RESUMO
BACKGROUND/AIM: The current therapeutic strategies for endometrial cancer are limited and unsatisfactory. Accumulating evidence suggest that microRNAs (miRNAs) participate in tumor growth and metastasis. Mesenchymal stem cells (MSCs) derived exosomes (Exos) are considered as better miRNA delivery vehicles. Here, we investigated the therapeutic effect of exosomal miR-499a-5p (miR-499) in human endometrial cancer metastasis. METHODS: Microarray analysis and RT-PCR were performed to detect the relative expression of miR-499 in endometrial cancer tissues and cell lines. MSC-derived Exos were characterized by transmission electron microscope (TEM), Western blot (WB), and nanoparticle tracking analysis (NTA). miR-499 was loading into Exos using electroporation. Cell proliferation and angiogenesis capacity were tested by 5-ethynyl-29-deoxyuridine (EdU) assay and tube formation assay, respectively. Dual-luciferase reporter assay (DLR) was used to confirm the connection of miR-499 and VAV3. RESULTS: We found that the expression of miR-499 was significantly downregulated in cancer tissues compared with adjacent tissues in endometrial cancer patients. Moreover, exosomal miR-499 not only dramatically suppressed endometrial cancer cells proliferation, endothelial cells tube formation in vitro, but also inhibited tumor growth and angiogenesis in vivo. In addition, we confirmed that miR-499 directly targets the 3'UTR sequence of VAV3. CONCLUSION: The novel identified exosomal miR-499 functions as a tumor suppressor in endometrial cancer though regulating VAV3, and these findings could be a valid molecular target for endometrial cancer therapy.
RESUMO
Objective To study the characteristics of microscopic spread of esophageal squamous-cell carcinoma (ESCC) and the influence of clinicopathological features on it to help define the clinical target volume (CTV) margin in radiotherapy.Methods Sixty-four surgical specimens of ESCC were observed for longitudinal microscopic spread per centimeter both proximally and distally from the tumor.The shrinkage ratio of each specimen was calculated and used for tissue incision.Results The further the distance beyond the tumor, the lower the incidence there was of microscopic spread.Positive rates of microscopic spread in group 3 cm of proximal and distal were 4.8% and 6.9%, respectively, and in group 4 cm were both 3.6%.Tumors longer than 5 cm in length,with poorer differentiation, lymph nodes metastasis and more aggressive phase had higher positive rates (79.3% vs 45.7%,77.4% vs 45.5%,76.0% vs 51.2%,70.5% vs 40.0%,χ2=7.52,6.86,3.91,5.36;P=0.006,0.009,0.042,0.021).Differentiation and tumor length were main factors contributing to microscopic spread (χ2=0.19,4.82;P=0.020,0.017).Conclusions To cover 95% of the microscopic spread,a margin of 3.0 cm proximal and 4.0 cm distal beyond gross tumor volume is needed and as to 90%, a margin of 3.0 cm both proximal and distal is needed.Moreover, the influence of pathological features should be taken into account.
