| 1: Cancer
Genet Cytogenet. 2005 Sep;161(2):140-5. |
|
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Identification of oligodendroglioma specific chromosomal
copy number changes in the glioblastoma MI-4 cell line by array-CGH and FISH
analyses.
Magnani
I, Ramona
RF, Roversi
G, Beghini
A, Pfundt
R, Schoenmakers
EF, Larizza
L.
Department of Biology and Genetics, University of Milan, via Viotti3/5,
20133 Milan, Italy.
Glioblastomas, the most frequent and malignant glial tumors, are known to be
phenotypically heterogeneous. A low fraction of glioblastomas is associated
with specific chromosomal losses at 1p and 19q, which are commonly found in
oligodendrogliomas and are generally considered to be a primary event in the
development of these tumors. Subsequent progression of oligodendroglial
tumors appears to be triggered by additional molecular features underlying
the transition to anaplastic oligodendroglioma and glioblastoma multiforme
(GBM) such as deletions of 9p and 10q, and alterations of CDKN2A (p16),
which is located at 9p21. These findings strengthen the view that GBM on
rare occasions may develop from oligodendroglial differentiated cells. In
the present study, we evaluated the newly established MI-4 glioblastoma cell
line, which displays 1p and 19q specific alterations targeting preferential
regions of allelic loss in glial neoplasms, by array-CGH and fluorescence in
situ hybridization (FISH) analyses that were combined to obtain a high
resolution map of targeted chromosome rearrangements and copy number changes
throughout the genome. Genome-wide and chromosome 19 full coverage array-CGH
analysis of the MI-4 cell line revealed that in this particular cell line,
1p-specific loss, including the CDKN2 (p18) gene, is not accompanied by loss
of the previously described 19q13.3 tumor suppressor candidate region.
Interestingly, the array-CGH (CGHa) profile showed an increase in copy
number along most of 19q including the AKT2 oncogene and the KLKs gene
family, which have previously been shown to be amplified in pancreatic
carcinomas and upregulated in several tumors, respectively. The concomitant
1p partial loss and chromosome 19 alterations, with the +7 and -10-specific
GBM markers associated with homozygous deletion of 9p21.3 including CDKN2A
(p16), are distinct features of the glioblastoma MI-4 cell line,
illustrating its origin from an olidodendroglial tumor. Based on these
results, we conclude that the MI-4 glioblastoma cell line might function as
a model system for investigations into the behavior of a defined
oligodendroglioma subtype.
PMID: 16102584 [PubMed - in process]
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| 2: Cancer Res. 2005 Aug
15;65(16):7462-9. |
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The protein kinase Cbeta-selective inhibitor, Enzastaurin
(LY317615.HCl), suppresses signaling through the AKT pathway, induces
apoptosis, and suppresses growth of human colon cancer and glioblastoma
xenografts.
Graff
JR, McNulty
AM, Hanna
KR, Konicek
BW, Lynch
RL, Bailey
SN, Banks
C, Capen
A, Goode
R, Lewis
JE, Sams
L, Huss
KL, Campbell
RM, Iversen
PW, Neubauer
BL, Brown
TJ, Musib
L, Geeganage
S, Thornton
D.
Lilly Research Labs, Eli Lilly and Company, Indianapolis, Indiana 46285,
USA. graff_jeremy@lilly.com
Activation of protein kinase Cbeta (PKCbeta) has been repeatedly implicated
in tumor-induced angiogenesis. The PKCbeta-selective inhibitor, Enzastaurin
(LY317615.HCl), suppresses angiogenesis and was advanced for clinical
development based upon this antiangiogenic activity. Activation of PKCbeta
has now also been implicated in tumor cell proliferation, apoptosis, and
tumor invasiveness. Herein, we show that Enzastaurin has a direct effect on
human tumor cells, inducing apoptosis and suppressing the proliferation of
cultured tumor cells. Enzastaurin treatment also suppresses the
phosphorylation of GSK3betaser9, ribosomal protein S6(S240/244), and AKT(Thr308).
Oral dosing with Enzastaurin to yield plasma concentrations similar to those
achieved in clinical trials significantly suppresses the growth of human
glioblastoma and colon carcinoma xenografts. As in cultured tumor cells,
Enzastaurin treatment suppresses the phosphorylation of GSK3beta in these
xenograft tumor tissues. Enzastaurin treatment also suppresses GSK3beta
phosphorylation to a similar extent in peripheral blood mononuclear cells (PBMCs)
from these treated mice. These data show that Enzastaurin has a direct
antitumor effect and that Enzastaurin treatment suppresses GSK3beta
phosphorylation in both tumor tissue and in PBMCs, suggesting that GSK3beta
phosphorylation may serve as a reliable pharmacodynamic marker for
Enzastaurin activity. With previously published reports, these data support
the notion that Enzastaurin suppresses tumor growth through multiple
mechanisms: direct suppression of tumor cell proliferation and the induction
of tumor cell death coupled to the indirect effect of suppressing
tumor-induced angiogenesis.
PMID: 16103100 [PubMed - in process]
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| 3: Cancer Res. 2005 Aug
15;65(16):7429-35. |
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Perifosine inhibits multiple signaling pathways in glial
progenitors and cooperates with temozolomide to arrest cell proliferation in
gliomas in vivo.
Momota
H, Nerio
E, Holland
EC.
Department of Cancer Biology and Genetics and Surgery (Neurosurgery) and
Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021,
USA.
