Publications (63) View all
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Article: [Treatment of brain tumor patients: hyperthermia, hyperbaric oxygenation, electric fields or nanoparticles].
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ABSTRACT: Despite considerable advancements in the therapy of malignant glioma in recent years with modern radiation and surgical techniques, alkylating and antiangiogenic chemotherapy, as well as molecular-based treatment decisions, treatment outcomes are mostly unsatisfactory. Understandably, patients often ask for experimental, sometimes unusual therapeutic modalities and this should be integrated into the clinical practice. In addition to experimental therapeutic approaches based on novel drugs, viral agents, immunotherapy and radiation approaches, experimental procedures of interest for patients particularly encompass mechanical approaches with the aim at physically altering the tumor tissue by temperature, oxygenation or magnetization. These mechanical procedures are based on intuitive concepts and promise fewer side effects than other experimental approaches. In addition, the requirements for approval by medical device regulations in terms of proof of efficacy are generally less stringent. As a consequence approaches, such as hyperbaric oxygenation, hyperthermia and electric fields, which are often heavily advertised and in part reimbursed by health insurances, have been used for many years, often by centers not specialized in the treatment of brain tumor patients, although sound data from prospective controlled clinical trials that determine which patients in which situation may benefit, are generally lacking. In this review we review these clinical therapeutic approaches.Der Nervenarzt 07/2012; 83(8):982-7. · 0.68 Impact Factor -
Article: Suppression of proinvasive RGS4 by mTOR inhibition optimizes glioma treatment.
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ABSTRACT: An essential mode of acquired resistance to radiotherapy (RT) appears to be promotion of tumor cell motility and invasiveness in various cancer types, including glioblastoma, a process resembling 'evasive resistance'. Hence, a logical advancement of RT would be to identify suitable complementary treatment strategies, ideally targeting cell motility. Here we report that the combination of focal RT and mammalian target of rapamycin (mTOR) inhibition using clinically relevant concentrations of temsirolimus (CCI-779) prolongs survival in a syngeneic mouse glioma model through additive cytostatic effects. In vitro, the mTOR inhibitor CCI-779 exerted marked anti-invasive effects, irrespective of the phosphatase and tensin homolog deleted on chromosome 10 status and counteracted the proinvasive effect of sublethal irradiation. Mechanistically, we identified regulator of G-protein signaling 4 (RGS4) as a novel target of mTOR inhibition and a key driver of glioblastoma invasiveness, sensitive to the anti-invasive properties of CCI-779. Notably, suppression of RGS4-dependent glioma cell invasion was signaled through both mTOR complexes, mTORC1 and mTORC2, in a concentration-dependent manner, indicating that high doses of CCI-779 may overcome tumor-cell resistance associated with the sole inhibition of mTORC1. We conclude that combined RT and mTOR inhibition is a promising therapeutic option that warrants further clinical investigation in upfront glioblastoma therapy.Oncogene advance online publication, 7 May 2012; doi:10.1038/onc.2012.137.Oncogene 05/2012; · 6.37 Impact Factor -
Article: Chemotherapie bei Gliomen
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ABSTRACT: Aktuelle Strategien der Primärtherapie von Gliomen zielen auf eine Ergänzung der kombinierten Radiochemotherapie mit Temozolomid um zumeist zielgerichtete Therapeutika. Alternativ werden bei Patienten, bei denen aufgrund der Aktivität des DNA-Reparaturenzyms O6-Methyl-Guanyl-Methyl-Transferase (MGMT) ein geringeres Ansprechen auf Alkylanzien wie Temozolomid postuliert wird, alkylanzienfreie Kombinationstherapien mit der Radiotherapie getestet. Zielgerichtete Therapeutika wie z.B. Cilengitid, Enzastaurin, Temsirolimus, Cediranib, Epidermal-Growth-Factor-Receptor- (EGFR-)Inhibitoren oder der monoklonale Vascular-Endothelial-Growth-Factor- (VEGF-)Antikörper Bevacizumab werden als Monotherapie im Rezidiv und in den genannten Kombinationen in der Primärtherapie untersucht. Nachdem aus den bisherigen Therapiestudien abgeleitet werden kann, dass diese zielgerichteten Therapien, wenn überhaupt, jeweils nur für einen Teil der Patienten wirksam sind, wird die nächste relevante Entwicklung der Therapie von Gliomen durch die Bestimmung prädiktiver Signaturen erwartet. Current strategies for the treatment of gliomas aim at combining mainly targeted therapy with pivotal temozolomide radiochemotherapy. Alternatively, gliomas can be specifically addressed with respect to the activity of O6-methyl-guanyl-methyl-transferase (MGMT), a