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Intraoperative consultation in the diagnosis of pediatric
brain tumors.
Adesina
AM.
Department of Pathology, Texas Children's Hospital, Baylor College of
Medicine, Houston, Texas 77030, USA. aadesina@bcm.tmc.edu
CONTEXT: The prevalence of brain tumors in the pediatric population differs
from that in the adult population. Similarly, the frequency and location of
the different histologic types of brain tumors vary significantly between
the pediatric and adult populations. OBJECTIVE: To familiarize the
pathologist with the pediatric brain tumors encountered during
intraoperative consultation and with the appropriate differential diagnoses
in this setting. DATA SOURCES: The medical literature and the author's
experience and expertise. CONCLUSION: Compared with adult brain tumors,
pediatric brain tumors present different challenges and distinct
differential diagnoses that the pathologist should be aware of during
intraoperative consultation.
PMID: 16329737 [PubMed - in process]
 
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Different angiogenic phenotypes in primary and secondary
glioblastomas.
Karcher
S, Steiner
HH, Ahmadi
R, Zoubaa
S, Vasvari
G, Bauer
H, Unterberg
A, Herold-Mende
C.
Molecular Biology Laboratory, Neurosurgery Hospital, University of
Heidelberg, INF 400, Heidelberg, Germany.
Primary and secondary glioblastomas (pGBM, sGBM) are supposed to evolve
through different genetic pathways, including EGF receptor and PDGF and its
receptor and thus genes that are involved in tumor-induced angiogenesis.
However, whether other angiogenic cytokines are also differentially
expressed in these glioblastoma subtypes is not known so far, but this
knowledge might be important to optimize an antiangiogenic therapy.
Therefore, we studied the expression of several angiogenic cytokines,
including VEGF-A, HGF, bFGF, PDGF-AB, PDGF-BB, G-CSF and GM-CSF in pGBMs and
sGBMs as well as in gliomas WHO III, the precursor lesions of sGBMs. In
tumor tissues, expression of all cytokines was observed albeit with marked
differences concerning intensity and distribution pattern. Quantification of
the cytokines in the supernatant of 30 tissue-corresponding glioma cultures
revealed a predominant expression of VEGF-A in pGBMs and significantly
higher expression levels of PDGF-AB in sGBMs. HGF and bFGF were determined
in nearly all tumor cultures but with no GBM subtype or malignancy-related
differences. Interestingly, GM-CSF and especially G-CSF were produced less
frequently by tumor cells. However, GM-CSF secretion occurred together with
an increased number of simultaneously secreted cytokines and correlated with
a worse patient prognosis and may thus represent a more aggressive
angiogenic phenotype. Finally, we confirmed an independent contribution of
each tumor-derived cytokine analyzed to tumor-induced vascularization. Our
data indicate that an optimal antiangiogenic therapy may require targeting
of multiple angiogenic pathways that seem to differ markedly in pGBMs and
sGBMs. (c) 2005 Wiley-Liss, Inc.
PMID: 16331629 [PubMed - as supplied by publisher]
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Telomerase inhibition by stable RNA interference impairs
tumor growth and angiogenesis in glioblastoma xenografts.
Pallini
R, Sorrentino
A, Pierconti
F, Maggiano
N, Faggi
R, Montano
N, Maira
G, Larocca
LM, Levi
A, Falchetti
ML.
Institute of Neurosurgery, Catholic University School of Medicine, Rome,
Italy.
Telomerase is highly expressed in advanced stages of most cancers where it
allows the clonal expansion of transformed cells by counteracting telomere
erosion. Telomerase may also contribute to tumor progression through still
undefined cell growth-promoting functions. Here, we inhibited telomerase
activity in 2 human glioblastoma (GBM) cell lines, TB10 and U87MG, by
targeting the catalytic subunit, hTERT, via stable RNA interference (RNAi).
Although the reduction in telomerase activity had no effect on GBM cell
growth in vitro, the development of tumors in subcutaneously and
intracranially grafted nude mice was significantly inhibited by
antitelomerase RNAi. The in vivo effect was observed within a relatively
small number of population doublings, suggesting that telomerase inhibition
may hinder cancer cell growth in vivo prior to a substantial shortening of
telomere length. Tumor xenografts that arose from telomerase-inhibited GBM
cells also showed a less-malignant phenotype due both to the absence of
massive necrosis and to reduced angiogenesis. (c) 2005 Wiley-Liss, Inc.
