Glioblastoma multiforme is one of the most aggressive malignant brain tumours with limited therapeutics options. Standard therapy is maximal surgical resection and adjuvant concurrent chemo-radiotherapy and maintenance therapy with temozolomide. This approach improves median and 5-year survival in comparison with postsurgical radiotherapy alone. Additional predictive and prognostic biomarkers are necessary, especially due to the development of targeted therapy--antibodies and tyrosine kinase inhibitors. These new therapeutic approaches are under intensive investigation. The most promising data currently available are for anti-angiogenic therapies, such as bevacizumab and cediranib. This review presents a summary of the possible role of targeted therapy in the treatment of glioblastoma multiforme.

• MeSH
• glioblastom terapie   MeSH
• kombinovaná terapie MeSH
• lidé MeSH
• nádory mozku terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

• MeSH
• dospělí MeSH
• glioblastom diagnostické zobrazování   MeSH
• lidé MeSH
• myelografie * MeSH
• nádory míchy diagnostické zobrazování   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

• MeSH
• dějiny 20. století MeSH
• glioblastom dějiny   MeSH
• hudba dějiny   MeSH
• nádory mozku dějiny   MeSH
• významné osobnosti * MeSH
• Check Tag
• dějiny 20. století MeSH
• Publikační typ
• anglický abstrakt MeSH
• biografie MeSH
• časopisecké články MeSH
• historické články MeSH
• Geografické názvy
• Spojené státy americké MeSH

• O autorovi
• Gershwin, G

• MeSH
• glioblastom patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů * MeSH
• nádory mozku patologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH

BACKGROUND: Glioblastoma multiforme is the most frequent primary brain tumor in adults. Despite advances in surgery, radiotherapy and chemotherapy, its treatment remains unsatisfactory with very limited overall survival. In the year 2001, in cooperation with Department of Neurosurgery, Nemocnice Na Homolce and Nuclear Research Institute in Rez, we have started to treat glioblastoma patients with boron neutron capture therapy (BNCT). METHODS AND RESULTS: Cells of malignant brain tumors, especially that of glioblastomas, are able to accumulate boron compounds. If BNCT should be successful, it is necessary to reach selective accumulation of sufficient amount of 10B in the tumor and low accumulation in the normal brain tissue. After BSH administration, radiation with low energy thermal neutrons is delivered. It results in nuclear capture and fission reactions with subsequent selective damage of tumor cells. At the time of analysis 9 patients have been enrolled. Therapy was completed in 5 patients. Treatment has been very well tolerated. We observed minimal acute toxicity associated with radiation and no laboratory abnormalities after administrations of BSH. Unfortunately treatment results were quite unsatisfactory. The median time to progression and overall survival were shorter then expected with conventional treatment. CONCLUSIONS: BNCT is very well tolerated with only a modest toxicity. In contrast to standard radiation, BNCT patients receive only one dose of radiation. Nevertheless, in this small pilot study first results were inferior when compared either to outcomes of conventional therapy or to results reported from other BNCT groups. It might be explained that lower dose of radiation had been used. Further study will show whether the higher dose radiation can improve treatment results.

• MeSH
• dospělí MeSH
• glioblastom radioterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory mozku radioterapie   MeSH
• terapie metodou neutronového záchytu (bor-10) * škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Nestin is a protein belonging to class VI of intermediate filaments that is produced in stem/progenitor cells in the mammalian CNS during development and is consecutively replaced by other intermediate filament proteins (neurofilaments, GFAP). Down-regulated nestin may be re-expressed in the adult organism under certain pathological conditions (brain injury, ischemia, inflammation, neoplastic transformation). Our work focused on a detailed study of the nestin cytoskeleton in cell lines derived from glioblastoma multiforme, because re-expression of nestin together with down-regulation of GFAP has been previously reported in this type of brain tumor. METHODS: Two cell lines were derived from the tumor tissue of patients treated for glioblastoma multiforme. Nestin and other cytoskeletal proteins were visualized using imunocytochemical methods: indirect immunofluorescence and immunogold-labelling. RESULTS: Using epifluorescence and confocal microscopy, we described the morphology of nestin-positive intermediate filaments in glioblastoma cells of both primary cultures and the derived cell lines, as well as the reorganization of nestin during mitosis. Our most important result came through transmission electron microscopy and provided clear evidence that nestin is present in the cell nucleus. CONCLUSION: Detailed information concerning the pattern of the nestin cytoskeleton in glioblastoma cell lines and especially the demonstration of nestin in the nucleus represent an important background for further studies of nestin re-expression in relationship to tumor malignancy and invasive potential.

