Cell-free DNA and tumor exosome cargo as diagnostic and prognostic marker for prostate cancer

According to the Global Cancer Statistics 2020, prostate cancer (PCa) is the second most commonly diagnosed male cancer and second leading cause of cancer death among men globally. Prostate cancer is known to be more aggressive among men of African origin with reasons not fully known. Previous studies have revealed PCa to be of a serious disease burden among African populations with PCa being the major cause of male cancer mortality. Prostate specific antigen (PSA) has long been introduced as a biomarker for screening in PCa diagnosis. However, serum PSA has low sensitivity for PCa diagnosis which has led to serious harm such as overdiagnosis and other complications of treatment for indolent disease. This makes it imperative to search for other novel biomarkers with high sensitivity and specificity for early diagnosis and management of prostate cancer. This study was aimed to characterize plasma and urinary cfDNA and tumour exosome cargo as diagnostic biomarker for PCa in South African populations with the goal of discovery of reliable, non-invasive, and novel biomarkers of PCa. We performed miRNA sequencing of exosomal RNA extracted from high and low Gleason's score PCa plasma samples. We performed differential expression (DE) of TCGA data and exosomal miRNA data and which we identified 185 miRNA and 65 miRNAs respectively. A comparison of the differential expressed TCGA miRNA and exosomal miRNA showed 13 miRNAs common between the two data with 7 of the 13 miRNAs expressed in the same direction. We further validated the expression of the 7 miRNAs using real time PCR in exosomal miRNA of high and low Gleason's score PCa samples and benign prostatic hyperplasia (BPH). We also performed whole exome sequencing of urinary cell free DNA and we identified 31 mutated genes. We reported for the first time an association between 27 of these genes and PCa in African populations. Four of the genes have earlier been identified as promising biomarker for prostate cancer diagnosis among African men. We also performed real time PCR quantification of cell free DNA to determine the concentration and DNA integrity of cfDNA in PCa and BPH of plasma and urine samples and which we were able to identify significantly higher plasma cfDNA level in PCa than BPH samples. We identified herein putative diagnostic biomarkers in plasma and urinary cfDNA and exosomes cargo for diagnosis of PCa in South African populations

Salivary creatinine as a diagnostic tool for evaluating patients with chronic kidney disease

Magister Scientiae Dentium - MSc(Dent)BACKGROUND Preliminary studies have shown the potential use of saliva in the diagnosis of chronic kidney disease (CKD). For saliva to completely replace serum as a diagnostic and monitoring tool for CKD, studies must be done to determine its effectiveness as a substitute in diagnosing chronic kidney disease, at each stage of the disease. Aim: The aim of the study was to evaluate the role of saliva as a safe and non-invasive alternative to serum, for creatinine estimation, in all stages of chronic kidney disease. METHOD A cross sectional study was conducted at the Renal Unit of Tygerberg Hospital, on 230 patients at all stages of CKD. Informed consent was obtained; thereafter saliva and serum samples were collected for creatinine analysis. Correlation between serum and salivary creatinine was determined using Spearman's correlation test. Receiver Operating Characteristics (ROC) analysis was used to determine the diagnostic ability of salivary creatinine and a cut-off value for sensitivity and specificity of salivary creatinine to diagnose CKD with GFR < 60ml/min was obtained. RESULTS Serum creatinine values ranged from 46?mol/L to 1581?mol/L with a median value of 134?mol/L. Salivary creatinine values ranged from 3?mol/L to 400?mol/L with a median of 11?mol/L. Spearman's correlation analysis showed a strong positive correlation (r = 0.82) between serum and salivary creatinine values for all CKD stages. Linear regression analysis of serum and salivary creatinine for CKD patients was significant in all CKD stages, except for stage 1. Area under the curve for salivary creatinine was 0.839. A cut-off value of 8.50?mol/L showed a sensitivity of 78.3% and specificity of 74.0% at eGFR < 60ml/min, for classifying patients as having CKD

Oral medicine case book 74: marijuana-induced Oral Leukoplakia

A 55-year-old male presented at the Oral Medicine Clinic of the University of the Western Cape, Oral Health Centre, Tygerberg Campus, for the evaluation of a persistent white patch on his right edentulous mandibular ridge. He had been referred from the Prosthodontics Clinic where he was seen for complete denture rehabilitation. The patient had no significant medical history and informed us that he had been smoking marijuana five times a day for more than twenty years and consumed alcohol occassionally. He had never worn a dental prosthesis and did not use tobacco in any form.DHE

