-
The Solitary Enhancing Cerebral Lesion: Can FLAIR Aid the
Differentiation between Glioma and Metastasis?
Tang
YM, Ngai
S, Stuckey
S.
Department of Radiology, Princess Alexandra Hospital, Brisbane, Australia.
BACKGROUND AND PURPOSE: The purpose of this study is to investigate the
diagnostic utility of fluid-attenuated inversion recovery (FLAIR) in
differentiating between glioma and metastasis by assessing for nonenhancing
adjacent cortical signal intensity abnormality in patients who present with
a solitary enhancing cerebral lesion. METHODS: After approval from the
institutional ethics committee was obtained, the MR imaging studies of 70
patients with a solitary enhancing lesion, without previous surgery or
treatment, were reviewed. The axial FLAIR studies were initially reviewed
for cortical involvement. If cortex involvement was detected, comparison
with the axial T1, with and without gadolinium enhancement, was made to
determine whether the cortex involvement was in an area without enhancement.
If this was the case, the study was considered positive for glioma.
Statistical analysis consisted of binary logistic regression and a 2 x 2
contingency table. RESULTS: Involvement of the adjacent cortex with FLAIR
signal intensity abnormality but without enhancement was seen in 19 of 70
patients; 16 were gliomas and 3 were solitary metastasis. The sensitivity
and specificity of this finding were 44% and 91%, respectively. The positive
predictive value for glioma was 84%. CONCLUSION: FLAIR, when interpreted in
concert with pre- and postgadolinium T1-weighted images, may be useful in
differentiating glioma from metastasis when a solitary enhancing cerebral
lesion is present. The presence of nonenhancing adjacent cortical
involvement in a solitary enhancing lesion is a frequent and relatively
specific sign.
PMID: 16552003 [PubMed - in process]
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-
Quantitative Short Echo Time 1H-MR Spectroscopy of
Untreated Pediatric Brain Tumors: Preoperative Diagnosis and
Characterization.
Panigrahy
A, Krieger
MD, Gonzalez-Gomez
I, Liu
X, McComb
JG, Finlay
JL, Nelson
MD Jr, Gilles
FH, Bluml
S.
Department of Radiology, the Division of Neurosurgery, the Department of
Neuropathology, and the Childrens Center for Cancer and Blood Diseases,
Childrens Hospital Los Angeles, Los Angeles, Calif; and the Rudi Schulte
Research Institute, Santa Barbara, Calif.
PURPOSE: Our aims were to evaluate the metabolic profiles of pediatric brain
tumors with short echo time (TE) MR spectroscopy and absolute quantitation
of metabolite concentrations (in mmol/kg of tissue) and to describe
metabolic features that distinguish individual tumor types and that may help
to improve preoperative diagnosis of specific tumors. METHODS: MR imaging
examinations of 60 patients with untreated brain tumors (14 medulloblastomas,
5 anaplastic astrocytomas, 3 low-grade astrocytomas, 17 pilocytic
astrocytomas, 4 anaplastic ependymomas, 5 ependymomas, 3 choroid plexus
papillomas, 3 choroid plexus carcinomas, and 6 pineal germinomas) were
reviewed. Single-voxel proton MR spectroscopy with a TE of 35 ms was
performed and absolute metabolite concentrations were determined by using
fully automated quantitation. RESULTS: Taurine (Tau) was significantly
elevated in medulloblastomas (P < .00001) compared with all other tumors
pooled (All Other). Tau was also observed consistently, at lower
concentration, in pineal germinomas. Creatine (Cr) was significantly reduced
in pilocytic astrocytomas, distinguishing them from All Other (P <
.000001). The MR spectra of choroid plexus papillomas exhibited low Cr (P
< .01) concentrations; however, myoinositol was elevated (P < .01) and
total choline (tCho) (P < .0001) was reduced relative to All Other.
Choroid plexus carcinomas had low Cr (P < .01 versus All Other) and the
lowest Cr/tCho ratio (P < .0001 versus All Other) among all tumors
studied. Guanidinoacetate was reduced in low-grade astrocytomas and
anaplastic astrocytomas (P < .00001) versus All Other, whereas ependymoma
and anaplastic ependymomas exhibited particularly low N-acetylaspartate (P
< .00001 versus All Other). CONCLUSION: Quantitative proton MR
spectroscopy reveals features of pediatric brain tumors that are likely to
improve preoperative diagnoses.
PMID: 16551993 [PubMed - as supplied by publisher]
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-
Update on brain tumor imaging: from anatomy to
physiology.
Cha
S.
Department of Radiology and Neurological Surgery, University of California,
San Francisco, San Francisco, Calif.
PMID: 16551981 [PubMed - in process]
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| 4: Cancer.
2006 Jan 15;106(2):453-65. |
|
-
Estimating the optimal radiotherapy utilization for
carcinoma of the central nervous system, thyroid carcinoma, and carcinoma of
unknown primary origin from evidence-based clinical guidelines.
Delaney
G, Jacob
S, Barton
M.
Collaboration for Cancer Outcomes Research and Evaluation, Liverpool
Hospital, Sydney, New South Wales, Australia. geoff.delaney@swsahs.nsw.gov.au
BACKGROUND: In this one in a series of articles, the objective was to
estimate the ideal proportion of patients with cancer who should receive
radiotherapy at least once during the course of their illness based on the
best available evidence. This estimate should be useful in planning for
future radiotherapy facilities. Optimal rates of radiotherapy for patients
with central nervous system (CNS) carcinoma, thyroid carcinoma, or carcinoma
of unknown primary site (CUP) have not been studied previously. METHODS: A
systematic review of evidence-based treatment guidelines for the treatment
of CNS carcinoma, CUP, and thyroid carcinoma was undertaken. An optimal
radiotherapy utilization tree was constructed for each of these malignancies
depicting the indications for radiotherapy at various stages of disease. The
proportion of patients who had clinical attributes that indicated a possible
benefit from radiotherapy was calculated by adding epidemiological data to
the radiotherapy utilization tree. The optimal proportion of patients who
should receive radiotherapy was then calculated using specialized
decision-analysis software. Sensitivity analyses using univariate analysis
and Monte Carlo simulations were performed. RESULTS: The optimal rates of
radiotherapy utilization for carcinoma of the CNS, thyroid carcinoma, and
CUP were 92%, 10%, and 61%, respectively. Comparison with actual rates of
utilization in South Australia, Sweden, and the U.S. suggested an
under-utilization of radiotherapy for CNS carcinoma and CUP. However, the
actual rates of radiotherapy for thyroid carcinoma exceeded the optimal rate
for some jurisdictions, although some data may have included radioactive
iodine, which was not included in the current project. CONCLUSIONS: It was
possible to estimate optimal radiotherapy utilization rates based on
evidence. This methodology allowed a comparison of optimal rates with actual
rates to identify areas in which improvements in the evidence-based use of
radiotherapy can be made, and it may provide valuable data for future
radiotherapy service planning.
PMID: 16355366 [PubMed - indexed for MEDLINE]
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| 5: Cancer.
2006 Jan 15;106(2):396-402. |
|
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Functional outcome after low-grade astrocytoma treatment
in childhood.
Aarsen
FK, Paquier
PF, Reddingius
RE, Streng
IC, Arts
WF, Evera-Preesman
M, Catsman-Berrevoets
CE.
