| 1: Cancer. 2005 Jun 24; [Epub
ahead of print] |
|
-
The prognostic relevance of molecular alterations in
glioblastomas for patients age < 50 years.
Korshunov
A, Sycheva
R, Golanov
A.
Department of Neuropathology, N. N. Burdenko Neurosurgical Institute,
Moscow, Russia.
BACKGROUND: In patients with glioblastoma, age < 50 years was identified
as a consistent prognostic variable. In addition, the prognosis for these
patients may be determined by a complex interaction between age and genetic
alterations. The objective of the current study was the molecular analysis
of glioblastomas from adult patients age < 50 years ("young
adults"). METHODS: The authors analyzed a set of 189 glioblastoma
specimens. Fluorescence in situ hybridization was performed with a set of 10
chromosome probes (1p36, 1q25, centomere probe 7 [CEP7], 7p12/epidermal
growth factor receptor gene (EGFR), CEP9, 9p21/p16, CEP10, 10q23/phosphatase
and tesnin homolog gene (PTEN), 19p13, and 19q13). RESULTS: Patient age <
40 years was associated strongly with a favorable prognosis. Patients age
>/= 40 years frequently showed EGFR amplification, loss of 9p, loss of
10q, and gain of chromosome 19. The patients with - 19q were age < 40
years. The survival was shorter for patients with EGFR amplification, gain
of chromosome 7, loss of 9p, loss of 10q, and gain of chromosome 19. In
contrast, the patients who had tumors with gain of chromosome 9 or loss of
19q had more favorable outcomes. In a multivariate analysis, gain of
chromosome 9 (P = 0.026) and loss of 10q23 (P = 0.007) reached the level of
independent prognostic value. In addition, the prognostic value of molecular
alterations in patients age < 40 years and patients age > 40 years
were examined separately. Consequently, EGFR amplification, - 9p, and + 9
were significant for both age groups, whereas gain of chromosome 7 and loss
of 10q showed clinical importance only among patients age > 40 years.
CONCLUSIONS: Adult patients age < 50 years with glioblastoma had
molecularly distinct disease, and the age-dependent heterogeneity seen on
the chromosomal level also applied at the clinical level. Cancer 2005. (c)
2005 American Cancer Society.
PMID: 15981281 [PubMed - as supplied by publisher]
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| 2: Clin
Cancer Res. 2005 Jan 1;11(1):249-58. |
|
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Minichromosome maintenance protein 3 elicits a
cancer-restricted immune response in patients with brain malignancies and is
a strong independent predictor of survival in patients with anaplastic
astrocytoma.
Soling
A, Sackewitz
M, Volkmar
M, Schaarschmidt
D, Jacob
R, Holzhausen
HJ, Rainov
NG.
Department of Neurosurgery, Martin Luther University Halle-Wittenberg,
Halle, Germany. ariane.soeling@medizin.uni-halle.de
PURPOSE: The identification of new molecular markers in astrocytic tumors
may help to understand the biology of these tumors in more detail.
Informative tumor markers may represent prognostic factors for response to
therapy and outcome as well as potential targets for novel anticancer
therapies. EXPERIMENTAL DESIGN: Tumor-associated antigens were identified by
immunoscreening of a human glioma cDNA expression library with allogeneic
sera from patients with diffuse astrocytoma (WHO grades 2-4). The expression
of one of the identified antigens, the replication licensing factor
minichromosome maintenance protein 3 (MCM3), was analyzed by
immunohistochemistry in 142 primary and 27 recurrent astrocytomas (WHO
grades 2-4). In addition, 98 serum specimens from patients with primary and
secondary brain malignancies and 30 serum specimens from healthy controls
were examined by serologic immunoscreening for immunoreactivity with MCM3.
RESULTS: MCM3 is overexpressed in human astrocytic tumors and elicits a
cancer-restricted humoral immune response in 9.3% (9 of 97) of patients with
brain tumors (n = 95) and brain metastases (n = 2) but not in healthy
controls. Expression of MCM3 in diffuse astrocytoma is significantly
associated with age (P < 0.001), histologic grade (P < 0.001), time to
recurrence (P = 0.01), and expression of the proliferation marker Ki-67 (P
< 0.001) but not with sex (P = 0.800). Univariate and multivariate Cox
regression analysis confirmed MCM3 expression as an independent predictor of
poor outcome in astrocytoma patients (P < 0.001 for both). CONCLUSIONS:
MCM3 may represent a glioma-associated antigen with significant prognostic
role as well as have some potential as a target for cancer-directed therapy.
PMID: 15671553 [PubMed - indexed for MEDLINE]
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| 3: Int
J Cancer. 2005 Jun 28; [Epub ahead of print] |
|
-
Ribozyme-targeting reveals the rate-limiting role of
pleiotrophin in glioblastoma.
Grzelinski
M, Bader
N, Czubayko
F, Aigner
A.
Department of Pharmacology and Toxicology, Philipps-University School of
Medicine, Marburg, Germany.
Glioblastomas (GBMs) are the most frequent malignant brain tumors with very
limited treatment options and nearly all GBM patients dying within 1 year.
Pleiotrophin (PTN, HB-GAM, HBNF, OSF-1) is a secreted growth factor that
shows mitogenic, chemotactic and transforming activity. While PTN expression
is tightly regulated during embryogenesis and very limited in normal adult
tissues, a marked PTN upregulation is seen in tumors including
glioblastomas. Targeting of the PTN receptors, ALK and RPTP-zeta, indicates
a contribution of PTN-activated signaling pathways in glioblastomas.
However, the relevance of PTN expression itself is unknown especially since,
besides PTN, at least one more growth factor, midkine (MK), signals through
ALK and is expressed in glioblastoma. Here we demonstrate the biologic
relevance of PTN in 2 glioblastoma cell lines in vitro and in vivo. We show
that stable ribozyme-targeting leads to a robust reduction of PTN mRNA and
protein levels. This results in decreased cell proliferation, cell migration
and soft agar colony formation in vitro. Comparing clonal
ribozyme-transfected cells with different residual PTN levels, we establish
a PTN gene-dose effect of glioblastoma cell proliferation. In a subcutaneous
tumor xenograft mouse model, in vivo growth is markedly reduced upon PTN
depletion, which is paralleled by decreased PTN serum levels. Furthermore,
the immunohistochemical analysis of the tumors shows reduced angiogenesis in
PTN-depleted tumors. We conclude that PTN is a rate-limiting growth factor
in glioblastoma. Since PTN is overexpressed in glioblastomas but rarely
found in normal tissue, PTN may represent an attractive therapeutic target.
(c) 2005 Wiley-Liss, Inc.
PMID: 15986444 [PubMed - as supplied by publisher]
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| 4: Int
J Cancer. 2005 Jun 28; [Epub ahead of print] |
|
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PPARgamma-dependent effects of conjugated linoleic acid
on the human glioblastoma cell line (ADF).
Cimini
A, Cristiano
L, Colafarina
S, Benedetti
E, Di
Loreto S, Festuccia
C, Amicarelli
F, Canuto
RA, Ceru
MP.
Department of Basic and Applied Biology, University of L'Aquila, L'Aquila,
Italy.
Conjugated linoleic acid (CLA) has been shown to exert beneficial effects
against carcinogenesis, atherosclerosis and diabetes. It has been
demonstrated that CLA modulates lipid metabolism through the activation of
peroxisome proliferator-activated receptors (PPARs). The PPAR family
comprises 3 closely related gene products, PPAR alpha, beta/delta and gamma,
differing for tissue distribution, developmental expression and ligand
specificity. It has also been demonstrated that activated PPARgamma results
in growth inhibition and differentiation of transformed cells. These
observations stimulated a great interest toward PPARgamma ligands as
potential anticancer drugs to be used in a differentiation therapy.
Glioblastomas are the most commonly diagnosed primary tumors of the brain in
humans. The prognosis of patients with high-grade gliomas is poor and only
marginally improved by chemotherapy. The aim of this work was to study the
effects of CLA and of a specific synthetic PPARgamma ligand on cell growth,
differentiation and death of a human glioblastoma cell line as well as on
parameters responsible for the metastatic behavior of this tumor. We
demonstrate here that CLA and PPARgamma agonist strongly inhibit cell growth
and proliferation rate and induce apoptosis. Moreover, both treatments
decrease cell migration and invasiveness. The results obtained show that CLA
acts, directly or indirectly, as a PPARgamma activator, strongly suggesting
that this naturally occurring fatty acid may be used as brain antitumor drug
and as a chemopreventive agent. Moreover, the gamma-agonist, once
experimented and validated on man, may represent a useful coadjuvant in
glioblastoma therapy and in the prevention of recurrences. (c) 2005
Wiley-Liss, Inc.