Diagnostic Potential of Salivary Exosomes in Oral Cancer

“Omics” based concepts and techniques are gaining momentum in the field of oral medicine, spurred on by rapid advancements within the field of precision diagnostics and therapeutics. Oral cancer, specifically oral squamous cell carcinoma is the most common head and neck cancer, posing both diagnostic and prognostic challenges globally. Saliva offers several advantages as a diagnostic tool and has gained recognition as a biological medium for liquid biopsy. Salivary biomarkers, such as exosomes not only contain the full spectrum of genomic, lipidomic and proteomic material from its cell of origin, but are also more stable and consistently measurable in saliva due to their phospholipid structural protection of their merchandise/contents. Salivary exosomes are mediators in communication and transfer of contents between cancer and normal cells and thus key role players in mediating the tumor environment. Even though exosomes have been widely employed to investigate systemic diseases including head and neck cancers, unraveling the biologic mechanisms, scope of application of salivary tumor-derived exosomes and overcoming restrictions in this emergent field of saliva-exosomics warrants further investigation

Potential of miRNAs in Plasma Extracellular Vesicle for the Stratification of Prostate Cancer in a South African Population

Prostate cancer (PCa) is the most common cause of cancer death among African men. The analysis of microRNAs (miRNAs) in plasma extracellular vesicles (EVs) can be utilized as a non-invasive tool for the diagnosis of PCa. In this study, we used small RNA sequencing to profile miRNAs cargo in plasma EVs from South African PCa patients. We evaluated the differential expression of miRNAs between low and high Gleason scores in the plasma EVs of South African patients and in the prostatic tissue from data available in the Cancer Genome Atlas (TCGA) Data Portal. We identified 7 miRNAs differently expressed in both EVs and prostatic tissues. We evaluated their expression using qPCR in a larger cohort of 10 patients with benign prostatic hyperplasia (BPH) and 24 patients with PCa. Here, we reported that the ratio between two of these miRNAs (i.e., miR-194-5p/miR-16-5p) showed a higher concentration in PCa compared to BPH and in metastatic PCa compared to localized PCa. We explored for the first time the profiling of miRNAs cargo in plasma EVs as a tool for the identification of putative markers in the South African population. Our finding indicated the ratio miR-194-5p/miR-16-5p as a non-invasive marker for the evaluation of PCa aggressiveness in this population

Detection of Cancer-Associated Gene Mutations in Urinary Cell-Free DNA among Prostate Cancer Patients in South Africa

Prostate cancer (PCa) is the most common cause of cancer death among African men. The presence of tumor-specific variations in cell-free DNA (cfDNA), such as mutations, microsatellite instability, and DNA methylation, has been explored as a source of biomarkers for cancer diagnosis. In this study, we investigated the diagnostic role of cfDNA among South African PCa patients. We performed whole exome sequencing (WES) of urinary cfDNA. We identified a novel panel of 31 significantly deregulated somatic mutated genes between PCa and benign prostatic hyperplasia (BPH). Additionally, we performed whole-genome sequencing (WGS) on matching PCa and normal prostate tissue in an independent PCa cohort from South Africa. Our results suggest that the mutations are of germline origin as they were also found in the normal prostate tissue. In conclusion, our study contributes to the knowledge of cfDNA as a biomarker for diagnosing PCa in the South African population

The Role of Travel Medicine in Managing Future Pandemics:Lessons Learned from Global Infectious Disease Outbreaks

In an increasingly interconnected world shaped by globalization, international travel plays a significant role in facilitating the spread of infectious diseases. Travel medicine plays a vital role in preventing and controlling the spread of infectious diseases. This specialized field focuses on providing pre-travel advice, administering necessary vaccinations, promoting preventive measures during travel, and offering post-travel care. Risk assessment is essential to evaluate potential hazards associated with specific destinations. Factors such as disease prevalence, healthcare infrastructure, vaccination requirements, environmental, as well as cultural influences are considered. Through this process, the risks can be effectively managed by formulating appropriate strategies. Preventive measures are crucial to minimize the transmission of infectious diseases during travel. These include compulsory vaccinations based on destination-specific requirements, recommended travel restrictions when necessary, and quarantine protocols for individuals exhibiting symptoms. Enhanced surveillance efforts combined with promotion of personal hygiene practices aid further prevention. Educating travelers about safe food handling practices also serves as an effective measure against many infections. Effective pandemic management requires collaboration among countries and international organizations. Travel medicine Professionals work alongside public health authorities to provide accurate information, vaccine administration services, and increased awareness about preventive measures. This collaborative effort facilitates timely response mechanisms ensuring global protection from emerging threats like pandemics