RESUMEN
OBJECTIVE: Precancerous lesions of gastric cancer (PLGC) are key pathological stages in the transformation of gastric "inflammation-cancer", and timely and effective intervention at this stage is of great importance in the prevention and treatment of gastric cancer. Zhiwei Fuwei Pills (ZWFW), as a traditional Chinese medicine formulation, has been proven to have good clinical efficacy in the treatment of PLGC, but its specific mechanism of action has not been fully explained. Thus, this study validated the efficacy and explored the potential mechanisms of ZWFW in treating PLGC by integrating network pharmacology analyses and experimental verification. METHODS: The TCMSP database was used to obtain the active ingredients of ZWFW and their corresponding targets, and the GeneCards database was used to retrieve PLGC-related targets. The intersecting targets between ZWFW and PLGC were obtained through mapping, and protein-protein interaction (PPI) networks and "drug-active ingredient-target" networks were constructed by using Cytoscape software. The DAVID database was used for GO functional enrichment analysis and KEGG pathway enrichment analysis. AutoDockTools software was used for molecular docking of key active ingredients and key targets. In order to verify the analysis results of network pharmacology, TEM and H&E were used to observe the effects of different dosage groups of ZWFW on gastric mucosal microvasculature in PLGC rats. Subsequently, the ELISA, IF, IHC, RT-PCR and western blot were used to detected the expression levels of relevant targets in the tissues, so as to verify the potential mechanism of ZWFW in intervening PLGC. RESULTS: After the screening, 258 effective active ingredients and 325 targets were obtained, and 1294 disease-related targets were determined, resulting in 139 intersection targets through mapping. The KEGG enrichment results showed that PI3K/Akt and HIF-1 signaling pathway might play important roles in the treatment mechanism of PLGC. The molecular docking results showed that active ingredients of ZWFW all had a strong affinity and stable structure with key targets, including AKT1 and VEGF. In vivo experiments confirmed that ZWFW could improve gastric mucosal microvascular abnormalities in PLGC, effectively intervene in gastric mucosal pathological grading. Meanwhile, compared with the model group, this formulation could reduce the expression levels of PI3K, Akt, mTOR, HIF-1α, and VEGF in gastric mucosa, showing a dose-effect relationship. CONCLUSION: ZWFW can intervene in the neovascularization and pathological evolution of PLGC, and this mechanism of action may be achieved by inhibiting abnormal activation of the PI3K/Akt/mTOR/HIF-1α/VEGF signaling pathway.
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Medicamentos Herbarios Chinos , Neovascularización Patológica , Farmacología en Red , Lesiones Precancerosas , Neoplasias Gástricas , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Animales , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Neovascularización Patológica/tratamiento farmacológico , Masculino , Lesiones Precancerosas/tratamiento farmacológico , Lesiones Precancerosas/patología , Mapas de Interacción de Proteínas , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ratas Sprague-Dawley , Ratas , Simulación del Acoplamiento Molecular , AngiogénesisRESUMEN
Line-field confocal optical coherence tomography (LC-OCT) is a new technology for skin cancer diagnostics. However, the interobserver agreement (IOA) of known image markers of keratinocyte carcinomas (KC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), as well as precursors, SCC in situ (CIS) and actinic keratosis (AK), remains unexplored. This study determined IOA on the presence or absence of 10 key LC-OCT image markers of KC and precursors, among evaluators new to LC-OCT with different levels of dermatologic imaging experience. Secondly, the frequency and association between reported image markers and lesion types, was determined. Six evaluators blinded to histopathologic diagnoses, assessed 75 LC-OCT images of KC (21 SCC; 21 BCC), CIS (12), and AK (21). For each image, evaluators independently reported the presence or absence of 10 predefined key image markers of KCs and precursors described in an LC-OCT literature review. Evaluators were stratified by experience-level as experienced (3) or novices (3) based on previous OCT and reflectance confocal microscopy usage. IOA was tested for all groups, using Conger's kappa coefficient (κ). The frequency of reported image marker and their association with lesion-types, were calculated as proportions and odds ratios (OR), respectively. Overall IOA was highest for the image markers lobules (κ = 0.68, 95% confidence interval (CI) 0.57;0.78) and clefting (κ = 0.63, CI 0.52;0.74), typically seen in BCC (94%;OR 143.2 and 158.7, respectively, p < 0.001), followed by severe dysplasia (κ = 0.42, CI 0.31;0.53), observed primarily in CIS (79%;OR 7.1, p < 0.001). The remaining seven image-markers had lower IOA (κ = 0.06-0.32) and were more evenly observed across lesion types. The lowest IOA was noted for a well-defined (κ = 0.07, CI 0;0.15) and interrupted dermal-epidermal junction (DEJ) (κ = 0.06, CI -0.002;0.13). IOA was higher for all image markers among experienced evaluators versus novices. This study shows varying IOA for 10 key image markers of KC and precursors in LC-OCT images among evaluators new to the technology. IOA was highest for the assessments of lobules, clefting, and severe dysplasia while lowest for the assessment of the DEJ integrity.
