UGT1A1 regulatory variant with potential effect on efficacy of HIV and cancer drugs commonly prescribed in South Africa

2021 ◽  
Vol 22 (15) ◽  
pp. 963-972
Author(s):  
Jenny Mary Mathew ◽  
Phelelani Thokozani Mpangase ◽  
Dhriti Sengupta ◽  
Stanford Kwenda ◽  
Demetra Mavri-Damelin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
South Africa ◽  
Potential Effect ◽  
Drug Clearance ◽  
Bioinformatic Pipeline ◽  
Immunodeficiency Virus ◽  
Regulatory Variant ◽  
Drug Doses ◽  
Hiv And Cancer ◽  
Alternative Drugs

Aim: Despite the high disease burden of human immunodeficiency virus (HIV) infection and colorectal cancer (CRC) in South Africa (SA), treatment-relevant pharmacogenetic variants are understudied. Materials & methods: Using publicly available genotype and gene expression data, a bioinformatic pipeline was developed to identify liver expression quantitative trait loci (eQTLs). Results: A novel cis-eQTL, rs28967009, was identified for UGT1A1, which is predicted to upregulate UGT1A1 expression thereby potentially affecting the metabolism of dolutegravir and irinotecan, which are extensively prescribed in SA for HIV and colorectal cancer treatment, respectively. Conclusion: As increased UGT1A1 expression could affect the clinical outcome of dolutegravir and irinotecan treatment by increasing drug clearance, patients with the rs28967009A variant may require increased drug doses to reach therapeutic levels or should be prescribed alternative drugs.

scholarly journals Epithelial-Mesenchymal Transition and MicroRNAs in Colorectal Cancer Chemoresistance to FOLFOX

Pharmaceutics ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 75
Author(s):  
Paula I. Escalante ◽  
Luis A. Quiñones ◽  
Héctor R. Contreras
Keyword(s):  
Colorectal Cancer ◽  
Tumor Cells ◽  
Methylenetetrahydrofolate Reductase ◽  
Epithelial Mesenchymal Transition ◽  
Late Onset ◽  
Dihydropyrimidine Dehydrogenase ◽  
Acquired Resistance ◽  
Potential Effect ◽  
Mesenchymal Transition ◽  
Folfox Chemotherapy

The FOLFOX scheme, based on the association of 5-fluorouracil and oxaliplatin, is the most frequently indicated chemotherapy scheme for patients diagnosed with metastatic colorectal cancer. Nevertheless, development of chemoresistance is one of the major challenges associated with this disease. It has been reported that epithelial-mesenchymal transition (EMT) is implicated in microRNA-driven modulation of tumor cells response to 5-fluorouracil and oxaliplatin. Moreover, from pharmacogenomic research, it is known that overexpression of genes encoding dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase (TYMS), methylenetetrahydrofolate reductase (MTHFR), the DNA repair enzymes ERCC1, ERCC2, and XRCC1, and the phase 2 enzyme GSTP1 impair the response to FOLFOX. It has been observed that EMT is associated with overexpression of DPYD, TYMS, ERCC1, and GSTP1. In this review, we investigated the role of miRNAs as EMT promotors in tumor cells, and its potential effect on the upregulation of DPYD, TYMS, MTHFR, ERCC1, ERCC2, XRCC1, and GSTP1 expression, which would lead to resistance of CRC tumor cells to 5-fluorouracil and oxaliplatin. This constitutes a potential mechanism of epigenetic regulation involved in late-onset of acquired resistance in mCRC patients under FOLFOX chemotherapy. Expression of these biomarker microRNAs could serve as tools for personalized medicine, and as potential therapeutic targets in the future.

scholarly journals Chromosomal radiosensitivity of human immunodeficiency virus positive/negative cervical cancer patients in South Africa

2015 ◽  
Vol 13 (1) ◽  
pp. 130-136 ◽  
Author(s):  
OLIVIA HERD ◽  
FLAVIA FRANCIES ◽  
JEFFREY KOTZEN ◽  
TRUDY SMITH ◽  
ZWIDE NXUMALO ◽  
...  
Keyword(s):  
South Africa ◽  
Cervical Cancer ◽  
Human Immunodeficiency Virus ◽  
Cancer Patients ◽  
Immunodeficiency Virus

scholarly journals Die vroeë kommunikasieontwikkeling van ’n groep babas met pediatriese MIV/VIGS in sorgsentrums

2003 ◽  
Vol 8 (2) ◽  
Author(s):  
Isabel Bam ◽  
Alta Kritzinger ◽  
Brenda Louw
Keyword(s):  
South Africa ◽  
Human Immunodeficiency Virus ◽  
Primary Prevention ◽  
Full Text ◽  
Unique Combination ◽  
Developmental Needs ◽  
Early Management ◽  
Secondary Interventions ◽  
Immunodeficiency Virus ◽  
High Prevalence

