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1. Retrospective analysis of treatment outcome in 315 patients with oligodendroglial brain tumors

Author

Trippel M, Tilgner J, Wille C, Graf E, Vesper J, Nikkhah G, and Ostertag CB

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Although chemotherapy with procarbazine, lomustine and vincristine (PCV) is considered to be well tolerated, side effects frequently lead to dose reduction or even discontinuation of treatment of oligodendroglial brain tumors. The primary objective of the analysis was to retrospectively compare progression-free survival (PFS) after PCV vs. PC chemotherapy (without vincristine to avoid side effects). Patients were retrospectively identified from a database containing our patients between 1990 and 2003. For the selected cases, all histopathology reports were re-evaluated by a local neuropathologist. Based on the updated histology data, patients were included in the study if they had at least one histological diagnosis of an oligodendroglial tumor. PFS after start of PCV (n = 61) and PC (n = 84) chemotherapy identical (median 30 months). Multivariate analysis adjusting for prognostic imbalances favouring the PC group showed a minor, statistically non-significant benefit for PCV (hazard ratio 0.81, 95% confidence interval 0.53–1.25; p = 0.346). Younger age (< 50 y) was a statistically significant predictor of longer PFS. Significant advantages in terms of overall survival after first diagnosis of oligodendroglial tumor (OS, n = 315) were found for patients < 50 y (p < 0.001), oligodendrogliomas versus oligoastrocytomas (p = 0.002), and WHO°II vs. °III (p < 0.001). Three risk groups regarding OS were identified. Findings support the hypothesis that PC may be as effective as PCV chemotherapy, while avoiding the additonal risks of vincristine. Younger age, lower tumor grade and histology of an oligodendroglioma were identified to be favorable prognostic factors.

Published
2009
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2. Tiefe Hirnstimulation

Author

Schulze-Bonhage, A. and Nikkhah, G.

Abstract

Zusammenfassung: Eine Vielzahl derzeit stattfindender prospektiver Studien zur Analyse der tiefen Hirnstimulation belegt das hohe Interesse an diesem Therapieverfahren zur Behandlung von Epilepsien. Mit dem Abschluss der SANTE-Studie zur Stimulation des N. anterior des Thalamus wurden erstmals bei einer großen Patientenkohorte der signifikante Effekt einer Tiefenhirnstimulation dokumentiert und eine Zulassung zur Behandlung seitens der Food and Drug Administration (FDA) erreicht. Weitere in dieser Übersicht beschriebene Studien, die z. T. derzeit Patienten aufnehmen, werden bei ausreichender Rekrutierung wesentlich zur Klärung des Stellenwerts der tiefen Hirnstimulation bei pharmakorefraktären Epilepsien beitragen.

Published
2024
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27. Correlation of 18F-fluoroethyl tyrosine positron-emission tomography uptake values and histomorphological findings by stereotactic serial biopsy in newly diagnosed brain tumors using a refined software tool

Author

Lopez WO, Cordeiro JG, Albicker U, Doostkam S, Nikkhah G, Kirch RD, Trippel M, and Reithmeier T

Subjects
18F-FET-PET, biopsy-targeting, Stereotactic serial biopsy, management of brain tumors, new software module, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282, newly diagnosed brain lesions
Abstract

