Imipramine impedes glioma progression by inhibiting YAP as a Hippo pathway independent manner and synergizes with temozolomide.

Patients with malignant glioma often suffered from depression, which leads to an increased risk of detrimental outcomes. Imipramine, an FDA-approved tricyclic antidepressant, has been commonly used to relieve depressive symptoms in the clinic. Recently, imipramine has been reported to participate in the suppression of tumour progression in several human cancers, including prostate cancer, colon cancer and lymphomas. However, the effect of imipramine on malignant glioma is largely unclear. Here, we show that imipramine significantly retarded proliferation of immortalized and primary glioma cells. Mechanistically, imipramine suppressed tumour proliferation by inhibiting yes-associated protein (YAP), a recognized oncogene in glioma, independent of Hippo pathway. In addition to inhibiting YAP transcription, imipramine also promoted the subcellular translocation of YAP from nucleus into cytoplasm. Consistently, imipramine administration significantly reduced orthotopic tumour progression and prolonged survival of tumour-bearing mice. Moreover, exogenous overexpression of YAP partially restored the inhibitory effect of imipramine on glioma progression. Most importantly, compared with imipramine or temozolomide (TMZ) monotherapy, combination therapy with imipramine and TMZ exhibited enhanced inhibitory effect on glioma growth both in vitro and in vivo, suggesting the synergism of both agents. In conclusion, we found that tricyclic antidepressant imipramine impedes glioma progression by inhibiting YAP. In addition, combination therapy with imipramine and TMZ may potentially serve as promising anti-glioma regimens, thus predicting a broad prospect of clinical application.

Specific knockdown of hippocampal astroglial EphB2 improves synaptic function via inhibition of D-serine secretion in APP/PS1 mice.

Increasing evidence emphasizes the protective role of Eph receptors in synaptic function in the pathological development of Alzheimer's disease (AD); however, their roles in the regulation of hippocampal astrocytes remain largely unknown. Here, we directly investigated the function of astroglial EphB2 on synaptic plasticity in APP/PS1 mice. Using cell isolation and transgene technologies, we first isolated hippocampal astrocytes and evaluated the expression levels of ephrinB ligands and EphB receptors. Then, we stereotaxically injected EphB2-Flox-AAV into the hippocampus of GFAP-cre/APP/PS1 mice and further evaluated hippocampal synaptic plasticity and astroglial function. Interestingly, astrocytic EphB2 expression was significantly increased in APP/PS1 mice in contrast to its expression profile in neurons. Moreover, depressing this astroglial EphB2 upregulation enhanced hippocampal synaptic plasticity, which results from harmful D-serine release. These results provide evidence of the different expression profiles and function of EphB2 between astrocytes and neurons in AD pathology.

Delivery of Doxorubicin from Hyaluronic Acid-Modified Glutathione-Responsive Ferrocene Micelles for Combination Cancer Therapy.

A combination of different chemotherapy approaches can obtain the best response for many cancers. However, the greatest challenge is the development of a nanoparticle formulation that can encapsulate different chemotherapeutic agents to achieve the proper synergetic chemotherapy for the tumor. Here, amphiphilic ferrocenium-tetradecyl (Fe-C14) was constructed to form cationic micelles in an aqueous solution via self-assembly. Then, it was coated by hyaluronic acid (HA) through electrostatic interactions to generate HA-Fe-C14 micelles. The HA-Fe-C14 micelles were used to deliver doxorubicin (DOX), and it showed that the DOX could be released rapidly under a high-GSH tumor environment. The HA-Fe-C14/DOX micelles were able to accumulate efficiently in tumor and showed significant anticancer effect both in vitro and in vivo. These results suggest that HA-Fe-C14/DOX micelles are a useful drug delivery system that enhances synergic antitumor treatment effects.

Ubiquitin-specific protease 22 promotes the proliferation, migration and invasion of glioma cells.

