Onyx in treatment of large and giant cerebral aneurysms and arteriovenous malformations.
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Biomedical subjects
Liang-fu Zhou
Publications and source records attributed to Liang-fu Zhou.
U0126 prevents ERK pathway phosphorylation and interleukin-1beta mRNA production after cerebral ischemia.
OBJECTIVE: To study the role of extracellular signal-regulated kinase (ERK) in cerebral ischemia and the mechanism of protective effects of U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio] butadiene) on ischemic brain. METHODS: Mice underwent left middle cerebral artery occlusion (MCAO) by introducing a suture in the lumen. U0126 was injected intravenously through the internal jugular vein. The immuno-activity of phosphorylated ERK1/2 (pERK1/2), phosphorylated mitogen activated protein kinase kinase (pMEK), and phosphorylated Elk-1 (pElk-1) was assessed by Western blot analysis and immunohistochemistry. Interleukin (IL)-1beta mRNA level was measured by ribonuclease protection assay. RESULTS: Phosphorylated ERK1/2 in 2 hours MCAO mice was down-regulated after intravenous injection of U0126. The inhibition was dose dependent and treatment time related. pMEK and pElk-1 were also reduced in a similar fashion after U0126 treatment. IL-1beta mRNA increased after 1 and 2 hours of MCAO. After injection of U0126, it was down-regulated during 1 to 4 hours after MCAO. CONCLUSION: Intravenous administration of the MEK inhibitor U0126 inhibits pMEK, pERK1/2, and pElk-1 up-regulation induced by cerebral ischemia. The protective effect of U0126 against ischemic injury is probably resulted from the reduction of IL-1beta mRNA via the inhibition of ERK pathway.
Animals↗
[Identification of a novel inheritable CCM1 gene mutation of 671del AT in a Chinese family with cerebral cavernous malformation].
OBJECTIVE: To investigate the hereditary characters of familial cerebral cavernous malformation (FCCM) and the novel gene mutation in a Chinese family. METHODS: Head MRI examination and clinical neurological check were performed on a Chinese family with one proband of FCCM, female, 27 years old, and 16 family members, 9 males and 12 females, and 19 controls, including patients with sporadic CCM and other diseases and healthy persons. DNA was extracted from the white blood cells of the peripheral blood of the subjects. PCR and DNA direct sequencing were used to detect the mutation in CCM1 gene. RESULTS: Head MRI found 11 FCCM patients in the 16 family members of the proband (69%), the youngest one being 4 years old, including multiple intracranial lesions in 7 patients and single lesion in 4. Relevant clinical manifestations were found in 6 out of the 11 family members. Nucleotide sequence analysis of the proband and other affected family members revealed a deletion frameshift mutation of A and T at nucleotides (nt) 671 and 672 in exon 13 of the CCM1 gene, resulting in truncated encoding KRIT1 protein. No mutation was detected in the healthy family members and the controls. CONCLUSION: A novel inheritable CCM1 gene mutation of 671del AT has been found in patients with FCCM.
Adolescent↗
[Gamma knife radiosurgery for trigeminal schwannomas].
OBJECTIVE: To evaluate the role of gamma knife (GK) in the treatment of trigeminal schwannomas. METHODS: From June 1994 to June 2000, 38 patients with trigeminal schwannoma treated with GK radiosurgery were reviewed. GK was the primary treatment modality in 30 cases and followed microsurgery in 8 cases. Of the 38 tumors, 12 had small cysts within the tumors, the rest were solid. The mean diameter of the 38 tumors was 32 mm (range: 16 approximately 48 mm) and the tumors ranged in volume from 2 to 33 cm(3) (with a mean mean volume of 9 cm(3)). The maximum dose irradiated to tumor was 20 to 33 Gy (mean: 26 Gy), the tumor margin dose ranged from 11 to 15 Gy (mean: 13 Gy). RESULTS: 35 patients had been followed for 26 to 98 months (mean: 65 months). 20 had been followed more than 60 months. Mild numbness or diplopia relieved completely in 12 patients after GK treatment. Improvement of neurological deficits was seen in 11, unchanged dysfunction or slightly worsening of trigeminal nerve deficits in 9. Three patients had mild worsened symptoms at different time because of tumor progression. Tumor growth control: tumor disappeared after GK treatment was observed in 5 cases from 18 to 36 months after, a marked decrease in volume was observed in 24 cases, unchange in 2 cases and increase in 3 cases at 5, 26, and 60 months after respectively. One patient with resolved symptom refused to have MRI examination for more than 6 years. Of the three increased tumors, one recurrent malignant schwannoma elapsed 26 months after GK treatment. The second was a small tumor and started to progress 5 years after, but after second GK treatment, the tumor decreased again. The third was large tumor and was subtotally removed through surgery because of tumor swelling 5 months after. At last follow-up, the residual tumor remained stable. The control rate of the 35 tumors was 91% (32/35). CONCLUSION: Small and middle-size trigeminal schwannomas are the best candidates for GK radiosurgery. The control dose is 13 to 14 Gy.
