| 1: Br J Cancer.
2005 Sep 20; [Epub ahead of print] |
|
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hERG1 channels are overexpressed in glioblastoma
multiforme and modulate VEGF secretion in glioblastoma cell lines.
Masi
A, Becchetti
A, Restano-Cassulini
R, Polvani
S, Hofmann
G, Buccoliero
AM, Paglierani
M, Pollo
B, Taddei
GL, Gallina
P, Di
Lorenzo N, Franceschetti
S, Wanke
E, Arcangeli
A.
Department of Experimental Pathology and Oncology, University of Firenze,
Viale GB Morgagni, 50, 50134 Firenze, Italy.
Recent studies have led to considerable advancement in our understanding of
the molecular mechanisms that underlie the relentless cell growth and
invasiveness of human gliomas. Partial understanding of these mechanisms has
(1) improved the classification for gliomas, by identifying prognostic
subgroups, and (2) pointed to novel potential therapeutic targets. Some
classes of ion channels have turned out to be involved in the pathogenesis
and malignancy of gliomas. We studied the expression and properties of K(+)
channels in primary cultures obtained from surgical specimens: human ether a
go-go related (hERG)1 voltage-dependent K(+) channels, which have been found
to be overexpressed in various human cancers, and human ether a go-go-like 2
channels, that share many of hERG1's biophysical features. The expression
pattern of these two channels was compared to that of the classical inward
rectifying K(+) channels, IRK, that are widely expressed in astrocytic cells
and classically considered a marker of astrocytic differentiation. In our
study, hERG1 was found to be specifically overexpressed in high-grade
astrocytomas, that is, glioblastoma multiforme (GBM). In addition, we
present evidence that, in GBM cell lines, hERG1 channel activity actively
contributes to malignancy by promoting vascular endothelial growth factor
secretion, thus stimulating the neoangiogenesis typical of high-grade
gliomas. Our data provide important confirmation for studies proposing the
hERG1 channel as a molecular marker of tumour progression and a possible
target for novel anticancer therapies.British Journal of Cancer advance
online publication, 20 September 2005; doi:10.1038/sj.bjc.6602775
www.bjcancer.com.
PMID: 16175187 [PubMed - as supplied by publisher]
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| 2: Br J Cancer.
2005 Aug 22;93(4):412-7. |
|
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Salvage high-dose chemotherapy for children with
extragonadal germ-cell tumours.
De
Giorgi U, Rosti
G, Slavin
S, Yaniv
I, Harousseau
JL, Ladenstein
R, Demirer
T, Dini
G; on
the behalf of the European Group for Blood and Marrow Transplantation Solid
Tumours and Paediatric Disease Working Parties.
Istituto Oncologico Romagnolo-Department of Oncology/Haematology, Santa
Maria delle Croci Hospital, Ravenna, Italy. ugo_degiorgi@yahoo.com
We reviewed the European Group for Blood and Marrow Transplantation (EBMT)
experience with salvage high-dose chemotherapy (HDC) in paediatric patients
with extragonadal germ-cell tumour (GCT). A total of 23 children with
extragonadal GCT, median age 12 years (range 1-20), were treated with
salvage HDC with haematopoietic progenitor cell support. The GCT primary
location was intracranial site in nine cases, sacrococcyx in eight,
retroperitoneum in four, and mediastinum in two. In all, 22 patients had a
nongerminomatous GCT and one germinoma. Nine patients received HDC in first-
and 14 in second- or third-relapse situation. No toxic deaths occurred.
Overall, 16 of 23 patients (70%) achieved a complete remission. With a
median follow-up of 66 months (range 31-173 months), 10 (43%) are
continuously disease-free. Of six patients who had a disease recurrence
after HDC, one achieved a disease-free status with surgical resection
followed by chemotherapy and radiotherapy. In total, 11 patients (48%) are
currently disease-free. Eight of 14 patients (57%) with extracranial primary
and three of nine patients (33%) with intracranial primary GCT are currently
disease-free. HDC induced impressive long-term remissions as salvage
treatment in children with extragonadal extracranial GCTs. Salvage HDC
should be investigated in prospective trials in these patients.
PMID: 16106248 [PubMed - indexed for MEDLINE]
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| 3: Cancer. 2005 Sep 21; [Epub
ahead of print] |
|
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A Phase I study of concurrent RMP-7 and carboplatin with
radiation therapy for children with newly diagnosed brainstem gliomas.
Packer
RJ, Krailo
M, Mehta
M, Warren
K, Allen
J, Jakacki
R, Villablanca
JG, Chiba
A, Reaman
G.
Division of Neurology, Children's National Medical Center, Washington, DC.
BACKGROUND: Ninety percent of children with diffuse, intrinsic brainstem
tumors will die within 18 months of diagnosis. Radiotherapy is of transient
benefit to these children, and a potential way to improve its efficacy is to
add radiosensitizers. Carboplatin is antineoplastic and radiosensitizing;
however, its delivery to the primary tumor site is problematic. RMP-7 is a
bradykinin analog that causes selective permeability of the
blood-brain-tumor interface. The objective of this Phase I study was to
determine the toxicity and feasibility of delivering RMP-7 and carboplatin
for 5 successive days during radiotherapy to children with newly diagnosed,
diffuse, intrinsic brainstem gliomas. METHODS: RMP-7 was given prior to the
end of carboplatin infusion. Local radiotherapy, in dose fractions of 180
centigrays (cGy) per day (to a total dose of 5940 cGy), was given within 4
hours of completion of drug delivery. Duration of treatment was escalated in
a stepwise, weekly fashion in cohorts of 3 patients, until there was
treatment-limiting toxicity or until radiotherapy was completed. Thirteen
patients were treated, and their median age was 7 years (age range, 3-12
yrs). RESULTS: One child died early during treatment of progressive disease
and was not assessable for toxicity. Treatment for 3 weeks, 4 weeks, and 5
weeks was tolerated well, with mild flushing, tachycardia, nausea, emesis,
dizziness, and abdominal pain. One of 3 children treated at the full
duration of therapy (33 doses over 7 weeks) developed dose-limiting
hepatotoxicity and neutropenia. The estimated median survival was 328 days,
and 1 patient remained free of disease progression for > 400 days after
the initiation of treatment. CONCLUSIONS: The results of this study
confirmed the feasibility of giving RMP-7 and carboplatin daily during
radiotherapy to children with brainstem tumors. Cancer 2005. (c) 2005
American Cancer Society.
PMID: 16177987 [PubMed - as supplied by publisher]
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| 4: Childs
Nerv Syst. 2005 Jun;21(6):477-81. Epub 2004 Sep 15. |
|
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Management of pilocytic astrocytoma with diffuse
leptomeningeal spread: two cases and review of the literature.
Aryan
HE, Meltzer
HS, Lu
DC, Ozgur
BM, Levy
ML, Bruce
DA.
