| 1: Arch Neurol. 2004 Nov;61(11):1800-4. |
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Psychiatric symptoms and brain tumors: a brief historical
overview.
Jarquin-Valdivia AA.
Departments of Neurology and Anesthesiology and the Internal Medicine
Division of Neurocritical Care, Vanderbilt University Medical Center,
Nashville, Tenn. 37212, USA. adrian.a.jarquin-valdivia@vanderbilt.edu
PMID: 15534193 [PubMed - in process]
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| 2: Clin Cancer Res. 2004 Nov 1;10(21):7182-91. |
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Correlation of molecular genetics with molecular and
morphological imaging in gliomas with an oligodendroglial component.
Walker C, du Plessis DG, Fildes D, Haylock B, Husband D, Jenkinson MD,
Joyce KA, Broome J, Kopitski K, Prosser J, Smith T, Vinjamuri S, Warnke PC.
JK Douglas Laboratories and Clatterbridge Centre for Oncology, Clatterbridge
Hospital, Bebington, Wirral, United Kingdom. carol.walker@ccrt.nhs.uk
PURPOSE: Since the recognition that oligodendrogliomas may be
chemosensitive, their diagnosis and clinical management has become highly
controversial. Histopathology diagnosis remains challenging and new tools
such as molecular genetics or molecular imaging require evaluation.
EXPERIMENTAL DESIGN: In a single-center, population-based prospective study,
allelic imbalance in chromosomes 1p36, 19q13, 17p13, 10p12-15, and 10q22-26
has been investigated in 19 oligodendroglioma WHO grade 2 (OII), 20
oligoastrocytoma WHO grade 2 (OAII), 8 oligodendroglioma WHO grade 3 (OIII),
and 12 oligoastrocytoma WHO grade 3 (OAIII), and compared with pretherapy
histopathology, computed tomography and/or magnetic resonance (CT and/or
MR), [fluorine-18]fluoro-2-deoxyglucose (18F-FDG), and thallium-201
single-photon emission computed tomography (201Tl SPECT). RESULTS: In 50
cases, 18F-FDG uptake correlated with 201Tl uptake; however, 8 cases had
increased 201Tl uptake but were hypometabolic for 18F-FDG, and 1 case was
hypermetabolic with normal 201Tl uptake. Sixteen cases enhanced on CT/MR but
failed to show 201Tl uptake; and 2 low-grade non-enhancing
oligodendrogliomas had increased 201Tl uptake. Increased metabolism was more
likely in high-grade cases, with 201Tl uptake more strongly correlated with
grade than was 18F-FDG uptake. Tumors with 1p/19q loss were more likely to
show increased 201Tl uptake and, to a lesser degree, increased 18F-FDG
uptake than those without these losses. Elevated metabolism in 28% of
low-grade tumors was significantly more common in tumors with 1p/19q loss,
and increased uptake of both 18F-FDG and 201Tl in low-grade cases was found
only in those with 1p/19q loss. CONCLUSIONS: In this study, dissociation of
uptake of contrast agents and radiotracers suggests independent deregulation
of the blood-brain barrier breakdown and metabolism during disease
progression of oligodendroglial neoplasms, and the association of elevated
metabolism with 1p/19q loss, particularly in low-grade tumors, may have
implications for clinical management.
PMID: 15534091 [PubMed - in process]
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| 3: Clin Cancer Res. 2004 Nov 1;10(21):7163-70. |
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Delineation of brain tumor extent with [11C]L-methionine
positron emission tomography: local comparison with stereotactic
histopathology.
Kracht LW, Miletic H, Busch S, Jacobs AH, Voges J, Hoevels M, Klein JC,
Herholz K, Heiss WD.
Max-Planck-Institute for Neurological Research, Cologne, Germany.
PURPOSE: Methyl-[11C]L-methionine ([11C]MET) positron emission tomography
(PET) in brain tumors reflects amino acid transport and has been shown to be
more sensitive than magnetic resonance imaging in stereotactic biopsy
planning. It remains unclear whether the increased [11C]MET uptake is
limited to solid tumor tissue or even detects infiltrating tumor parts.
EXPERIMENTAL DESIGN: In 30 patients, a primary or recurrent brain tumor was
suspected on magnetic resonance imaging. Patients were investigated with
[11C]MET-PET before stereotactic biopsy. The biopsy trajectories were
plotted into the [11C]MET-PET images with a newly designed C-based software
program. The exact local [11C]MET uptake was determined within rectangular
regions of interest of 4 mm in width and length aligned with the biopsy
specimen. Individual histologic specimens were rated for the presence of
solid tumor tissue, infiltration area, and nontumorous tissue changes.
