Brain gliomas Biological characteristics and correlation with the status of adjacent corticospinal tracts

Malignant behaviors of brain gliomas include proliferation and infiltration.It remains unclear which behavior influences the status of adjacent corticospinal tracts.Diffusion tensor imaging can show the status of brain white matter fiber tracts.Ki-67 and CD44/matrix metalloproteinase 9 are sensitive markers for reflecting the proliferation and infiltration of tumor cells.The present study analyzed pre-operative diffusion tensor images of 24 patients with pathologically confirmed World Health Organization glioma（Ⅰ-Ⅳ）.We observed lapse,infiltration and destruction of the peri-tumor corticospinal tract following reconstruction,and simultaneously detected the expression of Ki-67,CD44/matrix metalloproteinase 9 in samples.Expression of CD44 and matrix metalloproteinase 9was not significantly correlated to the status of the peri-tumor corticospinal tract（r = 1.597,4.859;P = 0.450,0.088）,while Ki-67 expression significantly correlated to its status（r= 6.590,P = 0.037）.These findings demonstrate that highly proliferative gliomas result in damage to the peripheral corticospinal tract.

THE USE OF ANTI-HUMAN GLIOMA MONOCLONAL ANTIBODIES FOR TARGETING CHEMOTHERAPY OF BRAIN GLIOMAS(PREPARATION AND CYTOTOXIC PROPERTIES OF ANTIBODY-ADRIAMYCIN IMMUNOCONJUGATES)

Immunoconjugates are antibody-drug hybrid molecules which combine the exquisite selectivity or monoclonal antibodies with the potent toxicity of anticancer agents. A monoclonal antibody SZ39 against human brain gliomas was used as a drug carrier. Adriamycin (ADR) was bound covalently to SZ39 to form a SZ39-ADR conjugate. The cytotoxic activity of the SZ39-ADR conjugate was tested in vitro and demonstrated potent and specific killing of cells derived from a human malignant glioma. 50% inhibitory concentration (IC50) for SZ39-ADR to 'target' cells was 8.14×10-9 M. An index of specificity between 'target' and 'non-target' cells was calculated to be 88-fold. These data suggest that the SZ39-ADR may use as a potent and cell type-specific agent and is a likely candidate for the targeting chemotherapy of malignant gliotnas.

THE USE OF ANTIHUMAN GLIOMA MONOCLONAL ANTIBODIES FOR TARGETING CHEMOTHERAPY OF BRAIN GLIOMAS(POTENT SUPPRESSION OF MALIGNANT GLIOMA GROWTH WITH IMMUNOCONJUGATES IN VIVO)

Athymic nude mice bearing subcutaneous and intracerebral human glioma xenografts were used to assess the therapeutic efficacy of monoclonal anti-body-adriamycin immunoconjugates against malignant gliomas in vivo. Immunoconjugates showed a significantly stronger antitumor effect with a T/C (treated/ control tumor volume) of 30% as compared with free drug (T/C of 84%). The targeting treatment with immunoconjugates significantly prolonged 54% of median survival time of nude mice. Side effects of immunoconjugates on the normal bone marrow and small intestines were much slighter than those of the free drug. The results of this study indicate that the use of monoclonal antibodies as carriers of anti-tumor agents may have many therapeutic advantages and potential for the treatment of brain gliomas.

IMMUNOHISTOCHEMICAL DETECTION OF P73 PRODUCTIN BRAIN GLIOMAS

Objective: To elucidate the role of p73 in the genesisor development of glioma. Methods: P73 and p53expression of 63 gliomas were detected by immunohistochemistry. Results: Out of the 63 gliomas, 17 casesappeared p73 positive. The positive-rate in high gradegliomas was higher than that in low grade gliomas(x2=4.75, P<0.05). Among the 17 cases with p73-positivegliomas, 12 cases overexpressed p53 proteill. Conclusion:Overexpression of wild p73 may involve in the genesis ordevelopment of glioma.

