Microbiome Dysbiosis, Dietary Intake and Lifestyle-Associated Factors Involve in Epigenetic Modulations in Colorectal Cancer: A Narrative Review.

Background: Colorectal cancer is the second cause of cancer mortality and the third most commonly diagnosed cancer worldwide. Current data available implicate epigenetic modulations in colorectal cancer development. The health of the large bowel is impacted by gut microbiome dysbiosis, which may lead to colon and rectum cancers. The release of microbial metabolites and toxins by these microbiotas has been shown to activate epigenetic processes leading to colorectal cancer development. Increased consumption of a 'Westernized diet' and certain lifestyle factors such as excessive consumption of alcohol have been associated with colorectal cancer.Purpose: In this review, we seek to examine current knowledge on the involvement of gut microbiota, dietary factors, and alcohol consumption in colorectal cancer development through epigenetic modulations.Methods: A review of several published articles focusing on the mechanism of how changes in the gut microbiome, diet, and excessive alcohol consumption contribute to colorectal cancer development and the potential of using these factors as biomarkers for colorectal cancer diagnosis.Conclusions: This review presents scientific findings that provide a hopeful future for manipulating gut microbiome, diet, and alcohol consumption in colorectal cancer patients' management and care.

Thyroid hormone profile in preeclampsia patients: a case control study.

Objective: Preeclamptic women are reported to have a higher incidence of thyroid dysfunction that correlates with the severity of preeclampsia. The aim of this study was to assess thyroid hormone profiles in in pregnant women with preeclampsia and gestational hypertension and the risk for thyroid dysfunction.Methods: In this study, age-matched pregnant females in the second trimester of pregnancy, diagnosed with preeclampsia (PE), gestational hypertension (GH), as cases, and apparently healthy normotensive (NT) pregnant woman as controls were recruited. Blood samples were drawn for the assessment of thyroid hormone (TSH, FT3 and FT4) levels and thyroid dysfunction.Results: Out of the total of 133 pregnant women recruited for this study, sub-clinical hypothyroidism was the only thyroid dysfunction common to all study groups, with a prevalence of 3.3% in both PE and NT groups, and 4.3% in the GH group. 1% of women in the PE group had sub-clinical hyperthyroidism, compared to 3.3% in the NT group. Although TSH and FT3 were elevated in normotensives, mean differences between the three groups were not statistically significant. However, mean FT4 levels in the GH group (12.99 ± 1.24) and PE group (12.33 ± 2.26), when compared to the control group (11.55 ± 1.94), were significantly higher (p < 0.05).Conclusion: Undiagnosed subclinical hypothyroidism was found in all the categories of pregnant women studied, which if uncontrolled, could increase the risk of pregnancy-related complications, especially in pregnant women with preeclampsia and gestational hypertension.

Haptoglobin phenotypes with weak antioxidant capacity increase risk factors of cardiovascular disease in Ghanaian HIV-infected patients on highly active antiretroviral therapy.

OBJECTIVE: Highly active antiretroviral therapy (HAART) has considerably reduced HIV/AIDS-related morbidity and mortality; however, the therapy has been associated with the development of cardiovascular disease (CVD), and genetic predisposition factors may aggravate disease outcome. This study was aimed at investigating the relationship between haptoglobin phenotypes and risk factors of CVD in HIV patients. METHODS: A total of 105 HIV sero-positive patients on HAART and 75 HIV-infected HAART-naïve individuals were enrolled in the study. Socio-demographics and clinical characteristics of the participants were obtained using a well-structured questionnaire. Lipid profile, lactate dehydrogenase (LDH) and haptoglobin (Hp) phenotypes were analysed from serum whiles haemoglobin (Hb) level, CD4+ cell count and HIV viral RNA load were determined using whole blood. RESULTS: Atherogenic index of plasma (AIP) was significantly higher in patients on HAART than the naïve group (P < 0.05). Age, BMI, visceral fat, systolic blood pressure LDH and lipid variables strongly and positively correlated with AIP (P < 0.05), with the exception of HDL-c (P < 0.001) which showed a negative correlation. HAART was associated with hypertension (χ2  = 4.33, P = 0.037), hypercholesterolaemia (χ2  = 10.99, P < 0.001), elevated LDL-c (χ2 = 10.30, P < 0.001) and decreased HDL-c (χ2  = 3.87, P = 0.09). Hp2-2 and Hp0 collectively was strongly associated with hypertension (OR = 2.54, P = 0.011), obesity (OR = 5.97, P < 0.001) and hypercholesterolaemia (OR = 2.99, P < 0.001). CONCLUSION: HIV/AIDS patients on HAART expressing Hp phenotypes with weak antioxidant capacity have an increased risk of developing CVD.

