International Conference on Neuro Oncology and Brain Tumor July 21-22, 2016 Brisbane, Australia

Session Introduction

Bhat Krishna

University of Texas, M.D. Anderson Cancer Center

Title: cancer stem cells were identified as distinct subtypes with their individual progenies

Biography:

Dr.Bhat,Krishna P is an Associate Professor at the University of Texas MD Anderson Cancer Center. Research in her lab is directed towards understanding the basis for sensitivity and resistance to cancer therapeutics and optimizing their use.He has published on this topic for the past 15 years. Several of his recent publications have described the mechanism of action of epigenetically targeted agents such as histone deacetylase inhibitors, either as single agents or in combination with other therapies.He has authored over 50 original research papers, invited reviews and book chapters.

Abstract:

In glioblastoma (GBM), Proneural (PN) and Mesenchymal (MES) cancer stem cells (CSCs) were identified as distinct subtypes with their individual progenies (non-CSCs). Here we report that following irradiation, intercellular extrinsic signals from senescent non-CSCs provoke PN CSCs’ compensatory growth, thereby resulting in persistent transcriptomic and phenotypic transformation toward more malignant MES CSCs (PN-MES transition: PMT). PMT of CSCs is accompanied with the activated wound healing pathway, which is significantly associated with poorer prognosis of GBM patients. During PMT of CSCs, a CSC marker CD133 is lost, while CDX expression evolves. These CDX-positive, but not CDX-negative GBM cells are highly tumorigenic and multipotent in vivo, suggesting CDX as a novel MES CSC marker. Inhibition of CDX attenuates clonogenicity and radioresistance. Lastly, CDX and CD133 expressions are independently instructive for poorer prognosis of MES and PN GBM, respectively. Together, irradiation to GBM tumors induces damaged non-CSC-driven PMT of CSCs developing a malignant phenotype, and CDX is a clinically relevant functional marker for MES GBM stemness.

Session Introduction

Dima suki

University of Texas , USA

Title: Long-Term Survival in Patients with Glioblastoma Multiforme: Frequency and Prognostic Factors

Biography:

Dr. Dima Suki completed her PhD from The University of Texas Houston Health Science Center.rnShe is Professor at The University of Texas MD Anderson Cancer Center in the Department ofrnNeurosurgery, as well as Director of Protocol Development and Data Management, and Co-Directorrnof Clinical Research. She also is adjunct Professor at Baylor College of Medicine, Department ofrnNeurosurgery. Dr. Suki serves on numerous committees, including the Institutional Review Board,rnwhere she is currently Associate Chair. Dr. Suki has over 100 peer-reviewed publications inrnscientific journals and has authored 7 book chapters and books. She serves on editorial advisoryrnboards for several scientific journals.

Abstract:

Glioblastoma multiforme (GBM) is a highly aggressive and rapidly fatal primary brainrntumor. Median patient survival is 12-14 months. Few treated patients survive beyond 5 years.rnVariation in characteristics such as age, performance status, and extent of resection (EOR) canrnextend survival for a few months. However, factors associated with long-term survivals of ≥5 yearsrnare largely unknown, and identifying them may provide insight into GBM and its management. Wernidentified consecutive patients surviving >5 years after initial GBM resection. Their prospectivelyrncollected demographics, clinical, imaging, and treatment data were retrospectively reviewed andrnanalyzed (under an IRB-approved protocol) from 6/1/1993 to 5/31/2010 (to allow for 5-yearsrnsurvival). EOR was measured volumetrically using pre- and post-op MRI’s. Among 701 newlyrndiagnosed GBM patients, 72 patients (10%) survived ≥5 years; the cohort’s overall median survivalrnwas 13.6 months. Four factors correlated significantly with longer survival on both univariate andrnmultivariate analyses: age, KPS, necrosis on the MRI, and EOR. These factors allowedrnclassification of patients into 4 groups whose >5 years survival varied widely. For patients withrn100% resections, >5-years survival is 50% for Group A, 21% for Group B, 13% for Group C, andrn2% for Group D. The corresponding numbers for patients with <100% resection are: 8% (Group A),rn13% (Group B), 1% (Group C), and 1% (Group D). This is the largest series of long-term GBMrnsurvivors (>5 years), emphasizing the importance of patient selection and of maximizing the EOR.

Fares Nigim,

Harvard Medical School, USA

Title: Reactive Oxygen Species Induction in Oncolytic Virus Therapy of Glioblastoma

Biography:

Fares Nigim, MD currenty works under Brain Tumor Research Center at Massachusetts General Hospital and belongs to Harvard Medical School in Boston, Massachusetts with research interest upon neurooncology and neurology as an neurologist rn

Abstract:

