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Liangfu Zhou

Publications and source records attributed to Liangfu Zhou.

14 recordsLinked to original sources

EMP3 overexpression is associated with oligodendroglial tumors retaining chromosome arms 1p and 19q.

The epithelial membrane protein 3 (EMP3) gene located on chromosome 19q13 has been implicated as a candidate tumor suppressor gene (TSG) in neuroblastomas and gliomas. The aim of this study was to investigate whether EMP3 is involved in oligodendroglial tumors (OTs), which frequently carry combined chromosomes 1p and 19q deletion. We first investigated the transcript level of EMP3 in a cohort of 57 OTs by quantitative real-time RT-PCR. Our results showed that 10 (18%) tumors had reduced EMP3 expression level compared to normal brains. Six of these tumors carried chromosome 19q13 deletion but no statistical correlation was found between the 2 parameters. Intriguingly, a similar proportion (11 of 57, 19%) of tumors displayed EMP3 overexpression, with 8 of them having transcript level >10-fold higher than normal brain. All 11 OTs retained chromosomes 1p36 and 19q13, and a significant association was found between EMP3 overexpression and balanced chromosomes 1p36 and 19q13 (p = 0.004). The methylation status of EMP3 was evaluated by bisulfite sequencing in 29 OTs with diverse expression levels. All tumors except 3 showed aberrant methylation of EMP3 and no correlation was observed between transcript level and methylation status, suggesting that methylation alone does not mediate transcriptional down-regulation of EMP3 in OTs. In conclusion, our study demonstrates that EMP3 overexpression is involved in OTs retaining chromosomes 1p and 19q and does not support EMP3 as the target TSG on chromosome 19q13 in OTs.

Adolescent↗

Proliferative status of tumor stem cells may be correlated with malignancy grade of human astrocytomas.

Tumor stem cells are implicated in tumor initiation and maintenance. Recent studies have shown that a subpopulation of cells isolated from brain tumors can form neurospheres in vitro, and have multiple characteristic properties observed in neural stem cells. In vivo implantation of these cells can induce tumors that phenocopy original tumors, suggesting that tumor stem cells are involved in brain carcinogenesis. We found that a population of cells in human glioblastoma multiforme expressed multiple protein markers of neural stem cells including nestin, TUC-4, doublecortin and beta III-tubulin. In contrast, these markers were not expressed in human capillary hemangioblastoma or meningioma. Double immunolabeling showed that a portion of doublecortin-, beta III-tubulin-, TUC-4- and nestin-positive cells express Ki67 antigen, a cell proliferation marker. To investigate further whether these properties of tumor stem cells are correlated with their biological behavior, immunohistochemistry was performed on brain sections from astrocytomas of different grades using antibodies against neural stem cell markers. The number of cells expressing Ki67 antigen and neural stem cell markers was increased in relation to worsening histological grade of astrocytomas, indicating that the capacity for tumor stem cell proliferation may be clinically relevant. Thus, tumor stem cells in astrocytomas may be involved in carcinogenesis.

Adolescent↗

Chronic treatment with minocycline preserves adult new neurons and reduces functional impairment after focal cerebral ischemia.

BACKGROUND AND PURPOSE: Evidence suggests that activated microglia are detrimental to the survival of new hippocampal neurons, whereas blocking inflammation has been shown to restore hippocampal neurogenesis after cranial irradiation and seizure. The aim of this current study is to determine the effect of minocycline on neurogenesis and functional recovery after cerebral focal ischemia. METHODS: Four days after temporary middle cerebral artery occlusion, minocycline was administered intraperitoneally for 4 weeks. BrdU was given on days 4 to 7 after middle cerebral artery occlusion to track cell proliferation. The number of remaining new neurons and activated microglia were quantified in the dentate gyrus. Infarct volume was measured to assess the treatment effect of minocycline. Motor and cognitive functions were evaluated 6 weeks after middle cerebral artery occlusion. RESULTS: Minocycline delivered 4 days after middle cerebral artery occlusion for 4 weeks did not result in reduction in infarct size but significantly decreased the number of activated microglia in the dentate gyrus. Minocycline also significantly increased the number of newborn neurons that coexpressing BrdU and NeuN without significantly affecting progenitor cell proliferation in the dentate gyrus. Lastly, minocycline significantly improved motor coordination on the rotor rod, reduced the preferential use of the unaffected limb during exploration, reduced the frequency of footfalls in the affected limb when traversing on a horizontal ladder, and improved spatial learning and memory in the water maze test. CONCLUSIONS: Minocycline reduces functional impairment caused by cerebral focal ischemia. The improved function is associated with enhanced neurogenesis and reduced microglia activation in the dentate gyrus and possibly improved neural environment after chronic treatment with minocycline.

