S1633 Abnormal Angiogenesis in Barrett's Mucosa Demonstrated In Vivo by Confocal Endomicroscopy. Underlying Molecular Mechanisms Include Increased and Aberrant Expression of Importin α, VEGF VRGFR2 and COX2. Implications for Esophageal Neoplasia

2010 ◽  
Vol 138 (5) ◽  
pp. S-242-S-243
Author(s):  
Tamara Matysiak-Budnik ◽  
Emmanuel Coron ◽  
Jean-François Mosnier ◽  
Marc Le Rhun ◽  
Jean-Paul Galmiche ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Aberrant Expression ◽  
Esophageal Neoplasia ◽  
Confocal Endomicroscopy ◽  
Barrett’S Mucosa ◽  
Importin Α ◽  
Barrett's Mucosa

scholarly journals Endoscopic Resection and Radiofrequency Ablation for Early Esophageal Neoplasia

2016 ◽  
Vol 34 (5) ◽  
pp. 469-475 ◽  
Author(s):  
Kamar Belghazi ◽  
Jacques Bergman ◽  
Roos E. Pouw
Keyword(s):  
Radiofrequency Ablation ◽  
Endoscopic Resection ◽  
Additional Treatment ◽  
Optimal Decision ◽  
Histological Evaluation ◽  
Endoscopic Management ◽  
Esophageal Neoplasia ◽  
Neoplastic Lesions ◽  
Barrett’S Mucosa ◽  
Barrett's Mucosa

Background: In the last few decades, endoscopic treatment of early neoplastic lesions in the esophagus has established itself as a valid and less invasive alternative to surgical resection. Endoscopic resection (ER) is the cornerstone of endoscopic therapy. Next to the curative potential of ER, by removing neoplastic lesions, ER may also serve as a diagnostic tool. The relatively large tissue specimens obtained with ER enable accurate histological staging of a lesion, allowing for optimal decision-making for further patient management. ER was pioneered in Japan, mainly for the resection of gastric lesions and squamous esophageal neoplasia, and also Western countries have been increasingly implementing ER in the treatment of early gastroesophageal neoplasia, mostly associated with Barrett's esophagus (BE). In BE, however, there is still a risk of metachronous lesions in the remainder of the Barrett's after focal ER. Additional treatment of all Barrett's mucosa is therefore advised. Currently, the most effective method for this is by using radiofrequency ablation (RFA). This review will provide an overview of indications for ER and RFA. Key Messages and Conclusions: Endoscopic management of early esophageal neoplasia is a safe and valid alternative to surgery and is nowadays the treatment of choice. ER is the mainstay of endoscopic management of early esophageal neoplasia since it allows for removal of neoplastic lesions and provides a large tissue specimen for histological evaluation. In case of early neoplasia in BE, focal ER should be complemented by eradication of the remaining Barrett's mucosa. RFA has proven to be a safe and effective modality to achieve complete eradication of Barrett's mucosa.

scholarly journals LINC00152 Acts as a Potential Marker in Gliomas and Promotes Tumor Proliferation and Invasion Through The LINC00152/miR-107/RAB10 Axis

2021 ◽  
Author(s):  
qing liu ◽  
gang peng ◽  
Jun Su ◽  
zeyou wang ◽  
songhua xiao
Keyword(s):  
Molecular Mechanisms ◽  
Bioinformatics Analysis ◽  
Experimental Studies ◽  
Pivotal Role ◽  
Aberrant Expression ◽  
Potential Marker ◽  
Induced Apoptosis ◽  
Proliferation And Invasion

Abstract Aberrant expression of long noncoding RNAs plays a pivotal role in tumorigenesis. Recently, several studies have showed that the LINC00152 gene is upregulated in a variety of tumors and plays an oncogene role; however, its underlying molecular mechanisms in glioblastoma remain unclear. In this study, we found that LINC00152 was upregulated in gliomas and its expression was significantly associated with high tumor aggressiveness and poor outcomes for glioma patients through bioinformatics analysis. Functionally, the knockdown of LINC00152 not only inhibited malignant behaviors of glioma, such as proliferation and invasion of glioma cells and induced apoptosis in vitro but also suppressed tumorigenesis in vivo. Mechanistically, results of the bioinformatics analysis and experimental studies confirmed that LINC00152 and RAB10 as the targets of miR-107, and LINC00152 might act as a sponge for miR-107 to regulate the expression of RAB10 in glioblastoma. Additionally, silencing miR-107 reversed the effects induced by LINC00152 knockdown on glioblastoma cells both in vitro and in vivo. Taken together, our data suggested that LINC00152 is a candidate prognostic marker of glioma, and that the LINC00152/MIR-107/RAB10 axis plays a pivotal role in regulation of the glioma malignancy, and therefore, targeting the axis might be an effective therapeutic strategy to treat glioma.