Risk Factors and Predictive Nomogram for Survival in Elderly Patients with Brain Glioma

Objective To determine the factors that contribute to the survival of elderly individuals diagnosed with brain glioma and develop a prognostic nomogram.Methods Data from elderly individuals(age≥65 years)histologically diagnosed with brain glioma were sourced from the Surveillance,Epidemiology,and End Results(SEER)database.The dataset was randomly divided into a training cohort and an internal validation cohort at a 6:4 ratio.Additionally,data obtained from Tangdu Hospital constituted an external validation cohort for the study.The identification of independent prognostic factors was achieved through the least absolute shrinkage and selection operator(LASSO)and multivariate Cox regression analysis,enabling the construction of a nomogram.Model performance was evaluated using C-index,ROC curves,calibration plot and decision curve analysis(DCA).Results A cohort of 20483 elderly glioma patients was selected from the SEER database.Five prognostic factors(age,marital status,histological type,stage,and treatment)were found to significantly impact overall survival(OS)and cancer-specific survival(CSS),with tumor location emerging as a sixth variable independently linked to CSS.Subsequently,nomogram models were developed to predict the probabilities of survival at 6,12,and 24 months.The assessment findings from the validation queue indicate a that the model exhibited strong performance.Conclusion Our nomograms serve as valuable prognostic tools for assessing the survival probability of elderly glioma patients.They can potentially assist in risk stratification and clinical decision-making.

Therapeutic Effects of Stereotactic Radiotherapy on 389 Cases of Brain Glioma

Objective： To investigate the treatment effectiveness and side effects of stereotactic radiotherapy for brain glioma. Methods： From Jun. 1995 to Dec. 1998, 389 cases of brain gliomas were treated by stereotactic radiotherapy, among which 151 cases were treated by stereotactic radiosurgery （SRS） and the other 238 cases, by fractionated stereotactic radiotherapy （FSRT）. In the SRS group, the marginal tumor dose was 20 to 30 Gy （median, 2.6 Gy）. One to 6 isocenters （median, 2.48） and 5 to 21 irradiation arcs （median, 8.45） were applied. In the FSRT group, the per-fraction marginal tumor dose was 8 to 12 Gy with 1 to 6 isocenters （median, 2.53）, 6 to 20 irradiation arcs （median, 8.25） and 2-5 fractions delivered everyday or every other day. Results： Three months after treatment, the complete and partial response rates were 13.9% and 45.7% in SRS group respectively. The stable disease rate was 17.2%. The total effective rate was 76.8%. In FSRT group, the complete and partial remission rates were 19.7% and 47.9% respectively. The stable disease rate was 20.6%. The total effective rate was 88.2%. The total effective rate of FSRT group was higher than that in SRS group （X^2=9.874, P=0.020）. The 1-year, 3-year and 5-year survival rate of all patients was 54.3%, 29.3%, 16.5% respectively. The 1-year, 3-year and 5-year survival rate in SRS group and FSRT group was 52.3% vs 26.5%, 11.9% vs 55.5%, and 31.1 vs 19.3% respectively. There was no significant difference between the two groups （X^2=2.16, P=0.1417）. The brain edema caused by the main radiation was more severe in the SRS group than in FSRT group （X^2=4.916, P=0.027）. Conclusion： It is effective for brain glioma to be treated by stereotactic radiotherapy. Compared with SRS, the FSRT has the advantage of good effect and less side response.

Highly Sensitive MoS_2–Indocyanine Green Hybrid for Photoacoustic Imaging of Orthotopic Brain Glioma at Deep Site

Photoacoustic technology in combination with molecular imaging is a highly effective method for accurately diagnosing brain glioma. For glioma detection at a deeper site, contrast agents with higher photoacoustic imaging sensitivity are needed. Herein, we report a MoS_2–ICG hybrid with indocyanine green(ICG) conjugated to the surface of MoS_2 nanosheets. The hybrid significantly enhanced photoacoustic imaging sensitivity compared to MoS_2 nanosheets. This conjugation results in remarkably high optical absorbance across a broad near-infrared spectrum, redshifting of the ICG absorption peak and photothermal/photoacoustic conversion efficiency enhancement of ICG. A tumor mass of 3.5 mm beneath the mouse scalp was clearly visualized by using MoS_2–ICG as a contrast agent for the in vivo photoacoustic imaging of orthotopic glioma, which is nearly twofold deeper than the tumors imaged in our previous report using MoS_2 nanosheet. Thus, combined with its good stability and high biocompatibility, the MoS_2–ICG hybrid developed in this study has a great potential for high-efficiency tumor molecular imaging in translational medicine.

