-
Expression of cytoplasmic and nuclear Survivin in primary
and secondary human glioblastoma.
Xie
D, Zeng
YX, Wang
HJ, Wen
JM, Tao
Y, Sham
JS, Guan
XY.
1State Key Laboratory of Oncology in Southern China, Cancer Center, Sun
Yat-Sen University, Guangzhou, China.
Clinically, human glioblastoma (GBM) may develop de novo or from a low-grade
glioma (secondary GBM), and molecular alterations in the two pathways may
differ. This study examined the status of Survivin expression and apoptosis
in 30 primary and 26 secondary GBMs. Our results show that cytoplasmic
Survivin positivity was significantly (P<0.001) more frequent in primary
GBMs (83%) than that in secondary GBMs (46%). In addition, an inverse
correlation of cytoplasmc Survivin positivity with GBM apoptotic index, and
a positive association between cytoplasmic Survivin and size of the tumours
were observed. These results suggest that cytoplasmic Survivin, via its
antiapoptotic function, may be involved in the tumorigenesis of many primary
GBMs, but only in a small fraction of secondary GBMs. Furthermore, the
overall progression times from low-grade precursor lesions to secondary GBMs
were significantly shorter (P<0.05) in cytoplasmic Survivin-positive
cases (mean, 15.6 months) than those in Survivin-negative cases (mean, 23.8
moths), and the positive expression level of Survivin in cytoplasm was
upregulated in most secondary GBMs when compared to matched pre-existing
low-graded lesions. These results suggest that the increased accumulation of
Survivin in the cytoplasm of more malignant glioma cells may prove to be a
selective advantage, thus accelerating progression to a more aggressive
phenotype.British Journal of Cancer (2006) 94, 108-114.
doi:10.1038/sj.bjc.6602904 www.bjcancer.com Published online 13 December
2005.
PMID: 16404364 [PubMed - in process]
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| 2: Cancer.
2005 Nov 15;104(10):2168-73. |
|
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Stereotactic radiosurgery (SRS): treatment option for
recurrent glioblastoma multiforme (GBM).
Combs
SE, Widmer
V, Thilmann
C, Hof
H, Debus
J, Schulz-Ertner
D.
Department of Radiation Oncology, University of Heidelberg, Heidelberg,
Germany. Stephanie.Combs@med.uni-heidelberg.de
BACKGROUND: This article describes the results of a study of stereotactic
radiosurgery (SRS) in the treatment of patients with recurrent malignant
glioma. METHODS: Thirty-two patients with recurrent glioblastoma multiforme
(GBM) were treated for 36 lesions with SRS from 1993 to 2001. Nineteen
patients were male and 13 were female. The median age at primary diagnosis
of the tumor was 56 years (range, 33-76 yrs). At the time of initial
diagnosis a total neurosurgical resection was performed in 7, a subtotal
resection in 21, and a biopsy in 4 patients. Histology evaluations revealed
glioblastoma multiforme (WHO Grade IV) in all 32 patients. In all patients
radiotherapy was performed as the first-line therapy, applied as
fractionated external beam radiotherapy. The median interval between primary
irradiation and reirradiation was 10 months. The median dose applied was 15
Gy (range, 10-20 Gy) prescribed to the 80% isodose line that encompassed the
target volume. No concomitant chemotherapy was applied. RESULTS: Treatment
was well tolerated by all patients. No acute toxicities > CTC Grade II
occurred. No severe long-term toxicities including radionecrosis were
observed. The median follow-up time was 13 months (range, 1-89 mo). All
patients died of tumor progression during follow-up. The median overall
survival from primary diagnosis of the tumor was 22 months (range, 9-133
mo). The survival rate at 1 year was 90%, and 49% and 26% at 2 and 3 years,
respectively. Median overall survival after SRS was 10 months. At 6 and 12
months after SRS, survival rates were 72% and 28%, respectively. Median
progression-free survival after SRS was 7 months. CONCLUSIONS: SRS offers
effective treatment as a salvage therapy for a subgroup of patients with
smaller lesions of recurrent GBM. Copyright 2005 American Cancer Society
PMID: 16220556 [PubMed - indexed for MEDLINE]
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Activation of RhoB by Hypoxia Controls Hypoxia-Inducible
Factor-1{alpha} Stabilization through Glycogen Synthase Kinase-3 in U87
Glioblastoma Cells.
Skuli
N, Monferran
S, Delmas
C, Lajoie-Mazenc
I, Favre
G, Toulas
C, Cohen-Jonathan-Moyal
E.
Institut National de la Sante et de la Recherche Medicale U563, Departement
d'Innovation Therapeutique et Oncologie Moleculaire and Departement de
Radiotherapie, Centre de Lutte Contre le Cancer Claudius Regaud, Toulouse
Cedex, France.