scholarly journals Circular RNA Hsa_Circ_0002483 Promotes Growth and Invasion of Lung Adenocarcinoma by Sponging miR-125a-3p

2021 ◽  
Author(s):  
Jun Wan ◽  
Guanggui Ding ◽  
Min Zhou ◽  
Xiean Ling ◽  
ZhanPeng Rao
Keyword(s):  
Lung Adenocarcinoma ◽  
Colony Formation ◽  
Molecular Mechanisms ◽  
Specific Binding ◽  
Tumor Model ◽  
Circular Rnas ◽  
Aberrant Expression ◽  
Tissue Samples

Abstract Background: Increasing evidence indicates that the aberrant expression of circular RNAs (circRNAs) is involved in the pathogenesis and progression of lung adenocarcinoma (LUAC). However, the function and molecular mechanisms of hsa_circ_0002483 (circ_0002483) in LUAC remain unclear. Methods: The association between circ_0002483 expression and clinicopathological characteristics and prognosis in patients with LUAC was analyzed by fluorescence in situ hybridization. The functional experiments such as MTT, colony formation and Transwell assays and a subcutaneous tumor model were conducted to determine the role of circ_0002483 in LUAC cells. The specific binding between circ_0002483 and miR-125a-3p was validated by RNA immunoprecipitation, luciferase gene report and qRT-PCR assays. The effects of circ_0002483 on miR-125a-3p-mediated C-C motif chemokine ligand 4 (CCL4)-CCR5 axis were assessed by Western blot analysis.Results: We found that circ_0002483 was upregulated in LUAC tissue samples and associated with TNM stage and poor survival in patients with LUAC. Knockdown of circ_0002483 inhibited proliferation, colony formation and invasion of A549 and PC9 cells in vitro, whereas overexpression of circ_0002483 harbored the opposite effects. Furthermore, circ_0002483 sponged miR-125a-3p and negatively modulated its expression. CCL4 was identified as a direct target of miR-125a-3p. The rescue experiments showed that miR-125a-3p mimics reversed the tumor-promoting effects of circ_0002483 by targeting CCL4-CCR5 axis in A549 and PC9 cells. In addition, the in vivo experiment further validated that knockdown of circ_0002483 repressed tumor growth. Conclusions: Our findings demonstrated that circ_0002483 could act as a sponge of miR-125a-3p to upregulate CCL4-CCR5 axis, contributing to the tumorigenesis of LUAC, and represent a potential therapeutic target for LUAC.

scholarly journals CircRNA CDR1as Promotes Glioma Progression by Regulating miR-514a-3p/STAT3 Signaling Pathway

2020 ◽  
Author(s):  
Yiqun Cao ◽  
Wentao Yang ◽  
Deheng Li ◽  
Liangdong Li ◽  
Xin Chen ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cell Lines ◽  
Glioma Cell ◽  
Molecular Mechanisms ◽  
Migration And Invasion ◽  
Aberrant Expression ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Regulated Expression

Abstract Background The pathogenesis of glioma is very complicated and the molecular mechanisms have not been clearly demonstrated so far. CircRNA CDR1as as non-coding RNA was highly expressed in multiple human cancers and promoted tumorigenesis and cancer progression. However, there were no reports to address the roles of CDR1as in glioma.Methods In this study, we used glioma cell lines to investigate the function of CDR1as. Cell viability, colony formation, migration, invasion, gene expression, luciferase activity, miRNA-circRNA interaction, protein-circRNA interaction, and tumor formation in vivo were assessed.Results We found that CDR1as is up-regulated in human glioma tissues and cell lines, and its expression is significantly associated with the prognosis of patients with glioma. Loss-of-function studies revealed that CDR1as increases glioma cell proliferation, migration, and invasion in vitro and tumor growth in vivo. We showed that CDR1as can bind miR-514a-3p and act as a sponge of miR-514a-3p. Furthermore, we identified that the expression of STAT3 is regulated by miR-514a-3p and CDR1as as the direct target of miR-514a-3p. Additionally, the decreased glioma cell malignancy by CDR1as knockdown can be reversed by miR-514a-3p inhibitor and overexpression of STAT3. CDR1as knockdown can result in the down-regulated expression of PCNA, Ki67, N-cadherin, and MMP9 and up-regulated expression of E-cadherin. Moreover, the aberrant expression of these genes by CDR1as knockdown also can be reversed by miR-514a-3p inhibitor and overexpression of STAT3.Conclusions Taken together, our findings uncover the molecular mechanisms of CDR1as-mediated the progression of glioma through the miR-514a-3p/STAT3 signaling pathway. These results will provide a theoretical basis for further understanding of the molecular mechanisms of glioma tumorigenesis and developing new therapeutic targets.

