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1.
World Neurosurg ; 189: e841-e856, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38986944

ABSTRACT

OBJECTIVE: We designed this study to introduce the surgical strategy cerebrospinal fluid (CSF) decompression in treatment of Chiari malformation type I and compared CSF decompression with other surgical strategies to provide a solid basis for patient counseling. METHODS: The study enrolled 528 consecutive patients with CMI who underwent surgical interventions from 2012 to 2022. The surgical strategy for these patients was bony and dural decompression, anatomical reduction of herniated tonsils, or CSF decompression. Short-term results were determined after 3 months; long-term outcomes were evaluated at last follow-up (at least 18 months). RESULTS: CSF decompression was independently associated with better long- or short-term primary outcomes than anatomical reduction of herniated tonsils or bony and dural decompression (P < 0.001). Compared with short-term, the long-term outcomes were better in patients who underwent CSF decompression (P = 0.035), but were worse in patients with bony and dural decompression (P = 0.03). Specific surgical techniques cannot affect the long- and short-term outcomes of patients with Chiari malformation type I. CSF decompression provided better long-term syringomyelia improvement than short-term (181/218, 83% vs. 169/218, 77.5%; P < 0.001). CONCLUSIONS: CSF decompression, but not a specific surgical technique or operative method, was associated with favorable neurological outcomes in ADULT patients with Chiari malformation type I. The surgical technique and operative method should be selected according to the characteristics of each patient and the intraoperative condition to normalize CSF circulation at the craniovertebral junction area. The intraoperative target, smooth CSF flow out from the fourth ventricle and in to the bilateral Luschka foramina, could be observed.


Subject(s)
Arnold-Chiari Malformation , Decompression, Surgical , Humans , Arnold-Chiari Malformation/surgery , Arnold-Chiari Malformation/diagnostic imaging , Female , Male , Adult , Decompression, Surgical/methods , Treatment Outcome , Middle Aged , Young Adult , Adolescent , Syringomyelia/surgery , Syringomyelia/diagnostic imaging , Aged , Neurosurgical Procedures/methods , Retrospective Studies , Dura Mater/surgery
2.
Stem Cell Res ; 60: 102659, 2022 04.
Article in English | MEDLINE | ID: mdl-35124538

ABSTRACT

A 45-year-old Han Male from China contributed peripheral blood mononuclear cells induced by reprogramming human OKSM transcription factors (OCT3/4, KLF4 SOX2 and C-MYC) with a non-integrated additional vector system. Immunological markers confirmed the pluripotent nature of IPSC. Spontaneous tridermal differentiation confirmed the differentiation ability of IPSC with normal karyotype.


Subject(s)
Induced Pluripotent Stem Cells , Cell Differentiation , Cellular Reprogramming , China , Humans , Induced Pluripotent Stem Cells/metabolism , Leukocytes, Mononuclear , Male , Middle Aged , Transcription Factors/genetics , Transcription Factors/metabolism
3.
Stem Cell Res ; 60: 102645, 2022 04.
Article in English | MEDLINE | ID: mdl-35093714

ABSTRACT

With the development of cytology, the establishment of cell models in vitro has become a powerful means to study the mechanism and treatment of diseases. Here we successfully generated the IPSC-derived modeling system of a 25-year-old healthy male. His peripheral blood mononuclear cells (PBMC) were reprogrammed using human OKSM (SOX2, OCT3/4, KLF4, and C-MYC) transcription factors using a non-integrated additional vector system. Immunocytochemistry demonstrated that IPSCS expressed all the markers of pluripotency and demonstrated their ability to differentiate spontaneously from three hypoderms in vitro. Karyotype is normal.


Subject(s)
Induced Pluripotent Stem Cells , Adult , Asian People , Cell Differentiation , China , Humans , Leukocytes, Mononuclear , Male , Transcription Factors/genetics
4.
Stem Cell Res ; 53: 102314, 2021 05.
Article in English | MEDLINE | ID: mdl-33799282

ABSTRACT

A healthy 31-year-old Chinese Han female donated peripheral blood mononuclear cells (PBMC). Her PBMCs were reprogrammed with human OKSM (OCT3/4, KLF4 SOX2, and c-MYC) transcription factors by the non-integrating episomal vector system. Immunocytochemistry for pluripotency markers confirmed the pluripotency of transgene-free iPSCs. Their ability to differentiate spontaneously three germ layers in vitro is also confirmed. The iPSC line displayed a normal karyotype. This model can be used as a control in pathological mechanism studies.


