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Cerebral alveolar echinoccosis mimicking primary brain
tumor.
Senturk
S, Oguz
KK, Soylemezoglu
F, Inci
S.
Department of Radiology, Hacettepe University, Sihhiye, Ankara, Turkey.
We present a case of cerebral infestation by Echinococcosis multilocularis
mimicking an infiltrative primary brain tumor. A heavily calcified mass
invading the midbrain enhanced in a cauliflower-like fashion with small
peripheral nodules present on MR imaging. Perfusion-weighted MR imaging
revealed low relative cerebral blood volume within the calcified lesion and
peripheral hyperemia. Single-voxel proton MR spectroscopy with an echo time
of 135 milliseconds was normal.
PMID: 16484422 [PubMed - in process]
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Permeability versus cerebral blood volume measurement in
brain tumor evaluation: comparative clinical value and advice to authors.
Lev
MH, Vedolin
L.
Massachusetts General Hospital, Boston, Massachusetts, USA.
Publication Types:
PMID: 16484421 [PubMed - in process]
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Comparison of microvascular permeability measurements,
K(trans), determined with conventional steady-state T1-weighted and
first-pass T2*-weighted MR imaging methods in gliomas and meningiomas.
Cha
S, Yang
L, Johnson
G, Lai
A, Chen
MH, Tihan
T, Wendland
M, Dillon
WP.
Department of Radiology, University of California at San Francisco, San
Francisco, California 94143, USA.
BACKGROUND AND PURPOSE: The widely accepted MR method for quantitating brain
tumor microvascular permeability, K(trans), is the steady-state T1-weighted
gradient-echo method (ssT1). Recently the first-pass T2*-weighted (fpT2*)
method has been used to derive both relative cerebral blood volume (rCBV)
and K(trans). We hypothesized that K(trans) derived from the ssT1 and the
fpT2* methods will correlate differently in gliomas and meningiomas because
of the unique differences in morphologic and functional status of each tumor
vascular network. METHODS: Before surgery, 27 patients with newly diagnosed
gliomas (WHO grade I-IV; n = 20) or meningiomas (n = 7) underwent
conventional anatomic MR imaging and 12 dynamic ssT1 acquisitions followed
by 60 dynamic fpT2* images before and after gadopentate dimeglumine
administration. The 3 hemodynamic variables-fpT2* rCBV, fpT2* K(trans), and
ssT1 K(trans)-were calculated in anatomically identical locations and
correlated with glioma grade. The fpT2* K(trans) values were compared with
ssT1 K(trans) for gliomas and meningiomas. RESULTS: All 3 hemodynamic
variables displayed distinct distributions among grades 2, 3, and 4 gliomas
by using the Kruskal-Wallis test. Only K(trans) values, and not rCBV, could
differentiate between grade 4 and lower-grade gliomas by using the Wilcoxon
rank sum test. The fpT2* K(trans) was highly predictive of ssT1 K(trans) for
gliomas, with an estimated regression coefficient of 0.49 (P < .001). For
meningiomas, however, fpT2* K(trans) values correlated poorly with ssT1
K(trans) values (r = 0.26; P = .74). CONCLUSION: Compared with rCBV, K(trans)
values derived from either ssT1 or fpT2* were more predictive of glioma
grade. The fpT2* K(trans) was highly correlated with ssT1 K(trans) in
gliomas but not in meningiomas.
PMID: 16484420 [PubMed - in process]
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Effects of dexamethasone on cerebral perfusion and water
diffusion in patients with high-grade glioma.
Bastin
ME, Carpenter
TK, Armitage
PA, Sinha
S, Wardlaw
JM, Whittle
IR.
Department of Medical and Radiological Sciences, University of Edinburgh,
Western General Hospital, Edinburgh, United Kingdom.
BACKGROUND AND PURPOSE: The mechanisms by which the glucocorticoid
dexamethasone produces its therapeutic action in patients with intracranial
tumors still remain unclear. The purpose of this study was to investigate
whether dexamethasone affects cerebral perfusion and water molecule
diffusion by using quantitative dynamic susceptibility contrast perfusion MR
imaging (DSC-MR imaging) and diffusion tensor MR imaging (DT-MR imaging).