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Carcinoma Basocelular , Carcinoma de Células Escamosas , Queratinocitos , Queratosis Actínica , Variaciones Dependientes del Observador , Neoplasias Cutáneas , Tomografía de Coherencia Óptica , Humanos , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/diagnóstico , Tomografía de Coherencia Óptica/métodos , Carcinoma Basocelular/diagnóstico por imagen , Carcinoma Basocelular/patología , Carcinoma Basocelular/diagnóstico , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/patología , Queratinocitos/patología , Queratosis Actínica/diagnóstico por imagen , Queratosis Actínica/patología , Queratosis Actínica/diagnóstico , Microscopía Confocal/métodos , Lesiones Precancerosas/diagnóstico por imagen , Lesiones Precancerosas/patología , Femenino , Masculino , Anciano , Persona de Mediana EdadAsunto(s)
Quiste Pancreático , Neoplasias Pancreáticas , Lesiones Precancerosas , Humanos , Páncreas/patología , Páncreas/diagnóstico por imagen , Quiste Pancreático/diagnóstico , Quiste Pancreático/patología , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/prevención & control , Tomografía Computarizada por Rayos X , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/patologíaRESUMEN
A bibliometric analysis of studies dedicated to autoimmune gastritis (AIG) recently published demonstrated a noteworthy surge in publications over the last three years. This can be explained by numerous publications from different regions of the world reporting the results of several studies that stimulated reassessment of our view of AIG as a precancerous condition. Follow-up studies and retrospective analyses showed that the risk of gastric cancer (GC) in AIG patients is much lower than expected if the patients ever being infected with Helicobacter pylori (H. pylori) were excluded. The low prevalence of precancerous lesions, such as the incomplete type of intestinal metaplasia, may explain the low risk of GC in AIG patients because the spasmolytic polypeptide-expressing metaplasia commonly observed in AIG does not involve clonal reprogramming of the gastric gland and can be considered as an adaptive change rather than a true precancerous lesion. However, changes in gastric secretion due to the progression of gastric atrophy during the course of AIG cause changes in the gastric mic-robiome, stimulating the growth of bacterial species such as streptococci, which may promote the development of precancerous lesions and GC. Thus, Streptococcus anginosus exhibited a robust proinflammatory response and induced the gastritis-atrophy-metaplasia-dysplasia sequence in mice, reproducing the well-established process for carcinogenesis associated with H. pylori. Prospective studies in H. pylori-naïve patients evaluating gastric microbiome changes during the long-term course of AIG might provide an explanation for the enigmatic increase in GC incidence in the last decades in younger cohorts, which has been reported in economically developed countries.
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Enfermedades Autoinmunes , Bibliometría , Mucosa Gástrica , Gastritis , Infecciones por Helicobacter , Helicobacter pylori , Lesiones Precancerosas , Neoplasias Gástricas , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/patología , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/epidemiología , Humanos , Gastritis/inmunología , Gastritis/microbiología , Gastritis/epidemiología , Gastritis/patología , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/inmunología , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Helicobacter pylori/aislamiento & purificación , Helicobacter pylori/inmunología , Helicobacter pylori/patogenicidad , Lesiones Precancerosas/inmunología , Lesiones Precancerosas/microbiología , Lesiones Precancerosas/patología , Lesiones Precancerosas/epidemiología , Animales , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/epidemiología , Mucosa Gástrica/patología , Mucosa Gástrica/inmunología , Mucosa Gástrica/microbiología , Metaplasia , Factores de Riesgo , Estómago/patología , Estómago/inmunología , Estómago/microbiología , Microbioma Gastrointestinal/inmunología , RatonesRESUMEN
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.