Hypoxia is a crucial factor in tumor aggressiveness and resistance to
treatment, particularly in glioma. Our previous results have shown that
inhibiting the small GTPase RhoB increased oxygenation of U87 human
glioblastoma xenografts, in part, by regulating angiogenesis. We
investigated here whether RhoB might also control a signaling pathway that
would permit glioma cells to adapt to hypoxia. We first showed that
silencing RhoB with siRNA induced degradation and inhibition of the
transcriptional activity of the hypoxia-inducible factor by the proteasome
in U87 hypoxic cells. This RhoB-dependent degradation of hypoxia-inducible
factor-1alpha in hypoxic conditions was mediated by the Akt/glycogen
synthase kinase-3beta pathway. While investigating how hypoxia could
activate this signaling pathway, using the GST-Rhotekin RBD pulldown assay,
we showed the early activation of RhoB by reactive oxygen species under
hypoxic conditions and, subsequently, its participation in the ensuing
cellular adaptation to hypoxia. Overall, therefore, our results have not
only highlighted a new signaling pathway for hypoxia controlled by the small
GTPase RhoB, but they also strongly implicate RhoB as a potentially
important therapeutic target for decreasing tumor hypoxia. (Cancer Res 2006;
66(1): 482-9).
PMID: 16397264 [PubMed - in process]
-
-
Distinct Transcription Profiles of Primary and Secondary
Glioblastoma Subgroups.
Tso
CL, Freije
WA, Day
A, Chen
Z, Merriman
B, Perlina
A, Lee
Y, Dia
EQ, Yoshimoto
K, Mischel
PS, Liau
LM, Cloughesy
TF, Nelson
SF.
Departments of Human Genetics, Medicine/Hematology-Oncology, Pathology and
Laboratory Medicine, Neurosurgery, and Neurology, David Geffen School of
Medicine, and Jonsson Comprehensive Cancer Center, University of California
at Los Angeles, Los Angeles, California.
Glioblastomas are invasive and aggressive tumors of the brain, generally
considered to arise from glial cells. A subset of these cancers develops
from lower-grade gliomas and can thus be clinically classified as
"secondary," whereas some glioblastomas occur with no prior
evidence of a lower-grade tumor and can be clinically classified as
"primary." Substantial genetic differences between these groups of
glioblastomas have been identified previously. We used large-scale
expression analyses to identify glioblastoma-associated genes (GAG) that are
associated with a more malignant phenotype via comparison with lower-grade
astrocytomas. We have further defined gene expression differences that
distinguish primary and secondary glioblastomas. GAGs distinct to primary or
secondary tumors provided information on the heterogeneous properties and
apparently distinct oncogenic mechanisms of these tumors. Secondary GAGs
primarily include mitotic cell cycle components, suggesting the loss of
function in prominent cell cycle regulators, whereas primary GAGs highlight
genes typical of a stromal response, suggesting the importance of
extracellular signaling. Immunohistochemical staining of glioblastoma tissue
arrays confirmed expression differences. These data highlight that the
development of gene pathway-targeted therapies may need to be specifically
tailored to each subtype of glioblastoma. (Cancer Res 2006; 66(1): 159-67).
PMID: 16397228 [PubMed - as supplied by publisher]
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Motexafin-gadolinium taken up in vitro by at least 90% of
glioblastoma cell nuclei.
De
Stasio G, Rajesh
D, Ford
JM, Daniels
MJ, Erhardt
RJ, Frazer
BH, Tyliszczak
T, Gilles
MK, Conhaim
RL, Howard
SP, Fowler
JF, Esteve
F, Mehta
MP.
Department of Physics and Synchrotron Radiation Center, University of
Wisconsin-Madison, Stoughton, Winconsin 53589, USA. pupa@src.wisc.edu
PURPOSE: We present preclinical data showing the in vitro intranuclear
uptake of motexafin gadolinium by glioblastoma multiforme cells, which could
serve as a prelude to the future development of radiosensitizing techniques,
such as gadolinium synchrotron stereotactic radiotherapy (GdSSR), a new
putative treatment for glioblastoma multiforme. EXPERIMENTAL DESIGN: In this
approach, administration of a tumor-seeking Gd-containing compound would be
followed by stereotactic external beam radiotherapy with 51-keV photons from
a synchrotron source. At least two criteria must be satisfied before this
therapy can be established: Gd must accumulate in cancer cells and spare the
normal tissue; Gd must be present in almost all the cancer cell nuclei. We
address the in vitro intranuclear uptake of motexafin gadolinium in this
article. We analyzed the Gd distribution with subcellular resolution in four
human glioblastoma cell lines, using three independent methods: two novel
synchrotron spectromicroscopic techniques and one confocal microscopy. We
present in vitro evidence that the majority of the cell nuclei take up
motexafin gadolinium, a drug that is known to selectively reach glioblastoma
multiforme. RESULTS: With all three methods, we found Gd in at least 90% of
the cell nuclei. The results are highly reproducible across different cell
lines. The present data provide evidence for further studies, with the goal
of developing GdSSR, a process that will require further in vivo animal and
future clinical studies.
PMID: 16397044 [PubMed - in process]
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Dysplastic ganglioneurocytoma with increased glucose
metabolism: a heterotopia with unique histopathology.