METHODS: Ten consecutive patients with glioblastoma multiforme underwent
DSC-MR imaging and DT-MR imaging before and 48-72 hours after dexamethasone
treatment (16 mg/day). Cerebral blood flow (CBF), cerebral blood volume (CBV),
mean transit time (MTT), and water mean diffusivity (<D>) were
measured for enhancing tumor, nonenhancing peritumoral edematous brain, and
normal-appearing contralateral white matter before and after steroid
therapy. The percentage change in CBF, CBV, MTT, and <D> for the 3
tissue types was calculated for each patient, a mean value obtained for the
population, and the statistical significance determined by using a
paired-samples Student t test. RESULTS: After dexamethasone treatment, there
was no significant change in tumor CBF, CBV, or MTT. Edematous brain CBV and
MTT were also unchanged. There was, however, an increase in edematous brain
CBF (11.6%; P = .05). <D> was reduced in both enhancing tumor (-5.8%;
P = .001) and edematous brain (-6.0%; P < .001). There was no significant
change in CBF, CBV, MTT, or <D> for normal-appearing contralateral
white matter after treatment. CONCLUSION: These data suggest that
dexamethasone does not significantly affect tumor blood flow but may, by
reducing peritumoral water content and local tissue pressure, subtly
increase perfusion in the edematous brain.
PMID: 16484419 [PubMed - in process]
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Prevalence and rupture rate of cerebral aneurysms
discovered during intra-arterial chemotherapy of brain tumors.
Bourekas
EC, Newton
HB, Figg
GM, Slone
HW.
Section of Neuroradiology, Department of Neurology, Ohio State University
College of Medicine and Public Health, Columbus, USA.
BACKGROUND: During the administration of intra-arterial (IA) chemotherapy
for the treatment of brain tumors (BTs), angiography may demonstrate
asymptomatic, incidental cerebral aneurysms. The prevalence and complication
rate of incidental aneurysms in patients undergoing IA chemotherapy remains
unknown. It remains unclear whether the presence of an aneurysm represents
an increased risk or a contraindication to this form of treatment. METHODS:
We performed a chart and angiography review of BT patients receiving IA
chemotherapy over the previous 16 months. Seventy-eight patients were
identified with primary (39) and metastatic (39) BTs. RESULTS: The cohort
consisted of 40 men and 38 women, with a mean age of 47.8 years (range,
22-80 years). During initial angiography, 8 patients (10.3%) were identified
with incidental cerebral aneurysms. The aneurysms were saccular and varied
in size from 2-4 mm (mean, 3 mm). Seven of the 8 patients continued IA
chemotherapy after detection of the aneurysm, for a total of 35 IA
procedures. Of these 7 patients, 5 expired from nonaneurysmal complications
(mean survival, 5.4 months; range, 2-10 months); 4 from the primary tumor,
and one from an infected craniotomy site. Two patients continue to survive;
one remains in treatment, and the other has completed 12 months of IA
therapy. There were no aneurysmal complications during or after IA treatment
in any of the BT patients. CONCLUSION: Incidental aneurysms may be more
common in patients with BTs than the general population. In our patient
population, there was no indication that an incidental aneurysm was reason
to preclude or delay the use of IA chemotherapy.
PMID: 16484396 [PubMed - in process]
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A case report of a recurrent intracranial ependymoma
treated with temozolomide in remission 10 years after completing
chemotherapy.
Rehman
S, Brock
C, Newlands
ES.
Department of Medical Oncology, Christie Hospital, Manchester, UK.
shazzarehman@hotmail.com
Publication Types:
PMID: 16462515 [PubMed - indexed for MEDLINE]
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The association between antihypertensive drugs and glioma.
Houben
MP, Coebergh
JW, Herings
RM, Casparie
MK, Tijssen
CC, van
Duijn CM, Stricker
BH.
[1] 1Department of Neurology, St Elisabeth Hospital, PO Box 90151, 5000 LC
Tilburg, The Netherlands [2] 2Department of Epidemiology & Biostatistics,
Erasmus MC, Rotterdam, The Netherlands.
We pursued an association between hypertension and gliomas by investigating
whether antihypertensive drugs (AHD) are associated with an increased glioma
risk by a population-based nested case-control study using the PHARMO
database; this links dispensing records of prescription drugs to hospital
discharge data on an individual basis. Pathological data were derived from
the Dutch nationwide registry of histo- and cytopathology. A total of 306
glioma cases incident between 1997 and 2003 were matched to 1108 controls
for year of birth, sex, geographical region and duration of follow-up.
