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1.
Rev Cardiovasc Med ; 24(6): 169, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39077521

RESUMEN

High-throughput metabolomics techniques are a useful tool to understand many disease conditions including cardiovascular disease such as valvular heart disease(s) (VHD). VHD involves damage to heart valves, mostly presenting as stenosis, regurgitation or prolapse and can be classified into degenerative, rheumatic, congenital, or prosthetic valve disease. Gaps remain in our understanding of the pathogenesis of the common VHD. It is now fitting to place into perspective the contribution of metabolomics in the mechanism of development, diagnosis, and prognosis of VHD. A structured search for metabolomics studies centred on human VHD was undertaken. Biomarkers associated with the pathogenesis of bicuspid aortic valve disease, mitral valve disease, rheumatic heart disease, and degenerative aortic valve stenosis are reviewed and discussed. In addition, metabolic biomarkers reported to prognosticate patient outcomes of post-valve repair or replacement are highlighted. Finally, we also review the pitfalls and limitations to consider when designing metabolomics studies, especially from a clinician's viewpoint. In the future, reliable and simple metabolic biomarker(s) may supplement the existing diagnostic tools in the early diagnosis of VHD.

2.
Exp Dermatol ; 32(5): 570-587, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36562321

RESUMEN

Raised dermal scars including hypertrophic, and keloid scars as well as scalp-associated fibrosing Folliculitis Keloidalis Nuchae (FKN) are a group of fibrotic raised dermal lesions that mostly occur following cutaneous injury. They are characterized by increased extracellular matrix (ECM) deposition, primarily excessive collagen type 1 production by hyperproliferative fibroblasts. The extent of ECM deposition is thought to be proportional to the severity of local skin inflammation leading to excessive fibrosis of the dermis. Due to a lack of suitable study models, therapy for raised dermal scars remains ill-defined. Immune cells and their associated markers have been strongly associated with dermal fibrosis. Therefore, modulation of the immune system and use of anti-inflammatory cytokines are of potential interest in the management of dermal fibrosis. In this review, we will discuss the importance of immune factors in the pathogenesis of raised dermal scarring. The aim here is to provide an up-to-date comprehensive review of the literature, from PubMed, Scopus, and other relevant search engines in order to describe the known immunological factors associated with raised dermal scarring. The importance of immune cells including mast cells, macrophages, lymphocytes, and relevant molecules such as cytokines, chemokines, and growth factors, antibodies, transcription factors, and other immune-associated molecules as well as tissue lymphoid aggregates identified within raised dermal scars will be presented. A growing body of evidence points to a shift from proinflammatory Th1 response to regulatory/anti-inflammatory Th2 response being associated with the development of fibrogenesis in raised dermal scarring. In summary, a better understanding of immune cells and associated molecular markers in dermal fibrosis will likely enable future development of potential immune-modulated therapeutic, diagnostic, and theranostic targets in raised dermal scarring.


Asunto(s)
Cicatriz Hipertrófica , Queloide , Humanos , Cicatriz Hipertrófica/metabolismo , Queloide/metabolismo , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Fibrosis , Citocinas
3.
Biometals ; 34(5): 1141-1153, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34365580

RESUMEN

Cadmium is a toxic metal and poses a high environmental risk to animals and humans, alike. It is thus pertinent to search for medicinal plants in protecting against cadmium toxicity. This study aims at investigating the ability of aqueous extract of Persea americana seeds (AEPA) in ameliorating the toxic effects of cadmium in the kidneys of cadmium-exposed Wistar rats. Male Wistar rats were grouped into five, of six animals each. Different groups of animals received normal saline (control group), 200 mg/kg body weight AEPA, 400 mg/kg AEPA, and standard drug, Livolin Forte, respectively. A last group of animals was left untreated. To induce toxicity, all animals, except the control group, were exposed to cadmium (200 mg/L, as CdCl2) in their main drinking water for 21 days. Biochemical analysis of serum kidney markers, oxidative stress and antioxidant status, as well as anti-inflammatory activities, was done using standard methods and kits. In silico analysis was performed on phytochemicals reported to be abundant in AEPA. Treatment with 400 mg/kg AEPA significantly reversed (P ≤ 0.05) the adverse effect of cadmium on serum creatinine, urea, uric acid and blood urea nitrogen, and restored (P ≤ 0.05) antioxidant status, evidenced by its significant effect on superoxide dismutase, catalase, glutathione-S-transferase, glutathione peroxidase, reduced glutathione, and lipid peroxidation activities. AEPA, at 400 mg/kg also exhibited significant anti-inflammatory effects, which was shown by reduced interleukin-2 and tumour necrosis factor α activities. Molecular docking of phytochemicals with the selected protein target also confirmed the therapeutic potential of AEPA. The study concluded that aqueous extract of AEPA protects against cadmium-induced kidney toxicity and inflammation.