Division of Neurosurgery, University of California at San Diego, San Diego,
CA 92103, USA. hearyan@ucsd.edu
INTRODUCTION: Leptomeningeal dissemination of juvenile pilocytic astrocytoma
(JPA) is a rare event. We report two children with disseminated JPAs treated
with a chemotherapeutic agent, temozolomide, after progression of the
disease despite surgery, traditional chemotherapy, and/or radiation therapy.
CASE REPORTS: Patient 1 presented with hydrocephalus and progressive lower
extremity weakness, and was found to have a suprasellar mass as well as
extensive spinal disease. Ventriculoperitoneal shunting, decompressive
laminectomy with spinal tumor debulking, and chemotherapy with carboplatin
and vincristine were initially employed. However, disease progressed and
craniospinal irradiation and temozolomide were used. Patient 1 remains in a
fair condition today, 2 years later. Patient 2 presented at 8 months of age
with failure to thrive. Imaging revealed a cystic lesion in the hypothalamic
region with extensive subarachnoid metastatic disease to the spine. Biopsy
was performed followed by chemotherapy with vincristine,
cyclohexylchloroethylnitrosourea (CCNU), 6-TG, and procarbazine. Due to the
continued progression of the disease, cytoreductive surgery was performed
and her chemotherapeutic regimen was switched to temozolomide. Two years
after initial presentation patient 2 is clinically much improved with stable
residual disease. DISCUSSION: We review the literature and discuss treatment
strategies for this challenging disease.
Publication Types:
- Case Reports
- Review
- Review of Reported Cases
PMID: 15378329 [PubMed - indexed for MEDLINE]
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| 5: Clin Neuropathol.
2005 Sep-Oct;24(5):219-24. |
|
Correlation between histological grade and MIB-1 and p53
immunoreactivity in meningiomas.
Ozen
O, Demirhan
B, Altinors
N.
Department of Pathology, Baskent University Faculty of Medicine, Ankara,
Turkey. ozlemo@baskent-ank.edu.tr
OBJECTIVE: Meningiomas for the most part are slow-growing benign tumors, but
complete removal can be difficult and recurrence is an issue. The aim of
this study was to re-evaluate tumors diagnosed as meningioma previously in
our hospital, according to the latest World Health Organization
classification. We also examined the relationships among parameters such as
brain invasion, histological grade and Ki-67 and p53 expression in these
tumors. MATERIALS AND METHODS: Meningioma biopsy specimens numbering 60 (48
grade I, 11 grade II, and 1 grade III tumors) were examined
immunohistochemically using monoclonal antibodies for Ki-67 (MIB-1) and p53
protein. The MIB-1 labeling index (LI) for each tumor was calculated as a
percentage based on the number of stained cells per total cells counted. The
level of p53 expression in each sample was semiquantatively evaluated as
< 1%, 1 - 10%, 10 - 70%, or > 70%. Any value > 1% was accepted as
presence of p53 expression. RESULTS: Of the 60 meningiomas, 7 (11.7%)
exhibited brain invasion. The mean MIB-1 LI values for the grade I and grade
II tumors were 1.1% and 2.3%, respectively. The corresponding levels of p53
protein expression in these groups were 54.1% and 72.7%. The MIB-1 LI and
the level of p53 expression in the one grade III meningioma were 6.7% and 10
- 70%, respectively. Histological grade was significantly correlated with
MIB-1 LI and with p53 expression (p < 0.01 for both). Brain invasion was
not correlated with histological grade, MIB-1 LI, or p53 expression.
CONCLUSION: The results indicate that MIB-1 LI and p53 protein expression
are good indicators of histological grade in meningioma and may be
particularly valuable for distinguishing borderline atypical meningiomas.
The number of cases was limited, but the findings also suggest that brain
invasion is a prognostic parameter independent of grade, MIB-1 LI and p53
expression.
PMID: 16167545 [PubMed - in process]
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| 6: Clin Neuropathol.
2005 Sep-Oct;24(5):209-18. |
|
Association of chromosome 7, chromosome 10 and EGFR gene
amplification in glioblastoma multiforme.
Lopez-Gines
C, Cerda-Nicolas
M, Gil-Benso
R, Pellin
A, Lopez-Guerrero
JA, Callaghan
R, Benito
R, Roldan
P, Piquer
J, Llacer
J, Barbera
J.
Department of Pathology, Medical School, University of Valencia, Spain.
concha.lopez@uv.es
Glioblastoma multiforme (GBM) is characterized by intratumoral heterogeneity
in both histomorphological and genetic changes, displaying a wide variety of
numerical chromosome aberrations, the most common of which are trisomy 7 and
monosomy 10. The amplification of the epidermal growth factor receptor
(EGFR) gene is the most frequently reported genetic abnormality. The
associations between these parameters and their implication in the tumoral
progression are poorly understood. We performed simultaneous fluorescence in
situ hybridization (FISH) with centromeric DNA probes for chromosomes 7 and
10 in smear preparations, and EGFR gene amplification by PCR from 25 cases
of GBM. Trisomy/ polysomy for chromosome 7 was present in 76% of cases and
monosomy 10 in 68%. Both alterations were associated in 56% of cases. The
EGFR gene was amplified in 52% of tumors; in 44% associated with trisomy/
polysomy 7, and in 36% with monosomy 10. The three parameters were
associated together in 28% of cases. Kaplan-Meier survival rate analysis
demonstrated lower survival rates in patients with monosomy 10, trisomy 7,
and monosomy associated with trisomy 7. The other combinations were not
different in frequency in relation to survival. In the present study,
trisomy/polysomy 7 and monosomy 10 have been found to be frequently
associated. The combination of both anomalies is probably important in the
tumorigenesis of glioblastoma. Moreover, this association is apparently
independent of EGFR gene amplification, which could be a later event in this
process.
PMID: 16167544 [PubMed - in process]
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| 7: Clin Neuropathol.
2005 Sep-Oct;24(5):201-8. |
|
Immunotreatment in patients with glioblastoma
multiforme--a histopathological evaluation of reactive and inflammatory
changes.
Persson
A, Skagerberg
G, Salford
LG, Englund
E; Brain
Immuno-Gene Tumour Therapy Group.
Department of Pathology, Division of Neuropathology, University Hospital,
Lund, Sweden. Annette.Persson@med.lu.se
Glioblastoma multiforme (GBM) is the most common highly malignant brain
tumor and is also one among the most therapy-resistant human neoplasias. At
the University Hospital in Lund, a group of patients with GBM were treated
with a new therapy form attempting immunization by glioma cells transfected
to produce interferon-gamma. The purpose of this report was to evaluate
tumor material from the first nine patients treated with this therapy,
assessing the levels of inflammatory/reactive cells (lymphocytes and
macrophages). Tumor biopsies from surgery performed at different time points
during treatment were analyzed with conventional histotechnical methods and
immunohistochemistry. A post-mortem neuropathological investigation with a
whole brain assessment was achieved in 5 immunized patients. The results
show that cytotoxic T lymphocytes exhibited a mild increase during
immunotreatment. This increase indicates an invoked stimulation of a
cytotoxic T cell reaction, which may prove beneficial when immunization is
adequately manipulated in dosage and timing.
