increased by 0.05-0.4 mg/ml W (p < 0.0001). In THP-1 cells, W (0.05-0.4 mg/ml) decreased TNF-α, IL-1β and IL-6 levels (p < 0.0001). At 24 h, GSH levels were decreased in PBMC's, whilst increased in THP-1 cells by 0.2-0.4 mg/ml W (p < 0.0001). At 72 h, W (0.1-0.4 mg/ml) decreased GSH levels in both cell lines (p < 0.0001). At 24 h, W (0.2-0.4 mg/ml) increased PBMC caspase (-8, -3/7) activities whereas W (0.05, 0.1, 0.4 mg/ml) increased THP-1 caspase (-9, -3/7) activities (p < 0.0001). At 72 h, PBMC caspase (-8, -9, -3/7) activities were increased at 0.05-0.1 mg/ml W (p < 0.0001). In THP-1 cells, caspase (-8, -9, -3/7) activities and ATP levels were increased by 0.1-0.2 mg/ml W whereas decreased by 0.05 and 0.4 mg/ml W (72 h, p < 0.0001).

Conclusion: In PBMC's and THP-1 cells, W proved to effectively modulate antioxidant activity, inflammatory cytokines and cell death. In THP-1 cells, W decreased pro-inflammatory cytokine levels, which may alleviate cancer cachexia and excessive leukaemic cell growth.
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http://dx.doi.org/10.1186/s12906-018-2192-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891897PMC
April 2018

Consumption of processed food dietary patterns in four African populations.

Public Health Nutr 2018 06 1;21(8):1529-1537. Epub 2018 Feb 1.

5Department of Nutrition,Harvard T.H. Chan School of Public Health,Boston,MA,USA.

Objective: To identify predominant dietary patterns in four African populations and examine their association with obesity.

Design: Cross-sectional study.Setting/SubjectsWe used data from the Africa/Harvard School of Public Health Partnership for Cohort Research and Training (PaCT) pilot study established to investigate the feasibility of a multi-country longitudinal study of non-communicable chronic disease in sub-Saharan Africa. We applied principal component analysis to dietary intake data collected from an FFQ developed for PaCT to ascertain dietary patterns in Tanzania, South Africa, and peri-urban and rural Uganda. The sample consisted of 444 women and 294 men.

Results: We identified two dietary patterns: the Mixed Diet pattern characterized by high intakes of unprocessed foods such as vegetables and fresh fish, but also cold cuts and refined grains; and the Processed Diet pattern characterized by high intakes of salad dressing, cold cuts and sweets. Women in the highest tertile of the Processed Diet pattern score were 3·00 times more likely to be overweight (95 % CI 1·66, 5·45; prevalence=74 %) and 4·24 times more likely to be obese (95 % CI 2·23, 8·05; prevalence=44 %) than women in this pattern's lowest tertile (both P<0·0001; prevalence=47 and 14 %, respectively). We found similarly strong associations in men. There was no association between the Mixed Diet pattern and overweight or obesity.

Conclusions: We identified two major dietary patterns in several African populations, a Mixed Diet pattern and a Processed Diet pattern. The Processed Diet pattern was associated with obesity.
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http://dx.doi.org/10.1017/S136898001700386XDOI Listing
June 2018

Decisional control preferences among patients with advanced cancer: An international multicenter cross-sectional survey.

Palliat Med 2018 04 13;32(4):870-880. Epub 2017 Dec 13.

1 Department of Palliative Care, Rehabilitation, and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background: Understanding patients' decision control preferences is important in providing quality cancer care. Patients' decisional control preference can be either active (patients prefer to make decisions themselves), shared (collaborative between patient, their physician, and/or family), or passive (patients prefer that the decisions are made by either the physician and/or their family).

Aim: To determine the frequency and predictors of passive decision control preferences among advanced cancer patients. We also determined the concordance between actual decision-making and decision control preferences and its association with patient satisfaction.

Design: In this cross-sectional survey of advanced cancer patients referred to palliative care across 11 countries, we evaluated sociodemographic variables, Control Preference Scale, and satisfaction with the decisions and care.

Results: A total of 1490 participants were evaluable. Shared, active, and passive decision control preferences were 33%, 44%, and 23%, respectively. Passive decision control preferences (odds ratio, p value) was more frequent in India (4.34, <0.001), Jordan (3.41, <0.001), and France (3.27, <0.001). Concordance between the actual decision-making and decision control preferences was highest in the United States ( k = 0.74) and lowest in Brazil (0.34). Passive decision control preference was significantly associated with (odds ratio per point, p value) better performance status (0.99/point, 0.017), higher education (0.64, 0.001), and country of origin (Brazil (0.26, <0.0001), Singapore (0.25, 0.0003), South Africa (0.32, 0.0002), and Jordan (2.33, 0.0037)).

Conclusion: Passive decision control preferences were less common (23%) than shared and active decision control preference even among developing countries. Significant predictors of passive decision control preferences were performance status, education, and country of origin.
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http://dx.doi.org/10.1177/0269216317747442DOI Listing
April 2018

Perception of Curability Among Advanced Cancer Patients: An International Collaborative Study.

Oncologist 2018 04 20;23(4):501-506. Epub 2017 Nov 20.

