-
MR Imaging Correlates of Survival in Patients with
High-Grade Gliomas.
Pope
WB, Sayre
J, Perlina
A, Villablanca
JP, Mischel
PS, Cloughesy
TF.
Department of Radiological Sciences, David Geffen School of Medicine at UCLA
Medical Center, Los Angeles, CA.
BACKGROUND AND PURPOSE: For patients with malignant gliomas, clinical
data-including age, perioperative Karnofsky Performance Status (KPS), and
tumor resection-and tumor imaging features-including necrosis and edema-have
been found to correlate with survival. The purpose of this study was to
assess the validity of these results and determine whether other imaging
features are useful in predicting survival. METHODS: We analyzed the
relationship between 15 imaging variables obtained from contrast-enhanced MR
imaging scans and survival in patients with grade III (n = 43) and grade IV
(n = 110) glioblastoma multiforme (GBM) gliomas. Image analysis was
performed by 2 neuroradiologists who were blinded to clinical data. The
Kaplan-Meier method was used to estimate survival probabilities. Univariable
Cox models were used to assess the impact of imaging features on survival. A
recursive partitioning analysis also was performed. RESULTS: As expected,
age and KPS scores had significant prognostic value for both tumor grades.
The extent of resection was not a statistically meaningful predictor of
survival. For GBM, univariable analysis revealed the following imaging
features to be significant, (hazard ratios in parentheses):
noncontrast-enhancing tumor (nCET, 0.55), edema (1.62), satellites (1.74),
and multifocality (4.34). For grade III tumors, the Cox hazard ratio for
necrosis was 4.43 (P = .014) and correlated with a poor outcome and survival
rates comparable to GBM patients. Lack of nCET, multifocality, and satellite
lesions also were correlated with shortened survival. CONCLUSION: Of 15
tumor imaging features in GBM patients, only nCET, edema, and
multifocality/satellites are statistically significant prognostic
indicators. The survival advantage of nCET is a novel finding.
PMID: 16286386 [PubMed - in process]
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-
Is volume transfer coefficient (ktrans) related to
histologic grade in human gliomas?
Patankar
TF, Haroon
HA, Mills
SJ, Baleriaux
D, Buckley
DL, Parker
GJ, Jackson
A.
Imaging Science and Biomedical Engineering, University of Manchester,
Manchester, United Kingdom.
PURPOSE: The purpose of this study was to examine the relationship between
contrast transfer coefficient [K(trans)] and grade in gliomas. MATERIAL AND
METHODS: Median values of K(trans), CBV(T1), and of the 95th percentile
(95%) of the distribution (K(trans) [95%] and CBV(T1) [95%]) were calculated
in 39 patients with glioma. Group comparisons and post hoc pairwise
comparisons were performed. The relationship between variables and grade
used Spearman rho and canonical discriminant analysis. The separation of
high- from low-grade tumors was separately assessed by using Mann-Whitney U
tests and logistic regression. Receiver operator curve analysis was
performed for high- and low-grade tumors and grade III and grade IV tumors.
RESULTS: There were significant differences between grades for all variables
(P < .001). Pairwise comparisons demonstrated significant differences
between grades II and III and II and IV for all variables except K(trans),
which did not show significance in the grade II and III comparison, and
between III and IV for CBV(T1) and CBV(T1) (95%; P < .01). All variables
correlated with grade (P < .01). Discriminant analysis showed independent
relation between both CBV(T1) and K(trans) (95%) and grade, and the
canonical function produced a total correct classification of 74.4% of
cases. Logistic regression analysis for low- versus high-grade tumors showed
K(trans) (95%) and CBV(T1) to be independent factors (P < .01 and P <
.05). CONCLUSION: There are strong independent relationships between both
CBV and K(trans) and histologic grade in gliomas. Both measurements show
good discriminative power in distinguishing between low- and high-grade
tumors with diagnostic sensitivity and specificity >90%.
PMID: 16286385 [PubMed - in process]
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-
Central neurogenic hyperventilation: a case report and
discussion of pathophysiology.
Tarulli
AW, Lim
C, Bui
JD, Saper
CB, Alexander
MP.
Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA
02215, USA. atarulli@caregroup.harvard.edu
BACKGROUND: Central neurogenic hyperventilation is a rare condition with
poorly understood pathophysiology. OBJECTIVE: To describe a patient with
central neurogenic hyperventilation caused by an infiltrative brainstem
lymphoma. CONCLUSION: Based on analysis of this patient and other case
reports, we propose that central neurogenic hyperventilation is uniquely the
result of infiltrative tumors that stimulate pontine respiratory centers and
central chemoreceptors.
Publication Types:
PMID: 16216951 [PubMed - indexed for MEDLINE]
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-
Delayed neurotoxicity in primary central nervous system
lymphoma.
Omuro
AM, Ben-Porat
LS, Panageas
KS, Kim
AK, Correa
DD, Yahalom
J, Deangelis
LM, Abrey
LE.
Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York,
NY 10021, USA.
BACKGROUND: Treatment for primary central nervous lymphoma (PCNSL) with
chemotherapy and radiotherapy has resulted in improved survival, but some
patients develop neurologic deterioration that represents a
treatment-related toxic effect. This delayed neurotoxicity has been poorly
defined in the literature, and the underlying mechanisms are unknown.
OBJECTIVE: To describe the clinical findings, time course, and
pathophysiologic mechanisms associated with neurotoxicity in an attempt to
generate hypotheses for future studies that address prevention and treatment
of this complication of successful PCNSL therapy. DESIGN: Retrospective
review. SETTING: Department of Neurology, Memorial Sloan-Kettering Cancer
Center. PATIENTS: One hundred eighty-five patients treated for PCNSL,
including 43 who developed neurotoxicity. MAIN OUTCOME MEASURES: Potential
risk factors, clinical course, and neuropsychological, neuroimaging, and
histologic findings. RESULTS: The 5-year cumulative incidence of
neurotoxicity was 24%; this incidence increases over time. Neurotoxicity
presented as a rapidly progressive subcortical dementia characterized by
psychomotor slowing, executive and memory dysfunction, behavioral changes,
gait ataxia, and incontinence. Imaging findings revealed diffuse white
matter disease and cortical-subcortical atrophy. Available autopsy data
showed white matter damage with gliosis, thickening of small vessels, and
demyelination. Statistical analyses were performed, accounting for death as
a competing risk. Older age (P = .01), mental status changes at diagnosis (P
= .04), female sex (P = .05), and radiotherapy (P<.001) predicted
neurotoxicity on univariate analysis, but only radiotherapy remained
significant in the multivariate setting. CONCLUSION: These findings suggest
that the core pathophysiologic mechanism is the interruption of
frontal-subcortical circuits mediated by radiation damage, possibly caused
by progressive microvascular alterations, loss of oligodendrocyte
progenitors, or oxidative stress.
PMID: 16216945 [PubMed - indexed for MEDLINE]
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Lipoma of the tuber cinereum.
Chu
AY, Rorke
LB, Hood
IC.
Department of Pathology and Laboratory Medicine, Hospital of the University
of Pennsylvania, Philadelphia, Pa, USA.
Publication Types:
PMID: 15859652 [PubMed - indexed for MEDLINE]
  
-
| 6: Cancer.
2005 Nov 15; [Epub ahead of print] |
|
-
Long-term survivors after gamma knife radiosurgery for
brain metastases.
Kondziolka
D, Martin
JJ, Flickinger
JC, Friedland
DM, Brufsky
AM, Baar
J, Agarwala
S, Kirkwood
JM, Lunsford
LD.
