Henry A. Adeola

Emergence of keratin 17 vs. loss of keratin 13: Their reciprocal immunohistochemical profiles in oral carcinoma in situ

To evaluate differential expressions for keratin (K) subtypes 13 and 17 in oral borderline malignancies, we examined 67 surgical specimens of the oral mucosa for their immunohistochemical profiles. From those specimens, 173 foci of epithelial dysplasia, 152 foci of carcinoma in situ (CIS), and 82 foci of squamous cell carcinoma (SCC) were selected according to our diagnostic criteria, along with 20 areas of normal epithelia. In normal epithelia, there was no K17 positivity (0%), whereas definite K13 positivity (100%) was observed. The same tendencies were obtained in mild (undefined) and moderate (true) epithelial dysplasias (K17: 0%; K13: 100%). In contrast, all CIS (100%) had K17 positivities, while K13 positivities were lost in many of them (7%). Similar tendencies were confirmed in invasive SCC (K17: 100%, K13: 4%). Simultaneous immunopositivities for K17 and K13 were found only in SCC (7%) and CIS (4%) foci with distinct keratinization. These foci also showed K10 positivities, though K10 positive areas were not identical to K13 positive areas. The results indicate that expressions of K17 and K13 are reciprocal in oral epithelial lesions and that the K17 emergence is related to malignancies.

Inflammatory histopathogenesis of nasopalatine duct cyst: a clinicopathological study of 41 cases

OBJECTIVE The aim of this study is to characterize immunohistochemical profiles of lining epithelia of nasopalatine duct cyst (NPC) as well as to correlate those findings with their clinicopathological features to understand the histopathogenesis of NPC. MATERIALS AND METHODS Forty-one surgical specimens from NPC were examined for clinical profiles and expression of keratin-7, 13, MUC-1, and P63 by immunohistochemistry, compared to radicular cyst (RC) and maxillary sinusitis. RESULTS Nasopalatine duct cyst was clinically characterized by male predominant occurrence: 44% of the cases involved tooth roots, and 70% with inflammatory backgrounds. Lining epithelia of NPCs without daughter cysts were immunohistochemically distinguished into three layers: a keratin 7-positive (+) ciliated cell layer in the surface, a keratin-13+ middle layer, and a MUC-1+/P63+ lower half, indicating that they were not respiratory epithelia, and the same layering pattern was observed in RC. However, those immunolocalization patterns of the main cyst lining with daughter cyst were exactly the same as those of daughter cyst linings as well as duct epithelia of mucous glands. CONCLUSIONS Two possible histopathogenesis of NPC were clarified: one was inflammatory cyst like RC and the other was salivary duct cyst-like mucocele.

Discovery of novel candidate urinary protein biomarkers for prostate cancer in a multiethnic cohort of South African patients via label-free mass spectrometry

Improvement in diagnostic accuracy of prostate cancer (PCa) progression using MS‐based methods to analyze biomarkers in our African, Caucasian, and Mixed Ancestry patients can advance early detection and treatment monitoring.

Novel potential serological prostate cancer biomarkers using CT100+ cancer antigen microarray platform in a multi-cultural South African cohort

There is a growing need for high throughput diagnostic tools for early diagnosis and treatment monitoring of prostate cancer (PCa) in Africa. The role of cancer-testis antigens (CTAs) in PCa in men of African descent is poorly researched. Hence, we aimed to elucidate the role of 123 Tumour Associated Antigens (TAAs) using antigen microarray platform in blood samples (N = 67) from a South African PCa, Benign prostatic hyperplasia (BPH) and disease control (DC) cohort. Linear (fold-over-cutoff) and differential expression quantitation of autoantibody signal intensities were performed. Molecular signatures of candidate PCa antigen biomarkers were identified and analyzed for ethnic group variation. Potential cancer diagnostic and immunotherapeutic inferences were drawn. We identified a total of 41 potential diagnostic/therapeutic antigen biomarkers for PCa. By linear quantitation, four antigens, GAGE1, ROPN1, SPANXA1 and PRKCZ were found to have higher autoantibody titres in PCa serum as compared with BPH where MAGEB1 and PRKCZ were highly expressed. Also, p53 S15A and p53 S46A were found highly expressed in the disease control group. Statistical analysis by differential expression revealed twenty-four antigens as upregulated in PCa samples, while 11 were downregulated in comparison to BPH and DC (FDR = 0.01). FGFR2, COL6A1and CALM1 were verifiable biomarkers of PCa analysis using urinary shotgun proteomics. Functional pathway annotation of identified biomarkers revealed similar enrichment both at genomic and proteomic level and ethnic variations were observed. Cancer antigen arrays are emerging useful in potential diagnostic and immunotherapeutic antigen biomarker discovery.

Seminal Fluid-Mediated Inflammation in Physiology and Pathology of the Female Reproductive Tract

Inflammation is a multifaceted process involving a host of resident and recruited immune cells that eliminate the insult or injury and initiate tissue repair. In the female reproductive tract (FMRT), inflammation-mediated alterations in epithelial, vascular, and immune functions are important components of complex physiological processes and many local and systemic pathologies. It is well established that intracoital and postcoital function of seminal fluid (SF) goes beyond nutritive support for the spermatozoa cells. SF, in particular, the inflammatory bioactive lipids, and prostaglandins present in vast quantities in SF, have a role in localized immune modulation and regulation of pathways that can exacerbate inflammation in the FMRT. In sexually active women SF-mediated inflammation has been implicated in physiologic processes such as ovulation, implantation, and parturition while also enhancing tumorigenesis and susceptibility to infection. This review highlights the molecular mechanism by which SF regulates inflammatory pathways in the FMRT and how alterations in these pathways contribute to physiology and pathology of the female reproductive function. In addition, based on findings from TaqMan® 96-Well Plate Arrays, on neoplastic cervical cells treated with SF, we discuss new findings on the role of SF as a potent driver of inflammatory and tumorigenic pathways in the cervix.