OBJECTIF: La thérapie antirétrovirale hautement active (HAART) a considérablement réduit la morbidité et la mortalité liées au VIH/SIDA; cependant, le traitement a été associé au développement de maladie cardiovasculaire (MCV) et des facteurs de prédisposition génétique pourraient aggraver l'évolution de la maladie. Cette étude visait à étudier la relation entre les phénotypes de l'haptoglobine et les facteurs de risque de MCV chez les patients VIH. MÉTHODES: Un total de 105 patients VIH positifs sous HAART et 75 personnes infectés par le VIH mais naïfs au HAART ont été recrutés pour l'étude. Les caractéristiques sociodémographiques et cliniques des participants ont été obtenues à l'aide d'un questionnaire bien structuré. Le profil lipidique, les phénotypes de la lactate déshydrogénase (LDH) et de l' haptoglobine (Hp) ont été analysés à partir du sérum tandis que le taux d'hémoglobine (Hb), la numération des cellules CD4+ et la charge d'ARN viral du VIH ont été déterminés en utilisant du sang total. RÉSULTATS: L'indice athérogène du plasma (IAP) était significativement plus élevé chez les patients sous HAART que chez le groupe naïf (p <0,05). Les variables âge, IMC, graisse viscérale, tension artérielle systolique, LDH et lipides étaient fortement et positivement corrélées à l'IAP (p < 0,05), à l'exception du HDL-c (p < 0,001) qui présentait une corrélation négative. L'HAART a été associée à l'hypertension (χ2 = 4,33; p = 0,037), l'hypercholestérolémie (χ2 = 10,99; p <0,001), une LDL-c élevée (χ2 = 10,30; p <0,001) et une diminution de HDL-c (χ2 = 3,87; p = 0,09). Ensemble, Hp2-2 et Hp0 étaient fortement associés à l'hypertension (OR = 2,54; p = 0,011), à l'obésité (OR = 5,97; p <0,001) et à l'hypercholestérolémie (OR = 2,99; p <0,001). CONCLUSION: Les patients VIH/SIDA sous HAART exprimant des phénotypes Hp à faible capacité antioxydante ont un risque accru de développer une maladie cardiovasculaire.

Obesity and Testosterone Levels in Ghanaian Men With Type 2 Diabetes.

Testosterone plays a vital role in obesity, glucose homeostasis, and lipid metabolism. The aim of this study was to investigate androgen levels and its association with obesity in Ghanaian men with type 2 diabetes. The study showed that serum total and free testosterone concentrations were lower in male patients with type 2 diabetes and that obesity was strongly associated with low levels of total and free testosterone in Ghanaian men with type 2 diabetes.

Comparative Determination of Glomerular Filtration Rate Estimation Formulae in Type 2 Diabetic Patients: An Observational Study.

Assessing glomerular filtration rate (GFR) involves collecting timed urine samples for 24 hours, requiring significant time and resources in the clinical setting. Using predictive GFR formulae to assess renal function may be a better alternative. Our goal was to determine which predictive GFR formula had the highest level of concordance with the GFR that has been measured in a resource-poor setting. This is an observational study. We selected fifty (50) individuals diagnosed with type 2 diabetes (T2DM) in Kumasi, Ghana. The sociodemographic and clinical characteristics were obtained using a structured questionnaire. Urine was obtained from each subject over 24 hours. The levels of glucose (FBG) and creatinine in patients' blood, as well as the levels of creatinine in their urine, were measured after the patients had fasted overnight. Participants had a mean age of 57.4 ± 10.7 (years), BMI of 27.8 ± 4.1 (kg/m2), FBG of 9.0 ± 3.1 (mmol/L), and creatinine concentrations of 95.6 ± 29.1 (µmol/L). A Krouwer plot was used to compare the measured GFR with three formulae: Chronic Kidney Disease Epidemiology (CKD-EPI), Modification of Diet in Renal Disease (MDRD), and Cockroft-Gault (CG) for GFR prediction. Among the 3 estimates, CG showed nonsignificance (p > 0.05) with the measured GFR. The primary finding was that the GFR calculated using the CG formula was not different from the GFR measured, suggesting that CG is the most appropriate alternative GFR estimate among a cross-section of T2DM patients in Ghana.