Scientific literature addressing brain glioma in the Web of Science A 10-year bibliometric analysis

Brain glioma is a hot topic in recent years; however, brain glioma remains poorly understood. A bibliometric analysis based on the Science Citation Index （SCI） published by the Institute of Scientific Information （ISI） was performed to identify the global research and to improve the understanding of research trends in the brain glioma field from 2001 to 2010. During 2001 to 2010, there were 8 413 papers addressing brain glioma added to the SCI, and this trend is increasing annually. Of these reports, 6 945 papers are written in English. Journals published in the United States had the most papers, including ten core source titles. The Journal of Neuro-Oncology published the most articles followed by Cancer Research. Furthermore, the University of California San Francisco, is the most productive institution for publishing articles in the brain glioma field. Finally, this study highlights the topics in brain glioma research that are being published around th~ world.

Isolation,cultivation and identification of brain glioma stem cells by magnetic bead sorting

This study describes a detailed process for obtaining brain glioma stem cells from freshly dissected human brain glioma samples using an immunomagnetic bead technique combined with serum-free media pressure screening. Furthermore, the proliferation, differentiation and self-renewal biological features of brain glioma stem cells were identified. Results showed that a small number of CD133 positive tumor cells isolated from brain glioma samples survived as a cell suspension in serum-free media and proliferated. Subcultured CD133 positive cells maintained a potent self-renewal and proliferative ability, and expressed the stem cell-specific markers CD133 and nestin. After incubation with fetal bovine serum, the number of glial fibrillary acidic protein and microtubule associated protein 2 positive cells increased significantly, indicating that the cultured brain glioma stem cells can differentiate into astrocytes and neurons. Western blot analysis showed that tumor suppressor phosphatase and tensin homolog was highly expressed in tumor spheres compared with the differentiated tumor cells. These experimental findings indicate that the immunomagnetic beads technique is a useful method to obtain brain glioma stem cells from human brain tumors.

AKT1 and AKT2 Promote Malignant Transformation in Human Brain Glioma LN229 Cells

OBJECTIVE To confirm the role played by AKT1 and AKT2 in the β- catenin/Tcf-4 signaling pathway in promoting malignant transfor- mation of glioma cells. METHODS LN229 cells were divided into five groups： a control group, acetone （ACE）group, acetylsalicylic acid （ASA; aspirin） group, ASA＋AKT1 plasmid group and ASA＋AKT2 plasmid group. Western blot and PCR were used to detect the expression of AKT1 and AKT2 after dealing with ASA and transferring AKTI/2 genes into LN229 cells. Cell proliferation was determined by flow cytometry, cell invasion was evaluated by transwell assay and cell apoptosis was detected with annexin V staining. The molecules regulating proliferation and invasion were examined by western blot analysis. RESULTS Aspirin down-regulates AKT1 and AKT2 expression by modulating β-cateninfrcf-4 activity. AKT1 and AKT2 can enhance cell proliferation and invasion by up-regulating the expression of cyclin-D and matrix metalloprotein-9 （MMP-9） in LN229 glioma cells. CONCLUSION AKT1 and AKT2 play an important role in the β- catenin/Tcf-4 signaling pathway promoting malignant transformation; AKT1 is more effective than AKT2. AKT1 and AKT2 may be potential targets for brain glioma therapy and an effective way to prevent metastasis of gliomas.

Prediction of malignancy selective neural networks degree in brain glioma using ensemble

A clustering algorithm based selective neural networks ensemble （CLUSEN） is proposed to predict the degree of malignancy in brain glioma. Since the degree prediction of malignancy is critical before brain surgery, many learning methods are used like rule induction algorithm, single neural networks, support vector machines, etc. Ensemble learning methods can improve the generalization of single learning machine, and are becoming popular in the machine learning and medical data processing communities. The procedure of CLUSEN can efficiently remove redundancy learning individuals and help improve the diversity of ensemble methods. CLUSEN is used to predict the degree of malignancy in brain glioma. Experimental results on a set of brain glioma data show that, compared to support vector machines, rule induction and single neural networks, the classification accuracy of CLUSEN is higher.