Ubiquitin-specific protease 22 (USP22), as one of the 11 death-from-cancer signature genes, presented high expression in a variety of tumors. Previous studies showed that USP22 played a significant role in cell-cycle, oncogenesis, clinicopathology and survival. Our studies have presented USP22 was over-expressed in glioma tissue and the patients with high expression of USP22 had a poor survival than that with low expression of USP22. However, the concrete effect of USP22 on biological behavior in glioma cells has been rarely reported. The study aimed to clear the effect of USP22 on cell proliferation, migration and invasion in glioma. Using siRNA, USP22 was knocked down in U251 and U87 glioma cells and successful transfection effect was validated. Cell proliferation, migration and invasion were observed by the methods of EdU, Wound healing and Transwell assay, separately. At the same time, the expression of MMP2 was detected by Gelatin zymography after transfecting siRNAs. After the knockdown of USP22 by siRNA, the abilities of glioma cell proliferation, migration and invasion were decreased, accompanying, the expression of MMP2 was also decreased. We drew a conclusion that USP22 could increase the abilities of proliferation, migration and invasion of glioma cells, and promote the growth and development of glioma.

Near-infrared light-activated red-emitting upconverting nanoplatform for T1-weighted magnetic resonance imaging and photodynamic therapy.

Photodynamic therapy (PDT) has increasingly become an efficient and attractive cancer treatment modality based on reactive oxygen species (ROS) that can induce tumor death after irradiation with ultraviolet or visible light. Herein, to overcome the limited tissue penetration in traditional PDT, a novel near-infrared (NIR) light-activated NaScF4: 40% Yb, 2% Er@CaF2 upconversion nanoparticle (rUCNP) is successfully designed and synthesized. Chlorin e6, a photosensitizer and a chelating agent for Mn2+, is loaded into human serum albumin (HSA) that further conjugates onto rUCNPs. To increase the ability to target glioma tumor, an acyclic Arg-Gly-Asp peptide (cRGDyK) is linked to rUCNPs@HSA(Ce6-Mn). This nanoplatform enables efficient adsorption and conversion of NIR light (980 nm) into bright red emission (660 nm), which can trigger the photosensitizer Ce6-Mn complex for PDT and T1-weighted magnetic resonance imaging (T1-weighted MRI) for glioma diagnosis. Our in vitro and in vivo experiments demonstrate that NIR light-activated and glioma tumor-targeted PDT can generate large amounts of intracellular ROS that induce U87 cell apoptosis and suppress glioma tumor growth owing to the deep tissue penetration of irradiated light and excellent tumor-targeting ability. Thus, this nanoplatform holds potential for applications in T1-weighted MRI diagnosis and PDT of glioma for antitumor therapy. STATEMENT OF SIGNIFICANCE: A near-infrared (NIR) light-activated nanoplatform for photodynamic therapy (PDT) was designed and synthesized. The Red-to-Green (R/G) ratio of NaScF4: 40% Yb, 2% Er almost reached 9, a value that was much higher than that of a traditional Yb/Er-codoped upconversion nanoparticle (rUCNP). By depositing a CaF2 shell, the red-emission intensities of the rUCNPs were seven times strong as that of NaScF4: 40% Yb, 2% Er. The enhanced red-emitting rUCNPs could be applied in many fields such as bioimaging, controlled release, and real-time diagnosis. The nanoplatform had a strong active glioma-targeting ability, and all results achieved on subcutaneous glioma demonstrated that our NIR light-activated red-emitting upconverting nanoplatform was efficient for PDT. By loading Ce6-Mn complex into rUCNPs@HSA-RGD, the nanoplatform could be used as a T1-weighted magnetic resonance imaging agent for tumor diagnosis.

pH-Responsive Magnetic Mesoporous Silica-Based Nanoplatform for Synergistic Photodynamic Therapy/Chemotherapy.