Department of Pediatric Neurology, Erasmus Medical Center/Sophia Children's
Hospital, Rotterdam, The Netherlands. f.aarsen@erasmusmc.nl
BACKGROUND: The relatively high survival rate of patients with low-grade
astrocytoma necessitates increasing attention to physical and psychosocial
outcomes. The objective of the current study was to investigate functional
outcomes among children who were treated for low-grade or pilocytic
astrocytoma in different areas of the brain. METHODS: Functional outcomes
were evaluated in the following domains: impairments, disabilities,
handicaps, and quality of life (QOL). In a consecutive series, 38 children
were included. Follow-up ranged from 3 years and 7 months to 11 years and 4
months after diagnosis. RESULTS: Approximately 61% of children had
impairments and 10% had a severe disability. Handicaps were found in the
domains of relationships, school, and behavior. Children who were treated
for supratentorial tumors required significantly more special education, and
children who were treated for infratentorial tumors had significantly more
behavioral and social problems. QOL was decreased significantly in all
domains except emotions. Children who had a diagnosis in adolescence
reported a lower QOL in social functioning compared with younger children.
Data analysis revealed that some deficits suddenly became apparent years
after diagnosis. CONCLUSIONS: At long-term follow-up, children who had
low-grade or pilocytic astrocytomas were found to have poor functional
outcomes, depending on tumor site, age, and recurrence. Children without
deficits may develop severe cognitive, social, and behavioral deficits years
after diagnosis, because of the phenomenon of "growing into
deficit." Therefore, the authors suggest a long-term follow-up of
children who are treated for low-grade or pilocytic astrocytomas at a young
age to detect and subsequently offer support focused on the medical and
cognitive impairments as well as on the behavioral and social consequences
of their disease.
PMID: 16353203 [PubMed - indexed for MEDLINE]
-
| 6: Cancer.
2006 Jan 15;106(2):388-95. |
|
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Identification of relevant prognostic histopathologic
features in 69 intracranial ependymomas, excluding myxopapillary ependymomas
and subependymomas.
Kurt
E, Zheng
PP, Hop
WC, van
der Weiden M, Bol
M, van
den Bent MJ, Avezaat
CJ, Kros
JM.
Department of Neurosurgery, Erasmus Medical Center, Rotterdam, The
Netherlands.
BACKGROUND: The results of attempts to identify histopathologic parameters
that contribute to the clinical outcome of patients with ependymomas have
been controversial. This may be due to the relative rareness of ependymomas.
Furthermore, in many investigations, myxopapillary ependymomas and
subependymomas were included and may have confounded results, because those
tumors should be considered clinicopathologic entities distinct from the
other ependymomas. METHODS: In this retrospective study, the influence of
the histologic subtype of ependymoma and of individual histologic features
on the outcome of 69 patients with ependymomas was investigated.
Myxopapillary ependymomas, subependymomas, and ependymomas with spinal
localizations were excluded from the analysis. The ependymomas were
subdivided into cellular, papillary, clear cell, and tanycytic subtypes. The
study extended over a period of 30 years. RESULTS: No differences in
clinical outcome between the four histologic subtypes of ependymomas were
revealed. Neither tumor localization (either infratentorial or
supratentorial), patient age, nor gender affected survival. The survival of
patients who underwent complete tumor resection differed significantly from
that of patients who underwent partial resection. In univariate analysis,
the features of nuclear atypia, the mitotic index, and the MIB-1 labeling
index (LI) significantly influenced survival. With regard to survival, the
presence of microcysts, blood vessel density, and the feature of vascular
hyalinization demonstrated a trend but did not reach significance. In
multivariate analysis, only the mitotic index and the MIB-1 LI were
identified as factors with independent prognostic significance (P = 0.027
and P = 0.023, respectively). Both proliferation indices were correlated
strongly with each other. CONCLUSIONS: The results of the univariate
analysis indicated that, for patients with intracranial ependymoma, nuclear
atypia, the mitotic index, and the MIB-1 LI significantly influenced
survival. In the multivariate analysis, the mitotic index and the MIB-1 LI
were the only features that had independent prognostic significance. Because
both showed strong correlations, only one of them should be included in a
grading scheme for intracranial ependymomas.
PMID: 16342252 [PubMed - indexed for MEDLINE]
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| 7: Cancer.
2006 Jan 15;106(2):383-7. |
|
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Initial response to glucocorticoids.
Mathew
BS, Carson
KA, Grossman
SA.
Department of Radiation Oncology, Regional Cancer Center, Trivandrum, India.
BACKGROUND: Known prognostic variables in patients with primary central
nervous system lymphomas (PCNSL) include age, Karnofsky performance status,
involvement of deep regions of the brain, intensity of blood-brain barrier
disruption, and treatment with radiation and chemotherapy. PCNSL often
responds transiently to glucocorticoids administered to control neurologic
symptoms before radiation or chemotherapy. This retrospective chart review
was designed to estimate the prognostic significance of a clinical or
radiologic response to initial glucocorticoid therapy. METHODS: By using
data from The Johns Hopkins Cancer Registry from January 1980 to June 2001,
a total of 76 human immunodeficiency virus (HIV)-negative adults with newly
diagnosed PCNSL were identified. Nineteen patients with uninformative
medical records were excluded from the study. RESULTS: The median survival
of the remaining 57 patients was 11.8 months. The median survival for the 48
patients who had clinical response to initial steroid therapy was 17.9
months, and for nonresponders, it was 5.5 months (P = 0.05). The 16 patients
with documented radiologic response had a median survival of 117.0 months
compared with 5.5 months for nonresponders (P = 0.001). After adjusting for
known prognostic factors (age and treatment), significant reduction in risk
of death was noted in patients who had either clinical (hazard ratio [HR] =
0.40; 95% confidence interval [CI], 0.16-0.99}) or radiologic response (HR =
0.14; 95% CI, 0.04-0.46) to glucocorticoids given before radiation or
chemotherapy. CONCLUSION: This analysis suggests that initial response to
treatment with glucocorticoids may be an important prognostic factor in
patients with PCNSL.
PMID: 16342251 [PubMed - indexed for MEDLINE]
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-
Octreotide, a somatostatin analogue, mediates its
antiproliferative action in pituitary tumor cells by altering
phosphatidylinositol 3-kinase signaling and inducing Zac1 expression.
Theodoropoulou
M, Zhang
J, Laupheimer
S, Paez-Pereda
M, Erneux
C, Florio
T, Pagotto
U, Stalla
GK.
Department of Endocrinology, Max Planck Institute of Psychiatry,
Kraepelinstrasse 10, D-80804 Munich, Germany. marily@mpipsykl.mpg.de
Somatostatin limits cell growth by inhibiting the proliferative activity of
growth factor receptors. In this study, it is shown that in pituitary tumor
cells, the somatostatin analogue octreotide produces its antiproliferative
action by inducing the expression the tumor suppressor gene Zac1. ZAC/Zac1
induces cell cycle arrest and apoptosis and is highly expressed in normal
pituitary, mammary, and ovarian glands but is down-regulated in pituitary,
breast, and ovarian tumors. Knocking down Zac1 by RNA interference abolished
the antiproliferative effect of octreotide in pituitary tumor cells,
indicating that Zac1 is necessary for the action of octreotide. The effect
of octreotide on Zac1 expression was pertussis toxin sensitive and was
abolished after transfection with a dominant negative vector for SHP-1. Zac1
is a target of the phosphatidylinositol 3-kinase (PI3K) survival pathway.
Octreotide treatment decreased the tyrosine phosphorylation levels of the
PI3K regulatory subunit p85, induced dephosphorylation of phosphoinositide-dependent
kinase 1 (PDK1) and Akt, and activated glycogen synthase kinase 3beta (GSKbeta).