PMID: 15986437 [PubMed - as supplied by publisher]
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| 5: Int
J Cancer. 2005 Jun 28; [Epub ahead of print] |
|
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Protein phosphatase activity of PTEN inhibited the
invasion of glioma cells with epidermal growth factor receptor mutation type
III expression.
Cai
XM, Tao
BB, Wang
LY, Liang
YL, Jin
JW, Yang
Y, Hu
YL, Zha
XL.
Department of Biochemistry and Molecular Biology, Shanghai Medical College,
Fudan University, Shanghai, China.
PTEN is a major tumor suppressor gene that has been shown to inhibit cell
invasion. Its mutation has been found in 20-40% of malignant gliomas.
Meanwhile, the type III EGFR mutation (EGFRvIII), which was frequently found
in gliomas, promoted cell invasion. In the present study, the effects of
PTEN on cell invasion were investigated in U87DeltaEGFR glioblastoma cells
with EGFRvIII expression but missing PTEN. The cell invasion was
downregulated by transfection of phosphatase-active forms of PTEN (wild-type
and G129E) but not by PTEN (C124A) with an inactive phosphatase domain; the
effects were correlated with decreased tyrosine phosphatase levels of FAK at
Tyr(397), which was increased by EGFRvIII. Overexpression of FAK mutant
(Y397F) could partially mimic the effect of PTEN on cell invasion. Although
EGFRvIII increased the levels of P-Akt and PTEN eliminated it, PI-3K
inhibitors, wortmannin or Ly294002, could not decrease the cell invasion. In
conclusion, PTEN could inhibit cell invasion even in the presence of the
constitutively active EGFR; this inhibition depended on its protein
phosphatase activity, partially by dephosphorylating FAK, but not depended
on its lipid phosphatase activity. (c) 2005 Wiley-Liss, Inc.
PMID: 15986432 [PubMed - as supplied by publisher]
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| 6: Int
J Cancer. 2005 Jun 28; [Epub ahead of print] |
|
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Incidence of intracranial meningiomas in Denmark,
Finland, Norway and Sweden, 1968-1997.
Klaeboe
L, Lonn
S, Scheie
D, Auvinen
A, Christensen
HC, Feychting
M, Johansen
C, Salminen
T, Tynes
T.
Institute of Population-Based Cancer Research, Cancer Registry of Norway,
Oslo, Norway.
It has been reported that the incidence of meningioma increased in several
industrialized countries in the late 1970s and early 1980s. The aim of this
study was to evaluate the time trends in incidence of meningiomas in
Denmark, Finland, Norway and Sweden, with emphasis on the age distribution
and sex ratio. Information about cases of meningiomas in people aged 15-84
years was obtained from the cancer registries of these Nordic countries for
the years 1968-1997, and estimates of person-years at risk were calculated
from information provided by the national population registries.
Age-specific incidence rates per 100,000 and incidence rate ratios were
calculated for 3-year periods. The female:male ratios were also evaluated.
The combined incidence among men increased from 1.4 to 1.9 per 100,000
during the follow-up period, the corresponding rates for women were 2.6 and
4.5. The female:male ratio increased over time for several age groups and
was as high as 3.5:1 in the group aged 40-44 years in the latest follow-up
period (1993-1997). In summary, our results provide some support for the
idea that the introduction of computed tomography in the late 1970s has had
an impact on the detection of cases in people aged 60 and over. The decrease
in the rate or detection postmortem has affected the incidence time trend,
but it also coincides with widespread use of new imaging technologies. The
increasing trend shown for the female:male ratio in the group aged 35-59
years is consistent with the possibility that increasing use of hormones may
affect the incidence of meningiomas in women. (c) 2005 Wiley-Liss, Inc.
PMID: 15986431 [PubMed - as supplied by publisher]
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| 7: Int
J Radiat Oncol Biol Phys. 2005 Jul 15;62(4):1253. |
|
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Activation patterns of epidermal growth factor-receptor
signaling in glioblastoma multiforme: In regard to Chakravarti et al. (Int J
Radiat Oncol Biol Phys 2005;62:318-327).
Altundag
K, Altundag
O, Gunduz
E, Boruban
C.
Department of Medical Oncology, Hacettepe University Institute of Oncology,
Ankara, Turkey.
Publication Types:
PMID: 15990031 [PubMed - in process]
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| 8: Int
J Radiat Oncol Biol Phys. 2005 Jul 15;62(4):1133-9. |
|
-
Treatment of recurrent glioblastoma multiforme with
GliaSite brachytherapy.
Chan
TA, Weingart
JD, Parisi
M, Hughes
MA, Olivi
A, Borzillary
S, Alahakone
D, Detorie
NA, Wharam
MD, Kleinberg
L.
Department of Radiation Oncology, The Johns Hopkins School of Medicine,
Baltimore, MD; Department of Molecular Radiation Sciences, The Johns Hopkins
School of Medicine, Baltimore, MD.
Purpose: In this study, we assess the efficacy of GliaSite brachytherapy in
the treatment of patients with recurrent glioblastoma multiforme (GBM).
Methods and Materials: Between 1999 and 2004, 24 patients with recurrent
glioblastoma multiforme were treated with the GliaSite Radiation Therapy
System (RTS). The GliaSite is an inflatable balloon catheter that is placed
in the resection cavity at the time of surgical resection. Low-dose-rate
radiation is then delivered locally by temporarily inflating the balloon
with an aqueous solution of organically bound (125)I (Iotrex [sodium
3-((125)I)-iodo-4-hydroxybenzenesulfonate]). Patients at the Johns Hopkins
Hospital with recurrent GBM, who were previously treated with surgery and
external beam radiotherapy, underwent surgical resection followed by
GliaSite balloon implantation. Subsequently, the patients received radiation
therapy using the GliaSite to a mean dose of 53.1 Gy. Ten patients were
male, and 14 patients were female. The mean age was 48.1 years. All patients
had pathologically confirmed recurrent GBM. The median Karnofsky performance
status (KPS) was 80. Median follow-up time was 21.8 months. Results: At the
time of analysis, 18 patients (75%) had died; 6 patients (25%) were alive.
Median survival from diagnosis for all patients was 23.3 months. Median
survival after GliaSite brachytherapy was 9.1 months. Patients with a KPS
>/=70 had a median survival of 9.3 months, whereas patients with a KPS
<70 had a median survival of 3.1 months (p < 0.003). Survival was not
significantly different between patients receiving 45 Gy and patients
receiving a dose greater than 45 Gy. Acute side effects were minor,
consisting of mild nausea and/or headache. One patient developed a wound
infection. No incidents of meningitis were observed. Late sequelae were
rare, but 2 incidents of symptomatic radiation necrosis were observed. One
patient developed transient expressive aphasia. Conclusions: GliaSite
radiotherapy confers a prolongation of survival in patients with recurrent
glioblastoma multiforme compared to historical controls with recurrent GBM.
GliaSite therapy leads to a favorable survival outcome of 9.3 months in
patients with KPS >/=70, but only 3.1 months in patients with KPS <70.
Favorable survival is observed for patients within each recursive
partitioning analysis class. Treatment with GliaSite is safe and generally
well tolerated. Additional data are needed to fully assess the therapeutic
benefit of GliaSite brachytherapy for recurrent GBM.
PMID: 15990019 [PubMed - in process]
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| 9: Int
J Radiat Oncol Biol Phys. 2005 Jul 15;62(4):1125-32. |
|
-
The impact of whole-brain radiation therapy on the
long-term control and morbidity of patients surviving more than one year
after gamma knife radiosurgery for brain metastases.
Varlotto
JM, Flickinger
JC, Niranjan
A, Bhatnagar
A, Kondziolka
D, Lunsford
LD.
Department of Radiation Oncology, University of Pittsburgh Medical Center
and the Center for Image-Guided Neurosurgery, Pittsburgh, PA.