Department of Neurological Surgery, University of Pittsburgh School of
Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
BACKGROUND: Stereotactic radiosurgery, with or without whole-brain radiation
therapy, has become a valued management choice for patients with brain
metastases, although their median survival remains limited. In patients who
receive successful extracranial cancer care, patients who have controlled
intracranial disease are living longer. The authors evaluated all brain
metastasis in patients who lived for >/= 4 years after radiosurgery to
determine clinical and treatment patterns potentially responsible for their
outcome. METHODS: Six hundred seventy-seven patients with brain metastases
underwent 781 radiosurgery procedures between 1988 and 2000. Data from the
entire series were reviewed; and, if patients had >/= 4 years of
survival, then they were evaluated for information on brain and extracranial
treatment, symptoms, imaging responses, need for further care, and
management morbidity. These long-term survivors were compared with a cohort
who lived for < 3 months after radiosurgery (n = 100 patients). RESULTS:
Forty-four patients (6.5%) survived for > 4 years after radiosurgery
(mean, 69 mos with 16 patients still alive). The mean age at radiosurgery
was 53 years (maximum age, 72 yrs), and the median Karnofsky performance
score (KPS) was 90. The lung (n = 15 patients), breast (n = 9 patients),
kidney (n = 7 patients), and skin (melanoma; n = 6 patients) were the most
frequent primary sites. Two or more organ sites outside the brain were
involved in 18 patients (41%), the primary tumor plus lymph nodes were
involved in 10 patients (23%), only the primary tumor was involved in 9
patients (20%), and only brain disease was involved in 7 patients (16%),
indicating that extended survival was possible even in patients with
multiorgan disease. Serial imaging of 133 tumors showed that 99 tumors were
smaller (74%), 22 tumors were unchanged (17%), and 12 tumors were larger
(9%). Four patients had a permanent neurologic deficit after brain tumor
management, and six patients underwent a resection after radiosurgery.
Compared with the patients who had limited survival (< 3 mos), long-term
survivors had a higher initial KPS (P = 0.01), fewer brain metastases (P =
0.04), and less extracranial disease (P < 0.00005). CONCLUSIONS: Although
the expected survival of patients with brain metastases may be limited,
selected patients with effective intracranial and extracranial care for
malignant disease can have prolonged, good-quality survival. The extent of
extracranial disease at the time of radiosurgery was predictive of outcome,
but this does not necessarily mean that patients cannot live for years if
treatment is effective. Cancer 2005. (c) 2005 American Cancer Society.
PMID: 16288488 [PubMed - as supplied by publisher]
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| 7: Cancer.
2005 Nov 15; [Epub ahead of print] |
|
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A population-based description of glioblastoma multiforme
in Los Angeles County, 1974-1999.
Chakrabarti
I, Cockburn
M, Cozen
W, Wang
YP, Preston-Martin
S.
Department of Neurosurgery, University of Southern California Keck School of
Medicine, Los Angeles, California.
BACKGROUND: There have been reports that the incidence rates of brain tumors
have increased over the past few decades, but most have considered all brain
tumors together. The authors analyzed the pattern of glioblastoma multiforme
(GBM) occurrence in Los Angeles County, California to shed light on the
incidence and descriptive epidemiology of this type of brain tumor. METHODS:
Data were obtained from the Los Angeles County Cancer Surveillance Program.
Incidence rates were analyzed by gender, race, age at diagnosis, period of
diagnosis (1974-1981, 1982-1988, or 1989-1999), and socioeconomic status
(SES). In addition, data were stratified according to anatomic subsite. A
multivariate model describing changes in rates by each of these variables
was constructed. RESULTS: Age-specific incidence rates (ASIR) rose sharply
after age 30 years. The peak ASIR was at age 70-74 years in males and at age
75-79 years in females. The age-adjusted incidence rate (AAIR) of GBM
increased from 1974 to 1999 by an estimated 2.4% per year among males and
2.8% per year among females. Overall, males had a 60% increased risk of
brain tumors compared with females. Males had a higher incidence of GBM
compared with females at each anatomic subsite except the posterior fossa.
The largest male:female ratio occurred in the occipital lobes. Non-Latino
whites had the highest incidence rates (2.5 per 100,000) followed by Latino
whites (1.8 per 100,000), and blacks (1.5 per 100,000). After 1989, compared
with the period before magnetic resonance imaging (MRI) was available, there
was an increase in GBM incidence rates among those with of higher SES that
was most pronounced in females. The incidence of GBM was highest for frontal
lobe tumors and for tumors that involved two or more lobes (overlapping
tumors), followed by tumors in the temporal and parietal lobes. In the
multivariate analysis, year of diagnosis, SES, gender, race (Latino but not
black), site, and age at diagnosis all were important predictors of
incidence rate. CONCLUSIONS: GBM incidence increased in Los Angeles County
over the last 30 years and especially after 1989, suggesting that the
introduction of MRI may have contributed to the increase. Individuals older
than age 65 years experienced the greatest increase in incidence over time.
Older age, male gender, higher SES, and non-Latino white race increased the
risk of GBM. Previously unreported incidence rates for GBM among Latino
whites were significantly lower than among non-Latino whites but were
intermediate between non-Latino whites and blacks. Cancer 2005. (c) 2005
American Cancer Society.
PMID: 16288487 [PubMed - as supplied by publisher]
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| 8: Cancer.
2005 Nov 14; [Epub ahead of print] |
|
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Survivin expression and its relation with proliferation,
apoptosis, and angiogenesis in brain gliomas.
Zhen
HN, Zhang
X, Hu
PZ, Yang
TT, Fei
Z, Zhang
JN, Fu
LA, He
XS, Ma
FC, Wang
XL.
Institute of Neurosurgery, Xijing Hospital, The Fourth Military Medical
University, Xi'an, The People's Republic of China.
BACKGROUND: An unbalance of cell proliferation and cell apoptosis is an
important mechanism in carcinogenesis, and angiogenesis also plays a crucial
role in tumorigenesis. Recently, survivin has been identified as an
important member of the inhibitor of apoptosis protein (IAP) family.
Although it has been shown that survivin is highly expressed in gliomas, and
is associated with tumorigenesis, progression, and poor prognosis of
gliomas, as yet the relation of survivin expression with proliferation,
apoptosis, and angiogenesis of gliomas it is still unclear. METHODS:
Eighty-three cases of brain glioma were chosen and protein expressions of
survivin and proliferating cell nuclear antigen (PCNA) in glioma cells and
Factor VIII-related antigen (FVIII-RAg) in vascular endothelial cells were
investigated by immunohistochemistry. Apoptotic cells of brain glioma were
screened by TdT-mediated dUTP nick end-labeling (TUNEL), and survivin
immunoreactivity score (IRS), proliferative index (PI), apoptotic index
(AI), overall daily growth (ODG), and microvessel density (MVD) in brain
gliomas were measured. RESULTS: The survivin IRS, PI, AI, ODG, and MVD of
brain gliomas were 3.75 +/- 3.89, 28.39 +/- 19.49%, 1.00 +/- 0.80%, 12.19
+/- 10.21%, and 62.75 +/- 31.50, respectively, and all of them increased
markedly with an increase in the pathologic grade of brain gliomas (P <
0.001 for all). PI, ODG, and MVD in the survivin-positive group were
significantly higher than those in the survivin-negative group (P < 0.001
for all). PI, ODG, and MVD were positively correlated with survivin IRS (P
< 0.001 for all). Although there was no significant difference between AI
in the survivin-positive group or in the survivin-negative group (P =
0.108), AI was inversely correlated with survivin IRS (P = 0.005).
CONCLUSIONS: Survivin is overexpressed in brain gliomas, which may play an
important role in malignant proliferation, antiapoptosis, and angiogenesis
of brain gliomas. Cancer 2005. (c) 2005 American Cancer Society.
