ABSTRACT
This study investigated the effect of TNP-470 in combination with carmustine (BCNU) on the growth of subcutaneously implanted human glioblastoma xenografts in nude mice. Human glioblastoma U-251 cells (1×10(7)) were injected into 24 nude mice subcutaneously. The tumor-bearing mice were randomly divided into 4 groups on the seventh day following tumor implantation: TNP-470 group, in which TNP-470 was given 30 mg/kg subcutaneously every other day 7 times; BCNU group, in which 20 mg/kg BCNU were injected into peritoneal cavity per 4 days 3 times; TNP-470 plus BCNU group, in which TNP-470 and BCNU were coadministered in the same manner as in the TNP-470 group and the BCNU group; control group, in which the mice were given 0.2 mL of the mixture including 3% ethanol, 5% acacia and 0.9% saline subcutaneously every other day 7 times. The tumor size and weights were measured. The tumor microvessel density (MVD) was determined by immunostaining by using goat-anti-mouse polyclonal antibody CD105. The results showed that on the 21th day following treatment, the volume of xenografts in the TNP-470 plus BCNU group was (108.93±17.63)mm(3), markedly lower than that in the TNP-470 group [(576.10±114.29)mm(3)] and the BCNU group [(473.01±48.04)mm(3)] (both P0.05). The inhibition rate of the tumor growth in the TNP-470 plus BCNU group was (92.80±11.37)%, notably higher than that in the TNP-470 group [(61.91±6.29)%] and the BCNU group [(68.73±9.65)%] (both P0.05). The MVD of xenografts in the TNP-470 plus BCNU group was decreased significantly as compared with that in the TNP-470 group or the BCNU group (both P0.05). It was concluded that the combination of TNP-470 and BCNU can significantly inhibit the growth of human glioblastoma xenografts in nude mice without evident side effects.
ABSTRACT
This study investigated the effect of TNP-470 in combination with carmustine (BCNU) on the growth of subcutaneously implanted human glioblastoma xenografts in nude mice. Human glioblastoma U-251 cells (1×10(7)) were injected into 24 nude mice subcutaneously. The tumor-bearing mice were randomly divided into 4 groups on the seventh day following tumor implantation: TNP-470 group, in which TNP-470 was given 30 mg/kg subcutaneously every other day 7 times; BCNU group, in which 20 mg/kg BCNU were injected into peritoneal cavity per 4 days 3 times; TNP-470 plus BCNU group, in which TNP-470 and BCNU were coadministered in the same manner as in the TNP-470 group and the BCNU group; control group, in which the mice were given 0.2 mL of the mixture including 3% ethanol, 5% acacia and 0.9% saline subcutaneously every other day 7 times. The tumor size and weights were measured. The tumor microvessel density (MVD) was determined by immunostaining by using goat-anti-mouse polyclonal antibody CD105. The results showed that on the 21th day following treatment, the volume of xenografts in the TNP-470 plus BCNU group was (108.93±17.63)mm(3), markedly lower than that in the TNP-470 group [(576.10±114.29)mm(3)] and the BCNU group [(473.01±48.04)mm(3)] (both P<0.01). And the xenograft volume in these 3 treatment groups was even much lower than that in the control group [(1512.61±470.25) mm(3)] (all P<0.01). There was no significant difference in the volume of xenografts between the TNP-470 group and the BCNU group (P>0.05). The inhibition rate of the tumor growth in the TNP-470 plus BCNU group was (92.80±11.37)%, notably higher than that in the TNP-470 group [(61.91±6.29)%] and the BCNU group [(68.73±9.65)%] (both P<0.01) on the 21th day following treatment. There was no significant difference in the inhibition rate of tumor growth between the TNP-470 group and the BCNU group (P>0.05). The MVD of xenografts in the TNP-470 plus BCNU group was decreased significantly as compared with that in the TNP-470 group or the BCNU group (both P<0.05). The MVD of xenografts in the 3 treatment groups was markedly reduced as compared with that in the control group (all P<0.05). No significant changes in weights were observed before and after the treatment in each group (all P>0.05). It was concluded that the combination of TNP-470 and BCNU can significantly inhibit the growth of human glioblastoma xenografts in nude mice without evident side effects.
