Ein neues Therapieschema für Glioblastoma multiforme : Ergebnis einer Analyse heutiger Behandlungskonzepte sowie der Biologie und Genetik des Tumors

For decades, the treatment of glioblastoma multiforme (GBM) has been among the most challenging fields in oncology. Their genetic heterogeneity, infiltrating growth, the high sensitivity and low regeneration capacity of the surrounding brain tissue and the selective permeability of the blood-brain barrier determine the therapeutic difficulties. A model is presented which explains the multitude of observed genetic variations as defects in redundant elements of the common cellular pathway of the two tumor suppresssors p53 and pRB. To find an answer for the lack of progress in the treatment of GBMs during the last thirty years more than 100 different treatment protocols for GBMs were reviewed. They included unusual fractionation schemes, brachytherapy, intraoperative irradiation, application of neutrons or BNCT, a plethora of chemotherapeutics, as well as novel gene and immunotherapy concepts. This has led to a new proposal with carbon-based ion beam therapy as central element. The multimodality regimen comprises surgery and adjuvant therapy, as well. However, in contrast to conventional treatments the algorithm is changed. The concept envisions an initial in vitro chemosensitivity assay and in case of lacking resistance a chemotherapy step with a BBB permeable drug. Tumor-conform ion beam therapy and a cytoreductive surgical step are to follow. By reducing the overall treatment time, the efficiency should further be increased. The suggested treatment scheme is considered safe. It is expected to yield survival rates which match at least the best results obtained up to now with less interventions at a good quality of life

Laser-driven ion accelerators for tumor therapy revisited

Ten years ago, the authors of this report published a first paper on the technical challenges that laser accelerators need to overcome before they could be applied to tumor therapy. Among the major issues were the maximum energy of the accelerated ions and their intensity, control and reproducibility of the laser-pulse output, quality assurance and patient safety. These issues remain today. While theoretical progress has been made for designing transport systems, for tailoring the plumes of laser-generated protons, and for suitable dose delivery, today’s best lasers are far from reaching performance levels, in both proton energy and intensity to seriously consider clinical ion beam therapy (IBT) application. This report details these points and substantiates that laser-based IBT is neither superior to IBT with conventional particle accelerators nor ready to replace it

Partial characterization of a new type of bovine papilloma viruses

Papilloma virus isolates from 13 individual bovine cutaneous warts were characterized by monospecific rabbit antisera and were shown to fall into two groups without detectable crossreactivity when tested by immune electron microscopy or complement fixation. cRNA transcribed from representatives of both groups did not hybridize with DNA from heterologous isolates. The two types of BPV also differed in the electrophoretic mobility of their proteins and in the molecular weight of their DNA (4.5 × 10 and 4.9 × 10, respectively). One isolate with DNA of 4.9 × 10 MW and one isolate with DNA of 4.5 × 10 MW were analyzed by cleavage of their DNA with the restriction endonucleases BamHI, EcoRI, HindII, HindlH, and HaeHI and physical maps were established. The two genomes differed completely in their cleavage pattern. The HindII cleavage pattern demonstrated the identity of the large DNA isolate with BPV 2 of Lancaster et al. (personal communication). The other apparently new type of bovine papilloma virus, which was detected twice thus far, is tentatively designated as BPV 3

Can in-vitro chemoresponse assays help find new treatment regimens for malignant gliomas?

Various in-vitro chemosensitivity and resistance assays (CSRAs) have been demonstrated to be helpful decision aids for non-neurological tumors. Here, we evaluated the performance characteristics of two CSRAs for glioblastoma (GB) cells. The chemoresponse of fresh GB cells from 30 patients was studied in vitro using the ATP tumor chemoresponse assay and the chemotherapy resistance assay (CTR-Test). Both assay platforms provided comparable results. Of seven different chemotherapeutic drugs and drug combinations tested in vitro, treosulfan plus cytarabine (TARA) was the most effective, followed by nimustine (ACNU) plus teniposide (VM26) and temozolomide (TMZ). Whereas ACNU/VM26 and TMZ have proven their clinical value for malignant gliomas in large randomized studies, TARA has not been successful in newly diagnosed gliomas. This seeming discrepancy between in vitro and clinical result might be explained by the pharmacological behavior of treosulfan. Our results show reasonable agreement between two cell-based CSRAs. They appear to confirm the clinical effectiveness of drugs used in GB treatment as long as pharmacological preconditions such as overcoming the blood-brain barrier are properly considered