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Zhang X.,Shandong University | Fang A.,Traffic Hospital of Shandong Province | Li P.,Shandong University | Li Z.,Shandong University | And 4 more authors.
PLoS ONE | Year: 2015

Resistance to cisplatin-based chemotherapy is a major cause of treatment failure in advanced bladder cancer (BC) patients. There is increasing evidence that microRNAs are involved in the development and progression of BC. However, little is known about the function of microRNAs in predicting the effect of adjuvant chemotherapy on BC survival and regulating response to cisplatin. To address this issue, we employed RT-qPCR to evaluate the clinical significance of miR-203 expression in 108 tissues of BC patients receiving cisplatinbased adjuvant chemotherapy, and performed in vitro studies to explore chemotherapeutic sensitivity to cisplatin in miR-203 overexpressing BC cells. We found miR-203 levels were significantly lower in BC progression group than non-progression group (P<0.001). ROC curve analysis illustrated miR-203 could significantly distinguish progressed patients from those without progression (P<0.001), yielding an area under the ROC curve of 0.839 (95% CI, 0.756-0.903). Moreover, low miR-203 expression correlated with shortened progression free survival (PFS) and overall survival (OS) of BC patients, and was an independent prognostic factor. Overexpression of miR-203 in 5637 and T24 BC cells could decrease cell viability, enhance cisplatin cytotoxicity, and promote apoptosis. Western blotting and luciferase reporter assay showed Bcl-w and Survivin were direct downstream targets of miR-203. There was also a significant inverse association between miR-203 and Bcl-w or Survivin expression in BC tissues (r = -0.781, -0.740, both P<0.001). In conclusion, decreased miR-203 predicts progression and poor prognosis for BC patients treated with cisplatin-based chemotherapy while miR-203 overexpression can enhance cisplatin sensitization by promoting apoptosis via directly targeting Bcl-w and Survivin. © 2015 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Source

Zhang Y.,Nanjing Medical University | Sun W.,Traffic Hospital of Shandong Province | Zhang F.,Nanjing Medical University | Huang J.,Nanjing Medical University | Fan Z.,Nanjing Medical University
Experimental and Therapeutic Medicine | Year: 2013

Pancreaticobiliary maljunction (PBM) is an unusual anomalous condition in which the pancreatic duct and bile duct merge outside the duodenal wall and form a long common channel. Pancreas divisum (PD) is a congenital anomaly in which the dorsal and ventral pancreatic ducts fail to fuse. Endoscopic retrograde cholangiopancreatography (ERCP) is the gold standard for diagnosing PD and magnetic resonance cholangiopancreatography (MRCP) is the non-invasive choice. In this study, four cases of patients with unusual PBM in addition to PD are described. The patients presented with abdominal pain, which was caused by distal biliary stricture diagnosed by MRCP. The patients received ERCP and had a good prognosis. Source

Zhang X.,Shandong University | Fang A.,Traffic Hospital of Shandong Province | Wang J.,Shandong University | Yang Y.,Shandong University | And 3 more authors.
Oncotarget | Year: 2016

High recurrence rates of non-muscle invasive bladder cancer (NMIBC) in patients require lifelong testing and monitoring. The aim of this study is to develop a simplified RT-qPCR method (RT-qPCR-D) which directly quantifies cell-free miR-155 in urine without RNA extraction, and assess it as a potential tool in NMIBC detection. A pilot study including 60 urine samples was used to investigate the feasibility of RTqPCR- D in detecting cell-free miR-155. Then, miR-155 levels were quantified in a large independent cohort of urine from 162 NIMBC patients, 76 cystitis patients, and 86 healthy donors using the RT-qPCR-D method. Changes of cell-free miR-155 before and after operation were also analyzed in 32 NIMBC patients. In pilot study, we found a significant linear association between RT-qPCR and RT-qPCR-D in urinary miR-155 detection. Both methods showed cell-free miR-155 were significantly increased in NMIBC patients, and could reflect their expression in tissues. Then, the increased expression of cell-free miR-155 was successfully validated in 162 NIMBC patients when compared with cystitis patients and healthy donors. Moreover, it distinguished NMIBC patients from others with 80.2% sensitivity and 84.6% specificity, which was superior to urine cytology. Cell-free miR-155 correlated with NMIBC stage and grade, and was an independent factor for predicting recurrence and progression to muscle invasion. In addition, cell-free miR-155 was significantly decreased after NMIBC patients underwent transurethral bladder resection. In conclusion, detection of cell-free miR-155 in urine using RT-qPCR-D is a simple and noninvasive approach which may be used for NMIBC diagnosis and prognosis prediction. Source

Yang H.,Shandong University | Yang H.,Xintai People Hospital Affiliated to Taian Medical University | Lu Y.,Traffic Hospital of Shandong Province | Ma S.,Shandong University | And 4 more authors.
Journal of Stroke and Cerebrovascular Diseases | Year: 2015

Ischemic stroke is one of the leading causes of morbidity and mortality worldwide and characterized by defective angiogenesis. The functional sequences (RGDs, GRGDSPASSPISC) derived from fibronectin have been confirmed to augment angiogenesis in vivo and in vitro. However, delivery of peptides into the brain parenchyma has been hampered by the presence of the blood-brain barrier (BBB). We fused RGDs with penetratin (Antp) derived from Drosophila antennapedia homeodomain protein to improve the penetration of peptides through BBB into ischemic hemisphere. We found Antp-RGDs successfully not only penetrate the SH-SY5Y cells but also penetrated through BBB into ischemic hemisphere by intraperitoneal injection. In addition, application of Antp-RGDs to the focal cerebral ischemic reperfusion injury in rats resulted in the reduction of cerebral ischemic volume and the improvement of neurologic score according to the 21-point score. We further demonstrated that activation of phosphorylation-extracellular-signal related kinase 1/2 (p-ERK 1/2) and upregulation of gene VEGF resulted from post-treatment with Antp-RGDs 2 hours after reperfusion onset might at least partly contribute to the benefic changes after focal cerebral ischemic reperfusion injury in rats. Our data suggested that Antp-RGDs may serve as an attractive therapeutic intervention for treating ischemic stroke. © 2015 National Stroke Association. Source

Guan Y.-Y.,Traffic Hospital of Shandong Province | Song C.,Traffic Hospital of Shandong Province | Lei P.-S.,Peking Union Medical College
Journal of Asian Natural Products Research | Year: 2014

In order to simplify the synthesis of OSW-1's disaccharide side chain and explore the structure-activity relationship of OSW-1, three 16α-O-maltose OSW-1 analogs carrying three maltose side chains bearing different protections were designed and synthesized. © 2013 Taylor & Francis. Source

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