RESULTS: Receiver operating characteristics analysis demonstrated a
sensitivity of 87% and specificity of 89% for the detection of tumor tissue
at a threshold of 1.3-fold [11C]MET uptake relative to normal brain tissue.
At this threshold, only 13 of 100 tumor positive specimen were false
negative mainly in grade 2 astrocytoma. In grade 2 astrocytoma, mean
[11C]MET uptake in the infiltration area was significantly higher than in
solid tumor tissue (P < 0.003). CONCLUSIONS: [11C]MET-PET detects solid
parts of brain tumors, as well as the infiltration area at high sensitivity
and specificity. High [11C]MET uptake in infiltrating tumor of astrocytoma
WHO grade 2 reflects high activity in this tumor compartment. Molecular
imaging, with [11C]MET, will guide improved management of patients with
brain tumors.
PMID: 15534088 [PubMed - in process]
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| 4: Clin Cancer Res. 2004 May 1;10(9):3104-9. |
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Very high frequency of hypermethylated genes in breast
cancer metastasis to the bone, brain, and lung.
Mehrotra J, Vali M, McVeigh M, Kominsky SL, Fackler MJ, Lahti-Domenici J,
Polyak K, Sacchi N, Garrett-Mayer E, Argani P, Sukumar S.
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Johns
Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
PURPOSE: Most often it is not the primary tumor, but metastasis to distant
organs that results in the death of breast cancer patients. To characterize
molecular alterations in breast cancer metastasis, we investigated the
frequency of hypermethylation of five genes (Cyclin D2, RAR-beta, Twist,
RASSF1A, and HIN-1) in metastasis to four common sites: lymph node, bone,
brain, and lung. EXPERIMENTAL DESIGN: Methylation-specific PCR for the five
genes was performed on DNA extracted from archival paraffin-embedded
specimens of paired primary breast cancer and its lymph nodes (LN)
metastasis (n = 25 each); in independent samples of metastasis to the bone
(n = 12), brain (n = 8), and lung (n = 10); and in normal bone, brain, and
lung (n = 22). RESULTS: No hypermethylation was detected in the five genes
in the normal host tissues. In paired samples, LN metastasis had a trend of
higher prevalence of methylation compared with the primary breast carcinoma
for all five genes with significance for HIN-1 (P = 0.04). Compared with the
primary breast carcinomas, all five genes had higher methylation frequencies
in the bone, brain, and lung metastasis, with HIN-1 and RAR-beta methylation
being significantly higher (P < 0.01) in each group. Loss of expression
of all five genes correlated, with a few exceptions, to hypermethylation of
their promoter sequences in metastatic carcinoma cells microdissected from
LNs. CONCLUSION: The frequent presence of hypermethylated genes in
locoregional and distant metastasis could render them particularly
susceptible to therapy targeted toward gene reactivation combining
demethylating agents, histone deacetylase inhibitors, and/or differentiating
agents.
PMID: 15131050 [PubMed - indexed for MEDLINE]
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| 5: Clin Cancer Res. 2004 May 1;10(9):2997-3006. |
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Somatostatin receptor subtype 2 is expressed by
supratentorial primitive neuroectodermal tumors of childhood and can be
targeted for somatostatin receptor imaging.
Fruhwald MC, Rickert CH, O'Dorisio MS, Madsen M, Warmuth-Metz M, Khanna
G, Paulus W, Kuhl J, Jurgens H, Schneider P, Muller HL.
Department of Pediatric Hematology and Oncology, University Children's
Hospital Muenster, Muenster, Germany. fruhwald@uni-muenster.de
PURPOSE: Although gliomas predominate among central nervous system (CNS)
neoplasms in adulthood, embryonal tumors are the most common malignant brain
tumors in children. Despite novel treatment approaches, including improved
radiotherapy and high-dose chemotherapy, survival rates remain
unsatisfactory. The timely diagnosis of residual or recurrent embryonal CNS
tumors and thus the earliest possible time point for intervention is often
hampered by inaccuracies of conventional imaging techniques. Novel and
refined imaging methodologies are urgently needed. EXPERIMENTAL DESIGN: We
have previously demonstrated the use of somatostatin receptor imaging (SRI)
in the diagnosis of recurrent and residual medulloblastomas. Here, we
evaluated somatostatin receptor type 2 (sst(2)) expression using an antibody
in an array of CNS tumors of childhood. Eight high-grade gliomas, 4 atypical
teratoid/rhabdoid tumors, 7 supratentorial primitive neuroectodermal tumors
(stPNET), 1 medulloepithelioma (ME), and 8 ependymomas were screened. Tumors
positive in vitro were additionally analyzed in vivo using SRI. RESULTS:
Abundant expression of somatostatin receptor type 2 in stPNET, a ME, and
ependymomas warranted in vivo imaging of 7 stPNET, 1 rhabdomyosarcoma, 3
ependymomas, 1 ME, and 1 glioblastoma. Although SRI was positive in 6/7
stPNET, 1 rhabdomyosarcoma, and 1 ME, none of the ependymomas nor the
glioblastoma could be imaged using SRI. In selected cases SRI was more
sensitive in the detection of relapse than conventional imaging by magnetic
resonance imaging and computed tomography. CONCLUSIONS: SRI should be
considered in the evaluation of residual or recurrent embryonal CNS tumors,
especially stPNET. The strengths of SRI lie in the differentiation of
reactive tissue changes versus residual or recurrent tumor, the detection of
small lesions, and possibly in the distinction of stPNET from gliomas.