Asunto(s)
Cadmio , Persea , Animales , Antiinflamatorios/metabolismo , Antiinflamatorios/farmacología , Antioxidantes/metabolismo , Antioxidantes/farmacología , Cadmio/metabolismo , Riñón/metabolismo , Peroxidación de Lípido , Masculino , Simulación del Acoplamiento Molecular , Estrés Oxidativo , Persea/metabolismo , Ratas , Ratas Wistar , Semillas
4.
Odontology ; 108(3): 450-461, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31641894

RESUMEN

Halitosis (bad breath) can be a cause of anxiety, depression and psychosocial stress, with pathological changes in the oral microbiota playing an important role in its development. Despite its prevalence, studies on the microbiology of halitosis are rare in Nigeria. This study determines the presence of five putative periodontal pathogens viz: Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia and Treponema denticola on the tongue dorsa of halitosis and non-halitosis patients using a 16S rDNA-directed polymerase chain reaction assay. Furthermore, an association of these bacteria with oral malodour [as assessed by volatile sulphur compounds (VSC) measurements] with a portable sulphide monitor, the Halimeter (Interscan Corp, Chatsworth, California), was performed. The results showed that the prevalence of halitosis in this environment as defined by VSC level above 160 ppb is 14.9%. Halitosis is affected by gender with males having it more than the females. Males also tend to present more with self-reported complaints of halitosis than females. Age does not appear to contribute to the incidence of halitosis. Fusobacterium nucleatum, P. gingivalis, P. intermedia are responsible for increased production of VSCs in halitosis patients while A. actinomycetemcomitans and T. denticola appear to play no part in the production of VSCs. Evaluation of halitogenic bacteria and VSCs may potentially become a surrogate biomarker for monitoring halitosis. Targeted assessment of putative halitogenic bacteria may provide a rapid point-of-care diagnostic tool for halitosis.


Asunto(s)
Halitosis , Femenino , Humanos , Masculino , Nigeria , Reacción en Cadena de la Polimerasa , Porphyromonas gingivalis , Compuestos de Azufre , Centros de Atención Terciaria , Lengua
5.
Oral Dis ; 25(1): 142-149, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30099823

RESUMEN

OBJECTIVES: Accurate diagnosis of salivary gland neoplasms (SGN) in many centers in Africa is limited by poor diagnostic resources and ancillary services. Hence, we have carried out a multicenter epidemiological study to understand the true burden of SGN in Nigeria. METHOD: In this descriptive cross-sectional study, we have deployed resources available to members of the African Oral Pathology Consortium (AOPRC) to examine the burden of salivary gland lesions in Nigeria, using a multicenter approach. Data from seven major tertiary health institutions in northern, western, and southern Nigeria were generated using a standardized data extraction format and analyzed using the Epi-info software (Version 7.0, Atlanta, USA). RESULT: Of the 497 cases examined across the seven centers, we observed that SGN occurred more in females than males. Overall, pleomorphic salivary adenoma (PA) was found to be the most common. PA was found to be the commonest benign SGN while adenocystic carcinoma (ADCC) was the commonest malignant SGN. Regional variations were observed for age group, diagnosis, and gender distribution. Significant statistical differences were found between males and females for malignant SGNs (p-value=0.037). CONCLUSION: We found regional variation in the pattern of distribution of SGN in Nigeria. This is the largest multicenter study of SGN in Nigeria, and our findings are robust and representative of the epidemiology of this neoplasm in Nigeria.


