| 1: AJNR Am J Neuroradiol. 2005 Jan;26(1):65-7. |
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Hypothalamic hamartoma associated with a craniopharyngeal
canal.
Kizilkilic O, Yalcin O, Yildirim T, Sener L, Parmaksiz G, Erdogan B.
Department of Radiology, Adana Teaching and Medical Research Center, Baskent
University, Adana, Turkey.
Hypothalamic hamartoma is a rare congenital lesion. We present the case of a
7-year-old girl who suffered from precocious puberty, the cause of which was
diagnosed by using MR imaging and CT as pedunculated hypothalamic hamartoma
associated with a large craniopharyngeal canal and sellar spine mimicking
pituitary duplication.
PMID: 15661703 [PubMed - in process]
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| 2: Cancer Res. 2005 Jan 1;65(1):236-45. |
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Glioma formation in neurofibromatosis 1 reflects
preferential activation of K-RAS in astrocytes.
Dasgupta B, Li W, Perry A, Gutmann DH.
Department of Neurology, Washington University School of Medicine, St.
Louis, MO 63110, USA.
Children with the tumor predisposition syndrome, neurofibromatosis 1 (NF1),
develop optic pathway gliomas. The NF1 gene product, neurofibromin,
functions as a negative regulator of RAS, such that NF1 inactivation results
in RAS hyperactivation. Recent studies have highlighted the divergent
biological and biochemical properties of the various RAS isoforms, which
prompted us to examine the consequence of Nf1 inactivation in astrocytes on
RAS isoform activation in vitro and in vivo. In this report, we show that
only K-RAS is activated in Nf1-/- astrocytes and that activation of K-RAS,
but not H-RAS, accounts for the proliferative advantage and abnormal actin
cytoskeleton-mediated processes observed in Nf1-/- astrocytes in vitro.
Moreover, dominant inhibitory K-RAS corrects these abnormalities in Nf1-/-
astrocytes invitro. Lastly, we show that Nf1+/- mice with astrocyte-specific
activated K-RAS expression in vivo develop optic pathway gliomas, similar to
our previously reported Nf1+/- mice with astrocyte Nf1 inactivation.
Collectively, our results show that K-RAS is the primary target for
neurofibromin GTPase-activating protein activity in vitro and in vivo and
that K-RAS activation in astrocytes recapitulates the biochemical,
biological, and tumorigenic properties of neurofibromin loss.
PMID: 15665300 [PubMed - in process]
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| 3: Cancer Res. 2005 Jan 1;65(1):99-104. |
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Expression-based discovery of variation in the human
glutathione S-transferase M3 promoter and functional analysis in a glioma
cell line using allele-specific chromatin immunoprecipitation.
Liu X, Campbell MR, Pittman GS, Faulkner EC, Watson MA, Bell DA.
Laboratory of Computational Biology and Risk Analysis, National Institute of
Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA.
Discovery and functional evaluation of biologically significant regulatory
single nucleotide polymorphisms (SNP) in carcinogen metabolism genes is a
difficult challenge because the phenotypic consequences may be both
transient and subtle. We have used a gene expression screening approach to
identify a functional regulatory SNP in glutathione S-transferase M3
(GSTM3). Anttila et al. proposed that variation in GSTM3 expression was
affected by exposure to cigarette smoke and inheritance of the GSTM1-null
genotype. To investigate the mechanism of GSTM3 expression was affected by
exposure to cigarette smoke and inheritance of the GSTM1-null genotype. To
investigate the mechanism of GSTM3 expression variation, we measured GSTM3
expression in lymphoblast cells from a human Centre d'Etude du Polymorphisme
Humain family and observed a low expression phenotype. Promoter sequencing
revealed two novel GSTM3 promoter SNPs: A/C and A/G SNPs, 63 and 783 bp
upstream of the codon 1 start site, respectively. In this pedigree, the two
children homozygous for the -63C/C genotype had 8-fold lower GSTM3
expression relative to the two children with the -63A/A genotype, with no
association between A-783G SNP and GSTM3 expression. Further evaluation
using genotyped glioma cell lines and with luciferase reporter constructs
showed that the -63C allele was associated with lower GSTM3 expression (P
< 0.0001 and P < 0.003). RNA pol II chromatin immunoprecipitation was
combined with quantitative probed-based allelic discrimination genotyping to
provide direct evidence of a 9-fold reduced RNA pol II binding capacity for
the -63C allele. These results show that the GSTM3 -63C allele strongly
affects gene expression in human cell lines and suggests that individuals
who carry the low expression allele may be deficient in glutathione
transferase catalyzed biological functions.
PMID: 15665284 [PubMed - in process]
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| 4: Childs Nerv Syst. 2005 Jan 26; [Epub ahead of print] |
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Meningioangiomatosis with meningioma: an uncommon
association of a rare entity-report of a case and review of the literature.