Subject(s)
Animals , Female , Humans , Mice , Angiogenesis Inhibitors , Antibiotics, Antineoplastic , Antineoplastic Agents, Alkylating , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Brain Neoplasms , Drug Therapy , Carmustine , Cell Line, Tumor , Cyclohexanes , Glioblastoma , Drug Therapy , Mice, Inbred BALB C , Mice, Nude , Sesquiterpenes , Xenograft Model Antitumor AssaysABSTRACT
In this study we implanted magnetically labeled neural stem cells (NSCs) in PD rats and then monitored their survival and migration in the host brain by magnetic resonance imaging (MRI). The mesencephalic NSCs were obtained from the brain of SD rats. Superparamagnetic iron oxide (SPIO) was transferred to NSCs by Lipofectamine transfection. Eighteen PD lesioned rats were selected for transplantation by evaluation of their rotational behavior in response to amphetamine and randomly assigned to 3 groups, i.e., sham group, PBS group and NSCs transplanted group, with 6 rats in each group. MR scanning was performed at 1, 2, 4, 6, 8 and 10 week(s) following transplantation. At the meantime, rotational behavior was assessed in each group. Our results showed that SPIO particles were clearly visible with Prissian blue staining in neurospheres and cells derived from NSCs. The rotational behavior of the NSCs transplanted group was remarkably improved compared with that of sham group and PBS group (P < 0.05). In vivo MR tracking of NSCs showed that SPIO labeling led to a strong susceptibility change of signal 1 week after transplantation on T2 weighted images. And a large circular hypointense signal appeared in the transplanted area on T2* gradient echo images. Ten weeks following transplantation, the hypointense signal on T2 weighted and T2* gradient echo images was still displayed. It is concluded that SPIO particles could label NSCs effectively, and MRI detection of SPIO labeled cells is a promising method and novel approach to analyzing the NSCs following transplantation in the treatment of PD.
ABSTRACT
In this study we implanted magnetically labeled neural stem cells (NSCs) in PD rats and then monitored their survival and migration in the host brain by magnetic resonance imaging (MRI).The mesencephalic NSCs were obtained from the brain of SD rats. Superparamagnetic iron oxide (SPIO) was transferred to NSCs by Lipofectamine transfection. Eighteen PD lesioned rats were selected for transplantation by evaluation of their rotational behavior in response to amphetamine and randomly assigned to 3 groups, i.e., sham group, PBS group and NSCs transplanted group, with 6 rats in each group. MR scanning was performed at 1, 2, 4, 6, 8 and 10 week(s) following transplantation.At the meantime, rotational behavior was assessed in each group. Our results showed that SPIO particles were clearly visible with Prissian blue staining in neurospheres and cells derived from NSCs.The rotational behavior of the NSCs transplanted group was remarkably improved compared with that of sham group and PBS group (P＜0.05). In vivo MR tracking of NSCs showed that SPIO labeling led to a strong susceptibility change of signal 1 week after transplantation on T2 weighted images.And a large circular hypointense signal appeared in the transplanted area on T2* gradient echo images.Ten weeks following transplantation, the hypointense signal on T2 weighted and T2* gradient echo images was still displayed. It is concluded that SPIO particles could label NSCs effectively, and MRI detection of SPIO labeled cells is a promising method and novel approach to analyzing the NSCs following transplantation in the treatment of PD.