Subject(s)
Induced Pluripotent Stem Cells , Adult , Cell Differentiation , China , Female , Genetic Background , Humans , Kruppel-Like Factor 4 , Leukocytes, Mononuclear , Transcription Factors
5.
World Neurosurg ; 118: e105-e114, 2018 Oct.
Article in English | MEDLINE | ID: mdl-29959074

ABSTRACT

OBJECTIVE: Spinal cord intramedullary cavernous malformation (SICM) is kind of rare vascular disease, and the therapeutic strategy is still under debate. The purpose of this article is to analyze outcome of SICM surgical resection and to find the possible factors indicating a better outcome. METHODS: A retrospective analysis of 83 patients with SICM in a single center from 2005 to 2017 was performed. Neurologic status was assessed using the McCormick Scale. Clinical information was collected and analyzed using multivariate logistic regression analysis. RESULTS: Eighty patients with SICM were included, 48% of whom were male (n = 40). The mean age was 39.0 years; 7% of patients (n = 6) had a family history and 4% of patients (n = 3) had multiple lesions; and 41% (n = 34) were found with definite hemorrhage. Before surgery, neurologic status of the patients was 43.4%, 31.3%, 13.3%, and 12.0% in grades I (n = 36), II (n = 26), III (n = 11), and IV (n = 10), respectively. Sixty-three patients received long-term follow-up, of whom 19 improved, 39 remained in stable condition, and 5 deteriorated. Patients with duration of symptoms less than 3 months showed a higher improved outcome rate than those with duration longer than 3 months. CONCLUSIONS: The finding suggests that if total resection of SICM is achievable, surgical therapy could be considered to avoid risks of severe complications followed by lesion bleeding. Early microsurgical resection (usually within 3 months) for patients with SICM can lead to better clinical outcomes.


Subject(s)
Hemangioma, Cavernous, Central Nervous System/diagnostic imaging , Hemangioma, Cavernous, Central Nervous System/surgery , Neurosurgical Procedures/trends , Spinal Cord Neoplasms/diagnostic imaging , Spinal Cord Neoplasms/surgery , Adult , Female , Follow-Up Studies , Humans , Male , Retrospective Studies , Time Factors , Treatment Outcome
6.
Aging (Albany NY) ; 10(5): 988-999, 2018 05 10.
Article in English | MEDLINE | ID: mdl-29746255

ABSTRACT

Glioblastoma (GBM) is the most commonly diagnosed solid tumor outside the central nervous system. However, genetic factors underlying GBM remain largely unclear. Previous studies indicated that Glial fibrillary acidic protein (GFAP) might play an important role in the aggressiveness of GBM and also contributed to its poor overall survival. The present study aims to test (1) the associations between GFAP single nucleotide polymorphisms (SNPs) and GBM cells chemoresistance and metastasis, and (2) the molecular mechanism accounting for their effects. Four tagging SNPs of GFAP were initially genotyped in 667 subjects and the significant SNP was further analyzed via online bioinformatical tools. SNP rs11558961 was found to be significantly associated with GBM susceptibility. It was predicted to influence microRNA(miR)-139 binding to 3'UTR of GFAP gene. In functional experiments, we found that cells transfected with rs11558961 G-allele constructs had lower baseline luciferase activities and were more responsive to miR-139 changes, compared to C-allele constructs. Moreover, rs11558961 C>G variant reduced the chemoresistance of GBM cells and migration capability. In conclusion, rs11558961 might influence the chemoresistance and progression of GBM cells via promoting the binding of miR-139, ultimately decrease the susceptibility of GBM. This investigation will shed light on the optimizing for clinical trial design and individualizing of therapeutic plans.


Subject(s)
Brain Neoplasms/genetics , Genetic Predisposition to Disease/genetics , Glial Fibrillary Acidic Protein/genetics , Glioblastoma/genetics , MicroRNAs/metabolism , Adult , Aged , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Drug Resistance, Neoplasm/genetics , Female , Gene Expression Regulation, Neoplastic/genetics , Genotype , Glioblastoma/metabolism , Glioblastoma/pathology , Humans , Male , MicroRNAs/genetics , Middle Aged , Polymorphism, Single Nucleotide
7.
Biomed Pharmacother ; 92: 879-887, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28601045

