Chunyan Xia

High bone sialoprotein (BSP) expression correlates with increased tumor grade and predicts a poorer prognosis of high-grade glioma patients.

Objectives To investigate the expression and prognostic value of bone sialoprotein (BSP) in glioma patients. Methods We determined the expression of BSP using real-time RT-PCR and immunohistochemistry in tissue microarrays containing 15 normal brain and 270 glioma samples. Cumulative survival was calculated by the Kaplan-Meier method and analyzed by the log-rank test. Univariate and multivariate analyses were performed by the stepwise forward Cox regression model. Results Both BSP mRNA and protein levels were significantly elevated in high-grade glioma tissues compared with those of normal brain and low-grade glioma tissues, and BSP expression positively correlated with tumor grade (P<0.001). Univariate and multivariate analysis showed high BSP expression was an independent prognostic factor for a shorter progression-free survival (PFS) and overall survival (OS) in both grade III and grade IV glioma patients [hazard ratio (HR) = 2.549 and 3.154 for grade III glioma, and HR = 1.637 and 1.574 for grade IV glioma, respectively]. Patients with low BSP expression had a significantly longer median OS and PFS than those with high BSP expression. Small extent of resection and lineage of astrocyte served as independent risk factors of both shorter PFS and OS in grade III glioma patients; GBM patients without O6-methylguanine (O6-meG) DNA methyltransferase (MGMT) methylation and Karnofsky performance score (KPS) less than 70 points were related to poor prognosis. Lack of radiotherapy related to shorter OS but not affect PFS in both grade III and grade IV glioma patients. Conclusion High BSP expression occurs in a significant subset of high-grade glioma patients and predicts a poorer outcome. The study identifies a potentially useful molecular marker for the categorization and targeted therapy of gliomas.

Intravascular myopericytoma beside the shinbone: a rare histological variant

As a rare variant, intravascular myopericytoma has been documented1 2 3 4; however, to the best of our knowledge, an intravascular myopericytoma with a particular growth pattern that presented multiple nodules located in the pre-existing vessels has not been reported. The patient was a 50-year-old man who had had a pain in the antelateral region of his left leg for 5 years and this had been aggravated for more than 3 years. The patient recalled that the pain started from an accidental bump by an angular object in the region of the pain 5 years ago, and was relieved after rest. Medical treatment had not improved the pain. His medical history was otherwise unremarkable. A physical examination of the left leg revealed no obvious lump, and tenderness and percussion pain were positive. An MRI scan showed an irregular circumscribed mass beside …

Potentials of the elevated circulating miR-185 level as a biomarker for early diagnosis of HBV-related liver fibrosis

Early diagnosis of liver fibrosis is critical for early intervention and prognosis of various chronic liver diseases. Conventional repeated histological assessment is impractical due to the associated invasiveness. In the current study, we evaluated circulating miR-185 as a potential biomarker to predict initiation and progression of liver fibrosis. We found that miR-185 was significantly up-regulated in blood specimens from patients with HBV-liver fibrosis and rats with liver fibrosis, the miR-185 levels were correlated with liver fibrosis progression, but not with the different viral loads in HBV-infected patients. miR-185 was observed in collagen deposition regions during advanced liver fibrosis. We found that differences in miR-185 levels facilitated the discrimination between early-staged or advanced-staged liver fibrosis and the healthy controls with high specificity, sensitivity, and likelihood ratio using receiver-operator characteristic analysis. miR-185 targeted SREBF1, and increased expression of COL1A1 and a-SMA genes that are hallmarks of liver fibrosis. Our data supported that circulating miR-185 levels could be used as potential biomarkers for the early diagnosis of liver fibrosis.

miR‑27a suppresses the clonogenic growth and migration of human glioblastoma multiforme cells by targeting BTG2.

miR-27a and BTG2 are implicated in gliomagenesis and glioma progression. However, hitherto, a link between miR-27a and BTG2 in glioma has not been reported. In the present study, we investigated the effects of miR-27a on the proliferation and invasiveness of glioblastoma cells in vitro and in a mouse xenograft model and further studied the relation between miR‑27a expression and its target gene BTG2, which was identified by computation prediction algorithms. Our MTT and clonogenic assays showed that miR-27a overexpression significantly increased the clonogenic growth of glioblastoma U87MG and U251MG cells. The Transwell assays further revealed that miR-27a overexpression markedly increased the number of migrated U87MG and U251MG cells. TargetScan and other prediction algorithms identified BTG2 as a target gene of miR-27a, which was confirmed by EGFP reporter and immunoblotting assays showing an inverse relation between miR-27a expression and endogenous BTG2 expression. BTG2 overexpression also increased the proliferation and invasiveness of glioblastoma cells and BTG2 functioned downstream of miR-27a in modulating the proliferation and migration of glioblastoma cells. In conclusion, miR-27a modulates human glioblastoma growth and invasion by targeting BTG2.

Higher LRRFIP1 expression in glioblastoma multiforme is associated with better response to teniposide, a type II topoisomerase inhibitor.

Previous studies from this laboratory indicated that microRNA-21 (miR-21) contributes to chemoresistance of glioblastoma multiforme (GBM) cells to teniposide, a type II topoisomerase inhibitor. We also showed that LRRFIP1 is a target of miR-21. In this study, we found that higher baseline LRRFIP1 expression in human GBM tissue (n=60) is associated with better prognosis upon later treatment with teniposide. Experiments in cultured U373MG cells showed enhanced toxicity of teniposide against U373MG cells transfected with a vector that resulted in LRRFIP1 overexpression (vs. cells transfected with control vector). Experiments in nude mice demonstrated better response of LRRFIP1 overexpressing xenografts to teniposide. These findings indicate that high baseline LRRFIP1 expression in GBM is associated with better response to teniposide, and encourage exploring LRRFIP1 as a target for GBM treatment.

An unusual skull lesion in a post-liver transplant patient.

A 40-year-old female, who had a history of chronic hepatitis B virus infection for 12 years, was diagnosed with primary hepatocellular carcinoma (HCC) in May 2005. The mass was in the left lobe of the liver, with 4 cm in diameter. She then underwent liver transplantation. After transplantation, she received standard immunosuppression regimen including tacrolimus, mycophenolate mofetil and corticosteroids. She was well with regular follow-up, and had no sign of recurrence. However, in a routine laboratory examination in February 2006, her serum concentration of a-foetoprotein (AFP) was 11 850 mg/L. A painless parietal mass was found by her at the same time. She was then admitted to the department of neurosurgery. Cranial computerized tomography (CT) and magnetic resonance imaging (MRI) scans revealed a 4.0 4.0 4.0 cm, dumb-bell shaped, well-defined, parenchymal, and osteolytic parietal mass with bone and duramater involvement, no perilesional reactive hyperostosis was found (Fig. 1A). Radionuclide bone imaging (isotope: 99mTc-HMDP) showed abnormal high uptake in the parietal bone. The lesion was suspected as metastases of HCC. We did not find any abnormality in either lung or grafted liver by chest and abdominal CT scans. In February 2006, the patient was referred to surgery. Tumour was completely removed including the invaded dural mater and adjacent bone. The dural mater and the skull were rebuilt with artificial tissue. The pathological findings confirmed a diagnosis of metastasis HCC (Fig. 1B). Immunohistochemistry showed the tumour to be strongly positive for AFP (Fig. 1C). After post-operative symptomatic treatment and gamma knife radiotherapy, the patient recovered well. She was still alive after 29 months of follow-up.