PMID: 16167543 [PubMed - in process]
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| 8: Int
J Radiat Oncol Biol Phys. 2005 Oct 1;63(2):511-9. |
|
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Reirradiation of recurrent high-grade gliomas using amino
acid PET (SPECT)/CT/MRI image fusion to determine gross tumor volume for
stereotactic fractionated radiotherapy.
Grosu
AL, Weber
WA, Franz
M, Stark
S, Piert
M, Thamm
R, Gumprecht
H, Schwaiger
M, Molls
M, Nieder
C.
Department of Radiation Oncology, Klinikum rechts der Isar, Technical
University of Munich, Munich, Germany.
Purpose: To develop a valid treatment strategy for recurrent high-grade
gliomas using stereotactic hypofractionated reirradiation based on biologic
imaging and temozolomide. Patients and Methods: The trial included a total
of 44 patients with recurrent high-grade gliomas (1 patient with anaplastic
oligodendroglioma, 8 with anaplastic astrocytoma, 33 with glioblastoma
multiforme, and 2 with gliosarcoma) after previous surgery and postoperative
conventional radiotherapy +/- chemotherapy. For fractionated stereotactic
radiotherapy (SFRT) treatment planning, the gross tumor volume was defined
by (11)C-methionine positron emission tomography (MET-PET) or
(123)I-alpha-methyl-tyrosine (IMT) single-photon computed emission
tomography (SPECT)/computed tomography (CT)/magnetic resonance imaging (MRI)
fusion in 82% of the patients and by CT/T1+gadolinium-MRI image fusion in
18% of the patients. Six fractions of 5 Gy were administered in 6 days. In
29 of 44 patients (66%), chemotherapy with temozolomide (200 mg/m(2) body
surface/day) was given in one to two cycles before and four to five cycles
after SFRT. The patients were evaluated in follow-up by clinical
investigators and MRI or CT every 3 months after SFRT until death. In cases
suspicious for radiation necrosis, a MET-PET or IMT-SPECT investigation was
performed. Results: The median survival time in the whole group was 8
months. Treatment planning based on PET(SPECT)/CT/MRI imaging was associated
with improved survival in comparison to treatment planning using CT/MRI
alone: median survival time 9 months vs. 5 months (p = 0.03, log-rank).
Median survival time were 11 months for patients who received SFRT based on
biologic imaging plus temozolomide and significantly lower, 6 months for
patients treated with SFRT without biologic imaging, without temozolomide or
without both (p = 0.008, log rank). The most important prognostic factor in
univariate analysis was a long interval between initial diagnosis and
recurrence (p = 0.0002, log-rank). In the multivariate model, time interval
to retreatment (p = 0.006) and temozolomide (p = 0.04) remained
statistically significant. No acute neurologic toxicity Grade 3 or higher
and no Grade 4 hematologic toxicity was observed. Conclusion: This is the
first study of biologic imaging optimized SFRT plus temozolomide in
recurrent high-grade gliomas. It demonstrates the feasibility and safety of
this approach. The most striking result of the trial is the statistically
significant longer survival time in the univariate analysis for patients
reirradiated using MET-PET or IMT-SPECT/CT/MRI image fusion in the treatment
planning, in comparison to patients treated based on MRI/CT alone.
Multivariate analysis confirmed a significant survival benefit from
multimodal treatment (i.e., addition of temozolomide), despite the limited
number of patients. Whether treatment planning with SPECT/PET independently
influences survival has to be studied in a larger series of patients.
PMID: 16168843 [PubMed - in process]
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| 9: Int
J Radiat Oncol Biol Phys. 2005 Oct 1;63(2):362-72. |
|
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Treatment planning with protons for pediatric
retinoblastoma, medulloblastoma, and pelvic sarcoma: How do protons compare
with other conformal techniques?
Lee
CT, Bilton
SD, Famiglietti
RM, Riley
BA, Mahajan
A, Chang
EL, Maor
MH, Woo
SY, Cox
JD, Smith
AR.
Department of Radiation Oncology, The University of Texas M. D. Anderson
Cancer Center, Houston, TX, USA.
Purpose: To calculate treatment plans and compare the dose distributions and
dose-volume histograms (DVHs) for photon three-dimensional conformal
radiation therapy (3D-CRT), electron therapy, intensity-modulated radiation
therapy (IMRT), and standard (nonintensity modulated) proton therapy in
three pediatric disease sites. Methods and Materials: The tumor volumes from
8 patients (3 retinoblastomas, 2 medulloblastomas, and 3 pelvic sarcomas)
were studied retrospectively to compare DVHs from proton therapy with
3D-CRT, electron therapy, and IMRT. In retinoblastoma, several planning
techniques were analyzed: A single electron appositional beam was compared
with a single 3D-CRT lateral beam, a 3D-CRT anterior beam paired with a
lateral beam, IMRT, and protons. In medulloblastoma, three posterior fossa
irradiation techniques were analyzed: 3D-CRT, IMRT, and protons.
Craniospinal irradiation (which consisted of composite plans of both the
posterior fossa and craniospinal components) was also evaluated, primarily
comparing spinal irradiation using 3D-CRT electrons, 3D-CRT photons, and
protons. Lastly, in pelvic sarcoma, 3D-CRT, IMRT, and proton plans were
assessed. Results: In retinoblastoma, protons resulted in the best target
coverage combined with the most orbital bone sparing (10% was the mean
orbital bone volume irradiated at >/=5 Gy for protons vs. 25% for 3D-CRT
electrons, 69% for IMRT, 41% for a single 3D lateral beam, 51% for a 3D
anterolateral beam with a lens block, and 65% for a 3D anterolateral beam
without a lens block). A single appositional electron field was the next
best technique followed by other planning approaches. In medulloblastoma,
for posterior fossa and craniospinal irradiation, protons resulted in the
least dose to the cochlea (for only posterior fossa irradiation at >/=20
Gy, 34% was the mean cochlear volume irradiated for protons, 87% for IMRT,
89% for 3D-CRT) and hypothalamus-pituitary axis (for only posterior fossa
irradiation at >/=10 Gy, 21% was the mean hypothalamus-pituitary volume
irradiated for protons, 81% for IMRT, 91% for 3D-CRT); additional dose
reductions to the optic chiasm, eyes, vertebrae, mandible, thyroid, lung,
kidneys, heart, and liver were seen. Intensity-modulated radiotherapy
appeared to be the second best technique for posterior fossa irradiation.
