|
|
|
|
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 |
|
|