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Biomarcadores de Tumor , Carcinoma de Células Escamosas , Queratina-19 , Leucoplasia Bucal , Neoplasias de la Boca , Fibrosis de la Submucosa Bucal , ARN Mensajero , Factor A de Crecimiento Endotelial Vascular , Humanos , Factor A de Crecimiento Endotelial Vascular/sangre , Factor A de Crecimiento Endotelial Vascular/genética , Neoplasias de la Boca/sangre , Neoplasias de la Boca/genética , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/diagnóstico , Masculino , ARN Mensajero/sangre , Fibrosis de la Submucosa Bucal/sangre , Fibrosis de la Submucosa Bucal/genética , Femenino , Leucoplasia Bucal/sangre , Leucoplasia Bucal/genética , Persona de Mediana Edad , Biomarcadores de Tumor/sangre , Queratina-19/sangre , Adulto , Liquen Plano Oral/sangre , Liquen Plano Oral/genética , Estudios de Casos y Controles , Lesiones Precancerosas/sangre , Lesiones Precancerosas/genética , Lesiones Precancerosas/diagnóstico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Detección Precoz del Cáncer/métodos , Anciano , Reacción en Cadena en Tiempo Real de la Polimerasa , Curva ROCRESUMEN
OBJECTIVE: To intelligently evaluate the invasiveness of pure ground-glass nodules with multiple classifications using deep learning. METHODS: pGGNs in 1136 patients were pathologically confirmed as lung precursor lesions [atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS)], minimally invasive adenocarcinoma (MIA), or invasive adenocarcinoma (IAC). Four different models [EfficientNet-b0 2D, dual-head ResNet_3D, a 3D model combining three features (3D_3F), and a 3D model combining 19 features (3D_19F)] were constructed to evaluate the invasiveness of pGGNs using the EfficientNet and ResNet networks. The Obuchowski index was used to evaluate the differences in diagnostic efficiency among the four models. RESULTS: The patients with pGGNs (360 men, 776 women; mean age, 54.63 ± 12.36 years) included 235 cases of AAH + AIS, 332 cases of MIA, and 569 cases of IAC. In the validation group, the areas under the curve in detecting the invasiveness of pGGNs as a three-category classification (AAH + AIS, MIA, IAC) were 0.8008, 0.8090, 0.8165, and 0.8158 for EfficientNet-b0 2D, dual-head ResNet_3D, 3D_3F, and 3D_19F, respectively, whereas the accuracies were 0.6422, 0.6158, 0.651, and 0.6364, respectively. The Obuchowski index revealed no significant differences in the diagnostic performance of the four models. CONCLUSIONS: The dual-head ResNet_3D_3F model had the highest diagnostic efficiency for evaluating the invasiveness of pGGNs in the four models.
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Neoplasias Pulmonares , Invasividad Neoplásica , Humanos , Persona de Mediana Edad , Femenino , Masculino , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/diagnóstico , Anciano , Adulto , Aprendizaje Profundo , Adenocarcinoma in Situ/patología , Lesiones Precancerosas/patología , Lesiones Precancerosas/diagnóstico , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/diagnóstico , Nódulos Pulmonares Múltiples/patología , Nódulos Pulmonares Múltiples/diagnóstico por imagen , Nódulos Pulmonares Múltiples/diagnóstico , Estudios RetrospectivosRESUMEN
Background: Limited epidemiological evidence suggests that exposure to trace elements adversely impacts the development of gastric precancerous lesions (GPL) and gastric cancer (GC). This study aimed to estimate the association of individual urinary exposure to multiple elements with GPL and GC. Methods: A case-control investigation was conducted in Anhui Province from March 2021 to December 2022. A total of 528 subjects (randomly sampled from 1,020 patients with GPL, 200 patients with GC, and 762 normal controls) were included in our study. Urinary levels of iron (Fe), copper (Cu), zinc (Zn), nickel (Ni), strontium (Sr), and Cesium (Cs) were measured using inductively coupled plasma mass spectrometry (ICP-MS). Four different statistical approaches were employed to explore the risk of GPL and GC with mixed exposure, including multivariate logistic regression, weighted quantile regression (WQS), quantile g-computation (Qgcomp), and the Bayesian kernel machine regression (BKMR) model. Results: The WQS model indicated that urinary exposure to a mixture of elements is positively correlated with both GPL and GC, with ORs for the mixture exposure of 1.34 (95% CI: 1.34-1.61) for GPL and 1.38 (95% CI: 1.27-1.50) for GC. The Qgcomp and BKMR models also demonstrated a statistically significant positive correlation between the mixture and both GPL and GC. Conclusion: Considering the limitations of case-control studies, future prospective studies are warranted to elucidate the combined effects and mechanisms of trace elements exposure on human health.