Therefore, in pituitary tumor cells, somatostatin analogues produce their
antiproliferative action by acting on the PI3K/Akt signaling pathway and
increasing Zac1 gene expression.
PMID: 16452215 [PubMed - indexed for MEDLINE]
-
-
Isolation of a natural inhibitor of human malignant glial
cell invasion: inter alpha-trypsin inhibitor heavy chain 2.
Werbowetski-Ogilvie
TE, Agar
NY, Waldkircher
de Oliveira RM, Faury
D, Antel
JP, Jabado
N, Del
Maestro RF.
Brain Tumour Research Centre, Montreal Neurological Institute, McGill
University, Montreal, Quebec, Canada.
Malignant central nervous system (CNS) tumors, such as glioblastoma
multiforme, invade the brain and disrupt normal tissue architecture, making
complete surgical removal virtually impossible. Here, we have developed and
optimized a purification strategy to isolate and identify natural inhibitors
of glioma cell invasion in a three-dimensional collagen type I matrix. Inter
alpha-trypsin inhibitor heavy chain 2 (ITI H2) was identified from the most
inhibitory fractions and its presence was confirmed both as a single protein
and in a bikunin-bound form. Stable overexpression in U251 glioma cells
validated ITI H2's strong inhibition of human glioma cell invasion together
with significant inhibition of cell proliferation and promotion of cell-cell
adhesion. Analysis of primary human brain tumors showed significantly higher
levels of ITI H2 in normal brain and low-grade tumors compared with
high-grade gliomas, indicating an inverse correlation with malignancy. The
phosphatidylinositol 3-kinase/Akt signaling cascade seemed to be one of the
pathways involved in the effect of ITI H2 on U251 cells. These findings
suggest that reduction of ITI H2 expression correlates with brain tumor
progression and that targeting factors responsible for its loss or restoring
the ITI supply exogenously may serve as potential therapeutic strategies for
a variety of CNS tumors.
PMID: 16452202 [PubMed - indexed for MEDLINE]
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-
Intracranial Rosai-Dorfman disease in a child mimicking
bilateral giant petroclival meningiomas: a case report and review of
literature.
Gupta
DK, Suri
A, Mahapatra
AK, Mehta
VS, Garg
A, Sarkar
C, Ahmad
FU.
Department of Neurosurgery, All India Institute of Medical Sciences, New
Delhi, 110029, India, drdeepakkumargupta@yahoo.com.
OBJECTIVES AND IMPORTANCE: Rosai-Dorfman disease (RDD) is a rare but
distinctive entity of unknown etiology; isolated intracranial RDD is
uncommon. Of 37 reported intracranial RDD cases, only three were reported in
children. CLINICAL PRESENTATION: We report an unusual case of a 15-year-old
boy presenting with 4 months history of raised intracranial pressure with
visual deterioration. Computed tomography and magnetic resonance imaging
revealed bilateral petroclival enhancing lesions with cavernous sinus
extension mimicking meningioma. However, histological examination was
diagnostic of RDD. INTERVENTION: The patient underwent extended right-sided
middle fossa approach and near-total tumor removal from petroclival region
and cavernous sinus on both sides in two stages 6 weeks apart. CONCLUSION:
Ours is the first case of pediatric isolated intracranial RDD presenting
with giant bilateral petroclival masses successfully managed with bilateral
extended middle fossa approach in two stages. An optimal treatment for RDD
is not established, but complete surgical resection alone seems effective.
PMID: 16552567 [PubMed - as supplied by publisher]
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Automated nuclear segmentation in the determination of
the Ki-67 labeling index in meningiomas.
Kim
YJ, Romeike
BF, Uszkoreit
J, Feiden
W.
Institute of Neuropathology, University of the Saarland, School of Medicine,
Homburg-Saar, Germany. yoo.jin.kim@uniklinikum-saarland.de
OBJECTIVE: Assessing the Ki-67 labeling index (LI) is laborious and time
consuming. Therefore, an automated computer-based method was developed,
which is able to identify and analyze immunolabeled and hematoxylin-stained
nuclei in digital images of routine immunohistochemical slides. MATERIAL AND
METHODS: The method is based on a plugin for the public domain image
analysis software ImageJ, which runs on every operating system (free
download at http://rsb.info.nih.gov/ij/). Percentage of Ki-67 immunostained
nuclei were determined in 5 high power fields (x40) of immunostained slides
(DAB detection technique, hematoxylin counterstain) of 20 Grade I, 20 Grade
II, and 10 Grade III meningiomas conventionally by two independent
investigators and automatically, respectively. The time effort was measured
for each counting procedure. RESULTS: Enumerating conventionally or
automatically did not reveal any significant differences in the mean
labeling indices. Ki-67 LIs discriminated sufficiently between meningiomas
of Grade I (median 1.7% Investigator 1 and 1.5% Investigator 2 vs. 1.5%
automatically), Grade II (7.6%, 8% vs. 7.3%), and Grade III meningiomas
(22%, 21% vs. 22%). The computer-based results correlated very closely with
those obtained by manual counting (correlation coefficient = 0.98). The mean
time effort for counting procedure per image was 374 s (130 s-435 s) for the
conventional and 11 s (7 s-12 s) for the automated method. CONCLUSIONS: The
described method can reliably assess the Ki-67 LI much faster than
conventional enumerating. The computerized method has the advantages of
objectivity, accuracy, repeatability, and ease of use. There is no request
for special stains nor special image acquiring systems. The plugin can be
downloaded at the "Morphometrie" section of http://www.uniklinikum-saarland.de/neuropathologie.
PMID: 16550739 [PubMed - in process]
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Inducible cyclooxygenase (COX-2) in glioblastoma--clinical
and immunohistochemical (COX-2-VEGF) correlations.
Buccoliero
AM, Caldarella
A, Gheri
CF, Taddei
A, Paglierani
M, Pepi
M, Mennonna
P, Taddei
GL.
Dipartimento di Patologia Umana e Oncologia, Universita degli Studi di
Firenze, Italy. ambuccoliero@unifi.it
Cyclooxygenase-2 (COX-2) is the inducible form of the enzyme responsible for
the first step in the prostaglandin synthesis. COX-2 upregulation is
demonstrated in different tumors. COX-2 products may modulate tumoral
growth, apoptosis, metastasis, multidrug resistance and angiogenesis.
Moreover, the antitumoral effect of the COX inhibitors has been documented.
We studied the immunohistochemical expression and the prognostic value of
COX-2 on 43 surgical specimens of glioblastoma-affected patients.
Furthermore, we evaluated the correlation between the immunohistochemical
expression of COX-2 and vascular endothelial growth factor (VEGF). Of the
glioblastomas, 63% resulted as COX-2-positive. Median survival of the
patients with COX-2-positive lesions was 10 months; median survival of the
patients with COX-2 negative glioblastoma was 21 months (NS). All 4 patients
who survived longer than 24 months had COX-2 negative lesions (p = 0.017).
Concordance between COX-2 and VEGF was documented in 60% of the cases. Our
findings show that glioblastoma can immunohistochemically express COX-2 and
that its expression is unrelated with VEGF and significantly less frequent
in the long survivors. Nevertheless, the absence of statistical correlation
with survival time advises further studies on larger series to ascertain the
concrete prognostic value of COX-2 in glioblastoma.
PMID: 16550738 [PubMed - in process]
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-
Cathepsin S expression: An independent prognostic factor
in glioblastoma tumours-a pilot study.