Department of Palliative Care, Rehabilitation, and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Barretos, Brazil.

Background: There are limited data on illness understanding and perception of cure among advanced cancer patients around the world. The aim of the study was to determine the frequency and factors associated with inaccurate perception of curability among advanced cancer patients receiving palliative care across the globe.

Materials And Methods: Secondary analysis of a study to understand the core concepts in end-of-life care among advanced cancer patients receiving palliative care from 11 countries across the world. Advanced cancer patients were surveyed using a Patient Illness Understanding survey and Control Preference Scale. Descriptive statistics and multicovariate logistic regression analysis were performed.

Results: Fifty-five percent (763/1,390) of patients receiving palliative care inaccurately reported that their cancer is curable. The median age was 58, 55% were female, 59% were married or had a partner, 48% were Catholic, and 35% were college educated. Sixty-eight percent perceived that the goal of therapy was "to get rid of their cancer," and 47% perceived themselves as "seriously ill." Multicovariate logistic regression analysis shows that accurate perception of curability was associated with female gender (odds ratio [OR] 0.73,  = .027), higher education (OR 0.37,  < .0001), unemployment status (OR 0.69,  = .02), and being from France (OR 0.26,  < .0001) and South Africa (OR 0.52,  = .034); inaccurate perception of curability was associated with better Karnofsky performance status (OR 1.02 per point,  = .0005), and being from Philippines (OR 15.49,  < .0001), Jordan (OR 8.43,  < .0001), Brazil (OR 2.17,  = .0037), and India (OR 2.47,  = .039).

Conclusion: Inaccurate perception of curability in advanced cancer patients is 55% and significantly differs by gender, education, performance status, employment status, and country of origin. Further studies are needed to develop strategies to reduce this misperception of curability in advanced cancer patients.

Implications For Practice: The findings of this study indicate that inaccurate perception of curability among advanced cancer patients is 55%. Inaccurate perception of curability significantly differs by gender, education, performance status, employment status, and country of origin. There is great need to facilitate improved patient-physician communication so as to improve health care outcomes and patient satisfaction.
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http://dx.doi.org/10.1634/theoncologist.2017-0264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896700PMC
April 2018

Centella asiatica Fraction-3 Suppresses the Nuclear Factor Erythroid 2-Related Factor 2 Anti-Oxidant Pathway and Enhances Reactive Oxygen Species-Mediated Cell Death in Cancerous Lung A549 Cells.

J Med Food 2017 Oct;20(10):959-968

1 Discipline of Medical Biochemistry and Chemical Pathology, Faculty of Health Sciences, Howard College, University of KwaZulu-Natal , Durban, South Africa .

Centella asiatica is a tropical medicinal plant that is commonly used in traditional medicine. Medicinal properties of C. asiatica include anti-oxidant, anti-inflammatory, and anti-cancer activity. We investigated the anti-oxidant and anti-proliferative/cytotoxic effects of a semi-purified fraction of C. asiatica ethanolic leaf extract (C3) in cancerous lung A549 cells. C3 was obtained by silica column fractionation and identified by using thin-layer chromatography and gas chromatography mass spectrometry. Cytotoxicity of C3 in A549 cells was evaluated (cell viability assay-WST-1; 24 h; [0.2-3 mg/mL]) to determine an inhibitory concentration (IC). Intracellular reactive oxygen species (IROS), mitochondrial membrane potential (flow cytometry), malondialdehyde (MDA), lactate dehydrogenase (LDH) (spectrophotometry), glutathione (GSH), oxidised glutathione (GSSG), adenosine triphosphate levels, caspase activity (luminometry), and DNA damage (comet assay) were evaluated. Protein expression (Nrf-2, p53, Bax, Bcl-2, and HSP-70) and gene expression (Nrf-2, GPx, SOD, CAT, c-myc, and OGG-1) were quantified by western blotting and quantitative polymerase chain reaction (qPCR), respectively. C3 dose dependently decreased A549 cell viability. The IC of C3 increased MDA, IROS, mitochondrial depolarization, LDH, caspase (-8, -9, -3/7) activity, DNA damage, GSH levels, Nrf-2 protein expression, HSP-70 protein expression, and OGG-1 gene expression (P < .05). GSSG levels, anti-oxidant (Nrf-2, GPx, SOD) gene expression, p53, Bax, and Bcl-2 protein expression were decreased by C3 (P < .02). C3 diminished the anti-oxidant gene expression and induced anti-proliferative/cytotoxic effects in A549 cells.
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http://dx.doi.org/10.1089/jmf.2017.0005DOI Listing
October 2017

Centella asiatica modulates cancer cachexia associated inflammatory cytokines and cell death in leukaemic THP-1 cells and peripheral blood mononuclear cells (PBMC's).

BMC Complement Altern Med 2017 Aug 1;17(1):377. Epub 2017 Aug 1.

African Cancer Institute, Faculty of Medicine and Health Sciences, Stellenbosch University, P.O. Box 241, Cape Town, 8000, South Africa.