William Omar Contreras Lopez,1,2 Joacir Graciolli Cordeiro,1 Ulrich Albicker,3 Soroush Doostkam,4 Guido Nikkhah,1,5 Robert D Kirch,6 Michael Trippel,1 ThomasReithmeier1,7 1Department of Stereotactic and Functional Neurosurgery, University Medical Center Freiburg, Freiburg im Breisgau, Germany; 2Division of Functional Neurosurgery, Department of Neurology, Hospital das Clinicas, University of São Paulo Medical School, São Paulo, Brazil; 3Inomed, Emmendingen, 4Department of Neuropathology, University Medical Center Freiburg, Freiburg im Breisgau, 5Department of Neurosurgery, University Clinic Erlangen, Erlangen, 6Neuroelectronic Systems, Department of Neurosurgery, University Medical Center Freiburg, Freiburg im Breisgau, 7Department of Neurosurgery, Schwabing Academic Teaching Hospital of Technical University and Ludwig Maximilian University of Munich, Munich, Germany Background: Magnetic resonance imaging (MRI) is the standard neuroimaging method to diagnose neoplastic brain lesions, as well as to perform stereotactic biopsy surgical planning. MRI has the advantage of providing structural anatomical details with high sensitivity, though histological specificity is limited. Although combining MRI with other imaging modalities, such as positron-emission tomography (PET), has proven to increment specificity, exact correlation between PET threshold uptake ratios (URs) and histological diagnosis and grading has not yet been described.Objectives: The aim of this study was to correlate exactly the histopathological criteria of the biopsy site to its PET uptake value with high spatial resolution (mm3), and to analyze the diagnostic value of PET using the amino acid O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) PET in patients with newly diagnosed brain lesions in comparison to histological findings obtained from stereotactic serial biopsy.Patients and methods: A total of 23 adult patients with newly diagnosed brain tumors on MRI were enrolled in this study. Subsequently to diagnoses, all patients underwent a 18F-FET PET-guided stereotactic biopsy, using an original newly developed software module, which is presented here. Conventional MRI, stereotactic computed tomography series, and 18F-FET PET images were semiautomatically fused, and hot-spot detection was performed for target planning. UR was determined using the uptake value from the biopsy sites in relation to the contralateral frontal white matter. UR values ≥1.6 were considered positive for glioma. High-grade glioma (HGG) was suspected with URs ≥3.0, while low-grade glioma (LGG) was suspected with URs between 1.6 and 3.0. Stereotactic serial biopsies along the trajectory at multiple sites were performed in millimeter steps, and the FET URs for each site were correlated exactly with a panel of 27 different histopathological markers. Comparisons between FET URs along the biopsy trajectories and the histological diagnoses were made with Pearson product-moment correlation coefficients. Analysis of variance was performed to test for significant differences in maximum UR between different tumor grades.Results: A total of 363 biopsy specimens were taken from 23 patients by stereotactic serial biopsies. Histological examination revealed eight patients (35%) with an LGG: one with a World Health Organization (WHO)-I lesion and seven with a WHO-II lesion. Thirteen (57%) patients revealed an HGG (two with a WHO-III and three with a WHO-IV tumor), and two patients (9%) showed a process that was neither HGG nor LGG (group X or no-grade group). The correlation matrix between histological findings and the UR revealed five strong correlations. Low cell density in tissue samples was found to have a significant negative correlation with the measured cortical uptake rate (r=-0.43, P=0.02), as well as moderate cell density (r=-0.48, P=0.02). Pathological patterns of proliferation (r=0.37, P=0.04), GFAP (r=0.37, P=0.04), and Olig2 (r=0.36, P=0.05) showed a significant positive correlation with cortical URs. Analysis of variance tests showed a significant difference between the LGG and the HGG groups (F=8.27, P

Published
2015

31. DiSCoVERing Innovative Therapies for Rare Tumors: Combining Genetically Accurate Disease Models with In Silico Analysis to Identify Novel Therapeutic Targets

Author

Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Chemical Engineering, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology. Department of Mathematics, Massachusetts Institute of Technology. Department of Mechanical Engineering, Koch Institute for Integrative Cancer Research at MIT, Archer, Tenley, Kim, Jong Wook, Ehrenberger, Tobias, Clemons, Paul A, Stewart, Michelle L., Shamji, Alykhan, Schreiber, Stuart, Fraenkel, Ernest, Pomeroy, Scott L., Mesirov, Jill P, Tamayo, Pablo, Hanaford, A. R., Price, A., Kahlert, U. D., Maciaczyk, J., Nikkhah, G., Dancik, V., Seashore-Ludlow, B., Viswanathan, V., Rees, M. G., Eberhart, C. G., Raabe, E. H., Schreiber, Stuart L., Mesirov, Jill P., Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Chemical Engineering, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology. Department of Mathematics, Massachusetts Institute of Technology. Department of Mechanical Engineering, Koch Institute for Integrative Cancer Research at MIT, Archer, Tenley, Kim, Jong Wook, Ehrenberger, Tobias, Clemons, Paul A, Stewart, Michelle L., Shamji, Alykhan, Schreiber, Stuart, Fraenkel, Ernest, Pomeroy, Scott L., Mesirov, Jill P, Tamayo, Pablo, Hanaford, A. R., Price, A., Kahlert, U. D., Maciaczyk, J., Nikkhah, G., Dancik, V., Seashore-Ludlow, B., Viswanathan, V., Rees, M. G., Eberhart, C. G., Raabe, E. H., Schreiber, Stuart L., and Mesirov, Jill P.