PMID: 15131035 [PubMed - indexed for MEDLINE]
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| 6: Int J Cancer. 2004 Nov 11 [Epub ahead of print] |
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Microarray-based gene expression profiling of benign,
atypical and anaplastic meningiomas identifies novel genes associated with
meningioma progression.
Wrobel G, Roerig P, Kokocinski F, Neben K, Hahn M, Reifenberger G,
Lichter P.
Division of Molecular Genetics, German Cancer Research Center, Heidelberg,
Germany.
To identify gene expression profiles associated with human meningiomas of
different World Health Organization (WHO) malignancy grades, we analyzed 30
tumors (13 benign meningiomas, WHO grade I; 12 atypical meningiomas, WHO
grade II; 5 anaplastic meningiomas, WHO grade III) for the expression of
2,600 genes using cDNA-microarray technology. Receiver operator curve (ROC)
analysis with a cutoff value of 45% selection probability identified 37
genes with decreased and 27 genes with increased expression in atypical and
anaplastic meningiomas, compared to benign meningiomas. Supervised
classification of the tumors did not reveal specific expression patterns
representative of each WHO grade. However, anaplastic meningiomas could be
distinguished from benign meningiomas by differential expression of a
distinct set of genes, including several ones associated with cell cycle
regulation and proliferation. Investigation of potential correlations
between microarray expression data and genomic aberrations, detected by
comparative genomic hybridization (CGH), demonstrated that losses on
chromosomes 10 and 14 were associated with distinct expression profiles,
including increased expression of several genes related to the insulin-like
growth factor (IGF) (IGF2, IGFBP3 and AKT3) or wingless (WNT) (CTNNB1,
CDK5R1, ENC1 and CCND1) pathways. Taken together, our microarray-based
expression profiling revealed interesting novel candidate genes and pathways
that may contribute to meningioma progression. (c) 2004 Wiley-Liss, Inc.
PMID: 15540215 [PubMed - as supplied by publisher]
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| 7: J Neuropathol Exp Neurol. 2004 Oct;63(10):1015-27. |
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Loss of tumor suppressor in lung cancer-1 (TSLC1)
expression in meningioma correlates with increased malignancy grade and
reduced patient survival.
Surace EI, Lusis E, Murakami Y, Scheithauer BW, Perry A, Gutmann DH.
partment of Neurology, Washington University School of Medicine, St. Louis,
MO 63110, USA.
Meningiomas represent the second most common central nervous system tumor
affecting adults. Two of the most frequent early events in meningioma
tumorigenesis involve loss of expression of the neurofibromatosis 2 (NF2)
and 4.1B genes. Recently, 4.1B was shown to interact with the tumor
suppressor in lung cancer-1 (TSLC1) protein, prompting us to examine the
expression of TSLC1 in meningiomas. We developed specific anti-TSLC1
antibodies to examine TSLC1 expression in normal human leptomeninges, human
meningioma cell lines, and human meningiomas of different pathological
grades by Western blot (n = 10) and immunohistochemistry (n = 123). Whereas
TSLC1 was expressed in normal human leptomeninges by immunohistochemistry,
TSLC1 expression was absent in 3 human malignant meningioma cell lines and
markedly reduced or absent in 30% of benign meningiomas by Western blot.
Restoration of TSLC1 expression in a TSLC1-deficient human meningioma cell
line resulted in reduced cell proliferation. In a series of 123 meningiomas
(98 adult and 25 pediatric), TSLC1 expression was absent in 48% of benign
(WHO grade I), 69% of atypical (grade II), and 85% of anaplastic (grade III)
meningiomas. Moreover, TSLC1 loss was associated with decreased patient
survival, within the overall group, and in the atypical meningiomas.
Collectively, these results suggest that TSLC1 plays an important role in
meningioma pathogenesis.
PMID: 15535129 [PubMed - in process]
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| 8: J Neurosurg. 2004 Nov;101 Suppl 3:406-12. |
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Long-term management of patients with multiple brain
metastases after shaped beam radiosurgery. Case report and review of the
literature.
Okunieff P, Schell MC, Ruo R, Hale ER, O'Dell WG, Pilcher W.