Background: Cancer cachexia is associated with increased pro-inflammatory cytokine levels. Centella asiatica (C. asiatica) possesses antioxidant, anti-inflammatory and anti-tumour potential. We investigated the modulation of antioxidants, cytokines and cell death by C. asiatica ethanolic leaf extract (C) in leukaemic THP-1 cells and normal peripheral blood mononuclear cells (PBMC's).

Methods: Cytotoxcity of C was determined at 24 and 72 h (h). Oxidant scavenging activity of C was evaluated using the 2, 2-diphenyl-1 picrylhydrazyl (DPPH) assay. Glutathione (GSH) levels, caspase (-8, -9, -3/7) activities and adenosine triphosphate (ATP) levels (Luminometry) were then assayed. The levels of tumour necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β and IL-10 were also assessed using enzyme-linked immunosorbant assay.

Results: C decreased PBMC viability between 33.25-74.55% (24 h: 0.2-0.8 mg/ml C and 72 h: 0.4-0.8 mg/ml C) and THP-1 viability by 28.404% (72 h: 0.8 mg/ml C) (p < 0.0001). Oxidant scavenging activity was increased by C (0.05-0.8 mg/ml) (p < 0.0001). PBMC TNF-α and IL-10 levels were decreased by C (0.05-0.8 mg/ml) (p < 0.0001). However, PBMC IL-6 and IL-1β concentrations were increased at 0.05-0.2 mg/ml C but decreased at 0.4 mg/ml C (p < 0.0001). In THP-1 cells, C (0.2-0.8 mg/ml) decreased IL-1β and IL-6 whereas increased IL-10 levels (p < 0.0001). In both cell lines, C (0.05-0.2 mg/ml, 24 and 72 h) increased GSH concentrations (p < 0.0001). At 24 h, caspase (-9, -3/7) activities was increased by C (0.05-0.8 mg/ml) in PBMC's whereas decreased by C (0.2-0.4 mg/ml) in THP-1 cells (p < 0.0001). At 72 h, C (0.05-0.8 mg/ml) decreased caspase (-9, -3/7) activities and ATP levels in both cell lines (p < 0.0001).

Conclusion: In PBMC's and THP-1 cells, C proved to effectively modulate antioxidant activity, inflammatory cytokines and cell death. In THP-1 cells, C decreased pro-inflammatory cytokine levels whereas it increased anti-inflammatory cytokine levels which may alleviate cancer cachexia.
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http://dx.doi.org/10.1186/s12906-017-1865-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5540453PMC
August 2017

Cisplatin-Associated Ototoxicity: A Review for the Health Professional.

J Toxicol 2016 27;2016:1809394. Epub 2016 Dec 27.

Discipline of Audiology, School of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa; African Cancer Institute, Faculty of Medicine and Health Sciences, Stellenbosch University, P.O. Box 241, Cape Town 8000, South Africa; Division of Community Health, Faculty of Medicine and Health Sciences, Stellenbosch University, P.O. Box 241, Cape Town 8000, South Africa.

Cisplatin is an effective drug used in the treatment of many cancers, yet its ototoxic potential places cancer patients, exposed to this drug, at risk of hearing loss, thus negatively impacting further on a patient's quality of life. It is paramount for health care practitioners managing such patients to be aware of cisplatin's ototoxic properties and the clinical signs to identify patients at risk of developing hearing loss. English peer-reviewed articles from January 1975 to July 2015 were assessed from PubMed, Science Direct, and Ebscohost. Seventy-nine articles and two books were identified for this review, using MeSH terms and keywords such as "ototoxicity", "cisplatin", "hearing loss", and "ototoxicity monitoring". This review provides an up-to-date overview of cisplatin-associated ototoxicity, namely, its clinical features, incidence rates, and molecular and cellular mechanisms and risk factors, to health care practitioners managing the patient with cancer, and highlights the need for a team-based approach to complement an audiological monitoring programme to mitigate any further loss in the quality of life of affected patients, as there is currently no otoprotective agent recommended routinely for the prevention of cisplatin-associated ototoxicity. It also sets the platform for effective dialogue towards policy formulation and strengthening of health systems in developing countries.
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http://dx.doi.org/10.1155/2016/1809394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5223030PMC
December 2016

An overview of cancer research in South African academic and research institutions, 2013 - 2014.

S Afr Med J 2016 May 10;106(6). Epub 2016 May 10.

Cancer Research Initiative, Faculty of Health Sciences, University of Cape Town, South Africa; Women's Health Research Unit, School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, South Africa.

Background And Objectives: Cancer is emerging as a critical public health problem in South Africa (SA). Recognising the importance of research in addressing the cancer burden, the Ministerial Advisory Committee on the Prevention and Control of Cancer (MACC) research working group undertook a review of the current cancer research landscape in SA and related this to the cancer burden.

Methods: Academic and research institutions in SA were contacted to provide information on the titles of all current and recently completed (2013/2014) cancer research projects. Three MACC research working group members used the project titles to independently classify the projects by type of research (basic, clinical and public health - projects could be classified in more than one category) and disease site. A more detailed classification of projects addressing the five most common cancers diagnosed in males and females in SA was conducted using an adapted Common Scientific Outline (CSO) categorisation.

