The influence of the gastric microbiota in gastric cancer development Pereira-Marques, Joana; Ferreira, Rui M.; Machado, Jose C. ...
Baillière's best practice & research. Clinical gastroenterology,
March-April 2021, 2021 Mar-Apr, 2021-03-00, 20210301, Letnik:
50-51
Journal Article
Recenzirano
Colonization of the stomach by Helicobacter pylori is the trigger for a series of gastric mucosal changes that culminate in gastric cancer. Infection with this bacterium is considered the major risk ...factor for this malignancy. The introduction of high-throughput sequencing technologies coupled to advanced computational pipelines offered an improved understanding of the microbiome, and it is now currently accepted that, besides H. pylori, the stomach harbours a complex microbial community. While it is well established that H. pylori plays a central role in gastric carcinogenesis, the significance of the non-H. pylori microbiota is yet to be clarified. This review will address the state of the art on the relationship between the gastric microbiota and gastric cancer development, and identify areas where additional research is needed before translating microbiome research into preventive and therapeutic strategies to reduce gastric cancer burden.
Photodynamic therapy (PDT) is a modern, non-invasive therapeutic method used for the destruction of various cells and tissues. It requires the simultaneous presence of three components: a ...photosensitizer (PS), a light source and oxygen. Precancerous skin lesions are conditions associated with a high likelihood of malignant transformation to squamous cell carcinoma. Data available so far indicate that PDT is a promising treatment method which can be successfully employed in several medical fields including dermatology, urology, ophthalmology, pneumology, cardiology, dentistry and immunology. Numerous authors therefore have studied this technique in order to improve its efficacy. As a result, significant advancement has been achieved with regard to PSs and drug delivery systems. Substantial progress was also obtained with respect to PDT for the treatment of precancerous skin lesions, several authors focusing their efforts on the study of daylight-PDT and on identifying methods of decreasing technique-related pain. This review reports on the most recent findings in PDT, with emphasis on cutaneous precancerous lesions.
Fufang E'jiao Jiang (FEJ) is a prominent traditional Chinese medicine prescription, which consists of Asini Corii Colla (Donkey-hide gelatin prepared by stewing and concentrating from the hide of ...Equus asinus Linnaeus., ACC), Codonopsis Radix (the dried roots of Codonopsis pilosula (Franch.) Nannf., CR), Ginseng Radix et Rhizoma Rubra (the steamed and dried root of Panax ginseng C.A. Mey., GRR), Crataegi Fructus (the mature fruits of Crataegus pinnatifida Bunge., CF), and Rehmanniae Radix Praeparata (the steamed and sun dried tuber of Rehmannia glutinosa (Gaertn.) Libosch. ex Fisch. & C.A. Mey., RRP). It is a popularly used prescription for “nourishing Qi and nourishing blood”.
To explore the potential mechanism of FEJ on precancerous lesion of gastric cancer in rats by combining network pharmacology and metabolomics.
Traditional Chinese Medicine Systems Pharmacology and Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine were used to identify the ingredients and potential targets of FEJ. GeneCards database was used to define PLGC-associated targets. We built a herb-component-disease-target network and analyzed the protein-protein interaction network. Underlying mechanisms were identified using Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. In addition, 40% ethanol, N-methyl-N′-nitro-N-nitroguanidine and irregular eating were used to establish PLGC rats model. We also evaluated the efficacy of FEJ on MNNG-induced PLGC rats by body weight, histopathology, blood routine and cytokine levels, while the predicted pathway was determined by the Western blot. Ultra-performance liquid chromatography-tandem mass spectrometry-based serum non-targeted metabolomics was used to select potential biomarkers and relevant pathways for FEJ in the treatment of PLGC.
Network pharmacology showed that FEJ exhibited anti-PLGC effects through regulating ALB, TNF, VEGFA, TP53, AKT1 and other targets, and the potential pathways mainly involved cancer-related, TNF, PI3K-AKT, HIF-1, and other signaling pathways. Animal experiments illustrated that FEJ could suppress inflammation, regulate gastrointestinal hormones, and inhibit the expression of PI3K/AKT/HIF-1α pathway-related proteins. Based on serum non-targeted metabolomics analysis, 12 differential metabolites responding to FEJ treatment were identified, and metabolic pathway analysis showed that the role of FEJ was concentrated in 6 metabolic pathways.
