| 1: AJNR
Am J Neuroradiol. 2006 Oct;27(9):1975-82. |
|
-
Comparing perfusion metrics obtained from a single
compartment versus pharmacokinetic modeling methods using dynamic
susceptibility contrast-enhanced perfusion MR imaging with glioma grade.
Law
M, Young
R, Babb
J, Rad
M, Sasaki
T, Zagzag
D, Johnson
G.
Department of Radiology, NYU Medical Center, New York, NY 10016, USA.
lawm01@med.nyu.edu
BACKGROUND AND PURPOSE: Numerous different parameters measured by perfusion
MR imaging can be used for characterizing gliomas. Parameters derived from 3
different analyses were correlated with histopathologically confirmed grade
in gliomas to determine which parameters best predict tumor grade. METHODS:
Seventy-four patients with gliomas underwent dynamic susceptibility
contrast-enhanced MR imaging (DSC MR imaging). Data were analyzed by 3
different algorithms. Analysis 1 estimated relative cerebral blood volume (rCBV)
by using a single compartment model. Analysis 2 estimated fractional plasma
volume (V(p)) and vascular transfer constant (K(trans)) by using a
2-compartment pharmacokinetic model. Analysis 3 estimated absolute cerebral
blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT)
by using a single compartment model and an automated arterial input
function. The Mann-Whitney U test was used make pairwise comparisons. Binary
logistic regression was used to assess whether rCBV, V(p), K(trans), CBV,
CBF, and MTT can discriminate high- from low-grade tumors. RESULTS: rCBV was
the best discriminator of tumor grade ype, followed by CBF, CBV, and K(trans).
Spearman rank correlation factors were the following: rCBV = 0.812 (P <
.0001), CBF = 0.677 (P < .0001), CBV = 0.604 (P < .0001), K(trans) =
0.457 (P < .0001), V(p) = 0.301 (P =.009), and MTT = 0.089 (P = .448).
rCBV was the best single predictor, and K(trans) with rCBV was the best set
of predictors of high-grade glioma. CONCLUSION: rCBV, CBF, CBV K(trans), and
V(p) measurements correlated well with histopathologic grade. rCBV was the
best predictor of glioma grade, and the combination of rCBV with K(trans)
was the best set of metrics to predict glioma grade.
PMID: 17032878 [PubMed - in process]
-
| 2: AJNR
Am J Neuroradiol. 2006 Oct;27(9):1969-74. |
|
-
Improved delineation of glioma margins and regions of
infiltration with the use of diffusion tensor imaging: an image-guided
biopsy study.
Price
SJ, Jena
R, Burnet
NG, Hutchinson
PJ, Dean
AF, Pena
A, Pickard
JD, Carpenter
TA, Gillard
JH.
Academic Neurosurgical Unit and Wolfson Brain Imaging Centre, Department pf
Radiology, University of Cambridge and Cambridge University Hospitals NHS
Foundation Trust, Addenbrooke's Hospital, Cambridge, United Kingdom. sjp58@cam.ac.uk
BACKGROUND AND PURPOSE: The efficacy of radiation therapy, the mainstay of
treatment for malignant gliomas, is limited by our inability to accurately
determine tumor margins. As a result, despite recent advances, the prognosis
remains appalling. Because gliomas preferentially infiltrate along white
matter tracks, methods that show white matter disruption should improve this
delineation. In this study, results of histologic examination from samples
obtained from image-guided brain biopsies were correlated with diffusion
tensor images. METHODS: Twenty patients requiring image-guided biopsies for
presumed gliomas were imaged preoperatively. Patients underwent image-guided
biopsies with multiple biopsies taken along a single track that went into
normal-appearing brain. Regions of interest were determined from the sites
of the biopsies, and diffusion tensor imaging findings were compared with
glioma histology. RESULTS: Using diffusion tissue signatures, it was
possible to differentiate gross tumor (reduction of the anisotropic
component, q > 12% from contralateral region), from tumor infiltration
(increase in the isotropic component, p > 10% from contralateral region).
This technique has a sensitivity of 98% and specificity of 81%. T2-weighted
abnormalities failed to identify the margin in half of all specimens.
CONCLUSION: Diffusion tensor imaging can better delineate the tumor margin
in gliomas. Such techniques can improve the delineation of the radiation
therapy target volume for gliomas and potentially can direct local therapies
for tumor infiltration.
PMID: 17032877 [PubMed - in process]
-
| 3: Br J Cancer.
2006 Oct 3; [Epub ahead of print] |
|
-
Temozolomide 3 weeks on and 1 week off as first-line
therapy for recurrent glioblastoma: phase II study from gruppo italiano
cooperativo di neuro-oncologia (GICNO).
Brandes
AA, Tosoni
A, Cavallo
G, Bertorelle
R, Gioia
V, Franceschi
E, Biscuola
M, Blatt
V, Crino
L, Ermani
M.
1Department of Medical Oncology, Bellaria Hospital, 40139 Bologna, Italy.
The efficacy of temozolomide strongly depends on O(6)-alkylguanine DNA-alkyl
transferase (AGAT), which repairs DNA damage caused by the drug itself.
Low-dose protracted temozolomide administration can decrease AGAT activity.
The main end point of the present study was therefore to test
progression-free survival at 6 months (PFS-6) in glioblastoma patients
following a prolonged temozolomide schedule. Chemonaive glioblastoma
patients with disease recurrence or progression after surgery and standard
radiotherapy were considered eligible. Chemotherapy cycles consisted of
temozolomide 75 mg/m(2)/daily for 21 days every 28 days until disease
progression. O(6)-methyl-guanine-DNA-methyl-tranferase (MGMT) was determined
in 22 patients (66.7%). A total of 33 patients (median age 57 years, range
31-71) with a median KPS of 90 (range 60-100) were accrued. The overall
response rate was 9%, and PFS-6 30.3% (95% CI:18-51%). No correlation was
found between the MGMT promoter methylation status of the tumours and the
overall response rate, time to progression and survival. In 153 treatment
cycles delivered, the most common grade 3/4 event was lymphopoenia. The
prolonged temozolomide schedule considered in the present study is followed
by a high PFS-6 rate; toxicity is acceptable. Further randomised trials
should therefore be conducted to confirm the efficacy of this
regimen.British Journal of Cancer advance online publication, 3 October
2006; doi:10.1038/sj.bjc.6603376 www.bjcancer.com.