Department of Radiation Oncology, James P Wilmot Cancer Center at the
University of Rochester Medical Center, NY 14642, USA.
paul_okunieff@urmc.rochester.edu
The role of radiosurgery in the treatment of patients with advanced-stage
metastatic disease is currently under debate. Previous randomized studies
have not consistently supported the use of radiosurgery to treat patients
with numbers of brain metastases. In negative-results studies, however,
intracranial tumor control was high but extracranial disease progressed;
thus, patient survival was not greatly affected, although neurocognitive
function was generally maintained until death. Because the future promises
improved systemic (extracranial) therapy, the successful control of brain
disease is that much more crucial. Thus, for selected patients with multiple
metastases to the brain who remain in good neurological condition,
aggressive lesion-targeting radiosurgery should be very useful. Although a
major limitation to success of this therapy is the lack of control of
extracranial disease in most patients, it is clear that well-designed,
aggressive treatment substantially decreases the progression of brain
metastases and also improves neurocognitive survival. The authors present
the management and a methodology for rational treatment of a patient with
breast cancer who has harbored 24 brain metastases during a 3-year period.
PMID: 15537197 [PubMed - in process]
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| 9: J Neurosurg. 2004 Nov;101 Suppl 3:390-5. |
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Dose fractionation in stereotactic radiotherapy for
parasellar meningiomas: radiobiological considerations of efficacy and optic
nerve tolerance.
Shrieve DC, Hazard L, Boucher K, Jensen RL.
Department of Radiation Oncology, The Huntsman Cancer Institute, University
of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA.
dennis.shrieve@hsc.utah.edu
OBJECT: Benign meningiomas have been shown to be equally well controlled
with single-dose radiosurgery (15 Gy) and fractionated doses of 54 Gy in 30
fractions after adequate follow up. For a subset of patients with
meningioma, the optic apparatus is dose limiting when considering
single-dose stereotactic radiosurgery, with tolerance estimated to be 8 to
10 Gy. Recently, hypofractionated regimens have been used to treat benign
meningiomas with a small number of fractions. An analysis of the expected
efficacy of hypofractionation compared with the estimated optic tolerance to
fractionated radiotherapy was undertaken. METHODS: Using the assumption that
15 Gy in one fraction and 54 Gy in 30 fractions are isoeffective for control
of benign meningioma, an alpha/beta for meningioma is calculated to be 3.28
Gy. Invoking a 10% error for these doses (15 Gy+/-10% is equivalent to 54
Gy+/-10%) results in upper and lower limits of the estimate for alpha/beta
of 3.85 Gy and 2.7 Gy. Using these estimates, isoeffect curves for control
of meningioma were constructed for fraction numbers of one to 45. Best
estimates of optic nerve/chiasm tolerance to single doses of radiation are 8
to 10 Gy, with the reported incidence of optic neuropathy increasing
significantly at higher doses. This is consistent with the optic ret model,
which also predicts for optic tolerance following fractionated radiotherapy.
Comparison of optic tolerance and estimates of efficacious doses at fraction
numbers between one and 30 were made. Statistical estimates of patient
numbers and duration of follow up required to rule out optic neuropathy
following radiotherapy were made. Single doses of radiation required to
treat benign meningioma optimally (13.5-16.5 Gy) clearly exceed the
estimated and reported clinical tolerance of the optic nerves and chiasm.
The application of equivalent biological doses in a small number of
fractions continues to exceed optic tolerance until at least 25 fractions
are applied. CONCLUSIONS: The use of small numbers of fractions to treat
patients with meningioma when portions of optic nerve or chiasm receive full
dose may result in undertreatment of the tumor and/or exceeding optic nerve
tolerance. In such cases standard fractionation is recommended. Ruling out a
low, yet unacceptable, risk of optic neuropathy may require the close study
of many patients with long-term follow-up evaluation.
PMID: 15537194 [PubMed - in process]
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| 10: J Nucl Med. 2004 Nov;45(11):1851-9. |
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Assessment of Hypoxia and Perfusion in Human Brain Tumors
Using PET with 18F-Fluoromisonidazole and 15O-H2O.
Bruehlmeier M, Roelcke U, Schubiger PA, Ametamey SM.
Paul Scherrer Institute, Center for Radiopharmaceutical Science, Villigen,
Switzerland.
