Vasohibin-1(VASH1) has recently been isolated as a novel negative feedback inhibitor of angiogenesis. Several studies have demonstrated that VASH1 plays important roles in tumor angiogenesis but the role of this angiogenic inhibitor in renal cell carcinoma (RCC) has not been elucidated until now. In this study, we investigated the expression pattern of VASH1 and the association with clinicopathological features in RCC. Expression of VASH1, hypoxia-inducible factor-1α (HIF-1α), and microvessel density (MVD, labeled by CD34) was assessed by immunohistochemistry in 46 RCC specimens and 20 adjacent nontumorous renal tissues (ANRTs). Correlation between vasohibin-1 and HIF-1α, MVD, and clinicopathological features was then investigated. In RCC, VASH1 was expressed mainly in the cytoplasm and membrane of tumor cells and partly in vascular endothelial cells. In ANRT, it was mainly expressed in the cytoplasm and membrane of renal tubular epithelial cells and partly in vascular endothelial cells and glomerular mesangial cells. The expression level of VASH1 in RCC tissue was significantly lower than that in ANRT and was significantly reduced with the increased degree of malignancy in RCC tissues. In addition, a significantly negative correlation was noted between VASH1 expression and HIF-1α expression and a significantly negative correlation was noted between VASH1 expression and MVD in RCC. Therefore, VASH1 expression is reduced and it associates with clinicopathological features in RCC. Based on our findings and the knowledge of other angiogenesis inhibitors, we postulate that VASH1 would potentially be a biomarker and a candidate for molecular targeted therapy for patients with RCC in the future.

Background/Aims: miR-146a has recently been shown to promote cell proliferation, migration, and invasion in many cancers, but the role of miR-146a in clear cell renal cell carcinoma (ccRCC) remains unclear. Methods: Reverse transcription quantitative PCR (RT-qPCR) was performed to investigate the mRNA expression of miR-146a and CADM2 in ccRCC tissues. The luciferase reporter assay, Western blotting, and ChIP assay were carried out to explore the promoter and the transcription factor of miR-146a. Moreover, the effect of miR-146a and CADM2 on ccRCC cells was explored using methyl thiazolyl tetrazolium, colony formation, and migration and invasion assays. The luciferase reporter assay, RT-qPCR, western blotting, and immunofluorescence assay were carried out to investigate whether CADM2 is directly regulated by miR-146a. A tumor xenograft model and immunohistochemical staining were used to examine the carcinogenic effect of miR-146a and CADM2 in vivo. Results: miR-146a has been shown to promote cell proliferation, migration, and invasion. Here, we found that miR-146a is highly expressed in ccRCC tissues, whereas CADM2 is down-regulated. Hypoxia can induce the expression of miR-146a by stimulating its promoter. In addition, we demonstrated that miR-146a promoted and CADM2 inhibited proliferation, migration, and invasion of ccRCC cells. The 3’ untranslated region (UTR) luciferase reporter assay identified that miR-146a targeted the 3’ UTR of CADM2 and negatively regulated its expression. Ectopic expression of CADM2 counteracted the promoting effect of miR-146a on cell proliferation, migration, invasion, and the epithelial–mesenchymal transition process. Conclusion: Together, the finding of down-regulation of CADM2 by miR-146a can provide new insights into ccRCC pathogenesis and might contribute to the development of novel therapeutic strategies.

Abstract. Malignant solitary fibrous tumors of the kidney are very rare. Two tumors in one kidney is particularly rare and has not been previously reported. Due to the non-specific clinical symptoms, it is difficult but also very significant to give a definite diagnosis. Here, we report a case of two renal masses in one kidney. A 56-year-old man was admitted to our hospital complaining of shortness of breath, weakness, hyperhidrosis and intermittent hypoglycemia of 1-year duration without gross hematuria or lumbago. Imaging studies revealed two masses manifesting as inhomogeneous, with soft-tissue density and having no clear boundaries with the kidney. The patient was initially diagnosed with spaceoccupying lesions of the left kidney (with suspicions of renal cell carcinoma) and left radical nephrectomy was performed. Histologically, the tumors consisted of ovoid or spindle cells, and a hemangiopericytoma-like pattern and cellular atypia was observed in certain areas. Mitotic figures were more than 4 per 10 high-power fields. Immunohistochemically the tumor cells were positive for CD34, CD99 and vimentin. Accordingly, a diagnosis of malignant solitary fibrous tumor of the left kidney (low-grade malignance) was established. Postoperative follow-up of 10 months did not find tumor recurrence or metastasis and hypoglycemia was resolved with the removal of the tumors.

Vasohibin-1 (VASH1) has recently been isolated as a novel inhibitor of angiogenesis. Several studies have demonstrated that VASH1 plays important roles in tumor angiogenesis but the role of this angiogenic inhibitor in renal cell carcinoma (RCC) has not been elucidated. We previously reported that VASH1 expression is reduced and is associated with clinicopathological features in RCC. In the present study, we investigated the biological effects of VASH1 in RCC by evaluating the effects of VASH1 on cell proliferation, cell cycle distribution, cell apoptosis and cell invasion in human umbilical vein endothelial cells (HUVECs) and 786-0 cells, and evaluating the effect of VASH1 on the growth of 786-0 cells in nude mice. A pReceiver-M61-VASH1 was transfected into HUVECs and 786-0 cells, and the expression level of VASH1 protein was examined by western blotting. Cell proliferation was detected by MTT assay, and cell cycle and apoptosis of HUVECs and 786-0 cells were analyzed by flow cytometry. The invasive ability of 786-0 cells was tested by Transwell assay. Finally, nude mouse models were established to evaluate the therapeutic effect of VASH1. The pReceiver-M61-VASH1 effectively induced the expression of VASH1 in HUVECs and 786-0 cells. VASH1 overexpression effectively inhibited cell proliferation, arrested the cell cycle in the G0/G1 phase and promoted cell apoptosis of HUVECs and 786-0 cells. VASH1 overexpression effectively inhibited the subcutaneous growth of 786-0 tumors in vivo. Therefore, VASH1 is a potential molecular-targeted therapy for patients with RCC.

Malignant rhabdoid tumors of the kidney (MRTKs) are extremely rare. Pure MRTKs in adult patients are particularly rare and have not been previously reported in China. Due to the non-specific clinical symptoms, it is difficult but also essential to be able to give a definite diagnosis. The present study reports a case of pure adult malignant rhabdoid tumor in a patient’s left kidney with characteristic clinicopathological features. Considering the fact that the characteristic findings are often not observed in clinical symptom and imaging studies, the histological features, immunohistochemical staining and cytogenetic studies may aid in confirming the diagnosis of pure MRTKs. Although pure adult MRTKs remain extremely uncommon, it is necessary to consider this possibility when such types of renal tumors are encountered.