PMID: 17024124 [PubMed - as supplied by publisher]
-
| 4: Childs
Nerv Syst. 2006 Sep 22; [Epub ahead of print] |
|
-
Invasive intracerebral schwannoma mimicking meningioma in
a child.
Bristol
RE, Coons
SW, Rekate
HL, Spetzler
RF.
Division of Neurological Surgery, Barrow Neurological Institute, St.
Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
CASE REPORT: An 8-year-old boy presented to the emergency department after a
generalized tonic-clonic seizure that lasted for 5 min. Magnetic resonance
imaging showed a 2x2 cm, intraaxial, contrast-enhanced cortical lesion in
the posterior right frontal lobe. On several images the lesion appeared to
be dural-based and was presumed to be a meningioma. The patient was placed
on dilantin and returned 1 month later for elective surgical resection.
OUTCOME: At surgery, a rim of intact pia was identified between the dura and
the tumor. Although initial frozen-section analysis was consistent with
meningioma, subsequent immunohistochemical staining and review at an outside
institution established the diagnosis of intracerebral schwannoma. The
patient's postoperative course was uncomplicated and he remains seizure-free
with no sign of recurrence at 18 months. CONCLUSION: Intracerebral
schwannomas are uncommon cortical lesions in children. Imaging
characteristics alone can be misleading; neuropathological support is
essential for accurate diagnosis.
PMID: 17021734 [PubMed - as supplied by publisher]
-
| 5: Childs
Nerv Syst. 2006 Sep 22; [Epub ahead of print] |
|
-
An unusual case of cervical clear-cell meningioma in
pediatric age.
Vural
M, Arslantas
A, Ciftci
E, Artan
S, Atasoy
MA.
Department of Neurosurgery, Eskisehir Osmangazi University Medical Faculty,
Eskisehir, Turkey.
INTRODUCTION AND BACKGROUND: A 4-year-old girl was admitted with complaints
of diplegia, right lower limb monoplegia, and left lower limb monoparesia.
Cervical magnetic resonance imaging revealed an intradural-extramedullary
tumor at the level of C1-C2. The tumor was resected totally. Histopathologic
diagnosis revealed clear-cell meningioma. DISCUSSION: Intraspinal clear-cell
meningioma (ICCM) is a rare aggressive variant of meningioma. There are only
25 cases reported to date, and only 13 of them are in pediatric age group.
Of these 25 ICCM cases, only two are at cervical region. This report is the
first ICCM case at upper cervical region (C1-C2) in both adult and pediatric
age populations.
PMID: 17021731 [PubMed - as supplied by publisher]
-
| 6: Childs
Nerv Syst. 2006 Oct 5; [Epub ahead of print] |
|
-
Diffuse high-grade gliomas as second malignant neoplasms
after radio-chemotherapy for pediatric malignancies.
Romeike
BF, Kim
YJ, Steudel
WI, Graf
N.
Institut fur Neuropathologie, Universitatsklinikum des Saarlandes, 66421,
Homburg/Saar, Germany, bernd.romeike@uniklinikum-saarland.de.
OBJECTS: Diffuse high-grade gliomas are known to develop in children after
cranial irradiation for other malignancies. Here, clinicopathological
characteristics are outlined. METHODS: Nine children received cranial
irradiation and chemotherapy for medulloblastoma (n=2) or acute
lymphoblastic leukemia (n=7). They developed a high-grade glioma 7-14 years
thereafter. Clinical charts, radiologic findings, and pathologic specimens
were reviewed. Archival material was stained immunohistochemically.
CONCLUSION: Gliomas evolving as second malignant neoplasms show
peculiarities and differ in some aspects from their "spontaneous"
counterparts. Most are supratentorial, contrast-enhancing, space-occupying
lesions. They are composed mainly of small undifferentiated cells, which are
mainly negative for glial fibrillary acidic protein and positive for
microtubule associated proteins 2 (MAP2). Epidermal growth factor receptor
labeling could not be detected in any of them. Ki67-labeling was usually
high, whereas p53- and h-ras p21-staining was variable. The median survival
was only 12 months despite intensive treatment.
PMID: 17021727 [PubMed - as supplied by publisher]
-
| 7: Childs
Nerv Syst. 2006 Sep 22; [Epub ahead of print] |
|
-
The role of diffusion-weighted magnetic resonance imaging
in pediatric brain tumors.
Kan
P, Liu
JK, Hedlund
G, Brockmeyer
DL, Walker
ML, Kestle
JR.
Department of Neurosurgery, Primary Children's Medical Center, University of
Utah School of Medicine, 100 North Medical Drive, Salt Lake City, UT, 84113,
USA, john.kestle@hsc.utah.edu.
OBJECTIVES: Diffusion-weighted imaging (DWI) may enhance the radiographic
diagnosis of pediatric brain tumors. This study reviews the DWI properties
of pediatric brain tumors at our institution and examines their relationship
to tumor grade and type. MATERIALS AND METHODS: The preoperative DWI and
apparent diffusion coefficient (ADC) characteristics of brain tumors in 41
children were compared with histologic diagnosis. Signal characteristics on
DWI and ADC maps correlated well with tumor grade. High-grade lesions were
hyperintense on DWI and hypointense on ADC maps. Sensitivity, specificity,
positive predictive value, and negative predictive value were 70, 100, 100,
and 91%, respectively. Signal characteristics did not differ among different
tumors of the same grade. All primitive neuroectodermal tumors showed
diffusion restriction whereas none of the ependymomas did. CONCLUSIONS: The
signal characteristics on DWI and ADC maps appeared to be strongly
correlated to grade in pediatric brain tumors and they may assist with
preoperative diagnostic predictions.