Yako
K, Nakazato
Y, Hirato
J, Tosaka
M, Ohtani
T, Ishiuchi
S, Saito
N, Sasaki
T.
Department of Neurosurgery, Gunma University Graduate School of Medicine,
Gunma, Japan.
A 1 year and 7 month old boy was incidentally found to have an intracranial
mass lesion at the frontal base. The mass was 45 x 54 x 47 mm in size,
contained a calcification, a few small cysts, and extended downward to the
sphenoid sinus and upper pharynx. The signal intensity of the lesion on
magnetic resonance imaging was iso-high on T1-weighted images, and slightly
high on T2-weighted images, and it did not enhance with gadolinium
injection. Although there was no obvious mass effect,
18F-fluorode-oxyglucose positron-emission tomography demonstrated increased
uptake, and a surgical resection was performed suspecting a neoplastic
lesion. Histologically, the lesion consisted of small to large anomalous
neurons and glial cells but lacked normal cortical architecture. Cellularity
was high in some portion with MIB-1 labeling index of 2%, but there was no
cellular atypia suggestive of neoplasm. Therefore, this lesion was
considered to be a dysplasia that does not fit into the previously described
entity. We suggest this lesion would be better described as dysplastic
ganglioneurocytoma.
Publication Types:
PMID: 16320821 [PubMed - indexed for MEDLINE]
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Recurrence and increased proliferation rate of a solitary
fibrous tumor in the central nervous system--case report and review of the
literature.
Ritz
R, Roser
F, Bornemann
A, Merkle
M, Freudenstein
D.
Department of Neurosurgery, University Hospital Tubingen, Hoppe-Seyler-Strasse
3, 72076 Tubingen, Germany. rainer.ritz@med.uni-tuebingen.de
Meningeal solitary fibrous tumors (SFTs) were at first estimated as rare
benign tumors which can be cured by total resection. To date, only 37
patients with intracranial SFTs have been reported. Therefore, the natural
history of this tumor entity needs more enlightenment. The authors report a
case of a 77-year-old female in whom a SFT with infiltration of the
transversal sinus was subtotally resected. After a short time, interval
tumor recurrence was seen, 2 years and 6 months later second surgery was
performed. Immunohistologically, in both specimens typical features for SFT
with positivity for CD34, vimentin and BCL-2 and negative for epithelial
membrane antigen was seen. No signs for malignancy occurred in the second
resection. Notably the MIB-1 index increased from 1 to 5%. In conclusion,
consequent long-time follow-up for SFTs are necessary, especially after
incomplete tumor resection.
Publication Types:
PMID: 16320818 [PubMed - indexed for MEDLINE]
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-
Ginseng saponin metabolite suppresses phorbol
ester-induced matrix metalloproteinase-9 expression through inhibition of
activator protein-1 and mitogen-activated protein kinase signaling pathways
in human astroglioma cells.
Jung
SH, Woo
MS, Kim
SY, Kim
WK, Hyun
JW, Kim
EJ, Kim
DH, Kim
HS.
Department of Neuroscience, Ewha Institute of Neuroscience, College of
Medicine, Ewha Woman's University, Seoul, South Korea.
Aberrant expression of matrix metalloproteinase-9 (MMP-9) is implicated in
the process of invasion and angiogenesis of malignant tumors as well as in
inflammatory diseases of the CNS. Therefore, the development of compounds
that can inhibit or suppress MMP-9 is required to treat brain tumors. We
investigated the effects of a ginseng saponin metabolite, compound K
(20-O-(beta-D-glucopyranosyl)-20(S)-protopanaxadiol), on MMP-9 expression in
human astroglioma cells. Compound K significantly inhibited the secretion
and protein expression of MMP-9 induced by PMA. The inhibitory effect of
compound K on MMP-9 expression correlated with decreased MMP-9 mRNA levels
and suppression of MMP-9 promoter activity. The compound K-mediated
inhibition of MMP-9 gene expression appears to occur via AP-1 because its
DNA-binding and transcriptional activities were suppressed by the agent.
Furthermore, compound K significantly repressed the PMA-mediated activation
of p38 MAPK, ERK and JNK, which are upstream modulators of AP-1. Finally,
compound K inhibited the in vitro invasiveness of glioma cells. Therefore,
inhibition of MMP-9 expression by compound K might have therapeutic
potential for controlling the growth and invasiveness of brain tumors.
Copyright 2005 Wiley-Liss, Inc.
PMID: 16049964 [PubMed - indexed for MEDLINE]
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-
Radiation dosimetry predicts IQ after conformal radiation
therapy in pediatric patients with localized ependymoma.
Merchant
TE, Kiehna
EN, Li
C, Xiong
X, Mulhern
RK.
Division of Radiation Oncology, St. Jude Children's Research Hospital,
Memphis, TN 38105, USA. thomas.merchant@stjude.org
PURPOSE: To assess the effects of radiation dose-volume distribution on the
trajectory of IQ development after conformal radiation therapy (CRT) in
pediatric patients with ependymoma. METHODS AND MATERIALS: The study
included 88 patients (median age, 2.8 years +/- 4.5 years) with localized
ependymoma who received CRT (54-59.4 Gy) that used a 1-cm margin on the
postoperative tumor bed. Patients were evaluated with tests that included IQ
measures at baseline (before CRT) and at 6, 12, 24, 36, 48, and 60 months.