Reactive Oxygen Species Induction in Oncolytic Virus Therapy of Glioblastomarnrn Reactive oxygen species (ROS) are signaling molecules that play versatile roles in regulating various cellular pathways in both physiological and pathological conditions such as cancer and virus infection. The effects of ROS on viral replication are context-dependent and the role of ROS in oncolytic virus therapy of cancer is poorly understood. In this study, we investigated ROS induction and its potential impacts on oncolytic herpes simplex virus (oHSV) therapy of the malignant brain tumor glioblastoma. We employed a clinically relevant glioblastoma model that is based on patient-derived glioblastoma stem cells (GSCs) that recapitulate the genotype and phenotype of primary tumors. Two oHSVs were used; G47Δ that lacks 34.5 and 47 and has a LacZ insertion inactivating ICP6, and MG18L that contains deletion of the Us3 gene and a LacZ insertion inactivating ICP6. Measurement of intracellular ROS by H2-DCFDA and Mito SOX assays showed that both oHSVs (G47Δ and MG18L) robustly induced intracellular ROS in GSCs at 24 and 48 hours post infection, which was specifically seen in infected cells. Antioxidants, reduced glutathione (GSH) and N-acetylcystein (NAC), potently suppressed oHSVs-induced intracellular ROS. Antioxidants-mediated suppression of intracellular ROS did not affect viral replication or viral spread. However, cell viability assays (MTS and Cell Titer Glo) and dead cell staining (trypan blue or propidium iodide) demonstrated that both antioxidants protected GSCs from early cell death caused by the viruses. Thus we show that oHSV is a potent inducer of ROS upon infection of GSCs. Our results also suggest that virus-induced ROS contribute to early cell death following oHSV therapy of glioblastoma.rnKey words: Reactive oxygen species (ROS), Glioblastoma stem cells (GSCs), Oncolytic herpes simplex virus (oHSV).rn

Fatemeh Nejatbakhshesfahani

Technical University of Munich, München, Germany

Title: Fingerprinting Heterogeneity of Glioma Using PET/MRI Information

Biography:

Fatemeh Nejatbakhshesfahani has completed his M. Sc. at the age of 25 from TUM University department of Biomedical Computing in Munich, Germany from 2013 to 2015 and she started Dr. rer in Human Biology studies from LMU University Radiology Clinic in 2016.

Abstract:

This projects is proposing a novel machine learning algorithm based on Generative Method to characterize intra-tumor heterogeneity of glioma. The algorithm was applied on dynamic [18F] FET-PET, [18F] Fmiso PET, rOEF, MRI T1, T2, T1W, T2W, FLAIR, DCE MRI and so on. This probabilistic model allows for different tumor boundaries in each channel, reflecting difference in tumor appearance across modalities. Classification result shows partly distributed feature maps in order to be able to select relevant features amongst wide patient data. The identified parts with different malignancy were discussed and validated according to first, the manual segmentations by clinical experts to investigate the performance on the tumor borders and second, graph maps to investigate the performance on the intra tumor regions. The main aim of the project is focused on the extraction of the additive information from PET and combining it with the MRI images information for each patient and relating them to the grade of malignancy.

Amir Nikouei

Shohada Tajrish Neurosurgical Center of Excellence, Iran

Title: conventional brain glioma resection versus neuronavigation system

Biography:

Dr.Amir Nikouei is from Shohada Tajrish Neurosurgical Center of Excellence, Functional Neurosurgery Research Center of Shohada Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran with research interest of neurology and neurosciences

Abstract:

Objective:rnExtent of tumor resection poses a special challenge for neurosurgeons. Image guided surgery (IGS) has become an established technology in surgical management of cerebral tumors, which provides detailed 3D localization of the lesion around important cerebrovasculature and tracts. Since there are few studies regarding using this technology as a part of standard care for patients with cerebral gliomas, we set out to determine whether IGS could improve extent of tumor resection in patients with cerebral gliomas involving eloquent cortical areas along with more desirable prognosis.rnMaterials and Methods:rnFrom January 2013 till October 2015, 26 patients with cerebral gliomas involving eloquent cortical areas were randomized equally into trial group (IGS) and control group (conventional surgery). Patients in trial group underwent functional multislice 3 Tesla Magnetic Resonance Imaging (MRI) and Diffusion Tensor Imaging (DTI) 48 hours before surgery. DTI datasets were merged with anatomical structures, and the relationship between the tumor and adjacent tracts were reconstructed for 3D visualization. Completeness of tumor resection, including volumetric analysis, was examined by early post-operative MRI.rnResults:rnThe statistic analysis confirmed well balance of main variations in both groups. Average mean pre-operative tumor volume in trial and control group was 70.37±7.96 cm3 and 68.82±7.85 cm3 respectively. No significant difference was observed between pre-operative tumor volumes in both groups (P value>0.05). Early post-operative MRI revealed 4.11±2.92 cm3 and 8.78±4.79 cm3 as mean residual tumor volume in trial and control group respectively (P value<0.05). Eleven patients (84.61%) in trial group experienced radical resection (>95%); however, radical resection was just achieved in 3 patients (23.07%) (P value<0.05). While there was no significant difference between mean Karnofsky performance scale (KPS) in both groups of patients before operation, 88.09±20.43 and 66.38±19.32 were recorded as mean KPS for trial and control group respectively (P value<0.05). In addition, excellent outcome ratio (KPS=90-100) was achieved in 76.92% of trial group, while this value was 30.76% in control group (P value<0.05).rnConclusions:rnIGS using neuronavigation system combined with DTI, allows 3D evaluation of the cerebral tumor and their adjacent structures, along with tract mapping for neurosurgeons. Furthermore, this technology can aid to plan the optimal trajectory and higher extent of tumor resection with minimal post-operative neurological deficits.rn

A. De Tommasi

University “A. Moro” of Bari, Italy

Title: PROGNOSTIC FACTORS IN GLIOBLASTOMA MULTIFORME: OUR EXPERIENCE.