ABSTRACT

Multiple cellular, molecular, and biochemical changes contribute to the etiology and treatment outcome of contusion spinal cord injury (SCI). MicroRNAs (miRNAs) aberrant expression have been found after SCI in recent studies. However, little is known about the functional significance of the unique role of miRNAs in SCI. Here, we established a rat SCI model and performed the miRNA microarray to analyze miRNAs expression at different times post-SCI. Microarray data revealed that 14 miRNAs were upregulated and 46 miRNAs were downregulated by 2 times compared with sham rat spinal cords, and miR-494 was one of the miRNAs being most significantly downregulated. Subsequently, we investigated miR-494 function and found that upregulation of miR-494 by agomir-494 improves functional recovery, reduces lesion size and inhibits apoptotic cell in rats following SCI. Moreover, our data showed that miR-494 suppresses phosphatase and tensin homolog (PTEN), a negative regulator of AKT/mTOR pathway, through directly targeting its 3'-UTR in BV-2 cells. Most importantly, we demonstrated that overexpression of miR-494 activates AKT/mTOR signaling pathway via inhibiting PTEN expression in rat SCI model. These findings suggested that miR-494 harbored the protective effect after SCI by modulating PTEN/AKT/mTOR pathway in rats and it is a potential candidate for SCI therapeutics.


Subject(s)
Apoptosis/genetics , MicroRNAs/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Recovery of Function , Spinal Cord Injuries/pathology , Spinal Cord Injuries/physiopathology , 3' Untranslated Regions/genetics , Animals , Antagomirs/pharmacology , Apoptosis/drug effects , Base Sequence , Disease Models, Animal , Female , Mice , MicroRNAs/genetics , PTEN Phosphohydrolase/metabolism , Rats, Sprague-Dawley , Recovery of Function/drug effects , Spinal Cord/drug effects , Spinal Cord/metabolism , Spinal Cord/pathology , Spinal Cord/physiopathology , Spinal Cord Injuries/genetics , TOR Serine-Threonine Kinases/metabolism , Up-Regulation/drug effects
8.
Int J Mol Sci ; 18(4)2017 Apr 01.
Article in English | MEDLINE | ID: mdl-28368292

ABSTRACT

Recent evidence has suggested that long non-coding RNAs (lncRNAs) may play a significant role in the pathogenesis of several neurological diseases, including spinal cord injury (SCI). However, little is known about the role of lncRNAs in SCI. The aim of the present study was to evaluate the potential functions of lncRNAs in SCI and to identify the underlying mechanisms of action. We firstly analyzed Gene Expression Omnibus (GEO) datasets to investigate aberrantly-expressed lncRNAs which might be involved in the pathogenesis of SCI. The long non-coding RNA X-inactive specific transcript (XIST) was found to be one of the most significantly upregulated lncRNAs in the GEO dataset analysis, and is associated with apoptosis. We, therefore, selected this as a candidate lncRNA and investigated its function. We found that knockdown of lncRNA-XIST by Lv-shRNA had a prominent protective effect on SCI recovery by suppressing apoptosis through reactivation of the PI3K/AKT signaling pathway in rat spinal cord tissue. In particular, our results suggested that lncRNA-XIST may act as a competitive endogenous RNA, effectively becoming a sink for miR-494, leading to derepression of its target gene, phosphatase and tensin homolog deleted on chromosome ten (PTEN). In addition, an inverse relationship between lncRNA-XIST and miR-494 was observed in spinal cord tissues of SCI rats. Further study demonstrated that antagomiR-494 could reverse the protective effects of lncRNA-XIST knockdown on SCI rats through blocking the PTEN/PI3K/AKT signaling pathway. These results suggested that lncRNA-XIST knockdown may play an important role in limiting neuronal apoptosis in rats following SCI, and that the observed protective effects of lncRNA-XIST knockdown might have been mediated by its regulation on the phosphorylation of AKT by competitively binding miR-494. These findings have revealed, for the first time, the importance of the XIST/miR-494/PTEN/AKT signaling axis in the pathogenesis of SCI and suggest that lncRNA-XIST may be a promising molecular target for SCI therapy.