Results: Information was available on 556 cancer research projects. Overall, 301 projects were classified as clinical, 254 as basic science and 71 as public health research. The most common cancers being researched were cancers of the breast (n=95 projects) and cervix (n=43), leukaemia (n=36), non-Hodgkin's lymphoma (n=35) and lung cancer (n=23). Classification of the five most common cancers in males and females in SA, using the adapted CSO categories, showed that the majority of projects related to treatment, with relatively few projects on prevention, survivorship and patient perspectives.

Conclusion: Our findings established that there is a dearth of public health cancer research in SA.
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http://dx.doi.org/10.7196/SAMJ.2016.v106i6.10314DOI Listing
May 2016

Tobacco and alcohol as risk factors for oesophageal cancer in a high incidence area in South Africa.

Cancer Epidemiol 2016 Apr 20;41:113-21. Epub 2016 Feb 20.

Centre for Occupational and Environmental Health Research, School of Public Health and Family Medicine, University of Cape Town, Observatory 7925, South Africa.

Background: The Eastern Cape Province of South Africa, which includes the former Transkei has high rates of squamous cell oesophageal cancer (OC), thought to be caused mainly by nutritional deficiencies and fungal contamination of staple maize. A hospital-based case-control study was conducted at three of the major referral hospitals in this region to measure, among other suspected risk factors, the relative importance of tobacco smoking and alcohol consumption for the disease in this population.

Methods: Incident cases (n=670) of OC and controls (n=1188) were interviewed using a structured questionnaire which included questions on tobacco and alcohol-related consumption. Odds ratios (ORs) with 95% confidence intervals for each of the risk factors were calculated using unconditional multiple logistic regression models.

Results: A monotonic dose-response was observed across the categories of each tobacco-related variable in both sexes. Males and females currently smoking a total of >14g of tobacco per day were observed to have over 4-times the odds of developing OC (males OR=4.36, 95% CI 2.24-8.48; females OR=4.56, 95% CI 1.46-14.30), with pipe smoking showing the strongest effect. Similar trends were observed for the alcohol-related variables. The quantity of ethanol consumed was the most important factor in OC development rather than any individual type of alcoholic beverage, especially in smokers. Males and females consuming >53g of ethanol per day had approximately 5-times greater odds in comparison to non-drinkers (males OR=4.72, 95% CI 2.64-8.41; females OR=5.24, 95% CI 3.34-8.23) and 8.5 greater odds in those who smoked >14g tobacco daily. The attributable fractions for smoking and alcohol consumption were 58% and 48% respectively, 64% for both factors combined.

Conclusion: Tobacco and alcohol use are major risk factors for OC development in this region.

Impact: This study provides evidence for further reinforcement of cessation of smoking and alcohol consumption to curb OC development.
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http://dx.doi.org/10.1016/j.canep.2016.02.001DOI Listing
April 2016

Coping with esophageal cancer approaches worldwide.

Ann N Y Acad Sci 2014 Sep;1325:138-58

Human Variome Project International Limited, Department of Pathology, Florey Neuroscience Institutes, The University of Melbourne, Melbourne, Australia.

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on approaches to the epidemiology, diagnosis, and treatment of esophageal cancer in Europe, South Africa, Kenya, Australia, and China; the molecular classification of esophageal cancers (including cancers at the gastroesophageal junction); the Japanese classification; the scope of the Human Variome Project; and the topographic-anatomic subclassification of adenocarcinomas of the gastroesophageal junction.
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http://dx.doi.org/10.1111/nyas.12522DOI Listing
September 2014

Cytokeratin expression in gastrointestinal stromal tumors: morphology, meaning, and mimicry.

Indian J Pathol Microbiol 2014 Apr-Jun;57(2):209-16

Department of Anatomical Pathology, School of Laboratory Medicine and Clinical Sciences, University of KwaZulu Natal & National Health Laboratory Service, South Africa.

Background: Gastrointestinal stromal tumors (GISTs) are biologically distinctive neoplasms harboring KIT and PDGFRA mutations. Cytokeratin expression in GISTs is an under-recognized diagnostic pitfall, especially in high grade GISTs with limited biopsy material and from metastatic sites.

Materials And Methods: We evaluated the histomorphology and expression of four 'broad-spectrum' cytokeratin markers, AE1-AE3, CAM 5.2, MNF-116, and 34βE12 in 64 GISTs diagnosed over a 68-month period. Individual cytokeratins 5, 6, 7, 8, 14, 17, 18, 19, and 20 were investigated in the 'broad-spectrum' cytokeratin-positive GISTs.

Results: Of 64 GISTs, 10 (15%) demonstrated cytokeratin immunopositivity. All 10, considered high risk by the National Institutes of Health consensus approach, were immunopositive for CAM 5.2 and MNF-116. Seven were AE1-AE3 immunopositive. Cytokeratins 8 and 18 were confirmed in 10 and 9 GISTs, respectively. One GIST demonstrated biphasic morphology with cytokeratin immunonegativity in low-grade spindle and immunopositivity in high-grade epithelioid foci. KIT and PDGFRA mutational analysis, undertaken in 5/10 cytokeratin-positive GISTs, harbored KIT exon 11 mutations.