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Lesiones Precancerosas , Neoplasias Gástricas , Oligoelementos , Humanos , Neoplasias Gástricas/orina , Neoplasias Gástricas/epidemiología , China/epidemiología , Masculino , Oligoelementos/orina , Femenino , Estudios de Casos y Controles , Persona de Mediana Edad , Lesiones Precancerosas/orina , Anciano , AdultoRESUMEN
OBJECTIVE: During the last decade, the management of gastric intestinal metaplasia (GIM) has been addressed by several distinct international evidence-based guidelines. In this review, we aimed to synthesise these guidelines and provide clinicians with a global perspective of the current recommendations for managing patients with GIM, as well as highlight evidence gaps that need to be addressed with future research. DESIGN: We conducted a systematic review of the literature for guidelines and consensus statements published between January 2010 and February 2023 that address the diagnosis and management of GIM. RESULTS: From 426 manuscripts identified, 16 guidelines were assessed. There was consistency across guidelines regarding the purpose of endoscopic surveillance of GIM, which is to identify prevalent neoplastic lesions and stage gastric preneoplastic conditions. The guidelines also agreed that only patients with high-risk GIM phenotypes (eg, corpus-extended GIM, OLGIM stages III/IV, incomplete GIM subtype), persistent refractory Helicobacter pylori infection or first-degree family history of gastric cancer should undergo regular-interval endoscopic surveillance. In contrast, low-risk phenotypes, which comprise most patients with GIM, do not require surveillance. Not all guidelines are aligned on histological staging systems. If surveillance is indicated, most guidelines recommend a 3-year interval, but there is some variability. All guidelines recommend H. pylori eradication as the only non-endoscopic intervention for gastric cancer prevention, while some offer additional recommendations regarding lifestyle modifications. While most guidelines allude to the importance of high-quality endoscopy for endoscopic surveillance, few detail important metrics apart from stating that a systematic gastric biopsy protocol should be followed. Notably, most guidelines comment on the role of endoscopy for gastric cancer screening and detection of gastric precancerous conditions, but with high heterogeneity, limited guidance regarding implementation, and lack of robust evidence. CONCLUSION: Despite heterogeneous populations and practices, international guidelines are generally aligned on the importance of GIM as a precancerous condition and the need for a risk-stratified approach to endoscopic surveillance, as well as H. pylori eradication when present. There is room for harmonisation of guidelines regarding (1) which populations merit index endoscopic screening for gastric cancer and GIM detection/staging; (2) objective metrics for high-quality endoscopy; (3) consensus on the need for histological staging and (4) non-endoscopic interventions for gastric cancer prevention apart from H. pylori eradication alone. Robust studies, ideally in the form of randomised trials, are needed to bridge the ample evidence gaps that exist.
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Metaplasia , Guías de Práctica Clínica como Asunto , Lesiones Precancerosas , Neoplasias Gástricas , Humanos , Metaplasia/patología , Neoplasias Gástricas/patología , Neoplasias Gástricas/diagnóstico , Lesiones Precancerosas/patología , Lesiones Precancerosas/terapia , Lesiones Precancerosas/diagnóstico , Infecciones por Helicobacter/patología , Infecciones por Helicobacter/diagnóstico , Gastroscopía/métodos , Helicobacter pyloriRESUMEN
Persistent high-risk human papillomaviruses (HR HPVs) infection leads to the development of squamous intraepithelial lesions in cervical cells that may lead to cancer. The telomere length, telomerase activity, and species composition of the vaginal microbiome may influence the dynamic of changes and the process of carcinogenesis. In the present study, we analyze relative telomere length (RTL), relative hTERT expression (gene for the telomerase component-reverse transcriptase) in cervical smear cells and vaginal microbiomes. Total RNA and DNA were isolated from tissue samples of 109 patients from the following groups: control, carrier, low-grade or high-grade squamous intraepithelial lesion (L SIL and H SIL, respectively), and cancer. The quantitative PCR method was used to measure telomere length and telomerase expression. Vaginal microbiome bacteria were divided into community state types using morphotype criteria. Significant differences between histopathology groups were confirmed for both relative telomere length and relative hTERT expression (p < 0.001 and p = 0.001, respectively). A significant difference in RTL was identified between carriers and H SIL (p adj < 0.001) groups, as well as between carriers and L SIL groups (p adj = 0.048). In both cases, RTL was lower among carriers. The highest relative hTERT expression level was recorded in the H SIL group, and the highest relative hTERT expression level was recorded between carriers and the H SIL group (p adj < 0.001). A correlation between genotype and biocenosis was identified for genotype 16+A (p < 0.001). The results suggest that identification of HPV infection, telomere length assessment, and hTERT expression measurement together may be more predictive than each of these analyses performed separately.
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Microbiota , Infecciones por Papillomavirus , Lesiones Precancerosas , Telomerasa , Telómero , Neoplasias del Cuello Uterino , Vagina , Humanos , Femenino , Telomerasa/metabolismo , Telomerasa/genética , Vagina/microbiología , Vagina/virología , Microbiota/genética , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/genética , Adulto , Telómero/metabolismo , Telómero/genética , Persona de Mediana Edad , Lesiones Precancerosas/virología , Lesiones Precancerosas/microbiología , Lesiones Precancerosas/genética , Lesiones Precancerosas/patología , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/microbiología , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Homeostasis del Telómero , Papillomaviridae/genéticaRESUMEN
The potential role of the transient receptor potential Vanilloid 1 (TRPV1) non-selective cation channel in gastric carcinogenesis remains unclear. The main objective of this study was to evaluate TRPV1 expression in gastric cancer (GC) and precursor lesions compared with controls. Patient inclusion was based on a retrospective review of pathology records. Patients were subdivided into five groups: Helicobacter pylori (H. pylori)-associated gastritis with gastric intestinal metaplasia (GIM) (n = 12), chronic atrophic gastritis (CAG) with GIM (n = 13), H. pylori-associated gastritis without GIM (n = 19), GC (n = 6) and controls (n = 5). TRPV1 expression was determined with immunohistochemistry and was significantly higher in patients with H. pylori-associated gastritis compared with controls (p = 0.002). TRPV1 expression was even higher in the presence of GIM compared with patients without GIM and controls (p < 0.001). There was a complete loss of TRPV1 expression in patients with GC. TRPV1 expression seems to contribute to gastric-mucosal inflammation and precursors of GC, which significantly increases in cancer precursor lesions but is completely lost in GC. These findings suggest TRPV1 expression to be a potential marker for precancerous conditions and a target for individualized treatment. Longitudinal studies are necessary to further address the role of TRPV1 in gastric carcinogenesis.
