Patients with stage III or IV of operative link for gastric intestinal metaplasia assessment (OLGIM) are at a higher risk of gastric cancer (GC). We aimed to construct a deep learning (DL) model ...based on magnifying endoscopy with narrow-band imaging (ME-NBI) to evaluate OLGIM staging.
This study included 4473 ME-NBI images obtained from 803 patients at three endoscopy centres. The endoscopic expert marked intestinal metaplasia (IM) regions on endoscopic images of the target biopsy sites. Faster Region-Convolutional Neural Network model was used to grade IM lesions and predict OLGIM staging.
The diagnostic performance of the model for IM grading in internal and external validation sets, as measured by the area under the curve (AUC), was 0.872 and 0.803, respectively. The accuracy of this model in predicting the high-risk stage of OLGIM was 84.0%, which was not statistically different from that of three junior (71.3%, p = 0.148) and three senior endoscopists (75.3%, p = 0.317) specially trained in endoscopic images corresponding to pathological IM grade, but higher than that of three untrained junior endoscopists (64.0%, p = 0.023).
This DL model can assist endoscopists in predicting OLGIM staging using ME-NBI without biopsy, thereby facilitating screening high-risk patients for GC.
Endoscopic submucosal dissection (ESD) for gastric neoplastic lesions removal is largely performed in Asian countries. Unfortunately, ESD diffusion, particularly for gastric lesion removal, is still ...limited in Western countries. We performed a systematic review of available data coming from Western centers. The en bloc and the R0 resection rates for all neoplastic lesions, including early gastric cancer (EGC) and dysplasia, were calculated, as well as the curative rate for EGC. Complications and the 1-month mortality rates were computed. A total of 22 studies from Europe (N = 15), Latina America (N = 6), and Canada (N = 1) were retrieved, with 1152 patients and 1210 lesions. The en bloc resection was successful in 96% 95% confidence interval (CI) 93–98 with a significant heterogeneity (I = 63.5%; P < 0.0001). The R0 was achieved in 84% (95% CI 79–89; I = 79.9%; P < 0.001). The resection rate was curative in 72% out of 340 patients with EGC (95% CI 65–79, I = 8%; P = 0.36). Overall, complications occurred in 9.5% of patients, including bleeding (5.8%), perforation (3.4%), and stenosis (0.35%). A total of three (0.26%) patients deceased within 1 month, but none was directly related to the procedure. Lesion recurrence was observed in 38 (3.5%; 95% CI 2.3–4.4) cases, including 21 EGC and 17 dysplasia. In Western countries, the en bloc and the R0 resections were successful in the large majority of cases, whilst the resection was curative in 72% of patients with EGC. The complications rate was acceptably low.
Gastric carcinoma (GC) is a complex multifactorial disease occurring as sequential events commonly referred to as the Correa’s cascade, a stepwise progression from non-active or chronic active ...gastritis, to gastric precancerous lesions, and finally, adenocarcinoma. Therefore, the identification of novel agents with multi-step actions on the Correa’s cascade and those functioning as multiple phenotypic regulators are the future direction for drug discovery. Recently, berberine (BBR) has gained traction owing to its pharmacological properties, including anti-inflammatory, anti-cancer, anti-ulcer, antibacterial, and immunopotentiation activities. In this article, we investigated and summarized the multi-step actions of BBR on Correa’s cascade and its underlying regulatory mechanism in gastric carcinogenesis for the first time, along with a discussion on the strength of BBR to prevent and treat GC. BBR was found to suppress H. pylori infection, control mucosal inflammation, and promote ulcer healing. In the gastric precancerous lesion phase, BBR could reverse mucosal atrophy and prevent lesions in intestinal metaplasia and dysplasia by regulating inflammatory cytokines, promoting cell apoptosis, regulating macrophage polarization, and regulating autophagy. Additionally, the therapeutic action of BBR on GC was partly realized through the inhibition of cell proliferation, migration, and angiogenesis; induction of apoptosis and autophagy, and enhancement of chemotherapeutic drug sensitivity. BBR exerted multi-step actions on the Correa’s cascade, thereby halting and even reversing gastric carcinogenesis in some cases. Thus, BBR could be used to prevent and treat GC. In conclusion, the therapeutic strategy underlying BBR’s multi-step action in the trilogy of Correa’s cascade may include “prevention of gastric mucosal inflammation (Phase 1); reversal of gastric precancerous lesions (Phase 2), and rescue of GC (Phase 3)”. The NF-κB, PI3K/Akt, and MAPK signaling pathways may be the key signaling transduction pathways underlying the treatment of gastric carcinogenesis using BBR. The advantage of BBR over conventional drugs is its multifaceted and long-term effects. This review is expected to provide preclinical evidence for using BBR to prevent gastric carcinogenesis and treat gastric cancer.