In silico verification and parallel reaction monitoring prevalidation of potential prostate cancer biomarkers

PURPOSE Targeted proteomics of potential biomarkers is often challenging. Hence, we developed an intermediate workflow to streamline potential urinary biomarkers of prostate cancer (PCa). MATERIALS & METHODS Using previously discovered potential PCa biomarkers; we selected proteotypic peptides for targeted validation. Preliminary in silico immunohistochemical and single reaction monitoring (SRM) verification was performed. Successful PTPs were then prevalidated using parallel reaction monitoring (PRM) and reconfirmed in 15 publicly available databases. RESULTS Stringency-based targetable potential biomarkers were shortlisted following in silico screening. PRM reveals top 12 potential biomarkers including the top ranking seven in silico verification-based biomarkers. Database reconfirmation showed differential expression between PCa and benign/normal prostatic urine samples. CONCLUSION The pragmatic penultimate screening step, described herein, would immensely improve targeted proteomics validation of potential disease biomarkers.

A multi-centre evaluation of oral cancer in Southern and Western Nigeria: An African oral pathology research consortium initiative

Introduction Oral cancer is a leading cause of cancer deaths among African populations. Lack of standard cancer registries and under-reporting has inaccurately depicted its magnitude in Nigeria. Development of multi-centre collaborative oral pathology networks such as the African Oral Pathology Research Consortium (AOPRC) facilitates skill and expertise exchange and fosters a robust and systematic investigation of oral diseases across Africa. Methods In this descriptive cross-sectional study, we have leveraged the auspices of the AOPRC to examine the burden of oral cancer in Nigeria, using a multi-centre approach. Data from 4 major tertiary health institutions in Western and Southern Nigeria was generated using a standardized data extraction format and analysed using the SPSS data analysis software (version 20.0; SPSS Inc. Chicago, IL). Results Of the 162 cases examined across the 4 centres, we observed that oral squamous cell carcinomas (OSCC) occurred mostly in the 6th and 7th decades of life and maxillary were more frequent than mandibular OSCC lesions. Regional variations were observed both for location, age group and gender distribution. Significant regional differences was found between poorly, moderately and well differentiated OSCC (p value = 0.0071). Conclusion A multi-centre collaborative oral pathology research approach is an effective way to achieve better insight into the patterns and distribution of various oral diseases in men of African descent. The wider outlook for AOPRC is to employ similar approaches to drive intensive oral pathology research targeted at addressing the current morbidity and mortality of various oral diseases across Africa.

Emerging proteomics biomarkers and prostate cancer burden in Africa

Various biomarkers have emerged via high throughput omics-based approaches for use in diagnosis, treatment, and monitoring of prostate cancer. Many of these have yet to be demonstrated as having value in routine clinical practice. Moreover, there is a dearth of information on validation of these emerging prostate biomarkers within African cohorts, despite the huge burden and aggressiveness of prostate cancer in men of African descent. This review focusses of the global landmark achievements in prostate cancer proteomics biomarker discovery and the potential for clinical implementation of these biomarkers in Africa. Biomarker validation processes at the preclinical, translational and clinical research level are discussed here, as are the challenges and prospects for the evaluation and use of novel proteomic prostate cancer biomarkers.

Omics-based molecular techniques in oral pathology centred cancer: prospect and challenges in Africa

BackgroundThe completion of the human genome project and the accomplished milestones in the human proteome project; as well as the progress made so far in computational bioinformatics and “big data” processing have contributed immensely to individualized/personalized medicine in the developed world.Main bodyAt the dawn of precision medicine, various omics-based therapies and bioengineering can now be applied accurately for the diagnosis, prognosis, treatment, and risk stratification of cancer in a manner that was hitherto not thought possible. The widespread introduction of genomics and other omics-based approaches into the postgraduate training curriculum of diverse medical and dental specialties, including pathology has improved the proficiency of practitioners in the use of novel molecular signatures in patient management. In addition, intricate details about disease disparity among different human populations are beginning to emerge. This would facilitate the use of tailor-made novel theranostic methods based on emerging molecular evidences.ConclusionIn this review, we examined the challenges and prospects of using currently available omics-based technologies vis-à-vis oral pathology as well as prompt cancer diagnosis and treatment in a resource limited setting.

The physician-scientists: rare species in Africa

There is paucity of physician-scientists in Africa, resulting in overt dependence of clinical practice on research findings from advanced “first world” countries. Physician-scientists include individuals with a medical degree alone or combined with other advanced degrees (e.g. MD/MBChB and PhD) with a career path in biomedical/ translational and patient-oriented/evaluative science research. The paucity of clinically trained research scientists in Africa could result in dire consequences as exemplified in the recent Ebola virus epidemic in West Africa, where shortage of skilled clinical scientists, played a major role in disease progression and mortality. Here we contextualise the role of physician-scientist in health care management, highlight factors limiting the training of physician-scientist in Africa and proffer implementable recommendations to address these factors.