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ABSTRACT: In our previous study, we detected decreased expression of phospho-Smad1/5/8 and its upstream signaling molecule, bone morphogenetic protein receptor IB subunit (BMPR-IB), in certain glioblastoma tissues, unlike normal brain tissues. In order to clarify the functional roles and mechanism of BMPR-IB in the development of glioblastoma, we studied the effects of BMPR-IB overexpression on glioblastoma cell lines in vitro and in vivo.
We selected glioblastoma cell lines U251, U87, SF763, which have different expression of BMPR-IB to be the research subjects. Colony formation analysis and FACS were used to detect the effects of BMPR-IB on the growth and proliferation of glioblastoma cells in vivo. Immunofluresence was used to detect the differentiation changes after BMPR-IB overexpression or knocking-down. Then we used subcutaneous and intracranial tumor models to study the effect of BMPR-IB on the growth and differentiation of glioblastoma cells in vivo. The genetic alterations involved in this process were examined by real-time PCR and western blot analysis.ed.
Forced BMPR-IB expression in malignant human glioma cells, which exhibit lower expression of BMPR-IB, induced the phosphorylation and nuclear localization of smad1/5/8 and arrested the cell cycle in G1. Additionally, BMPR-IB overexpression could suppress anchorage-independent growth and promote differentiation of theses glioblastoma cells. Furthermore, overexpression of BMPR-IB inhibited the growth of subcutaneous and intracranial tumor xenografts and prolonged the survival of mice injected intracranially with BMPR-IB-overexpressing glioblastoma cells. Conversely, inhibition of BMPR-IB caused SF763 malignant glioma cells, a line known to exhibit high BMPR-IB expression that does not form tumors when used for xenografts, to show increased growth and regain tumorigenicity in a nude mouse model system, ultimately shortening the survival of these mice. We also observed significant accumulation of p21 and p27kip1 proteins in response to BMPR-IB overexpression. Our study suggests that overexpression of BMPR-IB may arrest and induce the differentiation of glioblastoma cells due to upregulation of p21 and p27kip1 in vitro and that in vivo and decreased expression of BMPR-IB in human glioblastoma cells contributes to glioma tumorigenicity. BMPR-IB could represent a new potential therapeutic target for malignant human gliomas.
Journal of Experimental & Clinical Cancer Research 05/2012; 31:52. · 2.15 Impact Factor
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ABSTRACT: Recently, robotic systems have been introduced as a useful method for surgical procedures. But in the field of vascular interventional therapy, the development of robotic system is slower.
The purpose of the study is to verify the reliability and safety of vascular interventional robotic system used in angiography, by the way of in vitro preliminary experiments and animal experiments.
The approach is to employ a proprietary vascular interventional robot system to complete glass vessel models and animal angiogram experiments. This robot system consists of a console port (remote steering system), an assistant port (propelled and rotation system) and a hydraulic fixing device, upon which surgeons control remotely to make go forward and rotate in the glass vessel models and animal vessels, on the 3D operation interface. Consequently, the operation time and success rate are counted and evaluated.
In the glass vessel model experiments, the Catheter can enter various kinds of vessel models with inside diameter length greater than 3mm and angle less than 90(o). In the animal (adult dogs) experiments, surgeons can accomplish smoothly the angiogram of the renal artery, the vertebral renal and the arteria carotis communis, without any complications of surgery.
The angiogram by using vascular interventional robot system is safe and reliable. Surgeons can finish the angiogram in part by remote operation, and the result of angiogram can meet a number of simple expectations. However without wire control and force feedback systems, the applicability of this kind of robot system is not flexible enough and need to be improved in the future.
The Open Medical Informatics Journal 01/2011; 5(Suppl 1):46-9.
