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  Neuro-oncologi - Neuro-oncology - brain tumors - gliomas
 Latest news:  Diagnostic markers for glioblastoma.

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  Diagnostic markers for glioblastoma. Jung CS, Unterberg AW, Hartmann C.Histol Histopathol. 2011 Oct;26(10):1327-1341.PMID: 21870336

Glioblastoma (GBM) is the most malignant form of cerebral gliomas, and despite distinct progress in surgical resection, radiation and chemotherapy, the prognosis of patients with GBM is still very poor. In the past decades knowledge of genomics and proteomics and of diagnostic, prognostic, predictive and pharmakodynamic markers measured in cerebrospinal-fluid (CSF), serum, or tumor tissue biomarkers has improved. This review briefly compiles our concepts on diagnostic markers for GBM, focusing on the latest developments

 

 
 

Antiangiogenic therapy for patients with recurrent and newly diagnosed malignant gliomas. Shirai K, Siedow MR, Chakravarti A. J Oncol. 2012;2012:193436. Epub 2011 Jul 14.

Malignant gliomas have a poor prognosis despite advances in diagnosis and therapy. Although postoperative temozolomide and radiotherapy improve overall survival in glioblastoma patients, most patients experience a recurrence. The prognosis of recurrent malignant gliomas is dismal, and more effective therapeutic strategies are clearly needed. Antiangiogenesis is currently considered an attractive targeting therapy for malignant gliomas due to its important role in tumor growth. Clinical trials using bevacizumab have been performed for recurrent glioblastoma, and these studies have shown promising response rates along with progression-free survival. Based on the encouraging results, bevacizumab was approved by the FDA for the treatment of recurrent glioblastoma. In addition, bevacizumab has shown to be effective for recurrent anaplastic gliomas. Large phase III studies are currently ongoing to demonstrate the efficacy and safety of the addition of bevacizumab to temozolomide and radiotherapy for newly diagnosed glioblastoma. In contrast, several other antiangiogenic drugs have also been used in clinical trials. However, previous studies have not shown whether antiangiogenesis improves the overall survival of malignant gliomas. Specific severe side effects, difficult assessment of response, and lack of rational predictive markers are challenging problems. Further studies are warranted to establish the optimized antiangiogenesis therapy for malignant gliomas.

 
     
 

Strategies for enhancing antibody delivery to the brain. Frank RT, Aboody KS, Najbauer J. Biochim Biophys Acta. 2011 Jul 8. [Epub ahead of print]

Antibodies and antibody conjugates have emerged as important tools for cancer therapy. However, a major therapeutic challenge for the use of antibodies is their inability to cross the blood-brain barrier (BBB) to reach tumors localized in the central nervous system (CNS). Multiple methods have been developed to enhance antibody delivery to the CNS, including direct injection, mechanical or biochemical disruption of the BBB, conjugation to a 'molecular Trojan horse', cationization, encapsulation in nanoparticles and liposomes, and more recently, stem cell-mediated antibody delivery. In this review, we discuss each of these approaches, highlighting their successes and the obstacles that remain to be overcome.

 

 
     
  Depletion of drug-surviving glioma cells by a second phase treatment with low concentration of salinomycin Zahid M. Delwar, Dimitrios Avramidis, Åke Siden, Mabel Cruz, Juan Sebastian Yakisich. Accepted for publication: 14 June 2011.

Standard treatment for glioma includes surgery, radiotherapy and chemotherapy but the outcome of patients is very poor. Antineoplastic drugs are usually administered alone or in combination for variable times (continuously or in cycles) in a single phase schedule. In this study we explored in vitro the antiproliferative effect of a 2 phases treatment. In the first phase, glioma cells where treated for 3-4 weeks with hydroxyurea (HU) or aphidicolin and then for 4 weeks with salinomycin, a drug that preferentially inhibits the proliferation of cancer stem cells. We found that salinomycin, is able to slowly deplete the fraction of glioma cells that survive the exposure to HU or aphidicolin. Surviving cells were killed at salinomycin concentrations lower than those required to kill untreated cells. The fraction of surviving cell showed traits of senescence including increased activity of the senescence associated -β-galactosidase (SA-β-gal) marker. Our data suggest that drug-induced senescent cells may constitute a novel target for cancer treatment and can be exploited in a two phases therapeutic regimen

 

 
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