Exosomes-microRNAs interacted with gastric cancer and its microenvironment: a mini literature review

Exosomes have appeared as fundamental vehicle-modulated crosstalk among various cells in the tumor microenvironment. The systematic understanding of exosomes in gastric cancer (GC) enhances our comprehension about the tumor growth, metastasis, chemoresistance and diagnosis of cancers. The versatile functions of exosomes provide reasonable explanations about the propensity for GC metastasis. The selectively enriched components, especially some exosomal miRNAs, are potential noninvasive biomarkers for sensitive and specific GC diagnosis. Given the characteristics of exosomes, frontier researchers are stimulated to modulate the biogenesis, concentrations or release of exosomes so as to disturb malignant signals between cells. Abnormal expression profiles of exosomal miRNAs afford potential GC therapeutic or diagnostic strategies in future.

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MicroRNAs expression profiles as diagnostic biomarkers of gastric cancer: a systematic literature review

Biomarkers ◽

10.1080/1354750x.2018.1539765 ◽

2018 ◽

Vol 24 (2) ◽

pp. 110-119 ◽

Cited By ~ 10

Author(s):

Jovana Stojanovic ◽

Alessia Tognetto ◽

Danilo Francesco Tiziano ◽

Emanuele Leoncini ◽

Brunella Posteraro ◽

...

Keyword(s):

Gastric Cancer ◽

Literature Review ◽

Systematic Literature Review ◽

Expression Profiles ◽

Diagnostic Biomarkers

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Exosomal miR-196a-1 promotes gastric cancer cell invasion and metastasis by targeting SFRP1

Nanomedicine ◽

10.2217/nnm-2019-0053 ◽

2019 ◽

Vol 14 (19) ◽

pp. 2579-2593 ◽

Cited By ~ 5

Author(s):

Chun Feng ◽

Junjun She ◽

Xiaobing Chen ◽

Qunchao Zhang ◽

Xu Zhang ◽

...

Keyword(s):

Gastric Cancer ◽

Expression Profiles ◽

Mirna Microarray ◽

In Vivo Experiments ◽

Exosomal Mirnas ◽

Mirna Expression Profiles ◽

High Expression Level

Aim: To investigate the role of exosomal miRNAs on gastric cancer (GC) metastasis. Materials & methods: miRNA expression profiles of exosomes with distinct invasion potentials were analyzed using miRNA microarray and validated by quantitative real-time PCR. In vitro and in vivo experiments assessed the role of exosomal miR-196a-1 in GC's metastasis. Results: High expression level of exosomal miR-196a-1 expression was significantly associated with poor survival in GC. Exosomes that contained miR-196a-1 were secreted from high-invasive GC cells. Ectopic miR-196a-1 expression promoted invasion of low-invasive GC cells by targeting SFRP1. Conclusion: miR-196a-1 was delivered from high-invasive GC into low-invasive GC cells via exosomes and promoted metastasis to the liver in vitro and in vivo.

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Urinary MicroRNA Expression Analysis of miR-1, miR-215, miR-335, Let-7ain Childhood Nephrotic Syndrome

10.21203/rs.3.rs-1151594/v1 ◽

2021 ◽

Author(s):

C.D.Mohana Priya ◽

Vettriselvi Venkatesan ◽

P.Pricilla charmine ◽

G.Sangeetha Geminiganesan ◽

Sudha Ekambaram

Keyword(s):

Expression Profiles ◽

Urine Samples ◽

Control Group ◽

Healthy Controls ◽

Aberrant Expression ◽

Exosomal Mirnas ◽

Healthy Control ◽

Novel Biomarkers ◽

Steroid Sensitive ◽

Noninvasive Biomarkers

Abstract Background Recently, urinary exosomal miRNAs are gaining increasing attention as their expression profiles are often associated with specific diseases and they exhibit great potential as noninvasive biomarkers for the diagnosis of various diseases. The present study was aimed to evaluate the expression status of selected miRNAs (miR-1, miR-215-5p, miR-335-5p and let-7a-5p) in urine samples from children with NS [steroid sensitive (SSNS)] and [steroid resistant (SRNS)] along with healthy control group.Methods MicroRNA isolation was carried out in urine samples collected from SSNS (100 nos), SRNS (100 nos), and healthy controls (50 nos) using MiRNeasy Mini Kit, followed by cDNA conversion for all the four selected miRNAs using Taqman advanced miRNA cDNA synthesis kit and their expression was quantified by Taqman Advanced miRNA assay kits using Real Time PCR Machine and Rotogen-Q in SSNS and SRNS patients and healthy control subjects.ResultsQuantification of all the four miRNAs (miR-1, mir-215, miR-335, let 7a) were found to be upregulated in both SSNS and SRNS as compared to control group. Further, the comparison of microRNAs within the case groups revealed significant downregulation of three microRNAs - miR-1, miR-215, miR- 335 and upregulation of let-7a in SRNS group as compared to SSNS. The t-test performed for all the four miRNAs was found to be statistically significant. ConclusionsThe aberrant expression of all the four microRNAs in both SSNS and SRNS as compared to healthy subjects may serve as novel biomarkers to distinguish between NS and healthy controls. The differential expression of microRNA let-7a is useful to discriminate SSNS and SRNS.