Adolescent↗
[Immunohistochemical study on central nervous system cavernous hemangiomas].
OBJECTIVE: To explore the histological structure, angiogenesis, and proliferative activity of central nervous system cavernous hemangiomas. METHODS: 70 surgical samples of central nervous system cavernous hemangiomas and 20 normal brain vessel samples from patients of epilepsy and open craniocerebral trauma were stained immunohistochemically with CD34, a-SMA; VEGF, Flt-1; and TGFa, Ki67 respectively. A comparison analysis was made according to the expression intensity. RESULTS: CD34 and a-SMA were expressed in all the normal control brain vessel tissues in a manner of obvious and continuous staining. VEGF, Flt-1 and TGFa were not expressed obviously in the normal brain tissues. 47 and 50 out of the 70 cavernous hemangioma specimens were positively stained for CD34 and a-SMA respectively, and their expression was less continuous. 68 and 44 out of the 70 cavernous hemangioma specimens were positively stained for VEGF and Flt-1 respectively with diffuse distribution. 68 cavernous hemangioma specimens were positively stained for TGF-a. A significant difference in expression intensity was found for the above 5 factors between the normal control brain tissue and cavernous hemangiomas (all P < 0.05). No expression of Ki67 was detected in all samples. CONCLUSION: The biological characteristics of cavernous hemangiomas are mainly relevant to the immaturity of the vessel wall. A series of angiogenic factors play an important role in the development of the lesion. The proliferative activity of the cavernous hemangiomas needs to be studied further.
Actins↗
[Gamma knife radiosurgery for hemangioblastomas: clinical results and pathological findings].
OBJECTIVE: To retrospectively evaluate the effects of Gamma knife in the treatment of cerebral hemangioblastomas. METHODS: From 1993 to 1996, seventeen patients with 29 hemangioblastomas were treated with Gamma knife. The patients mean age was 35 years (range: 16 - 61 years). The mean tumor diameter was 16 mm (range: 6 - 55 mm). Thirteen patients had recurrent or residual hemangioblastomas. Four with primary hemangioblastomas were diagnosed using CT, MRI and DSA. The maximum dose to the tumors was 21.0 - 50.0 Gy, with mean dose of 33.7 Gy. The radiation dose to the periphery of tumors was 12.0 - 24.0 Gy, with mean dose of 17.6 Gy. RESULTS: All the patients had been followed up for 18 to 62 months, with mean 46 months. Five patients experienced clinical improvement and reduction in tumor volume, and 5 remained stable and tumor unchanged in volume during the follow-up period. Three patients died of tumor progression, surgery and cancer after treatment 18, 22, 25 months respectively. Four patients underwent surgery respectively at 3, 4, 29 and 48 months after gamma knife operation. The local control rate of the tumors at 1 year was 92%, 2 years 88%, 3 years 80% and 4 years 75%. Pathological findings in these patients showed varying degrees of small vessel thickening and occlusion together with degeneration, necrosis in the center of tumor and loss of tumor cells at periphery. CONCLUSIONS: Gamma knife is not adequately reliable for the control of hemangioblastoma cysts, it is an effective treatment of small or medium-size solid tumors, but long-term follow-up is needed. The recommended dose is 16 to 20 Gy.
Adolescent↗
[The clinical evaluation of patients with pituitary adenomas undergone transsphenoidal microsurgery].