PMID: 16284993 [PubMed - as supplied by publisher]
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Orthotopic growth of human glioma cells quantitatively
and qualitatively influences radiation-induced changes in gene expression.
Camphausen
K, Purow
B, Sproull
M, Scott
T, Ozawa
T, Deen
DF, Tofilon
PJ.
Radiation Oncology Branch, National Cancer Institute and National Institutes
of Neurological Disorder and Stroke, Bethesda, Maryland 20892, USA.
camphauk@mail.nih.gov
The effect of radiation on gene expression has been most frequently studied
using tissue culture models. To determine the influence of experimental
growth condition on radiation-induced changes in gene expression, microarray
analysis was done on two human glioma cell lines (U87 and U251) grown in
tissue culture and as s.c. or i.c. xenografts. Compared with tissue culture,
the number of genes, whose expression was affected by radiation in both cell
lines, was increased in the s.c. xenografts and further increased in the
orthotopic tumors. Furthermore, in each growth condition, radiation
modulated the expression of a different set of genes. In addition, whereas
there were few commonly affected genes after irradiation of U87 and U251 in
tissue culture, there were 729 common changes after orthotopic irradiation.
These results indicate that the influence of the orthotopic environment on
radiation-induced modulation of gene expression in glioma cells was both
quantitative and qualitative. Moreover, they suggest that investigations of
the functional consequence of radiation-induced gene expression will require
accounting for experimental growth conditions.
PMID: 16288029 [PubMed - in process]
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-
A review of clinical and histological features of Spanish
paediatric medulloblastomas during the last 21 years.
Urberuaga
A, Navajas
A, Burgos
J, Pijoan
JI.
Paediatric Oncology Unit, Hospital de Cruces, 48903, Barakaldo, Bizkaia,
Spain, aurberuaga@yahoo.es.
PURPOSE: To find any feature of prognostic significance among the clinical
and histological characteristics of paediatric patients diagnosed with
medulloblastoma (MB). MATERIALS AND METHODS: Clinical charts and paraffin
blocks of 79 paediatric patients from nine Spanish institutions diagnosed
with MB between 1980 and 2001 were reviewed retrospectively. Included
clinical and histological characteristics were age, sex, duration of
symptoms, physical signs on admission, tumour location, T and M stages of
Chang classification, hydrocephalus, cerebrospinal fluid shunt, surgical
resection, complications after surgery, MB subtype, desmoplasia, nodularity,
fibrilar pattern, nuclear pleomorphism, necrosis grade, proliferation index
and intra-tumoural vascularity. Overall and event-free survival (EFS)
univariate and multivariate analyses were assessed. RESULTS: Type of surgery
and necrosis grade appeared to be independent prognostic variables in
overall and EFSs. Although nuclear pleomorphism and intra-tumoural
vascularity showed a marginally statistical effect on overall survival (OS),
both had a significant influence on EFS. CONCLUSION: We have confirmed
surgical resection and added necrosis grade as independent prognostic
factors in terms of OS for children diagnosed with MB.
PMID: 16283195 [PubMed - as supplied by publisher]
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Childhood brain tumour information on the Internet in the
Chinese language.
Lau
L, Hargrave
DR, Bartels
U, Esquembre
C, Bouffet
E.
Paediatric Brain Tumour Programme, Division of Haematology/Oncology, The
Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G
1X8, Canada, eric.bouffet@sickkids.ca.
BACKGROUND: Internet information, now available in many different languages,
can become a major source of information for patients and families in their
own mother tongue. Chinese represent one of most frequently spoken language
in the world. The aims of this study were to critically appraise the
quantity and quality of Internet health information in childhood brain
tumour in the Chinese language and to identify sufficient quality websites
that can potentially be recommended to Chinese-speaking parents. METHODS:
Internet information on six common paediatric brain tumours was searched
using six commonly used Chinese search engines. Websites were assessed
systematically using two rating tools: DISCERN instrument and Checklist
Rating System Instrument. RESULTS: Out of 946 sites accessed, only 13
assessable Chinese websites, displaying Traditional Chinese characters and
providing information on brain tumour, were identified. Only four sites
included specific discussion on brain tumours in children. Ten websites
failed to provide satisfactory information on brain tumour as rated by
DISCERN instrument. Overall only 41% of the 13 specific items relevant to
brain tumours were mentioned (Checklist Rating System Instrument).
CONCLUSION: Only a few satisfactory websites can be recommended to
Chinese-speaking families for general information on brain tumour with
caution from health care providers that such information may not apply to
the child's individual condition.
PMID: 16283193 [PubMed - as supplied by publisher]
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Dominant-negative Rac increases both inherent and
ionizing radiation-induced cell migration in C6 rat glioma cells.
Hwang
SY, Jung
JW, Jeong
JS, Kim
YJ, Oh
ES, Kim
TH, Kim
JY, Cho
KH, Han
IO.
Research Institute, National Cancer Center, Goyang, Gyeonggi, Korea.
Rho-like GTPases, including Cdc42, Rac1 and RhoA, regulate distinct actin
cytoskeleton changes required for cell adhesion, migration and invasion. In
the present study, we examined the role of Rac signaling in inherent
migration, as well as radiation-induced migration, of rat glioma cells.
Stable overexpression of dominant-negative Rac1N17 in a C6 rat glioma cell
line (C6-RacN17) promoted cell migration, and ionizing radiation further
increased this migration. Migration was accompanied by decreased expression
of the focal adhesion molecules FAK and paxillin. Focal contacts and actin
stress fibers were also reduced in C6-RacN17 cells. Downstream effectors of
Rac include JNK and p38 MAP kinases. Irradiation transiently activated p38,
JNK and ERK1/2 MAP kinases in C6-RacN17 cells, while p38 and JNK were
constitutively activated in C6 control cells. Blocking JNK activity with JNK
inhibitor SP600125 inhibited migration, suggesting that the JNK pathway may
regulate radiation-induced, as well as inherent, migration of C6-RacN17
cells. Additionally, the radiation-induced migration increase was also
inhibited by SB203580, a specific inhibitor of p38 MAP kinase. However,
PD98059, a MEK kinase 1 inhibitor, failed to influence migration. This is
the first evidence that suppression of Rac signaling may be involved in
invasion or metastasis of glioma cells before and/or after radiotherapy.
These data further suggest that radiotherapy for malignant glioma needs to
be used with caution because of the potential for therapy-induced cell
migration or invasion and that pharmacological inhibition of cell migration
and invasion through targeting the Rac signaling pathway may represent a new
approach for improving the therapeutic efficacy of radiotherapy for
malignant glioma. (c) 2005 Wiley-Liss, Inc.
PMID: 16287069 [PubMed - as supplied by publisher]
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Proton beam radiotherapy versus fractionated stereotactic
radiotherapy for uveal melanomas: A comparative study.
Weber
DC, Bogner
J, Verwey
J, Georg
D, Dieckmann
K, Escude
L, Caro
M, Potter
R, Goitein
G, Lomax
AJ, Miralbell
R.