PMID: 16331616 [PubMed - as supplied by publisher]
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18F-Fluoro-L-Thymidine and 11C-Methylmethionine as
Markers of Increased Transport and Proliferation in Brain Tumors.
Jacobs
AH, Thomas
A, Kracht
LW, Li
H, Dittmar
C, Garlip
G, Galldiks
N, Klein
JC, Sobesky
J, Hilker
R, Vollmar
S, Herholz
K, Wienhard
K, Heiss
WD.
Max Planck Institute for Neurological Research, Cologne, Germany.
Because of the high glucose metabolism in normal brain tissue (18)F-FDG is
not the ideal tracer for the detection of gliomas. Methyl-(11)C-l-methionine
((11)C-MET) is better suited for imaging the extent of gliomas, because it
is transported specifically into tumors but only insignificantly into normal
brain. 3'-Deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) has been introduced as
a proliferation marker in a variety of neoplasias and has promising
potential for the detection of brain tumors, because its uptake in normal
brain is low. Additionally, the longer half-life might permit
differentiation between transport and intracellular phosphorylation.
METHODS: PET of (18)F-FLT and (11)C-MET was performed on 23 patients (age
range, 20-70 y) with histologically verified gliomas of different grades. On
all patients, conventional MRI was performed, and 16 patients additionally
underwent contrast-enhanced imaging. Images were coregistered, and the
volumes of abnormality were defined for PET and MRI. Uptake ratios and
standardized uptake values (SUVs) of various tumors and regions were
assessed by region-of-interest analysis. Kinetic modeling was performed on
14 patients for regional time-activity curves of (18)F-FLT from tumorous and
normal brain tissue. RESULTS: Sensitivity for the detection of tumors was
lower for (18)F-FLT than for (11)C-MET (78.3% vs. 91.3%), especially for
low-grade astrocytomas. Tumor volumes detected by (18)F-FLT and (11)C-MET
were larger than tumor regions displaying gadolinium enhancement (P <
0.01). Uptake ratios of (18)F-FLT were higher than uptake ratios of
(11)C-MET (P < 0.01). Uptake ratios of (18)F-FLT were higher in
glioblastomas than in astrocytomas (P < 0.01). Absolute radiotracer
uptake of (18)F-FLT was low and significantly lower than that of (11)C-MET
(SUV, 1.3 +/- 0.7 vs. 3.1 +/- 1.0; P < 0.01). Some tumor regions were
detected only by either (18)F-FLT (7 patients) or (11)C-MET (13 patients).
Kinetic modeling revealed that (18)F-FLT uptake in tumor tissue seems to be
predominantly due to elevated transport and net influx. However, a moderate
correlation was found between uptake ratio and phosphorylation rate k3 (r =
0.65 and P = 0.01 for grade II-IV gliomas; r = 0.76 and P < 0.01 for
grade III-IV tumors). CONCLUSION: (18)F-FLT is a promising tracer for the
detection and characterization of primary central nervous system tumors and
might help to differentiate between low- and high-grade gliomas. (18)F-FLT
uptake is mainly due to increased transport, but irreversible incorporation
by phosphorylation might also contribute. In some tumors and tumor areas,
(18)F-FLT uptake is not related to (11)C-MET uptake. In view of the high
sensitivity and specificity of (11)C-MET PET for imaging of gliomas, it
cannot be excluded that (18)F-FLT PET was false positive in these areas.
However, the discrepancies observed for the various imaging modalities
((18)F-FLT and (11)C-MET PET as well as gadolinium-enhanced MRI) yield
complementary information on the activity and the extent of gliomas and
might improve early evaluation of treatment effects, especially in patients
with high-grade gliomas. Further studies are needed, including coregistered
histology and kinetic analysis in patients undergoing chemotherapy.
PMID: 16330557 [PubMed - in process]
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Endothelial cell transplantation for gene therapy in
experimental gliomas.
Machein
MR, Knoth
R, Plate
KH.
Department of Neurosurgery, University of Freiburg School of Medicine,
Freiburg, Germany. machein@nz.ukl.uni-freiburg.de
OBJECTIVE: Malignant gliomas are prominent targets for cancer gene therapy
approaches because of their poor prognosis despite all available therapies.