By overcoming drug resistance and subsequently enhancing the treatment, the combination therapy of photodynamic therapy (PDT) and chemotherapy has promising potential for cancer treatment. However, the major challenge is how to establish an advanced nanoplatform that can be efficiently guided to tumor sites and can then stably release both chemotherapy drugs and a photosensitizer simultaneously and precisely. In this study, which considered the possibility and targeting efficiency of a magnetic targeting strategy, a novel Fe3O4@mSiO2(DOX)@HSA(Ce6) nanoplatform was successfully built; this platform could be employed as an efficient synergistic antitumor nanoplatform with magnetic guidance for highly specific targeting and retention. Doxorubicin (DOX) molecules were loaded into mesoporous silica with high loading capability, and the mesoporous channels were blocked by a polydopamine coating. Human serum albumin (HSA) was conjugated to the outer surface to increase the biocompatibility and blood circulation time, as well as to provide a vehicle for loading photosensitizer chlorin e6 (Ce6). The sustained release of DOX under acidic conditions and the PDT induced by red light exerted a synergistic inhibitory effect on glioma cells. Our experiments demonstrated that the pH-responsive Fe3O4@mSiO2(DOX)@HSA(Ce6) nanoplatform was guided to the tumor region by magnetic targeting and that the nanoplatform suppressed glioma tumor growth efficiently, implying that the system is a highly promising photodynamic therapy/chemotherapy combination nanoplatform with synergistic effects for cancer treatment.

Expression of WW domain-containing protein 2 is correlated with pathological grade and recurrence of glioma.

OBJECTIVE: WW domain-containing protein 2 (WWP2) is an E3 ubiquitin ligase, which belongs to the NEDD4-like protein family. Recently, it is reported to play a key role in tumorigenesis and development of tumors such as prostate and lung cancer. However, there has been not related report on glioma until now. The aim of this study is to detect the expression of WWP2 and analyze its correlation to the pathological grade and tumor recurrence in patients with glioma. MATERIALS AND METHODS: Western blot and immunohistochemistry were separately used to detect the expression of WWP2 protein in 31 brain glioma tissue samples and 80 brain glioma paraffin specimens. The method of Kaplan-Meier was used to analyze the correlation between the WWP2 expression and glioma recurrence. RESULTS: The protein expression level of WWP2 in glioma tissue was significantly higher than that in nontumorous brain tissue (P < 0.05), and the protein expression level of WWP2 in high-grade glioma (Grade III-IV) was significantly higher than that in low-grade glioma (Grade I-II) (P < 0.05). Kaplan-Meier analysis indicated that the patients with high WWP2 expression had significantly shorter tumor recurrence time than the patients with low WWP2 expression (P < 0.05). CONCLUSION: Our study suggests that WWP2 may play a role in the genesis and development of glioma; it may be a potential biomarker to predict pathological grade and tumor recurrence in patients with glioma.

ß-transducin repeat-containing E3 ubiquitin protein ligase inhibits migration, invasion and proliferation of glioma cells.

ß-transducin repeat-containing E3 ubiquitin protein ligase (ß-TrCP) serves as the substrate recognition subunit for the Skp1-Cullin1-F-box protein E3 ubiquitin ligase, which recognizes the double phosphorylated DSG (X)2+nS destruction motif in various substrates that are essential for numerous aspects of tumorigenesis and regulates several important signaling pathways. However, the biological significance of ß-TrCP in glioma progression remains largely unknown. A previous study by the authors demonstrated that the levels of ß-TrCP protein expression in brain glioma tissues were significantly lower compared with non-tumorous tissues and that higher grades of gliomas exhibited lower levels of ß-TrCP expression in comparison with lower glioma grades. In addition, low ß-TrCP expression was associated with poor prognosis in patients with glioma. Subsequently, the present study aimed to investigate the effect of ß-TrCP on migratory, invasive and proliferative abilities of glioma cells. ß-TrCP plasmids were transfected into cultured U251 and U87 glioma cells, and changes in migration, invasion and proliferation were analyzed using wound healing, Transwell and EdU assays. It was identified that the overexpression of ß-TrCP inhibited migration, invasion and proliferation in glioma cells. In summary, these results indicate that ß-TrCP may serve a protective role against the progression of glioma by suppressing cell migration, invasion and proliferation. The potential mechanism of ß-TrCP I glioma cells requires additional investigation.