Flannery
T, McQuaid
S, McGoohan
C, McConnell
RS, McGregor
G, Mirakhur
M, Hamilton
P, Diamond
J, Cran
G, Walker
B, Scott
C, Martin
L, Ellison
D, Patel
C, Nicholson
C, Mendelow
D, McCormick
D, Johnston
PG.
Department of Neurosurgery, Royal Victoria Hospital, Belfast, Northern
Ireland.
Cysteine proteinases have been implicated in astrocytoma invasion. We
recently demonstrated that cathepsin S (CatS) expression is up-regulated in
astrocytomas and provided evidence for a potential role in astrocytoma
invasion (Flannery et al., Am J Path 2003;163(1):175-82). We aimed to
evaluate the significance of CatS in human astrocytoma progression and as a
prognostic marker. Frozen tissue homogenates from 71 patients with
astrocytomas and 3 normal brain specimens were subjected to ELISA analyses.
Immunohistochemical analysis of CatS expression was performed on 126
paraffin-embedded tumour samples. Fifty-one astrocytoma cases were suitable
for both frozen tissue and paraffin tissue analysis. ELISA revealed minimal
expression of CatS in normal brain homogenates. CatS expression was
increased in grade IV tumours whereas astrocytoma grades I-III exhibited
lower values. Immunohistochemical analysis revealed a similar pattern of
expression. Moreover, high-CatS immunohistochemical scores in glioblastomas
were associated with significantly shorter survival (10 vs. 5 months, p =
0.014). With forced inclusion of patient age, radiation dose and Karnofsky
score in the Cox multivariate model, CatS score was found to be an
independent predictor of survival. CatS expression in astrocytomas is
associated with tumour progression and poor outcome in glioblastomas. CatS
may serve as a useful prognostic indicator and potential target for
anti-invasive therapy. (c) 2006 Wiley-Liss, Inc.
PMID: 16550604 [PubMed - as supplied by publisher]
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Simultaneous beam geometry and intensity map optimization
in intensity-modulated radiation therapy.
Lee
EK, Fox
T, Crocker
I.
Center for Operations Research in Medicine, School of Industrial and Systems
Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0205, USA.
evakylee@isye.gatech.edu
PURPOSE: In current intensity-modulated radiation therapy (IMRT) plan
optimization, the focus is on either finding optimal beam angles (or other
beam delivery parameters such as field segments, couch angles, gantry
angles) or optimal beam intensities. In this article we offer a mixed
integer programming (MIP) approach for simultaneously determining an optimal
intensity map and optimal beam angles for IMRT delivery. Using this
approach, we pursue an experimental study designed to (a) gauge differences
in plan quality metrics with respect to different tumor sites and different
MIP treatment planning models, and (b) test the concept of
critical-normal-tissue-ring--a tissue ring of 5 mm thickness drawn around
the planning target volume (PTV)--and its use for designing conformal plans.
METHODS AND MATERIALS: Our treatment planning models use two classes of
decision variables to capture the beam configuration and intensities
simultaneously. Binary (0/1) variables are used to capture "on" or
"off" or "yes" or "no" decisions for each
field, and nonnegative continuous variables are used to represent
intensities of beamlets. Binary and continuous variables are also used for
each voxel to capture dose level and dose deviation from target bounds.
Treatment planning models were designed to explicitly incorporate the
following planning constraints: (a) upper/lower/mean dose-based constraints,
(b) dose-volume and equivalent-uniform-dose (EUD) constraints for critical
structures, (c) homogeneity constraints (underdose/overdose) for PTV, (d)
coverage constraints for PTV, and (e) maximum number of beams allowed.
Within this constrained solution space, five optimization strategies
involving clinical objectives were analyzed: optimize total intensity to PTV,
optimize total intensity and then optimize conformity, optimize total
intensity and then optimize homogeneity, minimize total dose to critical
structures, minimize total dose to critical structures and optimize
conformity simultaneously. We emphasize that the objectives that include
optimizing conformity make use of the critical-normal-tissue-ring. Three
tumor sites: head-and-neck, pediatric brain, and prostate are used for
comparison. RESULTS: The critical-normal-tissue-ring acts as a good device
for enforcing conformity. Trends in the characteristics and quality of plans
resulting from each model were observed. Attempts to reduce dose to critical
structures tend to worsen PTV conformity (1.542 to 3.092) and homogeneity
(1.223 to 1.984), depending on the relative size and spatial distance of the
critical structures to the PTV. When the critical structures are relatively
small compared with the PTV (as in the case for the pediatric brain tumor,
where each is less than 15% in volume), dose reduction to critical
structures is accompanied by much worse scores in conformity (2.482) and
homogeneity (1.984). When the critical structures are larger, as in the case
of head-and-neck (approximately 50%), the conformity and homogeneity
deterioration is less significant (1.542 and 1.239, respectively). There is
a clear tradeoff between homogeneity, conformity, and minimum dose to organs
at risk (OARs). For head-and-neck and pediatric brain tumor, the model that
minimizes total dose to critical structures and optimizes conformity
simultaneously offers a compromise among these factors, resulting in reduced
critical structure dose with conformal and homogeneous plans. In the
prostate case, the tumor is smaller than the two large nearby critical
structures, and all models provide very homogeneous PTV dose distribution.
However, minimizing dose to critical structures worsens conformity, as it
spreads the radiation to the area surrounding the PTV. The maximum dose to
the critical structures also increases slightly. Compared with plans used in
the clinic which generally have uniformly spaced beam angles, the optimal
clinically acceptable plans obtained via the methods herein do not have
equispaced beams. The optimal beam angles returned appear to be nonintuitive,
and depend on PTV size and geometry and the spatial relationship between the
tumor and critical structures. CONCLUSIONS: The MIP model described allows
simultaneous optimization over the space of beamlet fluence weights and beam
and couch angles. Based on experiments with tumor data, this approach can
return good plans that are clinically acceptable and practical. This work
distinguishes itself from recent IMRT research in several ways. First, in
previous methods beam angles are selected before intensity map optimization.
Herein, we employ 0/1 variables to model the set of candidate beams, and
thereby allow the optimization process itself to select optimal beams.
Second, instead of incorporating dose-volume criteria within the objective
function as in previous work, herein, a combination of discrete and
continuous variables associated with each voxel provides a mechanism to
strictly enforce dose-volume criteria within the constraints. Third, using
the construct of critical-normal-tissue-ring within the objective function
can enhance the achievement of conformal plans. Based on the three tumor
sites considered, it appears that volume and spatial geometry with respect
to the PTV are important factors to consider when selecting objectives to
optimize, and in estimating how well suited a particular model is for
achieving a specified goal.
PMID: 16289912 [PubMed - indexed for MEDLINE]
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Phase II study of donepezil in irradiated brain tumor
patients: effect on cognitive function, mood, and quality of life.
Shaw
EG, Rosdhal
R, D'Agostino
RB Jr, Lovato
J, Naughton
MJ, Robbins
ME, Rapp
SR.