Abstract

We used human stem and progenitor cells to develop a genetically accurate novel model of MYC-driven Group 3 medulloblastoma. We also developed a new informatics method, Disease-model Signature versus Compound-Variety Enriched Response ("DiSCoVER"), to identify novel therapeutics that target this specific disease subtype. Experimental Design: Human neural stem and progenitor cells derived from the cerebellar anlage were transduced with oncogenic elements associated with aggressive medulloblastoma. An in silico analysis method for screening drug sensitivity databases (DiSCoVER) was used in multiple drug sensitivity datasets. We validated the top hits from this analysis in vitro and in vivo. Results: Human neural stem and progenitor cells transformed with c-MYC, dominant-negative p53, constitutively active AKT and hTERT formed tumors in mice that recapitulated Group 3 medulloblastoma in terms of pathology and expression profile. DiSCoVER analysis predicted that aggressive MYC-driven Group 3 medulloblastoma would be sensitive to cyclin-dependent kinase (CDK) inhibitors. The CDK 4/6 inhibitor palbociclib decreased proliferation, increased apoptosis, and significantly extended the survival of mice with orthotopic medulloblastoma xenografts. Conclusions: We present a new method to generate genetically accurate models of rare tumors, and a companion computational methodology to find therapeutic interventions that target them. We validated our human neural stem cell model of MYC-driven Group 3 medulloblastoma and showed that CDK 4/6 inhibitors are active against this subgroup. Our results suggest that palbociclib is a potential effective treatment for poor prognosis MYCdriven Group 3 medulloblastoma tumors in carefully selected patients., National Institutes of Health (U.S.) (grant R01 CA154480), National Institutes of Health (U.S.) (grant R01 109467), National Institutes of Health (U.S.) (grant R01GM074024), National Cancer Institute (U.S.). Cancer Target Discovery and Development Network (U01CA176152)

Published
2018

32. Gross total but not incomplete resection of glioblastoma prolongs survival in the era of radiochemotherapy†

Author

Kreth, F. -W, Thon, N., Simon, M., Westphal, M., Schackert, G., Nikkhah, G., Hentschel, B., Reifenberger, G., Pietsch, T., Weller, M., Tonn, J. -C, Kreth, F. -W, Thon, N., Simon, M., Westphal, M., Schackert, G., Nikkhah, G., Hentschel, B., Reifenberger, G., Pietsch, T., Weller, M., and Tonn, J. -C

Abstract

Background This prospective multicenter study assessed the prognostic influence of the extent of resection when compared with biopsy only in a contemporary patient population with newly diagnosed glioblastoma. Patients and methods Histology, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, and clinical data were centrally analyzed. Survival analyses were carried out with the Kaplan-Meier method. Prognostic factors were assessed with proportional hazard models. Results Of 345 patients, 273 underwent open tumor resection and 72 biopsies; 125 patients had gross total resections (GTRs) and 148, incomplete resections. Surgery-related morbidity was lower after biopsy (1.4% versus 12.1%, P = 0.007). 64.3% of patients received radiotherapy and chemotherapy (RT plus CT), 20.0% RT alone, 4.3% CT alone, and 11.3% best supportive care as an initial treatment. Patients ≤60 years with a Karnofsky performance score (KPS) of ≥90 were more likely to receive RT plus CT (P < 0.01). Median overall survival (OS) (progression free survival; PFS) ranged from 33.2 months (15 months) for patients with MGMT-methylated tumors after GTR and RT plus CT to 3.0 months (2.4 months) for biopsied patients receiving supportive care only. Favorable prognostic factors in multivariate analyses for OS were age ≤60 years [hazard ratio (HR) = 0.52; P < 0.001], preoperative KPS of ≥80 (HR = 0.55; P < 0.001), GTR (HR = 0.60; P = 0.003), MGMT promoter methylation (HR = 0.44; P < 0.001), and RT plus CT (HR = 0.18, P < 0.001); patients undergoing incomplete resection did not better than those receiving biopsy only (HR = 0.85; P = 0.31). Conclusions The value of incomplete resection remains questionable. If GTR cannot be safely achieved, biopsy only might be used as an alternative surgical strategy

Published
2017

37. High frequency stimulation of the Subthalamic Nucleus improves graft survival and functional outcome in a rat model of Parkinson’s disease

Author

Furlanetti, L, Cordeiro, J, Cordeiro, K, Garcia, J, Winkler, C, Döbrössy, M, and Nikkhah, G

Subjects
ddc: 610, Parkinson's disease, Parkinson’s disease, cell therapy, 610 Medical sciences, Medicine, nervous system diseases, deep brain stimulation
Abstract