PMID: 17021722 [PubMed - as supplied by publisher]
-
| 8: Clin
Cancer Res. 2006 Oct 1;12(19):5770-6. |
|
-
Randomized study of paclitaxel and tamoxifen deposition
into human brain tumors: implications for the treatment of metastatic brain
tumors.
Fine
RL, Chen
J, Balmaceda
C, Bruce
JN, Huang
M, Desai
M, Sisti
MB, McKhann
GM, Goodman
RR, Bertino
JS Jr, Nafziger
AN, Fetell
MR.
Experimental Therapeutics Program, Division of Medical Oncology,
Neurological Institute of New York, College of Physicians and Surgeons,
Columbia University, 650 West 168th Street, New York, NY 10032, USA.
PURPOSE: Drug resistance in brain tumors is partially mediated by the
blood-brain barrier of which a key component is P-glycoprotein, which is
highly expressed in cerebral capillaries. Tamoxifen is a nontoxic inhibitor
of P-glycoprotein. This trial assessed, in primary and metastatic brain
tumors, the differential deposition of paclitaxel and whether tamoxifen
could increase paclitaxel deposition. EXPERIMENTAL DESIGN: Patients for
surgical resection of their primary or metastatic brain tumors were
prospectively randomized to prior paclitaxel alone (175 mg/m(2)/i.v.) or
tamoxifen for 5 days followed by paclitaxel. Central and peripheral tumor,
surrounding normal brain and plasma, were analyzed for paclitaxel and
tamoxifen. RESULTS: Twenty-seven patients completed the study. Based on a
multivariate linear regression model, no significant differences in
paclitaxel concentrations between the two study arms were found after
adjusting for treatment group (tamoxifen versus control). However, in
analysis for tumor type, metastatic brain tumors had higher paclitaxel
concentrations in the tumor center (1.93-fold, P = 0.10) and in the tumor
periphery (2.46-fold, P = 0.039) compared with primary brain tumors.
Pharmacokinetic analyses showed comparable paclitaxel areas under the serum
concentration between treatment arms. CONCLUSIONS: Paclitaxel deposition was
not increased with this tamoxifen schedule as the low plasma concentrations
were likely secondary to concurrent use of P-450-inducing medications.
However, the statistically higher paclitaxel deposition in the periphery of
metastatic brain tumors provides functional evidence corroborating reports
of decreased P-glycoprotein expression in metastatic versus primary brain
tumors. This suggests that metastatic brain tumors may respond to paclitaxel
if it has proven clinical efficacy for the primary tumor's histopathology.
PMID: 17020983 [PubMed - in process]
-
| 9: Clin
Cancer Res. 2006 Oct 1;12(19):5698-704. |
|
-
YKL-40 and matrix metalloproteinase-9 as potential serum
biomarkers for patients with high-grade gliomas.
Hormigo
A, Gu
B, Karimi
S, Riedel
E, Panageas
KS, Edgar
MA, Tanwar
MK, Rao
JS, Fleisher
M, DeAngelis
LM, Holland
EC.
Clinical Laboratories, Neurosurgical Service, Department of Surgery,
Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY
10021, USA. hormigoa@mskcc.org
PURPOSE: Biomarkers can facilitate diagnosis, monitor treatment response,
and assess prognosis in some patients with cancer. YKL-40 and matrix
metalloproteinase-9 (MMP-9) are two proteins highly differentially expressed
by malignant gliomas. We obtained prospective longitudinal serum samples
from patients with gliomas to determine whether YKL-40 or MMP-9 could be
used as serum markers. EXPERIMENTAL DESIGN: Serum samples were obtained
concurrently with magnetic resonance imaging scans. YKL-40 and MMP-9 were
determined by ELISA and the values correlated with the patient's
radiographic status and survival. RESULTS: High-grade glioma patients who
underwent a surgical resection of their tumor had transient increase of both
YKL-40 and MMP-9 serum levels in the postoperative period. Glioblastoma
multiforme (GBM) patients with no radiographic evidence of disease (n = 10
patients, 50 samples) had a significantly lower level of YKL-40 and MMP-9
than patients with active tumor (n = 66 patients, 209 samples; P = 0.0003
and 0.0002, respectively). Anaplastic glioma patients with no radiographic
evidence of disease (n = 32 patients, 107 samples) also had a significantly
lower level of YKL-40 compared with those patients with active tumor (n = 48
patients, 199 samples; P = 0.04). There was a significant inverse
association between YKL-40 and survival in GBM, hazard ratio (hazard ratio,
1.4; P = 0.02), and anaplastic astrocytoma patients (hazard ratio, 2.2; P =
0.05). CONCLUSIONS: YKL-40 and MMP-9 can be monitored in patients' serum and
help confirm the absence of active disease in GBM and YKL-40 in anaplastic
glioma patients. YKL-40 can be used as predictor of survival in patients
with high-grade glioma. Longitudinal studies with a larger patient
population are needed to confirm these findings.
PMID: 17020973 [PubMed - in process]
-
| 10: Eur
J Cancer. 2006 Oct 4; [Epub ahead of print] |
|
-
Development of luciferase tagged brain tumour models in
mice for chemotherapy intervention studies.
Kemper
EM, Leenders
W, Kusters
B, Lyons
S, Buckle
T, Heerschap
A, Boogerd
W, Beijnen
JH, van
Tellingen O.
Department of Clinical Chemistry, The Netherlands Cancer Institute/Antoni
van Leeuwenhoek Huis, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
The blood-brain barrier (BBB) is considered one of the major causes for the
low efficacy of cytotoxic compounds against primary brain tumours. The aim
of this study was to develop intracranial tumour models in mice featuring
intact or locally disrupted BBB properties, which can be used in testing
chemotherapy against brain tumours. These tumours were established by
intracranial injection of suspensions of different tumour cell lines. All
cell lines had been transfected with luciferase to allow non-invasive
imaging of tumour development using a super-cooled CCD-camera. Following
their implantation, tumours developed which displayed the infiltrative,
invasive or expansive growth patterns that are also found in primary brain
cancer or brain metastases. Contrast-enhanced magnetic resonance imaging
showed that the Mel57, K1735Br2 and RG-2 lesions grow without disruption of
the BBB, whereas the BBB was leaky in the U87MG and VEGF-A-transfected Mel57
lesions. This was confirmed by immunohistochemistry. Bioluminescence
measurements allowed the visualisation of tumour burden already within 4
days after injection of the tumour cells. The applicability of our models
for performing efficacy studies was demonstrated in an experiment using
temozolomide as study drug. In conclusion, we have developed experimental
brain tumour models with partly disrupted, or completely intact BBB
properties. In vivo imaging by luciferase allows convenient follow-up of
tumour growth and these models will be useful for chemotherapeutic
intervention studies.