Department of Radiation Medicine, Paul Scherrer Institute, Villigen-PSI,
Switzerland. damien.weber@hcuge.ch
PURPOSE: A comparative treatment planning study was undertaken between
proton and photon therapy in uveal melanoma to assess the potential benefits
and limitations of these treatment modalities. A fixed proton horizontal
beam (OPTIS) and intensity-modulated spot-scanning proton therapy (IMPT),
with multiple noncoplanar beam arrangements, was compared with linear
accelerator-based stereotactic radiotherapy (SRT), using a static and a
dynamic micromultileaf collimator and intensity-modulated RT (IMRS). METHOD
AND MATERIALS: A planning CT scan was performed on a brain metastasis
patient, with a 3-mm acquisition slice spacing and the patient looking at a
luminous spot with the eyes in three different positions (neutral and 25
degrees right and left). Four different gross tumor volumes were defined for
each treatment technique. These target scenarios represented different
locations (involving vs. not involving the macula and temporal vs. nasal)
and volumes (10 x 6 mm vs. 16 x 10 mm) to challenge the proton and photon
treatment techniques. The planning target volume was defined as the gross
tumor volume plus 2 mm laterally and 3 mm craniocaudally for both
modalities. A dose homogeneity of 95-99% of the planning target volume was
used as the "goal" for all techniques. The dose constraint
(maximum) for the organs at risk (OARs) for both the proton and the SRT
photon plans was 27.5, 22.5, 20, and 9 CGE-Gy for the optic apparatus,
retina, lacrimal gland, and lens, respectively. The dose to the planning
target volume was 50 CGE-Gy in 10 CGE-Gy daily fractions. The plans for
proton and photon therapy were computed using the Paul Scherrer Institute
and BrainSCAN, version 5.2 (BrainLAB, Heimstetten, Germany) treatment
planning systems, respectively. Tumor and OARs dose-volume histograms were
calculated. The results were analyzed using the dose-volume histogram
parameters, conformity index (CI(95%)), and inhomogeneity coefficient.
RESULTS: Target coverage of all simulated uveal melanomas was equally
conformal with the photon and proton modalities. The median CI(95%) value
was 1.74, 1.86, and 1.83 for the static, dynamic, and IMSRT plans,
respectively. With proton planning, the median CI(95%) was 1.88 for OPTIS
and substantially improved with IMPT in some tumor cases (median CI(95%),
1.29). The tumor dose homogeneity in the proton plans was, however, always
better than with SRT photon planning (median inhomogeneity coefficient 0.1
and 0.15 vs. 0.46, 0.41, and 0.23 for the OPTIS and IMPT vs. the static,
dynamic, and IMSRT plans, respectively). Compared with the photon plans, the
use of protons did not lead to a substantial reduction in the homolateral
OAR total integral dose in the low- to high-dose level, except for the
lacrimal gland. The median maximal dose and dose at the 10% volume with the
static, dynamic, and IMSRT plans was 33-30.8, 31.8-28, and 35.8-49 Gy,
respectively, for the lacrimal gland, a critical organ. For protons, only
the OPTIS plans were better, with a median maximal dose and dose at the 10%
volume using OPTIS and IMPT of 19.2 and 8.8 and 25.6 and 23.6 CGE,
respectively. The contralateral OARs were completely spared with the proton
plans, but the median dose delivered to these structures was 1.2 Gy (range,
0-6.3 Gy) with the SRT photon plans. CONCLUSION: These results suggest that
the use of SRT photon techniques, compared with protons, can result in
similar levels of dose conformation. IMPT did not increase the degree of
conformality for this small tumor. Tumor dose inhomogeneity was, however,
always increased with photon planning. Except for the lacrimal gland, the
use of protons, with or without intensity modulation, did not increase
homolateral OAR dose sparing. The dose to all the contralateral OARs was,
however, completely eliminated with proton planning.
PMID: 16168832 [PubMed - indexed for MEDLINE]
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Tenascin-C protein is induced by Transforming Growth
Factor-ss1 but does not correlate with time to tumor progression in
high-grade gliomas.
Hau
P, Kunz-Schughart
LA, Rummele
P, Arslan
F, Dorfelt
A, Koch
H, Lohmeier
A, Hirschmann
B, Muller
A, Bogdahn
U, Bosserhoff
AK.
Department of Neurology, University of Regensburg, Universitatsstrasse 84,
93053, Regensburg, Germany, peter.hau@medbo.de.
BACKGROUND: Tenascin-C is an extracellular matrix protein known to correlate
with prognosis in patients with glioblastoma, probably by stimulation of
invasion and neoangiogenesis. Transforming Growth Factor-ss1 (TGF-ss1) plays
an important role in the biology of high-grade gliomas, partly by regulating
invasion of these tumors into parenchyma. This study was designed to
evaluate if TGF-ss1 induces the expression and deposition of Tenascin-C in
the extracellular matrix of high-grade gliomas which may be pivotal for the
invasion of these tumors into healthy parenchyma. METHODS: A series of 20
high-grade gliomas was stained immunohistochemically with Tenascin-C- and
TGF-ss1- specific antibodies. Expression levels of both proteins were
evaluated and correlated with each other, time to progression and molecular
and morphological markers of invasion. A quantitative PCR assay was
performed evaluating the induction of Tenascin-C mRNA by treatment with
TGF-ss1 in vitro. RESULTS: Tenascin-C was expressed in 18 of 19 (95%)
evaluable tumors, whereas 14 of 20 tumors (70%) expressed TGF-ss1 in a
significant percentage of cells. Treatment with TGF-ss1 did induce the
expression of Tenascin-C at the mRNA and protein level in vitro. The
expression of Tenascin-C and TGF-ss1 did neighter statistically correlate
with each other nor with time to progression. CONCLUSION: In our series,
Tenascin-C and TGF-ss1 were expressed in the vast majority of high-grade
gliomas. We could not detect a correlation of one of the proteins with time
to progression. Nevertheless, we describe induction of Tenascin-C by
TGF-ss1, possibly providing a mechanism for the invasion of high-grade
gliomas into healthy parenchyma.
PMID: 16292494 [PubMed - as supplied by publisher]
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Novel drug delivery system using thermoreversible
gelation polymer for malignant glioma.
Arai
T, Joki
T, Akiyama
M, Agawa
M, Mori
Y, Yoshioka
H, Abe
T.
Department of Neurosurgery, Jikei University School of Medicine, Tokyo,
Japan, takao-a@jikei.ac.jp.
Many approaches to local tumor treatment have been reported and their
efficacy demonstrated in patients with malignant glioma. We studied
thermoreversible gelation polymer (TGP) as a novel drug delivery system
(DDS) for treating this type of tumor. TGP exhibits sol-gel transition i.e.,
is water-soluble in the sol phase below the chosen sol-gel transiting
temperature and water-insoluble in the gel phase above this temperature. We
conjugated doxorubicin with TGP to prepare doxorubicin-TGP (DXR-TGP), then
studied the kinetics of doxorubicin release from TGP and the antitumor
activity of DXR-TGP in vitro and in vivo. The diffusive speed of doxorubicin
from TGP was 9.4x10(-7) cm(2)/s and doxorubicin was reliably released from
TGP. DXR-TGP showed antitumor activity against the human glioma cell lines
T98G and U87MG and in a subcutaneous tumor model in nude mice.
Pathologically, detection of the proliferation marker Ki-67 was considerably
lower in the DXR-TGP group than in the control group (30-40% vs. 60-70%,
respectively). This is to the best of our knowledge the first report of TGP
as a novel drug delivery system, and further we provide evidence that TGP
exhibits potential for use as a novel DDS for malignant glioma.
PMID: 16292493 [PubMed - as supplied by publisher]
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Radiation induced meningioma with a short latent period
following high dose cranial irradiation - Case report and literature review.
Choudhary
A, Pradhan
S, Huda
MF, Mohanty
S, Kumar
M.
Department of Neurosurgery, Institute of Medical Sciences, Banaras Hindu
University, Varanasi, 221 005, Uttar Pradesh, India.
Radiation induced meningiomas (RIM) are rare late complications in patients
who have received high dose irradiation for brain tumors. The mean latency
period for induction of RIM in most of the series is 18.7+/-10.2 years.
There are only 9 reported cases of RIM following high dose cranial
irradiation with unusually short latency periods of less than 5 years.