ABSTRACT
To evaluate the effect of wild-type p53 gene on the growth and radiotherapeutic sensitivity of human glioma cells, plasmid PC53-SN3 carrying wild-type p53 gene was transfected into U251 cells. p53 gene expression in transfected cells was detected by RT-PCR, and the cell growth inhibition and apoptosis in the absence or presence of irradiation were assessed by MTT and flow cytometry. The transfection of p53 gene into U251 cells was confirmed by RT-PCR. MTT showed that p53 gene alone induced strong inhibitory effect on the growth of U251 cells (inhibition rate (IR), (79.60 +/- 5.69)%). The killing effect of irradiation alone on U251 cells was not strong (IR: (17.06 +/- 4.35)% (17.39 +/- 1.67)% (18.73 +/- 4.68)%) and increased with the irradiation doses (3, 6, 9 Gy). When combined treatment of wild-type p53 gene transfection and irradiation was used, the effect was significantly increased (IR:(80.60 +/- 5.35)%. (90.30 +/- 1.67)%, (91.30 +/- 2.01)%). The apoptosis rate of U251 cells induced by p53 gene transfection was 17.38%. The rate induced by irradiation increased (4.61%, 4.84%, 5.40%) with the irradiation doses (3, 6, 9 Gy). The apoptosis rate was also significantly increased (17.80%, 20.03%, 22.34%) after combined treatment of p53 and irradiation with different doses (3, 6, 9 Gy). It is concluded that wild-type p53 gene and irradiation could result in synergistic inhibitory effect on the growth of human glioma cells.
Subject(s)
Apoptosis/radiation effects , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Genes, p53/radiation effects , Glioma/genetics , Glioma/pathology , Transfection , Tumor Cells, CulturedABSTRACT
To evaluate the effect of wild-type p53 gene on the growth and radiotherapeutic sensitivity of human glioma cells, plasmid PC53-SN3 carrying wild-type p53 gene was transfected into U251cells. p53 gene expression in transfected cells was detected by RT-PCR, and the cell growth inhibition and apoptosis in the absence or presence of irradiation were assessed by MTT and flow cytometry. The transfection of p53 gene into U251 cells was confirmed by RT-PCR. MTT showed that p53 gene alone induced strong inhibitory effect on the growth of U251 cells (inhibition rate (IR):(79.60±5.69) %). The killing effect of irradiation alone on U251 cells was not strong (IR: (17.06±4.35) %, (17.39±1.67) %, (18.73±4.68) %) and increased with the irradiation doses (3,6, 9 Gy). When combined treatment of wild-type p53 gene transfection and irradiation was used,the effect was significantly increased (IR:(80.60±5.35) %, (90.30±1.67) %, (91.30±2.01)%). The apoptosis rate of U251 cells induced by p53 gene transfection was 17.38 %. The rate induced by irradiation increased (4. 61%, 4. 84 %, 5.40 %) with the irradiation doses (3, 6, 9Gy). The apoptosis rate was also significantly increased (17.80 %, 20.03 %, 22.34%) after combined treatment of p53 and irradiation with different doses (3, 6, 9 Gy). It is concluded that wildtype p53 gene and irradiation could result in synergistic inhibitory effect on the growth of human glioma cells.
ABSTRACT
To evaluate the effects of wild-type p53 gene on the growth and chemotherapeutic sensitivity of human glioma cells, plasmid PC53-SN3 carrying wild-type p53 gene was transfected into U251 cells. p53 gene expression in transfected cells was detected by RT-PCR, the cell growth inhibition and apoptosis in either the absence or the presence of cisplatin was assessed by MTT and flow cytometry. The transfection of p53 gene into U251 cells was confirmed by RT-PCR. MTT showed that p53 gene by itself induced strong inhibition effect on the growth of U251 cells [inhibition rate, IR (79.60 +/- 5.69)%]. The killing effects of cisplatin by itself on U251 cells was not strong [IR (19.40 +/- 6.69)%, (24.41 +/- 2.68)%, (51.84 +/- 13.38)%, (66.22 +/- 5.02)%] and increased with the increase of cisplatin concentration (1, 2, 4, 8 micrograms/ml). When combined treatment of wild-type p53 gene transfection and cisplatin was used, that was significantly increased [IR (91.64 +/- 1.00)%, (94.98 +/- 1.67)%, (95.32 +/- 2.01)%, (95.65 +/- 1.00)%]. The apoptosis rate of U251 cells induced by p53 gene transfection was 17.38%. That induced by cisplatin increased (5.71%, 5.93%, 6.27%, and 6.81%) with the increase of cisplatin concentration (1, 2, 4, 8 micrograms/ml). The apoptosis rate was also significantly increased (23.50%, 23.54%, 23.89%, and 28.88%) after combined treatment of p53 and cisplatin with different concentration (1, 2, 4, 8 micrograms/ml). It is concluded that wild-type p53 gene and cisplatin could result in synergistic inhibition effects on the growth of human glioma cells.