PMID: 17027258 [PubMed - as supplied by publisher]
-
| 11: J
Neurol Neurosurg Psychiatry. 2006 Oct;77(10):1185-6. |
|
-
Neurological picture. Recurrent episodes of sudden
tetraplegia caused by an anterior cervical arachnoid cyst.
Maiuri
F, Iaconetta
G, Esposito
M.
Department of Neurological Sciences, Section of Neurosurgery, Federico II
University of Naples, Naples, Italy.
Publication Types:
PMID: 16980657 [PubMed - indexed for MEDLINE]
-
| 12: J Neurooncol.
2006 Sep 22; [Epub ahead of print] |
|
-
A North American brain tumor consortium (NABTC 99-04)
phase II trial of temozolomide plus thalidomide for recurrent glioblastoma
multiforme.
Groves
MD, Puduvalli
VK, Chang
SM, Conrad
CA, Gilbert
MR, Tremont-Lukats
IW, Liu
TJ, Peterson
P, Schiff
D, Cloughesy
TF, Wen
PY, Greenberg
H, Abrey
LE, Deangelis
LM, Hess
KR, Lamborn
KR, Prados
MD, Yung
WK.
Department of Neuro-Oncology, The University of Texas MD Anderson Cancer
Center, 1400 Holcombe, 431, Houston, TX, 77030, USA, mgroves@mdanderson.org.
BACKGROUND: Laboratory and clinical data suggest that the anti-angiogenic
agent, thalidomide, if combined with cytotoxic agents, may be effective
against recurrent glioblastoma multiforme (GBM). OBJECTIVES: To determine
6-month progression-free survival (6PFS) and toxicity of temozolomide plus
thalidomide in adults with recurrent GBM. PATIENTS AND METHODS: Eligible
patients had recurrent GBM after surgery, radiotherapy, and/or adjuvant
chemotherapy. Temozolomide was given at 150-200 mg/m(2)/day on days 1-5 of
each 28-day cycle. Thalidomide was given orally at 400 mg at bedtime (days
1-28) and increased to 1,200 mg as tolerated. Patients were evaluated with
magnetic resonance imaging scans every 56 days. The study was designed to
detect an increase of the historical 6PFS for GBM from 10 to 30%. RESULTS:
Forty-four patients were enrolled, 43 were evaluable for efficacy and
safety. The study population included 15 women, 29 men; median age was 53
years (range 32-84); median Karnofsky performance status was 80% (range
60-100%). Thirty-six (82%) patients were chemotherapy-naive. There were 57
reports of toxicity of grade 3 or greater. Non-fatal grade 3-4
granulocytopenia occurred in 15 patients (34%). The objective response rate
was 7%. The estimated probability of being progression-free at 6 months with
this therapy is 24% [95% confidence interval (C.I.) 12-38%]. The median time
to progression is 15 weeks (95% C.I. 10-20 weeks). There was no observed
correlation between serum levels of vascular endothelial growth factor,
basic fibroblast growth factor, and IL-8 and the 6PFS outcome. CONCLUSION:
This drug combination was reasonably safe, but with little indication of
improvement compared to temozolomide alone.
PMID: 17031561 [PubMed - as supplied by publisher]
-
| 13: J Neurooncol.
2006 Sep 20; [Epub ahead of print] |
|
-
Resveratrol inhibits cell growth and induces apoptosis of
rat C6 glioma cells.
Zhang
W, Fei
Z, Zhen
HN, Zhang
JN, Zhang
X.
Department of Neurosurgery, Neurosurgical Institute of Chinese PLA, Xijing
Hospital, Fourth Military Medical University, No. 127 West Chang'le Road,
Xi'an, 710032, Shaanxi Province, People's Republic of China, xzhang@fmmu.edu.cn.
Resveratrol (Res) has been reported to inhibit tumor initiation, promotion,
and progression in a variety of cell culture systems depending on the
specific cell type and cellular environment. In the present study, we
determined the effect of Res on the cell growth and apoptosis of rat glioma
C6 cell line as well as mouse fibroblast 3T3 cell line, in vitro.
Concurrently, we investigated whether caspase-3 is involved in the Res-induced
apoptosis of rat glioma cells. Exposure to Res exhibits a significant anti-proliferative
effect and induces an increase in the population of apoptotic cells on C6
cells in a concentration- and time-dependent manner, but not for normal 3T3
fibroblast cells, as measured by methyl thiazolyl tetrazolium assay and flow
cytometer. Distinguished increase of C6 cells in S phase is observed after
the treatment of Res as compared to insignificant change in cell cycle
distribution of 3T3 cells. TdT-mediated dUTP nick end labeling fluorescence
staining, HE staining, and scanning electron microscope revealed abnormal
morphology and ultrastructure in C6 cells treated with Res. Our data showed
that Res can increase the expression and induced the activation of caspase-3
in rat glioma C6 cells. These results suggest that Res has significant
apoptosis-inducing effect on C6 glioma cells other than normal fibroblast
3T3 cells in vitro and caspase-3 may act as a potential mediator in the
process.
PMID: 17031560 [PubMed - as supplied by publisher]
-
| 14: J Neurooncol.
2006 Sep 20; [Epub ahead of print] |
|
-
PLXDC1 (TEM7) is identified in a genome-wide expression
screen of glioblastoma endothelium.
Beaty
RM, Edwards
JB, Boon
K, Siu
IM, Conway
JE, Riggins
GJ.