Herein, we report a child diagnosed with RIM with an unusually short latency
period of 14 months. An 11-year old male child underwent gross total
resection of medulloblastoma. Following surgery he received high dose
craniospinal irradiation. Postoperative computed tomography scan (CT scan)
after 1 month did not show features of any residual tumor, recurrence or
tumor at a new site. The child was asymptomatic for 14 months and then
presented with complaints of headache and vomiting. CT scan head showed
multiple solid homogenously enhancing lesions in bilateral basifrontal and
right basitemporal region. Histopathology of the lesions turned out to be
atypical meningioma.
PMID: 16292489 [PubMed - as supplied by publisher]
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-
Phase II trial of temozolomide in children with recurrent
high-grade glioma.
Ruggiero
A, Cefalo
G, Garre
ML, Massimino
M, Colosimo
C, Attina
G, Lazzareschi
I, Maurizi
P, Ridola
V, Mazzarella
G, Caldarelli
M, Rocco
CD, Madon
E, Abate
ME, Clerico
A, Sandri
A, Riccardi
R.
Dipartimento di Scienze Pediatriche, Medico-Chirurgiche e di Neuroscienze
dello Sviluppo, Universita Cattolica, Rome, Italy, riccardi@rm.unicatt.it.
PURPOSE: The objective of the study was to evaluate the efficacy and
toxicity of Temozolomide (TMZ) administered for 5 consecutive days in three
daily dosing in children with recurrent or refractory high-grade glioma.
PATIENTS AND METHODS: Twenty-four patients with a median age of 10.5 years
were enrolled onto this open-label, multicenter, phase II study. The
patients were previously treated with surgical resection (17 of 24),
radiotherapy (19 of 24) and chemotherapy (18 of 24). Therapy was
administered orally three times a day for 5 consecutive days at the dose of
200 mg/m(2)/dx5 for chemotherapy naive patients. In patients heavily
pretreated with chemotherapy the starting dose was of 150 mg/m(2)/dx5.
RESULTS: A total of 95 cycles were administered. The median progression
free-survival (PFS) was 3 months for the entire group while disease
stabilization was obtained in 7 patients (29.1%), all with supratentorial
tumors. No CR or PR was observed. TMZ treatment showed a limited toxicity.
Thrombocytopenia was the most common hematological adverse effect. Our data
suggest a marginal activity of TMZ in children with recurrent high-grade
glioma.
PMID: 16292488 [PubMed - as supplied by publisher]
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Antioxidant enzymes in oligodendroglial brain tumors:
association with proliferation, apoptotic activity and survival.
Sally
J, Helena
B, Niina
P, Timo
J, Leo
P, Hannu
K, Pauli
H, Vuokko
K, Ylermi
S, Hannu
H.
Department of Pathology, Tampere University Hospital, Tampere, Finland,
sally.jarvela@sci.fi.
Purpose of the study was to investigate the relationship between antioxidant
enzyme expression and clinicopathological features in oligodendroglial
tumors. The expression of antioxidant enzymes and related proteins (AOEs),
manganese superoxide dismutase (MnSOD), thioredoxin (Trx), thioredoxin
reductase (TrxR) and gammaglutamylcysteine synthetase catalytic and
regulatory subunits (GLCL-C and GLCL-R), was studied in 85 oligodendroglial
tumors. The material included 71 primary (43 grade II and 28 grade III) and
14 recurrent (6 grade II and 8 grade III) tumors. Fifty-seven cases were
pure oligodendrogliomas and 28 were mixed oligoastrocytomas.
Immunoreactivity for MnSOD was found in 89%, Trx in 29%, TrxR in 76%, GLCL-C
in 70% and GLCL-R in 68% of cases. Increased Trx expression was associated
with higher tumor grade, cell proliferation and apoptosis (P=0.006, P=0.001
and P=0.003, Mann-Whitney test). Pure oligodendrogliomas showed more intense
staining than oligoastrocytomas, especially for MnSOD (P=0.002, Mann-Whitney
test). In the total series Trx was associated with poor prognosis in
univariate survival analysis (P=0.0343, log-rank test) and furthermore in
Cox multivariate analysis (P=0.009) along with age (P=0.002). The results
suggest that the expression of Trx has a correlation to patient outcome and
that there may be some association between AOEs, like MnSOD and Trx, and
clinicopathological features of oligodendrogliomas.
PMID: 16292483 [PubMed - as supplied by publisher]
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Systemic Temozolomide Combined with Loco-regional
Mitoxantrone in Treating Recurrent Glioblastoma.
Boiardi
A, Eoli
M, Salmaggi
A, Lamperti
E, Botturi
A, Broggi
G, Bissola
L, Finocchiaro
G, Silvani
A.
Department of Neuro-Oncology, Istituto Nazionale Neurologico "Carlo
Besta", Italy, boiardi@istituto-besta.it.
Twenty-two recurrent GBM patients were enrolled for second tumor debulking
with local positioning of a Rickam reservoir, in order to locally deliver
chemotherapy with the aim of controlling local tumor recurrence. We designed
a protocol using systemic temozolomide (150 mg/sqm days 1-5 every 28) in
association with mitoxantrone, delivered through the reservoir (4 mg/day 1-5
every 28) positioned into the area of tumor exeresis. After re-operation a
residual tumor mass no larger than 2 cm was identified in 18/22 patients.
The patients were treated with monthly cycles of chemotherapy until
evolution of the tumor, but in no case for more than 10 cycles. Responses
were evaluated by MRI scans performed every 2 months and images assessed
according to MacDonald's criteria. Response rate: no complete responses
(CR), 5 partial responses (PR), 13 stable disease (SD) and 4 progressive
disease (PD) occurred. The median progression-free survival (PFS) and
survival time (ST) of the whole group of treated patients was 7 and 11
months, respectively and more than a quarter of the patients survived over
18 months. During the study, the patients' compliance was complete and no
dropouts occurred. Hematological toxicity was mild and after repeated local
injections only minor neurological side-effects occurred. Despite some bias
in patients' selection not excluded in this pilot study, results are
interesting: the PFS was as long as the survival of recurrent GBM reported
in the literature.
PMID: 16283445 [PubMed - in process]
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-
Cell-specific but p53-independent regulation of vascular
endothelial growth factor expression by interferons in human glioblastoma
cells.
Yao
Y, Kubota
T, Sato
K, Takeuchi
H, Handa
Y, Matsukawa
S.
Department of Neurosurgery, University of Fukui, Matsuoka, Fukui, 910-1193,
Japan.
Vascular endothelial growth factor (VEGF) is a key mediator of tumor
angiogenesis. Interferons (IFNs) have been widely used in the treatment of
malignant or recurrent gliomas with only marginal benefit. The association
between IFNs and VEGF expression remains unclear and should be an
intensively investigated subject. The present study therefore examined the
effects of different types of IFNs on VEGF expression in human T98G, A172
and U251 glioblastoma cells by quantitative RT-PCR and ELISA. Both type I
(alpha, beta) and type II (gamma) IFNs upregulated VEGF expression in a
cell-specific but p53-independent manner. Actinomycin D experiments
demonstrated that IFNs did not alter VEGF mRNA stability. In contrast,
induction of VEGF mRNA by IFNs was blocked by the protein synthesis
inhibitor cycloheximide. Interestingly, cycloheximide also blocked
IFN-induced activation of the p44/p42 mitogen-activated protein kinase,
which was partially required for induction of VEGF by IFNs. These findings
suggest that VEGF might be an indirect target gene of IFNs, and might
provide insights into therapeutic applications of IFNs against
angiogenesis-dependent tumors.
PMID: 16283438 [PubMed - as supplied by publisher]
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Loss of 22q chromosome is related to glioma progression
and loss of 10q.