Biography:

A. De Tommasi currently working FROM 2010 – TO NOW BARI GENERAL HOSPITAL AND UNIVERSITY OF BARI HEALTHCARE – NEUROSURGERY CHAIRMAN AND HEAD OF THE NEUROSURGICAL AND NEUROTRAUMATOLOGICAL DEPARTMENT ,CLINICAL, SURGICAL, DIDACTIC AND ADMINISTRATIVE ACTIVITIES AND RESPONSIBILITIES,Faculty Lecturer in cranio-cerebral and vertebro-medullary Traumatology during FROM 1976 -TO 1991,From 1978 to 1993, Professor of Neurosurgery at the Nurses’ College at the Domenico Cotugno Hospital in Bari. From 1979 to 1995, Professor of Neurosurgery at the School for Technicians in Resuscitation and Anaesthesia at the De Bellis Institute in Castellana Grotte, Italy. Since l980, Professor of Neurosurgery and Neurotraumatology at the Faculty of Medicine at the University of Bari. Since l980, Professor of Neurosurgery and Neurotraumatology at the School of Specialization in Neurosurgery at the University of Bari.

Abstract:

INTRODUCTION: Glioblastoma Multiforme (GBM) is the most common and aggressive cerebral neoplasm in adults with an incidence of 5.26 cases per 100000 inhabitants per year. It usually occurs in the sixth and seventh decade of life. The prognosis is severe with an average survival of 12-18 months. Several studies have been conducted to identify the prognostic factors in GBM. The only fact resulting from these studies is the prognostic role of age. The importance of the subject’s functional status at diagnosis and of the lesion’s location is still unclear. MATERIALS AND METHODS: Our study is a retrospective analysis of 50 patients from 2010 to 2013. The average age is 63 years old with a M:F rate of 1.6. As far as the identification of prognostic factors is concerned, the following aspects have been taken into account: age, gender, Kasnofsky Performance Status (KPS) at the admission, lesion’s location, and the extent of surgical resection. At the admission, 18 % of patients had a KPS of 60 or lower, 75% showed a KPS value of 70 or 80, 6% had a KPS of 90, and none had a KPS of 100. After the operation, the situation changed with 62% of patients with a KPS of 90-100, 30% with a KPS of 70-80 and only 8% of subjects showing a KPS of 60 or lower. RESULTS: The univariate analysis results have been verified with a multivariate analysis for which the Cox model and the stepwise selection of variables have been used. The prognostic role of each risk factor has been evaluated with a survival analysis using the Cox model. The univariate analysis showed that an age of 65 or more, and a KPS of 80 or more are usually associated with a better outcome. Lesion’s location in eloquent area and the subtotal extent of surgical resection have a negative influence on survival (with no relevant statistical significance). Gender does not show a relation with the prognosis of subjects with glioblastoma multiforme. CONCLUSION: The first aspect emerging from our study is the importance of the surgery in improving the patient’s symptoms and functional status. The univariate analysis showed that age is the only risk factor with a statistical significant influence on survival. No association emerged between the extent of resection and the subject’s survival despite a p value close to 0.05. In multivariate analysis the p value is 0.08 with a OR of 2.35. Therefore, an explorative analysis of the interaction between the lesion’s location and the extent of resection was conducted so as to give a more appropriate interpretation of this result. This analysis highlighted that a greater extent of resection is associated with a better outcome in both cases where GBM is located in eloquent or non eloquent area. Keywords: glioblastoma multiforme, prognostic factors

Session Introduction

Sun Jin kim

University of Texas,USA

Title: Targeting the Microenvironment for Therapy of Primary and Metastatic Brain Tumors

Biography:

Dr. Sun Jin Kim received MD in 1986 and PhD in 1993 from the College of Medicine and the Graduate School of Seoul National University. He completed the residency in the Seoul National University Hospital and postdoctoral fellowship in the University of Texas MD Anderson Cancer Center. He was an invited scientist in the National Cancer Center Research Institute, Tokyo, Japan. He is a professor in the Department of Cancer Biology, UTMDACC and has published more than 80 papers in peer-reviewed journals. He has been involved in clinical translational research programs developing the clinical trials of novel molecules and protocols.

Abstract:

rnThe median survival of patients with the primary or metastatic brain tumor is limited due to resistance to all standard therapies. The mechanism of pan-resistance against the systemic therapy has been attributed to the blood-brain-barrier and/or p-glycoprotein, which prevent the drugs from reaching the brain lesions. We have recently reported that activated astrocytes and endothelial cells establish gap-junction communication channel with the tumor cells and protect tumor cells from chemotherapeutic agents by a mechanism involving the phosphorylation of endothelin receptors on tumor cells leading to up-regulation of multiple genes, among which are survival or anti-apoptotic genes. We translated in vitro observation into the preclinical in vivo models that nude mice bearing orthotopic human glioblastoma or metastatic human breast or lung cancers in brain were treated by the blockade of the endothelin axis, using the dual antagonist, macitentan, combined with taxol or temozolomide. The combination therapy significantly regressed the established primary or metastatic brain tumors and prolonged the disease free survival of mice for months after mice in other treatment groups died. Immunohistochemical analysis demonstrated that treatment with macitentan inhibited phosphorylation of the endothelin receptors A and B on tumor cells and tumor-associated endothelial cells. The addition of chemotherapeutic agents produced massive apoptosis in both tumor cells and dividing tumor-associated endothelial cells.rnInhibition of endothelin receptor phosphorylation on both tumor cells and tumor-associated endothelial cells inhibits survival pathways in these cells, which enhances their sensitivity to chemotherapy. Macitentan plus chemotherapy is well tolerated, produces durable responses, and clinical evaluation is ongoing.rn