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Infecciones por Helicobacter , Neoplasias Gástricas , Canales Catiónicos TRPV , Humanos , Canales Catiónicos TRPV/metabolismo , Canales Catiónicos TRPV/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Infecciones por Helicobacter/metabolismo , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/patología , Carcinogénesis/metabolismo , Carcinogénesis/patología , Estudios Retrospectivos , Lesiones Precancerosas/metabolismo , Lesiones Precancerosas/patología , Helicobacter pylori/patogenicidad , Metaplasia/metabolismo , Metaplasia/patología , Gastritis/metabolismo , Gastritis/patología , Gastritis/microbiología , Adulto , Inmunohistoquímica , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Gastritis Atrófica/metabolismo , Gastritis Atrófica/patologíaRESUMEN
This commentary offers a thoughtful discussion of the study by Wei et al. published in the journal on the role of Olfactomedin 4 (OLFM4) in incomplete intestinal metaplasia, a gastric precancerous condition. The original paper introduces OLFM4 as a novel biomarker with potential enhanced diagnostic efficacy compared to established markers. However, several methodological and interpretive considerations are noted. The histopathological findings could be refined by using higher magnification to better elucidate the cellular localization of OLFM4. Including high-resolution images for key stainings would enhance the study's robustness in expression profiling. The statistical approach could be strengthened by employing more rigorous, quantitative methodologies. Additionally, integrating immunofluorescence double-staining may improve the reliability of the results. Discrepancies in immunohistochemical signals across datasets suggest a need for further investigation into tissue section representativeness. Clarifying the term "precancerous lesions of gastric carcinoma cells" to align with widely accepted definitions would enhance clarity. The choice of the GES-1 cell model treated with MNNG could be reconsidered in favor of more established models such as organoids, air-liquid interface models, and gastric cancer-specific cell lines. The in vivo MNNG-alcohol combination model might require additional empirical support, given the limited and conflicting literature on this approach, to ensure an accurate portrayal of IM pathogenesis. The commentary concludes with a call for stringent and standardized methodologies in biomarker research to ensure the clinical applicability and reliability of biomarker studies, particularly in the context of gastric cancer detection and intervention.
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Biomarcadores de Tumor , Factor Estimulante de Colonias de Granulocitos , Lesiones Precancerosas , Neoplasias Gástricas , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Humanos , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/patología , Factor Estimulante de Colonias de Granulocitos/metabolismoRESUMEN
Gastric precancerous lesion (GPL) is a crucial stage in the development of gastric cancer, characterized by incomplete intestinal epithelial chemotaxis and heterogeneous hyperplasia with high malignant potential. Early intervention in GPL is vital for preventing gastric cancer. Additionally, there are shared risk factors and pathogenesis between tumors and coronary heart disease (CHD), with an increasing number of tumor patients GPL complicated with CHD due to improved survival rates. Reperfusion therapy in CHD can result in myocardial ischemia-reperfusion injury (MIRI). Traditional Chinese medicine (TCM) has demonstrated unique advantages in treating GPL and MIRI by promoting blood circulation and removing blood stasis. Panax ginseng total saponin (PNS), a component of TCM known for its blood circulation benefits, has shown positive effects in inhibiting tumor growth and improving myocardial ischemia. This study utilized a GPL-MIRI mouse model to investigate the effects of PNS in treatment. Results indicated that PNS significantly improved typical GPL lesions in mice, such as incomplete intestinal epithelialization and heteroplasia, and also reduced myocardial infarction. At the molecular level, PNS exhibited a bidirectional regulatory role in the GPL-MIRI model. It enhanced the autophagic process in gastric mucosal cells by inhibiting the PI3K/Akt/mTOR signaling pathway, while suppressed excessive autophagy in cardiomyocytes. These findings offer new insights and treatment strategies for managing GPL and MIRI using the TCM compound PNS.