Laigle-Donadey
F, Criniere
E, Benouaich
A, Lesueur
E, Mokhtari
K, Hoang-Xuan
K, Sanson
M.
Federation de neurologie Mazarin, Groupe hospitalier Pitie-Salpetriere,
47-83 bd de I'Hopital, 75013, Paris, France.
Loss of heterozygosity (LOH) of chromosome 22q has been investigated in 160
gliomas. LOH at one or more microsatellite increased with increasing grade
of the tumor (P < 0.01). LOH22q was more frequent in astrocytic tumors
(37%) compared to mixed or oligodendroglial tumors (21%) (P = 0.02). LOH22q
was correlated to 10q loss but not to 1p or 9p loss. Taken together, these
data suggest that LOH22q is an alteration associated with malignant
progression of gliomas.
PMID: 16283437 [PubMed - as supplied by publisher]
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Case report: cavernous sinus metastasis of the parotid
carcinoma: a very unusual case.
Yildirim
N, Oksuzoglu
B, Vural
M, Han
O, Zengin
N.
Department of Medical Oncology, Ankara Numune Research and Education
Hospital, Ankara, Turkey.
Cavernous sinus is an uncommon site of metastasis for the head and neck
tumors, and especially for the tumors of parotid gland. The case reported
here is the second reported case of parotid carcinoma metastatic to the
cavernous sinus, proven by histopathology. Also it is the first reported
parotid gland acinic cell carcinoma metastasis to the cavernous sinus.
Publication Types:
PMID: 15981110 [PubMed - indexed for MEDLINE]
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Frame-based stereotactic biopsy remains an important
diagnostic tool with distinct advantages over frameless stereotactic biopsy.
Smith
JS, Quinones-Hinojosa
A, Barbaro
NM, McDermott
MW.
Department of Neurological Surgery, Brain Tumor Research Center, University
of California at San Francisco, 505 Parnassus Avenue, 94143-0112 San
Francisco, California, USA. jsmith1@itsa.ucsf.edu
OBJECT: As the availability of image-guided surgical navigation systems has
increased, the application of frame-based biopsy has declined at our
institution, despite equivalent accuracy and safety. There are several cost
issues separating the use of surgical navigation systems and stereotactic
frames for simple biopsy which may have implications in this era of health
care cost control. We retrospectively reviewed the UCSF experience with
stereotactic brain biopsy from a 9 year period. METHODS: Data were collected
for 213 consecutive stereotactic brain biopsies performed at UCSF (139
frame-based and 74 frameless). There were no significant differences between
the frame-based and frameless biopsy groups with regard to patient
demographics, overall histopathology, proportion of nondiagnostic biopsies,
or incidence of complications. General anesthesia was used for 9 (6%) and 70
(95%) of the frame-based and frameless biopsy cases, respectively.
Frame-based biopsies required a mean of 114+/-3 min of operating room time,
while frameless biopsies required 185+/-6 min (P<0.0001). For patients
admitted to our neurosurgery service who underwent frame-based (n=110) or
frameless (n=52) biopsy within 24 h of admission, the mean lengths of
hospital stay were 1.8+/-0.2 and 3.2+/-0.6 days, respectively (P=0.007).
CONCLUSION: Frame-based and frameless stereotactic biopsy approaches were
equally effective at providing a tissue diagnosis with minimum morbidity and
mortality. The frame-based approach, however, required significantly less
anesthesia resources, less operating room time and shorter hospital stays,
and thus should still be considered a first-line approach for stereotactic
brain biopsy.
Publication Types:
PMID: 15981109 [PubMed - indexed for MEDLINE]
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Primary meningeal pheochromocytoma: case report.
Mercuri
S, Gazzeri
R, Galarza
M, Esposito
S, Giordano
M.
Dipartimento di scienze Neurologiche - Neurochirurgia, Rome, Italy.
OBJECTIVE AND IMPORTANCE: Intracranial pheochromocytomas are extremely rare
tumors. Reported cases include metastatic tumors without known cases of
primary pheochromocytomas. CLINICAL PRESENTATION: A female patient with a
history of a surgically treated adrenal pheochromocytoma presented 23 years
later with headache, nausea and blood hypertension. A head CT scan
demonstrated a right temporoparietal meningeal heterogeneous lesion with a
surrounding hyperdense ring. No other lesions were disclosed. INTERVENTION:
The lesion developed in the inner and outer surface of the dura without
brain infiltration and it was totally resected. The patient is free of
disease 6 years after brain surgery. CONCLUSION: To our knowledge this is
the first reported case of a primary meningeal pheochromocytoma.
Publication Types:
PMID: 15981108 [PubMed - indexed for MEDLINE]
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-
Surgical treatment of intramedullary spinal cord
metastases of systemic cancer: functional outcome and prognosis.
Gasser
T, Sandalcioglu
IE, Hamalawi
BE, van
de Nes JA, Stolke
D, Wiedemayer
H.
Department of Neurosurgery, Klinik und Poliklinik fur Neurochriurgie,
Universitatsklinikum Essen, Hufelandstrasse 55, D-45122 Essen, Germany.
thomas.gasser@uni-essen.de
OBJECTIVE: Intramedullary spinal cord metastases (ISCM) of systemic cancer
are rare. To date, patients with ISCM tend to benefit only to a limited
extend from surgery and adjuvant therapy. Subject of this investigation is
to assess predictive factors for surgical outcome and survival and to
evaluate the value of surgical radicality in the treatment of ISCM. PATIENTS
AND METHODS: Between 1990 and 2004, a series of 146 patients with
intramedullary tumors underwent surgical treatment in our institution. Among
these, 13 patients with intramedullary cancer metastases (7 adenocarcinomas,
3 poorly differentiated carcinomas, 3 sarcomas) were identified. Standard
microsurgical removal of the ISCM was performed. Functional outcome was
graded according to a standardized scale and factors influencing outcome and
survival were statistically analyzed. RESULTS: Median progression-free
survival was 13 weeks and median overall survival was 31 weeks. In 5
patients (38) the intramedullary lesion was the initial manifestation of the
malignant disease. All poorly differentiated carcinomas and all sarcomas
were resected incompletely. Surgical radicality presented a negative
predictive factor for functional outcome, increasing radicality leading to
functional deterioration. Age, sex, tumor localization, surgical radicality
and the presence of neoplastic meningeosis did not affect survival.
CONCLUSION: Surgery of ISCM can be performed with an acceptable operative
morbidity. Radicality depended on tumor histology. However, radical tumor
removal did not affect survival and was correlated with a poor functional
outcome. Therefore, complete surgical removal of ISCM should only be
intended in patients in whom an unproblematic excision is feasible.
Publication Types:
PMID: 15981107 [PubMed - indexed for MEDLINE]
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-
Predictors for patterns of brain relapse and overall
survival in patients with non-small cell lung cancer.
Tang
SG, Tseng
CK, Tsay
PK, Chen
CH, Chang
JW, Pai
PC, Hong
JH.
Department of Radiation Oncology, Chang Gung Memorial Hospital, Tao-Yuan
County, Kwei-Shan, Taiwan. simon@adm.cgmh.org.tw
Our goal was to investigate prognostic factors for different patterns of
brain relapse and overall survival so that treatments could be tailored and
treatment outcomes improved. We studied 292 patients with non-small cell
lung cancer (NSCLC) who had symptomatic, solitary, or multiple brain
metastases (isolated or not isolated from extracranial metastases) that had
developed early (<or=6 months) or late (>6 months) from initial
diagnosis. Factors affecting patterns of relapse and survival were analyzed
by univariate and multivariate analyses. Good ECOG performance status (PS)
at the time of NSCLC diagnosis was the most important factor that predicted
late (rather than early) relapse and improved survival, and was the only
factor that predicted isolated brain metastases. Patients whose lungs showed
a complete response (CR) to treatment had a higher rate of late brain
relapses than non-responders (NR) did (67.3% vs. 7.8%, P<0.001). CR
patients also experienced a longer median overall survival than NR patients.