Differential dose-volume histograms (DVH) were derived for total-brain,
supratentorial-brain, and right and left temporal-lobe volumes. The data
were partitioned into three dose intervals and integrated to create
variables that represent the fractional volume that received dose over the
specified intervals (e.g., V(0-20 Gy), V(20-40 Gy), V(40-65 Gy)) and modeled
with clinical variables to develop a regression equation to estimate IQ
after CRT. RESULTS: A total of 327 IQ tests were performed in 66 patients
with infratentorial tumors and 20 with supratentorial tumors. The median
follow-up was 29.4 months. For all patients, IQ was best estimated by age
(years) at CRT; percent volume of the supratentorial brain that received
doses between 0 and 20 Gy, 20 and 40 Gy, and 40 and 65 Gy; and time (months)
after CRT. Age contributed significantly to the intercept (p > 0.0001),
and the dose-volume coefficients were statistically significant (V(0-20 Gy),
p = 0.01; V(20-40 Gy), p < 0.001; V(40-65 Gy), p = 0.04). A similar model
was developed exclusively for patients with infratentorial tumors but not
supratentorial tumors. CONCLUSION: Radiation dosimetry can be used to
predict IQ after CRT in patients with localized ependymoma. The specificity
of models may be enhanced by grouping according to tumor location.
PMID: 16115736 [PubMed - indexed for MEDLINE]
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O-methylguanine DNA methyltransferase and p53 status
predict temozolomide sensitivity in human malignant glioma cells.
Hermisson
M, Klumpp
A, Wick
W, Wischhusen
J, Nagel
G, Roos
W, Kaina
B, Weller
M.
Laboratory of Molecular Neuro-Oncology, Department of General Neurology,
Hertie Institute for Clinical Brain Research, University of Tubingen, School
of Medicine, Tubingen, Germany.
Temozolomide (TMZ) is a methylating agent which prolongs survival when
administered during and after radiotherapy in the first-line treatment of
glioblastoma and which also has significant activity in recurrent disease.
O(6)-methylguanine DNA methyltransferase (MGMT) is a DNA repair enzyme
attributed a role in cancer cell resistance to O(6)-alkylating agent-based
chemotherapy. Using a panel of 12 human glioma cell lines, we here defined
the sensitivity to TMZ in acute cytotoxicity and clonogenic survival assays
in relation to MGMT, mismatch repair and p53 status and its modulation by
dexamethasone, irradiation and BCL-X(L). We found that the levels of MGMT
expression were a major predictor of TMZ sensitivity in human glioma cells.
MGMT activity and clonogenic survival after TMZ exposure are highly
correlated (p < 0.0001, r(2) = 0.92). In contrast, clonogenic survival
after TMZ exposure does not correlate with the expression levels of the
mismatch repair proteins mutS homologue 2, mutS homologue 6 or post-meiotic
segregation increased 2. The MGMT inhibitor O(6)-benzylguanine sensitizes
MGMT-positive glioma cells to TMZ whereas MGMT gene transfer into
MGMT-negative cells confers protection. The antiapoptotic BCL-X(L) protein
attenuates TMZ cytotoxicity in MGMT-negative LNT-229 but not in
MGMT-positive LN-18 cells. Neither ionizing radiation (4 Gy) nor clinically
relevant concentrations of dexamethasone modulate MGMT activity or TMZ
sensitivity. Abrogation of p53 wild-type function strongly attenuates TMZ
cytotoxicity. Conversely, p53 mimetic agents designed to stabilize the
wild-type conformation of p53 sensitize glioma cells for TMZ cytotoxicity.
Collectively, these results suggest that the determination of MGMT
expression and p53 status will help to identify glioma patients who will or
will not respond to TMZ.
PMID: 16405512 [PubMed - as supplied by publisher]
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-
Brain Metastases from Hepatocellular Carcinoma in US
Patients.
Seinfeld
J, Wagner
AS, Kleinschmidt-Demasters
BK.
Department of Neurosurgery, University of Colorado Health Sciences Center,
Denver, CO, USA.
Hepatocellular carcinoma (HCC) is a disease on the rise in the United
States, due to the epidemic of hepatitis C-induced liver disease. Better
chemotherapy options, aggressive surgery, and liver transplantation have led
to improved patient survival and an increase in late-appearing, distant
metastases from HCC. Brain metastases, although formerly thought of as rare
manifestations of HCC, may be more likely to come to clinical and
pathological attention than extrahepatic metastases in other sites since
they often produce clinical symptoms that necessitate neurosurgical
intervention and metastasis removal. In addition, brain metastases from HCC
are frequently associated with mass-producing hemorrhage, further requiring
evacuation. Hence, pathologists are relatively more likely to encounter
brain metastases from HCC as surgical specimens than metastases from HCC to
some other common sites of spread, such as bone, lymph nodes, or adrenal.