The high prevalence and serious sequelae of the pediatric human immunodeficiency virus (HIV/AIDS) in South Africa pose great challenges for clinicians involved in early intervention to develop appropriate interdisciplinary programmes for primary prevention of transmission of the virus as well as secondary interventions directed at the early management of the unique combination of serious health problems, neuro-developmental needs and caregiving circumstances of the infants. Opsomming Die hoë prevalensie en ernstige gevolge van die pediatriese menslike immuniteitsgebrek-virus (MIV/VIGS) in Suid-Afrika stel groot uitdagings aan klinici betrokke by vroeë intervensie om toepaslike interdissiplinêre programme te ontwikkel vir primêre voorkoming van oordrag van die virus asook sekondêre intervensies gerig op die vroeë hantering van die babas se unieke kombinasie van ernstige Gesondheids-probleme, neuro-ontwikkelingsbehoeftes en versorgingsomstandighede. *Please note: This is a reduced version of the abstract. Please refer to PDF for full text.

scholarly journals Immunogenicity of Novel DosR Regulon-Encoded Candidate Antigens of Mycobacterium tuberculosis in Three High-Burden Populations in Africa

2009 ◽  
Vol 16 (8) ◽  
pp. 1203-1212 ◽  
Author(s):  
Gillian F. Black ◽  
Bonnie A. Thiel ◽  
Martin O. Ota ◽  
Shreemanta K. Parida ◽  
Richard Adegbola ◽  
...  
Keyword(s):  
South Africa ◽  
Mycobacterium Tuberculosis ◽  
South African ◽  
The Gambia ◽  
Human Populations ◽  
Protein Antigens ◽  
Immunodeficiency Virus ◽  
Study Participants ◽  
Dosr Regulon ◽  
Interferon Responses

ABSTRACT Increasing knowledge about DosR regulon-encoded proteins has led us to produce novel Mycobacterium tuberculosis antigens for immunogenicity testing in human populations in three countries in Africa to which tuberculosis (TB) is endemic. A total of 131 tuberculin skin test-positive and/or ESAT-6/CFP10-positive, human immunodeficiency virus-negative adult household contacts of active pulmonary TB cases from South Africa (n = 56), The Gambia (n = 26), and Uganda (n = 49) were tested for gamma interferon responses to 7 classical and 51 DosR regulon-encoded M. tuberculosis recombinant protein antigens. ESAT-6/CFP10 fusion protein evoked responses in >75% of study participants in all three countries. Of the DosR regulon-encoded antigens tested, Rv1733c was the most commonly recognized by participants from both South Africa and Uganda and the third most commonly recognized antigen in The Gambia. The four most frequently recognized DosR regulon-encoded antigens in Uganda (Rv1733c, Rv0081, Rv1735c, and Rv1737c) included the three most immunogenic antigens in South Africa. In contrast, Rv3131 induced the highest percentage of responders in Gambian contacts (38%), compared to only 3.4% of Ugandan contacts and no South African contacts. Appreciable percentages of TB contacts with a high likelihood of latent M. tuberculosis infection responded to several novel DosR regulon-encoded M. tuberculosis proteins. In addition to significant similarities in antigen recognition profiles between the three African population groups, there were also disparities, which may stem from genetic differences between both pathogen and host populations. Our findings have implications for the selection of potential TB vaccine candidates and for determining biosignatures of latent M. tuberculosis infection, active TB disease, and protective immunity.

scholarly journals Left-Sided Colorectal Cancer Distinct in Indigenous African Patients Compared to Other Ethnic Groups in South Africa.

2021 ◽  
Author(s):  
M. McCabe ◽  
C. Penny ◽  
P. Magangane ◽  
S. Mirza ◽  
Y. Perner
Keyword(s):  
Colorectal Cancer ◽  
South Africa ◽  
Ethnic Groups ◽  
Mirna Expression ◽  
Expression Profiling ◽  
Expression Patterns ◽  
Molecular Characteristics ◽  
Anatomical Site ◽  
Molecular Features ◽  
Mirna Expression Profiling