Animals↗

Effect of fasudil hydrochloride, a protein kinase inhibitor, on cerebral vasospasm and delayed cerebral ischemic symptoms after aneurysmal subarachnoid hemorrhage.

The efficacy and safety of fasudil hydrochloride, a novel protein kinase inhibitor, were evaluated for the treatment of cerebral vasospasm and associated cerebral ischemic symptoms in patients with ruptured cerebral aneurysm. This randomized open trial with nimodipine as the control included 72 patients who underwent subarachnoid hemorrhage surgery for ruptured cerebral aneurysm of Hunt and Hess grades I to IV. For 14 days following surgery, patients were administered either 30 mg of fasudil hydrochloride by intravenous injection over a period of 30 minutes three times a day or 1 mg/hr of nimodipine by continuous intravenous infusion. Fasudil hydrochloride and nimodipine both showed inhibitory effects on cerebral vasospasm. The incidence of symptomatic vasospasm was five of 33 patients in the fasudil group and nine of 32 patients in the nimodipine group. Good recovery evaluated by the Glasgow Outcome Scale was achieved by 23 of 33 patients in the fasudil group and 19 of 34 patients in the nimodipine group. Both drugs significantly improved consciousness levels and neurological deficits such as aphasia. However, fasudil hydrochloride improved motor disturbance more than nimodipine. Adverse reactions occurred in 13 of 37 patients receiving fasudil hydrochloride and 15 of 35 patients receiving nimodipine. There were no serious adverse events in the fasudil group. The results of this clinical trial indicate that fasudil hydrochloride is a safe and efficient agent for suppressing cerebral vasospasm after subarachnoid hemorrhage surgery for ruptured cerebral aneurysm.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Promoter hypermethylation profile of RASSF1A, FHIT, and sFRP1 in intracranial primitive neuroectodermal tumors.

Medulloblastomas (MBs) and supratentorial primitive neuroectodermal tumors (SPNETs) are histologically alike intracranial PNETs found in different anatomical locations of the brain. Current evidence suggests that hypermethylation of promoter CpG islands is a common epigenetic event in a variety of human cancers. The aim of this study was to investigate whether promoter hypermethylation of putative tumor suppressor genes was involved in both types of intracranial PNETs. We examined the methylation status at promoter regions of RASSF1A, FHIT, and sFRP1 by methylation-specific polymerase chain reaction in a cohort of 25 primary MBs, 9 primary SPNETs, and 3 MB and 2 SPNET cell lines. Our results revealed no promoter hypermethylation of RASSF1A, FHIT, and sFRP1 in 2 normal cerebellar and 5 normal cerebral tissue specimens examined. In contrast, promoter hypermethylation of RASSF1A was detected in 100% of primary MBs, 67% (6/9) of primary SPNETs, and all PNET cell lines. The frequency of promoter hypermethylation of RASSF1A was significantly lower in SPNETs than in MBs (Fisher exact test, P = .014). Treatment of RASSF1A-deficient PNET cell lines with 5-aza-2'deoxycytidine, a demethylating agent, restored RASSF1A expression, providing evidence that promoter hypermethylation contributes to transcriptional silencing. In addition, promoter hypermethylation of FHIT and sFRP1 was detected in 22% (2/9) and 11% (1/9) of SPNETs, respectively, but not in any MBs studied. In conclusion, our study demonstrates that promoter hypermethylation of RASSF1A is a common event in intracranial PNETs, whereas FHIT and sFRP1 are epigenetically affected in a fraction of SPNETs.

Acid Anhydride Hydrolases↗

Image-guided resection of cerebral cavernous malformations.