Brain metastases from HCC are being increasingly documented in areas of the
world with high endemic rates such as Asia, but thus far have only very
rarely been reported in patients native to the United States. We describe
our institution's experience with three Caucasian US males, two with
hepatitis C as risk factors, who developed metastatic HCC to the brain. We
expect clinicians and pathologists will encounter more patients with HCC and
extrahepatic metastases, particularly those to brain, in the near future.
PMID: 16402279 [PubMed - in process]
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-
Tamoxifen paradoxically decreases Paclitaxel deposition
into cerebrospinal fluid of brain tumor patients.
Chen
J, Balmaceda
C, Bruce
JN, Sisti
MB, Huang
M, Cheung
YK, McKhann
GM, Goodman
RR, Fine
RL.
Experimental Therapeutics Program, Division of Medical Oncology, College of
Physicians and Surgeons of Columbia University, New York, NY, USA, rlf20@columbia.edu.
Background: P-glycoprotein (Pgp) mediates, in part, resistance to natural
product chemotherapy drugs which constitute over half of the available drugs
for cancer treatment. Tamoxifen (TAM) enhances intracellular deposition of
natural product chemotherapy in human cell lines by inhibition of Pgp. Pgp
is highly expressed in the choroid plexus and is thought to be a key
component of the blood-cerebrospinal fluid barrier (BCSFB). We conducted a
prospective, randomized study to assess if Pgp inhibition by TAM alters
deposition of paclitaxel in cerebrospinal fluid (CSF).Methods: Ten patients
with either primary or metastatic brain tumors were randomized to:
paclitaxel alone (175 mg/m(2)/IV) or a course of TAM (160 mg/m(2) PO BID on
Days 1-5) followed by paclitaxel (175 mg/m(2)/IV on Day 5). CSF and plasma
samples were obtained following paclitaxel infusion; paclitaxel and TAM
concentrations were measured by high-performance liquid chromatography
assays.Results: Paclitaxel was detected in the CSF of six of the 10
patients. Peak CSF paclitaxel concentrations of the paclitaxel and
paclitaxel-TAM groups ranged between 3.5-57.4 and 2.3-24.6 nM, respectively.
Though there was a 2.4-fold higher mean CSF paclitaxel concentration and a
3.7-fold higher median peak CSF:plasma paclitaxel ratio for those who
received paclitaxel alone as compared to combined paclitaxel-TAM, it was not
statistically significant (P = 0.22). In one patient enrolled to both arms,
higher CSF concentrations of paclitaxel and higher paclitaxel CSF: plasma
ratios were observed when given paclitaxel alone.Conclusions: The trend
towards lower paclitaxel CSF concentrations when given with TAM is
consistent with the published finding that Pgp's localization in the
endothelial cells of the choroid plexus works in an opposite direction and
keeps drugs in the CSF. Thus, agents which inhibit Pgp, such as TAM, may
increase efflux of Pgp substrates out of the BCSFB and may paradoxically
lower CSF concentrations of natural product chemotherapy drugs.
Conceptually, this finding implies that the Pgp in the BBB and BCSFB keeps
natural toxins such as paclitaxel, from entering the brain (BBB) and, if
they do enter the brain, keeps them in the CSF (BCSFB) where they may be
less harmful than if they re-entered the brain. Thus, our work supports this
novel idea and adds to the understanding of the functions of the BCSFB.
PMID: 16402278 [PubMed - in process]
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-
The Effects of Antisense AKT2 RNA on the Inhibition of
Malignant Glioma Cell Growth in vitro and in vivo.
Pu
P, Kang
C, Li
J, Jiang
H, Cheng
J.
Department of Neurosurgery, Tianjin Medical University General Hospital,
Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin,
People's Republic of China, pupeiyu33@hotmail.com, peiyupu@aol.com.
The oncogenic role of AKT2 in the development of malignant gliomas was
examined by using antisense approach. AKT2 expression was significantly
inhibited in rat C6 glioma cells transfected with antisense AKT2 cDNA
construct (LXSN-AS-AKT2). In addition, the transfected cells proliferated at
a lowered level and apoptosis was induced. For in vivo studies, parental C6
cells and C6 cells transfected with LXSN-AS-AKT2 were implanted
stereotactically into the right caudate nucleus of SD rats (control C6 group
and transfected group). The rats bearing well-established C6 gliomas were
treated with LXSN-AS-AKT2 DNA or LXSN (empty vector)-lipofectamine complexes
intratumorally (treated group and control treated group). The mean survival
of the rats of control C6 group and treated control group was 17.8+/-0.92
days and 17.5+/-1.10 days, respectively. The mean survival of the rats of
transfected and treated group was significantly prolonged. MR images
revealed distinct cerebral tumor foci in all of the control rats, whereas
four rats in transfected group did not develop tumors and the tumor foci in
five rats of treated group were regressed and disappeared. The expression of
AKT2, PCNA, MMP2/9, and cyclin D were inhibited in the tumors of rats in
transfected and treated groups while GFAP expression was increased. These
results suggest that AKT pathway may play an important role in the
development and progression of gliomas. Anti-AKT approach will open a new
perspective for a targeted molecular therapy of malignant gliomas.