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Autofagia , Daño por Reperfusión Miocárdica , Panax notoginseng , Saponinas , Transducción de Señal , Neoplasias Gástricas , Animales , Masculino , Ratones , Autofagia/efectos de los fármacos , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/metabolismo , Panax notoginseng/química , Fosfatidilinositol 3-Quinasas/metabolismo , Lesiones Precancerosas/tratamiento farmacológico , Lesiones Precancerosas/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Saponinas/farmacología , Saponinas/uso terapéutico , Transducción de Señal/efectos de los fármacos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
BACKGROUND: Lung cancer is the most common cause of cancer death worldwide and poses an immediate health threat. Despite decades of basic and clinical research, the 5-year survival rate for lung cancer patients is less than 10%.The most important drawbacks in efficient treatment of lung cancer are delayed diagnosis and absence of effective screening. Detection and study of precancerous lesions of the bronchial mucosa might be one of the turning points in understanding of neoplastic transformation. Therefore, it would be the most effective prevention and early treatment modality. We report a case of high-grade intraepithelial neoplasia of the bronchial mucosa in which a neoplastic growth in the lumen of intrinsic segment in the upper lobe of the left lung was detected on electronic bronchoscopy, and biopsy confirmed squamous papillary hyperplasia with high-grade intraepithelial neoplasia. CASE PRESENTATION: A 74-year-old male was admitted to the hospital due to a mass lesion in his left lung. After admission, computed tomography scan of the chest showed an intraluminal mass in the intrinsic segment of the upper lobe of the left lung and an enlarged left hilum. CONCLUSIONS: High-grade intraepithelial neoplasia of the bronchial mucosa is rare in the respiratory system. We report a case that can provide useful information for early diagnosis and treatment of the disease.
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Broncoscopía , Carcinoma in Situ , Tomografía Computarizada por Rayos X , Anciano , Humanos , Masculino , Biopsia , Bronquios/patología , Bronquios/diagnóstico por imagen , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/patología , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/prevención & control , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/patología , Mucosa Respiratoria/patología , Carcinoma Broncogénico/diagnóstico , Carcinoma Broncogénico/patologíaAsunto(s)
Fundus Gástrico , Hiperplasia , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Fundus Gástrico/patología , Fundus Gástrico/metabolismo , Transformación Celular Neoplásica , Mucina 5AC/metabolismo , Mucina 6/metabolismo , Adenocarcinoma/patología , Adenocarcinoma/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/diagnóstico , Proteínas Proto-Oncogénicas p21(ras)/genética , Lesiones Precancerosas/patología , Lesiones Precancerosas/metabolismo , Masculino , Mucosa Gástrica/patología , Mutación , Persona de Mediana Edad , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , FemeninoRESUMEN
BACKGROUND: The incidence of esophageal adenocarcinoma has recently increased in Asia, including Japan. A system to identify individuals at high risk for Barrett's esophagus (BE), a pre-cancerous condition of esophageal adenocarcinoma, among the general population is needed to perform endoscopic surveillance appropriately. We therefore developed risk prediction scores for BE at health checkups in Japan. METHODS: 4128 consecutive health checkup examinees were retrospectively enrolled from October 2021 to March 2022. A prediction score for BE was developed based on the linear transformation of ß-regression coefficients in a multivariable regression model incorporating BE predictors. Internal validation was performed by evaluating discrimination and calibration of the prediction model. RESULTS: Three prediction scores corresponding to BE based on its length were developed: all lengths, ≥ 1 cm, ≥ 2 cm. All scores were internally validated, and the model calibration was excellent. The performance of the prediction models was better for longer BE, with a c-statistic of 0.70 for BE ≥ 2 cm, than for shorter values. The prediction score for BE ≥ 2 cm yielded sensitivity and specificity of 52.9% and 78.6% in high-risk subjects and 91.2% and 29.3% in intermediate- or high-risk subjects, respectively. CONCLUSIONS: This prediction score can potentially increase the endoscopic detection of BE by identifying potentially high-risk individuals from the general population. This is the first report on developing a prediction score for BE that may suit the Japanese population.