Deb P, Gupta A, Sharma MC, Gaikwad S, Singh VP, Sarkar C.
Department of Pathology, All India Institute of Medical Sciences (AIIMS),
Ansari Nagar, New Delhi, 110029, India, meharsharma@hotmail.com.
INTRODUCTION: Meningioangiomatosis (MA) is a rare lesion, probably of
malformative origin, consisting of meningovascular proliferation and
leptomeningeal calcification. Patients with MA usually present with seizures
or persistent headaches. Neurofibromatosis may be associated in a variable
proportion of patients, while in others it may be sporadic. Surgical
treatment is usually recommended, and is gratifying in most cases. Rarely,
MA has been described coexisting with meningiomas, arteriovenous
malformations, encephaloceles, oligodendrogliomas, meningeal
haemangiopericytomas and orbital erosion. Among these, meningiomatosis with
meningioma is the most frequent combination. CASE REPORT: We report a case
of MA with meningioma in an 18-month-old girl, who presented with recurrent
seizures. DISCUSSION: In these situations, it is extremely important for the
pathologist to be aware of this entity and to distinguish it from other
lesions, like cortical invasion by a meningioma, intraparenchymal meningioma
and intracerebral schwannoma, which it may mimic.
PMID: 15674601 [PubMed - as supplied by publisher]
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| 5: Childs Nerv Syst. 2005 Jan 27; [Epub ahead of print] |
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Gliomatosis cerebri in children Case report and clinical
considerations.
Caroli E, Orlando ER, Ferrante L.
Department of Neurological Sciences, Neurosurgery, Policlinico S. Andrea,
University of Rome La Sapienza, Rome, Italy.
OBJECTIVE: Gliomatosis cerebri (GC) is an uncommon entity characterised by
the diffuse overgrowth of large parts of the brain by glial cells. Reports
in the literature often refer to adult patients, its occurrence in children
being even more rare. CASE REPORT: We report the case of an 8-year-old boy
with GC and discuss the problem of intra vitam diagnosis. CONCLUSIONS:
Diagnosis of GC is very difficult; thus, cases diagnosed during life are
rare.
PMID: 15674600 [PubMed - as supplied by publisher]
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| 6: Clin Cancer Res. 2005 Jan 1;11(1):341-50. |
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Development of a Syngeneic Rat Brain Tumor Model
Expressing EGFRvIII and Its Use for Molecular Targeting Studies with
Monoclonal Antibody L8A4.
Yang W, Barth RF, Wu G, Ciesielski MJ, Fenstermaker RA, Moffat BA, Ross
BD, Wikstrand CJ.
Department of Pathology, The Ohio State University, Columbus, Ohio.
PURPOSE: The goals of the present study were 2-fold: (a) to develop and
characterize a rat brain tumor model that could be used for studies of
molecular targeting of EGFRvIII and (b) to study the tumor localizing
properties of radiolabeled monoclonal antibody (mAb) L8A4, specifically
directed against EGFRvIII, following systemic, i.t., and convection enhanced
delivery to brain tumor-bearing rats.Experimental Design and RESULTS: F98
wild-type (F98(WT)) rat glioma cells were transfected with a gene encoding
human EGFRvIII, and following selection and cloning, a cell line, designated
F98(npEGFRvIII), was identified, which expressed a nonconstitutively
phosphorylated form of the receptor. As determined by a radioligand binding
assay, there were 1.2x10(5) EGFRvIII sites per cell compared with an
undetectable number on F98(WT) cells. The tumorigenicity of the
F98(npEGFRvIII)glioma was studied following i.c. implantation of 10(3),
10(4), or 10(5) cells into CD-Fischer rats. Mean survival times were 23, 17,
and 13 days, respectively, which were equivalent to those obtained with
F98(EGFR) and F98(WT) cells. As determined by magnetic resonance imaging,
the mean doubling times for the F98(WT) and F98(npEGFRvIII) gliomas were
similar (59.8 +/- 4.8 versus 52 +/- 3.3 hours). Following i.v.
administration to glioma-bearing rats, mAb L8A4 specifically targeted the
F98(npEGFRvIII) glioma, and at 24 hours, 7.7% of the injected dose per gram
(ID/g) localized in the tumor. This increased 5-fold to 39.5% ID/g following
i.t. injection and 7-fold to 59.8% ID/g at 24 hours following convection
enhanced delivery.CONCLUSIONS: Based on these data, we have concluded that
the F98(npEGFRvIII) glioma should be a valuable animal model for therapy
studies focusing on molecular targeting of EGFRvIII by receptor specific
mAbs.