Clinical outcomes and immunological response to SARS-CoV-2 infection among people living with HIV.

People living with HIV (PLWH) usually suffer from co-infections and co-morbidities including respiratory tract infections. SARS-CoV-2 has been reported to cause respiratory infections. There are uncertainties in the disease severity and immunological response among PLWH who are co-infected with COVID-19. This review outlines the current knowledge on the clinical outcomes and immunological response to SARS-CoV-2 among PLWH. Literature was searched in Google scholar, Scopus, PubMed, and Science Direct conforming with the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines from studies published from January 2020 to June 2023. A total of 81 studies from 25 countries were identified, and RT-PCR was used in confirming COVID-19 in 80 of the studies. Fifty-seven studies assessed risk factors and clinical outcomes in HIV patients co-infected with COVID-19. Thirty-nine of the studies indicated the following factors being associated with severe outcomes in HIV/SARS-CoV-2: older age, the male sex, African American race, smoking, obesity, cardiovascular diseases, low CD4+ count, high viral load, tuberculosis, high levels of inflammatory markers, chronic kidney disease, hypertension, diabetes, interruption, and delayed initiation of ART. The severe outcomes are patients' hospitalization, admission at intensive care unit, mechanical ventilation, and death. Twenty (20) studies, however, reported no difference in clinical presentation among co-infected compared to mono-infected individuals. Immune response to SARS-CoV-2 infection was investigated in 25 studies, with some of the studies reporting high levels of inflammatory markers, T cell exhaustion and lower positive conversion rate of IgG in PLWH. There is scanty information on the cytokines that predisposes to severity among HIV/SARS-CoV-2 co-infected individuals on combined ART. More research work should be carried out to validate co-infection-related cytokines and/or immune markers to SARS-CoV-2 among PLWH.

Differential expression of host oncogenes in human papillomavirus-associated nasopharyngeal and cervical epithelial cancers.

Human papillomavirus (HPV)-related cervical and nasopharyngeal cancers differ in molecular mechanisms underlying the oncogenic processes. The disparity may be attributed to differential expression of oncoproteins. The current study investigated the host oncogenes expression pattern in HPV-associated cervical and nasopharyngeal cancer. Formalin-fixed paraffin-embedded tissues originating from the nasopharyngeal and cervical regions were screened using Hematoxylin and Eosin staining. Genomic DNA and total RNA were extracted from confirmed cancer biopsies and non-cancer tissues (NC). HPV was detected by PCR using MY09/GP5+/6+ primers. Protein expression levels of AKT, IQGAP1, and MMP16 in HPV-infected cancers and controls were determined by immunohistochemistry. RT-qPCR was used to profile mRNAs of the oncogenes. AKT and IQGAP1 proteins were highly expressed in the epithelial cancers compared with the non-cancer tissues (p < 0.05). IQGAP1 and MMP16 mRNAs level was significantly higher in the cancers than in the NC (p < 0.05), but not AKT mRNA levels. MMP16 protein was ubiquitously expressed in all tissues. AKT mRNA level was significantly elevated in CC compared with NPC (p < 0.001). However, the difference in AKT, IQGAP1 and MMP16 proteins level between CC and NPC was not significant (p > 0.05). The oncoproteins expression level between the HPV-positive and HPV-negative cancer biopsies showed no significant difference (p < 0.05). Current study reports AKT but not IQGAP1 and MMP16 mRNAs differentially expression in cervical and nasopharyngeal cancers, independent of HPV infection status.

HPV18 L1 and long control region sequences variation and E6/E7 differential expression in nasopharyngeal and cervical cancers: a comparative study.