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Shuang Liu, Zengmin Tian,
Feng Yin,
Peng Zhang,
Yanrui W,
Xuefeng Ding,
Haitao Wu,
Yan Wu,
Xiaozhong Peng,
Jiangang Yuan,
Boqin Qiang,
Wenhong Fan,
Ming Fan
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ABSTRACT: Here we report the negative correlation of phosphorylation of Smad1 and BMPR-IB expression with the development of human glioma. Western blot analysis showed that expression of both phospho-Smad1/5/8 and BMPR-IB were decreased in malignant glioma tissues compared with normal brain tissues. Kaplan-Meier survival curves revealed that lower expression ratio of phospho-Smad1/5/8 to Smad1 expression significantly correlates with poor patient survival. Transient transfection of BMPR-IB activates Smad1 signaling and induces differentiation and apoptosis of U251 and U87 glioblastoma cells. The effects could be blocked by cotransfection of Smad6. These results might provide new molecular marker and target for glioma diagnosis and therapy.
Cancer Investigation 07/2009; 27(7):734-40. · 1.85 Impact Factor
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ABSTRACT: Mature dopaminergic neurons were generated from human fetal mesencephalic progenitors by co-culture with human fetal striatal-conditioned media (SCM) and exposure to lowered oxygen. Immunofluorescence analysis showed that cells cultured in differentiation media with embryonic SCM had a greater number of TH-positive neurons than those cultured in traditional media without SCM addition. The TH-positive neurons cultured in lowered oxygen (3-5% O(2)) had more branches and those branches were longer than those of neurons cultured under 20% O(2) culture conditions. Furthermore, more TH-positive cells with mature morphology were observed in the culture containing combined SCM addition and lowered oxygen. We also observed higher levels of dopamine release under the combined media conditions than observed under any individual media condition when depolarized by high K+ as determined by high-performance liquid chromatography (HPLC). Reverse transcription-polymerase chain reaction (RT-PCR) analyses showed that mRNA expressions of sonic hedgehog (SHH), glial cell derived neurotrophic factor (GDNF) and tyrosine hydroxylase (TH), which are linked to the generation of dopaminergic neurons, were increased after co-culture with SCM. Lowered O(2) significantly induced mRNA expression of erythropoietin (EPO) and P27, which affect neuronal differentiation, and was accompanied by upregulation of Nurr1, Pitx3 and dopamine transporter (DAT) mRNAs, which are correlated to the maturation of dopaminergic neurons. This study makes an important contribution to understanding the effects of hypoxia and SCM on the differentiation and maturation of TH-positive neurons derived from human fetal mesencephalic progenitors in vitro.
Brain research bulletin 06/2009; 80(1-2):62-8. · 2.18 Impact Factor
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ABSTRACT: To assess the clinical usefulness, accuracy, and safety of telemanipulation for frameless stereotactic surgery using the CAS-BH5 robot system, we prospectively evaluated 10 patients (age: 5-79 years; mean: 44 years) who underwent telemanipulation frameless stereotactic operations from September to December 2005. The CAS-BH5 robot system consists of three main parts: a planning subsystem, a surgical localization subsystem, and a telemanipulation subsystem. Specifically, CAS-BH5 is capable of network communication, video transmission, graphic simulation and human-machine interaction, and thus facilitates remote planning and transmission of neuronavigation data, monitoring and manipulating. Telemanipulation was performed via a digital data network with a speed of 2,000 kilobytes per second by a neurosurgeon in Beijing while the patients were located in Yan'an, 1,300 km away. Remote fiducial registration was performed with a mean accuracy of 1.05 mm and the standard difference between the planned and actual trajectory was 0.13 mm. The mean time from fiducial registration to closure was 30.2 +/- 1.66 min. At 12-month follow-up, 90% of patients had improved neurologically. There were no complications. This preliminary data indicates that telemanipulation in frameless stereotactic surgeries is feasible, reliable and safe. In the future, we believe that telemanipulation will facilitate collaboration between surgeons, enhance training, allow for sharing of resources, and have wide applications in the field of neurosurgery.