Selective deletion of apolipoprotein E in astrocytes ameliorates the spatial learning and memory deficits in Alzheimer's disease (APP/PS1) mice by inhibiting TGF-ß/Smad2/STAT3 signaling.

Astrocytes and apolipoprotein E (apoE) play critical roles in cognitive function, not only under physiological conditions but also in some pathological situations, particularly in the pathological progression of Alzheimer's disease (AD). The regulatory mechanisms underlying the effect of apoE, derived from astrocytes, on cognitive deficits during AD pathology development are unclear. In this study, we generated amyloid precursor protein/apoE knockout (APP/apoEKO) and APP/glial fibrillary acidic protein (GFAP)-apoEKO mice (the AD mice model used in this study was based on the APP-familial Alzheimer disease overexpression) to investigate the role of apoE, derived from astrocytes, in AD pathology and cognitive function. To explore the mechanism, we investigated the amyloidogenic process related transforming growth factor ß/mothers against decapentaplegic homolog 2/signal transducer and activator of transcription 3 (TGF-ß/Smad2/STAT3) signaling pathway and further confirmed by administering TGF-ß-overexpression adeno-associated virus (specific to astrocytes) to APP/GFAP-apoEKO mice and TGF-ß-inhibition adeno-associated virus (specific to astrocytes) to APP/WT mice. Whole body deletion of apoE significantly ameliorated the spatial learning and memory impairment, reduced amyloid ß-protein production and inhibited astrogliosis in APP/apoEKO mice, as well as specific deletion apoE in astrocytes in APP/GFAP-apoEKO mice. Moreover, amyloid ß-protein accumulation was increased due to promotion of amyloidogenesis of APP, and astrogliosis was upregulated by activation of TGF-ß/Smad2/STAT3 signaling. Furthermore, the overexpression of TGF-ß in astrocytes in APP/GFAP-apoEKO mice abrogated the effects of apoE knockout. In contrast, repression of TGF-ß in astrocytes of APP/WT mice exerted a therapeutic effect similar to apoE knockout. These data suggested that apoE derived from astrocytes contributes to the risk of AD through TGF-ß/Smad2/STAT3 signaling activation. These findings enhance our understanding of the role of apoE, derived from astrocytes, in AD and suggest it to be a potential biomarker and therapeutic target for AD.

Hypoxia-responsive ionizable liposome delivery siRNA for glioma therapy.

Here, we report the hypoxia-responsive ionizable liposomes to deliver small interference RNA (siRNA) anticancer drugs, which can selectively enhance cellular uptake of the siRNA under hypoxic and low-pH conditions to cure glioma. For this purpose, malate dehydrogenase lipid molecules were synthesized, which contain nitroimidazole groups that impart hypoxia sensitivity and specificity as hydrophobic tails, and tertiary amines as hydrophilic head groups. These malate dehydrogenase molecules, together with DSPE-PEG2000 and cholesterol, were self-assembled into O'1,O1-(3-(dimethylamino)propane-1,2-diyl) 16-bis(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl) di(hexadecanedioate) liposomes (MLP) to encapsulate siRNA through electrostatic interaction. Our study showed that the MLP could deliver polo-like kinase 1 siRNA (siPLK1) into glioma cells and effectively enhance the cellular uptake of MLP/siPLK1 because of increased positive charges induced by hypoxia and low pH. Moreover, MLP/siPLK1 was shown to be very effective in inhibiting the growth of glioma cells both in vitro and in vivo. Therefore, the MLP is a promising siRNA delivery system for tumor therapy.

Effect of ATorvastatin On Chronic subdural Hematoma (ATOCH): a study protocol for a randomized controlled trial.

