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8. An in vitro technology to score therapeutic efficacy and risk-potential of substances for targeting brain tumours

Author

Koch, K, Hartmann, R, Tsiampali, N, Uhlmann, C, He, X, Kamp, MA, Sabel, M, Barker, R, Willbold, D, Steiger, HJ, Maciaczyk, J, and Kahlert, UD

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Objective: The upregulation of anabolic processes to maintain high rates of cellular turnover is considered the cancers Achilles’ heel. The intervention in altered metabolic pathways of cancer cells have emerged as a promising strategy to develop new treatments and diagnostic procedures. Thereby,[for full text, please go to the a.m. URL], 71. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 9. Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie

Published
2020
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13. A novel receptor-specific anti-Notch therapy to block glioma cell invasion

Author

Herrera-Rios, D, Kahlert, U, Tsiampali, J, Koch, K, Steiger, HJ, and Maciaczyk, J

Subjects
endocrine system, ddc: 610, 610 Medical sciences, Medicine, nervous system diseases
Abstract

Objective: Glioma stem-like cells (GSCs) are the cardinal drivers for glioblastoma (GBM) progression and emergence of therapy resistance. Compounds blocking the important stem cell pathway Notch such as inhibitors of γ-secretase inhibitor (GSIs) have proven to possess therapeutic potential by [for full text, please go to the a.m. URL], 69. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Mexikanischen und Kolumbianischen Gesellschaft für Neurochirurgie

Published
2018
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14. Successful pain relief using Multiple Independent Current Control technology (MICC) and 3D-IlluminaTM programming platform following failure of the conventional SCS systems

Author

Maciaczyk, J, Koulousakis, A, Visser-Vandewalle, V, and Vesper, J

Subjects
ddc: 610, nervous system, integumentary system, 610 Medical sciences, Medicine, tissues
Abstract

Objective: Spinal cord stimulation (SCS) remains an important and clinically validated treatment option for chronic, intractable pain of the back and/or leg(s). Conventional SCS systems on the market are still working with either constant voltage or constant current technology delivering the stimulation[for full text, please go to the a.m. URL], 68. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 7. Joint Meeting mit der Society of British Neurological Surgeons (SBNS)

Published
2017
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15. Pharmacological WNT inhibition acts synergistically with chemo- and radiotherapy in glioblastoma through aldehyde dehydrogenase 3A1

Author

Suwala, A, Koch, K, Kahlert, UD, and Maciaczyk, J

Subjects
ddc: 610, fungi, 610 Medical sciences, Medicine, neoplasms, nervous system diseases
Abstract

Objective: Glioma Stem Cells (GSCs) are considered to be responsible for Glioblastoma's (GBM's) dismal prognosis. Wingless (WNT) promotes their radio- and chemoresistance. We were able to show that pharmacological WNT blockade by means of porcupine inhibition with LGK974 acts synergistically[for full text, please go to the a.m. URL], 68. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 7. Joint Meeting mit der Society of British Neurological Surgeons (SBNS)

Published
2017
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16. Burst or tonic stimulation? Results from a prospective placebo controlled, double blinded, study – 2y follow up

Author

Vesper, J, Slotty, PJ, Maciaczyk, J, and Schu, S

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Objective: Spinal cord stimulation is an established method for treatment of chronic pain in FBSS patients. In the last decades only tonic stimulation patterns were used to modulate the pain. There were several reports that indicate that burst stimulation offers other opportunities and advantages. The[for full text, please go to the a.m. URL], 68. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 7. Joint Meeting mit der Society of British Neurological Surgeons (SBNS)

Published
2017
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17. Technical aspects and outcome in Sphenopalatine ganglion stimulation (SPG) for Cluster headache