Subject(s)
Humans , Antineoplastic Agents , Pharmacology , Apoptosis , Cell Division , Cell Line, Tumor , Cisplatin , Pharmacology , Drug Resistance, Neoplasm , Genetics , Gene Expression Regulation, Neoplastic , Genetics , Genes, p53 , Genetics , Glioma , Genetics , Pathology , Recombinant Fusion Proteins , PhysiologyABSTRACT
Objective To explore the efficacy of large dose of magnesium sulfate used to treat patients with brain trauma. Methods According to standards 32 patients were chosen and divided into experimental group and control group at random. Sixteen patients in experimental group received 16 mmol magnesium sulfate intravenously over 15 minutes, followed by 65 mmol over 24 hours; while 16 patients in control group received nothing. Serum NSE, GCS and GOS of all the patients were measured after 3 days, 2 weeks and 6 months, respectively and the data were analyzed statistically. Results The serum NSE, GCS and GOS in experimental group were (24.8±19.2) μg/L, 12.3±3.3 and 3.6±1.4, respectively; while the serum NSE, GCS and GOS in control group were (49.7±23.1) μg/L, 9.8±2.8 and 3.1±1.6, respectively. Between the two groups the serum NSE and GCS were different significantly (P<0.01, P<0.05, respectively) while the GOS was not (P>0.05). Conclusions Large dose of magnesium sulfate is effective to treat patients with brain injury at least within a short term.
ABSTRACT
Objective To study the clinical significance of 3 dimensional time of flight magnetic resonance angiography(3D-TOF-MRA) for the pathogenesis of hemifacial spasm (HFS) and trigeminal neuralgia(TN).Methods 48 patients with HFS and 46 patients without HFS and 42 patients with TN and 40 patients without TN were examined by MRI and 3D-TOF-MRA by the enhancement of DTPA. Diagnosis of the presence of compressions in the root exit zone(REZ) of facial nerves and trigeminal nerves were done by two radiologists on an independent console. Results (1)In the patients, compression of the REZ of the facial nerves and trigeminal nerves were detected on 45 spastic sides (93.8%,neurovascular on 44 sides and tumor on 1 side) and 36 spastic sides ( 85.7%,neurovascular on 32 sides and tumor on 4 sides ), 8 and 4 on the asymptomatic sides (16.7% and 9.5%, all neurovascular ). In the controls, 4 and 5 sides ( 4.4% and 6.3% ) were found in the compression of the REZ of the facial nerves and trigeminal nerves. ( 2 ) The offending vessels of compression of the REZ of the facial nerves were the anterior inferior cerebellar artery (AICA) in 17 cases ( 38.6% ), the posterior inferior cerebellar artery (PICA) in 12 cases (27.3%), the vertebral artery (VA) in 6 cases (13.6%). The offending vessels of compression of the REZ of the trigeminal nerves were the superior cerebellar artery ( SCA ) in 18 cases ( 56.3% ), the anterior inferior cerebellar artery in 5 cases (15.6%), the difficult identified vessels (DIV) in 4 cases (12.5%). (3)The relative risks of microvascular compressions which cause HFS and TN were 26.6 and 9.84. (4) The compressions of the REZ of the facial nerves and trigeminal nerves were proved in 4 cases (neurovascular 3 cases and tumor 1 case) and 10 cases (neurovascular 6 cases and tumor 4 casee) in the operation.Conclusion MRI and enhanced 3D-TOF-MRA appeare to be the best imaging technology for the pathogenesis of HFS and TN now. The major causes of HFS and TN may be different neurovascular compressions in the REZ of the facial nerves and trigeminal nerves, some cases are caused by tumor compression.