BACKGROUND: Chronic subdural hematoma (CSDH) is a common disease that is more prevalent in older people. Surgical intervention is a safe treatment of choice. However, the recurrence rate is relatively high and the outcome is not always satisfactory among surgically treated patients. It is believed that aberrant angiogenesis and intracapsular inflammation contribute to the development of CSDH. Atorvastatin is reported to promote angiogenesis and suppress inflammation. We have recently shown that atorvastatin is effective to non-surgically reduce and eliminate CSDH with minimal side effects. Here, we report a clinical research trial protocol that is designed to evaluate the therapeutic effects of atorvastatin on CSDH. METHODS/DESIGN: We have designed a multi-center, randomized, placebo-controlled, double blind clinical trial for evaluating the efficacy of oral atorvastatin in reducing CSDH. We have so far recruited 96 patients with CT-confirmed or MRI-confirmed CSDHs from 16 medical centers in China. These patients were originally recruited for the Oriental Neurosurgical Evidence-based Study Team (ONET) study. After informed consent is provided, patients are randomized to receive either atorvastatin (oral 20 mg/night for 8 weeks) or placebo (dextrin for 8 weeks); and followed for 16 weeks after the treatment. The primary outcome is the change in hematoma volume at the end of 8-week treatment. Secondary outcomes include: changes in 1) the hematoma volume at the 4(th), 12(th), and 24(th) weeks; 2) Markwalder's Grading Scale and Glasgow Coma Scale (MGS-GCS); 3) Glasgow Outcome Score (GOS) and 4) Activities of Daily Life-the Barthel Index scale (ADL-BI). Safety will be assessed during the study by monitoring adverse events, laboratory tests, electrocardiography (ECG), measurements of vital signs (temperature, pulse, and blood pressure) and body weight. DISCUSSION: Results of this trial will provide critical information regarding whether atorvastatin is an effective and safe alternative to surgical treatment of CSDH. TRIAL REGISTRATION: ClinicalTrials.gov Identifier--NCT02024373 The date of trial registration: 7 August 2013.

FK506-binding protein 5 inhibits proliferation and stimulates apoptosis of glioma cells.

INTRODUCTION: FK506-binding protein 5 (FKBP5) is reported to act as a scaffolding protein for Akt to promote the dephosphorylation of AKT Ser473 and suppress pancreatic cancer growth. However, other studies have shown that FKBP5 promotes tumor growth and chemoresistance through regulating NF-κB signaling in other cancers. In this study, we attempted to investigate the role and mechanism of action of FKBP5 in the regulation of proliferation and apoptosis of glioma cells. MATERIAL AND METHODS: The glioma U251 cell line was used as the model. Cell proliferation was detected by MTT assay. Cell apoptosis was detected by annexin-V staining. Protein expression was detected by Western blot analysis. RESULTS: FKBP5 overexpression inhibited the proliferation of U251 cells significantly (p < 0.05), and promoted the apoptosis of U251 cells significantly (p < 0.05). In addition, FKBP5 overexpression inhibited the phosphorylation of Akt at Ser743, decreased the level of Bcl-2, increased the level of Bax, and enhanced the cleavage of caspase-9 and caspase-3 (p < 0.05 compared to control). In contrast, FKBP5 knockdown enhanced the proliferation of U251 cells, increased the phosphorylation of Akt significantly (p < 0.05), increased the expression of Bcl-2 and decreased the expression of Bax, and decreased the cleavage of caspase-9 and caspase-3 significantly (p < 0.05). CONCLUSIONS: FKBP5 plays the role of a tumor suppressor in glioma by inhibiting the activation of Akt and stimulating the intrinsic mitochondrial apoptotic pathway, and could be used as a new target for gene therapy of glioma.

Expression of ß-transducin repeat-containing E3 ubiquitin protein ligase in human glioma and its correlation with prognosis.

ß-transducin repeat-containing E3 ubiquitin protein ligase (ß-TrCP) targets a number of substrates essential for specific aspects of tumorigenesis. In addition, ß-TrCP regulates various important signaling pathways. As ß-TrCP is involved in regulating the ubiquitination and degradation of multiple oncogenes and tumor suppressors, the function of ß-TrCP varies between cancer types. At present, the association between ß-TrCP expression and clinicopathological factors in glioma is unknown. Therefore, the current study used western blotting and immunohistochemistry to investigate the expression of ß-TrCP protein in glioma tissue specimens. It was identified that ß-TrCP protein expression levels were significantly lower in glioma compared with non-tumorous human brain tissues. Furthermore, the higher the grade of glioma, the lower the level of ß-TrCP expression. Kaplan-Meier analysis demonstrated that patients with low ß-TrCP expression experienced significantly worse overall survival compared with patients with high ß-TrCP expression. The results indicate that downregulation of ß-TrCP may be associated with poor survival in patients with glioma. Together, the current data indicates that ß-TrCP may be applied as a useful indicator of glioma prognosis and may serve as an anticancer therapeutic target for glioma, however further investigation is required.