For spinal irradiation 3D-CRT electrons were better than 3D-CRT photons in
sparing dose to the thyroid, heart, lung, kidney, and liver. With pelvic
sarcoma, protons were superior in eliminating any dose to the ovaries (0% of
mean ovarian volume was irradiated at >/=2 Gy with protons) and to some
extent, the pelvic bones and vertebrae. Intensity-modulated radiotherapy did
show more bladder dose reduction than the other techniques in pelvic sarcoma
irradiation. Conclusions: In the diseases studied, using various techniques
of 3D-CRT, electrons, IMRT, and protons, protons are most optimal in
treating retinoblastomas, medulloblastomas (posterior fossa and
craniospinal), and pelvic sarcomas. Protons delivered superior target dose
coverage and sparing of normal structures. As dose-volume parameters are
expected to correlate with acute and late toxicity, proton therapy should
receive serious consideration as the preferred technique for the treatment
of pediatric tumors.
PMID: 16168831 [PubMed - in process]
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| 10: J
Clin Oncol. 2005 Sep 20;23(27):6647-56. |
|
-
Phase I trial of tipifarnib in patients with recurrent
malignant glioma taking enzyme-inducing antiepileptic drugs: a north
american brain tumor consortium study.
Cloughesy
TF, Kuhn
J, Robins
HI, Abrey
L, Wen
P, Fink
K, Lieberman
FS, Mehta
M, Chang
S, Yung
A, Deangelis
L, Schiff
D, Junck
L, Groves
M, Paquette
S, Wright
J, Lamborn
K, Sebti
SM, Prados
M.
Neuro-Oncology Program, David Geffen School of Medicine at University of
California, Los Angeles, 710 Westwood Plaza, Reed Bldg, Room I-230, Los
Angeles, CA 90095; e-mail: tcloughe@ucla.edu.
PURPOSE To determine the maximum-tolerated dose (MTD), toxicities, and
clinical effect of tipifarnib, a farnesyltransferase (FTase) inhibitor, in
patients with recurrent malignant glioma taking enzyme-inducing
antiepileptic drugs (EIAEDs). This study compares the pharmacokinetics and
pharmacodynamics of tipifarnib at MTD in patients on and off EIAEDs.
PATIENTS AND METHODS Recurrent malignant glioma patients were treated with
tipifarnib using an interpatient dose-escalation scheme. Pharmacokinetics
and pharmacodynamics were assessed. Results Twenty-three assessable patients
taking EIAEDs received tipifarnib in escalating doses from 300 to 700 mg bid
for 21 of 28 days. The dose-limiting toxicity was rash, and the MTD was 600
mg bid. There were significant differences in pharmacokinetic parameters at
300 mg bid between patients on and not on EIAEDs. When patients on EIAEDs
and not on EIAEDs were treated at MTD (600 and 300 mg bid, respectively),
the area under the plasma concentration-time curve (AUC)(0-12 hours) was
approximately two-fold lower in patients on EIAEDs. Farnesyltransferase
inhibition was noted at all tipifarnib dose levels, as measured in
peripheral-blood mononuclear cells (PBMC). CONCLUSION Toxicities and
pharmacokinetics differ significantly when comparing patients on or off
EIAEDs. EIAEDs significantly decreased the maximum concentration, AUC(0-12
hours), and predose trough concentrations of tipifarnib. Even in the
presence of EIAEDs, the levels of tipifarnib were still sufficient to
potently inhibit FTase activity in patient PBMCs. The relevance of these
important findings to clinical activity will be determined in ongoing
studies with larger numbers of patients.
PMID: 16170172 [PubMed - in process]
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| 11: J Neurochem.
2005 Sep;94(5):1457-70. Epub 2005 Jun 30. |
|
-
Integration of G protein signals by extracellular
signal-regulated protein kinases in SK-N-MC neuroepithelioma cells.
Chan
AS, Yeung
WW, Wong
YH.
Department of Biochemistry, the Molecular Neuroscience Center, and the
Biotechnology Research Institute, Hong Kong University of Science and
Technology, Clear Water Bay, Kowloon, Hong Kong.
Mammalian cells often receive multiple extracellular stimuli under
physiological conditions, and the various signaling inputs have to be
integrated for the processing of complex biological responses. G
protein-coupled receptors (GPCRs) are critical players in converting
extracellular stimuli into intracellular signals. In this report, we
examined the integration of different GPCR signals by mitogen-activated
protein kinases (MAPKs) using the SK-N-MC human brain neuroepithelioma cells
as a neuronal model. Stimulation of the Gi-coupled neuropeptide Y1 and
Gq-coupled muscarinic M1 acetylcholine receptors, but not the Gs-coupled
dopamine D1 receptor, led to the activation of extracellular
signal-regulated kinase (ERK). All three receptors were also capable of
stimulating c-Jun NH2-terminal kinases (JNK) and p38 MAPK. The Gi-mediated
ERK activation was completely suppressed upon inhibition of Src tyrosine
kinases by PP1, while the Gq-induced response was suppressed by both PP1 and
the Ca2+ chelator, BAPTA-AM. In contrast, activations of JNK and p38 by Gs-,
Gi-, and Gq-coupled receptors were sensitive to PP1 and BAPTA-AM
pretreatments. Simultaneous stimulation of Gi- and Gq-coupled receptors
resulted in the synergistic activation of ERK, but not JNK or p38 MAPK. The
Gi/Gq-induced synergistic ERK activation was PTX-sensitive, and appeared to
be a co-operative effect between Ca2+ and Src family tyrosine kinases.
Enhanced ERK activation was associated with an increase in CREB
phosphorylation, while the JNK and p38-responsive transcription factor ATF-2
was weakly enhanced upon Gi/Gq-induction. This report provides evidence that
G protein signals can be integrated at the level of MAPK, resulting in
differential effects on ERK, JNK and p38 MAPK in SK-N-MC cells.
PMID: 15992362 [PubMed - indexed for MEDLINE]
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| 12: J
Neurol Neurosurg Psychiatry. 2005 Oct;76(10):1425-30. |
|
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Long term experience of gamma knife radiosurgery for
benign skull base meningiomas.
Kreil
W, Luggin
J, Fuchs
I, Weigl
V, Eustacchio
S, Papaefthymiou
G.
Department of Neurosurgery, Medical University Graz, Auenbruggerplatz 29,
A-8036 Graz, Austria. wolfgang.kreil@meduni-graz.at.
OBJECTIVES: As most reports on the gamma knife have related only to short or
mid-term results, we decided to evaluate the effectiveness and toxicity of
radiosurgical treatment for benign skull base meningiomas in 200 patients
with a follow up of 5-12 years to define the role of gamma knife
radiosurgery (GKRS) for basal meningiomas and to provide further data for
comparison with other treatment options. METHODS: In total, 99 patients were
treated with a combination of microsurgical resection and GKRS. In 101
patients, GKRS was performed as the sole treatment option. Tumour volumes
ranged from 0.38 to 89.8 cm(3) (median 6.5 cm(3)), and doses of 7-25 Gy
(median 12 Gy) were given to the tumour borders at covering isodose volume
curves (range 20-80%, median 45%). RESULTS: The actuarial progression free
survival rate was 98.5% at 5 years and 97.2% at 10 years. Passing radiation
induced oedema occurred in two patients (1%). The neurological status
improved in 83 cases (41.5%), remained unaltered in 108 (54%), and
deteriorated in 9 (4.5%). Worsening was transient in seven patients (3.5%)
and unrelated to tumour or treatment in one (0.5%). Repeated microsurgical
resection was performed in five patients following GKRS (2.5%). CONCLUSIONS:
GKRS has proved to be an effective alternative to microsurgical resection,
radiotherapy, and Linac based radiosurgery for adjunctive and primary
treatment of selected patients with basal meningiomas. Because of the
excellent long term tumour control rate and low morbidity associated with
GKRS, this treatment option should be used more frequently in the
therapeutic management of benign skull base meningiomas.