BACKGROUND: The role of high-risk human papillomaviruses (hr-HPVs) in cervical cancer (CC) pathogenesis has long been established. Knowledge about the involvement of hr-HPVs in the etiology of nasopharyngeal cancers (NPC) was not well appreciated until the early 2000s when a clear link began to emerge. However, it is not clear whether HPV oncogenesis in the different epithelial cancers is associated with L1 gene and long-control region (LCR) sequences variation. This study aimed to investigate the HPV18 L1 gene and LCR sequences variation in cervical and nasopharyngeal biopsies, and assessed E6 and E7 genes expression level in both cancers. METHOD: Four-hundred and three (403) formalin-fixed paraffin-embedded tissues originating from nasopharyngeal (NPC) (279) and cervical (CC) (124) sites were collected from a pathology laboratory, Pathologist Without Borders, Accra, Ghana. Haematoxylin and eosin staining was carried out to confirm the presence of cancer on prepared biopsy sections. DNA was extracted from the confirmed cancer biopsies, followed by PCR using MY09/GP5+ /6+ primers to detect the presence of HPV and specific primers for the amplification of L1 gene and LCR. Sanger sequencing was carried out to determine HPV genotypes, and L1 and LCR sequences variant of HPV18s in CC and NPC biopsies. The HPV18 E6/E7 mRNA expression pattern in both cancers was determined using RT-qPCR. RESULTS: Most of the NPC (45%) and CC (55%) biopsies were HPV18 positive. Comparison of HPV18 L1 sequences obtained from cervical and nasopharyngeal cancer tissues, the L1 sequences from the NPC were highly dissimilar with a 59-100% variation among themselves, and in relation to the reference strains. However, the L1 sequences from the CC were more similar with a 91.0-100% variation among the amplified sequences. Also, the LCR sequences from CC were quite different relative to that of NPC. Results for the differential expression of E6/E7 in the two cancers showed a higher fold change in E6 expression in the CC tissues than the NPC tissues while a reverse expression pattern was found for E7 gene. CONCLUSION: The current study reports for the first-time variations in HPV18 L1 and LCR sequences, and differential expression of E6/E7 genes in NPC compared to CC, suggesting a possible adaptation mechanism of the virus at different cancer sites.

Epstein-Barr virus genotype-1 and Mediterranean + strain in gastric cancer biopsies of Ghanaian patients.

Gastric cancer (GC) prevalence is on the increase in Ghana, and Epstein-Barr virus (EBV) is one of the factors that have been implicated in the etiology of the cancer. It is therefore important to know the contribution of EBV genotype and strains that are associated with GC. In this study, we aimed at genotyping EBV and determining predominant strains in GC biopsies in Ghanaian patients. Genomic DNA was extracted from 55 GC biopsies (cases) and 63 normal gastric tissues (controls) were amplified by polymerase chain reaction (PCR) using specific primers for EBV detection and genotyping followed by PCR fragments sequencing. Epstein-Barr virus positivity were 67.3% and 49.2% in the GC and normal biopsies, respectively. Both cases and controls had the Mediterranean + strain of EBV. The predominant genotype of the virus in the GC cases was genotype-1 (75.7%) compared to 66.7% of genotype-2 among the control group. Infection was associated with GC in the study population (OR = 2.11, P = 0.014, 95% CI: 1.19 - 3.75), and EBV genotype-1 significantly increased the risk of GC (OR = 5.88, P < 0.0001, 95% CI: 3.18-10.88). The mean EBV load in the cases (3.507 ± 0.574) was significantly higher than in the controls (2.256 ± 0.756) (P < 0.0001). We conclude that EBV, especially Mediterranean + genotype-1, was the predominant strain in GC biopsies and GC type or progression is independent of the viral load.

Extracellular matrix metalloproteinases inducer gene polymorphism and reduced serum matrix metalloprotease-2 activity in preeclampsia patients.