Exposure was defined as cumulative duration of AHD use and, in an
alternative analysis, as cumulative dose. We estimated the magnitude of the
association with conditional logistic regression analysis. Cumulative use of
any AHD for more than 6 months was associated with an increased risk of
glioma (OR 1.45; 95% CI 1.03-2.04). After stratification for different
groups of AHD, no significantly increased risk of glioma was found for any
class of AHD. After excluding a latency period of 3 years before the date of
diagnosis, no association was found. In conclusion, the use of AHD seems to
be associated with an increased risk of glioma, but this is probably not
causal.British Journal of Cancer advance online publication, 21 February
2006; doi:10.1038/sj.bjc.6603000 www.bjcancer.com.
PMID: 16495922 [PubMed - as supplied by publisher]
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Glioma virotherapy: effects of innate immune suppression
and increased viral replication capacity.
Friedman
A, Tian
JP, Fulci
G, Chiocca
EA, Wang
J.
Mathematical Biosciences Institute.
Oncolytic viruses are genetically altered replication-competent viruses that
infect, and reproduce in, cancer cells but do not harm normal cells. On
lysis of the infected cells, the newly formed viruses burst out and infect
other tumor cells. Experiments with injecting mutant herpes simplex virus 1
(hrR3) into glioma implanted in brains of rats show lack of efficacy in
eradicating the cancer. This failure is attributed to interference by the
immune system. Initial pretreatment with immunosuppressive agent
cyclophosphamide reduces the percentage of immune cells. We introduce a
mathematical model and use it to determine how different protocols of
cyclophosphamide treatment and how increased burst size of the mutated virus
will affect the growth of the cancer. One of our conclusions is that the
diameter of the cancer will decrease from 4 mm to eventually 1 mm if the
burst size of the virus is triple that which is currently available. The
effect of repeated cyclophosphamide treatment is to maintain a low density
of uninfected cells in the tumor, thus reducing the probability of migration
of tumor cells to other locations in the brain. (Cancer Res 2006; 66(4):
2314-9).
PMID: 16489036 [PubMed - in process]
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Targeting of the Receptor Protein Tyrosine Phosphatase
{beta} with a Monoclonal Antibody Delays Tumor Growth in a Glioblastoma
Model.
Foehr
ED, Lorente
G, Kuo
J, Ram
R, Nikolich
K, Urfer
R.
AGY Therapeutics, Inc., South San Francisco, California.
The receptor protein tyrosine phosphatase beta (RPTPbeta) is a functional
biomarker for several solid tumor types. RPTPbeta expression is largely
restricted to the central nervous system and overexpressed primarily in
astrocytic tumors. RPTPbeta is known to facilitate tumor cell adhesion and
migration through interactions with extracellular matrix components and the
growth factor pleiotrophin. Here, we show that RPTPbeta is expressed in a
variety of solid tumor types with low expression in normal tissue. To assess
RPTPbeta as a potential target for treatment of glioblastoma and other
cancers, antibodies directed to RPTPbeta have been developed and profiled in
vitro and in vivo. The recombinant extracellular domain of human short
RPTPbeta was used to immunize mice and generate monoclonal antibodies that
selectively recognize RPTPbeta and bind to the antigen with low nanomolar
affinities. Moreover, these antibodies recognized the target on living tumor
cells as measured by flow cytometry. These antibodies killed glioma cells in
vitro when coupled to the cytotoxin saporin either directly or via a
secondary antibody. Finally, in vivo studies showed that an anti-RPTPbeta
immunotoxin (7E4B11-SAP) could significantly delay human U87 glioma tumors
in a mouse xenograft model. Unconjugated 7E4B11 provides a modest but
statistically significant tumor growth delay when delivered systemically in
mice bearing U87 glioma tumors. (Cancer Res 2006; 66(4): 2271-8).
PMID: 16489031 [PubMed - in process]
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-
Mouse Models of Human Cancers Consortium Workshop on
Nervous System Tumors.
Gutmann
DH, Maher
EA, Van
Dyke T.
Department of Neurology, Washington University School of Medicine, St.
