ABSTRACT
High grade gliomas are always the research focus in the field of neurosurgery due to their poor prognosis despite the current standard therapeutic regimen of surgical resection followed by radiation therapy and chemotherapy.Alkylating agent temozolomide has been established as the standard chemotherapy while its resistance inevitable during treatment.This phenomenon seriously influences the prognosis of patients suffering from high grade gliomas.This review aims to elucidate temozolomide chemoresistance mechanisms through three chapters including O6-methylguanine-DNA methyltransferase (MGMT) methylation,mismatch repair mutation and epigenetic regulation consisting of p21,chromatin and histone,Y-box binding protein-1 and microRNAs.
ABSTRACT
<p><b>OBJECTIVE</b>To analyze retrospectively the clinical symptoms, signs, radiological findings and results of treatment of posttraumatic syringomyelia.</p><p><b>METHODS</b>The data of 7 patients with posttraumatic syringomyelia confirmed by computerized tomography (CT) and magnetic resonance imaging (MRI) in our hospital between 1999 and 2004 were reviewed retrospectively. The patients underwent decompressive laminectomy or syringo-subarachnoid (S-S) shunting with microsurgery. Long-term follow-up was available (range: 13-65 months).</p><p><b>RESULTS</b>The major clinical manifestations of posttraumatic syringomyelia usually included the onset of increasing signs and the development of new symptoms after an apparently stable period. The clinical symptoms included pain, sensory disturbance, weakness, and problems in autonomic nerves. Syrinx existed merely at the cervical level in 4 cases and extended downward to the thoracic levels in the other 3 cases. One case underwent decompressive laminectomy, 6 cases were treated by S-S shunting. During the early postoperative period, all the patients showed an improvement of symptoms of syrinx without major complication or death. The decreased size or collapse of the syrinx was demonstrated by postoperative MRI.</p><p><b>CONCLUSIONS</b>Posttraumatic syringomyelia is a disabling sequela of spinal cord injury, developing months to years after spinal injury. MRI is the standard diagnostic technique for syringomyelia. The patients with posttraumatic syringomyelia combined with progressive neurological deterioration should be treated with operations. S-S shunting procedure is effective in some patients with posttraumatic syringomyelia. Decompressive procedure may be an alternative primary surgical treatment for patients with kyphosis and cord compression.</p>
Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Decompression, Surgical , Methods , Laminectomy , Magnetic Resonance Imaging , Retrospective Studies , Spinal Cord Injuries , Syringomyelia , General Surgery , Tomography, X-Ray ComputedABSTRACT
<p><b>OBJECTIVE</b>To investigate the therapeutic effect of Bcl-2 fusion protein on apoptosis in brain following traumatic brain injury.</p><p><b>METHODS</b>Bcl-2 gene was cloned by RT-PCR. Bcl-2 and EGFP genes were linked together and inserted into pAdeno-X vector. This recombinant vector was packaged into infectious adenovirus in HEK293 cells. Ninety Wistar rats were assigned randomly into experimental group (n=45) and control group (n=45). All rats were subjected to traumatic brain injury. Then recombinant adenovirus (for experimental group) or saline (for control group) was injected into the traumatic brain. The expression of Bcl-2 fusion protein was investigated by Western blotting, immunohistochemistry and fluorescence microscopy. Apoptosis in the injured brain was studied by TUNEL. Animals' behavior capacity was evaluated by tiltboard test.</p><p><b>RESULTS</b>In the experimental group, many fluorescent cells were found around the traumatic locus, which were also proven to be Bcl-2 positive by immunohistochemistry. On the contrary, few Bcl-2 positive cells and no fluorescent cell were detected in the control group. Bcl-2 expression of experimental group was much higher than that of control group, which was illustrated by Western blotting. The apoptosis index of experimental group was 0.027+/-0.005, and that of control group was 0.141+/-0.025 (P < 0.01). Two weeks after injury, animals of the experimental group behaved better than those of the control group.</p><p><b>CONCLUSIONS</b>A recombinant adenovirus vector expressing Bcl-2 fusion protein has been constructed. Bcl-2 fusion protein can suppress apoptosis and promote cell survival. Moreover, the behavior recovery of the injured animal is promoted. Bcl-2 fusion protein provides a way to track the target cells in vivo.</p>