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ADAMTS12 acts as a tumor microenvironment related cancer promoter in gastric cancer

Scientific Reports ◽

10.1038/s41598-021-90330-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yangming Hou ◽

Yingjuan Xu ◽

Dequan Wu

Keyword(s):

Gastric Cancer ◽

Tumor Microenvironment ◽

Immune Cell ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Tumor Promoter ◽

Protein Protein Interaction ◽

Oxidative Phosphorylation Pathway ◽

Cox Proportional Hazard Regression

AbstractThe infiltration degree of immune and stromal cells has been shown clinically significant in tumor microenvironment (TME). However, the utility of stromal and immune components in Gastric cancer (GC) has not been investigated in detail. In the present study, ESTIMATE and CIBERSORT algorithms were applied to calculate the immune/stromal scores and the proportion of tumor-infiltrating immune cell (TIC) in GC cohort, including 415 cases from The Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) were screened by Cox proportional hazard regression analysis and protein–protein interaction (PPI) network construction. Then ADAMTS12 was regarded as one of the most predictive factors. Further analysis showed that ADAMTS12 expression was significantly higher in tumor samples and correlated with poor prognosis. Gene Set Enrichment Analysis (GSEA) indicated that in high ADAMTS12 expression group gene sets were mainly enriched in cancer and immune-related activities. In the low ADAMTS12 expression group, the genes were enriched in the oxidative phosphorylation pathway. CIBERSORT analysis for the proportion of TICs revealed that ADAMTS12 expression was positively correlated with Macrophages M0/M1/M2 and negatively correlated with T cells follicular helper. Therefore, ADAMTS12 might be a tumor promoter and responsible for TME status and tumor energy metabolic conversion.

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695 Oral delivery of a microbial extracellular vesicle induces potent anti-tumor immunity in mice

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0695 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A737-A737

Author(s):

Loise Francisco-Anderson ◽

Mary Abdou ◽

Michael Goldberg ◽

Erin Troy ◽

...

Keyword(s):

Tumor Microenvironment ◽

Tumor Growth ◽

Extracellular Vesicles ◽

Tumor Immunity ◽

Extracellular Vesicle ◽

The Body ◽

Checkpoint Inhibition ◽

Small Intestinal ◽

The Impact

BackgroundThe small intestinal axis (SINTAX) is a network of anatomic and functional connections between the small intestine and the rest of the body. It acts as an immunosurveillance system, integrating signals from the environment that affect physiological processes throughout the body. The impact of events in the gut in the control of tumor immunity is beginning to be appreciated. We have previously shown that an orally delivered single strain of commensal bacteria induces anti-tumor immunity preclinically via pattern recognition receptor-mediated activation of innate and adaptive immunity. Some bacteria produce extracellular vesicles (EVs) that share molecular content with the parent bacterium in a particle that is roughly 1/1000th the volume in a non-replicating form. We report here an orally-delivered and gut-restricted bacterial EV which potently attenuates tumor growth to a greater extent than whole bacteria or checkpoint inhibition.MethodsEDP1908 is a preparation of extracellular vesicles produced by a gram-stain negative strain of bacterium of the Oscillospiraceae family isolated from a human donor. EDP1908 was selected for its immunostimulatory profile in a screen of EVs from a range of distinct microbial strains. Its mechanism of action was determined by ex vivo analysis of the tumor microenvironment (TME) and by in vitro functional studies with murine and human cells.ResultsOral treatment of tumor-bearing mice with EDP1908 shows superior control of tumor growth compared to checkpoint inhibition (anti-PD-1) or an intact microbe. EDP1908 significantly increased the percentage of IFNγ and TNF producing CD8+ CTLs, NK cells, NKT cells and CD4+ cells in the tumor microenvironment (TME). EDP1908 also increased tumor-infiltrating dendritic cells (DC1 and DC2). Analysis of cytokines in the TME showed significant increases in IP-10 and IFNg production in mice treated with EDP1908, creating an environment conducive to the recruitment and activation of anti-tumor lymphocytes.ConclusionsThis is the first report of striking anti-tumor effects of an orally delivered microbial extracellular vesicle. These data point to oral EVs as a new class of immunotherapeutic drugs. They are particularly effective at harnessing the biology of the small intestinal axis, acting locally on host cells in the gut to control distal immune responses within the TME. EDP1908 is in preclinical development for the treatment of cancer.Ethics ApprovalPreclinical murine studies were conducted under the approval of the Avastus Preclinical Services’ Ethics Board. Human in vitro samples were attained by approval of the IntegReview Ethics Board; informed consent was obtained from all subjects.