Session Introduction

Dongwoo John chang

CIGNA, Hospital, USA

Title: THE SUBTEMPORAL APPROACH IN CRANIAL NEUROSURGERY: A ROAD LESS TRAVELED

Biography:

Dr.Dongwoo John chang

Abstract:

THE SUBTEMPORAL APPROACH IN CRANIAL NEUROSURGERY: A ROAD LESS TRAVELED rnINTRODUCTIONrnThe subtemporal approach was popularized by Dr. Charles Drake for the microneurosurgical clipping of aneurysms of the distal basilar artery. The competing approach for such problems was and still is the transsylvian approach to the interpeduncular region. Because an increasing proportion of cerebral aneurysms, particularly those of the basilar artery, are treated by endovascular methods, it is probable that the subtemporal approach is being used less and less in contemporary neurosurgical practice. However, the elegance of this approach lends itself to the neurosurgical treatment of not only vascular lesions, but also for the definitive microsurgical management of tumorous lesions that occur in the deep, central portions of the cranial cavity.rnMETHODSrnRetrospective review of the clinical practice database of a single cerebrovascular/skull base neurosurgeon revealed that the following lesions were treated with the subtemporal approach and its variations: basilar apex aneurysm (small to giant sizes clipped with standard techniques and with hypothermic circulatory standstill), superior cerebellar artery aneurysm, posterior cerebral artery aneurysm, tentorial meningioma, parahippocampal (and other subtemporal) metastatic tumor, large mesencephalic lymphoma, giant pontomesencephalic region pilocytic astrocytoma, and chordoma.rnRESULTSrnThe subtemporal approach can be subdivided into 3 subcategories: (1) anterior subtemporal, (2) mid-subtemporal, and (3) posterior subtemporal. Excellent microsurgical exposure was obtained in all cases approached with each of the 3 variations of the subtemporal approach. Definitive lesionectomy (whether it was aneurysm clipping, lesion biopsy, or tumoral removal) was accomplished in all cases. Technical nuances to avoid surgical complications are discussed in this presentation, ranging from (and including) bony exposure, lumbar drainage, location/method of tentorial incision, and management of cerebral veins to the optimal mechanical trajectories of brain retractors that facilitate final surgical exposure while minimizing iatrogenic brain injury. The specific surgical approach was tailored to the anatomic details of the treated lesion—based on vascular, bony, and lesional anatomy—to arrive at the most applicable surgical approach.rnCONCLUSIONSrnThe subtemporal approaches provide orthogonal anatomic routes that often result in a short, direct route to neurosurgical lesions that occur at the tentorial incisura and in the interpeduncular cistern. The subtemporal approaches are useful for lesions that may originate in different anatomic compartments but have lesional extensions into the traditional “central” cranial compartment (pontomesencephalic, clival, and tentorial incisural regions), for which the classical subtemporal approach has been historically useused. Finally, anatomic insights gained from the use of the subtemporal approaches are particularly useful in the microneurosurgery of the mesial temporal lobe region, and vice versa.rn

Session Introduction

AnitaLivio

Western Sydney University,Australia

Title: The Role of Protein Arginine Methylation in Cell Cycle and Tumorigenesis of Brain Cancer Cell Lines

Biography:

Anita is a 2nd year PhD candidate at Western Sydney University and is collaborating with researchers at Hawkesbury Insititute for the Environment on another project. She completed her Bachelor of Science (Hons) in 2014, also at Western Sydney University.

Abstract:

Protein arginine methylation is a post-translational modification involved in many cellular processes, such as regulation of signal transduction, facilitating protein-protein interactions, RNA transport and splicing. It is becoming increasingly evident that protein arginine methylation is also an important regulator of the cell cycle and DNA damage repair pathways. Important regulatory proteins, such as cyclin D1, p53, p21, and the retinoblastoma protein are methylated or associate with protein arginine methyltransferases (PRMTs), the enzymes responsible for arginine methylation. PRMTs are often overexpressed in cancers, leading to aberrant methylation patterns correlating with poor recovery prognosis. Brain cancer is one of the most aggressive types of cancer- the 5 year survival rate for patients in Australia with brain cancer is only 20%. PRMT1 forms a complex, the methylosome, to initiate methylation of H4R3 to activate transcription of glioblastoma genes, such as EGFR, AKT3, and CDK6. PRMT5 overexpression correlates with increased cell proliferation and its knockdown resulted in cell cycle arrest leading to apoptosis. My study seeks to further investigate the role of protein arginine methylation in the cell cycle of glioblastoma cells, specifically through the interaction of mortalin with p53. Mortalin is normally found in neurons only; however it has also been found in glioblastoma tissues with expression levels correlating with tumor aggresivenss. Preliminary data have shown mortalin to be methylated on an arginine within the p53-binding domain, suggesting that methylation may play a role in the localisation of mortalin or its interaction with other proteins, e.g. p53.