Abstract Introduction: A large proportion of indigenous African (IA) colorectal cancer (CRC) patients in South Africa are young (<50years), with no unique histopathological or molecular characteristics. Anatomical site as well as microsatellite instability (MSI) status have shown to be associated with different clinicopathological and molecular features. This study aimed to ascertain key histopathological and miRNA expression patterns in microsatellite stable (MSS) and low-frequency MSI (MSI-L) patients, to provide insight into the mechanism of the disease. Methods: A retrospective cohort (2011-2015) of MSS/MSI-L CRC patient samples diagnosed at Charlotte Maxeke Johannesburg Academic Hospital was analyzed. Samples were categorized by site [Right colon cancer (RCC) versus left (LCC)], ethnicity [IA versus other ethnic groups (OEG)] and MSI status (MSI-L vs MSS). T-test, Fischer’s exact and Chi-square tests were conducted. Additional miRNA expression profiling was performed on IA patient samples. Results: IA patients with LCC demonstrated an increased prevalence in males, sigmoid colon, signet-ring-cell morphology, MSI-L with BAT25/26 marker instability and advanced disease association. MiRNA expression profiling revealed unique clustering, with dysregulation of let-7 and miRNA-125. Conclusion: This study revealed distinct histopathological features for LCC, and suggests BAT25/26, miRNAs let-7a-5p and miRNA-125a/b-5p as negative prognostic markers in African CRC patients. Larger confirmatory studies are recommended.

scholarly journals The silent pandemic in South Africa: Extra-pulmonary tuberculosis from head to heel

2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Camilla E. Le Roux ◽  
Sucari S.C. Vlok
Keyword(s):  
South Africa ◽  
Mycobacterium Tuberculosis ◽  
Pulmonary Tuberculosis ◽  
Communicable Disease ◽  
Diagnostic Dilemma ◽  
Extra Pulmonary Tuberculosis ◽  
Immunodeficiency Virus ◽  
Normal Chest Radiograph ◽  
Normal Chest ◽  
Extra Pulmonary

Extra-pulmonary tuberculosis (EPTB), caused by Mycobacterium tuberculosis, is the leading cause of communicable disease-related deaths in people with human immunodeficiency virus (HIV) worldwide and in South Africa. Mycobacterium tuberculosis disseminates haematogenously from an active primary lung focus and may affect extra-pulmonary sites in up to 15% of patients. Extra-pulmonary TB may present with a normal chest radiograph, which often causes a significant diagnostic dilemma. This review describes the main sites of involvement in EPTB, which is illustrated by local imaging examples.

scholarly journals Colorectal Cancer Incidence and Mortality Trends by Sex and Population Group in South Africa: 2002-2014.

2020 ◽  
Author(s):  
Lactatia Matsie Motsuku ◽  
Wenlong Carl Chen ◽  
Mazvita Molleen Muchengeti ◽  
Tamlyn Mac Quene ◽  
Patricia Kellett ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
South Africa ◽  
Black Males ◽  
Population Group ◽  
Black Population ◽  
Mortality Rates ◽  
P Value ◽  
Mortality Trends ◽  
Population Groups ◽  
Incidence And Mortality

Abstract BackgroundSouth Africa (SA) has experienced a rapid transition in the Human Development Index (HDI) over the past decade, which had an effect on the incidence and mortality rates of colorectal cancer (CRC). This study aims to provide CRC incidence and mortality trends by population group and sex in SA from 2002 to 2014.MethodsIncidence data were extracted from the South African National Cancer Registry and mortality data obtained from Statistics South Africa (STATS SA), for the period 2002 to 2014. Age-standardised incidence rates (ASIR) and age-standardised mortality rates (ASMR) were calculated using the STATS SA mid-year population as the denominator and the Segi world standard population data for standardisation. A Joinpoint regression analysis was computed for the CRC ASIR and ASMR by population group and sex.ResultsA total of 33,232 incident CRC cases and 26,836 CRC deaths were reported during the study period. Of the CRC cases reported, 54% were males and 46% were females, and among deaths reported, 47% were males and 53% were females. Overall, there was a 2.5% annual average percentage change (AAPC) increase in ASIR from 2002 to 2014 (95% CI: 0.6- 4.5, p-value <0.001). For ASMR overall, there was 1.3% increase from 2002 to 2014 (95% CI: 0.1- 2.6, p-value <0.001). The ASIR and ASMR among population groups were stable, with the exception of the Black population group. The ASIR increased consistently at 4.3% for black males (95% CI: 1.9- 6.7, p-value <0.001) and 3.4% for black females (95% CI: 1.5- 5.3, p-value <0.001) from 2002 to 2014, respectively. Similarly, ASMR for black males and females increased by 4.2% (95% CI: 2.0- 6.5, p-value <0.001) and 3.4% (, 95%CI: 2.0- 4.8, p-value <0.01) from 2002 to 2014, respectively.ConclusionsThe disparities in the CRC incidence and mortality trends may reflect socioeconomic inequalities across different population groups in SA. The rapid increase in CRC trends among the Black population group is concerning and requires further investigation and increased efforts for cancer prevention, early screening and diagnosis, as well as better access to cancer treatment.

Sign in / Sign up

Export Citation Format

Share Document