BackgroundCancer-associated fibroblasts (CAFs), one of the principal constituents of the tumor microenvironment, have a pivotal role in tumor progression. Dysregulation of microRNAs (miRNAs) in CAFs contributes to the tumor-promoting ability of CAFs. However, the mechanism underlying the involvement of miRNAs in CAFs of gastric cancer (GC) is not fully understood. This study aimed to explore the effects of miRNA-214 in CAFs on GC migration and invasion.MethodsThe primary CAFs and corresponding normal fibroblasts (NFs) were isolated. Cell counting kit-8, EdU cell proliferation staining and Transwell assays were used to determine the role of miRNA-214 in GC progression. Real-time polymerase chain reaction, Western blot analysis, and dual-luciferase reporter assay were performed to verify the target genes of miRNA-214. Immunofluorescence and Western blot analysis were applied to detect the expression of epithelial–mesenchymal transition (EMT) markers. Immunohistochemistry and in situ hybridization were implemented to analyze the fibroblast growth factor 9 (FGF9) and miRNA-214 expression in human GC tissues, respectively. Finally, to assess its prognostic relevance, Kaplan–Meier survival analysis was conducted.ResultsMiRNA-214 was significantly downregulated in CAFs of GC compared with NFs. The upregulation of miRNA-214 in CAFs inhibited GC cell migration and invasion in vitro but failed to affect proliferation. Moreover, GC cells cultured with conditioned medium from CAFs transfected with miR-214 mimic showed increased expression of E-cadherin and decreased expression of Vimentin, N-cadherin and Snail, indicating the suppression of EMT of GC cells. Furthermore, FGF9 was proved to be a direct target gene of miR-214. The expression of FGF9 was higher in CAFs than that in tumor cells not only in primary tumor but also in lymph node metastatic sites (30.0% vs 11.9%, P < 0.01 and 32.1% vs 12.3%, P < 0.01, respectively). Abnormal expression of FGF9 in CAFs of lymph node metastatic sites was significantly associated with poor prognosis in patients with GC (P < 0.05).ConclusionsThis study showed that miR-214 inhibited the tumor-promoting effect of CAFs on GC through targeting FGF9 in CAFs and regulating the EMT process in GC cells, suggesting miRNA-214/FGF9 in CAFs as a potential target for therapeutic approaches in GC.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0995-9) contains supplementary material, which is available to authorized users.
significantly positively correlated with latitude and temperature seasonality of the populations. In addition, root/shoot ratio and water-use efficiency showed significant variation in plasticity among populations in response to water availability, and plasticities of these two traits were significantly negatively correlated with longitude and positively correlated with precipitation seasonality. The observed geographic clines in plasticity suggest that phenotypic plasticity of S. canadensis may have evolved rapidly in regions with different climatic conditions, and this may have contributed to the spread of this invasive species.
The prostate specific membrane antigen (PSMA) is broadly overexpressed on prostate cancer (PCa) cell surfaces. In this study, we report the synthesis, characterization, in vitro binding assay, and in vivo magnetic resonance imaging (MRI) evaluation of PSMA targeting superparamagnetic iron oxide nanoparticles (SPIONs). PSMA-targeting polypeptide CQKHHNYLC was conjugated to SPIONs to form PSMA-targeting molecular MRI contrast agents. In vitro studies demonstrated specific uptake of polypeptide-SPIONs by PSMA expressing cells. In vivo MRI studies found that MRI signals in PSMA-expressing tumors could be specifically enhanced with polypeptide-SPION, and further Prussian blue staining showed heterogeneous deposition of SPIONs in the tumor tissues. Taken altogether, we have developed PSMA-targeting polypeptide-SPIONs that could specifically enhance MRI signal in tumor-bearing mice, which might provide a new strategy for the molecular imaging of PCa.
Video-assisted mediastinoscopy (VAM) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are the two most commonly used invasive methods for mediastinal staging of lung cancer. The objective of this review is to assess and compare the overall diagnostic values of VAM and EBUS-TBNA. PubMed, Embase, Web of Science and the Cochrane Library were searched for studies that evaluated EBUS-TBNA or VAM accuracy. Quantitative meta-analysis was used to pool sensitivity and specificity, and study quality was evaluated. Meta-regression was applied to indirectly compare EBUS-TBNA and VAM after adjusting quality score, study design, and station number. A total of ten studies with 999 EBUS-TBNA patients and seven studies with 915 VAM patients were included. Since the pooled specificity was 100% for both modalities, sensitivity was mainly analyzed. The pooled sensitivities for EBUS-TBNA and VAM were 0.84 (95% CI 0.79-0.88) and 0.86 (95% CI 0.82-0.90), respectively. Subgroup analyses of quality score, study design, station number and rapid on-site cytologic evaluation showed no significant influence on the overall sensitivity of the two modalities. After adjusting quality score, study design, and station number, the pooled sensitivities of VAM and EBUS-TBNA were not significantly different. However, more procedural complications and fewer false negatives (FN) were found with VAM than EBUS-TBNA. VAM and EBUS exhibited equally high diagnostic accuracy for mediastinal staging of lung cancer. Due to lower morbidity with EBUS-TBNA and fewer FN with VAM, EBUS-TBNA should be performed first, followed by VAM in the case of a negative needle result.
Background: To investigate the spectrum of CT and MRI findings of dysgerminoma of the ovary. Methods: CT and MRI imaging of 12 patients with 13 histologically proven dysgerminomas of the ovary were retrospectively reviewed. Patients , ages ranged from 6~27 years (mean, 17.2 years). Two observers evaluated the following CT and MRI features of the tumor by consensus: (i) location, shape, and size; (ii) attenuation, T2 signal intensity, and ADC value; (iii) patterns of contrast enhancement; (iv) presence of fibrovascular septa; (v) presence of necrosis, hemorrhage, and calcification; (vi) presence of "ovarian vascular pedicle" sign. We also noted the extent or stage of the tumors. Results: 75% lesions arised in the right ovary. Bilateral ovaries were involved in one case. Tumors displayed as a purely or predominantly solid mass (mean size, 17.0 ± 7.8 cm). Ten tumors were shaped multilobulated. The mean ADC value of lesions was 0.830 ± 0.154 × 10 − 3 mm 2 /s. Characteristic fibrovascular septa were observed in all lesions. Among them, classic septa were present in 69% lesions. They were thin, hypointense on T2WI with a linear intense enhancement indicating the blood vessels in septa. Due to the stromal edema, fibrovascular septa may become thick even amorphous in shape, hyperintense on T2WI and even low attenuation on CT with a slight enhancement except for a bright blood vessel on the edge. Massive necrosis was observed only in one lesion. Calcification was present in 3 of the 5 tumors on CT. "Ovarian vascular pedicle" sign was present in 12 lesions. Lymphadenopathy, retroperitoneal spread, and distant metastases combined with an implantation in Douglas' cul-de-sac were present in one patient respectively. Conclusion: On CT and MR images, ovarian dysgerminoma often appears as a large solid mass. The edematous condition of characteristic fibrovascular septa can be well displayed by imaging which then can guide the radiologists to make an accurate diagnosis. Calcifications often occur in the tumor. Nonspecific low ADC value and "ovarian vascular pedicle" sign may narrow the differential diagnosis.
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