Department of Neurosurgery, Johns Hopkins University Medical School, CRB II
Rm. 257 , 1550 Orleans Street, Baltimore, MD, 21231, USA, griggin1@jhmi.edu.
Glioblastomas are a highly aggressive brain tumor, with one of the highest
rates of new blood vessel formation. In this study we used a combined
experimental and bioinformatics strategy to determine which genes were
highly expressed and specific for glioblastoma endothelial cells (GBM-ECs),
compared to gene expression in normal tissue and endothelium. Starting from
fresh glioblastomas, several rounds of negative and positive selection were
used to isolate GBM-ECs and extract total RNA. Using Serial Analysis of Gene
Expression (SAGE), 116,259 transcript tags (35,833 unique tags) were
sequenced. From this expression analysis, we found 87 tags that were not
expressed in normal brain. Further subtraction of normal endothelium, bone
marrow, white blood cell and other normal tissue transcripts resulted in
just three gene transcripts, ANAPC10, PLXDC1(TEM7), and CYP27B1, that are
highly specific to GBM-ECs. Immunohistochemistry with an antibody for PLXDC1
showed protein expression in GBM microvasculature, but not in the normal
brain endothelium tested. Our results suggest that this study succeeded in
identifying GBM-EC specific genes. The entire gene expression profile for
the GBM-ECs and other tissues used in this study are available at SAGE Genie
(http://cgap.nci.nih.gov/SAGE). Functionally, the protein products of the
three tags most specific to GBM-ECs have been implicated in processes
critical to endothelial cell proliferation and differentiation, and are
potential targets for anti-angiogenesis based therapy.
PMID: 17031559 [PubMed - as supplied by publisher]
-
| 15: J Neurooncol.
2006 Sep 20; [Epub ahead of print] |
|
-
Survival and quality of life after hypofractionated
stereotactic radiotherapy for recurrent malignant glioma.
Ernst-Stecken
A, Ganslandt
O, Lambrecht
U, Sauer
R, Grabenbauer
G.
Department of Radiation Therapy, Novalis Shaped Beam Surgery Center,
University of Erlangen, Erlangen, Germany.
PURPOSE: To prospectively evaluate efficacy, side effects and quality of
life in patients with recurrent malignant glioma after hypofractionated
stereotactic radiotherapy. METHODS AND MATERIALS: From 1/2003 to 8/2005, 15
patients with recurrent malignant glioma were prospectively scheduled for
hfSRT with 5 x 7 Gy (90%-isodose). Median gross tumor volume and planning
target volume were 5.75 (range, 0.77-21.94) and 22.4 (range, 4.22-86.79) cc,
respectively. Irradiation was performed with the dedicated stereotactic
radiosurgery system Novalistrade mark (BrainLAB, Heimstetten, Germany).
RESULTS: Rates of remission, no change and progressive disease were 27%,
33%, and 40%, respectively, after a median follow-up of 9 months.
Progression-free survival rates at 6 and 12 months were 75% and 53%
respectively. Quality of life, measured by the European Organization for
Research and Treatment of Cancer Quality of Life Questionnaire scores could
be kept stable in two thirds of the patients for a median time of 9 months,
respectively. Conclusion: Hypofractionated stereotactic radiotherapy with 5
x 7 Gy of recurrent high grade glioma is an effective treatment that helps
to maintain quality of life for an acceptable period, comparable to the
results obtained with current chemotherapy schedules. Combined approaches of
radiotherapy, chemotherapy and other targeted therapies deserve further
inverstigation.
PMID: 17031558 [PubMed - as supplied by publisher]
-
| 16: J Neurooncol.
2006 Sep 23; [Epub ahead of print] |
|
-
Administration of temozolomide during and after
radiotherapy for newly diagnosed high-grade gliomas excluding glioblastoma
multiforme.
Banna
GL, Bettio
D, Scorsetti
M, Navarria
P, Simonelli
M, Rodriguez
Baena R, Aimar
E, Gaetani
P, Colombo
P, Rognone
F, Santoro
A.
Department of Medical Oncology and Hematology, Istituto Clinico Humanitas,
Via Manzoni, 56, 20089, Milano, Rozzano, Italy.
Primary brain high-grade gliomas, excluding glioblastoma are rare and
heterogeneous tumors, showing different characteristic mutations and a
better prognosis than glioblastomas. The addition of chemotherapy to the
radiotherapy in the newly diagnosed disease has not been established yet. We
treated 9 patients with newly diagnosed tumors with temozolomide at 75 mg/m2
for 7 days a week during standard radiotherapy, followed by six cycles at
200 mg/m2 on days 1-5 every 28 days. Fluorescence in situ hybridization for
the 1 p/19 q loss was performed in seven out of the 9 patients. With a
median follow-up of 15 months (range, 8-50), eight patients are alive and
one died from disease progression. Four patients had disease progression at
7, 15, 14 and 13 months from the diagnosis. The 1 p/19 q loss was found in 5
patients; three have no evidence of disease, one had partial disease
remission and one disease progression. Toxicities included one discitis
requiring treatment withdrawal and specific antibiotic therapy, and one
transient grade 3 psoriasiform reaction. Based on this small series of
patients, the addition of temozolomide to radiotherapy may be recommended.
PMID: 17031557 [PubMed - as supplied by publisher]
-
| 17: J Neurooncol.
2006 Sep 20; [Epub ahead of print] |
|
-
Local intracerebral administration of O(6)-benzylguanine
combined with systemic chemotherapy with temozolomide of a patient suffering
from a recurrent glioblastoma.
Koch
D, Hundsberger
T, Boor
S, Kaina
B.
Department of Neurosurgery, University of Mainz, Langenbeckstr. 1, 55131,
Mainz, Germany, koch@nc.klinik.uni-mainz.de.