PMID: 16402276 [PubMed - as supplied by publisher]
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Diffusion tensor imaging of intraaxial tumors at the
cervicomedullary and pontomedullary junctions. Report of two cases.
Phillips
NS, Sanford
RA, Helton
KJ, Boop
FA, Zou
P, Tekautz
T, Gajjar
A, Ogg
RJ.
Department of Radiological Sciences, St Jude Children's Research Hospital,
Memphis, Tennessee 38105, USA.
Brainstem gliomas are a heterogeneous group of lesions that account for 15%
of all pediatric tumors of the central nervous system. Diagnosis and
treatment planning for these tumors is based on the observation of Epstein
and Farmer that the growth of lesions with low malignant potential is
limited by the anatomical structures of the brainstem. Surgery is offered
only to those patients with a high probability of harboring a low-grade
tumor, because the attendant risk for significant morbidity outweighs the
therapeutic benefit of debulking the tumor in cases of high-grade tumors.
The authors report two cases that highlight the potential of diffusion
tensor (DT) imaging to identify local white matter tracts in the pons,
medulla, and cervical cord and to improve the preoperative assessment of
low-grade gliomas. Preoperative DT imaging in both cases demonstrated that
the white matter tracts were displaced by the bulk of the low-grade tumors
but were structurally preserved. Intraoperative and neurological findings
were consistent with the preoperative interpretation of the DT images. These
cases demonstrate that DT imaging is a useful method for visualizing the
relationship between tumor and normal brainstem white matter architecture,
as well as for improving the surgical evaluation and management of pediatric
brainstem tumors.
Publication Types:
PMID: 16383256 [PubMed - indexed for MEDLINE]
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Usefulness of constructive interference in steady-state
magnetic resonance imaging in the presurgical examination for lumbosacral
lipoma.
Hashiguchi
K, Morioka
T, Fukui
K, Miyagi
Y, Mihara
F, Yoshiura
T, Nagata
S, Sasaki
T.
Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu
University, Japan.
OBJECT: The aim of this study was to evaluate three-dimensional Fourier
transformation constructive interference in steady-state (CISS) imaging as a
preoperative investigation of anatomical structures around the lumbosacral
lipoma for surgical untethering of the spinal cord and debulking of the
lipoma. METHODS: The CISS imaging was used to visualize neural structures
around the lumbosacral lipoma in 13 cases and was compared with conventional
magnetic resonance imaging. In all cases, CISS images demonstrated the fine
structure of the spinal cord and nerve roots, with good contrast between
subarachnoid spaces and lipomas. The CISS findings were closely correlated
with microscopic observation and electrophysiological investigation during
surgery. In three of eight patients whose CISS images demonstrated abundant
nerve roots embedded in the lipoma, untethering of the conus medullaris was
not satisfactorily achieved. These three cases had obliteration of the
subarachnoid space by the lipomas at the bilateral sides of the cord. In two
cases with the vertebral misalignments scoliosis and lordosis, curvilinear
reconstruction of CISS images along the spinal cord clearly demonstrated a
neuroanatomy around the complicated lipomas. CONCLUSIONS: Using CISS imaging
is useful for establishing precise neuroanatomical information around
lumbosacral lipomas and for predicting the level of surgical difficulty.
Publication Types:
PMID: 16383253 [PubMed - indexed for MEDLINE]
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Immature teratomas of the central nervous system: is
adjuvant therapy mandatory?
Phi
JH, Kim
SK, Park
SH, Hong
SH, Wang
KC, Cho
BK.
Department of Neurosurgery, Seoul National University College of Medicine,
Clinical Research Institute, Seoul National University Hospital, Korea.
OBJECT: Immature teratomas of the central nervous system (CNS) are rare
neoplasms. Although adjuvant therapy is generally recommended after
resection, the exact role of each therapeutic modality is not yet
established. The purpose of this study was to analyze the
clinicopathological correlation and the role of resection to define the
optimal treatment modalities for immature teratomas of the CNS. METHODS:
Between 1987 and 2002, eight patients underwent radical surgery for a lesion
diagnosed as a CNS immature teratoma at the authors' institution. The
clinical courses of these patients and the pathological features of their
tumors were retrospectively reviewed. Gross-total resection (GTR) was
achieved in six patients at the initial operation. The mean follow-up period
was 75 months. Two patients received postoperative adjuvant therapies and
two patients did not, against medical advice. None of the four patients
experienced recurrence after long-term follow up. Another four patients, all
of whom underwent GTR of the tumor, did not receive adjuvant therapy as part
of a prospective treatment scheme. One of them exhibited early recurrence
and metastasis. The tumor had pathological features denoting a high-grade
(Norris Grade III) lesion and neurocytomatous differentiation. CONCLUSIONS:
Aggressive resection seems to be of utmost importance in the treatment of
immature teratomas of the CNS. Adjuvant chemotherapy and radiotherapy can be
deferred if GTR is achieved in low-grade, immature teratomas, but adjuvant
therapies may be warranted for high-grade ones.