Purpose: To better analyze how whole-brain radiotherapy (WBXRT) affects
long-term tumor control and toxicity from the initial stereotactic
radiosurgery (SRS) for brain metastases, we studied these outcomes in
patients who had survived at least 1 year from SRS. Methods and Materials:
We evaluated the results of gamma knife radiosurgery for 160 brain
metastases in 110 patients who were followed for a median of 18 months
(range, 12-122 months) after SRS. Eighty-two patients had a solitary brain
metastasis and 28 patients had multiple metastases. Seventy patients (116
tumors) were treated with initial radiosurgery and WBXRT, whereas 40
patients (44 lesions) initially received radiosurgery alone. Median
treatment volume was 1.9 cc in the entire group, 2.3 cc in the WBXRT group,
and 1.6 cc in the SRS alone group. Median tumor dose was 16 Gy (range, 12-21
Gy). Results: At 1, 3, and 5 years, local tumor control was 84.1% +/- 5.5%,
68.6% +/- 8.7%, and 68.6% +/- 8.7% with SRS alone compared with 93.1% +/-
2.4%, 87.7% +/- 4.9%, and 65.7% +/- 10.2%. with concurrent WBXRT and SRS (p
= 0.0228, univariate). We found that WBXRT improved local control in patient
subsets tumor volume >/=2 cc, peripheral dose </=16 Gy, single
metastases, nonradioresistant tumors, and lung cancer metastases (p =
0.0069, 0.0080, 0.0083, 0.0184, and 0.0348). Distal intracranial failure
developed at 1, 3, and 5 years in 26.0% +/- 7.1%, 74.5% +/- 9.4%, and 74.5%
+/- 9.4% with SRS alone compared with 20.7% +/- 4.9%, 49.0% +/- 8.7%, and
61.8% +/- 12.8% with concurrent WBXRT and SRS (p = 0.0657). We found a trend
for improved distal intracranial control with WBXRT for only
nonradioresistant tumors (p = 0.054). Postradiosurgery complications
developed in 2.8% +/- 1.2% and 10.7% +/- 3.5% at 1 and 3-5 years and was
unaffected by WBXRT (p = 0.7721). WBXRT did not improve survival in the
entire series (p = 0.5027) or in any subsets. Conclusions: In this
retrospective study of 1-year survivors of SRS for brain metastases, the
addition of concurrent WBXRT to SRS was associated with an improved local
control rate in patient subsets with tumor volume >/=2 cc, peripheral
dose </=16 Gy, single metastases, nonradioresistant tumors, and
specifically lung cancer metastases. A trend was noted for improved distal
intracranial control for patients having nonradioresistant tumors. Distant
intracranial relapse >1 year posttreatment is a significant problem with
or without initial WBXRT.
PMID: 15990018 [PubMed - in process]
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| 10: Int
J Radiat Oncol Biol Phys. 2005 Jun 22; [Epub ahead of print] |
|
-
Genetic analyses for predictors of radiation response in
glioblastoma.
Shih
HA, Betensky
RA, Dorfman
MV, Louis
DN, Loeffler
JS, Batchelor
TT.
Department of Radiation Oncology, Massachusetts General Hospital and Harvard
Medical School, Boston, Massachusetts.
PURPOSE: Radiotherapy (RT) for patients with glioblastoma improves survival
and is recommended for nearly all patients with this diagnosis. However, the
response to RT is variable in this patient population. Prior studies have
suggested that underlying genetic alterations in the tumor may account for
some of this treatment-related heterogeneity. It has been previously
reported that epidermal growth factor receptor (EGFR) gene amplification and
TP53 mutation correlate with the response to RT in patients with
glioblastoma. METHODS AND MATERIALS: We sought to identify molecular markers
that could predict the response to RT, progression-free survival after RT,
and overall survival among 75 glioblastoma patients treated with RT at a
single institution. Genetic analyses assessed EGFR amplification, TP53
mutations, CDKN2A/p16 deletion, and losses of chromosomes 1p, 10q, and 19q.
RESULTS: Unlike previous reports, no association of EGFR amplification with
response to RT, progression-free survival, or overall survival was found.
Moreover, no association was found between these endpoints and the other
genetic alterations assayed (TP53 mutation, CDKN2A/p16 deletion, loss of
heterozygosity 1p, loss of heterozygosity 10q, and loss of heterozygosity
19q). However, in accordance with recent observations that the prognostic
effects of genetic alterations in glioblastoma may depend on patient age, we
observed age-dependent prognostic effects of TP53 and CDKN2A/p16 alterations
in our patient population. For patients >/=57 years old, those harboring
TP53 mutations had a decreased overall survival compared with patients
without TP53 mutations. Similarly, deletion of CDKN2A/p16 in patients
>/=57 years was associated with decreased progression-free survival after
RT and a trend toward a shorter time to progression after RT compared with
similar patients without the deletion. CONCLUSION: These data contrast with
previous studies regarding the significant prognostic effect of EGFR with
respect to RT response. Although our observations regarding the
age-dependent prognostic effects of TP53 and CDKN2A/p16 are consistent with
a prior report regarding these alterations, the present results should be
considered preliminary, given the small sample size.
PMID: 15978739 [PubMed - as supplied by publisher]
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| 11: Int
J Radiat Oncol Biol Phys. 2005 Jun 1;62(2):614-5; author reply
615-6. |
|
Comment on:
In regard to Dr. Souhami et al. (Int J Radiat Oncol Biol
Phys 2004;60:853-860).
Kondziolka
D, Lunsford
LD, Flickinger
JC.
Publication Types:
PMID: 15890607 [PubMed - indexed for MEDLINE]
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| 12: Int
J Radiat Oncol Biol Phys. 2005 Jun 1;62(2):333-41. |
|
-
Treatment of pituitary adenomas by fractionated
stereotactic radiotherapy: a prospective study of 110 patients.
Colin
P, Jovenin
N, Delemer
B, Caron
J, Grulet
H, Hecart
AC, Lukas
C, Bazin
A, Bernard
MH, Scherpereel
B, Peruzzi
P, Nakib
I, Redon
C, Rousseaux
P.
Department of Radiation, Polyclinique Courlancy, Reims, France; Department
of Neurosurgery, Centre Hospitalier Universitaire Reims, Reims, France.
courlancy.colin@wanadoo.fr
PURPOSE: To optimize and reduce the toxicity of pituitary adenoma
irradiation by assessing the feasibility and effectiveness of fractionated
stereotactic radiotherapy (FSR). METHODS AND MATERIALS: Between 1990 and
1999, 110 consecutive patients, 47 with a functioning adenoma, were treated
according to a strategy of either early surgery and FSR (n = 89) or FSR only
(n = 21). Of the 110 patients, 75 had persistent macroscopic tumor and 47
persistent hormonal secretions; 15 were treated in the prophylactic setting.
The linear accelerator-delivered dose was 50.4 Gy (5 x 1.8 Gy weekly), with
a 2-mm safety margin. RESULTS: After a minimal follow-up of 48 months, only
1 patient had developed progression. Of the 110 patients, 27 (36%) had a
complete tumor response, 67 (89.3%) had an objective tumor response, 20
(42%) had a hormonal complete response, and 47 (100%) had a hormonal
objective tumor response. The proportion of patients without a complete
tumor response, objective tumor response, complete hormonal response, and
objective hormonal response was 85.1%, 62%, 83%, and 59.3% at 4 years and
49.3%, 9%, 59.3%, and 10.6% at 8 years, respectively. The sole unfavorable
predictive factor was preoperative SSE >20 mm for tumor response (p =
0.01) and growth hormone adenoma for the hormonal response (p <0.001). No
late complications, except for pituitary deficiency, were reported, with a
probability of requiring hormonal replacement of 28.5% and 35% at 4 and 8
years, respectively. Nonfunctioning status was the sole unfavorable factor
(p = 0.0016). CONCLUSIONS: Surgery plus FSR is safe and effective. FSR
focused to the target volume seems more suitable than standard radiotherapy,
and standard fractionation reduces the risk of optic neuropathy sometimes
observed after single-dose radiosurgery. Therefore, FSR allows us to
consider combined transrhinoseptal surgery and early radiotherapy, with a
curative goal without patient selection.
PMID: 15890572 [PubMed - indexed for MEDLINE]
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| 13: J
Natl Cancer Inst. 2005 May 18;97(10):765-77. |
|
-
p53-defective tumors with a functional
apoptosome-mediated pathway: a new therapeutic target.
Mashima
T, Oh-hara
T, Sato
S, Mochizuki
M, Sugimoto
Y, Yamazaki
K, Hamada
J, Tada
M, Moriuchi
T, Ishikawa
Y, Kato
Y, Tomoda
H, Yamori
T, Tsuruo
T.
Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo,
Japan.