DNA repairing enzyme, to test radiosensitizing combinations without temozolomide in this unfavorable group of patients. Compounds, such as cilengitide, enzastaurin, temsirolimus, cediranib, epidermal growth factor receptor (EGFR) inhibitors or the monoclonal anti-vascular endothelial growth factor (VEGF) antibody bevacizumab are being assessed as monotherapy for recurrence of malignant gliomas or in combination with radiotherapy or radiochemotherapy with temozolomide. Results from the published trials with these compounds indicate that, if at all, only subgroups of patients benefit from these forms of treatment. Hence, the next relevant step in glioma treatment will be the development of predictive signatures to identify these subgroups prior to a specific treatment. SchlüsselworteAnaplastische Gliome–Glioblastome–O6-Methyl-Guanyl-Methyl-Transferase–Radiotherapie–Zielgerichtete Therapien KeywordsAnaplastic glioma–Glioblastoma–O6-methyl-guanyl-methyl-transferase–Radiotherapy–Targeted therapyDer Onkologe 04/2012; 17(1):44-54. · 0.17 Impact Factor -
Article: Neuroradiologische Responsekriterien bei malignen Gliomen
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ABSTRACT: Die hier zusammengefassten neuen Responsekriterien der Arbeitsgruppe Response Assessment in Neuro-Oncology (RANO) stellen eine wichtige Neuerung in der Beurteilung des Therapieansprechens nicht nur in klinischen Studien, sondern auch in der täglichen Praxis bei der Behandlung von Patienten mit malignen Gliomen dar. Durch die Einführung neuer Substanzen in der Gliomtherapie wird die Beurteilung der Effektivität aufgrund des Einflusses auf die vaskuläre Biologie dieser Tumoren immer wichtiger. Durch die komplexer werdende Therapie maligner Gliome und die erhöhte Sensibilisierung für das Therapieansprechen im Rahmen klinischer Studien werden bildgebende und klinische Phänomene wie Pseudoprogression und Pseudoregression auch außerhalb klinischer Studien immer wichtiger. Auch in den neuen Responsekriterien sind neben der Magnetresonanztomographie klinische Parameter wie Steroidmedikation und neurologische Symptome essenzielle Kriterien. Sowohl Neuroradiologen als auch Neurologen/Neuroonkologen müssen sich dieser Kriterien wie auch der biologischen Besonderheiten der Therapien bewusst sein und über genügend Erfahrung verfügen, um das Therapieansprechen richtig beurteilen zu können. This article summarizes the new response criteria of the Response Assessment in Neuro-Oncology (RANO) working group and the clinical implications. The RANO criteria represent an important step forward in the accurate assessment of response to therapy in patients with malignant gliomas, not only in clinical trials but also in daily practice. The introduction of new substances to glioma therapy, such as antiangiogenic drugs, has complicated the assessment of efficacy by MRI due to profound effects on the vascular biology of these tumors. Moreover new treatment modalities have increased the incidence and awareness of imaging phenomena, such as pseudoprogression and pseudoresponse, not only within clinical trials but also outside. In addition to MRI the new RANO criteria also take clinical parameters, such as steroid medication and neurological symptoms, into account. Thus both neuroradiologists and neurologists/neurooncologists need to be aware of and experienced in applying these criteria when treating patients with malignant gliomas to be able to correctly assess the response to therapy. SchlüsselwörterGliome-RANO-Kriterien-MRT-Pseudoprogression-Pseudoregression KeywordsGlioma-RANO criteria-MRI-Pseudoprogression-PseudoregressionDer Nervenarzt 04/2012; 81(8):950-955. · 0.68 Impact Factor -
Article: [Neuroradiological response criteria for malignant gliomas].
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ABSTRACT: This article summarizes the new response criteria of the Response Assessment in Neuro-Oncology (RANO) working group and the clinical implications. The RANO criteria represent an important step forward in the accurate assessment of response to therapy in patients with malignant gliomas, not only in clinical trials but also in daily practice. The introduction of new substances to glioma therapy, such as antiangiogenic drugs, has complicated the assessment of efficacy by MRI due to profound effects on the vascular biology of these tumors. Moreover new treatment modalities have increased the incidence and awareness of imaging phenomena, such as pseudoprogression and pseudoresponse, not only within clinical trials but also outside. In addition to MRI the new RANO criteria also take clinical parameters, such as steroid medication and neurological symptoms, into account. Thus both neuroradiologists and neurologists/neurooncologists need to be aware of and experienced in applying these criteria when treating patients with malignant gliomas to be able to correctly assess the response to therapy.Der Nervenarzt 08/2010; 81(8):950-5. · 0.68 Impact Factor