scholarly journals Deoxycholic acid causes DNA damage while inducing apoptotic resistance through NF-κB activation in benign Barrett's epithelial cells

2011 ◽  
Vol 301 (2) ◽  
pp. G278-G286 ◽  
Author(s):  
Xiaofang Huo ◽  
Stefanie Juergens ◽  
Xi Zhang ◽  
Davood Rezaei ◽  
Chunhua Yu ◽  
...  
Keyword(s):  
Dna Damage ◽  
T Cells ◽  
Epithelial Cells ◽  
Barrett’S Esophagus ◽  
Barrett's Esophagus ◽  
Molecular Mechanisms ◽  
Deoxycholic Acid ◽  
Biopsy Specimens ◽  
Barrett’S Mucosa ◽  
Barrett's Mucosa

Gastroesophageal reflux is associated with adenocarcinoma in Barrett's esophagus, but the incidence of this tumor is rising, despite widespread use of acid-suppressing medications. This suggests that refluxed material other than acid might contribute to carcinogenesis. We looked for potentially carcinogenetic effects of two bile acids, deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA), on Barrett's epithelial cells in vitro and in vivo. We exposed Barrett's (BAR-T) cells to DCA or UDCA and studied the generation of reactive oxygen/nitrogen species (ROS/RNS); expression of phosphorylated H2AX (a marker of DNA damage), phosphorylated IkBα, and phosphorylated p65 (activated NF-κB pathway proteins); and apoptosis. During endoscopy in patients, we took biopsy specimens of Barrett's mucosa before and after esophageal perfusion with DCA or UDCA and assessed DNA damage and NF-κB activation. Exposure to DCA, but not UDCA, resulted in ROS/RNS production, DNA damage, and NF-κB activation but did not increase the rate of apoptosis in BAR-T cells. Pretreatment with N-acetyl-l-cysteine (a ROS scavenger) prevented DNA damage after DCA exposure, and DCA did induce apoptosis in cells treated with NF-κB inhibitors (BAY 11-7085 or AdIκB superrepressor). DNA damage and NF-κB activation were detected in biopsy specimens of Barrett's mucosa taken after esophageal perfusion with DCA, but not UDCA. These data show that, in Barrett's epithelial cells, DCA induces ROS/RNS production, which causes genotoxic injury, and simultaneously induces activation of the NF-κB pathway, which enables cells with DNA damage to resist apoptosis. We have demonstrated molecular mechanisms whereby bile reflux might contribute to carcinogenesis in Barrett's esophagus.

scholarly journals Circular RNA hsa_circ_0002483 promotes growth and invasion of lung adenocarcinoma by sponging miR-125a-3p

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jun Wan ◽  
Guanggui Ding ◽  
Min Zhou ◽  
Xiean Ling ◽  
Zhanpeng Rao
Keyword(s):  
Lung Adenocarcinoma ◽  
Colony Formation ◽  
Molecular Mechanisms ◽  
Specific Binding ◽  
Tumor Model ◽  
Circular Rnas ◽  
Aberrant Expression ◽  
Tissue Samples

Abstract Background Increasing evidence indicates that the aberrant expression of circular RNAs (circRNAs) is involved in the pathogenesis and progression of lung adenocarcinoma (LUAC). However, the function and molecular mechanisms of hsa_circ_0002483 (circ_0002483) in LUAC remain unclear. Methods The association between circ_0002483 expression and clinicopathological characteristics and prognosis in patients with LUAC was analyzed by fluorescence in situ hybridization. The functional experiments such as CCK-8, colony formation and Transwell assays and a subcutaneous tumor model were conducted to determine the role of circ_0002483 in LUAC cells. The specific binding between circ_0002483 and miR-125a-3p was validated by RNA immunoprecipitation, luciferase gene report and qRT-PCR assays. The effects of circ_0002483 on miR-125a-3p-mediated C-C motif chemokine ligand 4 (CCL4)-CCR5 axis were assessed by Western blot analysis. Results We found that circ_0002483 was upregulated in LUAC tissue samples and associated with Tumor Node Metastasis (TNM) stage and poor survival in patients with LUAC. Knockdown of circ_0002483 inhibited proliferation, colony formation and invasion of A549 and PC9 cells in vitro, whereas overexpression of circ_0002483 harbored the opposite effects. Furthermore, circ_0002483 sponged miR-125a-3p and negatively regulated its expression. CCL4 was identified as a direct target of miR-125a-3p. The rescue experiments showed that miR-125a-3p mimics reversed the tumor-promoting effects of circ_0002483 by targeting CCL4-CCR5 axis in A549 and PC9 cells. In addition, the in vivo experiment further validated that knockdown of circ_0002483 repressed tumor growth. Conclusions Our findings demonstrated that circ_0002483 could act as a sponge of miR-125a-3p to upregulate CCL4-CCR5 axis, contributing to the tumorigenesis of LUAC, and represent a potential therapeutic target for LUAC.