Asunto(s)
Neoplasias de las Glándulas Salivales/epidemiología , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Niño , Estudios Transversales , Femenino , Geografía , Humanos , Masculino , Persona de Mediana Edad , Nigeria/epidemiología , Patología Bucal , Estudios Retrospectivos , Centros de Atención Terciaria , Adulto Joven
6.
Cancer Cell Int ; 17: 61, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28592923

RESUMEN

BACKGROUND: The 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 BODY: At 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. CONCLUSION: In 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.

8.
Future Oncol ; 12(1): 43-57, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26615920

RESUMEN

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.


Asunto(s)
Biomarcadores de Tumor/biosíntesis , Proteínas de Neoplasias/biosíntesis , Neoplasias de la Próstata/orina , Proteómica , Biomarcadores de Tumor/orina , Simulación por Computador , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Proteínas de Neoplasias/orina , Neoplasias de la Próstata/patología
9.
PLoS One ; 19(5): e0303496, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38739622

RESUMEN

INTRODUCTION: Rheumatic heart disease (RHD), degenerative aortic stenosis (AS), and congenital valve diseases are prevalent in sub-Saharan Africa. Many knowledge gaps remain in understanding disease mechanisms, stratifying phenotypes, and prognostication. Therefore, we aimed to characterise patients through clinical profiling, imaging, histology, and molecular biomarkers to improve our understanding of the pathophysiology, diagnosis, and prognosis of RHD and AS. METHODS: In this cross-sectional, case-controlled study, we plan to recruit RHD and AS patients and compare them to matched controls. Living participants will undergo clinical assessment, echocardiography, CMR and blood sampling for circulatory biomarker analyses. Tissue samples will be obtained from patients undergoing valve replacement, while healthy tissues will be obtained from cadavers. Immunohistology, proteomics, metabolomics, and transcriptome analyses will be used to analyse circulatory- and tissue-specific biomarkers. Univariate and multivariate statistical analyses will be used for hypothesis testing and identification of important biomarkers. In summary, this study aims to delineate the pathophysiology of RHD and degenerative AS using multiparametric CMR imaging. In addition to discover novel biomarkers and explore the pathomechanisms associated with RHD and AS through high-throughput profiling of the tissue and blood proteome and metabolome and provide a proof of concept of the suitability of using cadaveric tissues as controls for cardiovascular disease studies.


Asunto(s)
Estenosis de la Válvula Aórtica , Biomarcadores , Cardiopatía Reumática , Humanos , Cardiopatía Reumática/diagnóstico por imagen , Cardiopatía Reumática/fisiopatología , Cardiopatía Reumática/metabolismo , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/metabolismo , Estenosis de la Válvula Aórtica/fisiopatología , Biomarcadores/metabolismo , Estudios de Casos y Controles , Estudios Transversales , Masculino , Femenino , Metabolómica/métodos , Ecocardiografía/métodos , Proteómica/métodos , Imagen por Resonancia Magnética/métodos , Multiómica
10.
Microrna ; 12(2): 87-91, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37076465

RESUMEN

BACKGROUND: Squamous cell carcinoma (SCC) is a non-melanoma skin cancer with several risk factors including age and sun exposure. The degree of histological differentiation is considered an independent predictor of recurrence, metastasis, and survival. MicroRNAs (miRNAs) are small non-coding RNAs that play an important role in regulating gene expression, culminating in the initiation and progression of multiple tumors. The aim of this study was to determine changes in miRNA expression as a result of the mode of differentiation in SCC. METHODS: We analyzed 29 SCC samples that were separated by mode of differentiation into well (n=4), moderate (n=20) and poor (n=5). Of the 29 samples, five had matched normal tissues, which were used as controls. Total RNA was extracted using the RNeasy FFPE kit, and miRNAs were quantified using Qiagen MiRCURY LNA miRNA PCR Assays. Ten miRNAs (hsa-miR-21, hsa-miR-146b-3p, hsa-miR-155-5p, hsa-miR-451a, hsa-miR-196-5p, hsa-miR-221-5p, hsa-miR-375, hsa-miR-205-5p, hsa-let-7d-5p and hsa-miR-491-5p) that have been previously differentiated in cancer, were quantified. A fold regulation above 1 indicated upregulation and below 1, downregulation. RESULTS: Hierarchical clustering showed that the miRNA expression profile in the moderately differentiated group was similar to the well-differentiated group. The miRNA with the greatest upregulation in the moderate group was hsa-miR-375, while in the well group, hsa-miR-491-5p showed the greatest downregulation. CONCLUSION: In conclusion, this study observed that the well and moderate groups had similar microRNA expression patterns compared to the poorly differentiated group. MicroRNA expression profiling may be used to better understand the factors underpinning mode of differentiation in SCC.