The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) is a
major determinant of methylating anticancer drug resistance. Inactivation of
MGMT by pseudosubstrate inhibitors, such as O(6)-benzylguanine (O(6)BG),
sensitizes tumor cells to O(6)-alkylating agents. However, systemic
administration of O(6)BG causes depletion of MGMT in all tissues of the
body. Therefore, dose reduction of O(6)-alkylating drugs administered
together with O(6)BG is required in order to avoid unwished toxic side
effects. To attenuate the increased systemic toxicity caused by MGMT
inhibitors, local MGMT inactivation would be desirable. Here, we report on
intracerebral treatment with O(6)BG of a patient suffering from glioblastoma.
O(6)BG was administered weekly in the tumor cavity by means of an Ommaya
reservoir. This application was well tolerated. Concomitant treatment with
temozolomide (Temodal) was associated with transient tumor stabilization
without detectable side effects. Although evidence is still lacking that
local O(6)BG administration caused MGMT to be depleted in the residual
tumor, the trial shows that intracerebral treatment with O(6)BG is feasible.
It might be a safe strategy for improving glioma therapy by treatment with
temozolomide (and presumably also other O(6)-alkylating drugs) concomitant
with O(6)BG without augmenting drug-induced systemic side effects.
PMID: 17031555 [PubMed - as supplied by publisher]
-
| 18: J Neurooncol.
2006 Sep 20; [Epub ahead of print] |
|
-
Safety and efficacy of convection-enhanced delivery of
ACNU, a hydrophilic nitrosourea, in intracranial brain tumor models.
Sugiyama
SI, Yamashita
Y, Kikuchi
T, Saito
R, Kumabe
T, Tominaga
T.
Department of Neurosurgery, Tohoku University Graduate School of Medicine,
1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan, yoji@nsg.med.tohoku.ac.jp.
Convection-enhanced delivery (CED) is a local infusion technique, which
delivers chemotherapeutic agents directly to the central nervous system,
circumventing the blood-brain barrier and reducing systemic side effects.
CED distribution is significantly increased if the infusate is hydrophilic.
This study evaluated the safety and efficacy of CED of nimustine
hydrochloride: 3-[(4-amino-2-methyl-5-pyrimidinyl)
methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU), a hydrophilic
nitrosourea, in rat 9 L: brain tumor models. The local neurotoxicity of ACNU
delivered via CED was examined in normal rat brains, and the maximum
tolerated dose (MTD) was estimated at 0.02 mg/rat. CED of ACNU at the MTD
produced significantly longer survival time than systemic administration (P
< 0.05, log-rank test). Long-term survival (80 days) and eradication of
the tumor occurred only in the CED-treated rats. The tissue concentration of
ACNU was measured by high-performance liquid chromatography, which revealed
that CED of ACNU at the dose of 100-fold less total drug than intravenous
injection carried almost equivalent concentrations of ACNU into rat brain
tissue. CED of hydrophilic ACNU is a promising strategy for treating brain
tumors.
PMID: 17031554 [PubMed - as supplied by publisher]
-
| 19: J Neurooncol.
2006 Sep 22; [Epub ahead of print] |
|
-
Phase II study of thalidomide and radiation in children
with newly diagnosed brain stem gliomas and glioblastoma multiforme.
Turner
CD, Chi
S, Marcus
KJ, Macdonald
T, Packer
RJ, Poussaint
TY, Vajapeyam
S, Ullrich
N, Goumnerova
LC, Scott
RM, Briody
C, Chordas
C, Zimmerman
MA, Kieran
MW.
Department of Pediatric Oncology, Dana-Farber Cancer Institute, 44 Binney
Street, SW 331, Boston, MA, 02115, USA, christopher_turner@dfci.harvard.edu.
A phase II study was conducted to assess the efficacy of administering daily
thalidomide concomitantly with radiation and continuing for up to 1 year
following radiation in children with brain stem gliomas (BSG) or
glioblastoma multiforme (GBM). Secondary objectives were to obtain
preliminary evidence of biologic activity of thalidomide and to evaluate
toxicities from chronic administration of thalidomide in this
population.Thirteen patients (2-14 years old) with newly diagnosed BSG (12
patients) or GBM (one patient) were enrolled between July 1999 and June
2000. All patients received focal radiotherapy to a total dose of 5,580 cGy.
Thalidomide was administered once daily beginning on the first day of
radiation and continued for 12 months or until the patient came off study.
The starting dose was 12 mg/kg (rounded down to the nearest 50 mg) and was
increased by 20% weekly, if tolerated, to 24 mg/kg or 1,000 mg (whichever
was lower). Advanced imaging techniques and urine and serum analysis for
anti-angiogenic markers were performed in some patients in an attempt to
correlate changes with clinical effect of therapy.No patients completed the
planned 12 months of thalidomide therapy and all have since died of disease
progression. The median duration of therapy was 5 months (range 2-11
months). Nine patients came off study for progressive disease (PD), three
patients due to toxicity and one patient withdrew consent. Several patients
on this study required more extended courses of high dose steroids than
would have been otherwise expected for this population due to significant
peritumoral edema and necrosis. No consistent pattern emerged from the
biologic correlative studies from 11 patients. However, advanced imaging
with techniques such as MR spectroscopy, MR perfusion and
18-fluorodeoxyglucose positron emission tomography (FDG-PET) were helpful in
distinguishing growing tumor from treatment effect and necrosis in some
patients.The median time to progression (TTP) was 5 months (range 2-11
months) and the median time to death (TTD) was 9 months (range 5-17 months).
In this small patient sample adding thalidomide to radiation did not improve
TTP or TTD from historical controls, however, toxicity appeared to be
increased.
PMID: 17031553 [PubMed - as supplied by publisher]
-
| 20: J Neurooncol.
2006 Sep 22; [Epub ahead of print] |
|
-
Monitoring the effects of BCNU chemotherapy Wafers (Gliadel((R)))
in glioblastoma multiforme with proton magnetic resonance spectroscopic
imaging at 3.0 Tesla.
Dyke
JP, Sanelli
PC, Voss
HU, Serventi
JV, Stieg
PE, Schwartz
TH, Ballon
D, Shungu
DC, Pannullo
SC.
Department of Radiology, Citigroup Biomedical Imaging Center, Weill Cornell
Medical College, 1300 York Avenue, Box 234, New York, NY, 10021, USA,
jpd2001@med.cornell.edu.