Session Introduction

md ali

professor from Iran university

Title: Multiple ring enhancing lesions on MRI of the brain in transplant recipient: A diagnostic dilemma

Biography:

Dr md from United States

Abstract:

Post-transplantation primary central nervous system lymphoma (PT-PCNSL) is a very rare tumor that can present from months to years after transplantation. Although it is frequently encountered in a renal transplant recipient, can certainly present in liver and other solid organ transplant recipients too. Its symptoms can be varied ranging from non-specific symptoms such as headache, gait disturbance, change in mental status to the focal neurological deficit. Inflammatory markers such as C-reactive protein, LDH, and ESR may be elevated whereas CSF analysis often is inconclusive. MRI is a better diagnostic modality than CT; however, it can still be difficult to diagnose accurately these ring-enhancing lesions given the wide-range of the differential. As a result, brain biopsy becomes mandatory to establish the diagnosis in most cases. Here we present a case of PT-PCNSL, who was initially misdiagnosed and treated as brain abscess until brain biopsy proved it otherwise Case: A 41-year-old Hispanic female with a past medical history of bacterial endocarditis, renal transplant (1994) secondary to glomerulonephritis treated with mycophenolate and tacrolimus presented with a transient change in mental status. She had stable vitals without neurological deficits and the spontaneous return of baseline mental status. Her MRI showed two ring-enhancing lesions in the right temporal and parietal lobe. Considering her previous history of endocarditis, current immunosuppression, MRI findings and non-specific neurological manifestation, she was treated as a brain abscess without any significant response. Her blood culture remained negative, and CSF analysis was unremarkable. Therefore, she underwent brain biopsy that characterized it to be diffuse large B-cell lymphoma that was assumed to be post-transplant. Her immunosuppression was withheld; subsequently she underwent tumor resection followed by Rituximab therapy with an effective response, and she is currently disease free Discussion: Although PT –PCNSL is a very rare entity, it is increasingly recognized in transplant recipient as the number of transplant recipients rises, and better survival outcomes are achieved. Early diagnosis is a harbinger of a better outcome. Therefore high index of clinical suspicion should always be exercised in this patient population. Chronic immunosuppression plays a critical role in the etiopathogenesis of these neoplasms and often, the treatment is withholding immunosuppression itself. PT-PCNSL is hard to diagnose, easy to miss and rather difficult to treat with variable prognosis Although the differential diagnosis of ring-enhancing lesions on MRI includes glioma, metastatic malignant lesions, bacterial and non-bacterial abscesses, toxoplasmosis, and multiple sclerosis plaques, clinicians must consider PT-PNCSL highly in transplant recipients.

Session Introduction

Tsz Wai Rosita Pang

University of Sydney,Australia

Title: Mechanism of Ultrasmall Superparamagnetic Iron Oxide Nanoparticles-induced Glioblastoma Multiforme Cytotoxicity: Effects on mitochondrial function

Biography:

Tsz Wai Rosita Pang is a PhD student at the Retinal & Developmental Neurobiology Laboratory, University of Sydney. Her research aims to find better treatments for Glioblastoma Multiforme, the most common and lethal type of brain tumours, with the use of ultrasmall superparamagnetic iron oxide nanoparticles.

Abstract:

This study investigated the in vitro cytotoxic effects of Ultrasmall Superparamagnetic Iron Oxide Nanoparticles (USPIONs) uptake on GBM function. USPIONs with a mean core diameter between 10 – 15 nm were loaded to CNS-1 cells cultures at different concentration (10-200µg/mL) and its cytotoxic effects were assessed in different time-point (2-24hr). Rat CNS-1 was chosen as our GBM model in this study because it was developed to obtain a histocompatible astrocytoma cell line with infiltrative and growth pattern similar to human gliomas. The uptake of USPIONs was analysed using the JEOL1011 transmission electron microscope (TEM) and the iron quantification was assessed using Graphite Furnace Atomic Absorption Spectrometry (GFAAS). The cell viability and the mitopotential were measured using the MUSE Count & Viability Kit and the MUSE Mitopotential Assay Kit. Bioenergetics was examined using Seahorse Mito Stress Test. TEM showed that USPIONs entered CNS-1 via clatherin coated pits which were then internalized in vacuoles. The biological effects of USPIONs on CNS-1 cell viability and mitopotential were dose and time-dependent. USPIONs at 5-200µg/mL decreased the cell viability of CNS-1 cells at 12 hr (Control: 100%±0, USPIONs: 74.62%±2.11, P <0.05). USPIONs at 10-200µg/mL increased the percentage of total depolarized cells at 12 hr (Control: 0.03±0.01, USPIONs: 0.37±0.12, P <0.05). Through these studies, it deepened our understanding of the cytotoxic effects of USPIONs on GBM function

Session Introduction

Sdahan Majumder

M. D. Anderson Cancer Center

Title: Mir-21–Sox2 axis delineates glioblastoma subtypes with prognostic impact

Biography:

Sadhan Majumder is a Professor of Genetics and Neuro-Oncology at M. D. Anderson Cancer Center, Houston, TX 77030, USA

Abstract:

Glioblastoma is the most aggressive human brain tumor. Although several molecular subtypes of glioblastoma are recognized, a robust molecular prognostic marker has yet to be identified. Here we report that the stemness regulator Sox2 is a new, clinically important target of microRNA-21 (miR-21) in glioblastoma, with implications for prognosis. Using the miR-21–Sox2 regulatory axis, about half of all glioblastoma tumors present in The Cancer Genome Atlas (TCGA) and in-house patient databases can be mathematically classified into high miR-21/low Sox2 (Class A) or low miR-21/high Sox2 (Class B) subtypes. This classification reflects phenotypically and molecularly distinct characteristics and is not captured by existing classifications. Supporting the distinct nature of the subtypes, gene set enrichment analysis of the TCGA dataset predicted that Class A and Class B tumors were significantly involved in immune/inflammatory response and in chromosome organization and nervous system development, respectively. Patients with Class B tumors had longer overall survival than those with Class A tumors. Analysis of both databases indicated that the Class A/Class B classification is a better predictor of patient survival than currently used parameters. Further, manipulation of miR-21–Sox2 levels in orthotopic mouse models supported the longer survival of the Class B subtype. The miR-21–Sox2 association was also found in mouse neural stem cells and in the mouse brain at different developmental stages, suggesting a role in normal development. Thus, this mechanism-based classification suggests the presence of two distinct populations of glioblastoma patients with distinguishable phenotypic characteristics and clinical outcomes.

