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Ao J.-Y.,Fudan University | Ao J.-Y.,Key Laboratory of Carcinogenesis and Cancer Invasion | Ao J.-Y.,Wenzhou University | Chai Z.-T.,Fudan University | And 17 more authors.
Tumor Biology

Robo1 is a member of the Robo immunoglobulin superfamily of proteins, and it plays an important role in angiogenesis and cancer. In this study, we investigate the role of roundabout 1 (Robo1) in tumor angiogenesis in hepatocellular carcinoma (HCC). Firstly, the relationship between Robo1 expression on tumors and patient’s survival and endothelial cells in tumor blood vessels and patient’s survival was studied. Secondly, Robo1 was overexpressed or knocked down in human umbilical vein endothelial cells (HUVECs). Cell proliferation, motility, and tube formation were compared in HUVEC with different Robo1 expression. Also, HUVECs with different Robo1 expression were mixed with HCCLM3 and HepG2 hepatoma cells and then implanted in a nude mouse model to examine the effects of Robo1 in endothelial cells on tumor growth and angiogenesis. Cell motility-related molecules were studied to investigate the potential mechanism how Robo1 promoted tumor angiogenesis in HCC. The disease-free survival of the patients with high Robo1 expression in tumoral endothelial cells was significantly shorter than that of those with low expression (P = 0.021). Overexpression of Robo1 in HUVECs resulted in increased proliferation, motility, and tube formation in vitro. In the implanted mixture of tumor cells and HUVECs with an increased Robo1 expression, tumor growth and microvessel density were enhanced compared with controls. Robo1 promoted cell division cycle 42 (Cdc42) expression in HUVECs, and a distorted actin cytoskeleton in HUVECs was observed when Robo1 expression was suppressed. In conclusion, Robo1 promoted angiogenesis in HCC mediated by Cdc42. © 2015, International Society of Oncology and BioMarkers (ISOBM). Source

Liu Z.,Shandong University | Liu Q.,Tianjin Medical University | Cai H.,Binzhou Medical College | Xu C.,Binzhou Medical College Affiliated Hospital | And 2 more authors.
Regulatory Peptides

Cerebral ischemia is one of the diseases that most compromise the human species. Therapeutic recovery of blood-brain barrier (BBB) disruption represents a novel promising approach to reduce brain injury after stroke. To determine the effects of calcitonin gene-related peptide (CGRP) on the BBB participate in stroke progression, rat cerebral ischemia reperfusion injury was induced by a 2-hour left transient middle cerebral artery occlusion (MCAO) using an intraluminal filament, followed by 46. h of reperfusion. CGRP (1 μg/ml) at the dose of 3 μg/kg (i.p.) was administered at the beginning of reperfusion. Subsequently, 48. h after MCAO, arterial blood pressure, infarct volume, water content, BBB permeability, BBB ultrastructure, levels of aquaporin-4 (AQP4) and its mRNA were evaluated. CGRP could reduce arterial blood pressure (P< 0.001), infarct volume (P< 0.05), cerebral edema (P< 0.01), BBB permeability (P< 0.05), AQP4 mRNA expression (P< 0.05) and AQP4 protein expression (P< 0.01). Furthermore, CGRP treatment improved ultrastructural damage of capillary endothelium cells and decreased the loss of the tight junction observed by transmission electronic microscopy (TEM) after 46. h of reperfusion. Our findings show that CGRP significantly reduced postischemic increase of brain edema with a 2-hour therapeutic window in the transient model of focal cerebral ischemia. Moreover, it seems that at least part of the anti-edematous effects of CGRP is due to decrease of BBB disruption by improving ultrastructural damage of capillary endothelium cells, enhancing basal membrane, and inhibiting AQP4 and its mRNA over-expression. The data of the present study provide a new possible approach for acute stroke therapy by administration of CGRP. © 2011 Elsevier B.V. Source