Louis, Missouri 63110, USA. gutmannd@neuro.wustl.edu
Nervous system tumors are clinically challenging neoplasms that form within
the central and peripheral nervous system. Although there have been many
clinical trials using novel agents for the treatment of primary brain
tumors, there have been few advances that positively affect overall patient
survival. Over the past several years, there has been significant progress
in the development of accurate small-animal spontaneous brain tumor models,
small-animal neuroimaging, and tools for the bioinformatic analysis of
complex molecular data sets, all of which have contributed to an improved
understanding of the pathogenesis of human brain tumors. Whereas these
models will continue to be of great value in basic science investigations,
they can also be used to identify and validate potential therapies for brain
tumors and to evaluate these drugs in preclinical trials. The National
Cancer Institute recently convened a workshop to review the current state of
small-animal brain tumor modeling and to make recommendations about the use
of these models to improve the clinical outcome for patients with brain
tumors. In this meeting report, we outline the current state of small-animal
models for brain tumors, the potential applications of these models, and the
recommendations made by the workshop participants for the use of mouse
models in the preclinical evaluation of potential brain tumor therapies.
Publication Types:
PMID: 16397207 [PubMed - indexed for MEDLINE]
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-
Epidermal growth factor receptor-targeted immunoliposomes
significantly enhance the efficacy of multiple anticancer drugs in vivo.
Mamot
C, Drummond
DC, Noble
CO, Kallab
V, Guo
Z, Hong
K, Kirpotin
DB, Park
JW.
Division of Hematology-Oncology, University of California at San Francisco,
94115, USA.
We previously reported the development of epidermal growth factor receptor (EGFR)-targeted
immunoliposomes that bind and internalize in tumor cells which overexpress
EGFR and/or mutant EGFR variant III (EGFRvIII), enabling intracellular
delivery of potent anticancer agents in vitro. We now describe in vivo
proof-of-concept for this approach for the delivery of multiple anticancer
drugs in EGFR-overexpressing tumor models. Anti-EGFR immunoliposomes were
constructed modularly with Fab' fragments of cetuximab (IMC-C225),
covalently linked to liposomes containing probes and/or anticancer drugs.
Pharmacokinetic and biodistribution studies confirmed long circulation times
(t(1/2) = 21 hours) and efficient accumulation in tumors (up to 15% ID/g)
irrespective of the presence of the targeting ligand. Although total
accumulations of anti-EGFR immunoliposomes and nontargeted liposomes in
EGFR-overexpressing tumors were comparable, only immunoliposomes
internalized extensively within tumor cells (92% of analyzed cells versus
<5% for nontargeted liposomes), indicating different mechanisms of
delivery at the cellular level. In vivo therapy studies in a series of
xenograft models featuring overexpression of EGFR and/or EGFRvIII showed the
superiority of immunoliposomal delivery of encapsulated drugs, which
included doxorubicin, epirubicin, and vinorelbine. For each of these drugs,
anti-EGFR immunoliposome delivery showed significant antitumor effects and
was significantly superior to all other treatments, including the
corresponding free or liposomal drug (P < 0.001-0.003). We conclude that
anti-EGFR immunoliposomes provide efficient and targeted drug delivery of
anticancer compounds and may represent a useful new treatment approach for
tumors that overexpress the EGFR.
PMID: 16357174 [PubMed - indexed for MEDLINE]
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-
Widespread CXCR4 activation in astrocytomas revealed by
phospho-CXCR4-specific antibodies.
Woerner
BM, Warrington
NM, Kung
AL, Perry
A, Rubin
JB.
Department of Pediatrics, Division of Pediatric Hematology/Oncology,
Washington University School of Medicine, St. Louis, MO 63110, USA.
The chemokine receptor CXCR4 is expressed in many cancers where it may
regulate tumor cell growth and migration. The role of CXCR4 in cancer will
depend on it being in an activated, signaling state. To better define the
significance of CXCR4 expression in cancer, we developed an antibody that
can distinguish CXCR4 phosphorylated on serine 339, a residue previously
identified as a site for ligand-induced phosphorylation. With this antibody,
we investigated the mechanisms of CXCR4 phosphorylation and evaluated the
phosphorylation status of CXCR4 in human astrocytomas. In vitro,
phosphorylation of serine 339 occurred in response to CXCL12 or epidermal
growth factor (EGF) treatment and was increased by protein kinase C
activation. In all grades of astrocytomas, CXCR4 was expressed in tumor
cells and some endothelial cells, whereas CXCL12 was present in endothelial
cells and infiltrating microglia. We found that CXCR4 phosphorylated on
serine 339 was present in tumor cells and vascular endothelial cells in all
grades of astrocytoma. These data indicate that CXCR4 is expressed and
activated in astrocytomas and that phosphorylation of CXCR4 can occur
through ligand activation or transactivation via the EGF receptor. These
studies extend the potential roles of CXCR4 in cancer to include functions
associated with benign (grade 1) tumors. The ability to distinguish
phosphorylated CXCR4 will be invaluable for the continued analysis of the
role of CXCR4 in cancer and the development of CXCR4 antagonist therapy for
patients suffering with primary tumors of the brain and other sites.