Session Introduction

Homayoun Hadizadeh Kharazi

Iran University of Medical Science

Title: The rule of imaging in Brain Tumor

Biography:

Homayoun Hadizadeh Kharazi has completed his Residency at the age of 34 years from Tehran Medical University and fellowship studies from Harvard Medical University School of Medicine. He is the director of Chairman of Radiology for 11 years in Iran Medical School, a premier. He has published more than 15 papers.

Abstract:

The rule of imaging in detecting grading, prognosis, post op. Evaluation and also post chemotherapy and post radiation: The rule of imaging in brain mass and post op., post radiation changes is a challenging subject. In this lecture I am going to show the benefit and weak point of conventional MRI with and without Gd. And shows the advantages and disadvantage of new technique including DWI, SWI, ASL and MRS and compare these new techniques to show the weak and positive points in each technique. In conventional MRI the size, signal intensity and enhancement of the lesion is challenging in term of pre operation or post operation/post radiation or post chemotherapy changes. MRS, DTI, SWI, DWI and ADC Map could be helpful.

Ehtesham Ghani,

Institute King Fahad Medical City Riyadh, Kingdom of Saudi

Title: Intracranial cystic meningiomas: a rare type of tumours

Biography:

Ehtesham Ghani MBBS, FCPS (Neurosurgery), Mahmoud Al-Yamany MD, FRCS (C),Affiliation: Department of Neurosurgery, National Neuroscience Institute, King Fahad Medical City, Riyadh, Saudi Arabia.Assistant Consultant in the Department of Neurosurgery at National Neuroscience Institute

Abstract:

Introduction: Intracranial cystic meningiomas are rare and preoperative diagnosis is difficult. The present study was performed to assess the clinical and radiological outcome of intracranial cystic meningiomas. Methods: We performed a retrospective analysis of 13 patients (mean age: 49.9 years) who underwent surgical resection of intracranial cystic meningiomas from January 2006 to February 2014. There were 5 male and 8 female patients. The Glasgow Outcome Scale was used to assess the clinical outcome at 6 months. Results: Headache was the main presenting clinical feature. Most of the tumours were located on the right side. The frontal convexity was the most common site. Gross total resection was performed in 10 patients. The most common histopathological type was meningothelial variety. Conclusion: Intracranial cystic meningiomas are usually benign that occur in relatively young patients. Resection of cysts that show contrast enhancement is essential to reduce recurrence. Key words: intracranial cystic meningioma, intratumoural cystic meningioma, peritumoural cystic meningioma, meningothelial meningioma.

Sdahan Majumder

M. D. Anderson Cancer Center

Title: Mir-21–Sox2 axis delineates glioblastoma subtypes with prognostic impact

Biography:

Sadhan Majumder is a Professor of Genetics and Neuro-Oncology at M. D. Anderson Cancer Center, Houston, TX 77030, USA

Abstract:

Glioblastoma is the most aggressive human brain tumor. Although several molecular subtypes of glioblastoma are recognized, a robust molecular prognostic marker has yet to be identified. Here we report that the stemness regulator Sox2 is a new, clinically important target of microRNA-21 (miR-21) in glioblastoma, with implications for prognosis. Using the miR-21–Sox2 regulatory axis, about half of all glioblastoma tumors present in The Cancer Genome Atlas (TCGA) and in-house patient databases can be mathematically classified into high miR-21/low Sox2 (Class A) or low miR-21/high Sox2 (Class B) subtypes. This classification reflects phenotypically and molecularly distinct characteristics and is not captured by existing classifications. Supporting the distinct nature of the subtypes, gene set enrichment analysis of the TCGA dataset predicted that Class A and Class B tumors were significantly involved in immune/inflammatory response and in chromosome organization and nervous system development, respectively. Patients with Class B tumors had longer overall survival than those with Class A tumors. Analysis of both databases indicated that the Class A/Class B classification is a better predictor of patient survival than currently used parameters. Further, manipulation of miR-21–Sox2 levels in orthotopic mouse models supported the longer survival of the Class B subtype. The miR-21–Sox2 association was also found in mouse neural stem cells and in the mouse brain at different developmental stages, suggesting a role in normal development. Thus, this mechanism-based classification suggests the presence of two distinct populations of glioblastoma patients with distinguishable phenotypic characteristics and clinical outcomes.

Session Introduction

Rheal A. Towner,

Oklahoma Medical Research Foundation, USA

Title: OKN-007 is a New Therapeutic Approach for Adult and Pediatric Glioblastomas

Biography:

Dr. Towner has completed his PhD at the age of 33 years from the University of Guelph in Canada and postdoctoral studies from the University of Queensland in Australia. He is the director of Advanced Magnetic Resonance Center at the Oklahoma Medical Research Foundation, a premier biomedical research institution. He has published more than 127 papers in reputed journals and has been serving as a charter member of the National Institutes of Health Clinical Molecular Imaging and Probe development (CMIP) study section, and an editorial board member of repute.