Hypoxia predicts poor treatment response of malignant tumors. We used PET
with (18)F-fluoromisonidazole ((18)F-FMISO) and (15)O-H(2)O to measure in
vivo hypoxia and perfusion in patients with brain tumors. METHODS: Eleven
patients with various brain tumors were investigated. We performed dynamic
(18)F-FMISO PET, including arterial blood sampling and the determination of
(18)F-FMISO stability in plasma with high-performance liquid chromatography
(HPLC). The (18)F-FMISO kinetics in normal brain and tumor were assessed
quantitatively using standard 2- and 3-compartment models. Tumor perfusion
((15)O-H(2)O) was measured immediately before (18)F-FMISO PET in 10 of the
11 patients. RESULTS: PET images acquired 150-170 min after injection
revealed increased (18)F-FMISO tumor uptake in all glioblastomas. This
increased uptake was reflected by (18)F-FMISO distribution volumes >1,
compared with (18)F-FMISO distribution volumes <1 in normal brain. The
(18)F-FMISO uptake rate K(1) was also higher in all glioblastomas than in
normal brain. In meningioma, which lacks the blood-brain barrier (BBB), a
higher K(1) was observed than in glioblastoma, whereas the (18)F-FMISO
distribution volume in meningioma was <1. Pixel-by-pixel image analysis
generally showed a positive correlation between (18)F-FMISO tumor uptake at
0-5 min after injection and perfusion ((15)O-H(2)O) with r values between
0.42 and 0.86, whereas late (18)F-FMISO images (150-170 min after injection)
were (with a single exception) independent of perfusion. Spatial comparison
of (18)F-FMISO with (15)O-H(2)O PET images in glioblastomas showed hypoxia
both in hypo- and hyperperfused tumor areas. HPLC analysis showed that most
of the (18)F-FMISO in plasma was still intact 90 min after injection,
accounting for 92%-96% of plasma radioactivity. CONCLUSION: Our data suggest
that late (18)F-FMISO PET images provide a spatial description of hypoxia in
brain tumors that is independent of BBB disruption and tumor perfusion. The
distribution volume is an appropriate measure to quantify (18)F-FMISO
uptake. The perfusion-hypoxia patterns described in glioblastoma suggest
that hypoxia in these tumors may develop irrespective of the magnitude of
perfusion.
PMID: 15534054 [PubMed - in process]
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| 11: Neurology. 2004 Nov 9;63(9):1753-4. |
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Unilateral localized hyperhidrosis associated with
frontal lobe meningioma.
Iseri PK, Bayramgurler D, Koc K.
Department of Neurology, University of Kocaeli, Derince, Izmit, Turkey.
metei@superonline.com
PMID: 15534278 [PubMed - in process]
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| 12: Neurosurgery. 2004 Sep;55(3):569-79; discussion 580-1. |
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Lesion-induced pseudo-dominance at functional magnetic
resonance imaging: implications for preoperative assessments.
Ulmer JL, Hacein-Bey L, Mathews VP, Mueller WM, DeYoe EA, Prost RW, Meyer
GA, Krouwer HG, Schmainda KM.
Division of Neuroradiology, Department of Radiology, Medical College of
Wisconsin, Milwaukee, Wisconsin, USA. julmer@mcw.edu
OBJECTIVE: To illustrate how lesion-induced neurovascular uncoupling at
functional magnetic resonance imaging (fMRI) can mimic hemispheric dominance
opposite the side of a lesion preoperatively. METHODS: We retrospectively
reviewed preoperative fMRI mapping data from 50 patients with focal brain
abnormalities to establish patterns of hemispheric dominance of language,
speech, visual, or motor system functions. Abnormalities included gliomas
(31 patients), arteriovenous malformations (AVMs) (11 patients), other
congenital lesions (4 patients), encephalomalacia (3 patients), and
tumefactive encephalitis (1 patient). A laterality ratio of fMRI hemispheric
dominance was compared with actual hemispheric dominance as verified by
electrocortical stimulation, Wada testing, postoperative and posttreatment
deficits, and/or lesion-induced deficits. fMRI activation maps were
generated with cross-correlation (P < 0.001) or t test (P < 0.001)
analysis. RESULTS: In 50 patients, a total of 85 functional areas were
within 5 mm of the edge of a potentially resectable lesion. In 23 of these
areas (27%), reduced fMRI signal in perilesional eloquent cortex in
conjunction with preserved or increased signal in homologous contralateral
brain areas revealed functional dominance opposite the side of the lesion.
This suggested possible lesion-induced transhemispheric cortical
reorganization to homologous brain regions (homotopic reorganization). In
seven patients, however, the fMRI data were inconsistent with other methods
of functional localization. In two patients with left inferior frontal gyrus
gliomas and in one patient with focal tumefactive meningoencephalitis, fMRI
incorrectly suggested strong right hemispheric speech dominance. In two
patients with lateral precentral gyrus region gliomas and one patient with a
left central sulcus AVM, the fMRI pattern incorrectly suggested primary
corticobulbar motor dominance contralateral to the side of the lesion. In a
patient with a right superior frontal gyrus AVM, fMRI revealed pronounced
left dominant supplementary motor area activity in response to a bilateral
complex motor task, but right superior frontal gyrus perilesional hemorrhage
and edema subsequently caused left upper-extremity plegia.