Preeclampsia increases the risk of pregnancy-related complications, nevertheless a successful spiral vessel remodeling, and trophoblast invasion reduces disorders of pregnancy. Matrix metalloproteinase-2 (MMP-2) clears the path for trophoblast invasion, and activation of MMP-2 largely depends on extracellular matrix metalloproteinases inducer (EMMPRIN) protein. This study aimed to investigate EMMPRIN gene polymorphism and MMP-2 activity in preeclampsia patients. Archival whole blood and serum samples of 74 preeclampsia and 66 normotensive pregnant women age-matched were used in this case-control study. Genomic DNA was extracted from the whole blood samples and EMMPRIN gene amplified with specific primers following fragments sequence mutation analysis. Serum MMP-2 activity was determined using enzyme-linked immunosorbent assay (ELISA) and socio-demographic data of participants retrieved from the database. Age of preeclampsia patients (32.78 ± 6.39) years and body mass index (BMI) (33.09 ± 7.27) kg/m2 compared with the normotensive counterparts (32.33 ± 5.56) years and (32.33 ± 5.56) kg/m2,respectively, were not statistically significant (P > 0.05). Serum matrix metalloprotease-2 (MMP-2) activity was significantly reduced in preeclampsia group (16.34 ± 7.07) compared with the normotensives (25.63 ± 4.56) (P < 0.001), and rs424243T/G variant (55.6%) was overrepresented among the cases compared with the normotensives (16.7%). The single-nucleotide polymorphism T/G was found to be associated with preeclampsia (odds ratio [OR] = 7.63; 95% confidence interval [CI] = 3.95-14.75; P < 0.0001). Decreased activity of MMP-2 and rs424243T/G SNP of EMMPRIN gene was reported in preeclampsia. These preliminary data warrant a further investigation into the relationship between EMMPRIN gene polymorphism and MMP-2 activity in preeclampsia.

Development of an Affordable ELISA Targeting the SARS-CoV-2 Nucleocapsid and Its Application to Samples from the Ongoing COVID-19 Epidemic in Ghana.

INTRODUCTION: The true nature of the population spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in populations is often not fully known as most cases, particularly in Africa, are asymptomatic. Finding the true magnitude of SARS-CoV-2 spread is crucial to provide actionable data about the epidemiological progress of the disease for researchers and policymakers. This study developed and optimized an antibody enzyme-linked immunosorbent assay (ELISA) using recombinant nucleocapsid antigen expressed in-house using a simple bacterial expression system. METHODS: Nucleocapsid protein from SARS-CoV-2 was expressed and purified from Escherichia coli. Plasma samples used for the assay development were obtained from Ghanaian SARS-CoV-2 seropositive individuals during the pandemic, while seronegative controls were plasma samples collected from blood donors before the coronavirus disease 2019 (COVID-19) pandemic. Another set of seronegative controls was collected during the COVID-19 pandemic. Antibody detection and levels within the samples were validated using commercial kits and Luminex. Analyses were performed using GraphPad Prism, and the sensitivity, specificity and background cut-off were calculated. RESULTS AND DISCUSSION: This low-cost ELISA (£0.96/test) assay has a high prediction of 98.9%, and sensitivity and specificity of 97% and 99%, respectively. The assay was subsequently used to screen plasma from SARS-CoV-2 RT-PCR-positive Ghanaians. The assay showed no significant difference in nucleocapsid antibody levels between symptomatic and asymptomatic, with an increase of the levels over time. This is in line with our previous publication. CONCLUSION: This study developed a low-cost and transferable assay that enables highly sensitive and specific detection of human anti-SARS-CoV-2 IgG antibodies. This assay can be modified to include additional antigens and used for continuous monitoring of sero-exposure to SARS-CoV-2 in West Africa.

Paradox of COVID-19 in pregnancy: are pregnant women more protected against or at elevated risk of severe COVID-19?

Many underlying medical conditions have been linked to worse COVID-19 prognosis. Based on reports on SARS-CoV-1 and Middle East respiratory syndrome infections, pregnancy has been considered a predisposing factor to severe COVID-19, with pregnant women being a high-risk group for several physiological reasons. Specifically, pregnant women undergo physiological adaptations that predispose them to severe respiratory viral diseases, including SARS-CoV-2. However, a significant amount of evidence suggests that the clinical outcome of COVID-19 among pregnant women is not different from the general population. In view of this, this report discusses the physiological conditions in pregnant women that adversely affect their immunity, cardiovascular homeostasis, and their endothelial and coagulopathic functions, thereby making them more prone to severe viral infections. We also discuss how these physiological adaptations appear to paradoxically offer protection against severe COVID-19 among pregnant women.