Abstract:

OKN-007 is a New Therapeutic Approach for Adult and Pediatric Glioblastomas: Adult glioblastomas (aGBM) are the most common malignant primary brain tumors worldwide. Pediatric glioblastomas (pGBM) are one of the leading causes of cancer-related deaths in children, with tumors essentially refractory to existing treatments. OKN-007 is a novel nitrone-based compound that has anti-cancer activity in both adult and pediatric GBM. Magnetic resonance imaging (MRI) techniques were used to assess the efficacy of OKN-007 in orthotopic aGBM rat (C6, F98) and mouse (GL261) models, as well as human xenograft aGBM rat (U87) and pGBM mouse (IC-3752GBM) models. OKN-007 was found to significantly decrease tumor volumes and increase animal survival in OKN-007-treated rodents compared to untreated animals, and increase diffusion and perfusion rates. OKN-007 also significantly reduced lipid tumor metabolism, and as significantly decreased tumor cell proliferation and microvessel density. Immunohistochemistry support data was also obtained for cell proliferation and tumor growth signaling. Microarray data indicates that OKN-007 in aGBM model is centrally controlled by the TGFβ1 (transforming growth factor β1) pathway. For pGBM, in relationship to the PDGFRα (platelet-derived growth factor receptor-α) pathway, OKN-007 was able to significantly decrease PDGFR-α and SULF2 immunoexpression, and significantly increase decorin expression. This study indicates that OKN-007 may be an effective anti-cancer agent for adult or pediatric patients with aGBMs or pGBMs, respectively by inhibiting cell proliferation and angiogenesis, possibly via the TGFβ1 and/or PDGFRα pathways, and could be considered as an additional therapy for both adult or pediatric brain tumor patients.

Session Introduction

Dongwoo John chang

Medical Director Neurosurgery and Spinal Surgery-CIGNA USA

Title: THE SUBTEMPORAL APPROACH IN CRANIAL NEUROSURGERY: A ROAD LESS TRAVELED

Biography:

Dongwoo John chang currently in a position Medical Director Neurosurgery and Spinal Surgery-CIGNA USA

Abstract:

Chronic pain syndrome (CPS) is currently seen as an independent disease requiring etiopathogenetic treatment. Optimal way for cancer patients is opioid therapy. By reason of permanent presence of symptoms, the method of choice are implantable close sterile systems that do not require regular invasive procedures with minimal side «opioid» effects, that allow to stop strong pain, including "breakthrough pain." Thus the functional neurosurgery takes the increasing place in oncology. First experience in Russia applying programmable morphine infusion pumps for severe cancer pain belonged to P.Herzen Moscow Oncology Research Institute. The most significant indications for pump implantation were: the presence of heavy cancer pain (VAS>60), inefficiency of previous narcotic analgesics at doses equivalent to 30 mg morphine, life expectancy more than 3 months, and positive morphine test. Morphine pump installed 62 patients in 2013-2015. All patients diagnosed with CPS intensity of 60-100 % by VAS (average 91,6 ± 6,9), 28 patients had severe neyropatic pain. Side effects of opioid therapy were present in all patients. Implantation and pump programming was carried out according to the accepted method. All the patient the intensity of pain in all patients decreased to 0-20 % by VAS (p-value= 0,000301). Morphine dose vary from 180 to 9500 mg/day. All treated patients completely stopped taking opioids. We registered increase of motion activity in 51 cases, absence of sedation effects, improved somatic status. However, 26 patients with a long history of receiving opioid (over six months) from the second day developed specific withdrawal symptoms caused by the termination of systemic effects of opiates, requiring symptomatic therapy for 4-10 days. All patients reported more effective pain relief, lack of systemic side effects and increase quality of life after the selection of the Individual mode morphine pump. In patients with refractory cancer pain, intrathecal drug therapy with programmable morphine pumps is associated with improved pain reporting, reduced breakthrough pain and a significant improvement in the quality of life.

Ganesh Kumar Chettiar,

Kasturba Medical College, India

Title: Morphometric study of corpus callosum in South Indian cadavers

Biography:

Dr. Ganesh Kumar Chettiar has completed his MD at the age of 37 years from Manipal University. He is an Associate Professor in the Department of Anatomy. He has published more than 25 papers in reputed journals.

Abstract:

Corpus callosum is the largest commissural type of white fiber which connects the two cerebral hemispheres. The purpose was to measure the dimensions of corpus callosum and its parts and also to know its location in the cerebral hemisphere of South Indian cadavers. Twenty mid-sagittal sections from formalin fixed brain specimens were used for this study and the parameters recorded were: distances from frontal pole to occipital pole (AB), inferior surface to the superior surface of the brain (CD), frontal pole of brain to genu (AG), occipital pole to splenium of corpus calloum (BS), from splenium to superior colliculus (Ls-SC) and inferior colliculus (Ls-IC), genu to fornix (GF), outer curvature O (G-S) and inner curvature I (G-S) from genu to splenium, the entire outer curvature (OUTCR) and inner curvature (INCUR) from beginning of rostrum to the end of splenium. We also measured the thickness of rostrum (R), genu (G), trunk (T), isthmus (I) and splenium (S). Statistical analysis showed significant correlation between A-B and B-S, O (G-S) and INCUR,O (G-S) and OUTCR, A-G and R, T and I. Highly significant correlation were found between C-D and Ls-IC, O (G-S) and I (G-S), I (G-S) and G-F, G-F and G. Very highly significant correlation were seen between I (G-S) and INCUR, Ls-SC and Ls-IC, T and S. This study on the morphometry could provide valuable data in the diagnosis of any lesions of the corpus callosum and we believe that the data are enlightening to the neurosurgeons and radiologists.