OBJECTIVE: To evaluate retrospectively the effectiveness of image-guided navigation techniques in the management of cerebral CMs. METHODS: Between July 1997 and January 2001, 44 patients underwent image-guided resection of cerebral CMs. To counteract brain shift, a small silicon catheter was implanted as a guide in the case of deep-seated lesions (except in the case of brain stem CMs) and before excision of multiple lesions. RESULTS: A total of 27 men and 17 women with a mean age of 35 years underwent surgical procedures (5 patients had multiple lesions). The lesions were located in the frontal (n = 14), lobe temporal lobe (n = 12), parietal lobe (n = 6), cerebellum (n = 6), thalamus (n = 5), pons (n = 5), and orbital region (n = 1). Under the guidance of a StealthStation navigator, total removal of the lesions was achieved in all patients. Follow-up revealed marked improvement of preoperative symptoms in 26 patients and no additional deficits in 13 patients. Five patients suffered from additional neurological deficits, but two of them gradually improved during the follow-up period. CONCLUSIONS: With the assistance of an image-guided surgical system, functional areas can be effectively avoided and surgical injury can be decreased. This system is well suited for accurate localization and safe resection of small, deep-seated CMs.

Adult↗

Neuronavigator-guided glioma surgery.

OBJECTIVE: To evaluate the effectiveness of neuronavigator-guided surgery for the resection of gliomas. METHODS: A total of 80 patients with gliomas underwent surgical treatment under the StealthStation neuronavigator to estimate the extent of the tumors. In 27 cases, the measurements of brain shifts at the dura, cortical surface and lesion margin were recorded during the operations. A technique termed "micro-catheter fence post" was used in superficial gliomas to compensate for brain shift. RESULTS: Mean fiducial error and predicted accuracy in the 80 cases were 2.03 mm +/- 0.89 mm and 2.43 mm +/- 0.99 mm, respectively. The shifts at the dura, cortical surface and lesion margin were 3.44 mm +/- 2.39 mm, 7.58 mm +/- 3.75 mm, and 6.55 mm +/- 3.19 mm, respectively. Although neuronavigation revealed residual tumors, operations were discontinued in 5 cases of deep-seated gliomas. In the other 75 cases, total tumor removals were achieved in 62 (82.7%), and subtotal removals were achieved in 13 (17.3%). Post-operation, neurological symptoms were improved or unchanged in 68 cases (85.0%), and worsened in 12 (15.0%). No deaths occurred during the operations and post-operations. CONCLUSIONS: Intraoperative brain shifts mainly contribute to the fail of spatial accuracy during neuronavigator-guided glioma surgery. The "micro-catheter fence post" technique used for glioma surgery is shown to be useful for compensating for intraoperative brain shifts. This technique, thus, contributes to an increase in total tumor removal and a decrease in surgical complications.

Adolescent↗

Effects of extracellular signal-regulated kinase (ERK) on focal cerebral ischemia.

OBJECTIVE: To determine the role of extracellular signal-regulated kinase (ERK)1/2 during focal cerebral ischemia. METHODS: Left middle cerebral artery occlusion (MCAO) was undergone after the introduction of a nylon suture to the left internal carotid artery in 70 male adult CD-1 mice. ERK 1/2 phosphorylation was detected using Western blot analysis, and the morphological feature was determined by immunohistochemistry. An ERK pathway inhibitor, 1,4-diamino-2,3-dicyano-1,4-bis[2-amino-phenylthio] butadiene (U0126), was administered intravenously 20 minutes before MCAO, and the neurological deficit levels and the infarct volumes were measured 24 hours after MCAO. RESULTS: Phosphorylated ERK 1/2 (pERK 1/2) activity increased after 30 minutes of MCAO and peaked at 2 hours. The immunohistochemical study displayed a large number of pERK 1/2 positive cells in the ischemic basal ganglion and surrounding cortex. Double-labeled fluorescent staining identified the pERK1/2 positive cells as neurons or astrocytes. In U0126 treated mice which had undergone 24 hours of MCAO, the neurological deficit levels and the infarct volumes were 44.6% and 45.8% respectively, less than those of the control mice. CONCLUSIONS: ERK plays an important role in focal cerebral ischemia and inhibition of the ERK pathway can help protect against ischemic brain injury, which may provide a therapeutic approach for cerebral ischemia.

Animals↗

[Image-guided microsurgery in resection of intracranial cavernous hemangioma].