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A TLR4 agonist improves immune checkpoint blockade treatment by increasing the ratio of effector to regulatory cells within the tumor microenvironment

Scientific Reports ◽

10.1038/s41598-021-94837-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

A. Farias ◽

A. Soto ◽

F. Puttur ◽

C. J. Goldin ◽

S. Sosa ◽

...

Keyword(s):

Tumor Microenvironment ◽

Tumor Growth ◽

Therapeutic Effect ◽

Immune Cells ◽

Immune Checkpoint ◽

Combined Treatment ◽

Immune Checkpoint Blockade ◽

Checkpoint Blockade ◽

Regulatory Cells ◽

Ifn Γ

AbstractBrucella lumazine synthase (BLS) is a homodecameric protein that activates dendritic cells via toll like receptor 4, inducing the secretion of pro-inflammatory cytokines and chemokines. We have previously shown that BLS has a therapeutic effect in B16 melanoma-bearing mice only when administered at early stages of tumor growth. In this work, we study the mechanisms underlying the therapeutic effect of BLS, by analyzing the tumor microenvironment. Administration of BLS at early stages of tumor growth induces high levels of serum IFN-γ, as well as an increment of hematopoietic immune cells within the tumor. Moreover, BLS-treatment increases the ratio of effector to regulatory cells. However, all treated mice eventually succumb to the tumors. Therefore, we combined BLS administration with anti-PD-1 treatment. Combined treatment increases the outcome of both monotherapies. In conclusion, we show that the absence of the therapeutic effect at late stages of tumor growth correlates with low levels of serum IFN-γ and lower infiltration of immune cells in the tumor, both of which are essential to delay tumor growth. Furthermore, the combined treatment of BLS and PD-1 blockade shows that BLS could be exploited as an essential immunomodulator in combination therapy with an immune checkpoint blockade to treat skin cancer.

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Intratumoral Canine Distemper Virus Infection Inhibits Tumor Growth by Modulation of the Tumor Microenvironment in a Murine Xenograft Model of Canine Histiocytic Sarcoma

International Journal of Molecular Sciences ◽

10.3390/ijms22073578 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3578

Author(s):

Federico Armando ◽

Adnan Fayyad ◽

Stefanie Arms ◽

Yvonne Barthel ◽

Dirk Schaudien ◽

...

Keyword(s):

Tumor Microenvironment ◽

Virus Infection ◽

Tumor Growth ◽

Canine Distemper Virus ◽

Xenograft Model ◽

Histiocytic Sarcoma ◽

Oncolytic Viruses ◽

Canine Distemper ◽

Murine Xenograft Model ◽

The Impact

Histiocytic sarcomas refer to highly aggressive tumors with a poor prognosis that respond poorly to conventional treatment approaches. Oncolytic viruses, which have gained significant traction as a cancer therapy in recent decades, represent a promising option for treating histiocytic sarcomas through their replication and/or by modulating the tumor microenvironment. The live attenuated canine distemper virus (CDV) vaccine strain Onderstepoort represents an attractive candidate for oncolytic viral therapy. In the present study, oncolytic virotherapy with CDV was used to investigate the impact of this virus infection on tumor cell growth through direct oncolytic effects or by virus-mediated modulation of the tumor microenvironment with special emphasis on angiogenesis, expression of selected MMPs and TIMP-1 and tumor-associated macrophages in a murine xenograft model of canine histiocytic sarcoma. Treatment of mice with xenotransplanted canine histiocytic sarcomas using CDV induced overt retardation in tumor progression accompanied by necrosis of neoplastic cells, increased numbers of intratumoral macrophages, reduced angiogenesis and modulation of the expression of MMPs and TIMP-1. The present data suggest that CDV inhibits tumor growth in a multifactorial way, including direct cell lysis and reduction of angiogenesis and modulation of MMPs and their inhibitor TIMP-1, providing further support for the concept of its role in oncolytic therapies.