PMID: 16170090 [PubMed - in process]
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| 13: J Neurooncol.
2005 Jul;73(3):277-8. |
|
-
Hemangiopericytoma in pregnancy: a case report.
Annunziato
M, Alessio
A, Stefano
M, Massimiliano
G, Marco
G, Carmelo
A, Giulio
M.
Publication Types:
PMID: 15980981 [PubMed - indexed for MEDLINE]
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| 14: J Neurooncol.
2005 Jul;73(3):273-5. |
|
-
Treatment of recurrent cerebellar hemangioblastoma with
external radiotherapy in a patient with von Hippel-Lindau disease: a case
report and review of the literature.
Ertas
G, Altundag
MB, Ucer
AR, Cankal
F, Altundag
K.
Department of Radiation Oncology, Ankara Oncology Hospital, Ankara, Turkey.
Von Hippel-Lindau Disease, a multisystem familial cancer syndrome, is
inherited as an autosomal-dominant trait. Common manifestations of the
disease are retinal, cerebellar and medullary hemangioblastomas; renal cysts
and carcinomas; pancreatic cysts; pheochromocytoma; and papilllary
cystadenoma of the epididym. We report the case of a 40-year-old man with
type I von Hippel-Lindau disease treated with external radiotherapy for
recurrent cerebellar hemangioblastoma.
PMID: 15980980 [PubMed - indexed for MEDLINE]
-
| 15: J Neurooncol.
2005 Jul;73(3):269-72. |
|
-
An unusual complication of cancer treatment for acute
lymphoblastic leukemia.
Riel-Romero
RM, Baumann
RJ, Smith
CD.
Department of Neurology, University of Kentucky, College of Medicine,
Lexington, Kentucky, USA. rmriel2@pop.uky.edu
Childhood cancer is a leading cause of mortality in children less than 15
years of age, accounting for about 10.4 of total childhood deaths [Robinson
LL: In: Pizzo PA, Polack DA (eds) Principles and Practice of Pediatric
Oncology, 3rd edn. Lippincott--Raven, Philadelphia--NewYork, 1997, pp.
1-10.]. As more aggressive therapeutic regimens have been adopted and
ostensibly cured patients are being followed for longer periods of time, it
has become increasingly clear that the treatment of cancer can have
significant late effects on the growing child, one of the more troublesome
of which is the induction of secondary malignancy. We report an 11-year-old
child who, as supported by both clinical course and neuroimaging studies,
developed an unusual complication eight years after completing therapy for
acute lymphoblastic leukemia, gliomatosis cerebri.
Publication Types:
PMID: 15980979 [PubMed - indexed for MEDLINE]
-
| 16: J Neurooncol.
2005 Jul;73(3):265-7. |
|
-
Paraganglioma in sella.
Zorlu
F, Selek
U, Ulger
S, Donmez
T, Erden
E.
Department of Radiation Oncology Faculty of Medicine, Hacettepe University,
Ankara, Turkey.
We report a very rare case of a paraganglioma arising from sellar and
suprasellar region which has been treated with radiotherapy following
multiple surgeries.
PMID: 15980978 [PubMed - indexed for MEDLINE]
-
| 17: J Neurooncol.
2005 Jul;73(3):241-52. |
|
-
Primary malignant rhabdoid tumor of the central nervous
system--a comprehensive review.
Tekkok
IH, Sav
A.
Department of Neurosurgery, Mersin University School of Medicine,
Zeytinlibahce Caddesi, 33079, Mersin, Turkey. tekkokih@hotmail.com
This paper presents the case of an eight-year-old girl who presented with
headache and vomiting and was found to harbor a right
fronto-temporo-parietal, partially cystic and centrally solid tumor that
measured 11 x 8 x 7 cm. This vascular tumor was gross totally removed. The
initial histopathologic diagnosis was hemangiopericytoma and the patient
received a total dose of 5330 cGy of external cranial radiation. Twelve
months later, the patient presented with left lower quadrant pain and
limping and the spinal MR scans showed metastases at T4-5, T7, T12-L1 and L3
levels. The voluminous lesion at T12-L1 was surgically removed.
Histopathological examination of both specimens revealed that both tumors in
fact were malignant rhabdoid tumor (MRT). The patient did not benefit from
spinal surgery and died 4 months later. A review of the literature has shown
that since Briner et al'. first report in 1985 [Pediatr Pathol 3: 117-118,
1985], 100 MRT cases have been published. More than two-thirds of reviewed
cases presented with local recurrence or subarachnoid spread after a mean
period of 6.9 months after diagnosis and died two months later.
Infratentorial and pineal location and surgery limited to biopsy were poor
prognostic indicators. Twenty-two cases remained alive at a mean period of
24.5 months. The longest survival with an intracranial MRT was 65 months. Of
those remaining alive, 15 had no evidence of disease (NED). Our case is the
first MRT case immunopositive for HMB-45 and has also shown that the MRT
cells grow aggressive over time as demonstrated by a four-fold increase in
MIB-1 labeling index.
Publication Types:
PMID: 15980975 [PubMed - indexed for MEDLINE]
-
| 18: J Neurooncol.
2005 Jul;73(3):225-38. |
|
-
Intratumoral injection of BCNU in ethanol (DTI-015)
results in enhanced delivery to tumor--a pharmacokinetic study.
Hamstra
DA, Moffat
BA, Hall
DE, Young
JM, Desmond
TJ, Carter
J, Pietronigro
D, Frey
KA, Rehemtulla
A, Ross
BD.
The Department of Radiation, The University of Michigan Medical Center, Ann
Arbor, MI 48109-0648, USA.
Solvent facilitated perfusion (SFP) has been proposed as a technique to
increase the delivery of chemotherapeutic agents to tumors. SFP entails
direct injection of the agent into the tumor in a water-miscible organic
solvent, and because the solvent moves easily through both aqueous solutions
and cellular membranes it drives the penetration of the solubilized
anticancer agent throughout the tumor. To test this hypothesis, we compared
the pharmacokinetics (PK) of 14C-labeled 1,3-bis-chlorethyl-1-nitrosourea
(BCNU) in intra-cerebral 9L rat gliomas after intravenous (IV) infusion in
90% saline--10% ethanol or direct intratumoral (IT) injection of 14C-BCNU in
100% ethanol (DTI-015). Treatment with DTI-015 yielded a peak radioactive
count (Cmax) for the 14C label that was 100-1000 fold higher in the tumor
than in all other tissues in addition to a concentration in the tumor that
was 100-fold higher than that achieved following IV infusion of 14C-BCNU.
