Day :
Keynote Forum
Michael Friebe,
Otto-von-Guericke-University, Germany
Keynote: Conceptual idea for brain tumour treatment through intra-arterial pathways
Time : 09:00-09:25
Biography:
Prof. Michael Friebe, PhD, has been involved in diagnostic imaging and image guided therapeutic products and services, asrnfounder / innovator / CEO investor, and scientist. Dr. Friebe currently is a Board Member of two startup R&D companies, as wellrnas investment partner of a medical technology startup-fund. He is an affiliated professor with the chair for Computer AidedrnMedical Procedures (CAMP) at TU München, and full professor of Image Guided Therapies at the Otto-von-Guericke-Universityrnin Magdeburg, Germany. He is listed inventor of more than 60 patent applications and the author of numerous papers.
Abstract:
There are many invasive (removal of the tumour tissuernthrough skull based access) and non-invasive medicalrntreatment strategies (mainly radiation therapy). Very oftenrnalso a combination of both.rnWe have created a new device, that would allow usingrnthe vascular structure as a possible pathway for treatingrnintracranial diseases. One option would be the placement ofrnradiation seeds directly into a brain tumour. The main issuesrnwith this catheter based approach are the defined puncture ofrnthe vessel, the prevention of liquid exchange (blood / brain),rnsealing of the vessel after the procedure, and the accuraternplacement and control of the procedure using externalrndiagnostic imaging.rnThe catheter based device (see figure), guided andrncontrolled by 3D X-ray (Artis Zeego, Siemens Healthcare,rnErlangen, Germany), is presented consisting of a one-sidedrntriple-hole balloon, a tube feeding this balloon and a secondrntube combined with a guide assistant for the puncture andrntreatment. 3D shaped X-ray markers allow accuraternplacement.rnThe presented pathway could be an alternative tumourrnaccess and particularly well suited for placements of smallrnradioactive seeds.
Keynote Forum
Sun Jin kim
University of Texas,USA
Keynote: Targeting the Microenvironment for Therapy of Primary and Metastatic Brain Tumors
Time : 09:00-02:30
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
Keynote Forum
Fares Nigim,
Harvard Medical School, USA
Keynote: Reactive Oxygen Species Induction in Oncolytic Virus Therapy of Glioblastoma
Time : 09:00-02:30
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 ï§34.5 and ï¡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
Keynote Forum
Dima suki
University of Texas , USA
Keynote: Long-Term Survival in Patients with Glioblastoma Multiforme: Frequency and Prognostic Factors
Time : 09:00-02:30
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.
Keynote Forum
Jun Hong,
National Health Insurance Service Ilsan Hospital, Korea
Keynote: Cancer in Dementia Patients
Time : 09:00-02:30
Biography:
Dr,Jun Hong is from National Health Insurance Service Ilsan Hospital, Korearn
Abstract:
Purpose: Life expectancy has increased enormously worldwide during the last century. As expected, this increase in longevity is paralleled by an increase in the prevalence of age-associated disorders. Among these, cancer and dementia are two often devastating conditions that increase with age.rnrnMothod: This retrospective cohort study used a population-based insurance claim dataset, merged with a cancer registry, to test the prevalence of cancers occurs at various primary sites after diagnosis of dementia.rnrnResults: The study included a cohort of 2235 patients who were first diagnosed as dementia between 2005 and 2014. The site of cancer and duration between the diagnosis of dementia and cancer were analyzed. Among the dementia cases, 337 patients (15%) were diagnosed with cancer during a observation period of 1-10 years. The occurrence of prostatic cancer is 46 cases (13.7 %), colon cancer 17 cases (5 %), stomach cancer 6 cases (1.7 %), lung cancer 4 cases (1.2 %), thyroid cancer 4 cases (1.2 %), breast cancer 3 cases (0.9 %), lung cancer 3 cases (0.9 %),, mouth and throat cancer 3 cases (0.9 %), kidney cancer 3 cases (0.9 %), small intestine cancer 1 cases (0.3 %), pancrease cancer 1 cases (0.3 %), skin cancer 1 cases (0.3 %), ovary cancer 1 cases (0.3 %), lymphoma cancer 1 cases (0.3 %), renal pelvis cancer 1 cases (0.3 %), other cancer 239 cases (70.9 %).rnrnConclusion: This study showed an relationship between cancer and dementia. Further studies focusing on colon and prostate cancers may help elucidate the underlying mechanism and expand the therapeutic strategies.rn
Keynote Forum
Ganesh Kumar Chettiar,
Kasturba Medical College, India
Keynote: Morphometric study of corpus callosum in South Indian cadavers
Time : 09:00-02:30
Biography:
rn 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.rn
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.
Keynote Forum
Amir Nikouei,
Keynote: Image Guided Surgery Using Neuronavigation System in Resection of Cerebral Gliomas Involving Eloquent Cortical Areas
Time : 09:00-02:30
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