ABSTRACT
AIM: To study effect of endogenous carbon monoxide on intracellular calcium concentration and explore the mechanism in brain protection of endogenous CO in focal cerebral ischemia in rats. METHODS: SD rats were divided into three groups randomly, which including hemin, ZnPP group and saline group as control. Respectively saline, hemin, ZnPP were injected intra-peritoneally twelve hours before middle cerebral artery was occluded. Twenty four hours after MCAO model was set up, the concentration of carbon monoxide in blood and intracellular calcium in neural cells was examined. RESULTS: Contrast to saline group, the concentration of CO in blood rose up while intracellular calcium in occluded side decreased in hemin group; the concentration of CO in blood went down while intracellular calcium in occluded side rose up in ZnPP group, there was significant difference among them (P0.05). CONCLUSIONS: It may be one of mechanisms on brain protection in ischemic cerebral tissue that carbon monoxide affected intracellular calcium concentration of neural cells by regulating Ca~(2+)-K~+ channel on cell membrane as a messenger gaseous molecular and neurotransmitter. [
ABSTRACT
Objective To summarize and discuss the therapy of patients with tentorial herniation due to post-traumatic acute diffuse brain swelling around operations to improve the therapeutic efficacy.Methods A retrospective study was accomplished on 70 patients with tentorial herniation due to post-traumatic acute diffuse brain swellin around operations.Results According to Glasgow outcome scale,44 of 70 cases got favorable outcome,including 37 cases good recovery and 7 cases moderate deficit.The 26 of 70 cases got unfavorable outcome,including 6 cases severe deficit,5 cases persistent vegetable status and 15 cases dead.Conclusions This comprehensive therapy improves the efficacy of patients with tentorial herniation due to post-traumatic acute diffuse brain swelling around operations,which is worth spreading and applying.
ABSTRACT
Objective To study the clinical significance of routine MRI and 3 dimensional time of flight magnetic resonance angiography (3D-TOF-MRA) for the pathogenesis of Trigeminal neuralgia (TN) Methods 32 patients with TN and 32 controls were observed by MRI and 3D-TOF-MRA by the enhancement of DTPA Diagnosis of the presence of compressions in the root exit zone (REZ) of the Trigeminal nerves were carried out by two radiologist on an independent console Results (1) In patients studied, compressions of the REZ of the nerves were detected with 29 on symptomatic sides (90 63%), neurovascular on 25 sides and tumor on 4 sides, and 2 on the asymptomatic sides(6 25%, all neurovascular) In the controls, 3 sides (4 26%, all neurovascular) were involved in the compressions of the REZ of the Trigeminal nerves (2) In 25 cases with TN of neurovascular etiology, the offending vessels were the superior cerebellar arteries in 17 cases (68%), anterior inferior cerebellar arteries in 2 cases, vertebral artery (VA) in 1 cases, difficultly identified vessels in 2 cases, vein in 2 cases, vascular malformation in 1 case (3) The RR of microvascular and tumor compressions which cause TN were 36 74 (4) The real microvascular compression and entrapping were only detected on the symptomatic sides of TN in 13 patients (52%) Conclusion MRI and 3D-TOF-MRA appeared to be the best imaging test for the pathogenesis of TN now The major causes of TN might be different neurovascular and tumor compressions in the REZ of the fifth cranial nerve, with real compression, entrapping or tight contact
ABSTRACT
An analysis of the time pattern of outpatients visits to our hospital from 1997 to 2000 led to the discovery of the variation pattern of each outpatient departments workload. This discovery has enabled the managers of the hospital to rationally deploy the manpower and material resources of various departments, make full use of limited resources, readjust the working hours and shifts of different kinds of staff, and work out a flexible system of working hours which is more scientific and more convenient to patients. Implementation of such a system has ensured that prompt delivery of medical service is accessible to patients even at the peak of visiting hours. Hence the reduction of patients time of waiting and the provision of a scientific guarantee for establishing a quality, efficient, low consumption and fast outpatient service system, meeting the medical needs of patients to the maximum and enhancing work efficiency.