Subject(s)
Apoptosis/genetics , MicroRNAs/genetics , Proto-Oncogene Proteins c-akt/genetics , RNA, Long Noncoding/genetics , Spinal Cord Injuries/genetics , Animals , Blotting, Western , Down-Regulation , Gene Expression Profiling/methods , Immunohistochemistry , Male , Neurons/metabolism , PTEN Phosphohydrolase/genetics , PTEN Phosphohydrolase/metabolism , Phosphorylation , Proto-Oncogene Proteins c-akt/metabolism , RNA Interference , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/genetics , Spinal Cord Injuries/metabolism
9.
Spine (Phila Pa 1976) ; 42(5): 291-297, 2017 Mar.
Article in English | MEDLINE | ID: mdl-25785959

ABSTRACT

STUDY DESIGN: The expression of HOXB13 and HOXA9 proteins was detected. OBJECTIVE: The purpose of this study was to investigate the molecular signature of spinal ependymoma (EPN) and astrocytoma, 2 most common types of intramedullary spinal tumor. SUMMARY OF BACKGROUND DATA: Intramedullary spinal tumor is unusual. It leads to high neurological morbidity and mortality without treatment. Till now, its molecular feature has been elucidated up to a little extent. METHODS: A total of 37 cases of spinal EPN, including 12 myxopapillary EPNs (MEPNs), 18 classic EPNs, and 7 anaplastic EPNs, and another 12 cases of astrocytoma were selected for this study. Immunohistochemical analysis of a large cohort of patients providing clinical tumor samples was performed to compare the expression of HOXB13 and HOXA9 not only between spinal EPN and astrocytoma but also among all 3 World Health Organization grades of spinal EPN. RESULTS: The results showed that HOXB13 and HOXA9 were selectively expressed in spinal EPN instead of astrocytoma. Furthermore, we found the strongest positive response of HOXB13 in MEPN whereas that of HOXA9 was ubiquitously detected in all subgroups of EPN. CONCLUSION: Both specificity and sensitivity of HOXB13 in MEPN indicated that HOXB13 might be a diagnostic marker to distinguish MEPN from other 2 types of EPN and a promising therapeutic target for MEPN. The strong immunoreactivity of HOXA9 in spinal EPN suggested an indispensable role in the progression of spinal EPN, and further research on its molecular function will provide new clues for the development of treatment options. LEVEL OF EVIDENCE: N /A.


Subject(s)
Astrocytoma/surgery , Ependymoma/surgery , Genes, Homeobox/genetics , Homeodomain Proteins/genetics , Spinal Cord Neoplasms/genetics , Adolescent , Adult , Astrocytoma/genetics , Ependymoma/genetics , Female , Homeodomain Proteins/immunology , Humans , Male , Middle Aged , Spinal Cord Neoplasms/surgery , Young Adult
10.
Onco Targets Ther ; 8: 1119-27, 2015.
Article in English | MEDLINE | ID: mdl-26056476

ABSTRACT

"Glioblastoma multiforme" (GBM) is the frequent form of malignant glioma. Immature colon carcinoma transcript-1 (ICT1) is essential for cell vitality and mitochondrial function and has been recognized in several human cancers. In the study reported here, we attempted to evaluate the functional role of ICT1 in GBM cells. Lentivirus-mediated RNA interference (RNAi) was applied to silence ICT1 expression in human GBM cell lines U251 and U87. Cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony-formation assays. Cell-cycle progression was determined by flow cytometry with propidium iodide staining. The results revealed that lentivirus-mediated short hairpin RNA (shRNA) can specifically suppress the expression of ICT1 in U251 and U87 cells. Functional investigations proved for the first time, as far as we are aware, that ICT1 knockdown significantly inhibited the proliferation of both cell lines. Moreover, the cell cycle of U251 cells was arrested at Gap 2 (G2)/mitotic (M) phase after ICT1 knockdown, with a concomitant accumulation of cells in the Sub-Gap 1 (G1) phase. This study highlights the crucial role of ICT1 in promoting GBM cell proliferation, and provides a foundation for further study into the clinical potential of lentivirus-mediated silencing of ICT1 for GBM therapy.

11.
Brain Res ; 1605: 31-8, 2015 Apr 24.
Article in English | MEDLINE | ID: mdl-25681550

ABSTRACT

Tumor suppressor p53 has recently been reported to have numerous functions independent of tumorigenesis, including neuronal survival during ischemia. The mammalian target of rapamycin (mTOR) signaling pathway plays a central role in the regulation of metabolism, cell growth, development, and cell survival. Our recent work has demonstrated the neuroprotective effects of the mTOR pathway. Considering that p53 is also an important regulator of mTOR, to further clarify the role of p53 and the mTOR signaling pathway in neuronal ischemic-reperfusion injury, we used mouse primary mixed cultured neurons with an oxygen glucose deprivation (OGD) model to mimic an ischemic-reperfusion injury in vitro. A lentiviral system was also used to inhibit or overexpress p53 to determine whether p53 alteration affects OGD and reperfusion injury. Our results show that activated p53 was induced and it suppressed mTOR expression in primary mixed cultured neurons after OGD and reperfusion. Inhibiting p53, using either a chemical inhibitor or lentiviral-mediated shRNA, exhibited neuroprotective effects in primary cultured neurons against OGD and reperfusion injury through the upregulation of mTOR activity. Such protective effects could be reversed by rapamycin, an mTOR inhibitor. Conversely, p53 overexpression tended to exacerbate the detrimental effects of OGD injury by downregulating mTOR activity. These results suggest that p53 inhibition has a pivotal protective effect against an in vitro ischemia-reperfusion injury via mTOR signaling and provides a potential and promising therapeutic target for stroke treatment.