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Methods for conducting international Delphi surveys to optimise global participation in core outcome set development: a case study in gastric cancer informed by a comprehensive literature review

Trials ◽

10.1186/s13063-021-05338-x ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Bilal Alkhaffaf ◽

Jane M. Blazeby ◽

Aleksandra Metryka ◽

Anne-Marie Glenny ◽

Ademola Adeyeye ◽

...

Keyword(s):

Gastric Cancer ◽

Literature Review ◽

Healthcare Professionals ◽

Vascular Malformations ◽

Methodological Approach ◽

Core Outcome Set ◽

Core Outcome ◽

Comprehensive Literature Review ◽

International Participation

Abstract Background Core outcome sets (COS) should be relevant to key stakeholders and widely applicable and usable. Ideally, they are developed for international use to allow optimal data synthesis from trials. Electronic Delphi surveys are commonly used to facilitate global participation; however, this has limitations. It is common for these surveys to be conducted in a single language potentially excluding those not fluent in that tongue. The aim of this study is to summarise current approaches for optimising international participation in Delphi studies and make recommendations for future practice. Methods A comprehensive literature review of current approaches to translating Delphi surveys for COS development was undertaken. A standardised methodology adapted from international guidance derived from 12 major sets of translation guidelines in the field of outcome reporting was developed. As a case study, this was applied to a COS project for surgical trials in gastric cancer to translate a Delphi survey into 7 target languages from regions active in gastric cancer research. Results Three hundred thirty-two abstracts were screened and four studies addressing COS development in rheumatoid and osteoarthritis, vascular malformations and polypharmacy were eligible for inclusion. There was wide variation in methodological approaches to translation, including the number of forward translations, the inclusion of back translation, the employment of cognitive debriefing and how discrepancies and disagreements were handled. Important considerations were identified during the development of the gastric cancer survey including establishing translation groups, timelines, understanding financial implications, strategies to maximise recruitment and regulatory approvals. The methodological approach to translating the Delphi surveys was easily reproducible by local collaborators and resulted in an additional 637 participants to the 315 recruited to complete the source language survey. Ninety-nine per cent of patients and 97% of healthcare professionals from non-English-speaking regions used translated surveys. Conclusion Consideration of the issues described will improve planning by other COS developers and can be used to widen international participation from both patients and healthcare professionals.

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A novel combination of serum microRNAs for the detection of early gastric cancer

Gastric Cancer ◽

10.1007/s10120-021-01161-0 ◽

2021 ◽

Author(s):

Seiichiro Abe ◽

Juntaro Matsuzaki ◽

Kazuki Sudo ◽

Ichiro Oda ◽

Hitoshi Katai ◽

...

Keyword(s):

Gastric Cancer ◽

Early Gastric Cancer ◽

Expression Profiles ◽

Characteristic Curve ◽

Area Under The Curve ◽

Cancer Center ◽

Serum Samples ◽

Retrospective Case ◽

Serum Mirnas ◽

Validation Set

Abstract Background The aim of this study was to identify serum miRNAs that discriminate early gastric cancer (EGC) samples from non-cancer controls using a large cohort. Methods This retrospective case–control study included 1417 serum samples from patients with EGC (seen at the National Cancer Center Hospital in Tokyo between 2008 and 2012) and 1417 age- and gender-matched non-cancer controls. The samples were randomly assigned to discovery and validation sets and the miRNA expression profiles of whole serum samples were comprehensively evaluated using a highly sensitive DNA chip (3D-Gene®) designed to detect 2565 miRNA sequences. Diagnostic models were constructed using the levels of several miRNAs in the discovery set, and the diagnostic performance of the model was evaluated in the validation set. Results The discovery set consisted of 708 samples from EGC patients and 709 samples from non-cancer controls, and the validation set consisted of 709 samples from EGC patients and 708 samples from non-cancer controls. The diagnostic EGC index was constructed using four miRNAs (miR-4257, miR-6785-5p, miR-187-5p, and miR-5739). In the discovery set, a receiver operating characteristic curve analysis of the EGC index revealed that the area under the curve (AUC) was 0.996 with a sensitivity of 0.983 and a specificity of 0.977. In the validation set, the AUC for the EGC index was 0.998 with a sensitivity of 0.996 and a specificity of 0.953. Conclusions A novel combination of four serum miRNAs could be a useful non-invasive diagnostic biomarker to detect EGC with high accuracy. A multicenter prospective study is ongoing to confirm the present observations.

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