Author

Vesper, J, Maciaczyk, J, and Slotty, PJ

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Objective: Cluster headache (CH) is a debilitating, severe form of headache. A novel non-systemic therapy has been developed that produces therapeutic electrical stimulation to the sphenopalatine ganglion (SPG). Our experiences with a transoral surgical technique for inserting the Pulsante SPG Microstimulator[for full text, please go to the a.m. URL], 68. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 7. Joint Meeting mit der Society of British Neurological Surgeons (SBNS)

Published
2017
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19. 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

20. Successful combination of SPG and ONS for cluster headache

Author

Vesper, J, Maciaczyk, J, Slotty, PJ, and Klenzner, T

Subjects
ddc: 610, Cluster headache, SPG, 610 Medical sciences, Medicine, ONS
Abstract

Objective: Different neuromodulation methods are established to treat chronic headache and several reports indicate that sphenopalatin ganglion (SPG) stimulation offers advantages in Cluster headache over other other stimulation methods as occipital nerve stimulation. Limited evidence exists for both[for full text, please go to the a.m. URL], 67. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 1. Joint Meeting mit der Koreanischen Gesellschaft für Neurochirurgie (KNS)

Published
2016
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21. Pharmacological WNT-inhibition acts synergistically with chemo- and radiotherapy by overcoming treatment-resistance in glioma stem cells

Author

Suwala, AK, Koch, K, Kahlert, UD, and Maciaczyk, J

Subjects
endocrine system, ddc: 610, therapy resistance, fungi, synergy, WNT inhibition, 610 Medical sciences, Medicine, neoplasms, nervous system diseases
Abstract

Objective: Glioma Stem Cells (GSCs) are considered to be responsible for dismal prognosis of Glioblastoma (GBM). WNT signaling is one of the major players in GSCs that promotes their radio- and chemoresistance. In this study we tested whether LGK974, an inhibitor of both canonical and non-canonical [for full text, please go to the a.m. URL], 67. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 1. Joint Meeting mit der Koreanischen Gesellschaft für Neurochirurgie (KNS)

Published
2016
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22. Cervical and high-thoracic dorsal root ganglion stimulation (DRG) in chronic pain

Author

Slotty, PJ, Schu, S, Maciaczyk, J, and Vesper, J

Subjects
ddc: 610, cervical, 610 Medical sciences, Medicine, Dorsal root ganglion Stimulati, chronic pain
Abstract

Objective: The dorsal root ganglion is a promising new target in neuromodulation of chronic pain states of different origin. Commonly used in the lumbar region, DRG can be used in the upper thoracic and cervical region with slight alterations of the surgical approach. Data on outcome and complications[for full text, please go to the a.m. URL], 67. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 1. Joint Meeting mit der Koreanischen Gesellschaft für Neurochirurgie (KNS)

Published
2016
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23. CBF1 is clinically prognostic and serves as a target to block cellular invasion and chemoresistance of EMT-like glioblastoma cells

Author

Maciaczyk, D, primary, Picard, D, additional, Zhao, L, additional, Koch, K, additional, Herrera-Rios, D, additional, Li, G, additional, Marquardt, V, additional, Pauck, D, additional, Hoerbelt, T, additional, Zhang, W, additional, Ouwens, D M, additional, Remke, M, additional, Jiang, T, additional, Steiger, H J, additional, Maciaczyk, J, additional, and Kahlert, U D, additional

Published
2017
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29. Novel inhibitor of the canonical WNT-pathway LGK974 impedes the in vitro growth of glioblastoma cell lines decreasing the tumor stem cell compartment

Author

Suwala, A, Kahlert, U, Eberhart, CG, and Maciaczyk, J

Subjects
ddc: 610, WNT pathway, porcupine inhibitor, glioblastoma, 610 Medical sciences, Medicine
Abstract

Objective: Developmentally conserved WNT-signaling pathway plays a crucial role in a physiological process of cell proliferation and migration. Moreover, it is associated with carcinogenesis and epithelial-to-mesenchymal-transition (EMT) in various tumors, including malignant gliomas. High WNT-activation[for full text, please go to the a.m. URL], 66. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)