BACKGROUND: Although cancer cells appear to maintain the machinery for
intrinsic apoptosis, defects in the pathway develop during malignant
transformation, preventing apoptosis from occurring. How to specifically
induce apoptosis in cancer cells remains unclear. METHODS: We determined the
apoptosome activity and p53 status of normal human cells and of lung, colon,
stomach, brain, and breast cancer cells by measuring cytochrome c-dependent
caspase activation and by DNA sequencing, respectively, and we used COMPARE
analysis to identify apoptosome-specific agonists. We compared cell death,
cytochrome c release, and caspase activation in NCI-H23 (lung cancer),
HCT-15 (colon cancer), and SF268 (brain cancer) cells treated with Triacsin
c, an inhibitor of acyl-CoA synthetase (ACS), or with vehicle. The cells
were mock, transiently, or stably transfected with genes for Triacsin
c-resistant ACSL5, dominant negative caspase-9, or apoptotic protease
activating factor-1 knockdown. We measured ACS activity and levels of
cardiolipin, a mitochondrial phospholipid, in mock and ACSL5-transduced
SF268 cells. Nude mice carrying NCI-H23 xenograft tumors (n = 10) were
treated with Triacsin c or vehicle, and xenograft tumor growth was assessed.
Groups were compared using two-sided Student t tests. RESULTS: Of 21
p53-defective tumor cell lines analyzed, 17 had higher apoptosome activity
than did normal cells. Triacsin c selectively induced apoptosome-mediated
death in tumor cells (caspase activity of Triacsin c-treated versus
untreated SF268 cells; means = 1020% and 100%, respectively; difference =
920%, 95% CI = 900% to 940%; P<.001). Expression of ACSL5 suppressed
Triacsin c-induced cytochrome c release and subsequent cell death (cell
survival of Triacsin c-treated mock- versus ACSL5-transduced SF268 cells;
means = 40% and 83%, respectively; difference = 43%, 95% CI = 39% to 47%;
P<.001). ACS was also essential to the maintenance of cardiolipin levels.
Finally, Triacsin c suppressed growth of xenograft tumors (relative tumor
volume on day 21 of Triacsin c-treated versus untreated mice; means = 4.6
and 9.6, respectively; difference = 5.0, 95% CI = 2.1 to 7.9; P = .006).
CONCLUSIONS: Many p53-defective tumors retain activity of the apoptosome,
which is therefore a potential target for cancer chemotherapy. Inhibition of
ACS may be a novel strategy to induce the death of p53-defective tumor
cells.
PMID: 15900046 [PubMed - indexed for MEDLINE]
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| 14: J
Neurol Neurosurg Psychiatry. 2005 Jun;76(6):804. |
|
-
Positional and sleep dyspnoea due to posterior exophytic
ependymoma of the medulla oblongata.
Maiuri
F, Esposito
M.
Dipartimento di Scienze Neurologiche, Clinica Neurochirurgica, Universit
Federico II, Via S. Pansini 5, Naples, Italy. frmaiuri@unina.it
<frmaiuri@unina.it>
Publication Types:
PMID: 15897502 [PubMed - indexed for MEDLINE]
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| 15: J Neurooncol.
2005 Jun;73(2):137-44. |
|
-
Utility of three-dimensional anisotropy contrast magnetic
resonance axonography for determining condition of the pyramidal tract in
glioblastoma patients with hemiparesis.
Beppu
T, Inoue
T, Kuzu
Y, Ogasawara
K, Ogawa
A, Sasaki
M.
Department of Neurosurgery, Iwate Medical University, 19-1, Uchimaru,
020-8505, Morioka, Japan, tbeppu@iwate-med.ac.jp.
Background and purpose: Three-dimensional anisotropy contrast magnetic
resonance axonography (3DAC) is a technique for diffusion weighted magnetic
resonance imaging (DWI) that offers reliable visualization of the pyramidal
tracts. This study evaluated condition of the pyramidal tract using 3DAC in
glioblastoma patients with hemiparesis. Methods: In 18 glioblastoma patients
before surgery, 3DAC findings of the pyramidal tract responsible for
hemiparesis were compared with finding from proton density-weighted imaging
(PDWI). To estimate extent of pyramidal tract destruction, fractional
anisotropy (FA) values using diffusion tensor magnetic resonance imaging
were examined for both the responsible and non-pathological pyramidal
tracts. Results: In all five patients for whom PDWI indicated no
hyperintense foci in the responsible pyramidal tract, 3DAC demonstrated no
change in color. When PDWI revealed hyperintense foci, 3DAC showed two types
of findings: no color change (five patients); or obscured dark area (six
patients). When 3DAC showed a dark area, mean FA value in the responsible
tract was significantly lower than that for the non-pathological
tract.Conclusion: When PDWI indicates hyperintense foci on the pyramidal
tract, 3DAC allows prediction of pyramidal tract condition, such as large
tumor invasion.
PMID: 15981104 [PubMed - in process]
-
| 16: J Neurooncol.
2005 Jun;73(2):125-30. |
|
-
Absence of histological signs of tumor progression in
recurrences of completely resected meningiomas.
Schiffer
D, Ghimenti
C, Fiano
V.
Department of Neuroscience, Department of Neuroscience, University of Turin,
Foundation Gruppo Policlinico di Monza, Via Cherasco 15, 10126, Turin,
Italy, davide.schiffer@unito.it.
In meningioma recurrences a tumor progression has been proposed on a
molecular genetic basis. From the histological point of view the problem has
not been sufficiently investigated. Recurrences mainly depend on tumor
location, histology, resection type and on the tumor growth in the adjacent
nervous tissue. Seventy-six completely resected recurrent meningiomas have
been studied. Most tumors were convexity or parasagittal meningiomas. The
number of recurrences studied per tumor varied from 1 to 5. Besides
histological methods, immunohistochemistry for Ki-67 MIB-1, TUNEL for
apoptosis, counts of mitoses and molecular genetics for CDKN2A were
performed. No variation of the mitotic index (MI) or MIB-1 labeling index
(LI) was observed in recurrences. Histological features, the number of
mitoses and the MIB-1 LI showed a great regional variability. Loss of
heterozygosity (LOH) of CDKN2A was found to be slightly more frequent in the
first recurrence than in the initial tumor, but it was lower in the
following recurrences. The nervous tissue adjacent to the tumor could
contain meningothelial cells and be responsible for recurrences. The number
of mitoses appeared to be the most important criterion for establishing the
tumor grade. The histological aspect does not change in recurrences and
there is no progression. The greater number of recurrences in atypical and
anaplastic tumors depends on their initial higher proliferation capacity.
The occurrence of tumor meningothelial cells in the adjacent nervous tissue
or in the thickened arachnoidal membrane can be responsible for recurrence.
PMID: 15981101 [PubMed - in process]
-
| 17: J Neurooncol.
2005 Jun;73(2):109-15. |
|
-
Assessment of tumor cell invasion factors in gliomatosis
cerebri.
Mawrin
C, Schneider
T, Firsching
R, Wiedemann
FR, Dietzmann
K, Bornemann
A, Romeike
BF, Sellhaus
B, von
Deimling A.
Institut fur Neuropathologie, Klinik fur, Institute of Neuropathology,
Otto-von-Guericke-University, Leipziger Strasse 44, D-39120, Magdeburg,
Germany, christian.mawrin@medizin.uni-magdeburg.de.
Gliomatosis cerebri (GC) is a rare brain tumor characterized by widespread
infiltration of large parts of the brain and sometimes even the spinal cord.
To determine the cause of this extraordinary degree of brain invasion, we
studied immunoexpression of factors associated with brain infiltration in
low-grade and high-grade tumor samples from nine GC cases. We further
determined the allelic status of the fibroblastic growth factor receptor 4
(FGFR4) gene at position 388 (arginine [Arg(388)] or glycine [Gly(388)]) in
eighteen GC patients, because the presence of at least one Arg(388) allele
has been suggested to favor tumor cell motility compared to tumor cells
homozygeous for the Gly(388) allele. Immunohistochemical analyses showed
that tumor samples from three GC cases expressed Tenascin-C, whereas six
cases had CD44 - immunopositive tumor samples. Expression of MMP-9 was not
observed in any of the nine GC patients. FGFR4 genotyping revealed the
presence of the Arg(388) in 72% of the eighteen GC cases, a frequency
similar to the one found in 21 common astrocytomas (71%). In tumor-free
control DNA, the Arg(388) phenotype was present in 60%. These data indicate
that CD44 expression might be related to the tumor infiltration in GC, and
that patients suffering from GC or other common astrocytomas do not have a
significantly increased frequency of the tumor cell motility-favoring
Arg(388) FGFR4 allele.
PMID: 15981099 [PubMed - in process]
-
| 18: J Neurooncol.
2005 Jun;73(2):101-8. |
|
-
CIC, a gene involved in cerebellar development and ErbB
signaling, is significantly expressed in medulloblastomas.
Lee
CJ, Chan
WI, Scotting
PJ.
EMBL-EBI, Wellcome Trust Genome Campus, Hinxton, UK.
In children, the majority of brain tumors arise in the cerebellum.