PMID: 16357147 [PubMed - indexed for MEDLINE]
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-
Gene expression profiles associated with treatment
response in oligodendrogliomas.
French
PJ, Swagemakers
SM, Nagel
JH, Kouwenhoven
MC, Brouwer
E, van
der Spek P, Luider
TM, Kros
JM, van
den Bent MJ, Sillevis
Smitt PA.
Department of Neurology, Cancer Genomics Center, Erasmus Medical Center,
Rotterdam, the Netherlands. p.french@erasmusmc.nl
Oligodendrogliomas are a specific subtype of brain tumor of which the
majority responds favorably to chemotherapy. In this study, we made use of
expression profiling to identify chemosensitive oligodendroglial tumors.
Correlation of expression profiles to loss of heterozygosity on 1p and 19q,
common chromosomal aberrations associated with response to treatment,
identified 376, 64, and 60 differentially expressed probe sets associated
with loss of 1p, 19q or 1p, and 19q, respectively. Correlation of expression
profiles to the tumors' response to treatment identified 16 differentially
expressed probe sets. Because transcripts associated with chemotherapeutic
response were identified independent of common chromosomal aberrations,
expression profiling may be used as an alternative approach to the tumors'
1p status to identify chemosensitive oligodendroglial tumors. Finally, we
correlated expression profiles to survival of the patient after diagnosis
and identified 103 differentially expressed probe sets. The observation that
many genes are differentially expressed between long and short survivors
indicates that the genetic background of the tumor is an important factor in
determining the prognosis of the patient. Furthermore, these transcripts can
help identify patient subgroups that are associated with favorable
prognosis. Our study is the first to correlate gene expression with
chromosomal aberrations and clinical performance (response to treatment and
survival) in oligodendrogliomas. The differentially expressed transcripts
can help identify patient subgroups with good prognosis and those that will
benefit from chemotherapeutic treatments.
PMID: 16357140 [PubMed - indexed for MEDLINE]
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Cyclophosphamide allows for in vivo dose reduction of a
potent oncolytic virus.
Kambara
H, Saeki
Y, Chiocca
EA.
Dardinger Center for Neuro-oncology and Neurosciences, Department of
Neurological Surgery, The Ohio State University Comprehensive Cancer Center,
Columbus, 43210, USA.
The success of cancer virotherapy depends on its efficacy versus toxicity
profile in human clinical trials. Progress towards clinical trials can be
hampered by the relatively elevated doses of oncolytic viruses administered
in animal models to achieve an anticancer effect and by the even higher
doses required in humans to approximate an animal bioequivalent dose. Such
elevated doses of injected viral proteins may also lead to undesirable
toxicities and are also very difficult to produce in a biotechnological
setting. We report that a relatively potent herpes simplex virus type 1
oncolytic virus (rQNestin34.5) produces 45% survivors at a dose of 3 x 10(4)
plaque-forming units (pfu) in a 9-day-old mouse model of human glioma.
Unlike our previous findings with less potent oncolytic viruses, though, the
preadministration of cyclophosphamide did not enhance this survival or
affect oncolytic virus tumor distribution and tumor volume. However, when
oncolytic virus doses were reduced (3 x 10(3) and 3 x 10(2) pfu),
cyclophosphamide significantly enhanced both animal survival and oncolytic
virus tumor distribution and also reduced tumor volumes. These findings thus
show that cyclophosphamide allows for dose reduction of doses of a
relatively potent oncolytic virus, a finding with implications for the
development of clinical trials.
PMID: 16357128 [PubMed - indexed for MEDLINE]
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Targeted Therapy for Glioblastoma Multiforme Neoplastic
Meningitis with Intrathecal Delivery of an Oncolytic Recombinant Poliovirus.
Ochiai
H, Campbell
SA, Archer
GE, Chewning
TA, Dragunsky
E, Ivanov
A, Gromeier
M, Sampson
JH.
Authors' Affiliations: Division of Neurosurgery, Department of Surgery;
Departments of Molecular Genetics and Microbiology and Pathology, Duke
University Medical Center, Durham, North Carolina; and Center of Biologics
Evaluation and Research, Food and Drug Administration, Rockville, Maryland.