Published
2015
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30. Hybrid stimulation treatment of dominant back pain patients with Precision Spectra™ system – German experience

Author

Maciaczyk, J, Koulousakis, A, Bara, G, Schu, S, Richter, R, Visser-Vanderwalle, V, and Vesper, J

Subjects
ddc: 610, integumentary system, subcutaneous stimulation, FBSS, 610 Medical sciences, Medicine, SCS
Abstract

Objective: Although spinal cord stimulation (SCS) is an established treatment option of chronic pain in patients with a failed back surgery syndrome (FBSS), a dominant lower back pain still remains a challenge. While novel SCS systems enable better targeting, a proportion of FBSS patients do not obtain[for full text, please go to the a.m. URL], 66. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)

Published
2015
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33. Infection rates of percutaneously implanted leads for spinal cord stimulation after a trial phase: 4-year follow-up

Author

Bara, GA, Slotty, PJ, Maciaczyk, J, Schu, S, and Vesper, J

Subjects
ddc: 610, infections, 610 Medical sciences, Medicine, SCS, trial phase
Abstract

Objective: Spinal Cord Stimulation is an established treatment for various chronic pain syndromes. In general the percutaneous lead is placed first and being externalized. Upon successful trial with an external pulse generator, the IPG is implanted. The externalized lead may be a potential pathway for[for full text, please go to the a.m. URL], 65. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)

Published
2014
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34. Predictability of dorsal root ganglion stimulation via prior transforaminal epidural injections for the treatment of peripheral neuropathies

Author

Bara, GA, Slotty, PJ, Maciaczyk, J, Schu, S, and Vesper, J

Subjects
ddc: 610, DRG, peripheral neuropathies, 610 Medical sciences, Medicine, PRT
Abstract

Objective: DRG stimulation is an emerging therapy for targeting radicular pain syndromes, which are hard to treat by conventional spinal cord stimulation. Traditionally the implant procedure requires intensive intra-operative testing of the paresthesia coverage in an awake surgery setting. Often patients[for full text, please go to the a.m. URL], 65. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)

Published
2014
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35. Occipital nerve stimulation for primary chronic headache disorders – A randomized trial on treatment efficacy

Author

Bara, GA, Slotty, PJ, Maciaczyk, J, Schu, S, and Vesper, J

Subjects
ddc: 610, randomized trial, 610 Medical sciences, Medicine, headache, ONS
Abstract

Objective: Migraine and other primary headache disorders are highly prevalent. A significant percentage of sufferers are refractory to conservative treatment. Occipital nerve stimulation (ONS) may provide pain relief in these patients. During ONS treatment, paraesthesia is generally experienced by the[for full text, please go to the a.m. URL], 65. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)

Published
2014
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36. Dorsal root ganglion stimulation for treatment of phantom limb pain

Author

Bara, GA, Slotty, PJ, Maciaczyk, J, Schu, S, and Vesper, J

Subjects
body regions, phantom limb pain, dorsal root ganglion, ddc: 610, pain, 610 Medical sciences, Medicine
Abstract

Objective: Spinal Cord Stimulation has been widely used in the treatment of stump pain following limb amputation. Phantom limb pain, however, is thought to be a difficult-to-treat chronic pain syndrome. Neither Spinal Cord Stimulation nor Motor Cortex Stimulation have proven their efficacy. Here we [for full text, please go to the a.m. URL], 65. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)

Published
2014
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37. 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

38. 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

39. 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

45. 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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46. The influence of in vitro conditions for the enrichment of stem-like cell population in primary human brain tumor cultures

Author

Kahlert, UD, Maciaczyk, D, Nikkhah, G, and Maciaczyk, J

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Objective: Recently demonstrated slowly proliferating stem-like cell population (BTSC) in malignant brain tumors, responsible for tumor initiation and propagation, allowed the identification of the molecular mechanisms underlying their resistance to both chemo- and radiotherapy. Reduction of BTSC population[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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