Conclusion: We hypothesize that cytokeratin expression exclusively in high risk GISTs is a consequence of tumor progression. Given the increasing number of commercially available broad-spectrum cytokeratin immunomarkers, including those reacting with cytokeratins 8 and 18, cytokeratin-positive GISTs must be differentiated from carcinomas, melanomas, and a range of cytokeratin-positive sarcomas to ensure optimal patient management and prognostication.
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http://dx.doi.org/10.4103/0377-4929.134665DOI Listing
April 2015

Diet and esophageal cancer risk in the Eastern Cape Province of South Africa.

Nutr Cancer 2014 30;66(5):791-9. Epub 2014 May 30.

a Oncology Research Unit , Medical Research Council , Overport , South Africa.

A multicenter hospital-based case-control study comprising 670 incident cases of esophageal cancer (EC) and 1188 controls, frequency-matched for age and sex, was conducted to evaluate the role of diet on EC development in the Eastern Cape Province, South Africa. A locally relevant lifestyle and dietary questionnaire was used. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were computed using unconditional multivariable logistic regression. Individually, maize or sorghum consumption vs. never or rare consumption were not associated with EC (P > 0.1). Males and females consuming green leafy vegetables 5-7 days/wk had 38% (P = 0.04) and 50% (P = 0.007) reduced odds of developing EC, respectively, compared with consumption ≤1 day/wk. A similar reduction in odds was observed with fruit consumption. Principal component factor analysis revealed 3 distinct dietary patterns. In females, high vs. low consumption of Pattern 1 (sorghum, green leafy vegetables, green legumes, fruits, meat) was inversely associated with EC development (OR = 0.54; 95% CI: 0.34-0.89), whereas for Pattern 2 (maize, wild greens-imifino, dry beans) the odds were elevated (OR = 1.67; 95% CI: 1.04-2.67). Compared with low adherence, high adherence to Pattern 3 (wheat-based products) reduced the odds by 35% for both sexes. This study provides further evidence on the role of diet in minimizing EC risk in this population.
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http://dx.doi.org/10.1080/01635581.2014.916321DOI Listing
February 2015

Pediatric plasmablastic lymphoma: a clinicopathologic study.

Int J Surg Pathol 2014 Oct 25;22(7):607-16. Epub 2014 Apr 25.

Department of Anatomical Pathology, School of Laboratory Medicine and Medical Sciences, and National Health Laboratory Service, Durban, KwaZulu-Natal, South Africa.

Plasmablastic lymphoma (PBL) is reported rarely in children. To date, 10 cases are documented in the English-language literature. This study, based on 13 biopsies from 11 HIV-positive children (9 males, 2 females), documents the clinicopathologic features of PBL. The CD4 count ranged from 9 to 800 cells/mm(3). All biopsies demonstrated exclusive plasmablastic morphology; CD20 immunonegativity; and VS38c, EMA, CD31, MUM-1, CD45, and CD79a immunopositivity. B-cell monoclonality was confirmed in all biopsies. Of 3 biopsies subjected to FISH investigation, 2 had a t(8,14) translocation. Nine patients with follow-up details were treated exclusively with HAART (highly active antiretroviral therapy) or with combinations of HAART, chemotherapy, and radiotherapy. Seven patients died. PBL histomorphology, disease stage, and treatment modalities employed were not predictive of outcome. The survival of 2 stage 4 patients for 3 and 8 years each, managed on HAART, chemotherapy, and radiotherapy, however, may justify a role for combined therapeutic modalities for PBL.
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http://dx.doi.org/10.1177/1066896914531815DOI Listing
October 2014

Brahmarasayana protects against Ethyl methanesulfonate or Methyl methanesulfonate induced chromosomal aberrations in mouse bone marrow cells.

BMC Complement Altern Med 2012 Aug 1;12:113. Epub 2012 Aug 1.

Division of Biotechnology, Manipal Life Sciences Centre, Manipal University, Planetarium, Complex, Manipal, Karnataka 576 104, India.

Background: Ayurveda, the traditional Indian system of medicine has given great emphasis to the promotion of health. Rasayana is one of the eight branches of Ayurveda which refers to rejuvenant therapy. It has been reported that rasayanas have immuno-modulatory, antioxidant and antitumor functions, however, the genotoxic potential and modulation of DNA repair of many rasayanas have not been evaluated.

Methods: The present study assessed the role of Brahmarasayana (BR) on Ethyl methanesulfonate (EMS)-and Methyl methanesulfonate (MMS)-induced genotoxicity and DNA repair in in vivo mouse test system. The mice were orally fed with BR (5 g or 8 mg / day) for two months and 24 h later EMS or MMS was given intraperitoneally. The genotoxicity was analyzed by chromosomal aberrations, sperm count, and sperm abnormalities.

Results: The results have revealed that BR did not induce significant chromosomal aberrations when compared to that of the control animals (p >0.05). On the other hand, the frequencies of chromosomal aberrations induced by EMS (240 mg / kg body weight) or MMS (125 mg / kg body weight) were significantly higher (p<0.05) to that of the control group. The treatment of BR for 60 days and single dose of EMS or MMS on day 61, resulted in significant (p <0.05) reduction in the frequency of chromosomal aberrations in comparison to EMS or MMS treatment alone, indicating a protective effect of BR. Constitutive base excision repair capacity was also increased in BR treated animals.