Subject(s)
Neurons/drug effects , Neuroprotective Agents/pharmacology , Reperfusion Injury/prevention & control , Signal Transduction/drug effects , TOR Serine-Threonine Kinases/metabolism , Tumor Suppressor Protein p53/antagonists & inhibitors , Animals , Benzothiazoles/pharmacology , Cells, Cultured , Female , Mice , Mice, Inbred C57BL , Neurons/metabolism , Neurons/pathology , Pregnancy , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Sirolimus/pharmacology , Toluene/analogs & derivatives , Toluene/pharmacology , Tumor Suppressor Protein p53/metabolism
12.
Exp Ther Med ; 9(1): 167-171, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25452796

ABSTRACT

Using microarray data, the present study identified differentially expressed microRNAs (miRNAs) and evaluated their regulatory characteristics in high-grade glioma patients, with the aim to further the understanding into the underlying etiology of the condition. Previously, studies have generally implemented regression or variance analysis, which ignores various background biological factors. However, in the present study, analysis was performed with microarray data collected from the Gene Expression Omnibus database using a partial least squares-based method, which is more sensitive in handling microarray data. Among the six identified differentially expressed miRNAs, hsa-miR-21 and hsa-miR-612 have been previously reported to be associated with glioma. In addition, the remaining miRNAs, hsa-miR-4680, hsa-miR-1908, hsa-miR-4656 and hsa-miR-4467, may also contribute to glioma progression since they are all associated with the tumorigenesis of other types of cancer. Moreover, the expression levels of hsa-miR-1908, hsa-miR-4656 and hsa-miR-4680 have been identified to significantly correlate with the survival rate. Enrichment analysis of the dysregulated target genes revealed that the selected miRNAs primarily affect biological processes in the nervous system and the protein phosphorylation process. Therefore, the results may offer a new understanding into the pathogenesis of high-grade glioma.

13.
Zhonghua Yi Xue Za Zhi ; 94(19): 1455-8, 2014 May 20.
Article in Chinese | MEDLINE | ID: mdl-25143162

ABSTRACT

OBJECTIVE: To explore the prognostic factors of intramedullary high grade astrocytomas. METHODS: Retrospective analyses were conducted for 21 surgical patients with high grade astrocytoma in spinal cord during 2008 to 2012 at our hospital. Their preoperative and postoperative profiles were recorded and evaluated by modified McCormick classification scheme. RESULTS: Their median age was 32.5 years. There were anaplastic astrocytoma (n = 14) and glioblastoma (n = 7). The prognoses of high grade astrocytomas were correlated with pathology grade and MIB-1 index. No statistic significance existed in age, gender, McCormick score, extent of resection, radiotherapy or chemotherapy. CONCLUSION: Intramedullary high grade astrocytoma has a low incidence, but its outcome is poor. Once definitely diagnosed, operation is recommended as early as possible. Frozen pathology should be performed to determine the extent of resection. After operation, chemotherapy and radiotherapy are also suggested.


Subject(s)
Astrocytoma , Spinal Cord Neoplasms , Adolescent , Adult , Aged , Astrocytoma/diagnosis , Astrocytoma/pathology , Astrocytoma/surgery , Child , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Spinal Cord Neoplasms/diagnosis , Spinal Cord Neoplasms/pathology , Spinal Cord Neoplasms/surgery , Young Adult
14.
Med Sci Monit ; 20: 802-6, 2014 May 15.
Article in English | MEDLINE | ID: mdl-24829084