scholarly journals OP13 Glyco-fingerprint as a relevant risk factor on colitis-associated cancer

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S012-S013
Author(s):  
A Dias ◽  
E Gomes ◽  
M Silva ◽  
 Fernandes ◽  
M Garrido ◽  
...  
Keyword(s):  
Risk Factor ◽  
Mouse Model ◽  
Molecular Mechanisms ◽  
In Vivo Studies ◽  
Inflammatory Disorder ◽  
Mice Model ◽  
Cross Sectional ◽  
Aberrant Expression ◽  
Colonic Cells

Abstract Background Ulcerative colitis (UC) is a chronic inflammatory disorder of the gastrointestinal tract being considered a serious risk factor for the development of colitis-associated cancer (CAC). However, the molecular mechanisms underlying CAC progression are still elusive. We previously showed that decreased expression of MGAT5 glycogene on intestinal T lymphocytes from UC patients was associated with a hyperimmune response and with disease severity (Dias, AM et al. HMG,2014; Dias, AM et al. PNAS, 2018). On the other hand, we also demonstrated that the aberrant expression of MGAT5 glycogene in gastrointestinal cancer cells was associated with tumour invasiveness and progression (Carvalho S et al., Oncogene 2015). However, whether this differential expression of glycans in colitis and cancer contexts mediated by MGAT5 glycogene constitutes a new mechanism in CAC remains completely unknown. Methods A well-characterised cohort of paraffin samples from CAC patients at different stages of carcinogenesis (colitis; dysplasia and colon cancer) were evaluated by immunohistochemistry, using specific lectins to evaluate the N-glycosylation profile either in stroma or in epithelial cells. Furthermore, in vivo studies (using Azoxymethane (AOM)/dextran sodium sulphate (DSS) to induce CAC) were conducted in MGAT5 wild-type and null mice. The combined glycoimmune profile of colonic cells was analysed by flow cytometry. Analysis of RNAseq data from colitis-associated cancer mice model (the AOM/DSS mouse model) was performed to decipher the glyco-fingerprint in colonic cells during colitis; low- and high-grade dysplasia and adenocarcinoma. Results Our cross-sectional study revealed a distinct glycoprofile in stroma, characterised by a decreased expression of branched N-glycans in colitis followed by increased expression in dysplasia and colon carcinoma stages corroborated by the RNASeq analysis on the colon of AOM/DSS mouse model. Additionally, colonic T cells isolated from both AOM/DSS MGAT5 WT and KO mice presented a distinct glycoprofile along CAC development. Conclusion Our preliminary results both from human and mice samples demonstrate a distinct glycoimmuno profile along the colitis-associated carcinoma cascade, which potentially represents a biomarker to early identify risk UC patients.

scholarly journals ENC1 Facilitates Colorectal Carcinoma Tumorigenesis and Metastasis via JAK2/STAT5/AKT Axis-Mediated Epithelial Mesenchymal Transition and Stemness

2021 ◽  
Vol 9 ◽  
Author(s):  
Ying Cui ◽  
Jiani Yang ◽  
Yibing Bai ◽  
QingWei Li ◽  
Yuanfei Yao ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Actin Binding ◽  
Phenotypic Traits ◽  
Aberrant Expression ◽  
Mesenchymal Transition ◽  
Computation Analysis

Ectodermal neural cortex 1 (ENC1) is an actin-binding protein and has been known to be upregulated in several cancers, but the molecular mechanisms through which it contributes to the pathology of CRC have largely been elusive. We utilized data mining and validated the aberrant expression of ENC1, following which phenotypic traits of malignancy were assessed in vitro. Ruxolitinib was used as a surrogate to compare the effects of ENC1 expression and silencing on the JAK-STAT-AKT pathway. In vivo models were employed to confirm the in vitro observations. Computation analysis, strengthened by in situ and in vitro data, confirmed the overexpression of ENC1 in CRC and predicted a poor prognosis, while enhanced cell proliferation, invasion, migration, EMT, and stemness were associated with ENC1 overexpression. Silencing of ENC1 downregulated the phenotypes. Additionally, silencing of ENC1 significantly reduced the activation of JAK2 and consequent activation of STAT5 and AKT comparable to ruxolitinib inhibition of JAK2. Silencing of ENC1 resulted in lesser tumor volumes and fewer numbers of tumors, in vivo. These data suggest that ENC1 induces CRC through the JAK2-STAT5-AKT axis. ENC1 is a suitable diagnostic marker for CRC detection, and ENC1 targeting therapies may suppress CRC progression.

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