Stereotactic and Functional Neurosurgery 02/2008; 86(1):54-61. · 1.85 Impact Factor
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Medical Imaging and Informatics, 2nd International Conference, MIMI 2007, Beijing, China, August 14-16, 2007, Revised Selected Papers; 01/2007
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ABSTRACT: A computer and robot assisted telesurgical system for stereotactic neurosurgery is presented in this paper. Using the user friendly interface for surgical planning, the surgeons can make the surgical planning on the model reconstructed in the computer, and marker registration is used to create the mapping between the patient's head and the 3D-brain model. When appropriate entrance position on the skull and entrance trajectory are determined through the surgical planning, they are exported to remote physical medical robotic system, via the Internet, for real-world execution. Remote robotic system is not only used as a navigational tool to direct the surgery planning, but also used as an instrument platform to assist surgeons to accomplish the operation. This computer and robot assisted tele-neurosurgery system has been successfully used in clinical application.
Intelligent Robots and Systems, 2003. (IROS 2003). Proceedings. 2003 IEEE/RSJ International Conference on; 11/2003
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ABSTRACT: Multiple subpial transection (MST) is one approach to the surgical treatment of intractable epilepsy with epileptogenic lesion located in functional areas. To verify the effect of MST, an experimental study was performed first, followed by clinical application.
On the basis of the experimental study, MST was performed in 200 intractable epileptic patients from 1991 to 2000. Of them, 80 cases underwent MST only while 120 others underwent MST combined with other techniques, such as corpus callosotomy, temporal lobectomy and focus resection. A series of modifications of the surgical techniques were made.
The results of the experimental study indicated that MST could inhibit the formation and spreading of epileptic discharge and limit the damage to neurons in a minimal area on the epileptogenic agent injected cortex. MST does not impair major functions of the cortex. After the clinical application and modifications, 160 patients were followed up for 1 to 8 years. Complete control of seizure was obtained in 100 cases (62.5%), significant reduction (more than 75%) in 32, reduction (more than 50%) in 20 and no change in 8. The total rate of effectiveness was 95.0%, and the significant rate of effectiveness was 82.5%. No functional defects were found in any patients.
The results indicate that MST is an effective approach to the surgical treatment of intractable epilepsy. MST can be combined with other approaches. The outcome of the subdivision of the MST only group indicates that MST on local epileptogenic lesion without structural changes is as effective as that of the combined operation group. To evade hemispheric disturbance, MST should be done first to avoid severe complications. Hemispherectomy should be performed only on poor effected cases of MST.
Chinese medical journal 08/2003; 116(7):1004-7. · 0.86 Impact Factor
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ABSTRACT: This paper introduces the research project of robot assisted minimally invasive neurosurgery. Using visualization technology, the system reconstructs and displays the 3D model of the patient's inner structure in the computer. Thus the surgeons can plan the surgery on the model in the computer. Marker registration is used to create the mapping between the patient's head and the 3D-brain model. Robot arm is used as a navigator to direct the surgery planning and as an instrument platform to assist surgeons to accomplish the operation. The results of the clinical application are given to show that the robotic system is effective.
Robotics and Automation, 2001. Proceedings 2001 ICRA. IEEE International Conference on; 02/2001
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Proceedings of the 2001 IEEE International Conference on Robotics and Automation, ICRA 2001, May 21-26, 2001, Seoul, Korea; 01/2001
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ABSTRACT: Telesurgery is an interdisciplinary field of teleoperated robotics and robot-assisted minimally invasive surgery, and has good promising future. In this work, the structure and work flow of the tele-neurosurgery are addressed at first. Then the key technologies involved, including our newly developed surgical robot, untouched methodology in localizing marks for registration, video overlay and surgical simulation, video transmission and network communication, and safeguards, are discussed, which guarantee the safety and feasibility of the clinical telesurgery. In the end, the first remote clinical stereo tactic neurosurgery is presented.
Robotics and Automation, 2004. Proceedings. ICRA '04. 2004 IEEE International Conference on;
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ABSTRACT: This work introduces a robot system for minimally invasive frameless stereotactic neurosurgery. The system consists of a robot arm for precise positioning of surgical tools, a vision system for intro-operative registration, and a preoperative planning system. The robot is a custom designed accurate arm with five degree-of-freedom. The vision system uses two cameras to automatically generate the target position of the robot The robot can be controlled autonomously as well as interactively through an intuitive way. Experiments and clinical trials approve the robot system is effective and powerful.
Robotics and Automation, 2004. Proceedings. ICRA '04. 2004 IEEE International Conference on;