ABSTRACT

BACKGROUND: This work aimed to evaluate the efficacy of virtual reality (VR) technology in neurosurgical anatomy through a comparison of the virtual 3D microanatomy of the suboccipital vertebral arteries and their bony structures as part of the resection of tumors in the craniovertebral junction (CVJ) of 20 patients compared to the actual microanatomy of the vertebral arteries of 15 cadaveric headsets. MATERIAL AND METHODS: The study was conducted with 2 groups of data: a VR group composed of 20 clinical cases and a physical body group (PB group) composed of 15 cadaveric headsets. In the VR group, the dissection and measurements of the vertebral arteries were simulated on a Dextroscope. In the PB group, the vertebral arteries in the cadaver heads were examined under a microscope and anatomical measurements of VA and bony structures were performed. The length and course of the vertebral arteries and its surrounding bony structures in each group were compared. RESULTS: The distances from the inferior part of the transverse process foramen (TPF) of C1 to the inferior part of TPF of C2 were 17.68±2.86 mm and 18.4±1.82 mm in the PB and VR groups, respectively. The distances between the middle point of the posterior arch of the atlas and the medial intersection of VA on the groove were 17.35±2.23 mm in the PB group and 18.13±2.58 mm in the VR group. The distances between the middle line and the entrance of VA to the lower rim of TPF of Atlas were 28.64±2.67 mm in PB group and 29.23±2.89 mm in VR group. The diameters of the vertebral artery (VA) at the end of the groove and foramen of C2 transverse process were 4.02±046 mm and 4.25±0.51 mm, respectively, in the PB group and 3.54±0.44 mm and 4.47±0.62 mm, respectively, in VR group. The distances between the VA lumen center and midline of the foramen magnum at the level of dural penetration was 10.4±1.13 mm in the PB group and 11.5±1.34 mm in the VR group (P>0.05). CONCLUSIONS: VR technology can accurately simulate the anatomical features of the suboccipital vertebral arteries and their bony structures, which facilitates the planning of individual surgeries in the CVJ.


Subject(s)
Neurosurgical Procedures/methods , Occipital Lobe/blood supply , Spine/anatomy & histology , User-Computer Interface , Vertebral Artery/anatomy & histology , Adult , Humans
15.
Asian Pac J Cancer Prev ; 15(7): 3145-9, 2014.
Article in English | MEDLINE | ID: mdl-24815461

ABSTRACT

Gene expression profiling facilitates the understanding of biological characteristics of gliomas. Previous studies mainly used regression/variance analysis without considering various background biological and environmental factors. The aim of this study was to investigate gene expression differences between grade III and IV gliomas through partial least squares (PLS) based analysis. The expression data set was from the Gene Expression Omnibus database. PLS based analysis was performed with the R statistical software. A total of 1,378 differentially expressed genes were identified. Survival analysis identified four pathways, including Prion diseases, colorectal cancer, CAMs, and PI3K-Akt signaling, which may be related with the prognosis of the patients. Network analysis identified two hub genes, ELAVL1 and FN1, which have been reported to be related with glioma previously. Our results provide new understanding of glioma pathogenesis and prognosis with the hope to offer theoretical support for future therapeutic studies.


Subject(s)
Brain Neoplasms/genetics , Brain Neoplasms/pathology , Gene Expression Profiling , Glioma/genetics , Glioma/pathology , ELAV Proteins/genetics , ELAV-Like Protein 1 , Fibronectins/genetics , Gene Expression Regulation, Neoplastic , Humans , Least-Squares Analysis , Neoplasm Grading , Prognosis
16.
Int J Med Sci ; 11(5): 488-93, 2014.
Article in English | MEDLINE | ID: mdl-24688313

ABSTRACT

Aberrant activation of hedgehog (Hh) signaling pathway plays an important role in the development and proliferation of glioblastoma (GBM) cells. However, its mechanism remains unknown. MicroRNAs (miRNAs) are short non-coding RNA molecules which are involved in the post-transcriptional regulation of genes, and enrolled in signaling transduction network in tumors. This study was designed to investigate the role of miRNAs targeting the Hh signaling pathway in GBMs. According to the expression level of Gli1 mRNA measured by real time PCR, GBM samples were assigned to Gli1 high or low expression group. MiRNA microarray was applied to screen the dysregulated miRNA. As a result, 17 miRNAs were differentially expressed between Gli1 high expression and low expression groups (p < 0.005). Thirteen miRNAs including miR-125b-1 were downregulated, while only 4 miRNAs including miR-144 were upregulated in Gli1 high expression group. In summary, our study presents a subset of miRNAs which target the Hh signaling pathway in GBMs, and throws some light on the aberrant activation mechanism.