Pathophysiological factors that might have caused neurovascular uncoupling
and facilitated pseudo-dominance at fMRI in these patients included direct
tumor infiltration, neovascularity, cerebrovascular inflammation, and
AVM-induced hemodynamic effects. Sixteen patients had proven (1 patient),
probable (2 patients), or possible (13 patients) but unproven lesion-induced
homotopic cortical reorganization. CONCLUSION: Lesion-induced neurovascular
uncoupling causing reduced fMRI signal in perilesional eloquent cortex, in
conjunction with normal or increased activity in homologous brain regions,
may simulate hemispheric dominance and lesion-induced homotopic cortical
reorganization.
PMID: 15335424 [PubMed - indexed for MEDLINE]
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| 13: Neurosurgery. 2004 Sep;55(3):551-60; discussion 560-1. |
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On-line flow cytometry for real-time surgical guidance.
Mesiwala AH, Scampavia LD, Rabinovitch PS, Ruzicka J, Rostomily RC.
Department of Neurological Surgery, University of Washington, Seattle,
Washington, USA.
OBJECTIVE: This study tests the feasibility of using on-line analysis of
tissue during surgical resection of brain tumors to provide biologically
relevant information in a clinically relevant time frame to augment surgical
decision making. For the purposes of establishing feasibility, we used
measurement of deoxyribonucleic acid (DNA) content as the end point for
analysis. METHODS: We investigated the feasibility of interfacing an
ultrasonic aspiration (USA) system with a flow cytometer (FC) capable of
analyzing DNA content (DNA-FC). The sampling system design, tissue
preparation requirements, and time requirements for each step of the on-line
analysis system were determined using fresh beef brain tissue samples. We
also compared DNA-FC measurements in 28 nonneoplastic human brain samples
with DNA-FC measurements in specimens of 11 glioma patients obtained from
central tumor regions and surgical margins after macroscopically gross total
tumor removal to estimate the potential for analysis of a biological marker
to influence surgical decision making. RESULTS: With minimal modification,
modern FC systems are fully capable of real-time, intraoperative analysis of
USA specimens. The total time required for on-line analysis of USA specimens
varies between 36 and 63 seconds; this time includes delivery from the tip
of the USA to complete analysis of the specimen. Approximately 60% of this
time is required for equilibration of the DNA stain. When compared with
values for nonneoplastic human brain samples, 50% of samples (10 of 20) from
macroscopically normal glioma surgical margins contained DNA-FC
abnormalities potentially indicating residual tumor. CONCLUSION: With an
interface of existing technologies, DNA content of brain tissue samples can
be analyzed in a meaningful time frame that has the potential to provide
real-time information for surgical guidance. The identification of DNA
content abnormalities in macroscopically normal tumor resection margins by
DNA-FC supports the practical potential for on-line analysis of a tumor
marker to guide surgical resections. The development of such a device would
provide neurosurgeons with an objective method for intraoperative analysis
of a clinically relevant biological parameter that can be measured in real
time.
PMID: 15335422 [PubMed - indexed for MEDLINE]
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| 14: Neurosurgery. 2004 Sep;55(3):539-47; discussion 547-50. |
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Variations on the standard transsphenoidal approach to
the sellar region, with emphasis on the extended approaches and parasellar
approaches: surgical experience in 105 cases.
Couldwell WT, Weiss MH, Rabb C, Liu JK, Apfelbaum RI, Fukushima T.
Department of Neurological Surgery, University of Utah, Salt Lake City,
Utah, USA. william.couldwell@hsc.utah.edu
OBJECTIVE: The traditional boundaries of the transsphenoidal approach may be
expanded to include the region from the cribriform plate of the anterior
cranial base to the inferior clivus in the anteroposterior plane, and
laterally to expose the cavernous cranial nerves and the optic canal. We
review our combined experience with these variations on the transsphenoidal
approach to various lesions of the sellar and parasellar region. METHODS:
From 1982 to 2003, we used the extended and parasellar transsphenoidal
approaches in 105 patients presenting with a variety of lesions of the
parasellar region. This study specifically reviews the breadth of
pathological lesions operated and the complications associated with the
approaches. RESULTS: Variations of the standard transsphenoidal approach
have been used in the following series: 30 cases of pituitary adenomas
extending laterally to involve the cavernous sinus, 27 craniopharyngiomas,
11 tuberculum/diaphragma sellae meningiomas, 10 sphenoid sinus mucoceles, 18
clivus chordomas, 4 cases of carcinoma of the sphenoid sinus, 2 cases of
breast carcinoma metastatic to the sella, and 3 cases of monostotic fibrous
dysplasia involving the clivus. There was no mortality in the series.