Establishment of a spinal cord injury model in adult rats by an electrocircuit-controlled impacting device and its pathological observations.

One of the crucial challenges in medicine is the treatment and rehabilitation of spinal cord injury (SCI). In this study, we established a stable and reproducible acute spinal cord injury model in adult rats. The SCI was inflicted by our self-innovated spinal cord impact device controlled by electrical circuit. The Basso, Beattie, and Bresnahan Locomotor Rating Scale (BBB) score, electrophysiology, histological, and immunohistochemical changes after SCI were observed. The BBB score of the injured rats began to increase from the 3rd day of SCI and reached at the score 7.2 ± 1.3 at the 28th day. The latency of cortical somatosensory evoked potentials (CSEP) was not observed 2 and 6 h after injury, but appeared 24 h after injury which was significantly prolonged. It recovered from day 3 gradually to 27.3 ± 2.7 ms on day 28. H&E staining showed that the structure of gray and white matter was disrupted after the SCI. The result also showed dramatic neuron degenerations, cellular swelling, and the proliferation of glial cells. The immunohistochemical analysis showed that the expression of neuron specific enolase (NSE) and neurofilament 200 (NF200) started lowering at 2 h and dropped to the bottom at 24 h. Their expression rebound from day 3 and yet to the original level at day 28 (P < 0.05). The number of cells expressing glial fibrillary acidic protein (GFAP) hiked from day 3, peaked at day 14, and began recovering from day 28 (P < 0.05). The changes of NSE, NF200, GFAP, and CSEP were significantly associated with the BBB score (P < 0.05). In conclusion, our self-innovated device can reproduce the injury model stably. The changes of NSE, NF, and GFAP after spinal cord injury reflect the characteristics of pathological change, which are closely associated with the functional recovery from the spinal cord injury.

Clinical value of multi-slice 3-dimensional computed tomographic angiography in the preoperative assessment of meningioma.

The aim of this study was to evaluate the clinical value of multislice 3-dimensional computed tomographic angiography (3D-CTA) in the preoperative assessment of meningiomas. A total of 331 cases with meningiomas confirmed by CT and MRI were examined using 3D-CTA. The locations of the tumors were observed to be as follows: parasagittal and falcine in 125 cases, sphenoidal in 39 cases, in the olfactory groove in 19 cases, tentorial in 21 cases, parasellar in 33 cases, petroclival in 29 cases, intraventricular in 7 cases and on the convexity of the brain in 58 cases. The reconstructed images were processed by shaded volume rendering, maximum intensity projection and color-shaded surface display. The 3D-CTA images were used to imitate the surgical approach. Surgery was performed according to the information provided in the 3D-CTA images. 3D-CTA provided clear 3D images of the meningioma and the relationship with the adjacent vessels and the skull base, and demonstrated the optimal surgical approach for removing the neoplasm. The results of 3D-CTA corresponded extremely well with the surgical observations. 3D-CTA is able to provide 3D images of the meningioma, adjacent vessels and the bones in the skull base. Furthermore, 3D-CTA supplies information vital in the selection of the optimal surgical approach and information that aids the management of the sinus during the surgery. 3D-CTA is of great value in the preoperative evaluation of meningiomas.

Changes in transcriptional factor binding capacity resulting from promoter region methylation induce aberrantly high GDNF expression in human glioma.