Subject(s)
Glioblastoma/genetics , Hedgehog Proteins/genetics , Signal Transduction , Transcription Factors/biosynthesis , Animals , Cell Proliferation , Gene Expression Regulation, Neoplastic , Glioblastoma/pathology , Hedgehog Proteins/metabolism , Humans , MicroRNAs/biosynthesis , RNA, Messenger/genetics , Transcription Factors/genetics , Zinc Finger Protein GLI1
17.
Int J Clin Exp Med ; 6(9): 814-21, 2013.
Article in English | MEDLINE | ID: mdl-24179577

ABSTRACT

Multiple SDAVFs are quite rare. We present two cases with double synchronous shunts and both were treated during one-stage interventional or surgical procedure. Unique images of the multiple SDAVFs as a PMAVF-like fistula were obtained. These interesting findings suggest the presence of multiple fistulas must be considered in patients being evaluated for SDAVF. A multidisciplinary approach to the management of multiple SDAVFs should depend on the anatomic location and angioarchitecture.

18.
J Neurosurg Spine ; 19(1): 3-11, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23662884

ABSTRACT

OBJECT: Little is known regarding the anaplastic variant of primary ependymomas that involve the spinal cord. The aim of this study was to evaluate the clinical characteristics and treatment outcomes of primary spinal anaplastic ependymomas (PSAEs). METHODS: Medical records were reviewed in 20 patients with pathologically proven PSAEs who underwent surgical treatment at the Department of Neurosurgery in Huashan Hospital between 1999 and 2008. RESULTS: This series included 7 women and 13 men between the ages of 2 and 67 years (mean 31.9 years). The mean preoperative course was 9.3 months (range 20 days to 48 months). The most common PSAE locations were the cervical and thoracic spinal cords. The most common presenting symptom was weakness, followed by numbness, bowel or bladder dysfunction, and pain. Gross-total resection (GTR) was achieved in 17 patients, and a subtotal removal was performed in 3 patients. Nine patients received radiation therapy and/or chemotherapy. The mean follow-up duration was 83.5 months. Functional assessment of the 10 patients available at the latest follow-up evaluation showed that 2 had worsened and 8 remained unchanged from their preoperative status. There were 2 local recurrences and 1 lung metastasis. CONCLUSIONS: Patients with PSAEs presented with a much shorter preoperative course than patients with Grade II ependymomas in previous studies. Patients with tumors that involved the cervical spinal cord experienced a worse outcome. Surgical removal of PSAEs, with the goal of GTR, is beneficial to patients. The role of radiation therapy and chemotherapy in PSAEs remains to be determined in further studies.


Subject(s)
Ependymoma/surgery , Neurosurgical Procedures/methods , Spinal Cord Neoplasms/surgery , Spine/surgery , Adolescent , Adult , Aged , Cervical Vertebrae/surgery , Child, Preschool , Ependymoma/drug therapy , Ependymoma/radiotherapy , Female , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm Metastasis/diagnosis , Neoplasm Recurrence, Local/diagnosis , Retrospective Studies , Spinal Cord Neoplasms/drug therapy , Spinal Cord Neoplasms/radiotherapy , Thoracic Vertebrae/surgery , Treatment Outcome , Young Adult
19.
Neurol India ; 60(6): 589-96, 2012.
Article in English | MEDLINE | ID: mdl-23287320

ABSTRACT

BACKGROUND: Hedgehog/Gli1 (HH/Gli1) pathway plays an important role in the patterning and development of the central nervous system during embryogenesis. Recent data have shown its potential involvement in a subset of human gliomas and inhibition of the pathway resulted in tumor suppression in both in vitro and in vivo studies. The underlying mechanisms of tumor suppression, however, remain to be fully elucidated. MATERIALS AND METHODS: Gli1 expression was investigated in 60 surgically resected glioma tissues (World Health Organization (WHO) III-IV). RESULTS: Gli1 was expressed in 43 gliomas with high Gli1 expression in nine cases, moderate expression in 21 cases, and low expression in 13 cases. Additionally, microvessel counts were higher in Gli1 positive gliomas than those in Gli1 negative gliomas. Gli1 expression in gliomas was positively correlated with microvessel density (MVD). To explore the molecular mechanisms of the phenotypic changes, we performed quantitative real-time polymerase chain reaction (PCR) and Western blot analysis to monitor the changes of a series of genes, which play critical roles in the regulation of glioma angiogenesis. In conclusion, HH/Gli1 pathway inhibition resulted in down-regulation of vascular endothelial growth factor (VEGF), matrix metalloproteinase 2 (MMP2), and matrix metalloproteinase 9 (MMP9) expressions, whereas this pathway activation led to up-regulation of VEGF, MMP2, and MMP9 expressions. These molecular changes of the HH/Gli1 pathway inhibited by indirect drug approach were consistent with Gli1 RNA-interference (RNAi) in glioma cell lines. CONCLUSION: Our findings demonstrated that the aberrantly active HH/Gli1 pathway contributed to angiogenesis in part through induction of VEGF, MMP2, and MMP9.