Carmustine wafers (Gliadel((R)) Wafer) are implanted at resection in some
patients with high-grade gliomas. Studies suggest that proton magnetic
resonance spectroscopic imaging ((1)H MRSI) demonstrates early changes
predictive of future failure or response to systemic chemotherapy. This
study explores (1)H MRSI as a means to assess peri-tumoral tissue response
post-resection and Gliadel((R)) implantation in patients with high-grade
gliomas. Pilot (1)H MRSI data are presented that demonstrate noninvasive,
serial monitoring of metabolic changes at the tumor site following
Gliadel((R)) implantation. Three patients with newly diagnosed glioblastoma
multiforme (GBM) underwent MRI and (1)H MRSI at 3.0 Tesla prior to resection
and at 3-5 and >/=12 weeks post-operatively. Baseline MRS spectra of
tumor tissue from all patients were characterized by marked increases of
choline (CHO) and lactate (LAC), and a decrease of N-acetylaspartate (NAA),
typical of GBM compared with normal contra-lateral brain tissue.
Post-operatively, spectra were analyzed from the resection cavity and
peri-tumoral regions and compared with normal tissue from the contra-lateral
brain at baseline. In 2 of 3 patients, peri-tumoral NAA/CRE increased and
CHO/NAA decreased compared to contra-lateral brain at 3-5 weeks compared
with baseline following Gliadel((R)) therapy and surgery but prior to
radiotherapy. This study indicates that (1)H MRSI has the ability to
localize regions of heterogeneous response following Gliadel treatment.
Although data are limited, these results suggest that metabolic indicators
of outcome can be successfully monitored pre- and post-surgical resection
and Gliadel implantation with (1)H MRSI. Additional study of patients
receiving Gliadel((R)) Wafers using (1)H MRSI may serve to aid clinicians in
assessing tumor regression and gauging efficacy of this chemotherapy
treatment.
PMID: 17031552 [PubMed - as supplied by publisher]
-
| 21: J Neurooncol.
2006 Oct 7; [Epub ahead of print] |
|
-
Huge lobar intracerebral hemorrhage by glioblastoma
multiforme.
Taniura
S, Okamoto
H, Tanabe
M, Kurosaki
M, Mizushima
M, Watanabe
T.
Department of Neurosurgery, Takashima Hospital, 6 Nishi-cho, Yonago,
Tottori-Pref, 683-0826, Japan, taniura@sanmedia.or.jp.
PMID: 17029015 [PubMed - as supplied by publisher]
-
| 22: J Neurooncol.
2006 Oct 7; [Epub ahead of print] |
|
-
Diffusion MRI in the early diagnosis of malignant glioma.
Baehring
JM, Bi
WL, Bannykh
S, Piepmeier
JM, Fulbright
RK.
Department of Neurology, Yale Brain Tumor Center, Yale University School of
Medicine, 333 Cedar Street, TMP410, New Haven, CT, 06510, USA.
OBJECTIVE : A subset of patients with malignant glioma comes to medical
attention before their masses show rim enhancement and central necrosis.
Tumors in those cases are frequently located in eloquent areas of the brain.
Tissue diagnosis is limited to stereotactic biopsy providing limited
material for accurate grading. We conducted this study to determine whether
imaging characteristics of early stages of malignant gliomas could aid in
timely definitive diagnosis. METHODS : We retrospectively analyzed patients
with newly diagnosed malignant glioma seen at the Yale Brain Tumor Center
between 2002 and 2005. Patients with typical radiographic presentation were
excluded. RESULTS : Of 89 patients, eight meeting the inclusion criteria
were identified. In five patients, patchy or small nodular enhancing lesions
without central necrosis were present within the tumor mass.
Diffusion-weighted imaging (DWI) showed areas of increased signal intensity
in all cases. Apparent diffusion coefficient maps (ADC) revealed low-signal
intensity in corresponding areas. At the time of imaging, biopsy was
performed in seven patients but diagnosis of malignant glioma could only be
established prior to further tumor growth in four cases. CONCLUSIONS : The
diagnosis in the early stages of malignant glioma can be challenging in a
subset of cases. Information obtained through DWI should be incorporated in
the clinical decision-making process. Mass lesions displaying decreased
water diffusion indicating high cellularity, are suggestive of a high-grade
glioma. Biopsies are recommended. However, even when biopsies are
inconclusive, a strong suspicion of malignant glioma should be considered.
PMID: 17029014 [PubMed - as supplied by publisher]
-
| 23: Neurosurgery. 2006
Oct;59(4):902-9; discussion 909-10. |
|
-
Defective receptor expression and dendritic cell
differentiation of monocytes in glioblastomas.
Ogden
AT, Horgan
D, Waziri
A, Anderson
D, Louca
J, McKhann
GM, Sisti
MB, Parsa
AT, Bruce
JN.
Department of Neurological Surgery, The Neurological Institute, Columbia
University, New York, New York 10032, USA. ato2@columbia.edu
OBJECTIVE: Better characterization of the changes that occur in the
circulating monocytes of patients with glioblastoma has become more
important recently as monocyte-derived dendritic cells are used as adjuvants
in the development of glioma vaccines. This study seeks to develop
understanding of the phenotypic changes that occur in circulating monocytes
of patients with intracranial cancer and to assess the ability of these
cells to differentiate into mature dendritic cells. METHODS: Monocyte
expression levels of HLA-ABC, HLA-DR, CD86, ICAM-1, TNFRII, and GMCSFR were
compared between three cohorts: patients with intracranial glioblastoma (n =
15), patients with intracranial metastases (n = 9), and a group of healthy
controls (n = 10). Monocytes were then tested for their ability to
differentiate into mature dentritic cells based on morphology, CD83
expression and high levels of co-stimulatory molecules. RESULTS:
Comprehensive analysis of monocyte receptor expression demonstrated
significantly reduced HLA-ABC, HLA-DR, CD86, ICAM-1, and TNFRII in patients
with glioblastoma but not in patients with intracranial metastases compared
with a group of healthy controls. GMCSFR expression was significantly
reduced in both patients with glioblastoma and intracranial metastases.