PMID: 15671565 [PubMed - in process]
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| 7: Clin Cancer Res. 2005 Jan 1;11(1):335-40. |
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Herstatin, an autoinhibitor of the epidermal growth
factor (EGF) receptor family, blocks the intracranial growth of
glioblastoma.
Staverosky JA, Muldoon LL, Guo S, Evans AJ, Neuwelt EA, Clinton GM.
Departments of Biochemistry and Molecular Biology, Neurology, Cell and
Developmental Biology, and Neurosurgery, Oregon Health &Science
University and Veterans Administration Medical Center, Portland, Oregon.
PURPOSE: Herstatin, an autoinhibitor of the epidermal growth factor (EGF)
receptor family, was evaluated for efficacy against human glioblastoma in
vitro and in vivo in a rat intracranial model.EXPERIMENTAL DESIGN:
Glioblastoma controlled by EGF receptor (EGFR; U87MG) or by the truncated
mutant, DeltaEGFR (U87MG/Delta), were transfected with Herstatin and
evaluated for in vitro and in vivo growth in nude rat brain. Cells treated
with purified Herstatin in vitro were evaluated for growth and signal
transduction.RESULTS: Herstatin expression prevented tumor formation by
U87MG and purified Herstatin inhibited their growth in vitro in a
dose-responsive fashion, whereas in vivo and in vitro growth of U87MG/Delta
was resistant to Herstatin. Inhibition of U87MG growth correlated with
suppressed EGF activation of EGFR and of Akt but not mitogen-activated
protein kinase signaling pathways, whereas DeltaEGFR activity and
intracellular signaling in U87MG/Delta were unaffected by Herstatin
treatment.CONCLUSIONS: Herstatin may have utility against glioblastoma
driven by the EGFR but not the mutant DeltaEGFR. Blockade of Akt but not the
mitogen-activated protein kinase signaling cascade appears to be critical
for suppression of intracranial tumor growth.
PMID: 15671564 [PubMed - in process]
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| 8: Clin Cancer Res. 2005 Jan 1;11(1):329-34. |
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Interstitial diphtheria toxin-epidermal growth factor
fusion protein therapy produces regressions of subcutaneous human
glioblastoma multiforme tumors in athymic nude mice.
Liu TF, Hall PD, Cohen KA, Willingham MC, Cai J, Thorburn A, Frankel AE.
Department of Medicine, Pathology, and Surgery, Wake Forest University
School of Medicine, Winston-Salem, North Carolina Department of
Pharmaceutical Sciences, Medical University Of South Carolina, Charleston,
South Carolina, USA.
PURPOSE: The novel fusion protein, DAB(389)EGF, composed of the catalytic
and translocation domains of diphtheria toxin (DAB(389)) fused with a
His-Ala linker to human epidermal growth factor (EGF) was tested for
antiglioma efficacy in an in vivo model of human glioma.EXPERIMENTAL DESIGN:
Female athymic nude mice (ages 4-6 weeks) were inoculated s.c. with 10
million U87MG human glioma cells in the right flank. When tumor volumes
reached approximately 100 mm(3) ( approximately 6-8 days), i.t. injections
of saline, DAB(389)IL2, or DAB(389)EGF 1, 3, 5 or 10 mug in 50 muL were
given every other day for three to six doses. Animals were monitored twice
daily and tumor measurements were made by calipers.RESULTS: The maximal
tolerated dose (MTD) of DAB(389)EGF was 3 mug every other day. Above the
MTD, animals experienced loss of activity, reduced oral intake, and
dehydration. Blood chemistries confirmed elevated blood urea nitrogen,
creatinine, aspartate transaminase, and alanine transaminase. Histopathology
revealed renal tubular necrosis. At the MTD, tumor regression was seen in
all animals. Relapses occurred in 4 of 16 (25%) of animals after 1 month.
These tumors contained EGF receptor, were sensitive in vitro to DAB(389)EGF,
and responded to a second course of i.t. DAB(389)EGF.CONCLUSIONS:
DAB(389)EGF fusion protein shows in vivo antiglioma efficacy in a s.c. tumor
model and warrants further preclinical testing in an i.c. tumor model for
eventual treatment of patients with recurrent or refractory EGF
receptor-positive glioblastoma multiforme.
PMID: 15671563 [PubMed - in process]
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| 9: Clin Cancer Res. 2005 Jan 1;11(1):267-72. |
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Loss of the AP-2{alpha} Transcription Factor Is
Associated with the Grade of Human Gliomas.
Heimberger AB, McGary EC, Suki D, Ruiz M, Wang H, Fuller GN, Bar-Eli M.
Departments of Neurosurgery, Cancer Biology, and Pathology, University of
Texas M.D. Anderson Cancer Center, Houston, Texas and Hilton Head Regional
Medical Center, Hilton Head, South Carolina.