OBJECTIVE: To evaluate the overall effect of transsphenoidal microsurgery for pituitary adenomas in recent 5 years and to discuss the surgical technique, application of new technology and postoperative follow-up results. METHODS: The clinical presentation, image characteristics, endocrinal findings, pathological types, tumor removal percentage, postoperative complication and follow-up of 1 462 patients with pituitary adenomas who underwent the transsphenoidal microsurgery from 1997 to 2002 were analysed retrospectively. RESULTS: Total rate of tumor removal for the patients achieved 97.0% in the patients with Hardy I adenomas, 95.2% with Hardy II, 90.5% with Hardy III, and 47.4% with Hardy IV respectively. A significant postoperative improvement both in clinical symptoms and endocrinal parameters was achieved. The tumor recurrence rate was 0.3%. CONCLUSIONS: With the improvement of microsurgical technique and application of novel technology, the indication of transsphenoidal microsurgery for pituitary adenomas was increasingly extended. Endoscope and(/or) neuronavigation-assisted microsurgery via transsphenoidal approach should be of the first choice for the treatment of pituitary adenomas. The routine postoperative radiotherapy is not required for patients with total tumor removal.
Adenoma↗
[Role of diffusion tensor imaging in neuronavigation surgery of brain tumors involving pyramidal tracts].
OBJECTIVE: To explore the role of diffusion tensor imaging (DTI) in neuronavigation surgery of brain tumors involving pyramidal tracts. METHODS: Forty-nine patients with brain tumors involving pyramidal tracts were randomly divided into trial group (DTI navigation) and control group (traditional navigation). The patients in trial group underwent DTI and T1 weighted 3D navigational magnetic resonance imaging (MRI) studies. The main white matter tracts were constructed by the DTI datasets, and merged to the anatomical structure, which was delineated by the T1-weighted three-dimensional fast spoiled gradient recalled sequence (3D/FSPGR). The relationship between the tumors and adjacent pyramidal tracts were segmented and reconstructed for three-dimensional visualization. RESULTS: In 25 patients of trial group and 24 patients of control group, the statistic analysis confirmed well balance of main variations. The tumors were completely resected in 12 patients (50.0%) of control group and in 20 patients (80.0%) of trial group (P < 0.05). Postoperative aggravated contralateral extremities weakness or hemiplegia due to pyramidal tract injury occurring in 75.0% cases of control group whereas only 20.0% patients in trial group (P < 0.01). The mean Karnofsky scale were 69.58 +/- 23.49 and 84.80 +/- 23.49 respectively in control and trial groups (P < 0.05). The excellent outcome ratio (Karnofsky scale = 90 - 100) was 37.5% in control group and 72.0% in trial group respectively (P < 0.05). CONCLUSIONS: DTI allows individual estimation of large fiber tracts of brain. Furthermore, to integrate spatial three-dimensional information concerning the white matter tracts into traditional neuronavigation images during surgery, was valuable in presenting topographical character of involving (shift or erosive) pyramidal tracts and relationship with the margins of neighboring tumors. The mapping of large fiber tracts was a safe, efficient, reliable technique. DTI should be routinely used in neuronavigation surgery of brain tumor involving pyramidal tracts to plan the optimal trajectory and ensure total resection of the lesions during operation, as well as to decrease potential disability after operation and to shorten the length of hospitalization.
Adolescent↗
Transcriptional inactivation of TP73 expression in oligodendroglial tumors.
The TP73 gene, located on chromosome 1p36.3, encodes a product that shares significant structural homology with the tumor suppressor TP53. The aim of this study was to investigate whether TP73 is involved in the development of oligodendroglial tumors, which frequently carry deletions involving 1p36.3. Semi-quantitative reverse transcription-polymerase chain reaction was used to determine TP73 transcript levels. Ten of 24 (42%) tumors showed negligible to more than 5-fold reduction in TP73 expression when compared to normal brain level. To identify potential mechanisms that may modulate TP73 transcription in oligodendroglial tumors, we performed mutation analysis on the TP73 gene. No somatic mutations were however detected in the gene sequence. We then evaluated the possible involvement of epigenetic change in TP73 expression. Bisulfite genomic sequencing detected aberrant hypermethylation at the 5' region upstream and including the first exon of the TP73 gene in 17 of 44 (39%) oligodendroglial tumors, whereas normal brain tissues showed no methylation in the same region examined. Moreover, 6 of 10 (60%) tumors with negligible or decreased levels of TP73 transcripts were methylation-positive. In conclusion, our results showed that inactivation of TP73 occurs at the transcriptional level and is associated with promotor hypermethylation. Loss of or reduced TP73 transcript expression may contribute to the tumorigenesis of oligodendroglial tumors.
Adolescent↗