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Sijunzi decoction (SJZD), a traditional Chinese medicine formula, is commonly used in clinical practice for the treatment of gastric precancerous lesions (GPL). However, the mechanism of gastric ...protection is not fully understood.
The purpose of this study was to systematically evaluate the efficacy of SJZD in blocking the development of GPL and to reveal the underlying mechanism.
First, we established a rat model of GPL, which was induced by N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) combined with an irregular diet and 40% ethanol. The efficacy of SJZD was evaluated based on pathological sections and serum biochemical indices. Then, the pharmacodynamic mechanism of SJZD was revealed by quantitative proteomics based on stable isotope dimethyl labeling. At the same time, the pharmacodynamic mechanism was verified by quantitative metabolomics. In addition, the anti-gastritis effect of SJZD was confirmed by a serum pharmacology method in a cell model, and the functional mechanism was further verified.
We demonstrated that SJZD could block the development of GPL in the animal model. Proteomics and metabolomics revealed that SJZD blocks GPL development by regulating oxidative phosphorylation (OXPHOS). In addition, the serum pharmacology results showed that SJZD-containing serum (SJZD-CS) could inhibit apoptosis in MNNG-induced GES-1 cells. OXPHOS inhibitors could significantly reduce the protective effect of SJZD-CS.
SJZD effectively ameliorates GPL, and proteomics and metabolomics revealed that its protective effects are closely related to OXPHOS.
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Gallic acid (GA) is a natural polyphenolic compound derived from Rhus chinensis Mill. with a variety of biological activities such as astringent sweat, cough, dysentery, hemostasis, and ...detoxification, and is widely used in China as a treatment for cough, bleeding, and gastrointestinal disorders. In recent years, the anticancer activity of GA has been demonstrated in a variety of cancers, affecting multiple cellular pathways associated with cancer onset, development and progression.
To investigate the role and potential mechanism of GA on gastric precancerous lesions (GPL), the key turning point of gastritis to gastric cancer, with the aim of delaying, blocking or reversing the dynamic overall process of “inflammation-cancer transformation” and thus blocking GPL to prevent the development of gastric cancer.
In this study, we established N-Nitroso-N-methylurea (MNU)-induced GPL mice model and induced precancerous lesions of gastric cancer cells (MC), i.e. epithelial mesenchymal transition (EMT), in human gastric mucosal epithelial cells (GES-1) with N-methyl-N′-nitro-N-nitrosoguanidine (MNNG). We used conventional pathology, immunohistochemistry, RNA sequencing, Western blot and other techniques to study the therapeutic effect of GA on GPL and its possiblemechanism in vitro and in vivo.
The results showed that compared with normal GES-1 cells, MC cells had the characteristics of malignant cells such as abnormal proliferation, invasion and metastasis, accompanied by decreased expression of EMT-related protein E-cadherin and increased expression of N-cadherin and Vimentin. GA can inhibit the malignant behavior of MC cell proliferation and induce its G0/G1 phase arrest, which is achieved by downregulating the Wnt/β-catenin signaling pathway and thereby inhibiting the EMT process. However, when we incubated with the Wnt pathway activator (Wnt agonist 1), the effect of GA was reversed. Furthermore, analysis of human gastric specimens showed that activation of the Wnt/β-catenin pathway was significantly associated with GPL pathological changes. Meanwhile, GA reversed MNU-induced intestinal metaplasia and partial dysplasia in GPL mice.