BRCA1 gene polymorphism and finger dermatoglyphic patterns in Ghanaian breast cancer patients: a quantitative cross-sectional approach.

Introduction: breast cancer development is linked to mutant single nucleotide polymorphism of breast cancer type 1 (BRCA1) gene usually harboured within exon 11. It has also been linked to finger dermatoglyphics where certain patterns have been associated with breast cancer. This study suggests a possible relationship between finger dermatoglyphic patterns and single nucleotide polymorphism of BRCA1 gene. Methods: in a quantitative cross-sectional approach, finger dermatoglyphic patterns were obtained using the ink method from 70 female breast cancer patients and 70 age-matched apparently healthy females. Approximately 5 ml of venous blood was obtained from each participant from which DNA was extracted from the white blood cells collected after centrifugation. DNA was amplified and sequenced and the data aligned with the wildtype template of BRCA1 gene. Fingerprint patterns were analyzed with Chi-square. Mean frequency of fingerprint patterns was analyzed with independent student's t-test. Differences in data set with p<0.05 were statistically significant. Results: luminal B was the predominant breast cancer molecular subtype among the patients. The predominant fingerprint pattern among breast cancer participants was the loop. Six or more loops had higher frequency among breast cancer females. The predominant BRCA1 gene variant locations were c.34311, c.34320, and c.34321 with c.34311A>C being the predominant variant. Higher percentage frequency of six or more loops in relation to c.34311A>C was observed in apparently healthy females compared to breast cancer females. Conclusion: the study reports for the very first time in Ghana, BRCA1 gene variants and finger dermatoglyphics among breast cancer patients. Although the results are preliminary and inconclusive it creates an avenue for extended studies.

Helicobacter Pylori Variants with ABC-Type Tyrosine Phosphorylation Motif in Gastric Biopsies of Ghanaian Patients.

BACKGROUND: Helicobacter pylori pathogenicity and disease severity are determined by the tyrosine phosphorylation motifs of CagA protein. This study is aimed at detecting the presence of H. pylori and identifying the CagA tyrosine phosphorylation motifs in Ghanaian patients. Material and Methods. A total of 94 archival genomic DNA samples from gastric biopsies were used for the study, and H. pylori was detected by amplifying the 16S rRNA gene. The 3'-end variable region of the cagA gene was amplified, and the entire 3'-end was sequenced and translated into amino acids. RESULTS: H. pylori was detected in 53.2% (50/94) of the samples, and all the detected bacteria harboured the cagA gene. Two variants of the bacteria were identified based on the size of the amplified cagA gene: 207 bp and 285 bp. The 207 bp and 285 bp variants accounted for 74% and 22%, respectively, and 4% showed both fragments. Translated amino acid sequence of the cagA gene showed EPIYA-A, EPIYA-B, and EPIYA-C (ABC type) motifs, indicating the Western variant. The CagA protein C-terminal showed insertion of amino acids in the sequence flanking the EPIYA-A motif at the N-terminal and a complete deletion of the EPIYA-CC and EPIYA-CCC motifs together with the flanking sequences. CONCLUSIONS: H. pylori identified were Western variant (ABC type) with unique amino acid insertions, suggesting unique variants in Ghanaian patients. Further investigation is however required to understand the role of the molecular diversity of the variant in gastric disease outcome.

Reduced Serum Circulation of Cell-Free DNA Following Chemotherapy in Breast Cancer Patients.

Breast cancer is the most common malignancy in women, with alarming mortalities. Neoadjuvant treatments employ chemotherapy to shrink tumours to a well-defined size for a better surgical outcome. The current means of assessing effectiveness of chemotherapy management are imprecise. We previously showed that breast cancer patients have higher serum circulating cell-free DNA concentrations. cfDNA is degraded cellular DNA fragments released into the bloodstream. We further report on the utility of cfDNA in assessing the response to chemotherapy and its potential as a monitoring biomarker. A total of 32 newly diagnosed and treatment-naive female breast cancer patients and 32 healthy females as controls were included. Anthropometric, demographic and clinicopathological information of participants were recorded. Each participant donated 5 mL of venous blood from which sera were separated. Blood sampling was carried out before the commencement of chemotherapy (timepoint 1) and after the third cycle of chemotherapy (timepoint 2). qPCR was performed on the sera to quantify ALU 115 and 247 levels, and DNA integrity (ALU247/ALU115) was determined. ALU 115 and 247 levels were elevated in cancer patients but were significantly decreased after the third cycle of chemotherapy (T2) compared to T1. DNA integrity increased after the third cycle. Serum cfDNA may provide a relatively inexpensive and minimally invasive procedure to evaluate the response to chemotherapy in breast cancer.