PURPOSE: The toxicity and antitumor activity of regional intrathecal
delivery of an oncolytic recombinant poliovirus, PVS-RIPO, was evaluated in
rodent models of glioblastoma multiforme neoplastic meningitis.EXPERIMENTAL
DESIGN: To evaluate for toxicity, PVS-RIPO was administered into the spinal
cord of transgenic mice that express the human poliovirus receptor, CD155,
and into the intrathecal space of athymic rats without tumor. To evaluate
efficacy, two different doses of PVS-RIPO were administered intrathecally 3
days after athymic rats were inoculated intrathecally with an aggressive
human glioblastoma multiforme xenograft.RESULTS: No clinical or histologic
evidence of toxicity was found. In efficacy studies, median survival was
increased by 174.47% from 8.5 days in the group treated with UV
light-inactivated virus to 15 days in the rats treated with 1.0 x 10(7)
plaque-forming units (pfu) of PVS-RIPO (P < 0.0001). A similar increase
in median survival was seen in the group receiving 1.0 x 10(9) pfu PVS-RIPO
(P < 0.0001); however, there was no statistically significant
dose-response relationship (P = 0.345). In addition, 1 of 10 rats in
lower-dose PVS-RIPO-treated group and 3 of 10 rats in higher-dose
PVS-RIPO-treated group survived >60 days after tumor cell inoculation and
had no evidence of residual tumor at autopsy.CONCLUSION: These results
suggest that intrathecal treatment with PVS-RIPO may be useful for treatment
of neoplastic meningitis in patients with glioblastoma multiforme and
provides a rationale for clinical trials in this area.
PMID: 16489093 [PubMed - as supplied by publisher]
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Systemic anti-hepatocyte growth factor monoclonal
antibody therapy induces the regression of intracranial glioma xenografts.
Kim
KJ, Wang
L, Su
YC, Gillespie
GY, Salhotra
A, Lal
B, Laterra
J.
Authors' Affiliations: Galaxy Biotech, LLC, Mountain View, California.
PURPOSE: Hepatocyte growth factor (HGF) and its receptor Met are involved in
the initiation, progression, and metastasis of numerous systemic and central
nervous system tumors. Thus, an anti-HGF monoclonal antibody (mAb) capable
of blocking the HGF-Met interaction could have broad applicability in cancer
therapy.EXPERIMENTAL DESIGN: An anti-HGF mAb L2G7 that blocks binding of HGF
to Met was generated by hybridoma technology, and its ability to inhibit the
various biological activities of HGF was measured by in vitro assays. The
ability of L2G7 to inhibit the growth of tumors was determined by
establishing s.c. and intracranial xenografts of human U87 and U118 glioma
cell lines in nude mice, and treatment with 100 mug of L2G7 or control given
i.p. twice per week.RESULTS: MAb L2G7 strongly inhibited all biological
activities of HGF measured in vitro, including cell proliferation, cell
scattering, and endothelial tubule formation. Treatment with L2G7 completely
inhibited the growth of established s.c. xenografts in nude mice. Moreover,
systemic administration of L2G7 from day 5 induced the regression of
intracranial U87 xenografts and dramatically prolonged the survival of
tumor-bearing mice from a median of 39 to >90 days. L2G7 treatment of
large intracranial tumors (average tumor size, 26.7 mm(3)) from day 18
induced substantial tumor regression (control group, 134.3 mm(3); L2G7
treated group, 11.7 mm(3)) by day 29 and again prolonged animal
survival.CONCLUSIONS: These findings show that blocking the HGF-Met
interaction with systemically given anti-HGF mAb can have profound antitumor
effects even within the central nervous system, a site previously believed
to be resistant to systemic antibody-based therapeutics.
PMID: 16489086 [PubMed - in process]
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E2F1 identified by promoter and biochemical analysis as a
central target of glioblastoma cell-cycle arrest in response to ras
inhibition.
Blum
R, Nakdimon
I, Goldberg
L, Elkon
R, Shamir
R, Rechavi
G, Kloog
Y.
Department of Neurobiochemistry, The George S. Wise Faculty of Life
Sciences, Tel-Aviv University, Tel-Aviv, Israel.
Active Ras contributes to the malignant phenotype of glioblastoma multiforme.