Objective: Parkinson's disease (PD) is a neurodegenerative disease leading to progressive and disabling deterioration of motor and cognitive skills. Current surgical treatment by deep brain stimulation (DBS) of the subthalamic nucleus (STN) can temporarily improve motor symptoms. Alternative regenerative[for full text, please go to the a.m. URL], 65. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)

Published
2014
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38. MGMT Promoter Methylation Is a Strong Prognostic Biomarker for Benefit from Dose-Intensified Temozolomide Rechallenge in Progressive Glioblastoma: The DIRECTOR Trial

Author

Weller, Michael, Tabatabai, G, Kästner, B, Felsberg, J, Steinbach, J P, Wick, A, Schnell, O, Hau, P, Herrlinger, U, Sabel, M C, Wirsching, H G, Ketter, R, Bähr, O, Platten, M, Tonn, J C, Schlegel, U, Marosi, C, Goldbrunner, R, Stupp, R, Homicsko, K, Pichler, J, Nikkhah, G, Meixensberger, J, Vajkoczy, P, Kollias, S, Hüsing, J, Reifenberger, G, Wick, W, Weller, Michael, Tabatabai, G, Kästner, B, Felsberg, J, Steinbach, J P, Wick, A, Schnell, O, Hau, P, Herrlinger, U, Sabel, M C, Wirsching, H G, Ketter, R, Bähr, O, Platten, M, Tonn, J C, Schlegel, U, Marosi, C, Goldbrunner, R, Stupp, R, Homicsko, K, Pichler, J, Nikkhah, G, Meixensberger, J, Vajkoczy, P, Kollias, S, Hüsing, J, Reifenberger, G, and Wick, W

Abstract

PURPOSE Rechallenge with temozolomide (TMZ) at first progression of glioblastoma after temozolomide chemoradiotherapy (TMZ/RT→TMZ) has been studied in retrospective and single-arm prospective studies, applying temozolomide continuously or using 7/14 or 21/28 days schedules. The DIRECTOR trial sought to show superiority of the 7/14 regimen. PATIENTS AND METHODS Patients with glioblastoma at first progression after TMZ/RT→TMZ and at least two maintenance temozolomide cycles were randomized to Arm A [one week on (120 mg/m(2) per day)/one week off] or Arm B [3 weeks on (80 mg/m(2) per day)/one week off]. The primary endpoint was median time-to-treatment failure (TTF) defined as progression, premature temozolomide discontinuation for toxicity, or death from any cause. O(6)-methylguanine DNA methyltransferase (MGMT) promoter methylation was prospectively assessed by methylation-specific PCR. RESULTS Because of withdrawal of support, the trial was prematurely closed to accrual after 105 patients. There was a similar outcome in both arms for median TTF [A: 1.8 months; 95% confidence intervals (CI), 1.8-3.2 vs. B: 2.0 months; 95% CI, 1.8-3.5] and overall survival [A: 9.8 months (95% CI, 6.7-13.0) vs. B: 10.6 months (95% CI, 8.1-11.6)]. Median TTF in patients with MGMT-methylated tumors was 3.2 months (95% CI, 1.8-7.4) versus 1.8 months (95% CI, 1.8-2) in MGMT-unmethylated glioblastoma. Progression-free survival rates at 6 months (PFS-6) were 39.7% with versus 6.9% without MGMT promoter methylation. CONCLUSIONS Temozolomide rechallenge is a treatment option for MGMT promoter-methylated recurrent glioblastoma. Alternative strategies need to be considered for patients with progressive glioblastoma without MGMT promoter methylation. Clin Cancer Res; 1-8. ©2015 AACR.

Published
2015

39. Resistance to hypoxia-induced, BNIP3-mediated cell death contributes to the increase of CD133+ cell population in human glioblastoma-derived cultures in lowered oxygen tension

Author

Kahlert, U., Maciaczyk, D., Döbrössy, M., Herold-Mende, C.H., Nikkhah, G., and Maciaczyk, J.