High atherogenic index of plasma and cardiovascular risk factors among Ghanaian breast cancer patients.

Comorbidities impact negatively on breast cancer prognosis, especially in developing countries where cases are usually presented to clinics at advanced stages. This study aimed to determine the atherogenic index of plasma (AIP) and cardiovascular risk factors among Ghanaian women diagnosed with breast cancer. A total of 52 breast cancer patients were age-matched with 52 healthy controls. Sociodemographics of participants were obtained using a well-structured questionnaire. Pathological data of patients were obtained from medical records, and all clinical and anthropometric measurements were done using standard instruments. Lipid profile was determined from serum using enzymatic assays, and cardiovascular risk factors were calculated from estimated lipid parameters. Blood pressure, AIP, total cholesterol (T. chol), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-c) were significantly elevated (P < 0.05) in the breast cancer patients compared to the controls, but the reverse was observed for high-density lipoprotein cholesterol (HDL-c) (P < 0.01). Obesity (odds ratio [OR] = 2.51, P = 0.015), hypertension (OR = 4.04, P < 0.001), AIP (OR = 10.44, P < 0.001), and dyslipidemia (P < 0.01) were significantly associated with breast cancer. AIP correlated positively with age (r = 0.244, P < 0.05), body mass index (r = 0.225, P < 0.05), blood pressure (P < 0.01), T. chol (r =0.418, P< 0.01), and TG (r = 0.880, P < 0.01), but inversely correlated with HDL-c (r = -0.460, P < 0.01). A greater proportion (88%) of the patients presented with advanced breast cancer. AIP and cardiovascular risk factors were high in the breast cancer patients. Considering that AIP and cardiovascular disease risk factors are of interest in breast cancer patients, further studies are needed to understand the effect of AIP and cardiovascular risk factors on breast cancer outcomes.

Prospecting for Breast Cancer Blood Biomarkers: Death-Associated Protein Kinase 1 (DAPK1) as a Potential Candidate.

BACKGROUND: Breast cancer is the commonest malignancy in women worldwide. It is estimated to affect approximately 1.5 million women annually and responsible for the greatest number of cancer-related mortalities among women. In 2018, breast cancer mortalities stood at 627,000 women representing approximately 15% of all cancer deaths among women. In Ghana, breast cancer is the second leading cause of cancer deaths, with an incidence of 2,900 cases annually; one of eight women with the disease die. This gives impetus to the fight for improved early detection, treatment, and/management. In this light, we investigated the potential of death-associated protein kinase 1 (DAPK1) as a biomarker for breast cancer. As a tumour suppressor, its expression is activated by several carcinogens to influence cellular pathways that result in apoptosis, autophagy, immune response, and proliferation. AIM: To investigate DAPK1 as a blood biomarker for breast cancer. METHODS: Blood samples of participants diagnosed with breast cancer and healthy controls were collected and processed to obtain serum. Information on age, treatment, diagnosis, and pathology numbers was retrieved from folders. Pathology numbers were used to retrieve breast tissue blocks of patients at the Department of Pathology of the KBTH. Tissue blocks were sectioned and immunohistochemically stained with anti-DAPK1 and counterstained with hematoxylin to determine the DAPK1 expression levels. DAKP1 levels in blood sera were quantified using a commercial anti-DAPK1 ELISA kit. Case and control group means were compared using one-way ANOVA and Chi-square test. Statistical significance was set at p ≤ 0.05. Results and Discussion. DAPK1 levels were higher in sera and breast tissues of breast cancer patients than controls. The augmented DAPK1 expression can be interpreted as a stress response survival mechanism to remediate ongoing deleterious events in the cells orchestrated by carcinogenesis. In the presence of abundant DAPK1, the proliferative power of cells (both cancerous and noncancerous) is increased. This may explain why high DAPK1 expression strongly associates with aggressive breast cancer phenotypes like the ER-negative breast cancers, especially the triple-negative breast cancers (TNBC) which are the most aggressive, fast-growing, and highly metastatic. CONCLUSION: DAPK1 is highly expressed in sera and breast tissues of breast cancer patients than nonbreast cancer participants. The elevated expression of DAKP1 in circulation rather than in breast tissues makes it a candidate for use as a blood biomarker and potential use as therapeutic target in drug development.