Medulloblastomas, the most common of these, are believed to originate from
the granule cell lineage. We have recently identified a mammalian gene,
capicua (Cic), the ortholog of a Drosophila gene implicated in c-erbB (Egfr)
signaling, which is predominantly expressed during mouse granule cell
development. Its expression in medulloblastoma is therefore of particular
interest. In the present study the expression of human CIC in
medulloblastoma was analyzed. In silico SAGE analysis demonstrated that
medulloblastomas exhibited the highest level of CIC expression and
expression was most common in tumors of the CNS in general. RT-PCR and in
situ hybridization verified the expression of CIC in tumor cells, although
the level of expression varied between different medulloblastoma subtypes.
The expression of CIC did not correlate with other markers, such as
neurofilament, GFAP and Mib-1. In postnatally developing cerebellum, in
silico analysis and in situ hybridization both indicated a strong
correlation between Cic expression and the maturation profile of cerebellar
granule cell precursors. Expression of CIC is therefore a feature shared
between immature granule cells and the tumors derived from them. Cic has
been implicated as a mediator of ErbB signaling and this pathway has been
associated with a poor prognosis for medulloblastomas. Therefore, further
analysis of the role of Cic is likely to provide valuable insight into the
biology of these tumors. Additionally, study of genes such as CIC should
provide objective criteria by which, in combination with other markers and
clinical data, to categorize these tumors into subgroups that might allow
better allocation into specific treatment regimes.
PMID: 15981098 [PubMed - in process]
-
| 19: J Neurooncol.
2005 Jul;73(3):261-4. |
|
-
Temozolomide-induced partial response in a patient with
primary diffuse leptomeningeal gliomatosis.
Franceschi
E, Cavallo
G, Scopece
L, Esposti
RD, Paioli
G, Paioli
A, Palmerini
E, Foschini
MP, Marliani
AF, Crino
L.
Department of Medical Oncology, Bellaria Hospital, Via Altura 3, Bologna,
40139, Italy, giovanna.cavallo@ausl.bo.it.
Herein we describe the case of a patient with primary diffuse leptomeningeal
gliomatosis (PDLG). After surgery and ventriculoperitoneal shunt placement,
due to poor general conditions, the patient was not eligible for
radiotherapy. For this reason we decided to start a systemic chemotherapy
treatment with Temozolomide (150 mg/m(2) per day for 5 days every 4 weeks).
After three cycles a partial response was achieved with a clear improvement
of general conditions. In our knowledge, this is the first time that PDLG
treatment with Temozolomide has been described.
PMID: 15980977 [PubMed - in process]
-
| 20: J Neurooncol.
2005 Jul;73(3):239-40. |
|
-
Glioma dissemination along the corticospinal tract.
Pallud
J, Devaux
B, Daumas-Duport
C, Oppenheim
C, Roux
FX.
Service de Neurochirurgie, Department of Neurosurgery, Centre Hospitalier
Sainte-Anne, 1 rue Cabanis, 75674, Paris, France, johanpallud@hotmail.com.
PMID: 15980974 [PubMed - in process]
-
| 21: J Neurooncol.
2005 Jul;73(3):219-23. |
|
-
High throughput screening of meningioma biomarkers using
a tissue microarray.
Lusis
EA, Chicoine
MR, Perry
A.
Division of Neuropathology, Washington University School of Medicine, Campus
Box 8118, 660 South Euclid Ave, St. Louis, MO, 63110, USA, aperry@wustl.edu.
Meningiomas are histologically and clinically diverse CNS neoplasms with few
available immunohistochemical markers of differentiation and progression.
Therefore, we investigated a panel of potentially useful
meningioma-associated biomarkers using high throughput tissue microarray
immunohistochemistry (TMA-IHC) with a TMA that includes 9
hemangiopericytomas (HPCs) and 41 meningiomas spanning all grades, as well
as two subsets of atypical meningiomas, stratified according to clinical
behavior. Antibodies utilized were progesterone receptor (PR), epithelial
membrane antigen (EMA), cathepsin D, E-cadherin, platelet derived growth
factor (PDGF) receptor beta, PDGF BB ligand, survivin, epithelial growth
factor receptor (EGFR), and vascular endothelial growth factor (VEGF). In
most cases, frequencies of tumor positivity were similar to those previously
reported using whole section IHC. EMA, E-cadherin, and PDGFR-beta staining
patterns distinguished the anaplastic meningiomas from the HPCs (P <
0.001, P = 0.02, P = 0.015, respectively). As in prior studies, PR and
cathepsin D expression were inversely proportional to tumor grade. However,
PR and EGFR were also differentially expressed between symptomatic,
surgically resected benign meningiomas and incidental meningiomas found at
autopsy. We conclude that (1) TMA-IHC is an accurate and efficient way to
rapidly assess biomarkers in meningeal tumors, (2) EMA, E-cadherin, and
PDGFR-beta are useful in distinguishing anaplastic meningiomas from HPCs,
and (3) the expression patterns for incidental meningiomas differ slightly
from their surgically resected symptomatic counterparts.
PMID: 15980972 [PubMed - in process]
-
| 22: J Neurooncol.
2005 Jul;73(3):205-9. |
|
-
beta-catenin mutations in craniopharyngiomas and
pituitary adenomas.
Oikonomou
E, Barreto
DC, Soares
B, Marco
LD, Buchfelder
M, Adams
EF.
School of Health and Life Sciences, Biomedical Chemistry Research Group,
Aston University, Birmingham, B4 7ET, UK, e.f.adams@aston.ac.uk.
Craniopharyngiomas and pituitary adenomas are both tumors of the
hypothalamic and pituitary region, respectively that are frequently
associated with endocrine defects either because of direct involvement of
hormone producing cells (most pituitary tumors) or because of secondary
defects due to disturbance of hypothalamic function (some pituitary tumors
and craniopharyngiomas). Some studies suggest that mutant beta-catenin gene
cells in craniopharyngiomas and pituitary adenomas contribute to their
tumorigenesis. DNA was extracted from 73 cranial tumors and subjected to
polymerase chain reaction (PCR) with previously described primers
encompassing glycogen synthase kinase-3beta phosphorylation sites of the
beta-catenin gene. Sequenced PCR products for possible beta-catenin gene
mutations showed a total of 7/43 alterations in adamantinomatous
craniopharyngioma-derived DNA samples. Two previously described beta-catenin
mutations in codon 33 TCT(Ser) > TGT(Cys) and codon 37 TCT(Ser) >
TTT(Phe), whereas three novel mutations in codon 41 ACC(Thr) > ATC(Ile),
codon 33 TCT(Ser) > TAT(Tyr) and codon 32 GAC(Asp) > AAC(Asn) were
observed. None of the 22 pituitary adenomas and the eight papillary
craniopharyngiomas analyzed presented any sequence alterations. These
findings demonstrate an association between beta-catenin gene alterations
and craniopharyngiomas of the adamantinomatous type. Since this gene product
is involved with development, these results suggest that beta-catenin
mutations may contribute to the initiation and subsequent growth of
congenital craniopharyngiomas.
PMID: 15980970 [PubMed - in process]
-
| 23: J Neurooncol.
2005 Jul;73(3):199-204. |
|
-
Meningiomas expressing and responding to cholecystokinin
(CCK).
Oikonomou
E, Machado
AL, Buchfelder
M, Adams
EF.
School of Health and Life Sciences, Biomedical Chemistry Research Group,
Aston University, B4 7ET, Birmingham, UK, e.f.adams@aston.ac.uk.
The effect of cholecystokinin (CCK) on cultured human meningioma derived
cells was investigated. Exposure of meningioma cells for 6-12 days to CCK-8s
(2-200 nM) resulted in a dose dependent stimulation of cell growth to a
maximum of 1.1-fold over basal controls. A time course study showed
stimulation of cell growth at day 3 followed by increase throughout day 6.
The stimulatory effect of CCK on meningioma cell growth was completely
abolished by a CCK-B specific receptor antagonist, L-365,260.
Reverse-transcription of meningioma-derived RNA into cDNA followed by
amplification by the polymerase chain reaction using specific primers for
CCK peptide and its CCK-A and/B receptor revealed 100% presence of CCK
peptide and CCK-B receptors mRNA whereas CCK-A receptor was expressed in 66%
of the meningiomas. These results provide evidence that human meningioma
cells possess CCK peptide and its receptors the activation of which leads to
increase of cell growth possibly via an autocrine/paracrine mechanism.
PMID: 15980969 [PubMed - in process]
-
| 24: J Neurooncol.
2005 Jul;73(3):189-98. |
|
-
Gene expression profile induced by BCNU in human glioma
cell lines with differential MGMT expression.