Zhang L.-L.,Binzhou Medical College Affiliated Hospital | Tang Q.,University of Arizona | Wang Z.,Cleveland Clinic | Zhang X.-S.,Binzhou Medical College
International Journal of Clinical and Experimental Pathology

Alveolar soft part sarcoma (ASPS) is a rare malignant soft tissue tumor, mainly localized in the extremities, occurring principally in adolescents and young adults. ASPS is uncommon in the female genital tract, and only 37 cases have been reported so far, including 9 cases in the uterine corpus and 17 cases in the uterine cervix. We here reported a case of ASPS occurring in the lower uterine segment. The case showed typical histological and immunohistochemical features. The patient had pelvic and para-aortic lymph node metastasis. To the best of our knowledge, it is the first such case described. Source

Ma X.,Shanghai University | Xia C.,Shanghai University | Liu D.,Binzhou Medical College Affiliated Hospital | Liu H.,Shanghai University | And 2 more authors.
International Journal of Clinical and Experimental Pathology

Purpose: To analyze the clinical data, MRI, pathological diagnosis, treatment and long-term effects of benign notochordal cell tumor (BNCT), a newly described novel spine tumor. Methods: We retrospectively studied 11 patients' clinical data of the above. Results: The ratio of males to females was 4:7, and the average age was 49.2 years (range, 18-74 years). Cervical vertebra (5; 38.5%) and thoracic vertebra (5; 38.5%) were the most frequent site followed by the lumbar vertebra (3; 23%). Pain was the main symptom except case 2 who were diagnosed accidently because of prostate cancer. The mean delay from first clinical symptoms to diagnosis was ranged from 2 months to 20 years. MRI showed all BNCTs were osteolytic lesions with hypointense on T1-weighted sequences, hyperintense on T2-weighted sequences. There were 4 vertebral bodies with wedge fracture. There were two cases that had two noncontiguous vertebral bodies with BNCT. In histology, marrow replacement was noted by multivacuolated physaliphorous cells immunoreactive for CK, EMA and S100 protein. All 10 cases except case 2 had vertebral reconstruction and fixation with different methods. Of the 11 patients, 9 had full follow-up data which showed no evidence of recurrence or metastasis without further treatment. Conclusion: Noncontiguous multi-centricity BNCTs are rare. No specific vertebrae are more frequently involved. Once BNCT is diagnosed by pathology, the surgical intervention is necessary for the patients with obvious clinical symptoms although it is benign. There is no evidence of BNCT recurrence or metastasis. Source

Guo W.,Binzhou Medical College Affiliated Hospital | Feng G.,Binzhou Medical College | Miao Y.,Binzhou Medical College | Liu G.,Binzhou Medical College | Xu C.,Binzhou Medical College Affiliated Hospital
Immunopharmacology and Immunotoxicology

Brain edema is a major consequence of cerebral ischemia reperfusion. However, few effective therapeutic options are available for retarding the brain edema progression after cerebral ischemia. Recently, rapamycin has been shown to produce neuroprotective effects in rats after cerebral ischemia reperfusion. Whether rapamycin could alleviate this brain edema injury is still unclear. In this study, the rat stroke model was induced by a 1-h left transient middle cerebral artery occlusion using an intraluminal filament, followed by 48h of reperfusion. The effects of rapamycin (250μg/kg body weight, intraperitoneal; i.p.) on brain edema progression were evaluated. The results showed that rapamycin treatment significantly reduced the infarct volume, the water content of the brain tissue and the Evans blue extravasation through the blood-brain barrier (BBB). Rapamycin treatment could improve histological appearance of the brain tissue, increased the capillary lumen space and maintain the integrity of BBB. Rapamycin also inhibited matrix metalloproteinase 9 (MMP9) and aquaporin 4 (AQP4) expression. These data imply that rapamycin could improve brain edema progression after reperfusion injury through maintaining BBB integrity and inhibiting MMP9 and AQP4 expression. The data of this study provide a new possible approach for improving brain edema after cerebral ischemia reperfusion by administration of rapamycin. © 2014 Informa Healthcare USA, Inc. Source

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