Pathologic and auto-radiographic analysis of tissue sections following IT
injection of 14C-BCNU in ethanol into either tumor or normal rat brain
revealed both an enhanced local volume of distribution and an increased
concentration of BCNU delivered to tumor compared to non-tumor bearing
brain. To investigate the mechanism behind the SFP of BCNU to the tumor both
dynamic contrast and perfusion MRI were performed on 9L tumors before and
after treatment and demonstrated a decrease in tumor perfusion following IT
injection of DTI-015. Finally, initial PK of patient blood samples following
administration of DTI-015 into relapsed high-grade glioma indicated a
20-fold decrease in systemic exposure to BCNU compared to IV infusion of
BCNU providing further evidence for the enhanced therapeutic ratio observed
for DTI-015.
PMID: 15980973 [PubMed - indexed for MEDLINE]..
-
| 19: J Neurooncol.
2005 Jul;73(3):211-7. |
|
-
Tumoral micro-blood vessels and vascular microenvironment
in human astrocytic tumors. A transmission electron microscopy study.
Arismendi-Morillo
G, Castellano
A.
Biological Researches Institute, Faculty of Medicine, University of the
Zulia, Apartado 526, Maracaibo, 4003-A, Venezuela. gjam3000@hotmail.com
The development of peritumoral edema is thought to be due to extravasation
of plasma water and macromolecules through a defective blood-brain barrier
(BBB), but the exact mechanism by which occurs is poorly understood. The aim
of this study was analyze at submicroscopic level the morphological changes
in both micro-blood vessels and vascular microenvironment of astrocytic
tumors in an attempt of understanding the pathological aspects that may help
in the future researches for the design of future therapeutic strategies.
Biopsies of 25 patients with pathological diagnosis of astrocytic tumors
were examined with the transmission electron microscope. Both open and close
tight junctions were observed in the micro-blood vessels, inclusive in a
same tumor. Cytoskeletal disorganization associated with disintegrated
perijunctional actin filaments were seen. The paracellular space showed
enlargement and commonly occupied by fluid proteinaceous, endothelial cells
display oncotic and ischemic changes, basal lamina reveals enlargement,
edema, vacuolization and collagen fibers disposed in irregular array.
Pericytes exhibited edema and phagocytoced material, astrocytic
perivascular-feet showed signs of oncosis and necrosis, co-option vessels
totally surrounding by neoplastic cells also were seen. The ultrastructural
abnormalities observed in both junctional complexes and vascular
microenvironment suggest a multi-factorial pathobiology process, probably
hypoxia intratumoral, calcium overload in endothelial cells, and degradative
effects of metalloproteinases over the basal membrane appear as determinant
factors that leading to structural modifications of junctional complexes,
therefore, treatment with both HIF-1alpha and metalloproteinases inhibitors
possibly can contribute with the pharmacological handling of the peritumoral
edema associated with astrocytic tumors.
PMID: 15980971 [PubMed - indexed for MEDLINE]
-
| 20: J Neurosurg.
2005 Aug;103(2):224-32. |
|
Surgical management of the recurrence and regrowth of
craniopharyngiomas.
Minamida
Y, Mikami
T, Hashi
K, Houkin
K.
Department of Neurosurgery, Sapporo Medical University; and Pacific
Neurosurgical Consulting, Sapporo, Japan.
OBJECT: The authors performed a retrospective analysis of a consecutive
series of craniopharyngiomas and their recurrences, which were managed with
surgery alone. METHODS: In the past 20 years, 37 consecutive patients with
craniopharyngiomas underwent surgery without adjuvant radiotherapy. During
that period there was a consistent strategy that surgical management was the
first choice of treatment whenever possible. Of these 37 patients, 11
experienced tumor recurrence (29.7%) during the mean follow-up period of
11.1 years. Of these 11 patients, seven experienced recurrence after
neuroimaging-confirmed total removal, and four patients experienced
recurrence after partial or incomplete removal. In these 11 patients,
surgical removal was performed 17 times. Using a proper surgical approach
(mainly a basal interhemispheric approach) and meticulous microsurgical
techniques, total removal of the recurrent tumor was achieved in nine
surgeries (52.9). The mortality and morbidity rates associated with these 17
surgeries were 0% and 9.1%, respectively. In most cases, visual function was
preserved or improved and intellectual performance was also preserved.
CONCLUSIONS: Recurrence of craniopharyngioma can be safely managed by using
meticulous contemporary microsurgical techniques without additional
radiotherapy. The role of surgery and adjuvant radiotherapy for
craniopharyngiomas may vary in the future, depending on innovations in
treatment and technology. Nevertheless, surgery can be still a major
therapeutic option in the management of recurrent craniopharyngiomas.
PMID: 16175850 [PubMed - in process]
-
| 21: J Neurosurg.
2005 Aug;103(2):210-7. |
|
Case-control study of stereotactic radiosurgery for
recurrent glioblastoma multiforme.
Mahajan
A, McCutcheon
IE, Suki
D, Chang
EL, Hassenbusch
SJ, Weinberg
JS, Shiu
A, Maor
MH, Woo
SY.
Division of Radiation Oncology and the Department of Neurosurgery, The
University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
amahajan@mdanderson.org
OBJECT: The role of stereotactic radiosurgery (SRS) for recurrent
glioblastoma multiforme (GBM) was evaluated in a case-control study.
METHODS: All patients who underwent SRS for recurrent GBM before March 2003
formed the case group. A control group of patients who did not undergo SRS
was created from an institutional database, and each case was matched for
known prognostic factors in GBM. The medical and neuroimaging records of all
the patients were reviewed, and survival and treatment outcomes were
recorded. The case and control groups were well matched with regard to
demographics and pre-SRS interventions. In the control group, the date on
which magnetic resonance imaging identified a recurrent lesion that would
have been eligible for SRS was deemed the "SRS" date. The number
of surgeries performed in the control group was statistically higher than
that in the case group. The median duration of overall survival from
diagnosis was 26 months in the case group and 23 months in the control
group. From the date of SRS or "SRS", the median duration of
survival was 11 months in the case group and 10 months in the control group,
a difference that was not statistically significant. CONCLUSIONS: It appears
that a subgroup of patients with GBMs has a higher than expected median
survival duration despite the initial prognostic factors. In patients with
localized recurrences, survival may be prolonged by applying aggressive
local disease management by using either SRS or resection to equal
advantage.
PMID: 16175848 [PubMed - in process]
-
| 22: J Neurosurg.
2005 Aug;103(2):206-9. |
|
Linear accelerator surgery for meningiomas.