Recent studies showed that the Ras inhibitor farnesyl thiosalicylic acid
downregulates the transcription factor hypoxia-inducible factor-1alpha,
causing shutdown of glycolysis in U87 glioblastoma cells. Farnesyl
thiosalicylic acid also inhibited the growth of U87 cells. The way in which
Ras inhibition affects U87 cell proliferation was not clear. Here we applied
a computational method in which gene expression profile clustering is
combined with promoter sequence analysis to obtain global dissection of the
transcriptional response to farnesyl thiosalicylic acid in U87 cells. The
analysis revealed a prominent Ras-dependent cell-cycle arrest response, in
which a major component is highly enriched for the binding-site signature of
the transcription factor E2F1. Electrophoretic mobility shift assays
together with E2F-luciferase reporter assays showed that E2F1 was
inactivated by the Ras inhibitor. Inhibition of Ras by farnesyl
thiosalicylic acid promoted proteasomal degradation of cyclin D1, with a
concomitant decrease in phosphorylated retinoblastoma protein accompanied by
downregulation of E2F1 and decreased expression of key E2F1-regulated genes
critical for cell-cycle progression. U87 cell growth arrest induced by
farnesyl thiosalicylic acid was overridden by constitutive expression of
E2F1. Thus, downregulation of E2F1 and of hypoxia-inducible factor-1alpha
represents 2 distinct arms of the antioncogenic effect of Ras inhibitors in
glioblastoma. (c) 2006 Wiley-Liss, Inc.
PMID: 16496386 [PubMed - as supplied by publisher]
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Improved target volume definition for fractionated
stereotactic radiotherapy in patients with intracranial meningiomas by
correlation of CT, MRI, and [(68)Ga]-DOTATOC-PET.
Milker-Zabel
S, Zabel-du
Bois A, Henze
M, Huber
P, Schulz-Ertner
D, Hoess
A, Haberkorn
U, Debus
J.
Department of Radiation Oncology, Radiation Therapy.
PURPOSE: To evaluate the influence of (68)-Ga-labeled DOTA ((0))-D-Phe
((1))-Tyr ((3))-Octreotide positron emission tomography
([(68)Ga]-DOTATOC-PET) for target definition for fractionated stereotactic
radiotherapy (FSRT) as a complementary modality to computed tomography (CT)
and magnetic resonance imaging (MRI). Because meningiomas show a high
expression of somatostatin receptor subtype 2, somatostatin analogs such as
DOTATOC offer the possibility of receptor-targeted imaging. PATIENTS AND
METHODS: Twenty-six patients received stereotactic CT, MRI, and
[(68)Ga]-DOTATOC-PET as part of their treatment planning. Histology was:
World Health Organization (WHO) Grade 1 61.5%, WHO Grade 2 7.7%, WHO Grade 3
3.9%, and undetermined 26.9%. Six patients received radiotherapy as primary
treatment, 2 after subtotal resection; 17 patients were treated for
recurrent disease. Dynamic PET scans were acquired before radiotherapy over
60 min after intravenous injection of 156 +/- 29 MBq [(68)Ga]-DOTATOC. These
PET images were imported in the planning software for FSRT. Planning target
volume (PTV)-I outlined on CT and contrast-enhanced MRI was compared with
PTV-II outlined on PET. PTV-III was defined with CT, MRI, and PET and was
actually used for radiotherapy treatment. RESULTS: PTV-III was smaller than
PTV-I in 9 patients, the same size in 7 patients, and larger in 10 patients.
Median PTV-I was 49.6 cc, median PTV-III was 57.2 cc. In all patients
[(68)Ga]-DOTATOC-PET delivered additional information concerning tumor
extension. PTV-III was significantly modified based on DOTATOC-PET data in
19 patients. In 1 patient no tumor was exactly identified on CT/MRI but was
visible on PET. CONCLUSION: These data demonstrate that [(68)Ga]-DOTATOC-PET
improves target definition for FSRT in patients with intracranial
meningiomas. Radiation targeting with fused DOTATOC-PET, CT, and MRI
resulted in significant alterations in target definition in 73%.
PMID: 16488553 [PubMed - as supplied by publisher]
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Paraneoplastic cerebellar degeneration in olfactory
neuroepithelioma.
Maeda
K, Sasaki
T, Murata
Y, Kanasaki
M, Terashima
T, Kawai
H, Yasuda
H, Okabe
H, Tanaka
K.