Asunto(s)
Carcinoma de Células Escamosas , MicroARNs , Humanos , MicroARNs/genética , Perfilación de la Expresión Génica , Carcinoma de Células Escamosas/genética , Diferenciación Celular/genética , Reacción en Cadena de la Polimerasa
11.
Cells ; 12(22)2023 11 20.
Artículo en Inglés | MEDLINE | ID: mdl-37998398

RESUMEN

The rising mortality and morbidity rate of head and neck cancer (HNC) in Africa has been attributed to factors such as the poor state of health infrastructures, genetics, and late presentation resulting in the delayed diagnosis of these tumors. If well harnessed, emerging molecular and omics diagnostic technologies such as liquid biopsy can potentially play a major role in optimizing the management of HNC in Africa. However, to successfully apply liquid biopsy technology in the management of HNC in Africa, factors such as genetic, socioeconomic, environmental, and cultural acceptability of the technology must be given due consideration. This review outlines the role of circulating molecules such as tumor cells, tumor DNA, tumor RNA, proteins, and exosomes, in liquid biopsy technology for the management of HNC with a focus on studies conducted in Africa. The present state and the potential opportunities for the future use of liquid biopsy technology in the effective management of HNC in resource-limited settings such as Africa is further discussed.


Asunto(s)
Neoplasias de Cabeza y Cuello , Humanos , Neoplasias de Cabeza y Cuello/diagnóstico , Biopsia Líquida , África , ADN de Neoplasias , ARN
12.
Health Sci Rep ; 5(6): e958, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36447566

RESUMEN

Background and Aims: Lymphovascular invasion (LVI) is an indicator of lymph node metastasis and poor prognosis in various cancers including squamous cell carcinoma (SCC). Despite being easily resectable and having little potential for LVI; SCC displays aggressive behavior and often results in the death of the patient. With this in mind, it may be useful to investigate the clinical, pathological, and microRNA expression profile associated with LVI in SCC. Methods: We evaluated the histological hallmarks associated with LVI from 16 formalin fixed paraffin embedded (FFPE) tissue samples (10 LVI-, 6 LVI+). We also quantified the expression of 10 microRNAs (hsa-miR-21-5p, hsa-miR-21-3p, hsa-miR-155-5p, hsa-miR-196a-5p, hsa-miR-375, hsa-let-7d-5p, hsa-miR-146b-3p, hsa-miR-221-5p, hsa-miR-205-5p, hsa-miR-491-5p), which have been previously identified to play a role in SCC development, using real time-PCR with the Qiagen miRCURY LNA SYBR Green PCR Kit. Results: We observed a significant upregulation of microRNA-155, microRNA-196a, microRNA-375, and microRNA-221 in cases with lymphovascular invasion. Morphologically, we identified poor differentiation, dysplasia, loss of membrane polarity, high nuclear to cytoplasmic ratio, and the presence of squamous nests as defining features of LVI. Additionally, we found a gender bias and observed a tendency toward lymphatic invasion in lesions presenting around the perineal and abdominal regions. Conclusion: We speculate that this profile may have prognostic significance and could guide the clinician in their treatment protocols for patients matching our genetic, demographic, and morphologic profile.