Asunto(s)
Esófago de Barrett , Neoplasias Esofágicas , Humanos , Esófago de Barrett/epidemiología , Esófago de Barrett/patología , Esófago de Barrett/diagnóstico , Masculino , Japón/epidemiología , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Neoplasias Esofágicas/epidemiología , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patología , Medición de Riesgo/métodos , Adulto , Sensibilidad y Especificidad , Esofagoscopía/métodos , Factores de Riesgo , Adenocarcinoma/epidemiología , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Incidencia , Valor Predictivo de las Pruebas , Lesiones Precancerosas/epidemiología , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/patología , Pueblos del Este de AsiaRESUMEN
Rationale: Despite significant advances in precision treatments and immunotherapy, lung cancer is the most common cause of cancer death worldwide. To reduce incidence and improve survival rates, a deeper understanding of lung premalignancy and the multistep process of tumorigenesis is essential, allowing timely and effective intervention before cancer development. Objectives: To summarize existing information, identify knowledge gaps, formulate research questions, prioritize potential research topics, and propose strategies for future investigations into the premalignant progression in the lung. Methods: An international multidisciplinary team of basic, translational, and clinical scientists reviewed available data to develop and refine research questions pertaining to the transformation of premalignant lung lesions to advanced lung cancer. Results: This research statement identifies significant gaps in knowledge and proposes potential research questions aimed at expanding our understanding of the mechanisms underlying the progression of premalignant lung lesions to lung cancer in an effort to explore potential innovative modalities to intercept lung cancer at its nascent stages. Conclusions: The identified gaps in knowledge about the biological mechanisms of premalignant progression in the lung, together with ongoing challenges in screening, detection, and early intervention, highlight the critical need to prioritize research in this domain. Such focused investigations are essential to devise effective preventive strategies that may ultimately decrease lung cancer incidence and improve patient outcomes.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Lesiones Precancerosas , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Progresión de la Enfermedad , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Lesiones Precancerosas/patología , Lesiones Precancerosas/terapia , Sociedades Médicas , Estados UnidosRESUMEN
It takes more than 20 years for normal colorectal mucosa to develop into metastatic carcinoma. The long time window provides a golden opportunity for early detection to terminate the malignant progression. Here, we aim to enable liquid biopsy of T1a stage colorectal cancer (CRC) and precancerous advanced adenoma (AA) by profiling circulating small extracellular vesicle (sEV)-derived RNAs. We exhibited a full RNA landscape for the circulating sEVs isolated from 60 participants. A total of 58,333 annotated RNAs were detected from plasma sEVs, among which 1,615 and 888 sEV-RNAs were found differentially expressed in plasma from T1a stage CRC and AA compared to normal controls (NC). Then we further categorized these sEV-RNAs into six modules by a weighted gene coexpression network analysis and constructed a 60-gene t-SNE model consisting of the top 10 RNAs of each module that could well distinguish T1a stage CRC/AA from NC samples. Some sEV-RNAs were also identified as indicators of specific endoscopic and morphological features of different colorectal lesions. The top-ranked biomarkers were further verified by RT-qPCR, proving that these candidate sEV-RNAs successfully identified T1a stage CRC/AA from NC in another cohort of 124 participants. Finally, we adopted different algorithms to improve the performance of RT-qPCR-based models and successfully constructed an optimized classifier with 79.3% specificity and 99.0% sensitivity. In conclusion, circulating sEVs of T1a stage CRC and AA patients have distinct RNA profiles, which successfully enable the detection of both T1a stage CRC and AA via liquid biopsy.
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Adenoma , Biomarcadores de Tumor , Neoplasias Colorrectales , Vesículas Extracelulares , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/diagnóstico , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Adenoma/genética , Adenoma/sangre , Adenoma/patología , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Masculino , Femenino , Persona de Mediana Edad , Anciano , Biopsia Líquida/métodos , Lesiones Precancerosas/genética , Lesiones Precancerosas/sangre , Lesiones Precancerosas/patología , Estadificación de NeoplasiasRESUMEN
Early diagnosis of gastric cancer can improve the prognosis of patients, especially for those with early gastric cancer (EGC), but only 15% of patients, or less, are diagnosed with EGC and precancerous lesions. Magnifying endoscopy with narrow-band imaging (ME-NBI) can improve diagnostic accuracy. We assess the efficacy of ME-NBI in diagnosing ECG and precancerous lesions, especially some characteristics under NBI+ME. This was a retrospective analysis of 131 patients with EGC or gastric intraepithelial neoplasia (IN) who had undergone endoscopic submucosal dissection and were pathologically diagnosed with EGC or IN according to 2019 WHO criteria for gastrointestinal tract tumors. We studied the characteristics of lesions under ME-NBI ,compared the diagnostic efficacy of ME-NBI and white light endoscopy (WLI) plus biopsy, and investigated the effect of Helicobacter pylori infection on microvascular and microsurface pattern. The diagnostic accuracy of ME-NBI for EGC, high-grade IN (HGIN), and low-grade IN (LGIN) was 76.06%, 77.96%, and 77.06%, respectively. The accuracy of WLI plus biopsy in diagnosing the above lesions was 69.7%, 57.5%, and 60.53%, respectively. The rate of gyrus-like tubular pattern was highest in LGIN (60.46%), whereas the highest rate of papillary pattern was 57.14% in HGIN and villous tubular pattern was 52% in EGC. Demarcation lines have better sensitivity for differentiating EGC from IN (92.06%). The ME-NBI has higher diagnostic accuracy for EGC than WLI plus biopsy. Demarcation lines and villous and papillary-like microsurface patterns are more specific as EGC and HGIN characteristics. The cerebral gyrus-like microsurface pattern is more specific for LGIN.