Taken together, these results indicate that GA prevents the occurrence and development of GPL by inhibiting the Wnt/β-catenin signaling pathway and then inhibiting the EMT process, which may become potential candidates for the treatment of GPL.
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Introduction: Early detection of oral cancer by diagnosing the precancerous lesions is the best way for controlling and decreasing cancer’s mortality. Dentists have a significant role in early ...detection of precancerous lesions and their capability to detect is highly subjected to their levels of knowledge about these lesions. The aim of this study was to assess the level of knowledge, attitude and practice of general dentists in Yazd City regarding oral precancerous lesions.
Methods: In this cross-sectional study, 180 Yazd general dentists, were selected and they completed a questionnaire, which was consisted of two parts: demographic information and questions referring the knowledge, attitude and practice; data were analyzed using SPSS 16 software and ANOVA and T-test.
Results: Mean score of knowledge was 13.38 ± 2.49 from maximum 22 and mean score of attitudes was 19.35 ± 1.72 from maximum 21, which implies that the participants have a better attitude. No significant correlation was reported between knowledge and gender, years of graduation, workplace, work experience, and attending in retraining classes (P. -value=0.255). There was a significant correlation between attitude and years of graduation (P-value=0.056), which means that participants with 5 years of graduation or less had better attitude toward precancerous lesions.
Conclusion: General dentists of Yazd City have an average knowledge but a good attitude towards precancerous lesions of mouth. Regarding their practice, more than 50% of the participants referred to the orthopedic specialist in case of precancerous lesions.
Vitamin B12 depletion has been suggested to be associated with esophageal precancerous lesions (EPL). However, the potential mechanisms remain unclear.
This study aims to evaluate the role of vitamin ...B12 and its regulated epigenetic modification in EPL and provide preliminary information on the identification of potential molecular biomarkers for the early prediction of EPL.
We collected information and samples from the Early Diagnosis and Early Treatment Project of Esophageal Cancer database from 200 EPL cases and 200 matched controls. Vitamin B12, one-carbon metabolism biomarkers, genetic polymorphism of TCN2 C776G, and DNA methylation were compared. Preliminarily identified candidate promoters of differentially methylated CpG positions were further verified by targeted bisulfite sequencing.
EPL cases had significantly lower serum levels of vitamin B12 and transcobalamin II, and higher serum levels of homocysteine and 5-methyltetrahydrofolate than controls. The TCN2 C776G polymorphism was found to be associated with susceptibility to EPL and may interact with vitamin B12 nutritional status to influence the risk of EPL in male subjects. In addition, global hypomethylation related to vitamin B12 depletion was observed in EPL cases, along with region-specific hypermethylation of UGT2B15 and FGFR2 promoters.
This study suggests that vitamin B12 depletion may be associated with aberrant DNA methylation and increased risk of EPL through the one-carbon metabolism pathway, presents that the TCN2 C776G polymorphism may interact with vitamin B12 nutritional status to affect EPL risk in males, and also identifies specific locations in the UGT2B15 and FGFR2 promoters with potential as promising molecular biomarkers.
Gastric cancer (GC) is the fifth most common type of cancer and the third leading cause of death due to cancer worldwide. The gastric mucosa often undergoes many years of precancerous lesions of ...gastric cancer (PLGC) stages before progressing to gastric malignancy. Unfortunately, there are no effective Western drugs for patients with PLGC. In recent years, traditional Chinese medicine (TCM) has been proven effective in treating PLGC. Classical TCM formulas and chemical components isolated from some Chinese herbal medicines have been administered to treat PLGC, and the main advantage is their comprehensive intervention with multiple approaches and multiple targets. In this review, we focus on recent studies using TCM treatment for PLGC, including clinical observations and experimental research, with a focus on targets and mechanisms of drugs. This review provides some ideas and a theoretical basis for applying TCM to treat PLGC and prevent GC.