PURPOSE: The activator protein (AP)-2alpha transcription factor plays a
crucial role in the progression of several human tumors, including malignant
melanoma, prostate, and breast cancer. Loss of AP-2alpha results in
deregulation of several genes with AP-2alpha binding motifs such as
E-cadherin, p21(WAF1), MMP-2, MCAM/MUC18, VEGF, and c-KIT. The purpose of
our study was to determine AP-2alpha expression distribution among grades of
gliomas and any possible effect on prognosis.EXPERIMENTAL DESIGN: A tissue
microarray was assembled from all surgical glioma cases with available
tissue samples at M.D. Anderson Cancer Center since 1986 to include 72
glioblastomas, 49 anaplastic astrocytomas, 9 low-grade astrocytoma, 37
oligodendrogliomas, 37 anaplastic oligodendrogliomas, 15 mixed
oligoastrocytomas, 20 anaplastic mixed oligoastrocytomas, and 7
gliosarcomas. The microarray included normal brain tissue, and AP-2alpha
expression was determined by immunohistochemistry.RESULTS: AP-2alpha
expression was lost on 99% (P < 0.001) and 98% (P < 0.001) of
glioblastomas and anaplastic astrocytomas, respectively, compared with grade
2 astrocytomas and normal brain, all of which (100%) maintained expression
of AP-2alpha. The loss of AP-2alpha was a negative prognostic indicator
within the overall category of gliomas by univariate analysis (rate ratio,
4.30; 95% confidence interval, 2.60-7.10; P < 0.001). However, there was
no significant effect of loss of AP-2alpha expression on survival observed
after adjustment for patient age, Karnofsky Performance Scale score, tumor
grade, and extent of resection (rate ratio, 1.2; 95% confidence interval,
0.6-2.2; P = 0.6).CONCLUSIONS: AP-2alpha expression correlates inversely
with glioma grade, suggesting a direct role in glioma tumorigenicity,
possibly through subsequent deregulation of target genes. Of all the
previously characterized markers of progression, the loss of AP-2alpha would
be the most common (96.2%) molecular marker as an astrocytic tumor evolves
from grade 2 to 3.
PMID: 15671555 [PubMed - in process]
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| 10: Clin Cancer Res. 2004 Jul 15;10(14):4831-8. |
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Treatment of intracerebral neoplasia and neoplastic
meningitis with regional delivery of oncolytic recombinant poliovirus.
Ochiai H, Moore SA, Archer GE, Okamura T, Chewning TA, Marks JR, Sampson
JH, Gromeier M.
Department of Surgery, Duke University Medical Center, Durham, North
Carolina 27710, USA.
PURPOSE: Spread to the central nervous system (CNS) and the leptomeninges is
a frequent complication of systemic cancers that is associated with serious
morbidity and high mortality. We have evaluated a novel therapeutic approach
against CNS complications of breast cancer based on the human neuropathogen
poliovirus (PV). EXPERIMENTAL DESIGN: Susceptibility to PV infection and
ensuing rapid cell lysis is mediated by the cellular receptor of PV, CD155.
We evaluated CD155 expression in several human breast tumor tissue specimens
and cultured breast cancer cell lines. In addition, we tested an oncolytic
PV recombinant for efficacy in xenotransplantation models of neoplastic
meningitis and cerebral metastasis secondary to breast cancer. RESULTS: We
observed that breast cancer tissues and cell lines derived thereof express
CD155 at levels mediating exquisite sensitivity toward PV-induced oncolysis
in the latter. An association with the immunoglobulin superfamily molecule
CD155 renders breast cancer a likely target for oncolytic PV recombinants.
This assumption was confirmed in xenotransplantation models for neoplastic
meningitis or solitary cerebral metastasis, where local virus treatment
dramatically improved survival. CONCLUSIONS: Our findings suggest oncolytic
PV recombinants as a viable treatment option for CNS complications of breast
cancer.
PMID: 15269159 [PubMed - indexed for MEDLINE]
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| 11: Clin Neuropathol. 2004 Nov-Dec;23(6):298-303. |
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Malignant transformation of a spinal cord
ganglioglioma--case report and review of the literature.
Di Patre PL, Payer M, Brunea M, Delavelle J, De Tribolet N, Pizzolato G.
Department of Pathology, Neuropathology Unit, University Hospitals, Geneva,
Switzerland.
Gangliogliomas are tumors of mixed glial and neuronal phenotype that usually
have a benign clinical course. Rare cases display anaplastic features at the
time of first presentation or progress to anaplastic gliomas over extended
times. We report on a ganglioglioma of the spinal cord that recurred as a
malignant glioma one and a half years after resection. The initial neoplasm
was composed of a mixture of well-differentiated ganglionic and astrocytic
cells. The recurrent tumor was an anaplastic small-cell glioma. The sole
unusual aspect in the initial neoplasm was an abundance of small vessels
with calcified walls, which mimicked a vascular malformation.