• MeSH
• cytoskelet chemie   ultrastruktura   MeSH
• fluorescenční protilátková technika nepřímá MeSH
• glioblastom chemie   genetika   patologie   ultrastruktura   MeSH
• gliový fibrilární kyselý protein analýza   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nestin MeSH
• proteiny intermediálních filament analýza   MeSH
• proteiny nervové tkáně analýza   MeSH
• vimentin analýza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• gliový fibrilární kyselý protein MeSH
• NES protein, human MeSH Prohlížeč
• nestin MeSH
• proteiny intermediálních filament MeSH
• proteiny nervové tkáně MeSH
• vimentin MeSH

Glioblastoma multiforme (GBM) is the most malignant brain tumor in adults, exhibiting high mortality. Standard therapy (surgery, radiotherapy and chemotherapy with temozolomide) has only limited effectiveness. The progress in genomics regarding GBM, in the detection of new markers of oncogenesis, abnormalities in signalling pathways, tumor microenvironment, and pathological angiogenesis over the past decade are briefly discussed. The role of novel prognostic in this review biomarkers [isocitrate dehydrogenases 1 and 2, CpG island methylator phenotype, promoter methylation status of the MGMT (O-6-methylguanine-methyltransferase) gene] is also discussed. New targeted therapeutic approaches are classified into several functional subgroups, such as inhibitors of growth factors and their receptors, inhibitors of proteins of intracellular signaling pathways, epigenetic gene-expressing mechanisms, inhibitors of tumor angiogenesis, tumor imunotherapy and vaccines. Finally novel possibilities for GBM treatment are summarized in this review.

• MeSH
• cílená molekulární terapie MeSH
• genetická terapie MeSH
• glioblastom farmakoterapie   terapie   MeSH
• imunoterapie MeSH
• lidé MeSH
• nádory mozku farmakoterapie   terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Glioblastoma multiforme (GBM) represents approximately 60% of all brain tumors in adults. This malignancy shows a high biological and genetic heterogeneity associated with exceptional aggressiveness, leading to a poor survival of patients. This review provides a summary of the basic biology of GBM cells with emphasis on cell cycle and cytoskeletal apparatus of these cells, in particular microtubules. Their involvement in the important oncosuppressive process called mitotic catastrophe will next be discussed along with select examples of microtubule-targeting agents, which are currently explored in this respect such as benzimidazole carbamate compounds. Select microtubule-targeting agents, in particular benzimidazole carbamates, induce G2/M cell cycle arrest and mitotic catastrophe in tumor cells including GBM, resulting in phenotypically variable cell fates such as mitotic death or mitotic slippage with subsequent cell demise or permanent arrest leading to senescence. Their effect is coupled with low toxicity in normal cells and not developed chemoresistance. Given the lack of efficient cytostatics or modern molecular target-specific compounds in the treatment of GBM, drugs inducing mitotic catastrophe might offer a new, efficient alternative to the existing clinical management of this at present incurable malignancy.

• Klíčová slova
• benzimidazole carbamates, cell death, glioblastoma multiforme, microtubule-targeting agents, mitotic catastrophe,
• MeSH
• glioblastom * metabolismus   mortalita   terapie   MeSH
• kontrolní body fáze G2 buněčného cyklu * MeSH
• kontrolní body M fáze buněčného cyklu * MeSH
• lidé MeSH
• mitóza * MeSH
• nádory mozku * metabolismus   mortalita   patologie   terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor, with an incidence of 3.19 cases per 100,000 person years and remarkably poor prognosis showing a 5-year survival rate of 4-5%, and only a 26-33% survival rate at 2 years in clinical trials. OBJECTIVE: In this paper, we review the different types of treatment modalities based on the relevant databases. Methods of diagnosis will be described briefly. METHOD: Systemic compilation of the relevant literature. RESULTS & CONCLUSION: Today's treatments cannot cure GBM patients but only extend their overall survival. The use of chemoradiation, immunotherapy, and radio sensitizers as an adjuvant therapy cannot reduce the high rates of recurrence within a few months after treatment. Radiotherapy will remain the backbone of the treatment but new treatment modalities must be developed.