Publication Types:
PMID: 16383251 [PubMed - indexed for MEDLINE]
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Historical vignette: Harvey Cushing and Oskar Hirsch:
early forefathers of modern transsphenoidal surgery.
Liu
JK, Cohen-Gadol
AA, Laws
ER Jr, Cole
CD, Kan
P, Couldwell
WT.
Department of Neurosurgery, University of Utah School of Medicine, Salt Lake
City 84132, USA.
The transnasal transsphenoidal approach is the preferred route for removal
of most lesions of the sella turcica. The concept of transnasal surgery
traversing the sphenoid sinus to reach the sella has existed for nearly a
century. A comprehensive historical overview of the evolution of
transsphenoidal surgery has been reported previously. In the present
vignette, the authors focus on transsphenoidal surgery in the early 1900s,
particularly on the methods advocated by Harvey Cushing and Oskar Hirsch,
two prominent pituitary surgeons who pioneered the transsphenoidal
technique. Cushing championed the sublabial approach, whereas Hirsch was the
master of the endonasal route. Coincidentally, both surgeons independently
performed the submucous septal resection for the first time on June 4, 1910.
Although Cushing's and Hirsch's approaches were predicated on the work of
their predecessors, their transsphenoidal procedures became the two most
popular techniques and, for future generations of pituitary surgeons, laid
the foundation for modem transsphenoidal surgery. In this comparative
analysis, the authors compare the operative nuances of the approaches of
Cushing and Hirsch and describe the contributions of these pioneers to
modern transsphenoidal surgery.
Publication Types:
Personal Name as Subject:
PMID: 16381201 [PubMed - indexed for MEDLINE]
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Rathke cleft cyst of the sphenoid bone and nasopharynx.
Case illustration.
Ben
Hamouda K, Khaldi
M, Jemel
H, Ben
Ismail M, Zemmel
I.
Department of Neurosurgery, National Institute of Neurology, Tunis, Tunisia.
kbenhamouda@lycos.com
Publication Types:
PMID: 16381200 [PubMed - indexed for MEDLINE]
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Arachnoid cyst with associated arachnoiditis developing
after subarachnoid hemorrhage. Case report.
Tumialan
LM, Cawley
CM, Barrow
DL.
Department of Neurosurgery, Emory University School of Medicine, Atlanta,
Georgia, USA.
The authors report the case of a 53-year-old woman in whom a T1-T2 spinal
arachnoid cyst with associated arachnoiditis developed, compressing the
thoracic spinal cord 1 year after the patient had suffered a Hunt and Hess
Grade IV subarachnoid hemorrhage (SAH). Development of spinal arachnoiditis
with or without an arachnoid cyst is a rare complication of aneurysmal SAH.
Risk factors may include posterior circulation aneurysms, the extent and
severity of the hemorrhage, and the need for cerebrospinal fluid diversion.
Surgical drainage, shunt placement, or cyst excision, when possible, is the
mainstay of treatment.
Publication Types:
PMID: 16381198 [PubMed - indexed for MEDLINE]
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Rapid expansion of a previously asymptomatic
subependymoma. Case report.
Laxton
AW, Shannon
P, Nag
S, Farb
RI, Bernstein
M.
Division of Neurosurgery, Toronto Western Hospital, University Health
Network, University of Toronto, Ontario, Canada.
This 39-year-old man presented with a 6-month history of occipital
headaches. Magnetic resonance imaging revealed an irregularly shaped fourth
ventricle mass. One month after his initial presentation, he was admitted to
the hospital with significant tumor expansion and clinical deterioration. A
posterior fossa craniectomy was performed and the mass was resected.
Histopathological analysis of this tumor showed central necrosis with
associated edema in an otherwise typical and benign-appearing subependymoma.
To the authors' knowledge, this is the first reported case of rapid,
nonhemorrhagic expansion associated with necrosis in a previously
asymptomatic subependymoma.
Publication Types:
PMID: 16381197 [PubMed - indexed for MEDLINE]
| 21: Oncogene.
2006 Jan 9; [Epub ahead of print] |
|
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Linking DNA damage to medulloblastoma tumorigenesis in
patched heterozygous knockout mice.
Pazzaglia
S, Tanori
M, Mancuso
M, Rebessi
S, Leonardi
S, Di
Majo V, Covelli
V, Atkinson
MJ, Hahn
H, Saran
A.
1Biotechnology Unit, ENEA CR-Casaccia, Rome, Italy.