OBJECTIVE: To study the methods and effectiveness of image-guided microsurgery in resection of intracranial cavernous hemangioma. METHODS: Between July 1997 and January 2001, 44 patients with intracranial cavernous hemangioma, 27 males and 17 females with a mean age of 35 years, among which 5 cases had multiple lesions, underwent image-guided microsurgery. The locations of lesions included frontal lobe (n = 14), temporal lobe (n = 12), parietal lobe (n = 6), cerebellum (n = 6), thalamus (n = 5), pons (n = 5), and orbital lobe (n = 1). A small silicon catheter, used as a guider, was implanted to the deep-seated lesion (except the brain stem lesions) before excision of the lesion in order to prevent brain shift. RESULTS: Total removal of the lesions was achieved in all patients without operational death. Follow-up revealed marked improvement of symptoms in 26 case and no change of symptom(s) in 13 cases. 5 cases suffered from additional neurological deficits, mainly exacerbation of hemiparalysis and aphasia, the condition of two of which, however, gradually improved within the period of follow-up. No residue of lesion and relapse were found during follow up. CONCLUSION: With the assistance of the image-guided surgical system, functional area can be effectively avoided, and surgical injury can be decreased. It is well suited for accurate localization and safe resection of small, deep-seated cavernous malformations.

Adolescent↗

[Surgical management of dumbbell-shaped trigeminal neurinomas].

OBJECTIVE: To investigate the best surgical approach for the removal of dumbbell-shaped trigeminal neurinomas (DSTNs). METHODS: The clinical materials of 46 patients with DSTNs surgically treated were analysed retrospectively. The patients were divided into two groups. In the early group (1978 - 1984), a series of conventional intradural approaches were used, and in the late group (1985 - 2000), an epidural approach via the skull-base craniotomy was used. RESULTS: Total tumor removal was achieved in 42% (5/12) of the early group and 85% (29/34) of the late group (chi(2) = 8.8, P < 0.01). Temporary and permanent cranial nerve morbidities were 63% and 47% (chi(2) = 3.4, P > 0.05) in the early group and 48% and 15% in the late group (chi(2) = 6.1, P < 0.05). CONCLUSION: The best microsurgical approach for the removal of DSTNs is epiduro-transduro-transtentorial approach via skull-base craniotomy. It is not necessary to resect the petrous apex.

Adolescent↗

Long-term follow-up results of dural reconstruction without bone graft at anterior skull-base defects.

OBJECTIVE: To clarify whether it is necessary to reconstruct bone defects at the anterior skull base. METHODS: A long-term follow-up study of 50 patients with anterior skull-base defects in which the dura was reconstructed without bone grafts was conducted. CT and MRI examinations were taken periodically after surgery. RESULTS: The ordinates of the bone defects averaged 3.5 cm (range, 2 - 6 cm), and the abscissas averaged 2.8 cm (range, 2 - 5 cm). The abscissas of the bone defects measured 2 - 3 cm in 38 patients, 3 - 4 cm in 10 patients, and 4 - 5 cm in 2 patients. The follow-up ranged from 3 months to 5 years (average, 2 years). CONCLUSIONS: At normal intracranial pressure, if the dura mater is repaired properly at the skull-base defects and reinforced with a pedicled pericranial flap, encephalomeningocele and cerebrospinal fluid (CSF) leakage can be prevented. It may not be necessary to make free bone grafts when the size of the cranial base bone defect is smaller than 4 cm.

Adolescent↗

Biomechanical study of human dura and its substitutes.

OBJECTIVE: To investigate the biomechanical characters of human dura and its substitutes and to establish guidelines for selection of optimal repair materials for reconstruction of skull base defects. METHODS: A measurement of creep properties of human dura and its substitutes were conducted using biomechanical tests. The dynamic changes of biomechanical properties of canine dura obtained from skull base defects were observed as well. RESULTS: The creep properties of human dura presented a linear-relationship between initial strain and stress, and the creep strain increased slowly with time. The creep compliance formula for human dura and its substitutes was as follows: J (t) = J(0) + Kf (t). The initial compliance of canine dura in skull base defects was reduced by 35%, 46% and 50%, respectively 1, 3 and 6 months after surgery. CONCLUSION: The optimal material for the repair of skull base defects can be estimated using creep compliance analysis. The less the compliance, the better the property of anti-protrusion. Fresh human dura is the least compliant and then in increasing order are lyophilized human dura, fresh human pericranium, Terylene and silicon membranes. The pattern of biomechanical characteristics of the dura mater at skull base defects shows that the strain ability of the dura mater decreases distinctly for 1 - 3 months and then remains almost unchanged for 3 - 6 months after surgery.

Animals↗