13.
Cancers (Basel) ; 14(5)2022 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-35267452

RESUMEN

An important driving force for precision and individualized medicine is the provision of tailor-made care for patients on an individual basis, in accordance with best evidence practice. Liquid biopsy(LB) has emerged as a critical tool for the early diagnosis of cancer and for treatment monitoring, but its clinical utility for oral squamous cell carcinoma (OSCC) requires more research and validation. Hence, in this review, we have discussed the current applications of LB and the practicality of its routine use in Africa; the potential advantages of LB over the conventional "gold-standard" of tissue biopsy; and finally, practical considerations were discussed in three parts: pre-analytic, analytic processing, and the statistical quality and postprocessing phases. Although it is imperative to establish clinically validated and standardized working guidelines for various aspects of LB sample collection, processing, and analysis for optimal and reliable use, manpower and technological infrastructures may also be an important factor to consider for the routine clinical application of LB for OSCC. LB is poised as a non-invasive precision tool for personalized oral cancer medicine, particularly for OSCC in Africa, when fully embraced. The promising application of different LB approaches using various downstream analyses such as released circulating tumor cells (CTCs), cell free DNA (cfDNA), microRNA (miRNA), messenger RNA (mRNA), and salivary exosomes were discussed. A better understanding of the diagnostic and therapeutic biomarkers of OSCC, using LB applications, would significantly reduce the cost, provide an opportunity for prompt detection and early treatment, and a method to adequately monitor the effectiveness of the therapy for OSCC, which typically presents with ominous prognosis.

14.
J Biomol Struct Dyn ; 40(2): 848-859, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-32924840

RESUMEN

The worldwide expanding increment in cancer pervasiveness is disturbing and this disease ranks among the main causes of mortality in both developing and developed countries. Unfortunately, available treatment options come with serious side effects and do not guarantee complete success. Although numerous models have been proposed for the development of better therapeutic agent, however the exact mechanism are still poorly understood. This then calls for continued research aimed at developing new drugs as an alternative or adjuvant anticancer agents. Here we have identified five vital proteins (CDK-2, Bcl-2, CDK-6, VEGFR, and IGF-1R) that aid tumor growth and we inhibited the activity of these proteins with Puerarin. Puerarin is an isoflavonoid C-glycosides used as a therapeutic agent against various human ailments. Our findings revealed that Puerarin fulfilled Veber's rule. Added to this, CDK-6 and Bcl-2 had better glide scores for puerarin than the control (doxorubicin) and molecular simulation showed the stability of the complexes. These findings suggest that inhibiting CDK-6 and Bcl-2 with Puerarin could prove more effective in the management of cancer than doxorubicin. Overall, this study provides a new direction that could facilitate rational drug design for cancer.Communicated by Ramaswamy H. Sarma.


Asunto(s)
Antineoplásicos , Isoflavonas , Neoplasias , Antineoplásicos/farmacología , Apoptosis , Humanos , Isoflavonas/farmacología , Neoplasias/tratamiento farmacológico
15.
Pan Afr Med J ; 40: 42, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34795823

RESUMEN

The coronavirus disease (COVID-19) has impacted many facets of everyday daily life, resulting in far-reaching consequences on social interaction, regional and global economies, and healthcare delivery systems. Numerous reports have commented on the impact of the COVID-19 pandemic on medical education in various world regions. However, we know little about the influence of the pandemic on medical education in Africa. Here, we discuss the potential impact of COVID-19 on teaching and learning in undergraduate medical education in sub-Saharan Africa, illustrating some of the unexpected benefits and challenges the pandemic presents for medical education in sub-Saharan Africa.


Asunto(s)
COVID-19 , Atención a la Salud/organización & administración , Educación de Pregrado en Medicina/métodos , África del Sur del Sahara , Humanos , Aprendizaje , Enseñanza
16.
BMJ Open ; 11(7): e049922, 2021 07 08.
Artículo en Inglés | MEDLINE | ID: mdl-34244283