Based on network pharmacology, animal experiments and metabolomics, we found that FEJ might ameliorate gastric mucosal injury in PLGC rats by regulating gastrointestinal hormones and inhibiting inflammation, and its mechanism of action is related to the inhibition of excessive activation of PI3K/AKT/HIF-1α signaling pathway and regulation of disorders of body energy metabolism. This comprehensive strategy also provided a reasonable way for unveiling the pharmacodynamic mechanisms of multi-components, multi-targets, and multi-pathways in Traditional Chinese Medicine.
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•Network pharmacology was applied to identify the potential bioactive components in FEJ and predict its pathways in PLGC.•We evaluated the efficacy of FEJ on PLGC rats by animal experiment, and the predicted pathway was determined by the Western blot.•Metabolomics was used to monitor the changes of endogenous substances in PLGC rats after FEJ intervention.
Fuzheng Nizeng Decoction (FZNZ) has a history of decades in gastric precancerous lesions (GPL) treatment, which has shown clear clinical efficacy. Blocking GPL is a key measure to reduce the ...incidence of gastric cancer (GC). Therefore, we aim to investigate the mechanism of FZNZ-induced ferroptosis and endoplasmic reticulum (ER) in MNNG-induced gastric precancerous lesion (MC) cells, which has been rarely studied in Traditional Chinese Medicine (TCM).
First, CCK8 and lactate dehydrogenase assays were conducted to study the potential effect of FZNZ on MC cells. Second, combined transcriptomic and metabolomic analysis were used to explore the effect and mechanism of FZNZ. Functionally, the occurrence of ferroptosis was assessed by transmission electron microscopy morphological observation and measurement of ferrous iron levels, lipid peroxidation, and glutathione levels. Finally, the expression levels of mRNAs or proteins related to ferroptosis and ER stress were determined by qPCR or western blot assays, respectively.
FZNZ inhibited MC cells viability and induced cell death. By metabolomics coupled with transcriptomics analysis, we found that the mechanism of FZNZ treatment induced ferroptosis and was related to glutathione metabolism and ER stress. We then, for the first time, found that FZNZ induced ferroptosis, which contributed to an increase in intracellular ferrous iron, reactive oxygen species, and malondialdehyde and a decrease in glutathione. Meanwhile, the protein level of glutathione peroxidase 4 (GPX4) was decreased. The mRNA levels of ATF3/CHOP/CHAC1, which are related to ferroptosis and ER stress, were also upregulated.
Our results elaborate that FZNZ could induce ferroptosis and ER stress in MC cells, and reduce GPX4/GSH. ATF3/CHOP/CHAC1 may play a crosstalk role, which provides a new molecular mechanism for the treatment of GPL.
Effective screening and early detection are critical to improve the prognosis of gastric cancer (GC). Our study aims to explore noninvasive multianalytical biomarkers and construct integrative models ...for preliminary risk assessment and GC detection. Whole genomewide methylation marker discovery was conducted with CpG tandems target amplification (CTTA) in cfDNA from large asymptomatic screening participants in a high‐risk area of GC. The methylation and mutation candidates were validated simultaneously using one plasma from patients at various gastric lesion stages by multiplex profiling with Mutation Capsule Plus (MCP). Helicobacter pylori specific antibodies were detected with a recomLine assay. Integrated models were constructed and validated by the combination of multianalytical biomarkers. A total of 146 and 120 novel methylation markers were found in CpG islands and promoter regions across the genome with CTTA. The methylation markers together with the candidate mutations were validated with MCP and used to establish a 133‐methylation‐marker panel for risk assessment of suspicious precancerous lesions and GC cases and a 49‐methylation‐marker panel as well as a 144‐amplicon‐mutation panel for GC detection. An integrated model comprising both methylation and specific antibody panels performed better for risk assessment than a traditional model (AUC, 0.83 and 0.63, P < .001). A second model for GC detection integrating methylation and mutation panels also outperformed the traditional model (AUC, 0.82 and 0.68, P = .005). Our study established methylation, mutation and H. pylori‐specific antibody panels and constructed two integrated models for risk assessment and GC screening. Our findings provide new insights for a more precise GC screening strategy in the future.