Subjects
Hirntumorstammzellen, Hypoxie, ddc: 610, hypoxia, Apoptose, apoptosis, 610 Medical sciences, Medicine, brain tumor stem cells
Abstract

Objective: Brain tumor stem-like cells (BTSC) are responsible for tumor initiation, propagation and resistance to standard therapies. Previous reports showed hypoxia-induced increase of BTSC expressing CD133 together with over-expression of other stem cell-related genes and more pronounced clonogenic[for full text, please go to the a.m. URL], 63. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie (JNS)

Published
2012

40. Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial

Author

Wick, W, Platten, M, Meisner, C, Felsberg, J, Tabatabai, G, Simon, M, Nikkhah, G, Papsdorf, K, Steinbach, J P, Sabel, M, Combs, S E, Vesper, J, Braun, C, Meixensberger, J, Ketter, R, Mayer-Steinacker, R, Reifenberger, G, Weller, M, University of Zurich, and Wick, W

Subjects
610 Medicine & health, 2730 Oncology, 10044 Clinic for Radiation Oncology, 10040 Clinic for Neurology
Published
2012

41. The role of canonical WNT/beta-catenin signaling in glial brain tumors

Author

Maciaczyk, J., Kahlert, U., Maciaczyk, D., Simons, B., Orr, B., Eberhart, C., and Nikkhah, G.

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Objective: The canonical WNT/β-catenin pathway plays an important role in embryo- and carcinogenesis. Although β-catenin has been abnormally expressed in a variety of human cancers, little is known about its involvement in the biology of glial tumors. In this project the role of WNT/β-catenin[for full text, please go to the a.m. URL], 62. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgen (PNCH)

Published
2011

42. Neural transplantation in patients with Huntington's disease: preliminary risk and outcome assessment

Author

Nikkhah, G., Prokop, T., Maciaczyk, J., Piroth, T., Landwehrmeyer, B., and Trippel, M.

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Objective: Replacement of striatal projection neurons by transplantation of fetal whole ganglionic eminence (WGE)-derived cell suspensions is a novel therapeutic approach for the treatment of Huntington's disease (HD). Here, we present an interim analysis on the safety, side effects and functional[for full text, please go to the a.m. URL], 62. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgen (PNCH)

Published
2011

43. Safety and efficacy of microwire implantations in the setting of invasive monitoring in patients suffering from therapy-resistant epilepsy

Author

Trippel, M, Hefft, S, Cordeiro, JG, Reithmeier, T, Pinsker, MO, Schulze-Bonhage, A, and Nikkhah, G

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Objective: 2000, we have stereotactically implanted 669 deep brain electrodes in 212 patients suffering from pharmacologically intractable seizures to determine the epileptogenic focus. Methods: In a subgroup, 23 patients received 189 macroelectrodes. 77 of these electrodes were equipped with additional[for full text, please go to the a.m. URL], 62. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgen (PNCH)

Published
2011
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44. Safety and toxicity of fetal whole ganglionic eminence progenitor cell transplantation in Huntington's Disease patients

Author

Piroth, T, Schültke, E, Trippel, M, Maciaczyk, J, and Nikkhah, G

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Objective: The European multicentre trial MIG-HD aims on the replacement of lost striatal projection neurons using fetal progenitor cells. Available data from the German branch of the trial provides information on side effects and benefits. Risk assessment is based on pharmacological safety, involving[for full text, please go to the a.m. URL], 61. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC) im Rahmen der Neurowoche 2010

Published
2010
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45. Transfection of ganglionic eminence-derived cells from neural precursors using proneuronal genes increases the number of DARPP-32 positive neurones

Author

Pauly, MC, Kirch, R, Döbrössy, M, and Nikkhah, G

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Objective: Clinical transplantation of neuronal precursors has been shown to alter the progression of Huntington's disease (HD). Due to the limited availability of transplantable tissue, strategies to enhance the striatal population of fetal precursor cells are needed. In this study, the impact[for full text, please go to the a.m. URL], 61. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC) im Rahmen der Neurowoche 2010

Published
2010
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46. Ectopic dopaminergic progenitor cells from En1+/Otx2lacZ transgenic mice survive and functionally reinnervate the striatum following transplantation in a rat model of Parkinson's disease

Author

Hackl, C., Papazoglou, A., Ganser, C., Klein, A., Prakash, N., Wurst, E., and Nikkhah, G.

Subjects
nervous system, Midbrain/hindbrain boundary, Orthodenticle homolog 2 (Otx2), Neuron cell transplantation, DA progenitor domein, Ventral mesencephalon, Nucleus raphe
Abstract