Perifosine is an oral Akt inhibitor which exerts a marked cytotoxic effect
on human tumor cell lines, and is currently being tested in several phase II
trials for treatment of major human cancers. However, the efficacy of
perifosine in human gliomas has not been established. As Akt is activated in
approximately 70% of human glioblastomas, we investigated the impact of
perifosine on glia in culture and on a mouse glioma model in vivo. Here we
show that perifosine strongly reduces phosphorylation levels of Akt and
extracellular signal-regulated kinase (Erk) 1/2, induces cell cycle arrest
in G1 and G2, and causes dose-dependent growth inhibition of mouse glial
progenitors in which Akt and/or Ras-Erk 1/2 pathways are activated.
Furthermore, because temozolomide is a common oral alkylating agent used in
the treatment of gliomas, we investigated the effect of perifosine in
combination with temozolomide. We observed an enhanced effect when both were
used in culture. With these results, we combined perifosine and temozolomide
as treatment of platelet-derived growth factor B-driven gliomas in mice.
Animal studies showed that perifosine and temozolomide combination therapy
was more effective than temozolomide treatment alone (P < 0.01). These
results indicate that perifosine is an effective drug in gliomas in which
Akt and Ras-Erk 1/2 pathways are frequently activated, and may be a new
candidate for glioma treatment in the clinic.
PMID: 16103096 [PubMed - in process]
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| 4: Cancer Res. 2005 Aug
15;65(16):7301-9. |
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Protein kinase C-epsilon regulates the apoptosis and
survival of glioma cells.
Okhrimenko
H, Lu
W, Xiang
C, Hamburger
N, Kazimirsky
G, Brodie
C.
Gonda (Goldschmied) Medical Diagnosis Research Center, Faculty of
Life-Sciences, Bar-Ilan University, Ramat Gan, Israel.
In this study, we examined the role of protein kinase C (PKC)-epsilon in the
apoptosis and survival of glioma cells using tumor necrosis factor-related
apoptosis inducing ligand (TRAIL)-stimulated cells and silencing of
PKCepsilon expression. Treatment of glioma cells with TRAIL induced
activation, caspase-dependent cleavage, and down-regulation of PKCepsilon
within 3 to 5 hours of treatment. Overexpression of PKCepsilon inhibited the
apoptosis induced by TRAIL, acting downstream of caspase 8 and upstream of
Bid cleavage and cytochrome c release from the mitochondria. A
caspase-resistant PKCepsilon mutant (D383A) was more protective than
PKCepsilon, suggesting that both the cleavage of PKCepsilon and its
down-regulation contributed to the apoptotic effect of TRAIL. To further
study the role of PKCepsilon in glioma cell apoptosis, we employed short
interfering RNAs directed against the mRNA of PKCepsilon and found that
silencing of PKCepsilon expression induced apoptosis of various glioma cell
lines and primary glioma cultures. To delineate the molecular mechanisms
involved in the apoptosis induced by silencing of PKCepsilon, we examined
the expression and phosphorylation of various apoptosis-related proteins. We
found that knockdown of PKCepsilon did not affect the expression of Bcl2 and
Bax or the phosphorylation and expression of Erk1/2, c-Jun-NH2-kinase, p38,
or STAT, whereas it selectively reduced the expression of AKT. Similarly,
TRAIL reduced the expression of AKT in glioma cells and this decrease was
abolished in cells overexpressing PKCepsilon. Our results suggest that the
cleavage of PKCepsilon and its down-regulation play important roles in the
apoptotic effect of TRAIL. Moreover, PKCepsilon regulates AKT expression and
is essential for the survival of glioma cells.
PMID: 16103081 [PubMed - in process]
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| 5: Cancer Res. 2005 Aug
15;65(16):7194-204. |
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Combined immunostimulation and conditional cytotoxic gene
therapy provide long-term survival in a large glioma model.
Ali
S, King
GD, Curtin
JF, Candolfi
M, Xiong
W, Liu
C, Puntel
M, Cheng
Q, Prieto
J, Ribas
A, Kupiec-Weglinski
J, van
Rooijen N, Lassmann
H, Lowenstein
PR, Castro
MG.
Molecular Medicine and Gene Therapy Unit, University of Manchester,
Manchester, United Kingdom.
In spite of preclinical efficacy and recent randomized, controlled studies
with adenoviral vectors expressing herpes simplex virus-1 thymidine kinase
(HSV1-TK) showing statistically significant increases in survival, most
clinical trials using single therapies have failed to provide major
therapeutic breakthroughs. Because glioma is a disease with dismal prognosis
and rapid progression, it is an attractive target for gene therapy.
Preclinical models using microscopic brain tumor models (e.g., < or =0.3
mm3) may not reflect the pathophysiology and progression of large human
tumors. To overcome some of these limitations, we developed a syngeneic
large brain tumor model. In this model, administration of single therapeutic
modalities, either conditional cytotoxicity or immunostimulation, fail.
However, when various immunostimulatory therapies were delivered in
combination with conditional cytotoxicity (HSV1-TK), only the combined
delivery of fms-like tyrosine kinase ligand (Flt3L) and HSV1-TK
significantly prolonged the survival of large tumor-bearing animals (> or
=80%; P < or = 0.005). When either macrophages or CD4+ cells were
depleted before administration of viral therapy, TK + Flt3L therapy failed
to prolong survival. Meanwhile, depletion of CD8+ cells or natural killer
cells did not affect TK + Flt3L efficacy. Spinal cord of animals surviving 6
months after TK + Flt3L were evaluated for the presence of autoimmune
lesions. Whereas macrophages were present within the corticospinal tract and
low levels of T-cell infiltration were detected, these effects are not
indicative of an overt autoimmune disorder. We propose that combined Flt3L
and HSV1-TK adenoviral-mediated gene therapy may provide an effective
antiglioma treatment with increased efficacy in clinical trials of glioma.
