The deregulation of microRNAs has been reported to play a pivotal role in hepatocellular carcinoma (HCC). MiR-126-3p has been reported to be associated with poor prognosis in HCC. However the underlying mechanism of miR-126-3p in HCC remains unclear. The expression levels of miR-126-3p in HCC tissues and cells were detected by RT-PCR. Transwell assay and capillary tube formation assay were applied to assess the metastasis and angiogenesis in vitro. Nude mice subcutaneous tumor model was used to perform in vivo study. Dual- luciferase reporter assay was conducted to confirm the direct binding of miR-126-3p and target genes. The changes of biomarker protein levels were examined by western blot and Immunohistochemistry. We observed that the miR-126-3p expression levels in HCC tissues and cells were significantly down-regulated. Through gain- and loss- of function studies, we showed that miR-126-3p dramatically inhibited HCC cells from migrating and invading extracellular matrix gel and suppressed capillary tube formation of endothelial cells in vitro. Furthermore, overexpression of miR-126-3p significantly reduced the volume of tumor and microvessel density in vivo. LRP6 and PIK3R2 were identified as targets of miR-126-3p. Silencing LRP6 and PIK3R2 had similar effects of miR-126-3p restoration on metastasis and angiogenesis individually in HCC cells. Furthermore, the miR-126-3p level was inversely correlated with LRP6 and PIK3R2 in HCC tissues. In addition, the rescue experiments indicated that the metastasis and angiogenesis functions of miR-126-3p were mediated by LRP6 and PIK3R2. Our results demonstrates that deregulation of miR-126-3p contributes to metastasis and angiogenesis in HCC. The restoration of miR-126-3p expression may be a promising strategy for HCC therapy.

Hypoxia is a common feature of solid tumors, including HCC. And hypoxia has been reported to play an important role in HCC progression. However, the potential mechanism of miRNAs in hypoxia mediating HCC progression still remains unclear. The HCC cells were cultured in the atmosphere of 1 % oxygen to induce hypoxia. The microRNA microarray was employed to search for the hypoxia-inducible miRNAs. RT-PCR, western blot and immunohistochemistry were used to detect the RNA and protein levels. HUVEC were applied to explore the angiogenesis level. We found that miR-182 was upregulated in the hypoxia-based microarray. We then revealed that miR-182 was also significantly increased in the HCC tissues compared to the corresponding normal tissues. In vitro capilliary tube formation assays showed that the miR-182 promoted angiogenesis. RASA1 was demonstrated as the direct target of miR-182. In addition, the suppression of RASA1 phenocopied the pro-angiogenesis effects of miR-182. Besides, RASA1 was also decreased in the hypoxia HCC cells while the inhibition of miR-182 partially restored the level of RASA1. Our data showed that hypoxia regulated the expression of miR-182 and RASA1 to promote HCC angiogenesis.

Interleukin enhancer binding factor 2 (ILF2), a transcription factor, regulates cell growth by inhibiting the stabilization of mRNA. Currently, its role has gained recognition as a factor in the tumorigenic process. However, until now, little has been known about the detailed role ILF2 plays in hepatocellular carcinoma (HCC). In this study, we investigated the expression levels of ILF2 in HCC tissue with Western blot and immunohistochemical assays. To examine the effect of ILF2 on liver cancer cell growth and apoptosis, small interfering RNAs (siRNAs) targeting ILF2 were recombined to create lentiviral overexpression vectors. Our results showed higher expression levels of ILF2 mRNA and ILF2 protein in HCC tissue compared with matched peritumoral tissue. Expression of ILF2 may regulate cell growth and apoptosis in liver cancer cells via regulation of B-cell lymphoma 2 (Bcl-2), Bcl-2 related ovarian killer (Bok), Bcl-2-associated X protein (BAX), and cellular inhibitor of apoptosis 1 (cIAP1). Moreover, we inoculated nude mice with liver cancer cells to investigate the effect of ILF2 on tumorigenesis in vivo. As expected, a rapid growth was observed in cancer cells inoculated with a lentiviral vector coding Flag-ILF2 (Lenti-ILF2) compared with the control cells. Hence, these results promote a better understanding of ILF2’s potential role as a therapeutic target in HCC.