Publication Types:
PMID: 16361612 [PubMed - indexed for MEDLINE]
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Low-Grade and Anaplastic Gliomas: Differences in
Architecture Evaluated with Diffusion-Tensor MR Imaging.
Goebell
E, Paustenbach
S, Vaeterlein
O, Ding
XQ, Heese
O, Fiehler
J, Kucinski
T, Hagel
C, Westphal
M, Zeumer
H.
1 Departments of Neuroradiology, Neurosurgery, and Neuropathology,
University of Hamburg, Martinistrasse 52, 20251 Hamburg, Germany.
Purpose: To prospectively evaluate whether diffusion-tensor magnetic
resonance (MR) imaging depicts differences in World Health Organization
(WHO) grade II and III glial brain tumors on the basis of tumor architecture
and peritumoral tract invasion. Materials and Methods: The study protocol
was approved by the local ethics committee, and written informed consent was
obtained. Diffusion-tensor MR imaging was performed in 23 patients (15 men,
eight women; mean age, 47 years) with histologically confirmed brain gliomas.
Eleven of the 23 tumors were low-grade gliomas (WHO grade II) and 12 were
anaplastic gliomas (WHO grade III). Regions of interest were placed in the
tumor center, tumor border, normal-appearing white matter (NAWM) adjacent to
the tumor, and NAWM of the contralateral hemisphere. fractional anisotropy
(FA) ratios were calculated for regions of interest in relation to the NAWM
of the contralateral hemisphere. Pairwise comparisons were performed by
using the Mann-Whitney U test. Results: Median FA ratios for grade II versus
grade III gliomas were 0.406 versus 0.405, respectively, for tumor center,
0.733 versus 0.449, respectively, for tumor border, and 0.962 versus 0.943,
respectively, for NAWM adjacent to the tumor. Differences in FA ratio
between low-grade and high-grade tumors were significant in the tumor border
only (P = .01). Differences in FA ratio were not significant between
low-grade and high-grade gliomas in the tumor center or in the NAWM adjacent
to the tumor. Conclusion: The periphery of low-grade gliomas contains a
considerable amount of preserved fiber tracts. In high-grade gliomas,
however, most of these tracts are disarranged. Low FA ratios in the tumor
center are consistent with a high degree of disorganization of myelinated
fiber tracts in the center of both low-grade and high-grade gliomas. (c)
RSNA, 2006.
PMID: 16484348 [PubMed - as supplied by publisher]
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Primary diffuse multinodular leptomeningeal gliomatosis
Case report and review of the literature.
Debono
B, Derrey
S, Rabehenoina
C, Proust
F, Freger
P, Laquerriere
A.
Department of Neurosurgery, Rouen University Hospital-Charles Nicolle, 76031
Rouen Cedex, France.
BACKGROUND: Primary diffuse leptomeningeal gliomatosis is an exceptional
neoplasm, and only 30 cases have been reported in the literature. We report
a recent case and compare data with previously published observations.
METHODS: A 50-year-old man was admitted to the neurosurgery department for a
previous 4-month history of headache, associated with nonspecific
neurological signs. Biologic data and cerebrospinal fluid examination
suggested an inflammatory process. The patient was given an antituberculous
therapy. Magnetic resonance imaging revealed a multinodular enhancement of
spinal nerve roots. A biopsy of sacral rootlets was performed. Histological
examination revealed an anaplastic astrocytoma. Patient's status worsened,
and death occurred 7 months later. RESULTS: Complete neuraxis postmortem
examination revealed no intraparenchymatous glioma and was conclusive for
the diagnosis of primary leptomeningeal gliomatosis (astrocytic, World
Health Organization grade III), with a multinodular pattern in the spinal
cord, the brainstem, and the brain base with diffuse extension into the
cerebellar subarachnoid spaces. CONCLUSIONS: Our case illustrates the
diagnostic difficulties in making the premortem diagnosis. The review of the
literature indicates that there are no specific clinical or biologic signs.
Magnetic resonance imaging using T1-weighted images with gadolinium
enhancement and biopsy material may be useful diagnostic tools. In most
cases, autopsy evaluation alone permits definitive primary diffuse
leptomeningeal gliomatosis diagnosis. Whatever the histological
characteristics of proliferating cells are, the prognosis remains poor. No
prognostic factors have been shown to be correlated with survival time.
Unfortunately, no routine treatment has been yet proposed.
PMID: 16488248 [PubMed - in process]
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Volume 5, Number 9 - 27 February 2006