Department of Radiation Oncology, Wake Forest University School of Medicine,
Brain Tumor Center of Excellence of WFU, Winston-Salem, NC 27157-1030, USA.
eshaw@wfubmc.edu
PURPOSE: A prospective, open-label phase II study was conducted to determine
whether donepezil, a US Food and Drug Administration-approved reversible
acetylcholinesterase inhibitor used to treat mild to moderate Alzheimer's
type dementia, improved cognitive functioning, mood, and quality of life (QOL)
in irradiated brain tumor patients. PATIENTS AND METHODS: Thirty-four
patients received donepezil 5 mg/d for 6 weeks, then 10 mg/d for 18 weeks,
followed by a washout period of 6 weeks off drug. Outcomes were assessed at
baseline, 12, 24 (end of treatment), and 30 weeks (end of wash-out). All
tests were administered by a trained research nurse. RESULTS: Of 35 patients
who initiated the study, 24 patients (mean age, 45 years) remained on study
for 24 weeks and completed all outcome assessments. All 24 patients had a
primary brain tumor, mostly low-grade glioma. Scores significantly improved
between baseline (pretreatment) and week 24 on measures of
attention/concentration, verbal memory, and figural memory and a trend for
verbal fluency (all P < .05). Confused mood also improved from baseline
to 24 weeks (P = .004), with a trend for fatigue and anger (all P < .05).
Health-related QOL improved significantly from baseline to 24 weeks,
particularly, for brain specific concerns with a trend for improvement in
emotional and social functioning (all P < .05). CONCLUSION: Cognitive
functioning, mood, and health-related QOL were significantly improved
following a 24-week course of the acetylcholinesterase inhibitor donepezil.
Toxicities were minimal. We are planning a double blinded,
placebo-controlled, phase III trial of donepezil to confirm these favorable
results.
PMID: 16549835 [PubMed - in process]
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Expression of endothelins and their receptors in
glioblastoma cell lines.
Paolillo
M, Barbieri
A, Zanassi
P, Schinelli
S.
Dipartimento di Farmacologia Sperimentale ed Applicata, Universita di Pavia,
Viale Taramelli 14, 27100, Pavia, Italy.
The endothelins (ETs) are a family of three peptides named ET-1, ET-2 and
ET-3 that have been initially isolated as potent vasoactive peptides; ETs
are synthesized as precursor proteins (preproETs) and are activated by
proteolytic cleavage. ETs exert their biological effects through the
activation of two receptors subtypes, ETA and ETB. Recent studies have shown
that, besides its vascular effects, ET-1 appears to play a major role also
in the growth and progression of various types of cancers and ETA or ETB are
alternatively indicated as mediators of the ET-1 biological effects. In this
study we have investigated the expression and the amounts of preproET-1,
preproET-2, ETA and ETB receptors mRNA by classical RT-PCR and quantitative
real-time PCR in one human low grade astrocytoma cell line and eight human
glioblastoma cell lines. PCR products corresponding to ETB receptor and
preproET-1 were detectable in all the cell lines whilst ETA receptor and
preproET-2 were only detected in five cell lines. Quantitative real-time PCR
experiments showed wide differences in the amounts of mRNAs among the cell
lines examined. Range values were 0.23-4860.51 fg/mug total cDNA for
preproET-1; 0.13-3330.18 fg/mug total cDNA for preproET-2; 0.63-286.12 fg/mug
total cDNA for ETA and 14.40-6720.67 fg/mug total cDNA for ETB. We measured
the ET-1 released in the extracellular medium by an ELISA assay and we found
an excellent correlation (correlation coefficient r = 0.9526, P = 0.0003)
between the amounts of preproET-1 mRNA and released ET-1 peptide. Finally,
in the 1321N1 cell line ETB receptors are functionally coupled to
intracellular signaling pathways because the stimulation of ETB receptors by
ET-1 induces the phosphorylation of the extracellular regulated kinases (ERKs).
Although the majority of glioblastoma cell lines in culture express ET
isoforms and ET receptors, we conclude that ET-1 and the ETB receptors are
likely to mediate the effects of the ET system in glioblastoma cell lines.
PMID: 16557350 [PubMed - as supplied by publisher]
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Two distinct primary brain tumors, in same region of the
same patient: a case report.
Tugcu
B, Kepoglu
U, Gunal
M, Gunaldi
O, Karakaya
B, Demirgil
BT.
Department of Neurosurgery, 70. Yil Physical Therapy and Rehabilitation
Education and Training Hospital, Sirpsindigi sok Koskal Apt 31/7 Merter,
34010, Istanbul, Turkey, deniztugcu@superonline.com.
PMID: 16557348 [PubMed - as supplied by publisher]
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Primary midbrain cystic germinoma mimicking glioma: a
case with neuroendoscopic biopsy.
Uchino
M, Haga
D, Mito
T, Kuramitsu
T, Nakamura
N.
Department of Neurosurgery, Saiseikai Yokohama-shi Nambu Hospital,
Yokohama-shi, Kanagawa-ken, Japan, uchino0717@yahoo.co.jp.
Intracranial germinoma arising primarily in the midbrain is extremely rare.
We present the first reported case of cystic midbrain germinoma that lacked
evident solid components and mimicked a midbrain glioma. In a 22-year-old
man with headache and diplopia, magnetic resonance imaging showed a
ring-enhancing lesion in the midbrain. The preoperative diagnosis included
brain stem glioma, metastasis, and neuroepithelial cyst. A neuroendoscopic
biopsy specimen provided a histologic diagnosis of germinoma. The patient
responded well to chemotherapy and radiotherapy. The case illustrates the
diagnostic value of neuroendoscopic biopsy in the differential diagnosis of
brainstem lesions in adult. The possibilities considered should now include
germinoma.
PMID: 16557347 [PubMed - as supplied by publisher]
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A genetic strategy to overcome the senescence of primary
meningioma cell cultures.
Baia
GS, Slocum
AL, Hyer
JD, Misra
A, Sehati
N, Vandenberg
SR, Feuerstein
BG, Deen
DF, McDermott
MW, Lal
A.
Brain Tumor Research Center, Department of Neurological Surgery, University
of California, San Francisco, CA, 94143, USA.
Even though meningiomas are the second most common brain tumor in adults,
little is known about the molecular basis of their growth and development.
The lack of suitable cell culture model systems is an impediment to this
understanding. Most studies on meningiomas rely on primary, early passage
cell lines that eventually senesce or a few established cell lines that have
been derived from aggressive variants of meningiomas. We have isolated three
primary meningioma cell lines that are negative for telomerase activity. We
can overcome the senescence of a Grade III derived meningioma cell line by
expressing the telomerase catalytic subunit (hTERT), whereas Grade I
meningioma cell lines require the expression of the human papillomavirus E6
and E7 oncogenes in conjunction with hTERT. Meningioma cell lines,
immortalized in this manner, maintain their pre-transfection morphology and
form colonies in vitro. We have confirmed the meningothelial origin of these
cell lines by assessing expression of vimentin and desmoplakin,
characteristic markers for meningiomas. Additionally, we have karyotyped
these cell lines using array CGH and shown that they represent a spectrum of
the genetic diversity seen in primary meningiomas. Thus, these cell lines
represent novel cellular reagents for investigating the molecular
oncogenesis of meningiomas.
PMID: 16554968 [PubMed - as supplied by publisher]
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Unusual MR features of adult cerebellar medulloblastoma.
Gupta
A, Kasliwal
MK.
All India Institute of Medical Sciences, New Delhi, India, adityagupta71@hotmail.com.
PMID: 16554967 [PubMed - as supplied by publisher]
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Mechanisms of angiogenesis in gliomas.
Kargiotis
O, Rao
JS, Kyritsis
AP.
Neurosurgical Institute, University of Ioannina Medical School, Ioannina,
Greece.