Bandres
E, Andion
E, Escalada
A, Honorato
B, Catalan
V, Cubedo
E, Cordeu
L, Garcia
F, Zarate
R, Zabalegui
N, Garcia-Foncillas
J.
Laboratory of Biotechnology and Pharmacogenomics, University Clinic, Cancer
Center, University of Navarra, Avda Pio XII 36, 31008, Pamplona, Spain,
ebandres@unav.es.
Chemotherapy with the alkylating agent BCNU (1,3-bis
(2-chloroethyl)-1-nitrosourea) is the most commonly used chemotherapeutic
agent for gliomas. However, the usefulness of this agent is limited because
tumor cell resistance to BCNU is frequently found in clinical brain tumor
therapy. The O (6) -methylguanine-DNA methyltransferase protein (MGMT)
reverses alkylation at the O (6) position of guanine and we have reported
the role of MGMT in the response of brain tumors to alkylating agents.
However, the different mechanisms underlying the patterns related to MGMT
remain unclear. To better understand the molecular mechanism by which BCNU
exerts its effect in glioma cell lines according MGMT expression, we used
microarray technology to interrogate 3800 known genes and determine the gene
expression profiles altered by BCNU treatment. Our results showed that
treatment with BCNU alters the expression of a diverse group of genes in a
time-dependent manner. A subset of gene changes was found common in both
glioma cell lines and other subset is specific of each cell line. After 24 h
of BCNU treatment, up-regulation of transcription factors involved in the
nucleation of both RNA polymerase II and III transcription initiation
complexes was reported. Interestingly, BCNU promoted the expression of
actin-dependent regulators of chromatin. Similar effects were found with
higher BCNU doses in MGMT+ cell line showing a similar mechanism that in
MGMT-deficient cell with standard doses. Our data suggest that human glioma
cell lines treated with BCNU, independently of MGMT expression, show changes
in the expression of cell cycle and survival-related genes interfering the
transcription mechanisms and the chromatin regulation.
PMID: 15980968 [PubMed - in process]
-
| 25: J
Neuropathol Exp Neurol. 2005 Jun;64(6):523-8. |
|
HLA-E protects glioma cells from NKG2D-mediated immune
responses in vitro: implications for immune escape in vivo.
Wischhusen
J, Friese
MA, Mittelbronn
M, Meyermann
R, Weller
M.
Laboratory of Molecular Neuro-Oncology, Department of General Neurology,
Hertie Institute for ClinicaI Brain Research, University of Tubingen Medical
School, Tubingen, Germany. joerg.wischhusen@uni-tuebingen.de
The nonclassical MHC class I molecule HLA-E is the only known ligand for
CD94/NKG2A and CD94/NKG2C expressed on NK and CD8+ alphabeta and gammadelta
T cells. HLA-E may transmit either activating signals via CD94/NKG2C or
inhibitory signals mediated by CD94/NKG2A. Here we show that HLA-E is
expressed at mRNA and protein level in human long-term glioma cell lines,
primary ex vivo polyclonal glioblastoma cell cultures and surgical
glioblastoma specimens. Furthermore, immunohistochemistry revealed an
enhanced in vivo expression of HLA-E in gliomas of lower grades and a
massive overexpression in grade IV glioblastomas compared with normal CNS
tissue. An immune-inhibitory effect of HLA-E on tumor-specific CTL has
already been described. We show that siRNA-mediated silencing of HLA-E or
blocking of CD94/NKG2A enables NKG2D-mediated lysis of 51Cr-labeled tumor
cells by NK cells. Thus, our study provides the first evidence that
expression and interaction of HLA-E on cancer cells with CD94/NKG2A
expressed on lymphocytes compromises innate anti-tumor immune responses.
PMID: 15977644 [PubMed - in process]
-
| 26: J
Neuropathol Exp Neurol. 2005 Jun;64(6):479-89. |
|
Population-based studies on incidence, survival rates,
and genetic alterations in astrocytic and oligodendroglial gliomas.
Ohgaki
H, Kleihues
P.
Pathology Group, International Agency for Research on Cancer (HO), F-69372,
Lyon, France. ohgaki@iarc.fr
Published data on prognostic and predictive factors in patients with gliomas
are largely based on clinical trials and hospital-based studies. This review
summarizes data on incidence rates, survival, and genetic alterations from
population-based studies of astrocytic and oligodendrogliomas that were
carried out in the Canton of Zurich, Switzerland (approximately 1.16 million
inhabitants). A total of 987 cases were diagnosed between 1980 and 1994 and
patients were followed up at least until 1999. While survival rates for
pilocytic astrocytomas were excellent (96% at 10 years), the prognosis of
diffusely infiltrating gliomas was poorer, with median survival times (MST)
of 5.6 years for low-grade astrocytoma WHO grade II, 1.6 years for
anaplastic astrocytoma grade III, and 0.4 years for glioblastoma. For
oligodendrogliomas the MSTwas 11.6 years for grade II and 3.5 years for
grade III. TP53 mutations were most frequent in gemistocytic astrocytomas
(88%), followed by fibrillary astrocytomas (53%) and oligoastrocytomas
(44%), but infrequent (13%) in oligodendrogliomas. LOH 1p/19q typically
occurred in tumors without TP53 mutations and were most frequent in
oligodendrogliomas (69%), followed by oligoastrocytomas (45%), but were rare
in fibrillary astrocytomas (7%) and absent in gemistocytic astrocytomas.
Glioblastomas were most frequent (3.55 cases per 100,000 persons per year)
adjusted to the European Standard Population, amounting to 69% of total
incident cases. Observed survival rates were 42.4% at 6 months, 17.7% at one
year, and 3.3% at 2 years. For all age groups, survival was inversely
correlated with age, ranging from an MST of 8.8 months (<50 years) to 1.6
months (>80 years). In glioblastomas, LOH 10q was the most frequent
genetic alteration (69%), followed by EGFR amplification (34%), TP53
mutations (31%), p16INK4a deletion (31%), and PTEN mutations (24%). LOH 10q
occurred in association with any of the other genetic alterations, and was
the only alteration associated with shorter survival of glioblastoma
patients. Primary (de novo) glioblastomas prevailed (95%), while secondary
glioblastomas that progressed from low-grade or anaplastic gliomas were rare
(5%). Secondary glioblastomas were characterized by frequent LOH 10q (63%)
and TP53 mutations (65%). Of the TP53 mutations in secondary glioblastomas,
57% were in hot-spot codons 248 and 273, while in primary glioblastomas,
mutations were more evenly distributed. G:C-->A:T mutations at CpG sites
were more frequent in secondary than primary glioblastomas, suggesting that
the acquisition of TP53 mutations in these glioblastoma subtypes may occur
through different mechanisms.
PMID: 15977639 [PubMed - in process]
-
| 27: Neuroradiology. 2005
Jun 25; [Epub ahead of print] |
|
-
Meningioma growth and interferon beta-1b treated multiple
sclerosis: coincidence or relationship?
Drevelegas
A, Xinou
E, Karacostas
D, Parissis
D, Karkavelas
G, Milonas
I.
Department of Radiology, AHEPA University Hospital, Aristotele University
School of Medicine, S. Kiriakidi 1, Thessaloniki, 54636, Greece,
adrev@med.auth.gr.
Although the coincidence of multiple sclerosis (MS) and central nervous
system (CNS) tumors has been reported in over 30 cases in English
literature, meningioma growth was associated with interferon-beta (INF-b)
treated MS only in two of them. We report the case of a 19-year-old woman
with clinically possible, laboratory supported MS, and a concomitant right
intraventricular tumor with magnetic resonance imaging (MRI) characteristics
consistent with meningioma (similar signal with grey matter on T1 and
T2-weighted images and homogenous, intense enhancement). Two years after
initiation of INF-b treatment, follow-up brain MRI revealed enlargement of
the intraventricular mass and relative increase in the number of white
matter lesions without significant clinical deterioration. She underwent
almost total resection of the mass and histology confirmed the diagnosis of
papillary meningioma. Based on the immunohistochemistry results, we
speculate that INF-b resulted in meningioma growth by enhancing platelet
derived growth factor (PDGF) receptors or/and down-regulating transforming
growth factor receptors on the tumor itself.
PMID: 15981002 [PubMed - as supplied by publisher]
-
| 28: Neurosurgery. 2005
Jul;57(1 Suppl):128-39. |
|
-
Integration of [11C]Methionine-Positron Emission
Tomographic and Magnetic Resonance Imaging for Image-guided Surgical
Resection of Infiltrative Low-grade Brain Tumors in Children.
Pirotte
B, Goldman
S, Van
Bogaert P, David
P, Wikler
D, Rorive
S, Brotchi
J, Levivier
M.