DELETION AND 5'CPG ISLAND METHYLATION OF p15 GENE IN BRAIN GLIOMA

Objective: To investigate the abnormality of p15 gene in brain glioma and the correlation of it with occurrence or malignant progression of brain glioma. Methods: Deletion and 5'CPG island methylation of p15 gene were detected by the methods of PCR and PCR- based methylation in 56 cases of brain glioma. Results: Out of 43 cases of high grade glioma, 14 cases were found to have homozygous deletion of p15E1, while none of the 13 cases of low grade glioma was found to have deletion of p15E1 (P<0.05). Methylation of 5'CPG Island of p15 gene was found only in four cases of glioma. Conclusion: Abnormality of p15 gene may involved in the occurrence and malignant progression of brain glioma. Homozygous deletion of gene is the major mechanism of inactivation for p15 gene in brain glioma.

Abnormal expressions of proliferating cell nuclear antigen and P27 protein in brain glioma

Both proliferating cell nuclear antigen and P27 protein are important factors to regulate cell cycle. While, the combination of them can provide exactly objective markers to evaluate prognosis of patients with brain glioma needs to be further studied based on pathological level. OBJECTIVE： To observe the expressions of proliferating cell nuclear antigen and P27 protein in both injured and normal brain glioma tissues and analyze the effect of them on onset and development of brain glioma. DESIGN： Case contrast observation. SETTING： Department of Neurosurgery, the Second Affiliated Hospital of Xi＇an Jiaotong University. PARTICIPANTS： A total of 63 patients with brain glioma were selected from Department of Neurosurgery, the Second Affiliated Hospital of Xi＇an Jiaotong University from July 1996 to June 2000. There were 38 males and 25 females and their ages ranged from 23 to 71 years. Based on pathological classification and grading standards of brain glioma, patients were divided into grade I - II （n=30） and grade III- IV （n = 33）. All cases received one operation but no radiotherapy and chemiotherapy before operation. Sample tissues were collected from tumor parenchyma. Non-neoplastic brain tissues were collected from another 12 non-tumor subjects who received craniocerebral trauma infra-decompression and regarded as the control group. There were l0 males and 2 females and their ages ranged from 16 to 54 years. The experiment had got confirmed consent from local ethic committee and the collection was provided confirmed consent from patients and their relatives. All samples were restained with HE staining so as to diagnose as the brain glioma. While, all patients with brain glioma received radiotherapy after operation and their survival periods were followed up. METHODS： Primary lesion wax of brain glioma was cut into serial sections and stained with S-P immunohistochemical staining. Brown substance which was observed in tumor nucleus was regarded as the positive expressions of both proliferating cell nuclear antigen and P27 protein. Automatic imaging analytic system was used to quantitatively analyze staining results of tumor. MAIN OUTCOME MEASURES： To compare the expressions of proliferating cell nuclear antigen and P27 protein in brain glioma tissues and non-tumor brain tissues and investigate the effect of various sexes, ages, survival periods and severities on the expressions of them in brain tissues. RESULTS： There was no significant difference of sexes and ages in the expressions of proliferating cell nuclear antigen and P27 protein （P 〉 0.05）; however, the expressions of proliferating cell nuclear antigen and P27 protein were milder in non-tumor brain tissues than those in the brain glioma tissues （P 〈 0.05）. Expression of proliferating cell nuclear antigen in brain tissue of grade III- IV severity was stronger than that of grade I - II severity, and the expression in ≥ 5-year survival periods were also stronger than that in 〈 5-year survival periods （P 〈 0.05）. In addition, expression of P27 protein in brain tissue of grade III- IV severity was stronger than that of grade I - II severity, and the expression in ≥ 5-year survival periods were also stronger than that in 〈 5-year survival periods （P 〈 0.05）. CONCLUSION： Abnormal expressions of proliferating cell nuclear antigen and P27 protein in human brain glioma are closely related to onset, development and prognosis of tumor.