Permanent neurological complications included one case of monocular
blindness, one case of permanent diabetes insipidus, and two permanent
cavernous cranial neuropathies. There were four cases of internal carotid
artery hemorrhage, one of which required ligation of the cervical internal
carotid artery and resulted in hemiparesis. The incidence of postoperative
cerebrospinal fluid fistulae was 6% (6 of 105 cases). CONCLUSION: These
modifications of the standard transsphenoidal approach are useful for
lesions within the boundaries noted above, they offer excellent alternatives
to transcranial approaches for these lesions, and they avoid prolonged
exposure time and brain retraction. Technical details are discussed and
illustrative cases presented.
Publication Types:
PMID: 15335421 [PubMed - indexed for MEDLINE]
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| 15: Neurosurgery. 2004 Sep;55(3):506-17; discussion 517-8. |
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Changing neurosurgical workload in the United States,
1988-2001: craniotomy other than trauma in adults.
Barker FG 2nd, Amin-Hanjani S.
Neurosurgical Service, Massachusetts General Hospital, Department of Surgery
(Neurosurgery), Harvard Medical School, Boston, Massachusetts, USA.
barker@helix.mgh.harvard.edu
OBJECTIVE: Changes in neurosurgical workload can justify requests for
hospital resources and guide planning by neurosurgical training programs.
Most previous studies have used non-population-based data sources, such as
surveys of professional society members, to explore the neurosurgical
workload in the United States. METHODS: This is a retrospective cohort study
of patients in Diagnosis Related Group (DRG) 1 ("Craniotomy other than
trauma, age > 17") using the Nationwide Inpatient Sample.
Statistical methods were adjusted for complex survey methodology to generate
total United States caseload estimates. RESULTS: The total United States DRG
1 caseload increased from 70,800 admissions in 1988 to 105,300 admissions in
2001, a 50% relative increase (P < 0.001). For most diagnostic
categories, the relative caseload increase was similar to that for the whole
group. Patient age and sex distributions remained stable over time. Medical
comorbidities, such as hypertension, chronic pulmonary disease, diabetes,
and obesity, became more frequent. Elective admissions increased and
in-hospital mortality rates decreased. Length of hospital stay decreased
during the first half of the study period and then stabilized. Combined with
increasing caseload, this caused total annual inpatient DRG 1 days to
increase progressively after 1996. The number of United States hospitals
with DRG 1 admissions decreased over time. Per-hospital annual DRG 1
caseloads increased, especially at high-volume centers. For the largest 100
hospitals by DRG 1 caseload, total admissions increased from 8.5% of all
United States admissions (1988) to 9.4% (2001), whereas DRG 1 caseload
increased disproportionately, from 27% to 38% of the United States aggregate
caseload. This is evidence that progressive centralization of DRG 1
admissions took place during the study period. CONCLUSION: We documented an
increase in total caseload and centralization of care for DRG 1 in the
United States during the period 1988 to 2001. Defining the reasons for the
changes in neurosurgical workload we observed will require further research.
PMID: 15335418 [PubMed - indexed for MEDLINE]
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| 16: Neurosurgery. 2004 Sep;55(3):495-504; discussion 504-5. |
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Experimental radiobiological investigations into
radiosurgery: present understanding and future directions.
Niranjan A, Gobbel GT, Kondziolka D, Flickinger JC, Lunsford LD.
Department of Neurological Surgery, University of Pittsburgh, Center for
Image-Guided Neurosurgery, University of Pittsburgh Medical Center,
Pittsburgh, Pennsylvania, USA.
LARS LEKSELL BEGAN radiobiological investigations to study the effect of
high-dose focused radiation on the central nervous system more than 5
decades ago. Although the effects of radiosurgery on the brain tumor
microenvironment are still under investigation, radiosurgery has become a
preferred management modality for many intracranial tumors and vascular
malformations. The effects and the pathogenesis of biological effects after
radiosurgery may be unique. The need for basic research concerning the
radiobiological effects of high-dose, single-fraction, ionizing radiation on
nervous system tissue is crucial. Information from those studies would be
useful in devising strategies to avoid, prevent, or ameliorate damage to
normal tissue without compromising treatment efficacy. The development of
future applications of radiosurgery will depend on an increase in our
understanding of the radiobiology of radiosurgery, which in turn will affect
the efficacy of treatment. This article analyzes the current state of
radiosurgery research with regard to the nature of central nervous system
effects, the techniques developed to increase therapeutic efficacy,
investigations into the use of radiosurgery for functional disorders,
radiosurgery as a tool for investigations into basic central nervous system
biology, and the additional areas that require further investigation.