Endothelial cells (ECs) are considered attractive vehicles for cell-based
gene therapy because of their tropism to the tumor vasculature. In this
study, we investigated the potential of ECs to incorporate into glioma
vessels after intra-arterial or local application to establish whether ECs
can be used as cellular vectors for gene therapy in gliomas. METHODS:
Immortalized rat brain endothelial cells (BECs) were modified to express
either beta-galactosidase or green fluorescent protein (GFP). The ability of
transduced BECs to integrate into tumor vessels after interstitial
implantation was evaluated in C6 and 9L glioma models. The fate of GFP-BECs
was investigated after selective intracarotid injection into C6
tumor-bearing animals. RESULTS: The interstitially grafted BECs organized
themselves into vascular-like structures and integrated into the tumor
vasculature. Transgene expression was limited to 10 days after injection.
After selective intra-arterial injection, numerous GFP-BECs were adherent to
the vascular lumen at least 7 days after injection. These cells were evenly
distributed within small vessels and capillaries of the injected hemisphere
and did not home selectively to the tumor vessels. CONCLUSION: Cell-based
therapy approaches to brain tumor treatment using BECs as cellular vectors
might be hampered by the rapid downregulation of transgene expression and by
the fact that these cells do not home specifically to tumor vessels after
intra-arterial injection. Nevertheless, locoregional administration of BECs
might be an interesting approach for delivering molecules to brain tumors
when short-term expression of transgene in the perivascular space is
desirable.
PMID: 16331175 [PubMed - in process]
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Gamma knife surgery for low-grade gliomas.
Heppner
PA, Sheehan
JP, Steiner
LE.
The Lars Leksell Gamma Knife Center, Department of Neurological Surgery,
University of Virginia, Charlottesville, Virginia, USA.
OBJECT: Data regarding the long-term efficacy of Gamma knife surgery on a
large series of patients with low-grade gliomas is lacking. We aimed to
review the outcome of patients with low-grade gliomas undergoing Gamma knife
surgery at the Lars Leksell Gamma Knife Center at the University of Virginia
to clarify its role in the management of these lesions. METHODS: A
retrospective review of 49 patients treated between 1989 and 2003 was
conducted. The median follow up was 63 months. Gamma knife surgery was
generally performed for tumors in eloquent brain, residual tumor
post-surgery or for late progression after surgery. RESULTS: Median clinical
progression free survival was 44 months and median radiological progression
free survival was 37 months. Five-year radiological progression free
survival was 37% while clinical progression free survival was 41%. Mortality
due to tumor progression occurred in 7 patients (14%). Complete radiological
remission was seen in 14 patients (29%). Complications due to Gamma surgery
were seen in 4 patients (8%). Of these, two resolved without sequelae, one
required surgery for neurological decline and associated radiation induced
changes, and one patient suffered a permanent neurological deficit from
treatment. CONCLUSION: Gamma knife radiosurgery is a safe treatment for
low-grade gliomas and may be considered in patients with residual or
recurrent disease.
PMID: 16331161 [PubMed - in process]
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Epidemiology of intracranial meningioma.
Claus
EB, Bondy
ML, Schildkraut
JM, Wiemels
JL, Wrensch
M, Black
PM.
Department of Epidemiology and Public Health, Yale University School of
Medicine, New Haven, Connecticut 06520-8034, USA. elizabeth.claus@yale.edu
Meningiomas are the most frequently reported primary intracranial neoplasms,
accounting for approximately 25% of all such lesions diagnosed in the United
States. Few studies have examined the risk factors associated with a
diagnosis of meningioma with two categories of exposure, hormones (both
endogenous and exogenous) and radiation, most strongly associated with
meningioma risk. Limited data are also available on long-term outcomes for
meningioma patients, although it is clear that the disease is associated
with significant morbidity and mortality. Recent legislation passed in the
United States (The Benign Brain Tumor Cancer Registries Amendment Act [H.R.
5204]) mandates registration of benign brain tumors such as meningioma. This
will increase the focus on this disease over the coming years as well as
likely increase the reported prevalence of the disease. The increased
emphasis on research dedicated to the study of brain tumors coupled with the
advent of new tools in genetic and molecular epidemiology make the current
era an ideal time to advance knowledge for intracranial meningioma. This
review highlights current knowledge of meningioma epidemiology and new
directions for research efforts in this field.
PMID: 16331155 [PubMed - in process]
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Concomitant ectatic posterior communicating artery and
tentorial meningioma as a source of oculomotor palsy: case report.