Conclusion: The effect of BR, as it relates to antioxidant activity was not evident in liver tissue however rasayana treatment was observed to increase constitutive DNA base excision repair and reduce clastogenicity. Whilst, the molecular mechanisms of such repair need further exploration, this is the first report to demonstrate these effects and provides further evidence for the role of brahmarasayana in the possible improvement of quality of life.
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http://dx.doi.org/10.1186/1472-6882-12-113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3457898PMC
August 2012

Extra-uterine myoid tumours in patients with acquired immunodeficiency syndrome: a clinicopathological reappraisal.

Histopathology 2011 Dec;59(6):1122-34

Department of Anatomical Pathology, University of KwaZulu Natal, South Africa.

Aims: AIDS-associated myoid tumours (AIDS-MTs), often Epstein-Barr virus (EBV)-associated (EBV-positive MTs), include smooth muscle tumors (SMTs) and the relatively recently recognized myopericytomas (MPCTs). The myoid immunophenotype of AIDS-MTs has been documented inconsistently. The aim of this study was to reappraise the phenotypic and immunophenotypic features of extra-uterine AIDS-MTs and the clinical profile of afflicted patients.

Methods And Results: EBV early RNA in-situ hybridization testing on 27 AIDS-MTs from 25 patients identified 19 of 27 (70.4%) EBV-positive MTs and eight of 27 (29.6%) EBV-negative MTs. EBV-positive MTs comprised 12 of 19 EBV-positive SMTs [six leiomyomas, one smooth muscle tumour of uncertain malignant potential (STUMP), five leiomyosarcomas] and seven of 19 EBV-positive MPCTs [benign (five), malignant (two)]. The EBV-negative MTs, made up exclusively of EBV-negative SMTs, included angioleiomyoma (one), leiomyoma (one), STUMP (one) and leiomyosarcomas (five). Malignant AIDS-MTs demonstrated hypercellularity, pleomorphism, increased mitoses and necrosis. EBV-positive leiomyosarcomas retained a conspicuous fascicular architecture. Four of five EBV-negative leiomyosarcomas demonstrated marked pleomorphism. All EBV-positive MPCTs and two EBV-positive leiomyosarcomas contained aggregates of desmin-negative round and oval cells. Seventeen of 25 patients died, mainly from comorbid diseases.

Conclusion: While the reappraised spectrum of AIDS-MTs does not demonstrate divergent subtype-determined clinical behaviour, heightened awareness/recognition of this expanded spectrum will not only promote improved diagnosis of pleomorphic and myopericytic variants, which may be the sentinel clue to AIDS and its comorbidity, but will also facilitate distinction from histopathological mimics in specific anatomic locations.
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http://dx.doi.org/10.1111/j.1365-2559.2011.04049.xDOI Listing
December 2011

Fumonisin B1 and risk of hepatocellular carcinoma in two Chinese cohorts.

Food Chem Toxicol 2012 Mar 29;50(3-4):679-83. Epub 2011 Nov 29.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20852-7234, USA.

Fumonisin B1 (FB1), a mycotoxin that contaminates corn in certain climates, has been demonstrated to cause hepatocellular cancer (HCC) in animal models. Whether a relationship between FB1 and HCC exists in humans is not known. To examine the hypothesis, we conducted case-control studies nested within two large cohorts in China; the Haimen City Cohort and the General Population Study of the Nutritional Intervention Trials cohort in Linxian. In the Haimen City Cohort, nail FB1 levels were determined in 271 HCC cases and 280 controls. In the General Population Nutritional Intervention Trial, nail FB1 levels were determined in 72 HCC cases and 147 controls. In each population, odds ratios and 95% confidence intervals (95%CI) from logistic regression models estimated the association between measurable FB1 and HCC, adjusting for hepatitis B virus infection and other factors. A meta-analysis that included both populations was also conducted. The analysis revealed no statistically significant association between FB1 and HCC in either Haimen City (OR=1.10, 95%CI=0.64-1.89) or in Linxian (OR=1.47, 95%CI=0.70-3.07). Similarly, the pooled meta-analysis showed no statistically significant association between FB1 exposure and HCC (OR=1.22, 95%CI=0.79-1.89). These findings, although somewhat preliminary, do not support an associated between FB1 and HCC.
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http://dx.doi.org/10.1016/j.fct.2011.11.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3299856PMC
March 2012

Langerhans cells in anaplastic Kaposi sarcoma with a paucivascular phenotype: a potential diagnostic pitfall.

Pathol Int 2011 Apr 3;61(4):221-7. Epub 2011 Mar 3.

Department of Anatomical Pathology, Nelson R Mandela School of Medicine, University of KwaZulu Natal, Durban, KwaZulu Natal, South Africa.