Publication Types:
PMID: 15335417 [PubMed - indexed for MEDLINE]
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| 17: Oncogene. 2004 Nov 08 [Epub ahead of print] |
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Proteasome inhibitor PS-341 causes cell growth arrest and
apoptosis in human glioblastoma multiforme (GBM).
Yin D, Zhou H, Kumagai T, Liu G, Ong JM, Black KL, Koeffler HP.
1Division of Hematology/Oncology, Cedars-Sinai Medical Center, UCLA School
of Medicine, Los Angeles, CA 90048, USA.
The proteasome plays a pivotal role in controlling cell proliferation,
apoptosis, and differentiation in a variety of normal and tumor cells.
PS-341, a novel boronic acid dipeptide that inhibits 26S proteasome
activity, has prominent effects in vitro and in vivo against several solid
tumors. We examined its antiproliferation, proapoptotic effects using three
human glioblastoma multiforme (GBM) cell lines and five primary GBM
explants. PS-341 markedly inhibited proliferation of GBM cell lines and
explants in liquid and soft agar culture. These cells developed a G2/M cell
cycle arrest with a concomitant decreased percentage of cells in S phase (
approximately 2-fold), associated with an increased expression of p21(WAF1),
p27(KIP1), as well as cyclin B1 and decreased levels of CDK2, CDK4, and
E2F4. About 35-40% of the cells became apoptotic when exposed to PS-341
(10(-7) M, 24-48 h) as shown by Annexin V analysis; in concert with these
findings, immunobloting showed a C-terminal 85 kDa apoptotic fragment of
poly ADP-ribose polymerase (PARP), and a decreased level of Bcl2 and Bcl-xl.
PS-341 downregulated the expression of Bcl-2 and Bcl-xl in protein levels at
an early time of treatment. These changes occurred irrespective of the p53
mutational status of the cells. PS-341 activated JNK/c-Jun signaling in GBM
cells, and the JNK inhibitor SP600125 blocked the JNK signaling to reverse
partially the PS-341 growth inhibition. PS-341 (10(-7) M, 24 h) decreased
nuclear NF-kappaB levels as shown by Western blot, and reduced
transcriptional activity of NF-kappaB as measured by reporter assays in
these transformed cells. Also, PS-341 enhanced TRAIL (TNF-related
apoptosis-inducing ligand) and TNFalpha (tumor necrosis factor alpha)
induced cell death and apoptosis (two- to five-fold) in GBM cells. In
summary, PS-341 has profound effects on growth and apoptosis of GBM cells,
suggesting that PS-341 may be an effective therapy for patients with
gliomas.Oncogene advance online publication, 8 November 2004;
doi:10.1038/sj.onc.1208225.
PMID: 15531918 [PubMed - as supplied by publisher]
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| 18: Oncogene. 2004 Nov 08 [Epub ahead of print] |
|
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Rottlerin sensitizes glioma cells to TRAIL-induced
apoptosis by inhibition of Cdc2 and the subsequent downregulation of
survivin and XIAP.
Kim EH, Kim SU, Choi KS.
1Institute for Medical Sciences, Ajou University School of Medicine, Suwon
442-749, South Korea.
In the tumor necrosis factor-related apoptosis-inducing ligand
(TRAIL)-resistant glioma cells, treatment with TRAIL in combination with
subtoxic doses of rottlerin induced rapid apoptosis. While the proteolytic
processing of procaspase-3 by TRAIL was partially blocked in these cells,
treatment with rottlerin efficiently recovered TRAIL-induced activation of
caspases. Treatment with rottlerin significantly decreased Cdc2 activity
through the downregulation of cyclin A, cyclin B, and Cdc2 proteins, whereas
the sensitizing effect of rottlerin on TRAIL-induced apoptosis was
independent of PKCdelta activity. Furthermore, treatment with rottlerin
downregulated the protein levels of survivin and X-chromosome-linked IAP
(XIAP), two major caspase inhibitors. Forced expression of Cdc2 together
with cyclin B attenuated rottlerin-potentiated TRAIL-induced apoptosis by
over-riding the rottlerin-mediated downregulation of survivin and XIAP
protein levels. Taken together, inhibition of Cdc2 activity and the
subsequent downregulation of survivin and XIAP by subtoxic doses of
rottlerin contribute to amplification of caspase cascades, thereby
overcoming resistance of glioma cells to TRAIL-mediated apoptosis. Since
rottlerin can sensitize Bcl-2- or Bcl-xL-overexpressing glioma cells but not
human astrocytes to TRAIL-induced apoptosis, this combined treatment may
offer an attractive strategy for safely treating resistant gliomas.Oncogene
advance online publication, 8 November 2004; doi:10.1038/sj.onc.1208241.
PMID: 15531913 [PubMed - as supplied by publisher]
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Volume 3, Supplement 14 - 16 November 2004