What's new?
Genetic and epigenetic markers and environmental factors including Helicobacter pylori promote gastric cancer. Here, the authors established methylation, mutation and H. pylori‐specific antibody biomarker panels based on the analysis of precancerous lesions and gastric cancer cases to construct and validate two integrative models. The risk assessment model aimed to identify suspicious precancerous lesions and gastric cancer cases among asymptomatic screening participants and the detection model to further distinguish gastric cancer from suspected cases. The models showed better performance than a traditional model and high feasibility, paving the way for a noninvasive multianalytical approach for risk assessment and gastric cancer detection.
Abstract
Background
The question of whether eradication of
Helicobacter pylori
(Hp) can reverse gastric precancerous lesions, including intestinal metaplasia, remains uncertain, leading to ongoing ...debate. Therefore, a meta‐analysis was performed to evaluate the effect of Hp eradication on gastric precancerous lesions.
Materials and Methods
PubMed, Embase, Cochrane Library, Web of Science, Scopus database, and
ClinicalTrials.gov
were systematically searched from inception to April 2023 for studies that explored the impact of Hp eradication on gastric precancerous lesions. Risk ratios (RRs) and their 95% confidence intervals (95% CIs) were selected as the effect size. We used the random‐effects model to assess pooled data. We also performed quality assessments, subgroup analyses, and sensitivity analyses.
Results
Fifteen studies were included. Compared with placebo, Hp eradication could significantly prevent the progression of gastric precancerous lesions (RR = 0.87, 95% CI: 0.81–0.94,
p
< 0.01) and reverse them (RR = 1.32, 95% CI: 1.17–1.50,
p
< 0.01). Then, specific precancerous lesions were further explored. The progression of intestinal metaplasia was significantly prevented by Hp eradication compared to placebo or no treatment (RR = 0.80, 95% CI: 0.69–0.94,
p
< 0.01). Moreover, compared with placebo or no treatment, Hp eradication also improved chronic atrophic gastritis (RR = 1.84, 95% CI: 1.30–2.61,
p
< 0.01) and intestinal metaplasia (RR = 1.41, 95% CI: 1.15–1.73,
p
< 0.01). However, in terms of preventing dysplasia progression (RR = 0.86, 95% CI: 0.37–2.00) and improving dysplasia (RR = 0.89, 95% CI: 0.47–1.70), Hp eradication had no advantage compared to placebo or no treatment.
Conclusions
Hp eradication therapy could prevent the progression of gastric precancerous lesions and reverse them. Notably, intestinal metaplasia can be reversed, but this may only be appropriate for patients with epigenetic alterations and milder lesions.
There is increasing evidence for an association between periodontitis/tooth loss and oral, gastrointestinal, and pancreatic cancers. Periodontal disease, which is characterized by chronic ...inflammation and microbial dysbiosis, is a significant risk factor for orodigestive carcinogenesis. Porphyromonas gingivalis is proposed as a keystone pathogen in chronic periodontitis causing both dysbiosis and discordant immune response. The present review focuses on the growing recognition of a relationship between P. gingivalis and orodigestive cancers. Porphyromonas gingivalis has been recovered in abundance from oral squamous cell carcinoma (OSCC). Recently established tumorigenesis models have indicated a direct relationship between P. gingivalis and carcinogenesis. The bacterium upregulates specific receptors on OSCC cells and keratinocytes, induces epithelial-to-mesenchymal (EMT) transition of normal oral epithelial cells and activates metalloproteinase-9 and interleukin-8 in cultures of the carcinoma cells. In addition, P. gingivalis accelerates cell cycling and suppresses apoptosis in cultures of primary oral epithelial cells. In oral cancer cells, the cell cycle is arrested and there is no effect on apoptosis, but macro autophagy is increased. Porphyromonas gingivalis promotes distant metastasis and chemoresistance to anti-cancer agents and accelerates proliferation of oral tumor cells by affecting gene expression of defensins, by peptidyl-arginine deiminase and noncanonical activation of β-catenin. The pathogen also converts ethanol to the carcinogenic intermediate acetaldehyde. In addition, P. gingivalis can be implicated in precancerous gastric and colon lesions, esophageal squamous cell carcinoma, head and neck (larynx, throat, lip, mouth and salivary glands) carcinoma, and pancreatic cancer. The fact that distant organs can be involved clearly emphasizes that P. gingivalis has systemic tumorigenic effects in addition to the local effects in its native territory, the oral cavity. Although coinfection with other bacteria, viruses, and fungi occurs in periodontitis, P. gingivalis relates to cancer even in absence of periodontitis. Thus, there may be a direct relationship between P. gingivalis and orodigestive cancers.