PMID: 16103070 [PubMed - in process]
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| 6: Cancer Res. 2005 Aug
15;65(16):7121-6. |
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Integrative genomic analysis identifies NDRG2 as a
candidate tumor suppressor gene frequently inactivated in clinically
aggressive meningioma.
Lusis
EA, Watson
MA, Chicoine
MR, Lyman
M, Roerig
P, Reifenberger
G, Gutmann
DH, Perry
A.
Division of Neuropathology, Department of Pathology and Immunology,
Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Although meningiomas are common central nervous system tumors, little is
known about the genetic events responsible for malignant progression. In
this study, we employed gene expression profiling to identify transcripts
whose expression was lost in anaplastic (WHO grade III) versus benign (WHO
grade I) meningioma. Approximately 40% of genes down-regulated in anaplastic
meningioma were localized to chromosomes 1p and 14q. One specific gene
located at 14q11.2, NDRG2, was consistently down-regulated in grade III
meningioma, a finding which we validated at both the transcript and protein
levels in independent sets of clinically and pathologically diverse
meningiomas. Loss of NDRG2 expression was also seen in a subset of
lower-grade meningiomas, including atypical meningiomas (WHO grade II) with
clinically aggressive behavior. Furthermore, we found that the loss of NDRG2
expression was significantly associated with hypermethylation of the NDRG2
promoter. Collectively, these data identify NDRG2 as the first specific
candidate tumor suppressor gene on chromosome 14q that is inactivated during
meningioma progression. In addition, these findings highlight the utility of
combining genomic, epigenetic, and expression data to identify clinically
significant tumor biomarkers, and suggest that NDRG2 expression will be a
useful and functionally relevant biomarker to predict aggressive behavior in
patients with meningioma.
PMID: 16103061 [PubMed - in process]
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| 7: Clin Neuropathol.
2005 May-Jun;24(3):112-7. |
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Isolated Rosai Dorfman disease of the central nervous
system presenting as dural-based and intraparenchymal lesions.
Sundaram
C, Uppin
SG, Prasad
BC, Sahu
BP, Devi
MU, Prasad
VS, Purohit
AK.
Department of Pathology, Nizam's Institute of Medical Sciences, Hyderabad,
India. challa_sundaram@yahoo.com
OBJECTIVE: To report three patients with isolated Rosai Dorfman disease of
the central nervous system. CASE REPORTS: We report two patients with
dural-based lesions diagnosed imageologically as meningiomas, and one
patient with multiple intraparenchymal lesions diagnosed imageologically as
lymphoma. Two patients were males and one was female. All were above 35
years of age with no nodal or other system involvement. The diagnosis was
established on surgically excised masses during histopathology. One patient
died due to unrelated causes 10 years later and the other two are
symptom-free at 21.5- and 11.5-year-follow-up. CONCLUSIONS: Awareness of the
entity and consideration in the differential diagnosis of dural-based/intraparenchymal
lesions is necessary for diagnosis and prognosis.
Publication Types:
PMID: 15943162 [PubMed - indexed for MEDLINE]
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| 8: Clin Neuropathol.
2005 May-Jun;24(3):101-5. |
|
Extraventricular neurocytoma presenting with intratumoral
hemorrhage.
Ritz
R, Roser
F, Bornemann
A, Hahn
U, Freudenstein
D.
Department of Neurosurgery, University Hospital, Eberhard, Germany.
rainer.ritz@med.uni-tuebingen.de
A case of extraventricular neurocytoma with spontaneous intratumoral
hemorrhage is reported. A 47-year-old man presented with sudden left-sided
hemiparesis. Magnetic resonance imaging revealed a right parietal
subcortical mass with intratumoral hemorrhagic transformation and without
contact to the ventricular system. After complete microsurgical removal, the
tumor was histologically diagnosed as neurocytoma. Usually, the term "central
neurocytoma" is restricted to neurocytic neoplasms arising within the
cerebral ventricles. In the majority of the cases, these slow-growing,
generally circumscribed lesions become symptomatic by obstructive
hydrocephalus. Hemorrhagic onset is sporadically reported in the literature.
In contrast to central neurocytomas, neurocytic lesions located within the
brain parenchyma, so-called "extraventricular neurocytomas" are
very uncommon. To the knowledge of the authors, this is the first case of an
extraventricular neurocytoma with histological classic features presenting
with intratumoral hemorrhage in adults.
Publication Types:
PMID: 15943160 [PubMed - indexed for MEDLINE]
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| 9: Int
J Cancer. 2005 Aug 16; [Epub ahead of print] |
|
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Role of hepatocyte growth factor activator (HGF activator)
in invasive growth of human glioblastoma cells in vivo.
Uchinokura
S, Miyata
S, Fukushima
T, Itoh
H, Nakano
S, Wakisaka
S, Kataoka
H.
Second Department of Pathology, Faculty of Medicine, University of Miyazaki,
Kiyotake, Miyazaki, Japan.
Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional growth
factor that is involved in invasive growth of tumor cells via its receptor
MET, a protein product of c-met proto-oncogene. HGF activator (HGFA) is a
serine proteinase responsible for the activation of proform of HGF/SF (proHGF/SF).