Department of Neurosurgery, Erasme Hospital, Universite Libre de Bruxelles,
Brussels, Belgium.
OBJECTIVE: To evaluate the interest of integrating positron emission
tomography (PET) images with the radiolabeled tracer [(11)C]methionine (Met)
into the image-guided navigation planning of infiltrative low-grade brain
tumors (LGBTs) in children. METHODS: Twenty-two children underwent combined
Met-PET with magnetic resonance imaging (MRI) scans in the planning of a
navigation procedure. These children presented an LGBT (astrocytomas, 10;
oligodendrogliomas, 4; ependymomas, 4; gangliogliomas, 4) located close to
functional areas. Tumor boundaries were ill-defined on MRI (including
T2-weighted and fluid-attenuated inversion-recovery scans) and could not be
clearly identified for allowing a complete, or at least a large,
image-guided resection. The PET tracer Met was chosen because of its higher
sensitivity and specificity than MRI to detect tumor tissue. The level and
extension of MET uptake were analyzed to define the PET contour,
subsequently projected onto MRI scans to define a final target contour for
volumetric resection. The quality of tumor resection was assessed by an
early postoperative MRI and Met-PET workup. RESULTS: In 20 of the 22
children with ill-defined LGBTs, PET improved tumor delineation and
contributed to define a final target contour different from that obtained
with MRI alone. Met-PET guidance allowed a total resection of Met uptake in
17 cases that were considered total tumor resections because the operative
margin left in place contained nontumor tissue. CONCLUSION: These data
suggested that Met-PET guidance could help to improve the number of total
resections and the amount of tumor removed in infiltrative LGBTs in
children.
PMID: 15987579 [PubMed - in process]
-
| 29: Neurosurgery. 2005
Jul;57(1 Suppl):107-13. |
|
-
Intraoperative and Postoperative Gamma Detection of
Somatostatin Receptors in Bone-invasive en Plaque Meningiomas.
Gay
E, Vuillez
JP, Palombi
O, Brard
PY, Bessou
P, Passagia
JG.
Department of Neurosurgery, University Hospital, Grenoble, France.
OBJECTIVE: Scintigraphy with a radiolabeled somatostatin analog
((111)In-diethylenetriaminepenta-acetic acid octreotide) detects the
somatostatin receptors that are found in vitro in all meningiomas. Previous
studies have proved the benefit of radioimmunoguided surgery, with a
hand-held gamma probe, for the assessment and removal of neuroendocrine
tumors. We conducted a study to determine whether intraoperative
radiodetection of somatostatin receptors is feasible and could increase the
probability of complete meningioma resection, especially for bone-invasive
en plaque meningiomas, which are difficult to control surgically. METHODS:
Eighteen patients with en plaque sphenoid wing and cranial convexity
meningiomas were studied by preoperative and postoperative somatostatin
receptor scintigraphy. In 10 of them, intraoperative radiodetection with a
hand-held gamma probe was performed 24 hours after the intravenous
administration of (111)In-diethylenetriaminepenta-acetic acid octreotide.
This procedure was combined with a computer-aided navigation system.
RESULTS: All preoperative scintigrams were positive. Intraoperative gamma
probe detection was achieved for the invaded bone, dura, and periorbit of
sphenoid wing meningiomas. The average tumor/nontumor count ratio was 2:1,
with a maximum of 12:1, thus allowing precise detection capable of defining
the tumor margins. In three cases of sphenoid wing meningiomas,
postoperative scintigrams were helpful for the determination of recurrences
that magnetic resonance imaging failed to detect. CONCLUSION: These
preliminary data show that intraoperative radiodetection of somatostatin
receptors with a hand-held gamma probe is feasible and may be helpful to
guide the surgical removal of bone-invasive en plaque meningiomas.
Preoperative and postoperative scintigraphy may be useful for the management
and follow-up of patients with these tumors.
PMID: 15987576 [PubMed - in process]
-
| 30: Neurosurgery. 2005
Jul;57(1):190. |
|
-
Optic nerve glioma and optic neuritis mimicking one
another: case report.
Tumialan
LM, Dhall
SS, Biousse
V, Newman
NJ.
Department of Neurosurgery, Emory University School of Medicine, Atlanta,
Georgia.
OBJECTIVE AND IMPORTANCE: The clinical and radiographic presentations of
optic nerve gliomas and optic neuritis are for the most part distinct and
their diagnoses straightforward. We present two cases illustrating the
occasional difficulty one can encounter in distinguishing neoplastic from
inflammatory optic neuropathies. CLINICAL PRESENTATION: Patient 1 is a
17-year-old girl who presented with acute onset of pain and rapidly
progressive visual loss in the right eye. Patient 2 is a 38-year-old man who
presented with painless progressive visual loss in the left eye.
INTERVENTION: Patient 1 was initially diagnosed with idiopathic retrobulbar
optic neuritis. Interval increase of the optic nerve on magnetic resonance
imaging prompted a biopsy of the optic nerve, which revealed a pilocytic
astrocytoma. Patient 2 was found to have left optic nerve enhancement most
consistent with an optic nerve glioma. Before a biopsy, the patient
spontaneously improved without treatment, indicating an inflammatory
process. CONCLUSION: Differentiating between optic nerve neoplasm and
inflammation may be difficult. On occasion, the classic clinical finding of
pain with eye movement and the radiographic finding of enlargement and
enhancement of the optic nerve may be misleading. Open biopsy of the optic
nerve is indicated only after a completely negative metabolic, infectious,
and inflammatory workup; interval increase of the optic nerve on magnetic
resonance imaging; and failure of the patient to recover vision.
PMID: 15987555 [PubMed - in process]
-
| 31: Neurosurgery. 2005
Jul;57(1):141-153. |
|
-
Potent Mimicry of Fibronectin-induced Intracellular
Signaling in Glioma Cells by the Homodimeric Snake Venom Disintegrin
Contortrostatin.
Schmitmeier
S, Markland
FS, Schonthal
AH, Chen
TC.
Department of Biochemistry and Molecular Biology, Keck School of Medicine,
University of Southern California, and Kenneth Norris Jr. Comprehensive
Cancer Center, Los Angeles, California, and Institute for Clinical Chemistry
and Laboratory Diagnostics, Heinrich-Heine University Medical School,
Duesseldorf, Germany.
OBJECTIVE: The snake venom disintegrin contortrostatin (CN) is able to
inhibit tumor progression and angiogenesis in vivo and therefore is of
considerable interest as a potential antitumor drug. CN specifically binds
to certain integrins on the tumor cell and angiogenic endothelial cell
surface and inhibits their interaction with the extracellular matrix,
resulting in blockage of cell motility and invasiveness. To understand the
molecular consequences of CN binding to integrins, we set out to investigate
and compare the effects of CN and fibronectin (FN) on integrin-induced
signaling and the resulting alteration in cellular cytoskeletal morphology.
METHODS: Two different malignant glioma cell lines were exposed to soluble
or immobilized CN, FN, or both, and the consequences for intracellular
signaling and cellular adhesion to matrix were investigated. RESULTS: CN
binding to integrins can mimic the intracellular signaling cascade evoked by
FN, because the phosphorylation of the key signaling proteins focal adhesion
kinase, paxillin, and p130 Crk-associated substrate and the association of
Src with focal adhesion kinase are similar. However, CN is at least one
order of magnitude more potent than FN. When soluble CN is added to cells
that are already attached to an FN-coated matrix, it effectively disrupts
the binding of integrin to FN, leading to a decrease in integrin signaling,
which, in turn, results in the disruption of the cytoskeleton and cellular
detachment. CONCLUSION: Our results provide a mechanistic explanation of how
soluble CN might block cellular migration and invasion, namely, by
disrupting and preventing the binding of integrins to the extracellular
matrix. We envision that this property of CN could be used in the treatment
of gliomas, namely, by intratumoral infusion of CN to prevent glioma and
endothelial cell interactions with the extracellular matrix, leading to
inhibition of cell invasion.
PMID: 15987550 [PubMed - as supplied by publisher]
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| 32: Neurosurgery. 2005
Jul;57(1):77-90. |
|
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Facial and cochlear nerve function after surgery of
cerebellopontine angle meningiomas.
Nakamura
M, Roser
F, Dormiani
M, Matthies
C, Vorkapic
P, Samii
M.
Department of Neurosurgery, Nordstadt Hospital, Teaching Hospital Hannover
Medical School, Hannover, Germany.