Friedman
WA, Murad
GJ, Bradshaw
P, Amdur
RJ, Mendenhall
WM, Foote
KD, Bova
FJ.
Department of Neurosurgery, University of Florida, Gainesville, Florida
32610, USA. friedman@neurosurgery.ufl.edu
OBJECT: In this paper the authors review the results of a single-center
experience in the use of linear accelerator (LINAC) surgery for
radiosurgical treatment of meningiomas. METHODS: A retrospective analysis of
all patients treated with LINAC surgery for meningiomas between May 1989 and
December 2001 was performed. All patients participated in follow-up review
for a minimum of 2 years, and no patients were excluded. Two hundred ten
patients were treated during the study interval. The actuarial local control
rate for benign tumors was 100% at both 1 and 2 years, and 96% at 5 years.
The actuarial local control rate for atypical tumors was 100% at 1 year, 92%
at 2 years, and 77% at 5 years; and that for malignant tumors was 100% at
both 1 and 2 years, and only 19% at 5 years. Of the 210 patients 13 (6.2%)
experienced temporary radiation-induced complications, and only five (2.3%)
experienced permanent complications. In all patients with a permanent
complication the histological characteristics of the meningioma were
malignant. CONCLUSIONS: Linear accelerator surgery produced high local
control rates and very low rates of permanent morbidity in patients
harboring benign meningiomas.
PMID: 16175847 [PubMed - in process]
-
| 23: J Neurosurg.
2005 Jul;103(1):156-64. |
|
Active immunotherapy for advanced intracranial murine
tumors by using dendritic cell-tumor cell fusion vaccines.
Kjaergaard
J, Wang
LX, Kuriyama
H, Shu
S, Plautz
GE.
Center for Surgery Research, Cleveland Clinic Foundation, Cleveland, Ohio
44195, USA.
OBJECT: Immunotherapy for malignant brain tumors by active immunization or
adoptive transfer of tumor antigen-specific T lymphocytes has the potential
to make up for some of the limitations of current clinical therapy. In this
study, the authors tested whether active immunotherapy is curative in mice
bearing advanced, rapidly progressive intracranial tumors. METHODS: Tumor
vaccines were created through electrofusion of dendritic cells (DCs) and
irradiated tumor cells to form multinucleated heterokaryons that retained
the potent antigen processing and costimulatory function of DCs as well as
the entire complement of tumor antigens. Murine hosts bearing intracranial
GL261 glioma or MCA 205 fibrosarcoma were treated with a combination of
local cranial radiotherapy, intrasplenic vaccination with DC/tumor fusion
cells, and anti-OX40R (CD134) monoclonal antibody (mAb) 7 days after tumor
inoculation. Whereas control mice had a median survival of approximately 20
days, the treated mice underwent complete tumor regression that was
immunologically specific. Seven days after vaccination treated mice
demonstrated robust infiltration of CD4+ and CD8+ T cells, which was
exclusively confined to the tumor without apparent neurological toxicity.
Cured mice survived longer than 120 days with no evidence of tumor
recurrence and resisted intracranial tumor challenge. CONCLUSIONS: These
data indicate a strategy to achieve an antitumor response against tumors in
the central nervous system that is highly focused from both immunological
and anatomical perspectives.
PMID: 16121986 [PubMed - indexed for MEDLINE]..
-
| 24: J Neurosurg.
2005 Jul;103(1):31-7. |
|
Comment in:
Long-term outcome in patients harboring intracranial
ependymoma.
Kawabata
Y, Takahashi
JA, Arakawa
Y, Hashimoto
N.
Department of Neurosurgery, Kyoto University Graduate School of Medicine,
Sakyo-ku, Kyoto, Japan. ykawabata-kyt@umin.ac.jp
OBJECT: The prognostic significance of tumor grade and resection and the
efficacy of prophylactic radiation remain controversial in the management of
intracranial ependymoma. The outcomes in patients with intracranial
ependymoma treated at the Kyoto University Hospital were reviewed
retrospectively, and prognostic significance was analyzed. METHODS: Between
1972 and 2002, 29 patients were seen at the authors' institution. Eighteen
cases involved a Grade II lesion according to the World Health Organization
classification of ependymoma and 11 involved a Grade III lesion.
Postoperative radiation was applied in 24 cases and chemotherapy was
administered in nine. Overall survival and progression-free survival rates
were significantly higher in patients with Grade II ependymoma (p = 0.006
and 0.004, respectively) and in patients who had undergone gross-total
resection of the tumor (p = 0.002 and 0.04, respectively). Fourteen patients
relapsed from 10 to 120 months (median 39 months) after diagnosis. In nine
patients the ependymoma recurred only at the original tumor site. Three
patients experienced both local and distant relapse, whereas two others had
only a distant relapse. All relapses of the Grade II ependymoma initially
occurred at the primary tumor site. Histological grade and extent of
resection were significantly associated with tumor dissemination (p = 0.0034
and 0.0011, respectively). The field of postoperative radiation had no
impact on patient survival or lesion recurrence. CONCLUSIONS: Tumor grade
and resection are the two important prognostic factors with respect to
patient survival, tumor recurrence, and tumor dissemination. Considering
that relapses were predominantly local and that there was no apparent
benefit from prophylactic radiation, the authors concluded that
postoperative radiation should be focused on local control, especially for
Grade II ependymomas.
PMID: 16121970 [PubMed - indexed for MEDLINE]
-
| 25: J Neurosurg.
2005 Jul;103(1):4; discussion 4-5. |
|
Comment on:
Long-term outcome in patients harboring intracranial
ependymoma.
Boop
FA.
Publication Types:
PMID: 16121965 [PubMed - indexed for MEDLINE]
-
| 26: Neurol Res.
2005 Jul;27(5):516-21. |
|
-
Baseline 11C-methionine PET reflects the natural course
of grade 2 oligodendrogliomas.
Ribom
D, Smits
A.
Department of Neuroscience, Neurology, University Hospital, SE-751 85
Uppsala, Sweden. dan.ribom@lthalland.se
OBJECTIVES: The aim of the present study was to assess the usefulness of
positron emission tomography (PET) with the amino acid tracer 11C-methionine
(MET) as a predictor of time to progression (TTP) in patients with
supratentorial grade 2 gliomas. METHODS: Twenty-seven patients with glioma
grade 2 subjected to a baseline PET scan received no anti-tumour treatment
except for a diagnostic operation, and were followed until tumour
progression. The prognostic impact of the MET uptake and of other prognostic
factors was studied. RESULTS: Twenty-five of the patients (93%) experienced
tumour progression after a median of 103 weeks. Low uptake of MET was a
predictor for long TTP in patients with oligodendrogliomas (p = 0.04) but
not in astrocytomas/oligoastrocytomas. Other predictors for long TTP were
oligodendroglioma histology (p = 0.009) and seizures as presenting symptom
(p = 0.03). Favourable prognostic factors for overall survival were
oligodendroglioma histology (p = 0.002) and good performance status (p =
0.03). CONCLUSIONS: PET MET has a definite role in the therapeutic
management of grade 2 gliomas. However, for the optimal use of PET MET in
the clinical management of these patients, histological subclassification of
the tumour is required.