In our study, we examined the effects of engineered expression of HGFA on 2
human glioblastoma cell lines (YKG-1 and U251). Both cells expressed MET,
while only YKG-1 expressed endogenous proHGF/SF. Enhanced MET
phosphorylation and increased migratory activity were induced by the
expression of HGFA in YKG-1 cells in vitro in the presence of thrombin,
which is a known activator of proHGFA. In contrast, MET phosphorylation was
consistently observed in U251 that lacked endogenous HGF/SF, suggesting
ligand-independent activation of MET in this cell line. Consequently, the
expression of HGFA in U251 did not enhance the MET phosphorylation and
following cellular response even with the thrombin treatment. However,
addition of exogenous proHGF/SF resulted in enhanced migratory activity of
HGFA-expressing U251 cells in the presence of thrombin in vitro. The
engineered HGFA expression resulted in significantly enhanced tumor growth
with increased vascular density in vivo when YKG-1 cells were implanted in
nude mouse brain. This effect was not observed in U251 lacking endogenous
proHGF/SF. These results indicate the possible existence of multiple
mechanisms of MET activation in glioblastomas and that the activation system
of proHGF/SF is important in progression of glioblastomas that express
endogenous proHGF/SF and require ligand-dependent MET activation. (c) 2005
Wiley-Liss, Inc.
PMID: 16106403 [PubMed - as supplied by publisher]
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| 10: J
Clin Oncol. 2005 Aug 20;23(24):5511-9. |
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Neurocognitive consequences of risk-adapted therapy for
childhood medulloblastoma.
Mulhern
RK, Palmer
SL, Merchant
TE, Wallace
D, Kocak
M, Brouwers
P, Krull
K, Chintagumpala
M, Stargatt
R, Ashley
DM, Tyc
VL, Kun
L, Boyett
J, Gajjar
A.
Division of Neuro-Oncology, St Jude Children's Research Hospital, 332 N
Lauderdale, Memphis, TN 38105-2794; e-mail: amar.gajjar@stjude.org.
PURPOSE This prospective, longitudinal study examined the effects of
risk-adapted craniospinal irradiation (CSI) dose and the interactions of
dose with age and time from diagnosis on intelligence quotient (IQ) and
academic achievement (reading, spelling, and math) among patients treated
for medulloblastoma (MB). PATIENTS AND METHODS Patients received serial
neurocognitive testing spanning from 0 to 6.03 years after diagnosis (median,
3.14 years). The multi-institutional study included 111 patients, who were 3
to 20 years of age at diagnosis (median age, 7.4 years), treated for MB with
risk-adapted CSI followed by four cycles of high-dose chemotherapy (cyclophosphamide,
cisplatin, and vincristine) with stem-cell support. High-risk patients (HR;
n = 37) received CSI to 36 to 39.6 Gy and conformal boost treatment of the
primary site to 55.8 to 59.4 Gy. Average-risk patients (AR; n = 74) received
CSI to 23.4 Gy and conformal boost treatment of the posterior fossa to 36.0
Gy and primary site to 55.8 Gy. Results Multivariate modeling revealed
statistically significant declines in mean IQ (-1.59 points/yr; P = .006),
reading (-2.95 points/yr; P < .0001), spelling (-2.94 points/yr; P <
.0001), and math (-1.87 points/yr; P = .003) scores for the entire group.
The effects of risk-adapted radiation therapy on IQ, reading, and spelling
were moderated by age, with the greatest rates of decline observed for the
HR patients who were younger (< 7 years old) at diagnosis. CONCLUSION
Young age at diagnosis was the most prominent risk factor for neurocognitive
deficits among survivors of MB despite reductions in CSI dosing and efforts
to limit the boost volume. Younger patients exhibited substantial problems
with the development of reading skills.
PMID: 16110011 [PubMed - in process]
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| 11: J
Clin Oncol. 2005 Aug 20;23(24):5493-500. |
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Profile of daily life in children with brain tumors: an
assessment of health-related quality of life.
Bhat
SR, Goodwin
TL, Burwinkle
TM, Lansdale
MF, Dahl
GV, Huhn
SL, Gibbs
IC, Donaldson
SS, Rosenblum
RK, Varni
JW, Fisher
PG.
Stanford University Cancer Center, Room CC2220, 875 Blake Wilbur Dr,
Stanford, CA 94305-5826; e-mail: pfisher@stanford.edu.
PURPOSE The survival of children with CNS tumors approaches 70%, yet
health-related quality of life (HRQOL) has not been investigated rigorously
in this population. We aimed to show that universal assessment of HRQOL
could be obtained easily by using the PedsQL 4.0 and to provide a composite
profile of their daily lives. PATIENTS AND METHODS The PedsQL was
administered to all patients seen in the neuro-oncology clinic at Lucile
Packard Children's Hospital (Palo Alto, CA) from December 2001, to September
2002. Patients were compared with healthy controls by using two-sided t
tests to evaluate statistically significant differences. Results One hundred
thirty-four patients (73 male; mean age +/- standard deviation, 11.8 +/- 5.4
years; 55 had low-grade glioma, 32 had medulloblastoma/primitive
neuroectodermal tumor/embryonal tumor, 17 had malignant astrocytoma, nine
had germ-cell tumor, and 21 had other types of tumors) were assessed, each
in less than 20 minutes. Scores on both child and parent-proxy reports for
the total HRQOL, psychosocial, physical, emotional, social, and
school-functioning scales were all significantly lower than controls (P <
.01). Patients with low-grade glioma were reported to have the highest total
HRQOL. Children receiving radiation therapy (XRT) but no chemotherapy had
significantly lower total, psychosocial, emotional, and social functioning
than those receiving other treatments, including XRT plus chemotherapy.
CONCLUSION The PedsQL can be used to assess HRQOL rapidly and easily in
children with CNS tumors, who have significantly worse HRQOL than healthy
children. Children receiving XRT fare worse overall; chemotherapy added to
XRT does not seem to worsen HRQOL. Assessment of HRQOL should be included as
an outcome in future clinical trials.