ERBB1 Is Amplified and Overexpressed in High-grade Diffusely Infiltrative Pediatric Brain Stem Glioma

PURPOSE:This study was conducted to investigate the incidence of ERBB1 amplification and overexpression in samples of diffusely infiltrative (WHO grades Ⅱ-Ⅳ) pediatric brain stem glioma (BSG) and determine the relationship of these abnormalities to expression and mutation of TP53 and tumor grade. Experimental Design: After central pathology review, the incidence of ERBB1 amplification and overexpression was determined in 28 samples (18 surgical biopsy and 10 postmortem specimens) of BSG using quantitative PCR and immunohistochemistry,

Experimental study on dendritic cells pulsed with brain tumor stem cells for immunotherapy of glioma

Objective To investigate the effect of dendritic cells pulsed with brain tumor stem cells which are used to treat on intracranial glioma. Methods We obtained murine brain tumor stem cells by grow ing C6 cells in epidermal grow th factor/basic fibroblast grow th factor w ithout serum.Dendritic cells isolated from rat bone marrow w ere pulsed w ith BTSCs. Rat brain

Effects of comprehensive nursing on postoperative complications,mental status and quality of life in patients with glioma

BACKGROUND The complexity and refractory of brain glioma requires treatment that should involve a multidisciplinary approach to improve quality of care and fulfill patients’needs.AIM To explore the effects of comprehensive nursing on postoperative complications,psychological state and quality of life in patients with brain glioma.METHODS A total of 106 patients with confirmed brain gliomas admitted to Nanchong Central Hospital between January 2019 and May 2021 were selected by random sampling.They were categorized into an observation group and a control group using a random number table with 53 patients in each group.Patients in the observation group were given comprehensive nursing in addition to conventional nursing and patients in the control group were given conventional nursing.The overall incidence of postoperative complications including limb dysfunction,high fever and epilepsy was compared between the two groups.The mental status was evaluated in the two groups before and after intervention using self-rating anxiety scale(SAS)and self-rating depression scale(SDS).Quality of life was assessed and compared using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire between the two groups before and after the intervention.RESULTS After intervention,the overall incidence of postoperative complications was significantly lower in the observation group(7.55%)than that in the control group(20.75%)(P<0.05).Before intervention,there was no significant difference in SAS and SDS scores between the two groups(P>0.05).However,after intervention,scores of SAS and SDS decreased in the two groups compared with those before intervention,and the scores of SAS and SDS were lower in the observation group than in the control group(all P<0.05).There was no significant difference in quality of life between the two groups before the intervention(P>0.05).In contrast,quality of life increased in the two groups compared with those before intervention,and it was higher in the observation group than in the control group(P<0.05).CONCLUSION Comprehensive nursing can reduce the incidence of postoperative complications,improve the psychological state of anxiety and depression and improve quality of life in patients with brain glioma.

The top cited articles on glioma stem cells in Web of Science

BACKGROUND： Glioma is the most common intracranial tumor and has a poor patient prognosis. The presence of brain tumor stem cells was gradually being understood and recognized, which might be beneficial for the treatment of glioma. OBJECTIVE： To use bibliometric indexes to track study focuses on glioma stem cell, and to investigate the relationships among geographic origin, impact factors, and highly cited articles indexed in Web of Science. METHODS： A list of citation classics for glioma stem cells was generated by searching the database of Web of Science-Expanded using the terms ＂glioma stem cell＂ or ＂glioma, stem cell＇＂ or ＂brain tumor stem cell＂. The top 63 cited research articles which were cited more than 100 times were retrieved by reading the abstract or full text if needed. Each eligible article was reviewed for basic information on subject categories, country of origin, journals, authors, and source of journals. Inclusive criteria： （1） articles in the field of glioma stem cells which was cited more than 100 times; （2） fundamental research on humans or animals, clinical trials and case reports; （3） research article; （4） year of publication： 1899-2012; and （5） citation database： Science Citation Index-Expanded. Exclusive criteria： （1） articles needing to be manually searched or accessed only by telephone; （2） unpublished articles; and （3） reviews, conference proceedings, as well as corrected papers. RESULTS： Of 2 040 articles published, the 63 top-cited articles were published between 1992 and 2010. The number of citations ranged from 100 to 1 754, with a mean of 280 citations per article. These citation classics came from nineteen countries, of which 46 articles came from the United States. Duke University and University of California, San Francisco led the list of classics with seven papers each. The 63 top-cited articles were published in 28 journals, predominantly Cancer Research and Cancer Cell, followed by Cell Stem Cell and Nature. CONCLUSION： Our bibliometric analysis provides a historical perspective on the progress of glioma stem cell research. Articles originating from outstanding institutions of the United States and published in high-impact journals are most likely to be cited.