Anaplastic Kaposi sarcoma (AKS), a rare variant of Kaposi sarcoma, has a poorly recognized histomorphologic spectrum, including a paucivascular phenotype, that mimics a range of undifferentiated malignancies. This study, that highlights the hitherto undocumented phenomenon of S100-protein-positive Langerhans cells (SLCs) as a potential diagnostic pitfall in paucivascular AKS, involved review of nine such AKS that required diagnostic immunohistochemical (IHC) work-up. All biopsies had a predominant or exclusive spindle or epithelioid cell infiltrate. The first three tumors were diagnosed as malignant peripheral nerve sheath tumor (2) and metastatic melanoma (1), based on S100-protein immunopositivity. Biopsy of a co-existent pigmented sole lesion (patient 3) demonstrated nodular KS. Subsequent IHC investigation of these three tumors demonstrated an endothelial phenotype and HHV8 immunopositivity, confirming AKS. CD1a and langerin staining of the S100-protein-positive cells confirmed Langerhans cells as the cause of the diagnostic pitfall. Subsequently, six further paucivascular AKS with intratumoral SLCs were recognized on histomorphological and IHC appraisal. In conclusion, heightened awareness of the histomorphologic spectrum, appropriate IHC investigation, and informed appraisal thereof, are critical to the diagnosis of AKS with an undifferentiated phenotype, and the avoidance of IHC pitfalls, such as those caused by under-recognition and misinterpretation of bystander SLCs in AKS.
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http://dx.doi.org/10.1111/j.1440-1827.2011.02658.xDOI Listing
April 2011

Pediatric renal cryptococcosis: novel manifestations in the acquired immunodeficiency syndrome era.

Int J Surg Pathol 2011 Jun 18;19(3):386-92. Epub 2010 Jul 18.

Department of Anatomical Pathology, Nelson R Mandela School of Medicine, University of KwaZulu Natal & National Health Laboratory Service, Durban, KwaZulu Natal, South Africa.

Pediatric cryptococcosis has been documented in various organs, but pediatric renal cryptococcosis (RC) remains undocumented to date. The authors report RC in 2 children with AIDS, 7 and 9 years of age, with proteinuria. Both patients, on antiretroviral therapy (ARV) for 28 (patient 1) and 54 (patient 2) weeks each, had secured viral immunosuppression, but immune restoration was realized by patient 1 only. Cryptococcal immune reconstitution inflammatory syndrome (IRIS) was diagnosed on the renal biopsy from patient 1 based on the clinicopathological profile and the presence of segmental glomerular and an interstitial lymphoplasmacytic and granulomatous reaction to Cryptococcus neoformans, with a predominance of capsule-deficient fungal forms. The renal biopsy from patient 2 demonstrated typical HIV-associated nephropathy with focal intratubular and interstitial C neoformans yeasts. Pediatric AIDS-associated renal disease must be expanded to include RC and cryptococcal IRIS, and the kidney must be included as a potential sentinel site of IRIS.
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http://dx.doi.org/10.1177/1066896910373923DOI Listing
June 2011

Structure and natural occurrence of stereoisomers of the fumonisin B series mycotoxins.

J Agric Food Chem 2007 May 1;55(11):4388-94. Epub 2007 May 1.

Programme on Mycotoxins and Experimental Carcinogenesis, Medical Research Council, Tygerberg 7505, South Africa.

1H and 13C NMR spectroscopy of both fumonisin B3 and B4, as well as high-performance liquid chromatography (HPLC) analysis of samples of fumonisin B3 used as standards, showed in each case the presence of two stereoisomers, which could not be separated by preparative chromatography. The 2,3-anti relative configuration for the two minor stereoisomers of fumonisin B3 and B4 was deduced from the NMR data, and their 2S,3R absolute configurations were established by application of Mosher's method using the fumonisin B3 sample. Samples of fumonisin B3 and B4 can contain between 10 and 40% of fumonisin B compounds of the 3-epi series. The 3-epi-FB3, determined by HPLC with fluorescence detection of the o-phthaldialdehyde derivative and confirmed by liquid chromatography-tandem mass spectrometry, was found to occur naturally in a range of maize samples at levels much lower than FB3 (< 20%). The identification of members of the 3-epi-fumonisin B series provides insight into the order and selectivity of steps in fumonisin biosynthesis.
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http://dx.doi.org/10.1021/jf070061hDOI Listing
May 2007

Mycotoxin contamination of dietary and medicinal wild plants in the Eastern Cape Province of South Africa.

J Agric Food Chem 2006 Jul;54(15):5688-93

PROMEC Unit and Biostatistics Unit, Medical Research Council, P.O. Box 19070, Tygerberg 7505, South Africa.

Nineteen dietary and 30 medicinal wild plants used by residents of the Eastern Cape Province of South Africa were investigated for the presence of fumonisin B1 and aflatoxin B1. The plants were extracted in water, and cleanup was undertaken on immunoaffinity cartridges; analysis was by HPLC using fluorescence detection. None of the plant extracts contained detectable levels of aflatoxin B1; however, eight plants, four dietary and four medicinal, were positive for fumonisin B1 at levels ranging from 34 to 524 microg/kg and from 8 to 1553 microg/kg, respectively. The presence of fumonisin B1 was confirmed by LC-MS/MS using positive ion electrospray ionization. Fumonisin B1 provided characteristic fragment ions at m/z 704, 686, 546, 528, 370, and 352 corresponding to sequential loss of H2O and tricarboxylic acid moieties from the alkyl backbone. These results indicate that exposure to fumonisin B1 is much more widespread than initially thought and is the first report of mycotoxin contamination in South African medicinal and dietary wild plants.
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http://dx.doi.org/10.1021/jf060483bDOI Listing
July 2006

Production of fumonisin B and C analogues by several fusarium species.

