IDH mutations predict longer survival and response to temozolomide in secondary glioblastoma.

Recent studies have shown that isocitrate dehydrogenase 1/2 (IDH1/2) mutations occur frequently in secondary glioblastoma. This study aimed to investigate their impact on temozolomide chemosensitivity and relationship with O(6)-methylguanine DNA methyltransferase (MGMT) promoter methylation in secondary glioblastoma. Searches for IDH1 and IDH2 mutations, 1p19q codeletion, MGMT promoter methylation, and p53 expression were carried out in a series of 86 secondary glioblastomas and correlated with progression-free survival and overall survival. Response to temozolomide was evaluated by progression-free survival, as well as by tumor size on successive MRI scans, then correlated with molecular alterations. IDH (IDH1 or IDH2) mutations were found in 58/79 patients (73.4%). IDH mutation, MGMT promoter methylation, and 1p19q codeletion were associated with prolonged progression-free survival in univariate (P < 0.001, P < 0.001, P = 0.003, respectively) and multivariate analysis (P < 0.001, P < 0.001, P = 0.035, respectively). IDH mutation (P = 0.001) and MGMT promoter methylation (P = 0.011) were correlated with a higher rate of objective response to temozolomide. Further analysis of response to temozolomide showed that patients with both IDH mutation and MGMT promoter methylation had the best response rate to temozolomide. IDH mutation appears to be a significant marker of positive chemosensitivity in secondary glioblastoma. Use of IDH status combined with MGMT promoter status as a stratification factor seems appropriate in future clinical trials involving temozolomide for the treatment of patients with secondary glioblastoma.

Effects of brain-derived neurotrophic factor on healing of tibial fracture of rats / 中国组织工程研究

BACKGROUND: Recently, there are some researches show that the nutrition and control of nervous system play an important role in the growth of bone and healing of bone fracture.OBJECTIVE: To probe into the effects of brain-derived neurothophic factor on bone fracture healing and its biomechanic features.DESIGN: Randomized controlled study of experiment animals.SETTING: Traumatic orthopaedic and hematology department of a military medical university.MATERIALS: There were 16 SD rats with transverse fracture of shin,which were set up as intramedullary nail internal fixation. They were randomly divided into experiment group and control group with each of 8 mice.INTERVENTIONS: Rats in the experiment group were taken subcutaneous injection of brain derived neurotrophic factor(BDNF) every other day while control group was injected of saline. The shin of mice was collected to observe in the 2nd, 3rd, 4th and 5th weeks.MAIN OUTCOME MEASURES: Gross comparison of fracture healing of each group, biomechanical test and electro microscopic observation.RESULTS: It can be seen by gross observation 2 weeks after operation that the fracture area was linked by connective tissue in both groups and there was obvious movement. In the 3rd week, woven like bone healing could be seen in the experiment group whereas there was obvious fracture end movement in the control group. In the 4th week, bone healing could be seen in both groups, but the bone callus in the experiment group was much smaller with mild angled malformation. In the 5th week, the fracture line in the experiment group already disappeared and the molding of bone fracture was good while there was bigger bone callus in fracture end of the control group. The angle formed by sagittal planes of fracture in the 3rd, 4th and 5th week was(25.00 ± 1.82)°, (24.75 ± 2.50)°, (23.25 ± 3.77)° respectively in the experiment group and(32.00 ±2.45)°, (33.00 ±5.72)°, (29.25± 2.22)° respectively in the control group( P ＜ 0. 05) . The anti-fracture stress in each stage of the experiment group was better than that of the control group( P ＜ 0.05).CONCLUSION: Applying BDNF early and incessantly can stimulate all the stages of bone fracture healing.

Expression of nerve growth factor in sensory and motor Schwann cells / 中华显微外科杂志

Objective To study the expression of nerve growth factor (NGF) in sensory and motor Schwann cells and its significance in the nerve specific regeneration Method Sensory and motor Schwann cells were prepared in vitro,and each group of cells were cultured in common media and IL 1 media respectively The expression of NGF was measured by Sangwich ELISA Result Generally speaking,the expression level of sensory Schwann cells is higher than that of motor cells And the expression modes of the two types of cells are different,according to the timing and peak numbers Conclusion The NGF expressions of sensory and motor Schwann cells are different,such a difference may partly explain the mechanism of the nerve specific regeneration

The effect of allogeneic MHC Ⅰ gene modification on the immunologic character in bone marrow cells / 中国免疫学杂志

Objective:To observe the effect of allogeneic MHC Ⅰ gene modification on the immunologic character in bone marrow cells and to investigate the mechanism of induce immunologic tolerance of MHC Ⅰ.Methods:The retroviral expression vector of BALB/C mice H 2D d gene was constructed and transducted into C57BL/6 mice bone marrow cells And the expression of H 2D d on the infected cells was detected by FACS technique Then observe the MLR between the BALB/C mice spleen T cells and the C57BL/6 mice bone marrow cells modified with H 2D d gene by MTT assay The cytotoxic activity of BALB/C mice NK cells to the C57BL/6 mice bone marrow cells modified with H 2D d gene was detected by LDH release assay Results:Either stimulation or response ability of the C57BL/6 mice bone marrow cells to the T cell from BALB/C mice spleen was significantly decreased after modified with H 2D d gene The cytotoxic activity of BALB/C mice NK cells to the C57BL/6 mice bone marrow cells modified with allogeneic MHC Ⅰ gene was significantly lower than which to the C57BL/6 mice bone marrow cells non modified Conclusion:It's maybe a way to induce immunologic tolerance in bone marrow transplantation by the means of modify the bone marrow cells with the MHC Ⅰ gene of the recipient