PMID: 16110009 [PubMed - in process]
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| 12: J
Clin Oncol. 2005 Aug 20;23(24):5424-6. |
|
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Quality-of-Life Assessment in Pediatric Brain Tumor
Patients and Survivors: Lessons Learned and Challenges to Face.
Tao
ML, Parsons
SK.
PMID: 16110000 [PubMed - in process]
 
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| 13: J Neurooncol.
2005 May;72(3):271-2. |
|
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Pyramidal tract degeneration in astrocytoma.
Lahrmann
H, Horvath-Mechtler
B, Hitzenberger
P, Oberndorfer
S, Struhal
W, Grisold
W.
Neurological Department, Kaiser Franz Josef Hospital and Ludwig Boltzmann
Institute for Neurooncology, Kundratstr. 3, A-1100, Vienna, Austria.
heinz.lahrmann@wienkav.at
PMID: 15937652 [PubMed - indexed for MEDLINE]
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| 14: J Neurooncol.
2005 May;72(3):267-70. |
|
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Hemangioblastomatosis of the central nervous system
without von Hippel-Lindau disease: a case report.
Kato
M, Ohe
N, Okumura
A, Shinoda
J, Nomura
A, Shuin
T, Sakai
N.
Department of Neurosurgery, Gifu University School of Medicine, 1-1 Yanagido,
Gifu, 501-1194, Japan. masayasu@cc.gifu-u.ac.jp
We report a very rare case of hemangioblastomatosis in a patient without von
Hippel-Lindau disease (VHL). A 50-year-old woman had a history of surgical
procedures for total removal of a cerebellar hemangioblastoma (HB).
Twenty-one years after the last operation, she developed communicating
hydrocephalus; computed tomographic (CT) scans of the brain showed no
recurrence of HB in the posterior fossa. Subsequently, she underwent
placement of a ventriculo-peritoneal shunt. One year later, she was
readmitted because of progressive numbness and pain in the left lower limb.
Magnetic resonance imaging (MRI) showed multiple Gd-enhancing tumors around
the brain stem, in the cerebellum, and in the cervical and thoracolumbar
regions of the spine. She underwent surgical removal of the tumors in the
cerebellum and spinal cord. Although the extirpated tissues were
histopathologically verified HB with less than 1% MIB-1 labeling index,
surgery was followed by external beam radiation therapy with doses of 40 Gy
to the whole brain, 10 Gy to the posterior fossa and 30 Gy to the whole
spine. However, she subsequently developed quadriparesis and became
bedridden.
Publication Types:
PMID: 15937651 [PubMed - indexed for MEDLINE]
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| 15: J Neurooncol.
2005 May;72(3):239. |
|
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Undifferentiated sarcoma arising in the brain, 23 years
after curative treatment of an ependymoma.
Hofer
S, Seeger
H, Rordorf
T, Knuth
A, Janzer
R.
Department of Oncology, University Hospital Zurich, Ramistrasse 100, Zurich,
8091, Switzerland. ilvia.hofer@usz.ch
PMID: 15937646 [PubMed - indexed for MEDLINE]
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| 16: J Neurooncol.
2005 May;72(3):225-30. |
|
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Comparative genomic hybridization and mutation analyses
of sporadic schwannomas.
Ikeda
T, Hashimoto
S, Fukushige
S, Ohmori
H, Horii
A.
Department of Molecular Pathology, Tohoku University School of Medicine, 2-1
Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
Schwannomas of the vestibular nerve are the striking characteristics of
neurofibromatosis type 2 (NF2), an autosomal dominant hereditary disease.
The NF2 gene on 22q12 has been isolated as the gene responsible for NF2.
Previous studies have reported that 60% of sporadic schwannomas showed
inactivation of the NF2 gene, but genetic alterations of remaining 40%
tumors remain elusive. Moreover, detailed genetic alterations of this tumor
remain an open question. In this study, we analyzed genomic alterations in
17 sporadic schwannomas using comparative genomic hybridization (CGH). Loss
of chromosome 22q, including the NF2 locus, was the only notable abnormality
(5/17, 29%). Further, we performed fluorescence in situ hybridization
analysis with a genomic BAC clone harboring the NF2 gene and found that the
5 tumors with loss detected by CGH as well as three cases without such a
detectable loss by CGH, or a total, 8/17 (47%), showed loss of the NF2 locus.
Mutation search by PCR-SSCP followed by direct sequencing revealed that 71%
(12/17) of the tumors had one or two mutations in the NF2 gene. Our analyses
disclosed that 14 (82%) of 17 tumors had structural alteration of NF2; among
these 14 cases, 9 (64%) had two inactivating mutations in the NF2 gene,
either a somatic mutation in one allele coupled with loss of the other
allele or two independent somatic mutations. Our present results suggested
that (i) most of the sporadic schwannomas have two-hit mutations in the NF2
gene, and (ii) NF2 is the only major causative gene in the genesis of
schwannomas that is activated or inactivated by copy number alterations.
PMID: 15937644 [PubMed - indexed for MEDLINE]
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| 17: J
Neuropathol Exp Neurol. 2005 Aug;64(8):695-705. |
|
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Sphingosine kinase-1 expression correlates with poor
survival of patients with glioblastoma multiforme: roles of sphingosine
kinase isoforms in growth of glioblastoma cell lines.
Van
Brocklyn JR, Jackson
CA, Pearl
DK, Kotur
MS, Snyder
PJ, Prior
TW.
From the Division of Neuropathology (JRVB, CAJ, MSK), Department of
Pathology (PJS, TWP), and Department of Statistics (DKP), The Ohio State
University, Columbus, Ohio.