Patients with late brain relapses showed better median survival times (18
months vs. 4 months, P<0.0001) than patients with early relapses, and
this was an independent factor by Cox regression analysis. Our findings
provide a justification for enrolling patients with good PS and controlled
lung lesions into clinical trials for the prevention of early, non-isolated
brain relapse. More aggressive therapeutic approaches should be applied to
patients with late, isolated and solitary relapses to improve both quality
and quantity of life.
Publication Types:
PMID: 15981106 [PubMed - indexed for MEDLINE]
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Advances in surgical management of malignancies of the
cranial base: the extended transbasal approach.
Chandler
JP, Pelzer
HJ, Bendok
BB, Hunt
Batjer H, Salehi
SA.
Department of Neurological Surgery, Northwestern University Feinberg School
of Medicine and Center for Cranial Base Surgery, Chicago, 60611 Illinois,
USA. jchandler@nmff.org
The extended transbasal approach combines a bifrontal craniotomy with an
orbital nasal and potentially a sphenoethmoidal osteotomy to provide
excellent access to malignancies of the anterior, middle and posterior skull
base. The approach enables the en bloc resection of tumors within the
frontal lobes, orbits, paranasal sinuses and sphenoclival corridors without
brain retraction and may obviate the need for transfacial access. We present
our 7-year experience during which 29 patients underwent surgery with the
extended transbasal exposure. In 25 patients the extended transbasal
approach was used alone; in the remaining four it was combined with
additional approaches. With exception of two patients, all lesions were
removed en bloc. Reconstruction was accomplished with the use of pericranium
and in some instances a temporalis muscle pedicle or a gracilis
microvascular free flap. There were no mortalities associated with this
approach. Seven patients experienced infections, four patients experienced
cerebral spinal fluid (CSF) leakage, two patients who had received adjuvant
radiation experienced scalp necrosis, three patients experienced
pneumocephalus, and 29 patients experienced cranial neuropathies, the
majority of which were loss of olfaction. The average follow-up for our
patients was 34 months with a range of 2--62 months.
Publication Types:
PMID: 15981105 [PubMed - indexed for MEDLINE]
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Infrequent mutation of APC, AXIN1, and GSK3B in human
pituitary adenomas with abnormal accumulation of CTNNB1.
Sun
C, Yamato
T, Kondo
E, Furukawa
T, Ikeda
H, Horii
A.
Department of Molecular Pathology, Tohoku University School of Medicine, 2-1
Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. horii@mail.tains.tohoku.ac.jp
We analyzed mutation of the APC, AXIN1, and GSK3genes in 14 pituitary
adenomas with abnormal nuclear accumulations of CTNNB1. These tumors did not
harbor mutation of the CTNNB1 gene. The genes analyzed encode proteins
associated with ubiquitin-mediated degradation of CTNNB1. Although the
regions encoding functional domains of these protein products were analyzed,
no significant genetic alterations were found. Furthermore, the antibody for
the C-terminus of APC detected normal expression of the APC protein in these
pituitary adenomas. Our present results imply that an unknown mechanism(s)
accelerates the accumulation of CTNNB1 that plays an important role in the
pathogenesis of human pituitary adenomas. However, the possibility that
mutation of regions outside of our survey or epigenetic mechanism play an
important role cannot be excluded.
PMID: 15981102 [PubMed - indexed for MEDLINE]
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Cyclin D1 is overexpressed in atypical teratoid/rhabdoid
tumor with hSNF5/INI1 gene inactivation.
Fujisawa
H, Misaki
K, Takabatake
Y, Hasegawa
M, Yamashita
J.
Department of Neurosurgery, Division of Neuroscience, Graduate School of
Medical Science, Kanazawa University, 13-1 Takaramachi, 920-8641 Kanazawa,
Ishikawa, Japan. fujisawa@ns.m.kanazawa-u.ac.jp
OBJECT: Although atypical teratoid/rhabdoid tumor (AT/RT) is known to
generate through inactivation of the hSNF5/INI1 gene on chromosome 22q, the
downstream molecular mechanism remains unclear. We histologically and
molecularly reviewed our pediatric brain tumors for unrecognized AT/RTs and
evaluated the role of cyclin D1, a potential molecular target of hSNF5/INI1.
METHODS: We analyzed 16 tumors under three years of age: seven
medulloblastomas, three anaplastic ependymomas (E IIIs), two each of
supratentorial primitive neuroectodermal tumors (sPNETs) and choroid plexus
carcinomas (CPCs), and one each of neuroblastoma and pineoblastoma.
Immunohistochemistry for glial fibrillary acidic protein, vimentin,
epithelial membrane antigen, smooth muscle actin and cyclin D1 was
performed. Polymerase chain reaction (PCR)-single-strand conformation
polymorphism analysis with direct sequencing, differential PCR and
microsatellite analysis were conducted for hSNF5/INI1mutation, homozygous
deletion and loss of heterozygosity (LOH) on 22q, respectively. Because of
the presence of rhabdoid cells and the polyimmunophenotypic features, the
diagnosis was revised to AT/RT in five (31%) tumors, namely, two E IIIs and
one each of medulloblastoma, CPC and pineoblastoma. Three of them harbored
such hSNF5/INI1 aberrations as germline single base deletion (492/6 delC)
and missense mutation (C157T) together with LOH 22q or homozygous deletion.
Cyclin D1 was overexpressed in those three tumors but not in the two that
lacked hSNF5/INI1 inactivation. CONCLUSION: AT/RT can be misdiagnosed as a
variety of tumors, including ependymoma that potentially harbors LOH 22q.
Our data indicate that cyclin D1 is a target of hSNF5/INI1in primary tumors.
PMID: 15981100 [PubMed - indexed for MEDLINE]
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Apoptosis and proliferation: correlation with p53 in
astrocytic tumours.
Sarkar
C, Karak
AK, Nath
N, Sharma
MC, Mahapatra
AK, Chattopadhyay
P, Sinha
S.
Department of Pathology, All India Institute of Medical Sciences, Ansari
Nagar, 110029, New Delhi, India. drchitrasarkar@yahoo.com.
Apoptosis and cell proliferation occur simultaneously in tumour tissue with
tumour suppressor gene, p53 being one of the key players in the complex
relationship between these two key phenomena. We, as well as several other
groups, have earlier demonstrated the association of p53 immunopositivity
with increased degree of cell proliferation in astrocytic tumours. Here we
have studied the extent of apoptosis in 62 primary human astrocytic tumours
[25 Diffuse Astrocytoma (DA), 9 Anaplastic Astrocytoma (AA) and 28
Glioblastoma multiforme (GBM)] in relation to tumour grade, proliferative
status and p53 protein expression. Apoptosis was measured by the TUNEL assay
while, cell proliferation (MIB-1 index) and p53 protein immunoreactivity
were evaluated by immunohistochemical staining using MIB-1 and DO-1
monoclonal antibodies respectively. The apoptotic index (AI) was greater in
GBM than in AA or DA, and more in tumours with p53 immunopositivity than in
those without. The most striking observation was the strong correlation
between Apoptotic index (AI) and proliferation index (PI) in p53 negative
GBM (r=0.766, P < 0.005). However this was not observed in p53 +ve GBM or
in low grade DA either p53 positive or negative. Taking p53 negativity in
IHC as evidence of a functional gene/protein, this extends the link between
proliferation and apoptosis, hitherto observed only in cultured cells with
functional p53, to a subset of solid tumours.