Publication Types:
PMID: 15584215 [PubMed - indexed for MEDLINE]
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| 12: Clin Neuropathol. 2004 Nov-Dec;23(6):262-70. |
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MIB-1 labeling index in astrocytic tumors--a
clinicopathologic study.
Neder L, Colli BO, Machado HR, Carlotti CG Jr, Santos AC, Chimelli L.
Department of Pathology, Ribeirao Preto Medical School, Ribeirao Preto-SP,
Brazil. neder@fmrp.usp.br
BACKGROUND: Although neuroimage and surgical techniques have improved
substantially, the prognosis of patients with astrocytic tumors remains
unchanged. The purpose of this study was to evaluate the proliferative
activity in astrocytic tumors in different grades of malignancy and
correlate it to other clinical features. PATIENTS AND METHODS: From archival
paraffin-embedded surgical specimens of 40 patients of the Ribeirao Preto
Medical School with World Health Organization grade II (n = 10), grade III
(n = 5) and grade IV astrocytomas (n = 25), the MIB-1 labeling index (LI)
was determined using at least a half of the blocks per case. The results
were correlated to the biological behavior of the tumors. The aims of this
study were to determine the level of MIB-1 LI values (cut-off) that reflect
differences in biological behavior of these tumors, the impact on survival
of clinical features such as age, tumor location or extension of surgical
removal as well as the adjuvant therapy. RESULTS AND CONCLUSIONS: As
expected, a wide range of MIB-1 LI values was disclosed (mean of 2.35% in
grade II astrocytomas to 12.28% in glioblastomas). A close relationship was
found between MIB-1 LI and survival of patients with astrocytomas according
to the histological grade. All but 1 recurrent tumor presented higher MIB-1
LI in the second biopsy, and the mean MIB-1 LI of the patients who died in
the immediate postoperative period (n = 7) was higher in comparison to the
MIB-1 LI of the respective grade. Postoperative radiation therapy was an
important factor that affected the survival of patients with high-grade
astrocytomas (p = 0.006). MIB-1 LI cut-off of 3% divided the astrocytomas in
2 groups with significantly different survival (p < 0.001): median
survival time of 12 months (low-grade) versus 45 months (high-grade). On the
other hand, univariate analysis did not show any correlation between
survival and extension of surgical resection (radical versus partial),
tumor's location or patient's age at surgery.
PMID: 15584210 [PubMed - indexed for MEDLINE]
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| 13: Clin Neuropathol. 2004 Sep-Oct;23(5):232-7. |
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Extraskeletal myxoid chondrosarcoma of the jugular
foramen.
Cummings TJ, Bridge JA, Fukushima T.
Department of Pathology, Duke University Medical Center, Durham, NC 27710,
USA. cummi008@mc.duke.edu
OBJECTIVE: To report a case of an extraskeletal myxoid chondrosarcoma (EMC)
arising from the jugular foramen. EMCs are tumors usually seen in the deep
soft tissues of the extremities and are rarely seen within the intracranial
cavity. The histological differential diagnosis includes chordoma,
conventional chondrosarcoma and chordoid meningioma, among others. A
distinguishing feature of EMC is their characteristic reciprocal
translocation t(9;22)(q22;q12). MATERIAL: A 63-year-old man presented with
progressive hearing loss and gait imbalance. Magnetic resonance imaging
showed a heterogeneously enhancing 2.4 cm mass in the cerebellopontine
angle. A right far lateral transcondylar skull base approach with gross
total removal of the tumor was performed. Intraoperative findings showed
that the mass appeared to arise from the glossopharyngeal nerve within the
jugular foramen. METHOD: Histology, immunohistochemistry, and fluorescence
in situ hybridization studies were performed. RESULTS: Histological and
immunohistochemical studies were compatible with the diagnosis of EMC.
Fluorescence in situ hybridization studies showed disruption of the EWS gene
locus at 22q12 and added further support to the diagnosis. CONCLUSIONS: We
report a rare case of EMC arising from the jugular foramen, and the
diagnosis of EMC can be supported by confirmation of disruption of the EWS
gene locus.
Publication Types:
PMID: 15581026 [PubMed - indexed for MEDLINE]
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| 14: Clin Neuropathol. 2004 Sep-Oct;23(5):223-31. |
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Expression of multidrug transporters in dysembryoplastic
neuroepithelial tumors causing intractable epilepsy.
Vogelgesang S, Kunert-Keil C, Cascorbi I, Mosyagin I, Schroder E, Runge
U, Jedlitschky G, Kroemer HK, Oertel J, Gaab MR, Pahnke J, Walker LC, Warzok
RW.