Babbitz
JD, Harsh
GR 4th.
Department of Neurosurgery, Stanford University Medical Center, Stanford,
California 94305-5327, USA. JDBabb2@aol.com
OBJECTIVE AND IMPORTANCE: Although non-aneurysmal vascular compression of
the oculomotor nerve is rare, it should be considered in the evaluation of
unilateral oculomotor palsy. CLINICAL PRESENTATION: A 36-year-old
non-diabetic man presented with two months of intermittent retro-orbital
headache and third nerve paresis caused by compression of the oculomotor
nerve between an ectatic, atherosclerotic posterior communicating artery
(PComA) and a small tentorial meningioma. At operation, the subarachnoid
portion of the nerve, prevented from migrating posteriorly and laterally by
the meningioma, was grooved by the apex of the artery's loop. INTERVENTION:
Microvascular decompression (MVD) of the artery loop from the nerve and
resection of the meningioma were performed. Postoperatively, the patient's
retro-orbital headache and oculomotor paresis, with the exception of mild
anisocoria, resolved. Tumor infiltrating the posterior tentorium and lateral
cavernous sinus was treated by Cyberknife radiosurgery five months later.
One year after surgery, the patient had improvement in his headaches, full
extra-ocular movements, and minimal residual anisocoria. CONCLUSION: Only
one other report describes MVD of the third nerve from PComA compression. A
review is presented of MVD carried out for similar cases of non-aneurysmal
vascular compression of the oculomotor nerve. By analogy from cases in which
an aneurysm is the compressing vascular structure, prompt surgical treatment
is advocated. Complete evaluation of an isolated third nerve palsy should
include MRI sequences designed to detect vascular compression of cranial
nerves.
PMID: 16331147 [PubMed - in process]
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| 9: Oncogene.
2005 Dec 12; [Epub ahead of print] |
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Protection of glioblastoma cells from cisplatin
cytotoxicity via protein kinase Ciota-mediated attenuation of p38 MAP kinase
signaling.
Baldwin
RM, Garratt-Lalonde
M, Parolin
DA, Krzyzanowski
PM, Andrade
MA, Lorimer
IA.
[1] 1Ottawa Health Research Institute, Ottawa, Ontario, Canada [2]
2Department of Biochemistry, Microbiology and Immunology, University of
Ottawa, Ottawa, Ontario, Canada.
Glioblastoma multiforme is an aggressive form of brain cancer that responds
poorly to chemotherapy and is generally incurable. The basis for the poor
response of this cancer to chemotherapy is not well understood. The atypical
protein kinases C (PKCiota and PKCzeta) have previously been implicated in
leukaemia cell chemoresistance. To assess the role of atypical PKC in
glioblastoma cell chemoresistance, RNA interference was used to deplete
human glioblastoma cells of PKCiota. Transfection of cells with either of
two different RNA duplexes specific for PKCiota caused a partial
sensitisation to cell death induced by the chemotherapy agent cisplatin. To
screen for possible mechanisms for PKCiota-mediated chemoresistance,
microarray analysis of gene expression was performed on RNA from
glioblastoma cells that were either untreated or depleted of PKCiota. This
identified sets of genes that were regulated either positively or negatively
by PKCiota. Within the set of genes that were negatively regulated by
PKCiota, the function of the gene coding for GMFbeta, an enhancer of p38
mitogen-activated protein kinase (MAP kinase) signaling, was investigated
further, as the p38 MAP kinase pathway has been previously identified as a
key mediator of cisplatin cytotoxicity. The expression of both GMFbeta mRNA
and protein increased upon PKCiota depletion, and this was accompanied by an
increase in cisplatin-activated p38 MAP kinase signaling. Transient
overexpression of GMFbeta increased cisplatin-activated p38 MAP kinase
signaling and also sensitised cells to cisplatin cytotoxicity. The increase
in cisplatin cytotoxicity seen with PKCiota depletion was blocked by the p38
MAP kinase inhibitor SKF86002. These data show that PKCiota can confer
partial resistance to cisplatin in glioblastoma cells by suppressing
GMFbeta-mediated enhancement of p38 MAP kinase signaling.Oncogene advance
online publication, 12 December 2005; doi:10.1038/sj.onc.1209312.
PMID: 16331246 [PubMed - as supplied by publisher]
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Volume 4, Number 51 - 13 December 2005