Gliomas are the most frequent primary tumors of the central nervous system
in adults. Glioblastoma multiforme, the most aggressive form of astrocytic
tumors, displays a rapid progression that is accompanied by particular poor
prognosis of patients. Intense angiogenesis is a distinguishing pathologic
characteristic of these tumors and in fact, glioblastomas are of the most
highly vascularized malignant tumors. For this reason, research and therapy
strategies have focused on understanding the mechanisms leading to the
origin of tumor angiogenic blood vessels in order to develop new approaches
that effectively block angiogenesis and cause tumor regression. We discuss
here some important features of glioma angiogenesis and we present molecules
and factors and their possible functions and interactions that play a role
in neovascularization. In spite of the great progress that molecular biology
has achieved on investigating tumor angiogenesis, many aspects remain
obscure and the complexity of the angiogenic process stands for an obstacle
in identifying the exact and complete molecular pathways orchestrating new
blood vessels formation, which are necessary for the survival and expansion
of these tumors.
PMID: 16554966 [PubMed - as supplied by publisher]>>>
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Reduced Glioma Infiltration in Src-deficient Mice.
Lund
CV, Nguyen
MT, Owens
GC, Pakchoian
AJ, Shaterian
A, Kruse
CA, Eliceiri
BP.
Division of Cancer Biology , La Jolla Institute for Molecular Medicine, San
Diego, CA, 92121, USA.
Malignant brain tumors, such as glioblastoma, are characterized by extensive
angiogenesis and permeability of the blood-brain barrier (BBB). The
infiltration of glioma cells away from the primary tumor mass is a
pathological characteristic of glial tumors. The infiltrating tumor cells
represent a significant factor in tumor recurrence following surgical
debulking, radiation, and chemotherapy treatments. Vascular endothelial
growth factor (VEGF)-mediated vascular permeability (VP) has been associated
with the progression of glioma tumor growth and infiltration into
surrounding normal brain parenchyma. While VEGF induces a robust VP response
in control mice (src(+/+) or src(+/-)), the VP response is blocked in src(-/-)
mice that demonstrate a 'leakage-resistant phenotype' in the brain. We used
the Src-deficient mouse model to determine the role of Src in the
maintenance of the BBB following orthotopic implantation and growth of
glioma cells in the brain. Although solid tumor growth was the same in
control and src(-/-) mice, the infiltrating component of glioma growth was
reduced in src(-/-) mice. Characterization of the expression and
localization of the extracellular matrix (ECM) protein fibrinogen was
evaluated to determine the effect of a Src-mediated VP defect in the host
compartment. These studies indicate that the reduced VP of host brain blood
vessels of src(-/-) mice mediates a reduction in glioma cell invasion in a
mouse brain tumor xenograft model.
PMID: 16552622 [PubMed - as supplied by publisher]
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-
MRI measurement of the uptake and retention of motexafin
gadolinium in glioblastoma multiforme and uninvolved normal human brain.
Wu
GN, Ford
JM, Alger
JR.
Inter-Departmental Graduate Program in Biomedical Physics, University of
California at Los Angeles, Los Angeles, CA, USA.
PURPOSE: Motexafin gadolinium (MGd) is an investigational pharmaceutical
with radiation enhancing properties. Magnetic Resonance Imaging (MRI) was
used to measure brain and tumor MGd levels to evaluate (1) the degree to
which MGd passes through the intact blood brain barrier, and (2) the
retention of MGd in tumor in patients with glioblastoma multiforme (GBM).
METHODS AND MATERIALS: MRI studies were performed on GBM patients who
participated in a phase I clinical trial in which MGd was given during
standard fractionated radiation therapy. MGd was administered daily (Monday
to Friday) for five or 10 doses as a loading regimen, followed by three
times per week dosing as a maintenance schedule. T1-weighted MRI was
performed at intervals throughout the course of the MGd administration and
radiation therapy in the 33 participating patients. Eleven patients had pre-
and post-MGd scans, allowing for study of MGd's normal blood brain barrier
penetration. Twenty-two patients had adequate residual tumor for
measurements to evaluate MGd retention in tumor during the course of MGd and
radiation administration. RESULTS AND CONCLUSIONS: The studies of uninvolved
brain tissue support the conclusion that MGd does not cross the intact blood
brain barrier in detectable quantities. The tumor study showed MGd uptake
during loading and maintenance without measurably significant fall off on
non-dosage days during the maintenance dosing. Although the number of cases
is small, the 10-day loading regimen showed greater drug loading and
retention compared with the 5 days loading regimen.
PMID: 16547607 [PubMed - as supplied by publisher]>>>
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-
TRAIL-receptor expression is an independent prognostic
factor for survival in patients with a primary glioblastoma multiforme.
Kuijlen
JM, Mooij
JJ, Platteel
I, Hoving
EW, van
der Graaf WT, Span
MM, Hollema
H, den
Dunnen WF.
Department of Neurosurgery, University Hospital Groningen, Groningen, The
Netherlands.
PURPOSE: In order to improve the survival of patients with a glioblastoma
multiforme tumor (GBM), new therapeutic strategies must be developed. The
use of a death inducing ligand such as TRAIL (TNF Related Apoptosis Inducing
Ligand) seems a promising innovative therapy. The aim of this study was to
quantify the expression of the death regulating receptors TRAIL-R1, TRAIL-R2
and TRAIL on primary GBM specimens and to correlate this expression with
survival. EXPERIMENTAL DESIGN: Expression of TRAIL and TRAIL-receptors was
assessed by immunohistochemistry, both quantitatively (% of positive tumor
cells) and semi-quantitatively (staining intensity) within both the
perinecrotic and intermediate tumor zones of primary GBM specimens. RT-PCR
of GBM tissue was performed to show expression of TRAIL receptor mRNA.
RESULTS: Immunohistochemistry showed a slight diffuse intracytoplasmic and a
stronger membranous staining for TRAIL and TRAIL receptors in tumor cells.
Semi-quantitative expression of TRAIL showed a significantly higher
expression of TRAIL in the perinecrotic zone than in the intermediate zone
of the tumor (P=0.0001). TRAIL-R2 expression was significantly higher
expressed than TRAIL-R1 (P=0.005). The antigenic load of TRAIL-R2 was
positively correlated with survival (P=0.02). Multivariate analysis of
TRAIL-R1 within the study group (n=62) showed that age, gender, staining
intensity, antigenic load, % of TRAIL-R1 expression, were not statistically
correlated with survival however radiotherapy was significantly correlated
(multivariate analysis: age: P=0.15; gender: P=0.64; staining intensity:
P=0.17; antigenic load: P=0.056; % of TRAIL-R1 expression: P=0.058;
radiotherapy: P=0.0001). Subgroup analysis of patients who had received
radiotherapy (n=47) showed a significant association of % of TRAIL-R1
expression and the antigenic load of TRAIL-R1 with survival (multivariate
analysis: P=0.036, respectively, P=0.023). Multivariate analysis of TRAIL-R2
staining intensity and antigenic load, within the study group (P=0.004,
respectively, P=0.03) and the subgroup (P=0.002, respectively, P=0.004),
showed a significant association with survival. RT-PCR analysis detected a
negative relation between the amount of TRAIL-R1 mRNA and the WHO grade of
astrocytic tumors (P=0.03). CONCLUSIONS: TRAIL-R1 and TRAIL-R2 expression on
tumor cells are independent prognostic factors for survival in patients with
a glioblastoma multiforme. Both receptors could be targets for TRAIL
therapy. As TRAIL-R2 is more expressed, in comparison with TRAIL-R1, on GBM
tumor cells, TRAIL-R2 seems to be of more importance as a target for future
TRAIL therapy than TRAIL-R1.