Glial cell line-derived neurotrophic factor (GDNF), which belongs to transforming growth factor ß superfamily, plays important roles in glioma pathogenesis. Gdnf mRNA is aberrantly increased in glioma cells, but the underlying transcription mechanism is unclear. Here, we found that although the base sequence in the promoter region of the gdnf gene was unchanged in glioma cells, there were significant changes in the methylation level of promoter region I (P < 0.05) in both high- and low-grade glioma tissues. However, the methylation degree in promoter region II was notably decreased in low-grade glioma tissue compared to normal brain tissue (P < 0.05), and the demethylation sites were mainly located in the enhancer region. Conversely, methylation was markedly increased in high-grade glioma tissue (P < 0.05), and the sites with decreased methylation level were mainly located in the silencer region. The binding capacities of several transcriptional factors, such as activating protein 2, specificity protein 1, ETS-related gene 2, and cAMP response element binding protein, which specifically bind to regions with altered methylation status decreased along with the pathological grade of glioma, and the differences between high-grade glioma and normal brain tissue were significant (P < 0.05). The results suggest that changes in transcriptional factor binding capacity are due to changes in promoter region methylation and might be the underlying mechanism for aberrantly high gdnf expression in glioma.

[Application of diffusion tensor imaging in preoperation and postoperation patients of glioma with 3.0 Tesla MRI].

OBJECTIVE: To investigate the clinical usefulness of diffusion tensor imaging (DTI) in demonstrating between gliomas and surrounding fibers. METHODS: 24 patients of glioma (WHO grade: grade I - II 16 cases; grade III - IV 8 cases) were examined using DTI and conventional contrast-enhanced MRI of 3.0 T MRI scanner (GE company, America). After the initial data acquisition introduced into workstation, image analysis was performed with the use of functool software. Mean diffusivity (MD) and fractional anisotropy (FA) values were measured in regions of solid tumor, surrounding edema and normal white matter of the high grade cerebral gliomas. Differences in these values among the tissues were assessed on the high grade cerebral gliomas. Anatomic relationship between intracranial tumors and surrounding fibers was analysed on fractional anisotropic (FA) map, color-coded directional map, three-dimensional white matter tractography. All patients' symptoms were evaluated preoperative and postoperative respectively. RESULTS: The DTI patterns altered by the tumor were categorized as follows: displacement, infiltration and destruction. The tractography showed that the main influence in 16 cases of grade I - II glioma on adjacent white matter tracts was displacement, but infiltration and destruction were also revealed. The patients have definite improvement in symptoms. The destruction and infiltration of fiber tracts could be seen in all edema regions around grade III - IV gliomas in 8 cases. The patients have not definite improvement in symptoms. Apparently significant differences of MD were found in solid tumor, surrounding edema, compared with normal white matter regions (P < 0.05). But there was no significant difference among solid tumor and surrounding edema region (P > 0.05). There were significant differences of FA between solid tumor, surrounding edema and normal white matter region (P < 0.05). CONCLUSIONS: The DTI offered the optimal visualization of white matter tracts. DTI plays an important role in demonstrating relationship between gliomas and neighboring fibers. MD and FA values could be used to distinguish normal white matter from solid tumor and surrounding edema region of high grade glioma. The application of DTI in preoperation plays an guidance role in making microsurgery plans and the evaluation of brain functional recovery in postoperation. DTI should be of great value in the microsurgical planning as well as estimation and reduction of potential postoperative neurological deficits for the cerebral gliomas resection.

Construction of recombinant adenoviral vector overexpressing human HIF-1alpha gene.

Hypoxia inducible factor 1 (HIF-1) is a heterodimeric transcription factor that plays an important role in oxygen homeostasis. In response to low level of oxygen, subunit HIF-1alpha expression is upregulated and transactivates its target genes essential for energy metabolism, erythropoiesis and vascular development. HIF-1alpha is thought to be able to protect hypoxic cells from apoptosis or necrosis under ischemic and anoxic conditions, the major trauma factors that affect the recovery of brain and spinal cord injury. Here we report the construction of recombinant adenovirus vector overexpressing HIF-1alpha intended for gene therapy against desired neuronal injuries. The recombinant vector could be packaged and yielded significantly high viral titers at 2 x 10(13) CFU in HEK293T cells and good expression levels of HIF-1alpha when superinfected in Hela cells.