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Carcinoma in Situ , Detección Precoz del Cáncer , Gastroscopía , Imagen de Banda Estrecha , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Imagen de Banda Estrecha/métodos , Estudios Retrospectivos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Detección Precoz del Cáncer/métodos , Gastroscopía/métodos , Carcinoma in Situ/diagnóstico por imagen , Carcinoma in Situ/patología , Adulto , Lesiones Precancerosas/diagnóstico por imagen , Lesiones Precancerosas/patología , Lesiones Precancerosas/diagnóstico , Infecciones por Helicobacter/diagnóstico , Biopsia/métodos , Helicobacter pylori , Mucosa Gástrica/patología , Mucosa Gástrica/diagnóstico por imagen , Resección Endoscópica de la Mucosa/métodosRESUMEN
BACKGROUND: Oral cancer (OC) and oral potentially malignant disorders (OPMD) pose significant challenges to public health in Brazil. This study aimed to estimate the prevalence of oral cancer (OC) and oral potentially malignant disorders (OPMD) among patients who would be treated by Brazilian dentists during their careers. MATERIAL AND METHODS: Data on the number of dentists in Brazil were extracted from the 2022 census data, while incidence rates for OC cases were sourced from the Brazilian National Cancer Institute (INCA). Population estimates for Brazil and data on dental check-up rates were obtained from relevant national sources. RESULTS: Our analysis indicates that a general dentist in Brazil can expect to encounter on average two to three OC patients and on average 675 patients with OPMDs over a 35-year career. Regional disparities were observed, with certain regions showing higher than the average number of encounters due to low density of dentists in some rural districts. CONCLUSIONS: Brazilian dentists are likely to confront a substantial number of OC and OPMD cases during their professional tenure, emphasizing the need for public health policies aimed at enhancing dental surgeons' education in oral cancer prevention and early detection.
Asunto(s)
Neoplasias de la Boca , Humanos , Brasil/epidemiología , Neoplasias de la Boca/epidemiología , Prevalencia , Costo de Enfermedad , Lesiones Precancerosas/epidemiologíaRESUMEN
AIM: Esophageal cancer is a disease with high morbidity and mortality, exploring effective treatment methods is the key to the treatment of this disease. This study aims to compare the clinical efficacy and safety of multi-band mucosectomy (MBM) and endoscopic submucosal dissection (ESD) in the treatment of single early esophageal cancer (EEC) and precancerous lesions, and whether MBM can achieve better clinical effect as an effective treatment method. METHODS: The clinical data of 70 patients with EEC and precancerous lesions who were treated with MBM and ESD in the Fourth Affiliated Hospital of China Medical University from May 2021 to May 2023 and could be followed up were retrospectively analyzed. They were divided into two groups according to different treatment methods: MBM group (31 cases) and ESD group (39 cases). The general data, perioperative conditions, endoscopic treatment effect and pathological results of the two groups were compared. RESULTS: The duration of endoscopic treatment in MBM group was shorter than that in ESD group [36 (25~39) min vs 46 (41~57) min, p < 0.05], and there was no significant difference in the intraoperative bleeding rate between the two groups (12.90% vs 7.69%, p > 0.05). There was no significant difference in the rate of intraoperative perforation between the two groups (3.23% vs 7.69%, p > 0.05), and the hospitalization time in MBM group was shorter than that in ESD group [5 (4~7) days vs 8 (7~12) days, p < 0.05]. The hospitalization cost was less [2535 (2423~2786) dollars vs 4485 (3858~5794) dollars, p < 0.05]. No postoperative bleeding occurred in both groups. There was no statistically significant difference in postoperative stenosis rate between MBM group and ESD group (3.23% vs 12.82%, p > 0.05), and no statistically significant difference in postoperative local recurrence rate (12.90% vs 5.13%, p > 0.05). There was no significant difference in the rate of additional surgery (9.68% vs 2.56%, p > 0.05). The en bloc resection rate of MBM group was lower than that of ESD group (77.42% vs 97.44%, p < 0.05), but there was no significant difference in the complete resection rate between the two groups (87.10% vs 97.44%, p > 0.05). The postoperative pathological results of MBM group showed 13 cases of low-grade intraepithelial neoplasia (LGIN), 11 cases of high-grade intraepithelial neoplasia (HGIN), and 7 cases of canceration, while the postoperative pathological results of ESD group showed 10 cases of LGIN, 14 cases of HGIN, and 15 cases of canceration, with no statistical significance (p > 0.05). CONCLUSIONS: MBM and ESD are effective methods for the treatment of EEC and precancerous lesions. MBM has the advantages of short hospital stay, quick recovery and low cost. However, compared with MBM, ESD can improve the complete resection rate of the lesion, avoid the occurrence of positive incisal margin, and reduce the risk of secondary treatment and additional surgery.