Additionally, the monocytes of patients with glioblastoma showed a reduced
capacity to differentiate into mature dendritic cells as identified by CD83
expression, receptor expression, and morphology. CONCLUSION: Peripheral
monocytes are phenotypically altered in the setting of glioblastoma and
display a reduced functional capacity to differentiate into mature dendritic
cells.
PMID: 17038955 [PubMed - in process]
-
| 24: Pediatr Neurol.
2006 Jun;34(6):495-8. |
|
-
Secondary parkinsonism in childhood: A rare complication
after radiotherapy.
Voermans
NC, Bloem
BR, Janssens
G, Vogel
WV, Sie
LT.
Department of Neurology, Radboud University Nijmegen Medical Centre, the
Netherlands. n.voermans@neuro.umcn.nl
Secondary parkinsonism is uncommon in children and exceedingly rare after
cranial radiotherapy. This report describes a 14-year-old female who
presented with growth retardation as a result of a craniopharyngioma, which
was partially resected. A secondary hydrocephalus responded well to
shunting. She gradually developed a severe hypokinetic-rigid syndrome 6
months after radiotherapy (54 Gray in 30 daily fractions of 1.8 Gray). In
addition, her vigilance decreased. Magnetic resonance imaging revealed
increased signal intensity on T2-weighted images in the globus pallidus
bilaterally. Nuclear scans indicated only a marginal striatal dopaminergic
deficit and revealed decreased metabolism in the thalamus bilaterally.
Treatment with dopamine agonists resulted in minor improvement in motor
function. Magnetic resonance imaging investigations 3 months later disclosed
a decrease of signal intensity changes of the globus pallidus. Gradually,
bradykinesia diminished slightly and vigilance increased little. In
conclusion, secondary and partially reversible parkinsonism can occur in
children after radiotherapy. We suggest that focal encephalopathy resulting
from postradiation edema secondary to microangiopathy led to dysfunction of
the globus pallidus and thalamus.
Publication Types:
PMID: 16765832 [PubMed - indexed for MEDLINE]
-
| 25: Pediatr Neurol.
2006 Jun;34(6):478-80. |
|
-
Quadrigeminal cistern arachnoid cyst in a patient with
Kabuki syndrome.
Kara
B, Kayserili
H, Imer
M, Caliskan
M, Ozmen
M.
Department of Pediatrics, Kocaeli University, Faculty of Medicine, Kocaeli,
Turkey. bulentkara@excite.com
Kabuki syndrome is a rare dysmorphic disorder characterized by peculiar
facial appearance, developmental delay, skeletal abnormalities, mental
retardation, and dermatoglyphic abnormalities. Neurologic anomalies are
frequently observed. This report presents a 2-year-old male with Kabuki
syndrome who had a quadrigeminal cistern arachnoid cyst: the second case of
such an association to be reported in the literature.
Publication Types:
PMID: 16765828 [PubMed - indexed for MEDLINE]
-
| 26: Radiology. 2006
Oct;241(1):1-2. |
|
-
Will the combination of US contrast microbubbles and
high-intensity focused ultrasound enable noninvasive brain surgery?
Forsberg
F.
Department of Radiology, Thomas Jefferson University Hospital, Suite 763J,
Main Bldg, 132 S 10th St, Philadelphia, PA 19107, USA. flemming.forsberg@jefferson.edu
PMID: 16990665 [PubMed - indexed for MEDLINE]
-
| 27: Radiology. 2006
Oct;241(1):213-22. Epub 2006 Aug 14. |
|
-
Sensorimotor cortex localization: comparison of
magnetoencephalography, functional MR imaging, and intraoperative cortical
mapping.
Korvenoja
A, Kirveskari
E, Aronen
HJ, Avikainen
S, Brander
A, Huttunen
J, Ilmoniemi
RJ, Jaaskelainen
JE, Kovala
T, Makela
JP, Salli
E, Seppa
M.
Functional Brain Imaging Unit, Helsinki Brain Research Center, Medical
Imaging Center, University of Helsinki, Helsinki, Finland. antti.korvenoja@helsinki.fi
PURPOSE: To prospectively evaluate magnetoencephalography (MEG) and
functional magnetic resonance (MR) imaging, as compared with intraoperative
cortical mapping, for identification of the central sulcus. MATERIALS AND
METHODS: Fifteen patients (six men, nine women; age range, 25-58 years) with
a lesion near the primary sensorimotor cortex (13 gliomas, one cavernous
hemangioma, and one meningioma) were examined after institutional review
board approval and written informed consent from each patient were obtained.
At MEG, evoked magnetic fields to median nerve stimulation were recorded; at
functional MR imaging, hemodynamic responses to self-paced palmar flexion of
the wrist were imaged. General linear model analysis with contextual
clustering (P < .01) was used to analyze functional MR imaging data, and
dipole modeling was used to analyze MEG data. MEG and functional MR
localizations were compared with intraoperative cortical mappings. The
distance from the area of functional MR imaging activation to the tumor
margin was compared between the patients with discordant and those with
concordant intraoperative mapping findings by using unpaired t testing.
RESULTS: MEG depicted the central sulcus correctly in all 15 patients, as
verified at intraoperative mapping. The functional MR imaging localization
results agreed with the intraoperative mappings in 11 patients. In all four
patients with a false localization, the primary activation was in the
postcentral sulcus region, but it did not differ significantly from the
primary activation in the patients with correct localization with respect to
proximity to the tumor (P = .38). Furthermore, at functional MR imaging,
multiple nonprimary areas were activated, with considerable interindividual
variation. CONCLUSION: Although both MEG and functional MR imaging can
provide useful information for neurosurgical planning, in the present study,
MEG proved to be superior for locating the central sulcus. Activation of
multiple nonprimary cerebral areas may confound the interpretation of
functional MR imaging results. (c) RSNA, 2006.
PMID: 16908676 [PubMed - indexed for MEDLINE]
|
Volume 5, Number 42 - 18 October 2006