Subject(s)
Brain Neoplasms/complications , Glioma/complications , Hedgehog Proteins/metabolism , Neovascularization, Pathologic/etiology , Signal Transduction/genetics , Transcription Factors/metabolism , Cell Line, Tumor , Enzyme Inhibitors/pharmacology , Female , Gene Expression Regulation, Neoplastic/drug effects , Hedgehog Proteins/genetics , Humans , Male , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Patched Receptors , Platelet Endothelial Cell Adhesion Molecule-1/genetics , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , RNA Interference/physiology , RNA, Messenger/metabolism , Receptors, Cell Surface/metabolism , Statistics, Nonparametric , Transcription Factors/genetics , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism , Veratrum Alkaloids/pharmacology , Zinc Finger Protein GLI1
20.
Clin Neurol Neurosurg ; 113(10): 889-94, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21831519

ABSTRACT

OBJECTIVE: To evaluate the application of virtual reality technology in neurosurgical anatomy we compared the virtual three-dimensional (3D) microanatomy of the temporal bridging veins as part of the resection of tumors across the petrosal crest in 25 patients against the actual microanatomy of the temporal bridging veins on 20 cadaveric head sets. PATIENTS AND METHODS: The experiment was carried out by two groups of data: a virtual group made of 25 clinical cases and a physical body group made of 20 cadaveric head sets. In the physical body group, the temporal bridging veins on the cadaveric heads were examined under the microscope from the number of their tributaries to termination and measure the distance between emptying point on sinus of labbé vein and sigmoid transverse sinus. In the virtual group, the dissection of the temporal bridging veins was simulated on Dextroscope. We compared the anatomical features of temporal bridging veins in two groups. Virtual reality technology was used in the planning of 25 cases for which the anatomy of temporal bridging veins needed to be studied carefully by the neurosurgical team. RESULTS: Four basic configurations of veins were found: venous lakes running in the tentorium before emptying the sinuses 17.5% (7 hemispheres), candelabra of veins uniting to form one large drainage 40% (16 hemispheres), single independent draining veins 20% (8 hemispheres) and multiple independent draining veins 22.5% (9 hemispheres) in physical body group, venous lake16% (8 hemispheres), candelabra of veins uniting to form one large drainage 42% (21 hemispheres), single independent draining veins 18% (9 hemispheres) and multiple independent draining veins 24% (12 hemispheres) in virtual group. 213 tributaries (85 drainage to labbé veins) and 87 terminations of temporal bridging veins were found in cadaveric heads, whereas 167 tributaries (80 to labbé veins) and 81 terminations of temporal bridging veins were found in the virtual group. The distribution of anatomical terminations of temporal bridging veins were divided into three groups: transverse area 52.87% (46) tentorium area 24.13% (21) and petrosal area 23.10% (20) in physical body group, whereas 54.35% (50) 23.91% (22) and 21.74% (20) in virtual group, respectively. The proportion of fore-placed type veins of labbé is 7.69% in physical body group and 8.33% in virtual group (P>0.05). The distance from the emptying point of the labbé veins to the sigmoid transverse point in the virtual group was 18.75 ± 1.95 mm, in the physical body group was 20.12 ± 2.51 mm (P>0.05). The anatomical features of labbé veins found during the operation of the 25 patients with tumors extended from middle fossa to posterior fossa and were identical to what was seen in presurgical planning. CONCLUSIONS: Virtual reality technology can accurately simulate the anatomical feature of the temporal bridging veins which facilitates the planning of individual operations in neurosurgery.


Subject(s)
Cerebral Veins/anatomy & histology , Cranial Fossa, Middle/anatomy & histology , Cranial Fossa, Middle/surgery , Imaging, Three-Dimensional/methods , Infratentorial Neoplasms/surgery , Neurosurgical Procedures/methods , Skull Base Neoplasms/surgery , Surgery, Computer-Assisted/methods , Temporal Lobe/blood supply , User-Computer Interface , Cadaver , Female , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Meningioma/surgery , Middle Aged , Petrous Bone/anatomy & histology , Postoperative Complications
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