RESUMEN

INTRODUCTION: Human papillomavirus (HPV) is an established risk factor for oropharyngeal squamous cell carcinoma, regardless of a history of other known risk factors such as alcohol and tobacco. While cases of HPV-related oral squamous cell carcinoma (OSSC) are increasing in the USA, Europe and South Central Asian countries, little is known about the impact of the disease on the African continent. METHODS AND ANALYSIS: We describe a protocol for a systematic review to synthesise the best current evidence to assess the disease burden in Africa. Electronic databases including EBSCOhost, MEDLINE, CINAHL, ACADEMIC SEARCH COMPLETE, ScienceDirect, Web of Science, Scopus, SciCENTRAL, Cochrane Library, International Prospective Register of Systematic Reviews) and WorldCAT will be comprehensively searched for studies reporting on the defined outcomes, in Africa, published from 1985 (when HPV was first reported) to the latest current entries, with no language restriction. Supplemental handsearching of grey literature, conference abstract proceedings, reference lists of included studies and citations in Google Scholar will be conducted. Authors will be contacted, where necessary, to assist with missing data. A customised data extraction form, with specified criteria, will be used for data extraction. Overall study quality assessment will be done using an appropriate risk of bias tool suited to the study design. Where available, qualitative data from studies reporting on the outcomes will be captured on the data extraction form. Using Stata software, we will apply the random-effects meta-analysis model to aggregate prevalence estimates with 95% CI, incorporating the Freeman-Tukey transformation to account for between-study variability. A narrative report of the findings will be presented where data are insufficient in terms of the outcome/s. Subgroup analysis will be done subject to sufficient available data. ETHICS AND DISSEMINATION: Ethics approval or written consent is not required as the review will be conducted using published data. The findings will be distributed through a peer-review publication and conference presentation.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Infecciones por Papillomavirus , África/epidemiología , Carcinoma de Células Escamosas/epidemiología , Europa (Continente) , Humanos , Metaanálisis como Asunto , Neoplasias de la Boca/epidemiología , Infecciones por Papillomavirus/epidemiología , Prevalencia , Proyectos de Investigación , Carcinoma de Células Escamosas de Cabeza y Cuello , Revisiones Sistemáticas como Asunto
17.
Anticancer Agents Med Chem ; 21(2): 162-186, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32723261

RESUMEN

BACKGROUND: Cutaneous malignancies most commonly arise from skin epidermal cells. These cancers may rapidly progress from benign to a metastatic phase. Surgical resection represents the gold standard therapeutic treatment of non-metastatic skin cancer while chemo- and/or radiotherapy are often used against metastatic tumors. However, these therapeutic treatments are limited by the development of resistance and toxic side effects, resulting from the passive accumulation of cytotoxic drugs within healthy cells. OBJECTIVE: This review aims to elucidate how the use of monoclonal Antibodies (mAbs) targeting specific Tumor Associated Antigens (TAAs) is paving the way to improved treatment. These mAbs are used as therapeutic or diagnostic carriers that can specifically deliver cytotoxic molecules, fluorophores or radiolabels to cancer cells that overexpress specific target antigens. RESULTS: mAbs raised against TAAs are widely in use for e.g. differential diagnosis, prognosis and therapy of skin cancers. Antibody-Drug Conjugates (ADCs) particularly show remarkable potential. The safest ADCs reported to date use non-toxic photo-activatable Photosensitizers (PSs), allowing targeted Photodynamic Therapy (PDT) resulting in targeted delivery of PS into cancer cells and selective killing after light activation without harming the normal cell population. The use of near-infrared-emitting PSs enables both diagnostic and therapeutic applications upon light activation at the specific wavelengths. CONCLUSION: Antibody-based approaches are presenting an array of opportunities to complement and improve current methods employed for skin cancer diagnosis and treatment.


Asunto(s)
Antígenos de Neoplasias/inmunología , Antineoplásicos Inmunológicos/uso terapéutico , Inmunoconjugados/uso terapéutico , Fármacos Fotosensibilizantes/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Animales , Antígenos de Neoplasias/análisis , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/farmacología , Sistemas de Liberación de Medicamentos , Humanos , Inmunoconjugados/administración & dosificación , Inmunoconjugados/farmacología , Terapia Molecular Dirigida , Fotoquimioterapia , Fármacos Fotosensibilizantes/administración & dosificación , Fármacos Fotosensibilizantes/farmacología , Pronóstico , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/inmunología
18.
Biomed Pharmacother ; 141: 111809, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34144454