Sphingosine-1-phosphate is a bioactive lipid that is mitogenic for human
glioma cell lines by signaling through its G protein-coupled receptors. We
investigated the role of sphingosine-1-phosphate receptors and the enzymes
that form sphingosine-1-phosphate, sphingosine kinase (SphK)-1, and -2 in
human astrocytomas. Astrocytomas of various histologic grades expressed
three types of sphingosine-1-phosphate receptors, S1P1, S1P2, and S1P3;
however, no significant correlation with histologic grade or patient
survival was detected. Expression of SphK1, but not SphK2, in human
astrocytoma grade 4 (glioblastoma multiforme) tissue correlated with short
patient survival. Patients whose tumors had low SphK1 expression survived a
median 357 days, whereas those with high levels of SphK1 survived a median
102 days. Decreasing SphK1 expression using RNA interference or
pharmacologic inhibition of SphK significantly decreased the rate of
proliferation of U-1242 MG and U-87 MG glioblastoma cell lines. Surprisingly,
RNA interference to knockdown SphK2 expression inhibited glioblastoma cell
proliferation more potently than did SphK1 knockdown. SphK knockdown also
prevented cells from exiting G1 phase of the cell cycle and marginally
increased apoptosis. Thus, SphK isoforms may be major contributors to growth
of glioblastoma cells in vitro and to aggressive behavior of glioblastoma
multiforme.
PMID: 16106218 [PubMed - in process]
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| 18: Neurology. 2004 Dec
28;63(12):2360-2. |
|
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Correlations between molecular profile and radiologic
pattern in oligodendroglial tumors.
Laigle-Donadey
F, Martin-Duverneuil
N, Lejeune
J, Criniere
E, Capelle
L, Duffau
H, Cornu
P, Broet
P, Kujas
M, Mokhtari
K, Carpentier
A, Sanson
M, Hoang-Xuan
K, Thillet
J, Delattre
JY.
Federation de Neurologie Mazarin, Groupe Hospitalier Pitie-Salpetriere,
Paris, France.
OBJECTIVE: To investigate possible correlations between tumor location and
genetic alterations in a series of oligodendrogliomas. METHODS: A series of
158 consecutive oligodendrogliomas were retrospectively reviewed. In each
case, the radiologic picture and the chromosome 1p (chr 1p) status of the
tumor detected by the loss of heterozygosity technique were analyzed.
Correlation between tumor location and molecular profile was made by chi2
tests. RESULTS: Eighty-eight of the 158 patients had low-grade
oligodendrogliomas, and 70 had anaplastic oligodendrogliomas. Overall,
oligodendrogliomas with chr 1p loss were located preferentially in the
anterior part of the brain, whereas tumors with intact chr 1p affected
mainly the posterior part of the brain (p = 0.0038). In terms of lobar
involvement, a preferential location of oligodendrogliomas with chr 1p loss
was found in the frontal lobes as compared with the temporal, parietal, and
occipital tumors (p < 0.01). CONCLUSION: There is a significant
correlation between loss of heterozygosity on chromosome 1p and tumor
location in oligodendrogliomas, suggesting that subtypes of
oligodendrogliomas could derive from site-specific precursors.
Publication Types:
PMID: 15623700 [PubMed - indexed for MEDLINE]
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| 19: Neurology. 2004 Dec
28;63(12):2298-302. |
|
-
Resective reoperation for failed epilepsy surgery:
seizure outcome in 64 patients.
Siegel
AM, Cascino
GD, Meyer
FB, McClelland
RL, So
EL, Marsh
WR, Scheithauer
BW, Sharbrough
FW.
Division of Epilepsy, Mayo Clinic, Rochester, MN 55905, USA. gcasc
OBJECTIVE: To determine the surgical outcome and factors of predictive value
in patients undergoing reoperation for intractable partial epilepsy. METHODS:
The authors retrospectively studied the operative outcome in 64 consecutive
patients who underwent reoperation for intractable partial epilepsy.
Demographic data, results of comprehensive preoperative evaluations, and the
seizure and neurologic outcome after reoperation were determined. All
patients were followed a minimum of 1 year subsequent to their last
operative procedure. RESULTS: Fifty-three patients had two surgeries, and 11
patients had three or more operations. The first surgery involved a
lesionectomy (n = 33), "nonlesional" temporal lobe resection (n =
28), and a "nonlesional" extratemporal resection (n = 3). The mean
duration between the first and second procedure was 5.5 years. Fifty-five
patients underwent an intralobar reoperation, whereas nine had a resection
of a different lobe. After reoperation, 25 patients (39%) were free of
seizure, 6 patients (9%) had rare seizures, 12 patients (19%) had a
worthwhile improvement, and 21 patients (33%) failed to respond to surgery.
Predictors of seizure-free outcome were age at seizure onset >15 years (p
= 0.01), duration of epilepsy < or =5 years at the time of initial
surgery (p = 0.03), and focal interictal discharges in scalp EEG (p = 0.03).
Using a logistic regression model, two significant predictors emerged:
duration of epilepsy < or =5 years (odds ratio, 3.18; p = 0.04) and
preoperative focal interictal discharge (odds ratio, 4.45; p = 0.02).
Complications of reoperation included visual field deficits (n = 9), wound
infection (n = 2), subdural hematoma (n = 1), and hemiparesis (n = 1).
CONCLUSION: Reoperation may be an appropriate alternative form of treatment
for selected patients with intractable partial epilepsy who fail to respond
to initial surgery.