Department of Neuropathology, University of Greifswald, Germany.
sivogelg@uni-greifswald.de
OBJECTIVE: Dysembryoplastic neuroepithelial tumors (DNT) are relatively
benign brain lesions that often cause medically intractable epilepsy. There
is mounting evidence that multidrug transporters such as P-glycoprotein
(P-gp) or multidrug resistance-associated proteins (MRP) play an important
role in the development of resistance to antiepileptic drugs (AED). MATERIAL
AND METHODS: In the present study, we examined the expression of several
multidrug transporters in 14 cases of DNT. The peritumoral brain tissue as
well as 9 cases of arteriovenous malformations (AVM) served as controls.
P-gp, MRP2, MRP5 and breast cancer resistance protein (BCRP) expression was
evaluated qualitatively and quantitatively using immunohistochemistry.
RESULTS: All transporters were overexpressed quantitatively in DNT, but each
revealed a different labeling pattern. P-gp and BCRP were predominantly
located in the endothelium of brain vessels. MRP5 was detected primarily in
endothelial cells, but notably also in neurons. The expression of P-gp, MRP2
and MRP5 was low in AVM, whereas BCRP demonstrated strong staining.
Examination of MDR1 gene polymorphisms revealed no correlation with P-gp
expression whereas the MRP2 exon 10 G1249A polymorphism was associated with
different MRP2 labelling. CONCLUSIONS: Our results show that multidrug
transporters are overexpressed in DNT. This finding supports the view that
several of these transport proteins may play an important role in the
mechanisms of drug resistance in epileptic brain tissue.
PMID: 15581025 [PubMed - indexed for MEDLINE]
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| 15: Clin Neuropathol. 2004 Sep-Oct;23(5):218-22. |
|
Mixed cystic gliosarcoma and primitive neuroectodermal
tumor: a case report.
Dulai MS, Bosanko CM, Wang AM, Horoupian DS, Boodin S, Chen PY, Wilson
JD.
Department of Anatomic Pathology, William Beaumont Hospital, Royal Oak, MI
48073, USA.
The clinical and pathologic features of a mixed (composite) gliosarcoma and
primitive neuroectodermal tumor occurring in a 54-year-old male are
presented. A large cyst and the presence of Rosenthal fibers are also
unusual features of this tumor. To our knowledge, such a morphologically
variegated tumor has not previously been reported.
Publication Types:
PMID: 15581024 [PubMed - indexed for MEDLINE]
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| 16: Int J Cancer. 2005 Feb 10;113(4):581-7. |
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O6-methylguanine-DNA methyltransferase methylation and
TP53 mutation in malignant astrocytomas and their relationships with
clinical course.
Watanabe T, Katayama Y, Komine C, Yoshino A, Ogino A, Ohta T, Fukushima
T.
Department of Neurological Surgery, Nihon University School of Medicine,
30-1 Oyaguchi-kamumachi, Itabashi-ku, Tokyo 173-8610, Japan.
takao@med.nihon-u.ac.jp
Epigenetic silencing of O(6)-methylguanine-DNA methyltransferase (MGMT) by
promoter methylation can confer cancer cells with an increased sensitivity
to alkylating chemotherapeutic agents and a higher susceptibility to TP53
transition mutations. The aim of our study was to assess the correlation of
promoter methylation of the MGMT gene with TP53 mutations and the clinical
characteristics of malignant astrocytomas. We analyzed the MGMT promoter
methylation and TP53 mutations in 45 malignant astrocytomas (16 anaplastic
astrocytomas and 29 glioblastomas multiforme) treated prospectively with
1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-2(2-chloroethyl)-3-nitrosourea,
interferon-beta and radiation therapy, and evaluated their clinical
usefulness. MGMT promoter methylation was found in 17 (38%) of the 45 newly
diagnosed malignant astrocytomas. A clear trend existed between MGMT
methylation and G:C to A:T transition mutations of TP53 (p = 0.0596).
Patients with MGMT-methylated tumors displayed a greater chance of
responding to adjuvant therapy as compared with those with MGMT-unmethylated
tumors (p = 0.0393). TP53 mutation was not significantly associated with the
clinical response (p = 0.1310). While neither MGMT methylation nor TP53
mutation had a significant effect on prognosis of the whole population, the
presence of MGMT methylation emerged as a significant predictor of a longer
survival when exclusively analyzing 29 patients with glioblastomas
multiforme. These findings highlight the importance of MGMT methylation as a
specific predictive factor for responsiveness to nitrosourea chemotherapy.
PMID: 15455376 [PubMed - indexed for MEDLINE]
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| 17: Int J Radiat Oncol Biol Phys. 2005 Feb 1;61(2):529-34. |
|
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Irradiation combined with SU5416: Microvascular changes
and growth delay in a human xenograft glioblastoma tumor line.
Schuuring J, Bussink J, Bernsen HJ, Peeters W, van Der Kogel AJ.
Department ofNeurologyUniversity Medical Center, Nijmegen, The Netherlands;
Department of Neurology, Groene Hart Hospital, Gouda, The Netherlands.
PURPOSE: The combination of irradiation and the antiangiogenic compound
SU5416 was tested and compared with irradiation alone in a human
glioblastoma tumor line xenografted in nude mice. The aim of this study was
to monitor microenvironmental changes and growth delay. METHODS AND
MATERIALS: A human glioblastoma xenograft tumor line was implanted in nude
mice. Irradiations consisted of 10 Gy or 20 Gy with and without SU5416.
Several microenvironmental parameters (tumor cell hypoxia, tumor blood
perfusion, vascular volume, and microvascular density) were analyzed after
imunohistochemical staining. Tumor growth delay was monitored for up to 200
days after treatment. RESULTS: SU5416, when combined with irradiation, has
an additive effect over treatment with irradiation alone. Analysis of the
tumor microenvironment showed a decreased vascular density during treatment
with SU5416. In tumors regrowing after reaching only a partial remission,
vascular characteristics normalized shortly after cessation of SU5416.
However, in tumors regrowing after reaching a complete remission, permanent
microenvironmental changes and an increase of tumor necrosis with a
subsequent slower tumor regrowth was found. CONCLUSIONS: Permanent vascular
changes were seen after combined treatment resulting in complete remission.
Antiangiogenic treatment with SU5416 when combined with irradiation has an
additive effect over treatment with irradiation or antiangiogenic treatment
alone.
PMID: 15667976 [PubMed - in process]
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| 18: Int J Radiat Oncol Biol Phys. 2005 Feb 1;61(2):392-399. |
|
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Radiologic findings in patients treated with boron
neutron capture therapy for glioblastoma multiforme within EORTC trial
11961.
Vos MJ, Turowski B, Zanella FE, Paquis P, Siefert A, Hideghety K,
Haselsberger K, Grochulla F, Postma TJ, Wittig A, Heimans JJ, Slotman BJ,
Vandertop WP, Sauerwein W.
Department of ( *)Neurology, VU University Medical Center, Amsterdam, The
Netherlands.
PURPOSE: To assess the occurrence and development of cerebral radiologic
changes (cerebral atrophy and white matter lesions) in patients treated with
boron neutron capture therapy (BNCT) for primary supratentorial glioblastoma
multiforme within the European Organization for Research and Treatment of
Cancer (EORTC) trial 11961. METHODS AND MATERIALS: Magnetic resonance
imaging (MRI) scans were performed before and after surgery and at 1 week
and 2, 4.5, 6, 9, 12, 15, and 18 months after BNCT. For the current study,
MRI scans of all assessable patients were analyzed, with emphasis on
cerebral atrophy and white matter abnormalities. RESULTS: Twenty-six
patients had been treated with BNCT according to the EORTC trial 11961, of
whom 24 were assessable for the current study. The development of possible
BNCT-related cerebral changes was observed in 12 patients (50%), 10 of whom
had cerebral atrophy (42%) and 10 white matter changes (42%) after a median
interval of 7.5 and 4.5 months, respectively. CONCLUSION: In this study,
cerebral radiologic changes appeared in 50% of patients within the first
year after BNCT. Although a clear correlation between the BNCT dose and the
development of cerebral changes could not be demonstrated, a relationship
between the occurrence of these radiologic abnormalities and BNCT seems
likely.
PMID: 15667958 [PubMed - as supplied by publisher]
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| 19: Int J Radiat Oncol Biol Phys. 2005 Feb 1;61(2):374-9. |
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Stereotactic radiotherapy for localized low-grade gliomas
in children: Final results of a prospective trial.
Marcus KJ, Goumnerova L, Billett AL, Lavally B, Scott RM, Bishop K, Xu R,
Young Poussaint T, Kieran M, Kooy H, Pomeroy SL, Tarbell NJ.
Children's Hospital, Boston, MA, USA; Dana-Farber Cancer Institute, Boston,
MA, USA; Brigham and Women's Hospital, Boston, MA, USA.
PURPOSE: To evaluate the efficacy of stereotactic radiotherapy (SRT) for
small, localized, pediatric brain tumors and to determine the patterns of
failure. METHODS AND MATERIALS: A total of 81 patients were enrolled in an
institutional review board-approved prospective Dana-Farber Cancer Institute
protocol between 1992 and 1998. Of the 81 patients, 50 had low-grade
astrocytoma, 23 had residual or recurrent craniopharyngioma, 4 had posterior
fossa ependymoma, and 4 had other histologic types. All patients underwent
biopsy for diagnosis, with the exception of patients with neurofibromatosis
and radiographic evidence of an optic system tumor. The neurocognitive
outcome for all patients was also an endpoint of the study and will be
reported separately. This report focused on the patients with low-grade
gliomas only. Of the 50 patients, 26 were males and 24 females; the median
age was 9 years (range, 2-26 years). The indications for treatment of
patients with low-grade gliomas were progression during or after
chemotherapy or progression after surgery alone. SRT was delivered using a
dedicated 6-MV linear accelerator. Immobilization was accomplished with a
removable head-frame. CT and MRI fusion was used for treatment planning. The
target volume generally included the preoperative tumor plus a 2-mm margin
for the planning target volume. The median collimator size was 47.25 mm
(range, 30-60 mm). Three to nine arcs were used to deliver a mean total dose
of 52.2 Gy in 1.8-Gy daily fractions. RESULTS: With a median follow-up of
6.9 years (range, 0.9-10.2 years), the progression-free survival rate was
82.5% at 5 years and 65% at 8 years. The overall survival was 97.8% at 5
years and 82% at 8 years. Six patients had local progression. Two of the
patients with local progression had pathologic progression to anaplastic
astrocytoma 3 and 7 years after initial SRT. Five patients, all with optic
system/hypothalamic primary tumors, developed central nervous system
dissemination 1.0-7.4 years after SRT. One patient developed a presumed
radiation-induced primitive neuroectodermal tumor 6 years after initial
treatment. Six patients died, three of dissemination, two of progression to
higher grade tumors, and one of a secondary radiation-induced tumor. All 6
cases of local progression were within the primary tumor bed at the time of
progression and had received the full prescription dose. No marginal
failures occurred. CONCLUSION: Stereotactic radiotherapy provides excellent
local control for children with small, localized low-grade glial tumors.
Marginal failures have not been observed, supporting the use of limited
margins to minimize late sequelae using stereotactic immobilization and
planning techniques.
PMID: 15667955 [PubMed - in process]
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| 20: J Clin Oncol. 2005 Jan 20;23(3):525-31. |
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Phase I Clinical Trial of Mafosfamide in Infants and
Children Aged 3 Years or Younger With Newly Diagnosed Embryonal Tumors: A
Pediatric Brain Tumor Consortium Study (PBTC-001).
Blaney SM, Boyett J, Friedman H, Gajjar A, Geyer R, Horowtiz M, Hunt D,
Kieran M, Kun L, Packer R, Phillips P, Pollack IF, Prados M, Heideman R.
Texas Children's Cancer Center, 6621 Fannin, CC 1410.00, Houston, TX 77030;
e-mail: sblaney@txccc.org.
PURPOSE A phase I trial of intrathecal (IT) mafosfamide was performed to
determine the optimal dose, dose-limiting toxicities, and incidence and
severity of other toxicities when administered in association with
concomitant multiagent systemic chemotherapy to children younger than 3
years with newly diagnosed embryonal tumors. PATIENTS AND METHODS
Twenty-five assessable patients received IT mafosfamide at one of six dose
levels ranging from 5 mg to 17 mg. Patients were premedicated with
dexamethasone (0.15 mg/kg) and morphine (0.1 mg/kg) before receiving IT
mafosfamide. Serial samples of CSF for pharmacokinetic studies were obtained
in a subset of patients with Ommaya reservoirs. Results Irritability,
presumably secondary to pain or headache during mafosfamide administration,
was dose limiting in two of three patients at the 17-mg dose level. The
maximum-tolerated dose of IT mafosfamide following premedication with
dexamethasone and morphine was 14 mg. CONCLUSION The maximum tolerated dose
and recommended phase II dose of IT mafosfamide in patients younger than 3
years with newly diagnosed embryonal CNS tumors is 14 mg. A trial to assess
the efficacy of regional therapy with IT mafosfamide administered with
intensive systemic chemotherapy in children younger than 3 years with
primary intracranial embryonal tumors is now in progress.
PMID: 15659498 [PubMed - in process]
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| 21: J Clin Oncol. 2005 Jan 1;23(1):233-5. |
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Unusual cases in multiple myeloma and a dramatic response
in metastatic lung cancer: Case 3. Intracranial plasmacytoma with cranial
nerve neuropathy in multiple myeloma.
Montalban C, Martin-Aresti J, Patier JL, Millan JM, Cosio MG.
Department of Internal Medicine, Hospital Ramon y Cajal, Madrid, Spain.
Publication Types:
PMID: 15625378 [PubMed - indexed for MEDLINE]
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Volume 4, Number
6 - 1 February 2005