PMID: 16544055 [PubMed - as supplied by publisher]
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-
Molecular neuropathology of epilepsy-associated
glioneuronal malformations.
Becker
AJ, Blumcke
I, Urbach
H, Hans
V, Majores
M.
Department of Neuropathology, Bonn University Medical Center, Sigmund-Freud
Strasse 25, D-53105 Bonn, Germany. albert_becker@uni-bonn.de
Glioneuronal malformations (malformations of cortical development [MCD])
include focal cortical dysplasias (FCD) as well as highly differentiated
glioneuronal tumors (i.e. gangliogliomas) and constitute frequent findings
in patients with pharmacoresistent focal epilepsies. Tailored resection
strategies evolved as promising treatment options and allow a systematic
neuropathologic and molecular biologic examination of the epileptogenic area
in these patients. The histopathologic appearance and immunophenotype of
glioneuronal lesions are, however, characterized by numerous similarities
and suggest impaired proliferation, migration, and differentiation of neural
precursor cells to play a pathogenetic role. Recent studies point toward
molecular alterations within a variety of genes and pathways involved in
development of the central nervous system, neuronal growth, and maturation.
Compromised signaling within insulin- or reelin-transduction cascades are
common findings and were associated with specific MCD entities. Unraveling
pathogenic mechanisms may advance refined classification systems for
epilepsy-associated malformations and open new avenues for the development
of targeted treatment strategies in pharmacoresistent focal epilepsies
associated with cortical malformations.
Publication Types:
PMID: 16462201 [PubMed - indexed for MEDLINE]
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Transient cerebellar mutism caused by bilateral damage to
the dentate nuclei after the second posterior fossa surgery. Case report.
Kusano
Y, Tanaka
Y, Takasuna
H, Wada
N, Tada
T, Kakizawa
Y, Hongo
K.
Department of Neurosurgery, Shinshu University School of Medicine,
Matsumoto, Japan.
The authors report on the case of a 6-year-old boy who underwent resection
of a midline cerebellar tumor. The boy was able to speak fluently after the
operation. Magnetic resonance (MR) imaging showed that the right dentate
nucleus had been partially removed along with the tumor, but that the left
dentate nucleus remained with the residual tumor. A second operation was
performed to remove the residue, after which the child suffered mutism.
Three weeks post-surgery, he could only communicate through gestures. He
started speaking I week later and regained normal speech 2 months after the
operation. Final MR imaging revealed gross-total removal of the tumor and
dentate nucleus on the injured left side. The cerebellar mutism was
considered to have been caused by bilateral damage to the dentate nuclei and
not by unilateral damage.
Publication Types:
PMID: 16509510 [PubMed - indexed for MEDLINE]
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Contiguous conventional and plexiform schwannomas. Report
of two cases.
White
JB, Scheithauer
BW, Amrami
KK, Babovic-Vuksanovic
D, Spinner
RJ.
Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota 55905,
USA.
The authors present clinical, imaging, and histological features of two
adult patients found to harbor a conventional schwannoma contiguous with a
deep plexiform schwannoma. One patient had neurofibromatosis (NF) Type 2
(NF2), and both intracranial (bilateral oculomotor, trigeminal, acoustic,
and hypoglossal schwannomas as well as meningiomas) and intraspinal (schwannomas
and meningiomas) lesions. The proximal forearm lesions consisted of a
conventional schwannoma and an underlying plexiform component. The second
patient, who did not have NF2, presented with a similar enlarging mass in
the distal arm; two contiguous lesions were resected. Both patients
exhibited distinct, readily identifiable, magnetic resonance imaging
features. Plexiform schwannomas are rare lesions that occur sporadically or,
on occasion, in association with NF2 or meningiomas with or without multiple
schwannomas. The authors believe that a more careful examination of patients
with NF2 may show that these people have a higher incidence of plexiform
schwannoma than previously thought. Pathological confirmation is crucial in
distinguishing plexiform schwannomas from plexiform neurofibromas, because
the latter are directly associated with NF1 and have a significant tendency
to undergo malignant transformation. To the best of the authors' knowledge,
this is the first report of a conventional schwannoma contiguous with a deep
plexiform schwannoma.
Publication Types:
PMID: 16509508 [PubMed - indexed for MEDLINE]
-
Dobesilate inhibits the activation of signal transducer
and activator of transcription 3, and the expression of cyclin D1 and bcl-XL
in glioma cells.
Cuevas
P, Diaz-Gonzalez
D, Sanchez
I, Lozano
RM, Gimenez-Gallego
G, Dujovny
M.
Departamento de Investigacion, Hospital Universitario Ramon y Cajal,
Universidad de Alcala de Henares, Madrid, Spain; Department of Neurosurgery,
Wayne State University, Detroit, MI, USA.
OBJECTIVES: Because fibroblast growth factor (FGF) causes the intracellular
accumulation of activated signal transducer and activator of transcription 3
(STAT3), we assessed whether dobesilate, a synthetic FGF inhibitor that has
been reported to show antiproliferative and proapoptotic activities in
glioma cell cultures, down-regulates the STAT3 signaling pathway in growing
cultures of those cells. Because STAT3 signaling pathway plays pleiotropic
roles in tumor proliferation, maintenance of STAT3 in its inactive state may
prevent glioma growth and spreading.METHODS: Rat glioma C6 cells were
treated with dobesilate and cultures were evaluated immunocytochemically for
STAT3 activation and enhancement of the expression rate of cyclin D1 and
bcl-XL.RESULTS: Dobesilate abrogates the accumulation of activated STAT3 in
glioma cells. The decrease in the intracellular levels of activated STAT3 by
the dobesilate treatment runs parallel with a significant attenuation of
cyclin D1 and bcl-XL expression.CONCLUSION: Treatment with inhibitors of FGF
down-regulates the STAT3 signaling pathway. These alterations could be
correlated to the already observed inhibition of cell proliferation and
promotion of apoptosis in glioma cell cultures by dobesilate. The reported
results may open new avenues for developing new treatments against these
tumors.
PMID: 16551428 [PubMed - in process]
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-
MR signal of the solid portion of pilocytic astrocytoma
on T2-weighted images:is it useful for differentiation from medulloblastoma?
Arai
K, Sato
N, Aoki
J, Yagi
A, Taketomi-Takahashi
A, Morita
H, Koyama
Y, Oba
H, Ishiuchi
S, Saito
N, Endo
K.
Department of Diagnostic Radiology and Nuclear Medicine, Gunma University
Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma, Japan.
Background and purpose: Although imaging features of cerebellar pilocytic
astrocytoma and medulloblastoma have been described in many texts, original
comparisons of magnetic resonance intensity between these two tumours are
limited. In the present study the results of magnetic resonance imaging (MRI)
were reviewed, focusing especially on the signal intensity of the solid
portion of these neoplasms. Methods: MR images of ten cerebellar pilocytic
astrocytomas and ten medulloblastomas were reviewed. The signal intensities
of the solid components were graded on a scale of 1 to 5, with higher scores
indicating a signal intensity closer to that of water. The degree of
enhancement, tumour cysts and peripheral oedema were evaluated on MR images.
When the solid portion was heterogeneous (i.e. mixed signal intensity or
degree of enhancement), the dominant area was selected for evaluation.