• Klíčová slova
• Biologic agent, chemotherapy, glioblastoma multiforme, immunotherapy, radiation therapy, vaccination.,
• MeSH
• antitumorózní látky alkylující terapeutické užití   MeSH
• buněčná a tkáňová terapie MeSH
• dendritické buňky imunologie   metabolismus   MeSH
• glioblastom diagnóza   mortalita   terapie   MeSH
• imunoterapie MeSH
• kombinovaná terapie MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   MeSH
• nádory mozku diagnóza   mortalita   terapie   MeSH
• Poliovirus genetika   imunologie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antitumorózní látky alkylující MeSH
• monoklonální protilátky MeSH

BACKGROUNDS: Glioblastoma multiforme is the most common malignant primary tumor of the brain in adults. Standard therapy consists in maximal surgical resection and adjuvant concurrent chemoradiotherapy and adjuvant therapy with temozolomid. This approach improves survival in comparison with postsurgical radiotherapy alone. PATIENTS AND METHODS: Consecutive patients with histologically confirmed glioblastoma multiforme in the period from January 2003 to December 2009 underwent postoperative radiotherapy (1.8-2.0 Gy/d, total of 60 Gy) plus concurrent daily chemotherapy (temozolomide 75 mg/m2/d), followed by 6 cycles of temozolomide (150 to 200 mg/m2 for 5 days, every 28 days) and were analyzed retrospectively. The primary end point was to describe the correlation between known clinical factors, treatment and progression free survival (PFS) and overall survival (OS). We assessed the toxicity and safety of the chemoradiotherapy. RESULTS: Eighty-six patients (median age, 56 years; 60% male) were included. Most of them (> 80%) were of performance status (PS) 0-1 at the beginning of chemoradiotherapy. Total macroscopic resection was performed in 20% of the patients, subtotal in 65%, partial in 9%, and just biopsy in 6%. Median PFS was 7.0 months (2.0-35.5), median OS was 13.0 months (2.5-70). Postoperative performance status (PS), the extent of resection, and administration of planned treatment without reduction had statistically significant influences on PFS and OS. Median PFS and OS were 22.0, 7.0 and 6.0 months for PFS (p = 0.0018) in patients with PS O, 1 and 2 respectively and 32.0, 13.0 and 9.0 months for OS (p = 0.0023). Patients with total removal of tumor had longer PFS (14.0 vs 6.0 months, HR = 0.5688; p = 0.0301) and OS (23.0 vs 12.0 months, HR 0.4977; p = 0.0093), as did patients without dose reduction of radiotherapy and/or chemotherapy. Patients with radiotherapy dose of over 54 Gy had PFS 8.0 vs 3.0 months (HR = 0.3313; p = 0.0001) and OS 15.0 vs 5.0 months (HR = 0.1730; p < 0.0001). Similarly, treatment with concurrent chemotherapy for more than 40 days was also important: PFS 8.0 vs 5.0 months (HR = 0.5300; p = 0.0023) and OS 17.0 vs 9.5 months (HR = 0.5943; p = 0.0175). Age, gender and position of tumor had no significant influence. Treatment-related hematology toxicity grades 3 and 4 occurred relatively often: thrombocytopenia (9%), leukopenia (6%), neutropenia (6%) and lymphopenia (25%). Thrombo-embolic events were dominant in non-hematology toxicity. Serious toxicity occurred mainly in the subgroup of patients with PS 2. Treatment of progression was useful in selected patients. Second surgery was of the most benefit (OS 24.0 vs 12.5 months, HR = 0.5325; p = 0.0111). CONCLUSION: Postoperative performance status, extent of resection, successful administration of the majority of planned concurrent chemoradiotherapy and possibility of surgical treatment at the time of recurrence correlate with better prognosis for our patients with glioblastoma. Our experience indicates that performance status should be the main factor in decisions about treatment intensity. Treatment of malignant glioma requires a multidisciplinary team.

• MeSH
• dospělí MeSH
• glioblastom mortalita   terapie   MeSH
• Karnofského skóre MeSH
• kombinovaná terapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• mladý dospělý MeSH
• nádory mozku mortalita   terapie   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH