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Surajit Pathak,Alessia Rosaria Grillo,Melania Scarpa,Paola Brun,Renata D’Incà,Laura Nai,Antara Banerjee,Donatella Cavallo,Luisa Barzon,Giorgio Palù,Giacomo Carlo Sturniolo,Andrea Buda,Ignazio Castagli 생화학분자생물학회 2015 Experimental and molecular medicine Vol.47 No.-
Abnormal levels of microRNA (miR)-155, which regulate inflammation and immune responses, have been demonstrated in the colonic mucosa of patients with inflammatory bowel diseases (IBD), although its role in disease pathophysiology is unknown. We investigated the role of miR-155 in the acquisition and maintenance of an activated phenotype by intestinal myofibroblasts (IMF), a key cell population contributing to mucosal damage in IBD. IMF were isolated from colonic biopsies of healthy controls, ulcerative colitis (UC) and Crohn’s disease (CD) patients. MiR-155 in IMF was quantified by quantitative reverse transcription-PCR in basal condition and following exposure to TNF-α, interleukin (IL)-1β, lipopolysaccharide (LPS) or TGF-β1. The effects of miR-155 mimic or inhibitor transfection on cytokine release and suppressor of cytokine signaling 1 (SOCS1) expression were assessed by enzyme-linked immunosorbent assay and western blot, respectively. Regulation of the target gene SOCS1 expression by miR-155 was assessed using luciferase reporter construct. We found that miR-155 was significantly upregulated in UC as compared with control- and CD-derived IMF. Moreover, TNF-α and LPS, but not TGF-β1 and IL-1β, significantly increased miR-155 expression in IMF. Ectopic expression of miR-155 in control IMF augmented cytokines release, whereas it downregulated SOCS1 expression. MiR-155 knockdown in UC-IMF reduced cytokine production and enhanced SOCS1 expression. Luciferase reporter assay demonstrated that miR-155 directly targets SOCS1. Moreover, silencing of SOCS1 in control IMF significantly increased IL-6 and IL-8 release. In all, our data suggest that inflammatory mediators induce miR-155 expression in IMF of patients with UC. By downregulating the expression of SOCS1, miR-155 wires IMF inflammatory phenotype.
Lara C. Burg,Shenna Verheijen,Ruud L.M. Bekkers,Joanna IntHout,Robert W. Holloway,Salih Taskin,Sarah E. Ferguson,Yu Xue,Antonino Ditto,Glauco Baiocchi,Andrea Papadia,Giorgio Bogani,Alessandro Buda,Roy 대한부인종양학회 2022 Journal of Gynecologic Oncology Vol.33 No.5
Objective: The aim of this study was to assess the SLN detection rate in presumed early stage, low- and intermediate-risk endometrial cancers, the incidence of SLN metastases, and the negative predictive value of SLN mapping performed with indocyanine green (ICG). Methods: A systematic review with meta-analyses was conducted. Study inclusion criteria were A) low- and intermediate-risk endometrial cancer, B) the use of ICG per cervical injection; C) a minimum of twenty included patients per study. To assess the negative predictive value of SLN mapping, D) a subsequent lymphadenectomy was an additional inclusion criterion. Results: Fourteen studies were selected, involving 2,117 patients. The overall and bilateral SLN detection rates were 95.6% (95% confidence interval [CI]=92.4%–97.9%) and 76.5% (95% CI=68.1%–84.0%), respectively. The incidence of SLN metastases was 9.6% (95% CI=5.1%–15.2%) in patients with grade 1–2 endometrial cancer and 11.8% (95% CI=8.1%–16.1%) in patients with grade 1–3 endometrial cancer. The negative predictive value of SLN mapping was 100% (95% CI=98.8%–100%) in studies that included grade 1–2 endometrial cancer and 99.2% (95% CI=97.9%–99.9%) in studies that also included grade 3. Conclusion: SLN mapping with ICG is feasible with a high detection rate and negative predictive value in low- and intermediate-risk endometrial cancers. Given the incidence of SLN metastases is approximately 10% in those patients, SLN mapping may lead to stage shifting with potential therapeutic consequences. Given the high negative predictive value with SLN mapping, routine lymphadenectomy should be omitted in low- and intermediate- risk endometrial cancer.