RESUMEN

Oral mucocutaneous cancers (OMCs) are cancers that affect both the oral mucosa and perioral cutaneous structures. Common OMCs are squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and malignant melanoma (MM). Anatomical similarities and conventions which categorizes these lesions blur the magnitude of OMCs in diverse populations. The burden of OMC is high in the sub-Saharan Africa and Indian subcontinents, and the cost of management is prohibitive in the resource-limited, developing world. Hence, there is a pressing demand for the use of cost-effective in silico approaches to identify diagnostic tools and treatment targets for diseases with high burdens in these regions. Due to their ubiquitousness and accessibility, the use of therapeutic efficacy of plant bioactive compounds in the management of OMC is both appropriate and plausible. Furthermore, screening known mechanistic disease targets with well annotated plant bioactive compound libraries is poised to improve the routine management of OMCs provided that the requisite access to database resources are available and accessible. Using natural products minimizes the side effects and morbidities associated with conventional therapies. The development of innovative treatments approaches would tremendously benefit the African and Indian populace and reduce the mortalities associated with OMCs in the developing world. Hence, we discuss herein, the potential benefits, opportunities and challenges of using bioactive compound libraries in the management of OMCs.


Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias de la Boca/tratamiento farmacológico , Fitoterapia/métodos , Animales , Simulación por Computador , Humanos , Mucosa Bucal , Neoplasias de la Boca/genética
19.
Stem Cell Rev Rep ; 16(6): 1105-1120, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32789558

RESUMEN

The Primary Scarring Alopecias are characterised by the irreversible destruction and fibrosis of hair follicles, leading to permanent and often disfiguring loss of hair. The pathophysiology of these diseases is not well understood. However, follicular-fibrosis and loss of the stem-cell niche appears to be a common theme. This review explores the pathogenesis of primary scarring alopecias, asking what happens to the stem cells of the hair follicle and how they may contribute to the progression of these diseases. Bulge-resident cells are lost (leading to loss of capacity for hair growth) from the follicle either by inflammatory-mediate apoptosis or through epigenetic reprogramming to assume a mesenchymal-like identity. What proportion of bulge cells is lost to which process is unknown and probably differs depending on the individual PCA and its specific inflammatory cell infiltrate. The formation of fibroblast-like cells from follicular stem cells may also mean that the cells of the bulge have a direct role in the pathogenesis. The identification of specific cells involved in the pathogenesis of these diseases could provide unique diagnostic and therapeutic opportunities to prevent disease progression by preventing EMT and specific pro-fibrotic signals.


Asunto(s)
Alopecia/patología , Alopecia/terapia , Cicatriz/patología , Cicatriz/terapia , Nicho de Células Madre , Alopecia/inmunología , Animales , Biomarcadores/metabolismo , Cicatriz/inmunología , Fibrosis , Folículo Piloso/crecimiento & desarrollo , Folículo Piloso/patología , Humanos
20.
SA J Radiol ; 24(1): 1874, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32832118

RESUMEN

According to the South African Health Professions Act No. 56 of 1974, specific skills outcomes of MBChB programmes are that a medical graduate must be able to utilise diagnostic aids, interpret findings and make diagnoses. Imaging techniques are an integral part of the numerous diagnostic and therapeutic aids used in contemporary medical practice; however, in South Africa, no formal directives exist to guide programme directors or nuclear medicine departments regarding an appropriate undergraduate nuclear medicine educational module. As of 2013, six South African schools of medicine are involved in undergraduate nuclear medicine teaching, in which it forms part of clinical modules taught at varying stages in the academic curriculum. Against this backdrop is the inequitable distribution of nuclear medicine resources, training facilities and staffing in the local state health sector. Inadequate undergraduate teaching and provincial differences in nuclear medicine service provision suggest that many clinicians and graduating medical students are unaware of how radionuclide techniques can facilitate patient management. This high level of imaging illiteracy has been associated with lack of patient referral, poor quality and inadequate referral, poor knowledge of radiation doses and poor awareness of radiation risks. Here we highlight the challenges of undergraduate nuclear medicine teaching in South Africa, emphasising the need for the implementation of guidelines for undergraduate nuclear medicine education. Employing nationally accepted guidelines for undergraduate nuclear medicine teaching in South African MBChB programmes will contribute to the effective utilisation of nuclear medicine and molecular imaging as a diagnostic and therapeutic modality by newly qualified medical practitioners.

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