Publication Types:
PMID: 15623690 [PubMed - indexed for MEDLINE]
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| 20: Neuroradiology. 2005
May;47(5):334-43. Epub 2005 Apr 19. |
|
-
MR tractography with diffusion tensor imaging in clinical
routine.
Nguyen
TH, Yoshida
M, Stievenart
JL, Iba-Zizen
MT, Bellinger
L, Abanou
A, Kitahara
K, Cabanis
EA.
Department of Neuro-Imaging, Centre Hospitalier National d'Ophtalmologie des
XV-XX, UPMC Paris 6, CNRS UMR 6569, UPR 2147, Paris, France. thnguyenfr@yahoo.fr
Using MRI, we demonstrated that the depiction of the cerebral white matter
fiber tracts has become a routine procedure. Diffusion tensor (DT) sequences
may be analyzed with combined volume analysis and tractography extraction
software, giving indirect visualization of white matter connections. We
obtained DT data from 20 subjects with normal MR imaging and five patients
presenting cerebral diseases such as brain tumors, multiple sclerosis and
stroke, with five patients explored on two different MR scanners. Data were
transferred to dedicated workstations for anatomical realignment,
determination of voxel eigenvectors and calculation of fiber tract
orientations in a region of interest. In all subjects, axonal directions
underlying the main neuronal pathways could be delineated. Comparisons
between diseased regions and contralateral areas demonstrated changes in
voxel anisotropy in injured regions, revealing possible preferential fiber
orientations within diffuse T2 hyperintensities. Rapid data processing
allows imaging of the normal and diseased fiber pathways as part of the
routine MRI examination. Therefore, it appears that whenever white matter
disease is suspected a tractography can be performed with this fast and
simple method that we proved to be reliable and reproducible.
Publication Types:
PMID: 15838688 [PubMed - indexed for MEDLINE]
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| 21: Neuroradiology. 2005
May;47(5):352-61. Epub 2005 Apr 16. |
|
-
Magnetic resonance imaging in 120 patients with
intractable partial seizures: a preoperative assessment.
Lefkopoulos
A, Haritanti
A, Papadopoulou
E, Karanikolas
D, Fotiadis
N, Dimitriadis
AS.
Department of Radiology, AHEPA University Hospital, Thessaloniki, Greece.
leukanas@the.forthnet.gr
The aim of this study was to describe magnetic resonance imaging (MRI)
findings in patients with medically intractable epilepsy and to compare
different magnetic resonance (MR) sequences in order to establish a
dedicated and shorter scan time imaging protocol of choice. One hundred and
twenty patients with seizures that were refractory to medical treatment were
assessed by MRI with spin-echo (SE) T1, fast spin-echo (FSE) T2,
fluid-attenuated inversion recovery (FLAIR), inversion recovery (IR) and
contrast-enhanced T1 SE sequences. Pathological scans were acquired in 78
patients. Hippocampal sclerosis was detected in 30 patients (25%), cerebral,
tumoral, mass lesions in 12 patients (10%), vascular malformations in nine
patients (7.5%), cortical infarcts in eight patients (6.7%), cerebral
infections in four patients (4.2%) and developmental disorders in 15
patients (12.5%). The most common location of the lesions was the temporal
lobe (60%). Coronal, thin (slice thickness 4-5 mm) images have proven to be
the most useful in the assessment of the hippocampus. FLAIR and IR are
particularly useful in the detection of lesions abutting cerebrospinal fluid
(CSF) spaces and developmental disorders, respectively, while T1 SE
sequences before and after the intravenous administration of gadolinium
offer great facility in identifying space-occupying lesions and infections.
MRI is the most important diagnostic tool for the assessment of
epileptogenic foci, thus playing the primary role in indicating the type of
treatment to be applied.
PMID: 15834712 [PubMed - indexed for MEDLINE]
-
| 22: Oncogene. 2005 Aug
4;24(33):5198-206. |
|
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Shc3 affects human high-grade astrocytomas survival.
Magrassi
L, Conti
L, Lanterna
A, Zuccato
C, Marchionni
M, Cassini
P, Arienta
C, Cattaneo
E.
Neurochirurgia, Dipartimento di Chirurgia, Universita di Pavia, IRCCS
Policlinico S. Matteo, and IGM CNR, P.le Golgi 2, Pavia 27100, Italy.
magrassi@igm.cnr.it
A selective switch from expression of Shc1 gene to Shc3 occurs with
maturation of neuronal precursors into postmitotic neurons. Previous studies
showed that in the embryo, Shc1 is maximally expressed in dividing CNS stem
cells while it is silenced in mature neurons, where it is replaced by Shc3.
Under normal conditions Shc3 is never expressed by glial cells. We now show
that in human astrocytomas and glioblastomas, the normal pattern of
expression of Shc1/Shc3 is totally subverted, both proteins being present at
the same time and in the same cells. Our data indicate that Shc3 is
maximally expressed, together with Shc1, in glioblastoma, a highly
proliferative tumor with little, if any, indication of neuronal
differentiation. In primary cultures of glioblastoma, tumor cells maintain
Shc1 expression but downregulate Shc3. Analysis of the phosphorylation
status of Shc3 in human glioblastoma tumor samples in vivo indicates that it
is tyrosine phosphorylated. Finally, we found that the expression of
truncated variants of Shc3 with dominant-negative effects in human
high-grade glioma cells that maintain Shc3 expression in vitro leads to a
decreased Akt posphorylation and increased apoptosis, thus resulting in
impaired survival of the transfected cells. These data suggest that Shc
molecules play an important role in glioblastoma cell growth and survival.
PMID: 15870690 [PubMed - indexed for MEDLINE]
-
| 23: Surg Neurol.