OBJECTIVE: Meningiomas of the cerebellopontine angle (CPA) share a common
location, but their site of dural origin and their relationship to
surrounding neurovascular structures of the CPA are variable. The clinical
presentation and outcome after surgical resection are different because of
the diversity of this tumor entity. We report on a series of 421 patients
with CPA meningiomas, with special emphasis on the analysis of the
preoperative and postoperative facial and cochlear nerve function in
relation to the site of dural attachment and main tumor location in the CPA
cistern. METHODS: Among 421 patients, the charts of 347 patients with
complete clinical data, including the history and audiograms, imaging
studies, surgical records, discharge letters, histological records, and
follow-up records, were reviewed retrospectively. Data about preoperative
and postoperative facial nerve function were available in 334 patients, and
audiometric analysis was conducted in 333 patients. Patients with
neurofibromatosis Type 2 were excluded from the study. RESULTS: There were
270 women and 77 men, with a mean age of 53.4 years (range, 17.6-84 yr).
Among these patients, 32.9% of the tumors originated at the petrous ridge
anterior to the inner auditory canal (IAC) (Group 1), 22.2% showed
involvement of the IAC (Group 2), 20.2% were located superior to the IAC
(Group 3), 11.8% were inferior to the IAC (Group 4), and 12.9% were
posterior to the IAC, originating between the IAC and the sigmoid sinus
(Group 5). Patients presented with disturbance of Cranial Nerves V-VIII, the
lower cranial nerves, and ataxia, depending on the main tumor location.
Tumor resection was performed through a suboccipital-retrosigmoidal approach
in the semisitting position in 95% of the patients. A combined
supratentorial-infratentorial presigmoidal approach was performed in 5%.
Total tumor removal (Simpson Grade 1 and 2) was achieved in 85.9% and
subtotal removal in 14.1%. The best initial postoperative facial and
auditory nerve function was observed in tumors belonging to Groups 3 and 5.
Recovery from preoperative deafness was observed in 1.8% of patients. On
long-term follow-up, good facial nerve function (House-Brackmann Grade 1 or
2) was observed in 88.9% of patients. Hearing preservation among patients
with preoperative functional hearing was documented in 90.8% on long-term
follow-up. CONCLUSION: Although the outcome of facial and cochlear nerve
function is different in CPA meningiomas, depending on the topographic
classification of these tumors, preservation of the cochlear nerve is
possible in every tumor group and should be attempted in every patient with
CPA meningioma. It has to be kept in mind that recovery of hearing was also
observed in patients with preoperative profound hearing deficits.
PMID: 15987543 [PubMed - in process]
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| 33: Neurosurgery. 2004
Nov;55(5):1228; author reply 1228. |
|
Comment on:
Seeding of a cavernous angioma with Mycoplasma hominis:
case report.
Pozzati
E, Bortolotti
C, Lanzino
G.
Publication Types:
PMID: 15791744 [PubMed - indexed for MEDLINE]
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| 34: Oncogene. 2005 May
19;24(22):3632-42. |
|
-
Vasculostatin, a proteolytic fragment of brain
angiogenesis inhibitor 1, is an antiangiogenic and antitumorigenic factor.
Kaur
B, Brat
DJ, Devi
NS, Van
Meir EG.
Laboratory of Molecular Neuro-Oncology, Departments of Neurosurgery,
Hematology/Oncology, Winship Cancer Institute, Emory University, Atlanta, GA
30322, USA.
Brain angiogenesis inhibitor 1 (BAI1) is a transmembrane protein with
unknown function expressed primarily in normal but not tumoral brain. The
finding of thrombospondin type 1 repeats in its extracellular domain
suggested an antiangiogenic function, but the mechanisms by which a
transmembrane receptor could inhibit angiogenesis remained unexplained. Here
we demonstrate that BAI1 is proteolytically cleaved at a conserved
G-protein-coupled receptor proteolytic cleavage site (GPS), releasing its
120 kDa extracellular domain. We named this secreted fragment Vasculostatin
as it inhibited migration of endothelial cells in vitro and dramatically
reduced in vivo angiogenesis. Both constitutive and doxycycline-induced
expression of Vasculostatin elicited dose-dependent suppression of tumor
growth and vascular density in mice, implicating Vasculostatin in the
regulation of vascular homeostasis and tumor prevention. Generation of a
soluble antiangiogenic factor by cleavage of a pre-existing transmembrane
protein represents a novel mechanism for regulating vascular homeostasis and
preventing tumorigenesis. Modulation of this cleavage or delivery of
Vasculostatin may constitute novel treatment modalities for cancer and other
diseases of aberrant angiogenesis, especially in the brain.
PMID: 15782143 [PubMed - indexed for MEDLINE]
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| 35: Oncogene. 2005 Jun
16;24(26):4243-56. |
|
-
The EphA8 receptor induces sustained MAP kinase
activation to promote neurite outgrowth in neuronal cells.
Gu
C, Shim
S, Shin
J, Kim
J, Park
J, Han
K, Park
S.
Institute of Natural Science, Sookmyung Women's University, 53-12
Chungpa-Dong 2-Ka, Yongsan-Ku, Seoul 140-742, Korea.
Recent studies in our laboratory demonstrate that ligand-mediated activation
of the EphA8 receptor critically regulates cell adhesion and migration. In
this report, we show that the EphA8 receptor induces neurite outgrowth in
NG108-15 cells in the absence of ligand stimulation. Using various deletion
mutants lacking specific intracytoplasmic regions, we confirm that the
tyrosine kinase domain of EphA8 is important for inducing neurite outgrowth.
However, the tyrosine kinase activity of EphA8 is not crucial for neurite
outgrowth induction. Treatment with various inhibitors further reveals that
the mitogen-activated protein kinase (MAPK) signaling pathway is critical
for neurite outgrowth induced by EphA8. Consistent with these results, EphA8
expression induced a sustained increase in the activity of MAPK, whereas
ligand-mediated EphA8 activation had no further modulatory effects on MAP
kinase activity. Additionally, activated MAPK relocalized from the cytoplasm
to the nucleus in response to EphA8 transfection. These results collectively
suggest that the EphA8 receptor is capable of inducing a sustained increase
in MAPK activity, thereby promoting neurite outgrowth in neuronal cells.
PMID: 15782114 [PubMed - indexed for MEDLINE]
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| 36: Pediatr Neurosurg.
2005 Jan-Feb;41(1):52-3. |
|
-
Remote cerebellar hemorrhage after craniotomy.
Yang
BP, Yang
CW.
Division of Pediatric Neurosurgery, Children's Memorial Hospital,
Northwestern University Feinberg School of Medicine, Chicago, Ill., USA.
b.yang1@md.northwestern.edu
Publication Types:
PMID: 15886515 [PubMed - indexed for MEDLINE]
-
| 37: Pediatr Neurosurg.
2005 Jan-Feb;41(1):35-40. |
|
-
Human tail with noncontiguous intraspinal lipoma and
spinal cord tethering: case report and embryologic discussion.
Donovan
DJ, Pedersen
RC.
Neurosurgery Service, Department of Surgery, Tripler Army Medical Center,
Honolulu, Hawaii, USA. daniel.donovan@amedd.army.mil
Children born with a tail-like appendage have a rare malformation that is
frequently associated with abnormalities of the spine and spinal cord. A
contiguous fibrolipoma is usually seen extending from the subcutaneous
portion of the tail into the inferior spinal cord, resulting in tethered
cord syndrome. We present the case of a child born with a tail and
intraspinal lipoma that were not contiguous with each other, and were
separated by an intact layer of lumbosacral fascia. The tail and lipoma were
removed and the spinal cord untethered, and the child is neurologically
normal 2 years after surgery. The absence of a contiguous lipoma from the
tail to the spinal cord suggests that this condition may be principally
caused by a disorder of secondary neurulation and/or regression of the
normal embryonic tail bud. The embryology of the lower spine is reviewed and
possible etiologies discussed. Copyright 2005 S. Karger AG, Basel.
Publication Types:
PMID: 15886511 [PubMed - indexed for MEDLINE]
-
| 38: Pediatr Neurosurg.
2005 Jan-Feb;41(1):29-34. |
|
-
Hydrocephalus as the initial presentation of a spinal
cord astrocytoma associated with leptomeningeal spread.
Vassilyadi
M, Michaud
J.
Division of Neurosurgery and Department of Pathology and Laboratory
Medicine, University of Ottawa, Ottawa, Canada. vassilyadi@cheo.on.ca
A 3-year-old boy presented with headaches, vomiting, lethargy and
papilledema. Communicating hydrocephalus along with transependymal fluid
absorption and meningeal contrast enhancement was identified on CT. The
enhancement was initially thought to be the result of a partially treated
meningitis (child was previously on oral antibiotics for a presumed
mycoplasma pneumonia). A right ventricular-peritoneal shunt was placed. CSF
|
Volume 4, Number
28 - 4 July 2005