PMID: 15978178 [PubMed - indexed for MEDLINE]
-
| 27: Neurology. 2005 Jan
25;64(2):326-33. |
|
-
Reduced glutamine synthetase in hippocampal areas with
neuron loss in temporal lobe epilepsy.
van
der Hel WS, Notenboom
RG, Bos
IW, van
Rijen PC, van
Veelen CW, de
Graan PN.
Department of Pharmacology & Anatomy, Rudolf Magnus Institute of
Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
BACKGROUND: Increased levels of glutamate have been reported in the
epileptogenic hippocampus of patients with temporal lobe epilepsy (TLE).
This sustained increase, which may contribute to the initiation and
propagation of seizure activity, indicates impaired clearance of glutamate
released by neurons. Glutamate is predominantly cleared by glial cells
through the excitatory amino acid transporter 2 (EAAT2) and its subsequent
conversion to glutamine by the glial enzyme glutamine synthetase (GS).
METHODS: The authors examined the hippocampal distribution of GS, EAAT2, and
glial fibrillary acidic protein (GFAP) by immunohistochemistry in TLE
patients with (HS group) and without hippocampal sclerosis (non-HS group),
and in autopsy controls. In hippocampal homogenates the authors measured
relative protein amounts by immunoblotting and GS enzyme activity. RESULTS:
In the autopsy control and non-HS group GS immunoreactivity (IR) was
predominantly found in glia in the neuropil of the subiculum, of the
pyramidal cell layer of all CA fields, and in the supragranular layer of the
dentate gyrus. In the HS group, GS and EAAT2 IR were markedly reduced in
subfields showing neuron loss (CA1 and CA4), whereas GFAP IR was increased.
The reduction in GS IR in the HS group was confirmed by immunoblotting and
paralleled by decreased GS enzyme activity. CONCLUSIONS: Glial glutamine
synthetase is downregulated in the hippocampal sclerosis (HS) hippocampus of
temporal lobe epilepsy (TLE) patients in areas with severe neuron loss. This
downregulation appears to be pathology-related, rather than seizure-related,
and may be part of the mechanism underlying impaired glutamate clearance
found in the hippocampus of TLE patients with HS.
PMID: 15668432 [PubMed - indexed for MEDLINE]
-
| 28: Neurology. 2005 Jan
25;64(2):318-25. |
|
-
Whole-brain T2 mapping demonstrates occult abnormalities
in focal epilepsy.
Rugg-Gunn
FJ, Boulby
PA, Symms
MR, Barker
GJ, Duncan
JS.
MRI Unit, National Society for Epilepsy and Department of Clinical and
Experimental Epilepsy, Institute of Neurology, University College London,
UK.
OBJECTIVES: To examine the cerebral structure of 14 patients with partial
seizures and acquired lesions, 20 patients with malformations of cortical
development (MCDs), and 45 patients with partial seizures and normal
conventional MRI using whole-brain T2 mapping and statistical parametric
mapping (SPM). METHODS: T2 maps were calculated, and individual patients
were compared with a group of 30 control subjects using SPM. RESULTS: T2
mapping and objective voxel-by-voxel statistical comparison identified
regions of increased T2 signal in all 14 patients with acquired
nonprogressive cerebral lesions and partial seizures. In all of these, the
areas of increased T2 signal concurred with abnormalities identified on
visual inspection of conventional MRI. In 18 of 20 patients with MCDs, SPM
detected regions of increased T2 signal, all of which corresponded to
abnormalities identified on visual inspection of conventional MRI. In
addition, in both groups, there were areas that were normal on conventional
imaging, which demonstrated abnormal T2 signal. Voxel-by-voxel statistical
analysis identified increased T2 signal in 23 of the 45 patients with
cryptogenic focal epilepsy. In 20 of these, the areas of increased T2 signal
concurred with epileptiform EEG abnormality and clinical seizure semiology.
Group analysis of MRI-negative patients with electroclinical seizure onset
localizing to the left and right temporal and left and right frontal regions
revealed increased T2 signal within the white matter of each respective
lobe. CONCLUSIONS: T2 mapping analyzed using statistical parametric mapping
was sensitive in patients with malformations of cortical development and
acquired cerebral damage. Increased T2 signal in individual and grouped
MRI-negative patients suggests that minor structural abnormalities exist in
occult epileptogenic cerebral lesions.
PMID: 15668431 [PubMed - indexed for MEDLINE]
-
| 29: Oncogene. 2005 Sep 19;
[Epub ahead of print] |
|
-
Selective destruction of glioblastoma cells by
interference with the activity or expression of ATF5.
Angelastro
JM, Canoll
PD, Kuo
J, Weicker
M, Costa
A, Bruce
JN, Greene
LA.
Department of Pathology and Center for Neurobiology and Behavior, Columbia
University College of Physicians and Surgeons, New York, NY, USA.
Glioblastoma multifome is the most common and most aggressive primary brain
tumor with no current curative therapy. We found expression of the bZip
transcription factor ATF5 in all 29 human glioblastomas and eight human and
rat glioma cell lines assessed. ATF5 is not detectably expressed by mature
brain neurons and astrocytes, but is expressed by reactive astrocytes.
Interference with ATF5 function or expression in all glioma cell lines
tested causes marked apoptotic cell death. In contrast, such manipulations
do not affect survival of ATF5-expressing cultured astrocytes or of several
other cell types that express this protein. In a proof-of-principle
experiment, retroviral delivery of a function-blocking mutant form of ATF5
into a rat glioma model evokes death of the infected tumor cells, but not of
infected brain cells outside the tumors. The widespread expression of ATF5
in glioblastomas and the selective effect of interference with ATF5
function/expression on their survival suggest that ATF5 may be an attractive
target for therapeutic intervention in such tumors.Oncogene advance online
publication, 19 September 2005; doi:10.1038/sj.onc.1209116.
PMID: 16170340 [PubMed - as supplied by publisher]
-
| 30: Pediatr Neurosurg.
2005 May-Jun;41(3):137-40. |
|
-
The early years of hemispherectomy.
de
Almeida AN, Marino
R Jr.
University of Sao Paulo, Sao Paulo, Brazil. almeidaan@globe.com
Today, hemispherectomy is a well-established procedure for the treatment of
some sorts of catastrophic epilepsies. This, however, has not always been
the case. The technique was developed to deal with brain tumors; however,
the initial results were not remarkable. Moreover, when its morbidity became
evident, it was almost abandoned. Had it not been for a shift in its use,
with a huge increase in operations on patients with infantile hemiplegia,
this surgery would certainly have disappeared. This paper focuses on the
facts that surrounded these early years.
Publication Types:
PMID: 15995330 [PubMed - indexed for MEDLINE]
|
Volume 4, Number 40 - 27 September
2005