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•This review summarized the mainly classification of syndrome differentiation of PLGC.•This review summarized the therapy of Chinese medicine formulas or components on PLGC.•This review listed the pharmacological mechanisms of the TCM for PLGC.
Dendrobium chrysotoxum Lindl, a well-known traditional Chinese medicinal herb used in the treatment of gastric disease, is distinguished as the first of the “nine immortal grasses”. Dendrobium ...chrysotoxum Lindl and the traditional Chinese medicine prescriptions containing Dendrobium chrysotoxum Lindl are often prescribed clinically to treat chronic gastritis and precancerous lesions of gastric cancer (PLGC), showing favorable clinical effects and medicinal value in the prevention of gastric cancer. However, the effective ingredients and pharmacological mechanisms through which Dendrobium chrysotoxum Lindl prevents and treats PLGC have not been adequately identified or interpreted.
The present study aimed to evaluate the effective ingredients and pharmacological mechanisms of Dendrobium chrysotoxum Lindl in the prevention and treatment of PLGC using network pharmacology. In addition, in vitro verification was performed to evaluate the mechanism of action of Erianin, the main active ingredient in Dendrobium chrysotoxum Lindl, providing experimental evidence for the clinical use of Dendrobium chrysotoxum Lindl in the treatment of PLGC.
Using network pharmacology methods, the main ingredients in Dendrobium chrysotoxum Lindl were screened from the ETCM, BATMAN-TCM, and TCMID databases, and their potential targets were predicted using the Swiss Target Prediction platform. The targets related to PLGC were retrieved through the GeneCard database, and the targets common to the main ingredients of Dendrobium chrysotoxum Lindl and PLGC were analyzed. The protein-protein interaction (PPI) network was obtained via the STRING database and analyzed visually using Cytoscape 3.7.2. The underlying mechanisms of the common targets identified through gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were analyzed using DAVID online. The “component-target-pathway” networks of Dendrobium chrysotoxum Lindl and Erianin were visually constructed by Cytoscape 3.7.2. The biological activity evaluation of Erianin's effect on PLGC was carried out using MC cell lines, the PLGC cell model established using MNNG to induce damage in normal gastric mucosal epithelial cell (GES-1). After the intervention of different concentrations of Erianin, MC cell viability was explored using the MTT assays, cell migration was determined by wound healing assays, the cell cycle and apoptosis were analyzed using flow cytometry, and the expression levels of related proteins and their phosphorylation in the HRAS-PI3K-AKT signaling pathway were detected by Western blot.
The “component-target-pathway” network constructed in this study showed 37 active ingredients from Dendrobium chrysotoxum Lindl and 142 overlapping targets related to both Dendrobium chrysotoxum Lindl and PLGC. The targets were associated with a variety of cancer-related signaling pathways, including Pathways in cancer, PI3K-Akt signaling pathway, Rap1 signaling pathway, Focal adhesion, Ras signaling pathway, and MAPK signaling pathway. Notably, the network showed that Erianin, the primary active ingredient from Dendrobium chrysotoxum Lindl and the component associated with the most targets, could regulate Pathways in cancer, PI3K-AKT signaling pathway, Focal adhesion, Rap1 signaling pathway, cell cycle, and RAS signaling pathway in the treatment of PLGC. Verification through in vitro experiments found that Erianin can significantly inhibit MC cell viability, inhibit cell migration, block the cell cycle in the G2/M phase, and induce cell apoptosis in a dose-dependent manner. The results of the Western blot experiment further showed that Erianin can significantly decrease the protein expression levels of HRAS, AKT, p-AKT, MDM2, Cyclin D1, and p-Gsk3β, and increase the protein expression level of p21, which suggests that Erianin can treat PLGC by regulating the HRAS-PI3K-AKT signaling pathway.
This study explained the positive characteristics of multi-component, multi-target, and multi-approach intervention with Dendrobium chrysotoxum Lindl in the treatment of PLGC. Our results suggest that Erianin may be a promising candidate in the development of prevention and treatment methods for PLGC. This study provided experimental evidence for the clinical use of Dendrobium chrysotoxum Lindl to treat PLGC and prevent gastric cancer.
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