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1.
BMC Oral Health ; 24(1): 1062, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39261828

RESUMO

BACKGROUND: Oral cancers, which include tumors of the oral cavity, salivary glands, and pharynx, are becoming increasingly prevalent worldwide. Squamous cell carcinoma accounts for over 90% of malignant oral lesions, with oral squamous cell carcinoma (OSCC) being notably common in the Indian subcontinent and other regions of Asia. This is especially true in South-Central Asia, including Sri Lanka, where it is particularly prevalent among men. This study aims to evaluate the levels of Vascular Endothelial Growth Factor-A (VEGF-A) and Cytokeratin-19 (CK-19) mRNAs in whole blood as a potential method for the early detection of OSCC. METHODS: The study included 40 patients (each from OSCC, Oral Submucous Fibrosis (OSF), Oral Leukoplakia (OLK), Oral Lichen Planus (OLP), and 10 healthy controls. The expression levels of VEGF-A and CK-19 mRNAs were measured from extracellular RNA extracted from whole blood samples using real-time reverse transcription polymerase chain reaction (RT-PCR) with sequence-specific primers. Receiver operating characteristic (ROC) curve analysis was used to evaluate the effectiveness of these biomarkers in detecting OSCC. RESULTS: The results demonstrated a significant increase in blood transcripts of the candidate mRNAs CK-19 and VEGF-A in patients with OSCC, OSF, OLK, and OLP. The Wilcoxon signed-rank test revealed a p-value of 0.002 for each specific comparison between diseased patients and healthy controls (i.e., OSCC vs. HC, OSF vs. HC, OLP vs. HC, OLK vs. HC) for both CK-19 and VEGF-A. When these two biomarkers were used together, they provided a 60% predictive probability for patients with OSCC (p = 0.023). CONCLUSION: This study highlights the efficacy of blood mRNA transcriptome diagnostics in detecting OSCC. This innovative clinical approach has the potential to be a robust, efficient, and reliable tool for early cancer detection. Blood-based transcriptomes could be further explored for their effectiveness in various health contexts and for routine health monitoring.


Assuntos
Biomarcadores Tumorais , Carcinoma de Células Escamosas , Queratina-19 , Leucoplasia Oral , Neoplasias Bucais , Fibrose Oral Submucosa , RNA Mensageiro , Fator A de Crescimento do Endotélio Vascular , Humanos , Fator A de Crescimento do Endotélio Vascular/sangue , Fator A de Crescimento do Endotélio Vascular/genética , Neoplasias Bucais/sangue , Neoplasias Bucais/genética , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/diagnóstico , Masculino , RNA Mensageiro/sangue , Fibrose Oral Submucosa/sangue , Fibrose Oral Submucosa/genética , Feminino , Leucoplasia Oral/sangue , Leucoplasia Oral/genética , Pessoa de Meia-Idade , Biomarcadores Tumorais/sangue , Queratina-19/sangue , Adulto , Líquen Plano Bucal/sangue , Líquen Plano Bucal/genética , Estudos de Casos e Controles , Lesões Pré-Cancerosas/sangue , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/diagnóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Detecção Precoce de Câncer/métodos , Idoso , Reação em Cadeia da Polimerase em Tempo Real , Curva ROC
2.
J Clin Invest ; 131(22)2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34609968

RESUMO

Cutaneous leishmaniasis (CL) is caused by Leishmania donovani in Sri Lanka. Pentavalent antimonials (e.g., sodium stibogluconate [SSG]) remain first-line drugs for CL with no new effective treatments emerging. We studied whole blood and lesion transcriptomes from Sri Lankan patients with CL at presentation and during SSG treatment. From lesions but not whole blood, we identified differential expression of immune-related genes, including immune checkpoint molecules, after onset of treatment. Using spatial profiling and RNA-FISH, we confirmed reduced expression of programmed death-ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) proteins on treatment in lesions of a second validation cohort and further demonstrated significantly higher expression of these checkpoint molecules on parasite-infected compared with noninfected lesional CD68+ monocytes and macrophages. Crucially, early reduction in PD-L1 but not IDO1 expression was predictive of rate of clinical cure (HR = 4.88) and occurred in parallel with reduction in parasite load. Our data support a model whereby the initial anti-leishmanial activity of antimonial drugs alleviates checkpoint inhibition on T cells, facilitating immune-drug synergism and clinical cure. Our findings demonstrate that PD-L1 expression can be used as a predictor of rapidity of clinical response to SSG treatment in Sri Lanka and support further evaluation of PD-L1 as a host-directed therapeutic in leishmaniasis.


Assuntos
Antígeno B7-H1/fisiologia , Leishmaniose Cutânea/tratamento farmacológico , Adulto , Gluconato de Antimônio e Sódio/uso terapêutico , Antígeno B7-H1/análise , Feminino , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/análise , Leishmaniose Cutânea/imunologia , Masculino , Adulto Jovem
4.
BMC Res Notes ; 11(1): 481, 2018 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-30012215

RESUMO

OBJECTIVE: The study aimed to compare the usefulness of two staining methods for imprint cytology for diagnosis of Helicobacter pylori infection. Gastric biopsy specimens (from dyspeptic patients attending routine upper gastrointestinal endoscopy) were placed on glass slides to obtain imprints. The imprints were stained with Toluidine blue and Giemsa stains separately and observed under ×400 magnification using a light microscope. Imprinted biopsies were sectioned and stained with H & E stain and Giemsa stain for histological analysis. Diagnosis of H. pylori infection in both imprint and histological sections were confirmed by a consultant pathologist. The sensitivity, specificity, positive predictive value and negative predictive value of each stain were calculated and benchmarked against histological diagnosis. RESULTS: Of the 55 dyspeptic patients enrolled in the study, 5 were positive for H. pylori by Toluidine blue stain and 4 by Giemsa stain. The sensitivity of Toluidine blue stain (57.1%) was higher than Giemsa stain (42.9%) while the specificity of both stains was equal (97.9%). Giemsa stain gave a better discrimination for identification of H. pylori bacteria among the mucosal background. Imprint cytology is a rapid, simple and cost effective diagnosis method that can supplement histological diagnosis.


Assuntos
Infecções por Helicobacter/diagnóstico , Helicobacter pylori/isolamento & purificação , Coloração e Rotulagem , Adulto , Corantes Azur , Biópsia , Humanos , Sensibilidade e Especificidade , Sri Lanka
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