J Agric Food Chem 2005 Jun;53(12):4861-6

PROMEC Unit, Medical Research Council, P.O. Box 19070, Tygerberg 7505, South Africa.

Six strains of Fusarium verticillioides, two of F. oxysporum, one strain of F. proliferatum, and a strain of an unidentified species were cultured on maize patties and rice and evaluated for their ability to simultaneously produce fumonisin B (FB) and C (FC) series analogues. Fumonisins were quantified by LC-MS-MS using positive ion electrospray ionization. FC1 provided characteristic fragment ions at m/z 690, 672, 654, 532, 514, and 338 corresponding to sequential loss of H2O and tricarboxylic acid moieties from the alkyl backbone, while FC3 and FC4 provided equivalent product ions 16 and 32 amu lower than the corresponding FC1 fragments, respectively. All isolates cultured on maize produced FC4. All isolates except for that of F. proliferatum also produced FC1, and three of the six strains of F. verticillioides produced FC3. All isolates except those of F. oxysporum produced detectable amounts of FB1, FB2, and FB3. Isolates that produced fumonisin B analogues produced at least 10 fold more of the B series analogues than they did of the C series analogues. The results confirm that at least some strains of F. oxysporum produce FC, but not FB, fumonisin analogues and also suggest that the genetics and physiological regulation of fumonisin production may be more complicated than previously envisaged since some strains of F. verticillioides and F. proliferatum as well as the strain of the unidentified species can simultaneously produce both FB and FC analogues.
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http://dx.doi.org/10.1021/jf050307nDOI Listing
June 2005

Maté consumption and the risk of squamous cell esophageal cancer in uruguay.

Cancer Epidemiol Biomarkers Prev 2003 Jun;12(6):508-13

Promec Unit, Medical Research Council, Tygerberg, South Africa.

A retrospective hospital-based case-control study was carried out at the Oncology Institute of Montevideo, Uruguay, to investigate the role of maté consumption in esophageal cancer risk. The study included 344 cases with squamous cell carcinoma of the esophagus and 469 controls recruited between January 1988 and August 2000. Maté consumption was significantly associated with an increased risk of developing esophageal cancer and showed a clear dose response, with a relative risk of 2.84 [95% confidence interval (CI), 1.41-5.73] for those drinking more than 1 liter/day of maté as compared with nondrinkers. Subjects who self-reported drinking maté at a very hot temperature had an almost 2-fold increase in risk [odds ratio (OR), 1.87; 95% CI, 1.17-3.00] compared with those drinking warm to hot maté, after adjusting for cumulative consumption of maté. Maté amount and temperature were observed to have independent effects and, although no departure from multiplicativity was observed between the two covariates, those drinking more than 1 liter/day of maté at a very hot temperature had a 3-fold increase in risk (OR, 2.95; 95% CI, 1.30-6.74) compared with those drinking less than 0.5 liter/day of maté at a warm to hot temperature. Subjects with high cumulative exposure to maté in the presence of low alcohol and tobacco exposures presented a lower-risk estimate (OR, 1.52; 95% CI, 0.88-2.62), whereas those with high cumulative exposures to maté, alcohol, and tobacco presented a 7-fold increase in esophageal cancer risk (OR, 7.10; 95% CI, 3.75-13.46). The population-attributable fraction as a result of maté consumption was calculated to be 53%, of which the sole effect of amount and temperature was 14.8 and 12.6% respectively, and 14.9% was attributable to high maté consumption at high temperature.
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June 2003

Fumonisin mycotoxins in human hair.

Biomarkers 2003 Mar-Apr;8(2):110-8

Promec Unit, Medical Research Council, Tygerberg, South Africa.

This study shows for the first time the accumulation of fumonisin mycotoxins in human hair of population clusters exposed to contaminated maize, and thus the feasibility of human hair analysis for the assessment of past fumonisin exposure. Composite hair samples were obtained from the Bizana, Butterworth and Centane districts within the Transkei region of the Eastern Cape Province of South Africa. Following methanol extraction and strong anion exchange clean up, the fumonisins FB(1), FB(2) and FB(3) were detected using high performance liquid chromatography coupled to electrospray ionization-mass spectrometry (HPLC-ESI-MS). Hair from Centane and Butterworth showed mean levels of FB(1) of 26.7 and 23.5 microg kg(-1) hair, respectively. FB(2) was only detected in hair from Centane and in one sampling point in Butterworth, with mean levels of 6.5 and 5.7 microg kg(-1) hair, respectively. Hair samples from Bizana, on the other hand, were found to contain higher levels of FB(1) (mean 33.0 microg kg(-1) hair) and FB(2) (mean 11.1 microg kg(-1) hair). No samples contained more than trace levels of FB(3). Recoveries from spiked hair samples using this method ranged from 81% to 101%, demonstrating the applicability of hair analysis in assessing human exposure to fumonisin mycotoxins.
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http://dx.doi.org/10.1080/1354750031000081002DOI Listing
January 2004