Session Introduction

Usman Ali,

professor in neurology United states

Title: Multiple ring enhancing lesions on MRI of the brain in transplant recipient: A diagnostic dilemma

Biography:

Dr.usman Ali is an professor in neurology department ans as well as an a surgeon who has done many publications under Multiple ring enhancing lesions on MRI of the brain in transplant recipient: A diagnostic dilemma

Abstract:

Post-transplantation primary central nervous system lymphoma (PT-PCNSL) is a very rare tumor that can present from months to years after transplantation. Although it is frequently encountered in a renal transplant recipient, can certainly present in liver and other solid organ transplant recipients too. Its symptoms can be varied ranging from non-specific symptoms such as headache, gait disturbance, change in mental status to the focal neurological deficit. Inflammatory markers such as C-reactive protein, LDH, and ESR may be elevated whereas CSF analysis often is inconclusive. MRI is a better diagnostic modality than CT; however, it can still be difficult to diagnose accurately these ring-enhancing lesions given the wide-range of the differential. As a result, brain biopsy becomes mandatory to establish the diagnosis in most cases. Here we present a case of PT-PCNSL, who was initially misdiagnosed and treated as brain abscess until brain biopsy proved it otherwise Case: A 41-year-old Hispanic female with a past medical history of bacterial endocarditis, renal transplant (1994) secondary to glomerulonephritis treated with mycophenolate and tacrolimus presented with a transient change in mental status. She had stable vitals without neurological deficits and the spontaneous return of baseline mental status. Her MRI showed two ring-enhancing lesions in the right temporal and parietal lobe. Considering her previous history of endocarditis, current immunosuppression, MRI findings and non-specific neurological manifestation, she was treated as a brain abscess without any significant response. Her blood culture remained negative, and CSF analysis was unremarkable. Therefore, she underwent brain biopsy that characterized it to be diffuse large B-cell lymphoma that was assumed to be post-transplant. Her immunosuppression was withheld; subsequently she underwent tumor resection followed by Rituximab therapy with an effective response, and she is currently disease free Discussion: Although PT –PCNSL is a very rare entity, it is increasingly recognized in transplant recipient as the number of transplant recipients rises, and better survival outcomes are achieved. Early diagnosis is a harbinger of a better outcome. Therefore high index of clinical suspicion should always be exercised in this patient population. Chronic immunosuppression plays a critical role in the etiopathogenesis of these neoplasms and often, the treatment is withholding immunosuppression itself. PT-PCNSL is hard to diagnose, easy to miss and rather difficult to treat with variable prognosis Although the differential diagnosis of ring-enhancing lesions on MRI includes glioma, metastatic malignant lesions, bacterial and non-bacterial abscesses, toxoplasmosis, and multiple sclerosis plaques, clinicians must consider PT-PNCSL highly in transplant recipients.

Session Introduction

Julie Bolcaen

Ghent University

Title: Diagnosis of neuro-oncology

Biography:

Julie has finished her Master in Biomedical Sciences (option radiation science) at the Ghent University in 2011 with great distinction. She has a special interest in neurosciences and medical imaging of the brain. At the moment, Julie has been working as a Ph.D. student for 5 years at the department of nuclear medicine of Ghent University Hospital. Her focus is on PET/MRI imaging of high-grade brain tumors. Since 2013 she is a member of the organizing committee of the Belgian Molecular Imaging Community. Two papers were published in 2014 and 2 new papers are currently submitted.

Abstract:

Background: Discrimination between glioblastoma (GB) and radiation necrosis (RN) post-irradiation remains challenging but has a large impact on further treatment and prognosis. In this study, uptake of 18F-fluorodeoxyglucose (18F-FDG), 18F-fluoroethyltyrosine (18F-FET) and 18F-fluoromethylcholine (18F-FCho) positron emission tomography (PET) tracers were investigated in a F98 GB and RN rat model applying kinetic modeling (KM) and graphical analysis (GA), with the aim to clarify our previous results. Methods: Dynamic 18F-FDG (GB n=6 and RN n=5), 18F-FET (GB n=5 and RN n=5) and 18F-FCho PET (GB n=5 and RN n=5) were acquired with continuous arterial blood sampling. Arterial input function (AIF) corrections, KM and GA were performed. Results: The influx rate (Ki) of 18F-FDG uptake described by a 2-compartmental model (CM) or using Patlak GA, showed more trapping (k3) in GB (0.07 min-1) compared to RN (0.04 min-1) (p=0.017). K1 of 18F-FET was significantly higher in GB (0.06 ml/ccm/min) compared to RN (0.02 ml/ccm/min), quantified using a 1-CM and Logan GA (p=0.036). 18F-FCho was rapidly oxidized complicating data interpretation. Using a 1-CM and Logan GA no clear differences were found to discriminate GB from RN. Conclusions: Based on our results we concluded that using KM and GA both 18F-FDG and 18F-FET were able to discriminate GB from RN. Although KM is the only method for absolute quantification, based on our semi-quantitative results and due to the laborious set-up for obtaining an AIF, SUV is proposed for translation into the clinic. 18F-FCho PET did not allow discrimination between GB and RN.