Hemizygous Ptc1 mice have many features of Gorlin syndrome, including
predisposition to medulloblastoma development. Ionizing radiation synergize
with Ptc1 mutation to induce medulloblastoma only in neonatally exposed
mice. To explore the mechanisms underlying age-dependent susceptibility, we
irradiated Ptc(neo67/+) mice at postnatal day 1 (P1) or 10 (P10). We
observed a dramatic difference in medulloblastoma incidence, which ranged
from 81% in the cerebellum irradiated at P1 to 3% in the cerebellum
irradiated at P10. A stricking difference was also detected in the frequency
of cerebellar preneoplastic lesions (100 versus 14%). Our data also show
significantly lower induction of apoptosis in the cerebellum of
medulloblastoma-susceptible (P1) compared to -resistant (P10) mice, strongly
suggesting that medulloblastoma formation in Ptc1 mutants may be associated
with resistance to radiation-induced cell killing. Furthermore, in marked
contrast with P10 mice, cerebellum at P1 displays substantially increased
activation of the cell survival-promoting Akt/Pkb protein, and markedly
decreased p53 levels in response to radiation-induced genotoxic stress.
Overall, these results show that developing cerebellar granule neuron
precursors' (CGNPs) radiosensitivity to radiation-induced cell death
increases with progressing development and inversely correlates with their
ability to neoplastically transform.Oncogene advance online publication, 9
January 2006; doi:10.1038/sj.onc.1209032.
PMID: 16407852 [PubMed - as supplied by publisher]
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| 22: Oncogene.
2006 Jan 9; [Epub ahead of print] |
|
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CXCR4 expression mediates glioma cell invasiveness.
Ehtesham
M, Winston
JA, Kabos
P, Thompson
RC.
[1] 1Department of Neurological Surgery, Vanderbilt University Medical
Center, Nashville, TN, USA [2] 2Department of Cancer Biology, Vanderbilt
University Medical Center, Nashville, TN, USA [3] 3Vanderbilt Ingram Cancer
Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Glioblastoma multiforme is a highly invasive tumor bearing a dismal
prognosis. Experimental strategies that focus on the specific biological
cues governing the invasive capacity of these tumors may hold significant
therapeutic promise. In this context, we describe the in vitro and in vivo
association of the cell surface chemokine receptor, CXCR4, with the
development of an invasive phenotype in malignant glioblastoma. We
demonstrate that invasive populations of glioma cells overexpress CXCR4 at
the message and protein levels, and that this expression ranges from 25- to
89-fold higher than that found in noninvasive tumor cells. Furthermore,
neutralization of CXCR4 significantly impairs the in vitro invasive capacity
of malignant glial cells. In addition, glioma cells secrete CXCL12 and
demonstrate robust invasive capacity toward a CXCL12 gradient in vitro.
These findings underscore the importance of CXCR4 as a potential therapeutic
target for the treatment of invasive glioblastoma.Oncogene advance online
publication, 9 January 2006; doi:10.1038/sj.onc.1209302.
PMID: 16407848 [PubMed - as supplied by publisher]
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Low-Grade Gliomas: Dynamic Susceptibility-weighted
Contrast-enhanced Perfusion MR Imaging--Prediction of Patient Clinical
Response.
Law
M, Oh
S, Babb
JS, Wang
E, Inglese
M, Zagzag
D, Knopp
EA, Johnson
G.
1 Departments of Radiology, Pathology, and Neurosurgery, New York University
Medical Center, MRI Department, Schwartz Building, Basement HCC, 530 First
Ave, New York, NY 10016.
Purpose: To determine retrospectively whether relative cerebral blood volume
(CBV) measurements can be used to predict clinical response in patients with
low-grade gliomas. Materials and Methods: Approval for this retrospective
HIPAA-compliant study was obtained from the Institutional Board of Research
Associates, with waiver of informed consent. Thirty-five patients (23 male
and 12 female patients; median age, 39 years; range, 4-80 years) with
histologically diagnosed low-grade gliomas (21 low-grade astrocytomas and 14
low-grade oligodendrogliomas and low-grade mixed oligoastrocytomas) were
examined with dynamic susceptibility-weighted contrast material-enhanced
perfusion magnetic resonance (MR) imaging. Wilcoxon tests were used to
compare patients in different response categories (complete response,
stable, progressive, death) with respect to baseline relative CBV.
Kaplan-Meier survival curves, log-rank tests, and Weibull survival models
were used to characterize and evaluate the association of baseline relative
CBV with time to progression. Tumor volumes and relative CBV measurements
were obtained at initial examination and follow-up. Results: Lesions with
relative CBV less than 1.75 had a median time to progression of 4620 days
+/- 433 (standard deviation), and lesions with relative CBV more than 1.75
had a median time to progression of 245 days +/- 62. Patients who had an
adverse event (either death or progression) had significantly higher (P =
.003) relative CBV than did patients without adverse events (either complete
response or stable disease). Lesions with low baseline relative CBV had
stable tumor volumes at follow-up over time, whereas those with high
baseline relative CBV (>1.75) had progressively increasing tumor volumes
over time. Conclusion: Dynamic susceptibility-weighted contrast-enhanced
perfusion MR imaging can help to identify low-grade gliomas that will
progress rapidly and a subset of low-grade gliomas that have a propensity
for malignant transformation. (c) RSNA, 2006.
PMID: 16396838 [PubMed - as supplied by publisher]
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