PMID: 15981097 [PubMed - indexed for MEDLINE]
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Stereotactic interstitial radiosurgery for cerebral
metastases.
Curry
WT Jr, Cosgrove
GR, Hochberg
FH, Loeffler
J, Zervas
NT.
Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical
School, Boston, Massachusetts 02114, USA. wcurry@partners.org
OBJECT: The Photon Radiosurgery System (PRS) is a miniature x-ray generator
that can stereotactically irradiate intracranial tumors by using low-energy
photons. Treatment with the PRS typically occurs in conjunction with
stereotactic biopsy, thereby providing diagnosis and treatment in one
procedure. The authors review the treatment of patients with brain
metastases with the aid of the PRS and discuss the indications, advantages,
and limitations of this technique. METHODS: Clinical characteristics,
treatment parameters, neuroimaging-confirmed outcome, and survival were
reviewed in all patients with histologically verified brain metastases who
were treated with the PRS at the Massachusetts General Hospital between
December 1992 and November 2000. Local control of lesions was defined as
either stabilization or diminution in the size of the treated tumor as
confirmed by Gd-enhanced magnetic resonance imaging. Between December 1992
and November 2000, 72 intracranial metastatic lesions in 60 patients were
treated with the PRS. Primary tumors included lung (33 patients), melanoma
(15 patients), renal cell (five patients), breast (two patients), esophageal
(two patients), colon (one patient), and Merkle cell (one patient) cancers,
and malignant fibrous histiocytoma (one patient). Supratentorial metastases
were distributed throughout the cerebrum, with only one cerebellar
metastasis. The lesions ranged in diameter from 6 to 40 mm and were treated
with a minimal peripheral dose of 16 Gy (range 10-20 Gy). At the last
follow-up examination (median 6 months), local disease control had been
achieved in 48 (81%) of 59 tumors. An actuarial analysis demonstrated that
the survival rates at 6 and 12 months were 63 and 34%, respectively.
Patients with a single brain metastasis survived a mean of 11 months.
Complications included four patients with postoperative seizures, three with
symptomatic cerebral edema, two with hemorrhagic events, and three with
symptomatic radiation necrosis requiring surgery. CONCLUSIONS: Stereotactic
interstitial radiosurgery performed using the PRS can obtain local control
of cerebral metastases at rates that are comparable to those achieved
through open resection and external stereotactic radiosurgery. The major
advantage of using the PRS is that effective treatment can be accomplished
at the time of stereotactic biopsy.
PMID: 16266044 [PubMed - indexed for MEDLINE]
Interventional neuroradiology adjuncts and alternatives
in patients with head and neck vascular lesions.
Johnson
MH, Chiang
VL, Ross
DA.
Interventional Neuroradiology, Department of Diagnostic Radiology, Yale
University School of Medicine, 333 Cedar Street, PO Box 8042, New Haven, CT
06520-8042, USA. michele.h.johnson@yale.edu
Vascular lesions of the head and neck can result from a variety of
neoplastic and traumatic conditions that may cause local neurologic symptoms
or may compromise the carotid or vertebral arteries, leading to ischemic
deficits. Management of lesions involving vascular structures at the skull
base may require a temporary balloon occlusion tolerance test or
endovascular transarterial embolization as part of the preoperative
management. Endovascular techniques can also be used as a salvage measure
for severe head and neck bleeding and can assist with the management of
vascular injury occurring in the operative or perioperative setting.
Familiarity with the role of endovascular techniques in this group of
patients may favorably influence patient management and outcome.
Publication Types:
PMID: 15990044 [PubMed - indexed for MEDLINE]
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Bromophenol blue staining of tumors in a rat glioma
model.
Ozawa
T, Britz
GW, Kinder
DH, Spence
AM, VandenBerg
S, Lamborn
KR, Deen
DF, Berger
MS.
Department of Neurological Surgery, Brain Tumor Research Center, University
of California, San Francisco, California, USA.
OBJECTIVE: For patients with gliomas, decreasing the tumor burden with
macroscopic surgical resection may affect quality of life, time to tumor
progression, and survival. Injection of bromophenol blue (BPB) may enhance
intraoperative visualization of an infiltrating tumor and its margins and
improve the extent of resection. In this study, we investigated the uptake
of BPB in experimental rat brain tumors. METHODS: We first conducted a
toxicity study with bolus intravenous injections of 5, 60, and 360 mg/kg
doses of BPB in nontumor-bearing Fischer 344 rats. No adverse effects were
observed in any of the animals during the 60 day observation period. We then
injected 9L tumor cells intracerebrally into Fischer 344 rats and
approximately 2 weeks later, administered a bolus intravenous injection of 5
to 360 mg/kg BPB. Fifteen minutes after BPB injection, we sacrificed the
animals and removed their brains. In a subsequent study, we injected 180
mg/kg BPB and sacrificed animals at several time points to monitor tumor
staining over time. RESULTS: The stain was clearly visible and localized to
the tumor for all BPB concentrations 60 mg/kg or greater, and in an
additional experiment, we found that tumor staining persisted for at least 8
hours after BPB injection. CONCLUSION: We conclude that BPB helped visualize
experimental tumors at time points from a few minutes to several hours after
injection. Because BPB also proved to be nontoxic to the animals at
effective concentrations, we believe the compound may be potentially useful
in helping neurosurgeons visualize brain tumors in humans.
PMID: 16284574 [PubMed - in process]
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Local delivery of a synthetic endostatin fragment for the
treatment of experimental gliomas.
Pradilla
G, Legnani
FG, Petrangolini
G, Francescato
P, Chillemi
F, Tyler
BM, Gaini
SM, Brem
H, Olivi
A, DiMeco
F.
Department of Neurosurgery, School of Medicine, Johns Hopkins University,
Baltimore, Maryland, USA.
OBJECTIVE: Endostatin is an anti-angiogenic agent that blocks
matrix-metalloproteinase-2 and inhibits endothelial cell proliferation.
Currently, endostatin is available through recombinant technology, which
limits its broader use. In this study, a synthetic endostatin fragment (EF)
was analyzed to determine its anti-angiogenic properties when locally
delivered by controlled-release polymers and to establish its effect as a
treatment for experimental gliomas. METHODS: Cytotoxicity of EF against 9L
gliosarcoma and F98 glioma was determined in vitro. EF was loaded into
polyanhydride-poly-(bis-[carboxyphenoxy-propane]-sebacic-acid) (pCPP:SA)
polymers at increasing concentrations. Pharmacokinetics of the EF/polymer
formulations were defined in vitro. Anti-angiogenic properties of the
EF/polymer formulations were evaluated in the rat-cornea micropocket assay.
Toxicity and efficacy of locally delivered EF polymers either alone or
combined with systemic bischloroethylnitrosourea (carmustine) were
determined in rats intracranially challenged with 9L gliosarcoma. RESULTS:
EF showed scarce cytotoxicity against 9L and F98 in vitro. EF/pCPP:SA
formulations showed sustained release by day 19. Mean corneal angiogenesis
index 20 days after tumor implantation was 4.5 +/- 0.7 for corneas implanted
with 40% EF/pCPP:SA compared with controls (8.5 +/- 1.3, P = 0.02).
Intracranial efficacy studies showed that EF polymers alone did not prolong
animal survival. Combination of 40% EF/pCPP:SA polymers with systemic
bischloroethylnitrosourea (carmustine) prolonged survival (median survival
of 44 d, P = 0.001) and generated 33% long-term survivors. CONCLUSION:
Controlled-release polymers can effectively deliver a biologically active EF
in a sustained fashion. EF inhibits angiogenesis in vitro and in vivo, and
even though EF does not prolong survival as a single agent, it exhibits a
synergistic effect when combined w |
Volume 4, Number 48 - 23 November 2005