The diagnosis of Precancerous Lesions of Gastric Cancer (PLGC) is challenging in clinical practice. We conducted a clinical study by analyzing the information of relevant chromosome copy number ...variations (CNV) in the TCGA database followed by the UCAD technique to evaluate the value of Chromosomal Instability (CIN) assay in the diagnosis of PLGC.
Based on the screening of gastric cancer related data in TCGA database, CNV analysis was performed to explore the information of chromosome CNV related to gastric cancer. Based on the gastroscopic pathology results, 12 specimens of patients with severe atrophy were screened to analyze the paraffin specimens of gastric mucosa by UCAD technology, and to explore the influence of related factors on them.
The results of CNV in TCGA database suggested that chromosome 7, 8, and 17 amplification was obvious in patients with gastric cancer. UCAD results confirmed that in 12 patients with pathologic diagnosis of severe atrophy, five of them had positive results of CIN, with a positive detection rate of 41.7%, which was mainly manifested in chromosome seven and chromosome eight segments amplification. We also found that intestinalization and HP infection were less associated with CIN. And the sensitivity of CIN measurement results was significantly better than that of tumor indicators.
The findings suggest that the diagnosis of PLGC can be aided by UCAD detection of CIN, of which Chr7 and 8 may be closely related to PLGC.
Upper gastrointestinal (GI) cancers are the leading cause of cancer-related deaths worldwide. Early identification of precancerous lesions has been shown to minimize the incidence of GI cancers and ...substantiate the vital role of screening endoscopy. However, unlike GI cancers, precancerous lesions in the upper GI tract can be subtle and difficult to detect. Artificial intelligence techniques, especially deep learning algorithms with convolutional neural networks, might help endoscopists identify the precancerous lesions and reduce interobserver variability. In this review, a systematic literature search was undertaken of the Web of Science, PubMed, Cochrane Library and Embase, with an emphasis on the deep learning-based diagnosis of precancerous lesions in the upper GI tract. The status of deep learning algorithms in upper GI precancerous lesions has been systematically summarized. The challenges and recommendations targeting this field are comprehensively analyzed for future research.
Breast carcinoma is a multistep progressive disease. Precancerous prevention seems to be crucial. β-Boswellic acid (β-BA), the main component of the folk medicine
Boswellia serrata
(
B. serrata
), ...has been reported to be effective in various diseases including tumors. In this work, we demonstrated that β-BA could inhibit breast precancerous lesions in rat disease models. Consistently, β-BA could suppress proliferation and induce apoptosis on MCF-10AT without significantly influencing MCF-10A. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that β-BA may interfere with the metabolic pathway. Metabolism-related assays showed that β-BA suppressed glycolysis and reduced ATP production, which then activated the AMPK pathway and inhibited the mTOR pathway to limit MCF-10AT proliferation. Further molecular docking analysis suggested that GLUT1 might be the target of β-BA. Forced expression of GLUT1 could rescue the glycolysis suppression and survival limitation induced by β-BA on MCF-10AT. Taken together, β-BA could relieve precancerous lesions
in vivo
and
in vitro
through GLUT1 targeting-induced glycolysis suppression and AMPK/mTOR pathway alterations. Here, we offered a molecular basis for β-BA to be developed as a promising drug candidate for the prevention of breast precancerous lesions.
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