2005 Sep;64(3):242-8. |
|
-
Contralateral meningeal artery supply of paramedian
meningiomas.
Hattori
K, Miyachi
S, Kobayashi
N, Kojima
T, Hattori
K, Negoro
M, Yoshida
J, Nagasaka
T.
Department of Neurosurgery, Nagoya University Graduate School of Medicine,
Nagoya 466-8550, Japan.
BACKGROUND: When resecting at falcine or parasagittal portion of paramedian
meningiomas, intraoperative hemostasis often is difficult despite effective
management of ipsilateral meningeal arteries. We attribute such difficulties
to meningeal artery blood supply from the contralateral side. We
retrospectively studied feeding arteries from both sides in case of
paramedian meningioma in terms of patient and tumor characteristics. METHODS:
Forty-three patients with paramedian meningiomas underwent selective
internal and external carotid angiography. We investigated how contralateral
meningeal arterial feeders related to patient profiles and imaging,
histopathologic, and immunohistochemical findings. RESULTS: Contralateral
meningeal supply existed for 14 of 25 falcine meningiomas and 6 of 18
parasagittal meningiomas. Patients with contralateral feeders were 8.5 years
younger than the others (P = .027) and were more likely to have larger
tumors (P = .028). These were histopathologically malignant (P = .048),
while showing more proliferation followed by monoclonal antibody against the
Ki-67 antigen index (P = .012) and angiogenetic potential associated with
vascular endothelial growth factor expression (P = .0085). CONCLUSIONS:
Contralateral meningeal supply may reflect strong angiogenetic recruitment
from rapid tumor growth followed by high expression of vascular endothelial
growth factor. This angiographical feature may predict the aggressive growth
of paramedian meningiomas.
PMID: 16099256 [PubMed - in process]
-
| 24: Surg Neurol.
2005 Jul;64(1):86-9; discussion 89. |
|
-
Rapid expansion of a ventral arachnoid cyst after
syringo-subarachnoid shunting in the thoracic spinal cord: case report.
Jea
A, Navarro
R, Green
BA.
Department of Neurological Surgery, University of Miami School of Medicine,
Lois Pope LIFE Center, Miami, FL 33136, USA.
BACKGROUND: Intradural spinal arachnoid cysts have rarely been reported in
association with intramedullary cysts. These associated lesions most
commonly occur in the thoracic spine. CASE DESCRIPTION: We reported an
unusual balance of cerebrospinal fluid dynamics between an initially occult
arachnoid cyst and syringomyelia. The arachnoid cyst was not allowed to
express itself until the syrinx was decompressed with a syringo-subarachnoid
shunt. CONCLUSION: Only one other report in the literature described a
similar case; however, our case is the first to be confirmed by
intraoperative ultrasound.
Publication Types:
PMID: 15993198 [PubMed - indexed for MEDLINE]
-
| 25: Surg Neurol.
2005 Jul;64(1):83-5; discussion 85. |
|
-
Cervicothoracic spinal epidural cavernous hemangioma:
case report and review of the literature.
Minh
NH.
Department of Neurological Surgery, People's Hospital 115, Ho Chi Minh City
84-8, Vietnam. nhm9us@yahoo.com
Cavernous hemangiomas are vascular malformations that effect the central
nervous system. This pathology is frequently encountered in the cerebral
hemispheres, cerebellum, and brainstem. Cavernous hemangiomas, although
usually solitary, may be associated with the same lesion in other parts of
the central nervous system or other organ systems and may appear as sporadic
or familial cases. They are infrequently found at the spinal level; in
particular, pure cervicothoracic epidural location is rare. We report a case
with a purely spinal epidural cavernous hemangioma from C6 to T1 and discuss
the clinical, diagnostic, and therapeutic aspect of this unusual spinal
malformation.
Publication Types:
- Review
- Review of Reported Cases
PMID: 15993196 [PubMed - indexed for MEDLINE]
-
| 26: Surg Neurol.
2005 Jul;64(1):55-60; discussion 60. |
|
-
Papillary endothelial hyperplasia (Masson tumor) of the
petrous and jugulare region: case report and literature review.
Zhang
R, Zhou
LF, Mao
Y, Wang
Y.
Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fu
Dan University, Shanghai 200040, China. zhang_rong@cableplus.com.cn
OBJECTIVE: Intracranial papillary endothelial hyperplasia (PEH) is rare, and
only 13 cases have been reported intracranially in the literature. In this
article, we present a case of PEH involving petrous and jugular foramen
region due to the uncommon incidence. CASE DESCRIPTION: A 49-year-old female
patient with a 4-year history of left-sided hearing loss and facial palsy.
Magnetic resonance (MR) imaging disclosed the presence of a 6 x 6 x 5 cm
lobular mass occupying the left petrous and jugulare region. This mass was
hyperintense on both T1 and T2 weighted MR images and was enhanced strongly
with gadolinium. No edema was found around the lesion. Preoperative digital
subtraction angiogram examination showed that the lesion had a rich blood
supply. Therefore, polyvinyl alcohol embolization was carried out to reduce
bleeding during operation. A left-sided suboccipital extreme lateral
approach was applied for craniotomy. The lesion was extradural and highly
vascular with extension into the petrous bone. It was subtotally removed.
Postoperative course of the patient was stable. Her neurologic evaluation
was the same as preoperatively. CONCLUSION: Surgical excision of the lesion
is the main therapy. Radiotherapy should be given to patients whose lesion
cannot be totally removed.
Publication Types:
- Case Reports
- Review
- Review of Reported Cases
PMID: 15993184 [PubMed - indexed for MEDLINE]
|
Volume 4, Number 35 - 23 August 2005