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.

An Efficient Image Analysis Framework for the Classification of Glioma Brain Images Using CNN Approach

The identification of brain tumors is multifarious work for the separation of the similar intensity pixels from their surrounding neighbours.The detection of tumors is performed with the help of automatic computing technique as presented in the proposed work.The non-active cells in brain region are known to be benign and they will never cause the death of the patient.These non-active cells follow a uniform pattern in brain and have lower density than the surrounding pixels.The Magnetic Resonance(MR)image contrast is improved by the cost map construction technique.The deep learning algorithm for differentiating the normal brain MRI images from glioma cases is implemented in the proposed method.This technique permits to extract the linear features from the brain MR image and glioma tumors are detected based on these extracted features.Using k-mean clustering algorithm the tumor regions in glioma are classified.The proposed algorithm provides high sensitivity,specificity and tumor segmentation accuracy.

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.

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.

A Semi-automatic method for segmentation and 3D modeling of glioma tumors from brain MRI

This work presents an efficient method for volume rendering of glioma tumors from segmented 2D MRI Datasets with user interactive control, by replacing manual segmentation required in the state of art methods. The most common primary brain tumors are gliomas, evolving from the cerebral supportive cells. For clinical follow-up, the evaluation of the preoperative tumor volume is essential. Tumor portions were automatically segmented from 2D MR images using morphological filtering techniques. These segmented tumor slices were propagated and modeled with the software package. The 3D modeled tumor consists of gray level values of the original image with exact tumor boundary. Axial slices of FLAIR and T2 weighted images were used for extracting tumors. Volumetric assessment of tumor volume with manual segmentation of its outlines is a time-consuming process and is prone to error. These defects are overcome in this method. Authors verified the performance of our method on several sets of MRI scans. The 3D modeling was also done using segmented 2D slices with the help of medical software package called 3D DOCTOR for verification purposes. The results were validated with the ground truth models by the Radiologist.

Clinical Significance and Detection of Neuro-Peptide and Neurotensin in Patient s with Brain Glioma

Objective To investigate the change of neuropeptide Y(NPY)and neurotens in(NT)in pqtients with brain glioma.Method The concentration of NPY and NT in an d around brain glioma tissue and plasma were detected with inequilibrant radio－ imunology method.Result NPY concentrqtion in brain glioma tissue was obviously h igher than that in tissue around the tumor(P<0.01).The Concentration of NT in br ain glioma tissue was obviously higher that in tissue around the glioma(P<0.01). Conclusion Detection of NPY and NT in brain gliom aprovides basis for further st udy on brain glioma and explainning clinical and imaginal symjptom of brain glio ma.

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.

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.

Clinicopathological features and treatment outcomes of brain stem gliomas in Saudi population

AIM: To analyze experiences to identify treatment outcomes and prognostic factors in a Saudi population.METHODS: Medical records of patients with brainstem gliomas treated from July 2001 to December 2012 were reviewed to identify treatment outcomes of surgery, radiation therapy and chemotherapy and associated prognostic factors in a Saudi population.RESULTS: We analyzed 49 brain stem glioma(BSG) patients from July 2001 to December 2012; 31 of them were males(63.3%) with a median age of 12.6 years(range: 8-64 mo). Twenty-two patients(44.9%) had diffuse intrinsic pontine gliomas(DIPG) and 15(30.6%) presented with focal/tectal BSG. Histopathology was available in 30 patients(61.2%). Median survival time for the whole cohort was 1.5 years. One and two year OS rates were 51.1% and 41.9% respectively. Two year OS rates for focal/tectal, dorsally exophytic, cervicomedullary and DIPG tumors were 60%, 33.3%, 33.3% and 13.6% respectively(P < 0.0001). Significant prognostic factors related to OS were age at diagnosis(worse for > 18 years) P = 0.01, KPS < 70 P = 0.02, duration of symptoms(< 60 d) P = 0.002, histology(better for favorable) P = 0.002, surgery(maximal resection) P = 0.002, and concurrent chemotherapy with radiation therapy in DIPG(better if given) P = 0.01.CONCLUSION: BSG, especially the DIPG subgroup, had a dismal prognosis, needing more aggressive neurosurgical, radiation and chemotherapy techniques, while focal and tectal tumors were found to have a better prognosis.

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.

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.

Adaptability of language-related brain network in a low-grade glioma patient

Because functional magnetic resonance imaging can be used for dynamic observation of functional cortical changes after brain injuries, we followed up functional magnetic resonance imaging manifestations of a language-related brain network in a low-grade glioma patient. Disease progression and therapy during a 3-year period were followed up at different time points： before and after reoperation, after radiation therapy, and 1 year after irradiation. During the whole 3-year follow-up period, the patient exhibited no neurological deficits while functional magnetic resonance imaging revealed different topologies of the language-related brain network. During disease progression and after irradiation, the language-related brain network was extended or completely transferred to the nondominant （right） hemisphere. In addition, after reoperation and 1 year after irradiation, language areas were primarily found in the language dominant （left） hemisphere. Our results suggest a high level of adaptability of the language-related cortical network of the bilateral hemispheres in this low-grade glioma patient.

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,

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.

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.