Proton magnetic resonance spectroscopy predicts radiotherapy response and time-to-progression in high-grade gliomas after surgery

Background Reliable early prediction response to therapy and time-to-progression （TTP） remain an important goal of high-grade gliomas （HGGs） research. Proton magnetic resonance spectroscopy （1H-MRS） has been applied with variable success in clinical application, and we hypothesize that 1H-MRS in predictive value should perform well as a marker of TTP in patients treated with radiotherapy （RT） after surgery. Methods 1H-MRS was performed before surgery on 25 patients who had undergone resection of HGGs; then the ratios of lipid/creatine （Lip/Cr） and myo-inositol/creatine （ml/Cr） were determined in the solid tumor. RT response was classified as follows： complete resolution （CR）, partial response （PR）, stable disease （SD）, and progressive disease （PD） by comparison of pre-treatment and post-radiotherapy scans. TTP was defined at the time to radiographic progression by MacDonald criteria. Correlation was evaluated between the ratios of Lip/Cr, ml/Cr and treatment response, TTP. The chi-square test and Pearson correlation test were used for data analyses. Results Multivariate analysis revealed that the prognostic value of spectroscopic variables was independent of age, sex, WHO histologic grade, extent of surgery, and Karnofsky score （KPS）. The correlation between the ratios of lipid/Cr and TTP was significant （r=0.894, P=0.000）, and between the ratios of ml/Cr and TTP was also significant （r=0.891, P=-0.000）. As predicted, RT response correlated significantly with TTP （r=0.59, P=0.002）： median TTP was 49.9 days for patients with PD compared with 202.7 days for SD, 208.0 days for PR, and 234.5 days for CR. Conclusion The ratios of Lip/Cr and ml/Cr of the solid tumor region before surgery could provide important information in predicting RT response and TTP in patients with HGGs treated by radiation alone after surgery.

The use of a new functional glucose conjugate material, TPGS_(1000)-Glu, in treatment of brain glioma by incorporating into epirubicin liposomes

Most of antieancer agents can not be used for treatment of brain glioma due to the existence of the blood brain barrier （BBB）. The over-expression of glucose transporters （GLUTs） on the BBB and brain glioma cells enables the possibility that the GLUTs ligand modified drug carrier transports across the BBB, and targets to the brain glioma cells. The objectives of the present study were to synthesize a new glucose conjugate material, TPGS1000-Glu, develop a kind of TPGSI00o-Glu modified epirubicin liposomes, and evaluate their efficacy. The studies were performed on the BBB co-culture model and brain glioma cells in vitro. TPGS 1000-Glu was synthesized by conjugating TPGSlo00_COOH with 4-aminophenyl-[3-D-glucopyranoside （Glu）, and confirmed by MALDI-TOF-MS spectrum. TPGS^0oo-GIu modified epirubicin liposomes were prepared with a high drug encapsulation efficiency （〉97%）, a nanosize （approximately 90 nm）, and a minimal drug leakage in fetal bovine serum （FBS）-containing buffer system. The BBB co-culture model was established, and after applying TPGSl0oo-Glu modified epirubicin liposomes to the model, transport of liposomal drug across the BBB was evidenced. Besides, TPGS1000-Glu modified epirubicin liposomes showed the strongest cellular drug uptake and anti-glioma efficacy after transport across the BBB in vitro. The synthesized TPGS1000-Glu material could offer a new targeting ligand for the BBB, while the developed TPGS1000-Glu modified epirubicin liposomes might provide a potential anticancer formulation for treatment of brain glioma.