Results: On T2-weighted images, the signal intensity of the solid portion
was equal to that of cerebrospinal fluid (CSF) in 50% of pilocytic
astrocytomas. No medulloblastomas showed such hyperintensity. Most
medulloblastomas (80%) were isointense to grey matter. On T1-weighted
images, the signal intensity varied widely in pilocytic astrocytomas;
however, all medulloblastomas were iso- or hypointense to grey matter. The
MR enhancement pattern, cystic component and peripheral oedema all varied in
both tumour types and no specific features were identified. Conclusion: A
signal intensity of the solid portion isointense to CSF on T2-weighted
images was characteristic of cerebellar pilocytic astrocytomas; this was not
observed in medulloblastomas. Attention to T2-weighted imaging of the solid
portions of a tumour is easy and helpful in differentiating between
cerebellar pilocytic astrocytoma and medulloblastoma.
PMID: 16550430 [PubMed - as supplied by publisher]
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Lyme disease of the brainstem.
Kalina
P, Decker
A, Kornel
E, Halperin
JJ.
Department of Radiology, Mayo Clinic, Rochester, MN 55905, USA. kalina.peter@mayo.edu
Lyme disease is a multisystem infectious disease caused by the tick-borne
spirochete, Borrelia burgdorferi. Central nervous system (CNS) involvement
typically causes local inflammation, most commonly meningitis, but rarely
parenchymal brain involvement. We describe a patient who presented with
clinical findings suggesting a brainstem process. Magnetic resonance imaging
(MRI) and positron emission tomography (PET) suggested a brainstem neoplasm.
Prior to biopsy, laboratory evaluation led to the diagnosis of Lyme disease.
Clinical and imaging abnormalities improved markedly following antimicrobial
therapy. We describe Lyme disease involvement of the cerebellar peduncles
with hypermetabolism on PET. Although MRI is the primary imaging modality
for most suspected CNS pathology, the practical applications of PET continue
to expand.
Publication Types:
PMID: 16158278 [PubMed - indexed for MEDLINE]
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The nonspecific nature of proton spectroscopy in brain
masses in children: a series of demyelinating lesions.
Pandya
HG, Wilkinson
ID, Agarwal
SK, Griffiths
PD.
Academic Unit of Radiology, Floor C, Royal Hallamshire Hospital, Sheffield,
UK.
MRI imaging has significantly improved the detection of brain lesions over
the past few decades. It has high sensitivity to intracranial pathology but
confident preoperative tissue diagnosis is relatively unusual. MR
spectroscopy provides in-vivo biochemical information and has been used to
improve the low specificity of tumour diagnosis. During the last decade
there have been a number of reports making the case that proton spectroscopy
can distinguish different grades of glial tumours and in some situations
provide information on histological type. We report four children who
presented with neurological symptoms and focal masses on MRI. MRS in each of
them gave results consistent with textbook descriptions of malignancy, but
in all four cases the abnormalities were subsequently shown to be due to
demyelination. We reiterate that spectroscopic appearances are nonspecific
and spectroscopic data should be evaluated in the light of concurrent
imaging features and the clinical presentation.
Publication Types:
PMID: 15776226 [PubMed - indexed for MEDLINE]
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| 32: Oncogene.
2006 Mar 20; [Epub ahead of print] |
|
-
Characterization of an imatinib-sensitive subset of
high-grade human glioma cultures.
Hagerstrand
D, Hesselager
G, Achterberg
S, Wickenberg
Bolin U, Kowanetz
M, Kastemar
M, Heldin
CH, Isaksson
A, Nister
M, Ostman
A.
1Department of Oncology/Pathology, Karolinska Institutet, Cancer Center
Karolinska, Stockholm, Sweden.
High-grade gliomas, including glioblastomas, are malignant brain tumors for
which improved treatment is urgently needed. Genetic studies have
demonstrated the existence of biologically distinct subsets. Preliminary
studies have indicated that platelet-derived growth factor (PDGF) receptor
signaling contributes to the growth of some of these tumors. In this study,
human high-grade glioma primary cultures were analysed for sensitivity to
treatment with the PDGF receptor inhibitor imatinib/Glivec/Gleevec/STI571.
Six out of 15 cultures displayed more than 40% growth inhibition after
imatinib treatment, whereas seven cultures showed less than 20% growth
inhibition. In the sensitive cultures, apoptosis contributed to growth
inhibition. Platelet-derived growth factor receptor status correlated with
imatinib sensitivity. Supervised analyses of gene expression profiles and
real-time PCR analyses identified expression of the chemokine CXCL12/SDF-1 (stromal
cell-derived factor 1) as a predictor of imatinib sensitivity. Exogenous
addition of CXCL12 to imatinib-insensitive cultures conferred some imatinib
sensitivity. Finally, coregulation of CXCL12 and PDGF alpha-receptor was
observed in glioblastoma biopsies. We have thus defined the characteristics
of a novel imatinib-sensitive subset of glioma cultures, and provided
evidence for a functional relationship between imatinib sensitivity and
chemokine signaling. These findings will assist in the design and evaluation
of clinical trials exploring therapeutic effects of imatinib on malignant
brain tumors.Oncogene advance online publication, 20 March 2006;
doi:10.1038/sj.onc.1209497.
PMID: 16547494 [PubMed - as supplied by publisher]>>>
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Rapid increase in volume of multiple tumor cysts after
intracranial pressure reduction.
Taguchi
Y, Sakakibara
Y, Yoshida
H, Furuya
Y, Ikeda
R.
Division of Neurosurgery, St. Marianna University Yokohama City Seibu
Hospital, Yokohama, Japan. ytaguchi@marianna-u.ac.jp
Publication Types:
PMID: 16465087 [PubMed - indexed for MEDLINE]
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Infant with unusually large choroid plexus papilloma
undergoing emergency surgery. Case report with special emphasis on the
surgical strategy.
Picht
T, Jansons
J, van
Baalen A, Harder
A, Pietilae
TA.
Department of Neurosurgery, Charite, Universitatsmedizin Berlin, Campus
Benjamin Franklin, Berlin, Germany. thomas.picht@charite.de
Choroid plexus papillomas are one of the most common tumors of the nervous
system in infants. The most frequent early symptoms, megalocephalia and
vomiting, caused by elevated intracranial pressure often lead to a diagnosis
only at a critical clinical stage. This study describes a case of a
3-month-old infant with a choroid plexus papilloma measuring 7 x 8 x 6 cm
originating in the right lateral ventricle. The infant underwent emergency
surgery in an acutely deteriorated state, i.e., acute herniation symptoms
with fixed and dilated pupils. Despite of the size of the tumor, the
proximity to eloquent cortex, and clinically deteriorated state, the infant
recovered completely. Copyright (c) 2006 S. Karger AG, Basel.
Publication Types:
PMID: 16465083 [PubMed - indexed for MEDLINE]
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Endoscopic resection of an intraventricular
dysembryoplastic neuroepithelial tumor of the septum pellucidum.
Harter
DH, Omeis
I, Forman
S, Braun
A.
Department of Neurosurgery, Division of Pediatric Neurosurgery, New York
University, New York, NY 10016, USA. david.harter@med.nyu.edu
Tumors located in the region of the foramen of Monro often present with
signs and symptoms of obstructive hydrocephalus. Various types of lesions
occur in this location. We describe a case of a dysembryoplastic
neuroepithelial tumor of the septum pellucidum presenting with obstructive
hydrocephalus and its successful endoscopic excision. The surgical
considerations and pathologic findings are discussed. Copyright (c) 2006 S.
Karger AG, Basel.
Publication Types:
PMID: 16465080 [PubMed - indexed for MEDLINE]
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Central nervous system tumors in patients under three
years of age: treatment results of a single institute.
Varan
A, Akalan
N, Soylemezoglu
F, |
Volume 5, Number 13 - 27 March
2006