Genotypic Characterization of Epstein Barr Virus in Blood of Patients with Suspected Nasopharyngeal Carcinoma in Ghana.

Nasopharyngeal cancer (NPC) is associated with Epstein Barr virus (EBV) infection. However different viral strains have been implicated in NPC worldwide. This study aimed to detect and characterize EBV in patients diagnosed with NPC in Ghana. A total of 55 patients diagnosed with NPC by CT scan and endoscopy were age-matched with 53 controls without a known oncological disease. Venous blood was collected from the study participants and DNA extracted from the blood samples. Detection of EBV and genotyping were done by amplifying Epstein Barr nuclear antigen 1 (EBNA-1) and Epstein Barr nuclear antigen 2 (EBNA-2), respectively, using specific primers. Viral load in patients and controls was determined using real-time polymerase chain reaction. EBV positivity in controls (92%) was significantly greater than that of NPC patients (67%) (χ2 = 19.17, p < 0.0001), and viral infection was independent of gender (χ2 = 1.770, p = 0.1834). The predominant EBV genotypes in patients and controls were genotype 2 (52%) and genotype 1 (62%), respectively. Median EBV load was significantly higher in NPC patients than the control group (p < 0.01). In summary, prevalence of EBV genotype 2 infection was higher in NPC patients than the control group. Assessment of EBV load may be used as a biomarker for the diagnosis of NPC.

Imbalance of antioxidant enzymes activities and trace elements levels in Ghanaian HIV-infected patients.

Human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) have been associated with high oxidative stress in HIV patients. The disparity in antioxidant-oxidant levels in HIV patients favours viral replication and disease progression. This study aimed at determining the effect of ART on antioxidant enzymes activities and trace elements levels in Ghanaian HIV patients. A total of 242 participants; comprising of 105 HIV-infected patients on ART, 77 HIV-infected ART-naïve, and 60 HIV seronegative controls were recruited for the study. Whole blood was collected and used for haematological profiling, and the determination of CD4+ counts, superoxide dismutase (SOD) activity and trace element levels. Serum was used for liver function tests and the determination of glutathione reductase (GR) activity, and plasma was used to estimate reduced glutathione (GSH) levels. Low levels of haemoglobin (HB), hematocrit, mean cell volume (MCV) and mean cell hemoglobin (MCH), and trace elements were found in ART-naïve patients compared to those on ART and the seronegative controls. In the ART-naïve patients, glutathione reductase (GR) activity and reduced glutathione (GSH) level were significantly low compared to patients on ART and seronegative controls. Activity of SOD was significantly reduced in ART-naïve patients compared to those on ART and the control group, and manganese is the only trace element that showed a strong negative correlation with SOD activity and a positive and significant correlation with CD4+ count, and therefore needs to be investigated further. The study suggests that assessing antioxidant levels or enzymes activities of patients infected with HIV should be considered during therapy.

Dyslipidaemia is common among patients with type 2 diabetes: a cross-sectional study at Tema Port Clinic.

OBJECTIVE: This study aimed to evaluate dyslipidemia in Ghanaian subjects with type 2 diabetes. RESULTS: Hundred individuals with type 2 diabetes and 61 apparently healthy controls participated. The prevalence of hypercholesterolemia among persons with type 2 diabetes was 53%. Blood pressure, fasting blood glucose (FBG), triglyceride (TG), low-density lipoproteins (LDL) and alanine transaminase (ALT) levels were higher in persons with type 2 diabetes compared with the control group (p < 0.01). Positive correlations were found within persons with type 2 diabetes for triglyceride vs FBG; ALT vs age and aspartate transaminase (AST) vs TG (p < 0.05 respectively). This study demonstrated hyperlipidemia and poor liver health in persons with type 2 diabetes.