In spinal degenerative disease, an injectable liquid hydrogel can fill in defect entirely, lessen the danger of implant relocation and following loss of disc height, minimizing the operative trauma. Here, we propose an injectable in-situ chemically cross-linked hydrogel by a two-component reaction of liquid silk fibroin with liquid polyurethane at physiological temperature conditions. Confined compression tests and fatigue tests were reported to assess physical properties of the hydrogel. Impact of different diameter on the biomechanical behaviours was tested to evaluate the clinical potentiality of the hydrogel for replacing nucleus pulposus. Degradation behaviours in different solutions and animal experiments were also investigated to examine the tissue biocompatibility of the hydrogel. The hydrogel modulus was affected by the hydrogel geometrical (diameter) parameters. SF/PU composite hydrogel can survive a million cycles, unconstrained fatigue resistance. More importantly, in vivo biocompatibility using New Zealand white rabbits, showed good biocompatibility over a three-month period in culture. Particularly, they showed the significant clinical merit of providing stronger axial compressive stiffness on confined compression test. Based on the outcomes of the present research, the SF/PU composite hydrogel may provide significant advantages for use in future clinical application in replacing nucleus pulposus field.

To date, only 20 cases of Epstein-Barr virus (EBV)-associated intrahepatic cholangiocarcinomas (IHCCs) have been reported in the literature.Pathology records of IHCC from January 1, 2007 to December 31, 2013 were retrieved from our hospital. Clinical information related to EBV-associated IHCC were also obtained, including gender, age at initial diagnosis, tumor size, tumor-node-metastasis stage, and follow-up duration. Surgically resected stage-matched EBV-negative IHCCs with full follow-up were selected for comparison. All liver specimens were fixed in 10% neutral-buffered formalin and paraffin-embedded tissue blocks containing cholangiocarcinoma and nonneoplastic liver tissue. Hematoxylin and eosin-stained sections were present in all cases.Among 329 primary IHCC patients, intranuclear expression of EBV was only found in 11 patients (3.3%), with an age range of 30 to 67 years (mean, 53.2 years; median, 54 years). The group consisted of 4 male and 7 female patients (M:F ratio 1:1.8). Histopathological analysis showed 1 case (9.1%) belonged to the typical lymphoepithelioma-like carcinoma (LELC), primarily composed of undifferentiated tumor cells intimately admixed with abundant lymphoplasmacytic cells. Two cases (18.2%) belonged to the conventional-type IHCCs, showing irregularly shaped neoplastic glands and scattered lymphoplasmacytic infiltration. The remaining 8 cases (72.7%) belonged to the lymphoepithelioma-like cholangiocarcinomas (LELCCs), showing varied glandular differentiation and dense lymphoplasmacytic infiltration. The overall survival of EBV-positive IHCCs was not significantly different from that of EBV-negative IHCCs (P = 0.512).Our data demonstrate that EBV-associated IHCC is very rare and may be subclassified into 3 different pathological types including LELC, conventional-type IHCC and LELCC on the basis of the tumor cellular differentiation, and host cellular immune responses in the tumors. The etiological, clinical, pathological, and molecular features are needed to be future studied by multicentric efforts in recruiting more EBV-associated IHCC patients.

Schwannomas are mesenchymal tumors originating from Schwann cells in peripheral nerve sheaths. Although the tumor can be located in any part of the human body, the most common locations are the head, neck, trunk and extremities. Pancreatic schwannomas are rare. To our knowledge, only 64 cases of pancreatic schwannoma have been reported in the English literature over the past 40 years. In this paper, we present a pancreatic schwannoma in a 59-year-old female. Ultrasound, computed tomography and magnetic resonance imaging revealed the tumor located in the pancreatic body; however, accurate diagnosis was hard to obtain preoperatively and a pancreatic cystadenoma was preliminarily considered. During laparotomy, the mass was found in the body of the pancreas. An enlarged gallbladder with multiple stones was also observed. We performed central pancreatectomy, end-to-side pancreaticojejunostomy and cholecystectomy. Notably, central pancreatectomy has been reported in only one case prior to this report. The gross specimen showed a mass with a thin capsule, 1.6 cm × 1.1 cm × 1.1 cm in size. Microscopic examination showed that the tumor was mainly composed of spindle-shaped cells with palisading arrangement and no atypia, which is consistent with a benign tumor. Both hypercellular and hypocellular areas were visible. Immunohistochemical staining revealed strongly positive results for protein S-100. Finally, the tumor was diagnosed as a schwannoma of the pancreatic body. Postoperatively, the patient recovered well and left the hospital 6 d later. During the 53-mo follow-up period, the patient remained well and free of complications.