Cell based therapies for Parkinson's disease (PD) using neural stem cells to replace the lost dopamine neurons is currently an intense area of research. In this study we have evaluated the restorative potential of ectopic dopaminergic (DA) neurons derived from the rostral hindbrain (RH) of En1+/Otx2lacZ transgenic mice. The genetic modification of the DA progenitor domain in the En1+/Otx2lacZ mice is a gain of function resulting in the enlargement of the area containing DA neurons, as well as an increase in their absolute number in the midbrain/hindbrain region. Amphetamine-induced rotation performed after cell transplantation into the unilaterally 6-hydroxydopamine lesioned rat striatum revealed that animals with transgenic RH-derived DA grafts exhibited functional recovery similar to transgenic and wild-type ventral mesencephalon (VM) derived DA grafts. Morphological analyses revealed equivalent numbers of surviving DA neurons from both homotopic VM- and ectopic RH-derived grafts from transgenic donors with low numbers of surviving serotonergic (5-HT) neurons. Conversely, grafts derived from wild-type donors contained predominantly surviving DA neurons or 5-HT neurons when they were prepared from the VM or RH, respectively. The study demonstrates the pattern of survival and functional potential of ectopic DA neurons derived from the RH of En1+/Otx2lacZ transgenic mice and that cell transplantation is an important neurobiological tool to characterize newly generated DA neural stem cells in vivo.

Published
2010

47. Stereotactic implantation of depth electrodes in epileptology

Author

Trippel, M, Hefft, S, Cordeiro, JG, Reithmeier, T, Pinsker, MO, Schulze-Bonhage, AS, and Nikkhah, G

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Objective: Since 2000 we implanted 550 depth electrodes in 196 patients suffering from pharmacologically intractable seizures for diagnostic purposes. In a retrospective study we analyzed the benefit and the risk of stereotactic implantation of depth electrodes for presurgical invasive monitoring. [for full text, please go to the a.m. URL], 61. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC) im Rahmen der Neurowoche 2010

Published
2010
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49. Cilengitide treatment of newly diagnosed glioblastoma patients does not alter patterns of progression

Author

Eisele, G, Wick, A, Eisele, A C, Clément, P M, Tonn, J, Tabatabai, G, Ochsenbein, A, Schlegel, U, Neyns, B, Krex, D, Simon, M, Nikkhah, G, Picard, M, Stupp, R, Wick, W, Weller, M, Eisele, G, Wick, A, Eisele, A C, Clément, P M, Tonn, J, Tabatabai, G, Ochsenbein, A, Schlegel, U, Neyns, B, Krex, D, Simon, M, Nikkhah, G, Picard, M, Stupp, R, Wick, W, and Weller, M

Abstract

The integrin antagonist cilengitide has been explored as an adjunct with anti-angiogenic properties to standard of care temozolomide chemoradiotherapy (TMZ/RT → TMZ) in newly diagnosed glioblastoma. Preclinical data as well as anecdotal clinical observations indicate that anti-angiogenic treatment may result in altered patterns of tumor progression. Using a standardized approach, we analyzed patterns of progression on MRI in 21 patients enrolled onto a phase 2 trial of cilengitide added to TMZ/RT → TMZ in newly diagnosed glioblastoma. Thirty patients from the experimental treatment arm of the EORTC/NCIC pivotal TMZ trial served as a reference. MRIcro software was used to map location and extent of initial preoperative and recurrent tumors on MRI of both groups into the same stereotaxic space which were then analyzed using an automated tool of image analysis. Clinical and outcome data of the cilengitide-treated patients were similar to those of the EORTC/NCIC trial except for a higher proportion of patients with a methylated O(6)-methylguanyl-DNA-methyltransferase gene promoter. Analysis of recurrence pattern revealed neither a difference in the size of the recurrent tumor nor in the distance of the recurrences from the preoperative tumor location between groups. Overall frequencies of distant recurrences were 20 % in the reference group and 19 % (4/21 patients) in the cilengitide group. Compared with TMZ/RT → TMZ alone, the addition of cilengitide does not alter patterns of progression. This analysis does not support concerns that integrin antagonism by cilengitide may induce a more aggressive phenotype at progression, but also provides no evidence for an anti-invasive activity of cilengitide in patients with newly diagnosed glioblastoma.

Published
2014

50. Human-derived ventral mesencephalic dopaminergic grafts in a rat model of Parkinson's disease

Author

Rath, A., Papazoglou, A., Garcia, J., Krause, M., and Nikkhah, G.

Subjects
surgical procedures, operative, ddc: 610, 610 Medical sciences, Medicine
Abstract

Objective: Regenerative therapy in patients with Parkinson’s disease (PD) by transplantation of ventral mesencephalic (VM) dopaminergic grafts is a highly promising prospect for future clinical treatment. The aim of this study was to compare different transplantation strategies and grafting[for full text, please go to the a.m. URL], 60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit den Benelux-Ländern und Bulgarien

Published
2009

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