| 1: Arch Neurol. 2005 Jan;62(1):148-9. |
|
-
Neurosarcoidosis mimicking meningioma.
Rodriguez F, Link MJ, Driscoll CL, Giannini C.
PMID: 15642863 [PubMed - in process]
-
| 2: Cancer. 2005 Jan 7; [Epub ahead of print] |
|
-
Three-year recurrence-free survival in a patient with
recurrent medulloblastoma after resection, high-dose chemotherapy, and
intrathecal Yttrium-90-labeled DOTA(0)-D-Phe(1)-Tyr(3)-octreotide
radiopeptide brachytherapy.
Beutler D, Avoledo P, Reubi JC, Macke HR, Muller-Brand J, Merlo A, Kuhne
T.
Department of Oncology/Hematology, University Children's Hospital Basel,
Basel, Switzerland.
BACKGROUND: Most medulloblastomas express high levels of somatostatin type 2
receptors (sst2). DOTA(0)-D-Phe(1)-Tyr(3)-octreotide (DOTATOC) specifically
binds sst2 in the low nanomolar range. The cytotoxic effect is mediated by
the chelated, beta-emitting, metallic radionuclide Yttrium 90 ((90)Y). The
authors applied this innovative treatment option in a boy age 8 years who
presented with a recurrent medulloblastoma of the cauda equina: a
prognostically poor condition. Targeted radiotherapy was administered to
treat minimal sst2-expressing tumor remnants, which persisted despite
conventional and high-dose chemotherapy and intercurrent resection of the
lesion. METHODS: A medulloblastoma arising from the floor of the fourth
ventricle had been removed surgically; then, the patient was treated with
standard adjuvant chemotherapy and craniospinal irradiation according to the
prospective HIT '91 protocol. Complete remission was achieved for 20 months,
when a drop metastasis of the cauda equina manifested with sensorimotor
lumbosacral deficits and urinary incontinence. After four cycles of
neoadjuvant chemotherapy (which consisted of combined ifosfamide,
carboplatinum and etoposide), two cycles of high-dose chemotherapy and
autologous stem cell transplantation were performed; in between, the
responding residual tumor within the lumbosacral nerve fibers was
microscopically removed. Thereafter, an Indium-111-DOTATOC test injection
indicated sst2-expressing tumor remnants within the cauda equina. Con-
sequently, 4 cycles of [(90)Y]-DOTATOC (4 x 562.5 megabecquerels) were
injected directly into the cerebrospinal fluid in monthly intervals.
RESULTS: The consolidating intrathecal brachytherapy using [(90)Y]-DOTATOC
was tolerated well. A complete remission was achieved for a 3-year period.
The only remaining deficit was urinary incontinence. CONCLUSIONS:
Intrathecal administration of targeted radiopeptide brachytherapy in
combination with conventional and high-dose chemotherapy and surgical
removal represents a promising new option to treat recurrent medulloblastoma
and should be explored further. Cancer 2005. (c) 2005 American Cancer
Society.
PMID: 15641034 [PubMed - as supplied by publisher]
-
| 3: Cancer Genet Cytogenet. 2005 Jan 15;156(2):144-9. |
|
-
Genetic polymorphisms of GSTs and their association with
primary brain tumor incidence.
Pinarbasi H, Silig Y, Gurelik M.
Department of Biochemistry, Faculty of Medicine, Cumhuriyet University,
58140, Sivas, Turkey.
Glutathione S-transferases GSTM1, GSTT1, and GSTP1 are phase II
biotransformation enzymes that function on detoxification of a wide range of
exogenous agents including carcinogens. It has been shown that genetic
variations in these genes play an important role in determining the response
of an individual to environmental carcinogens. Some studies revealed a
statistically significant association between the polymorphisms in the genes
encoding GST enzymes and some cancers, although contrary reports exist. In
this study, the association between polymorphisms in these genes and primary
brain tumor incidence was investigated in 228 Turkish individuals (75
patients with primary brain tumor and 153 controls). The prevalence of GSTM1
null genotype in the case group was 43%, compared to 24% in the control
group, giving an odds ratio (OR) of 2.33 (95% confidence interval
CI=1.24-4.39). No association was observed between the GSTT1 or GSTP1
Ile105Val polymorphism and brain tumor incidence. Polymorphisms in GSTM1,
GSTT1, and GSTP1 did not show association with histopathologic type of brain
tumor (glioma or meningioma). Analysis of the polymorphisms in the studied
genes and smoking status of the brain tumor patients revealed no
statistically significant association. The presented data clearly suggest a
relation between brain tumor incidence with GSTM1 null genotype but not with
GSTT1 or GSTP1 gene variants.
PMID: 15642394 [PubMed - in process]
-
| 4: Clin Cancer Res. 2004 Sep 15;10(18 Pt 1):6222-30. |
|
-
Antiangiogenic therapy of cerebral melanoma metastases
results in sustained tumor progression via vessel co-option.
Leenders WP, Kusters B, Verrijp K, Maass C, Wesseling P, Heerschap A,
Ruiter D, Ryan A, de Waal R.
Department of Pathology, University Medical Centre St. Radboud, Nijmegen,
the Netherlands. w.leenders@pathol.umcn.nl
PURPOSE: In the brain, tumors may grow without inducing angiogenesis, via
co-option of the dense pre-existent capillary bed. The purpose of this study
was to investigate how this phenomenon influences the outcome of
antiangiogenic therapy. EXPERIMENTAL DESIGN: Mice carrying brain metastases
of the human, highly angiogenic melanoma cell line Mel57-VEGF-A were either
or not treated with different dosages of ZD6474, a vascular endothelial
growth factor (VEGF) receptor 2 tyrosine kinase inhibitor with additional
activity against epidermal growth factor receptor. Effect of treatment was
evaluated using contrast-enhanced magnetic resonance imaging (CE- MRI) and
(immuno)morphologic analysis. RESULTS: Placebo-treated Mel57-VEGF-A brain
metastases evoked an angiogenic response and were highlighted in CE-MRI.
After treatment with ZD6474 (100 mg/kg), CE-MRI failed to detect tumors in
either prevention or therapeutic treatment regimens. However,
(immuno)histologic analysis revealed the presence of numerous, small,
nonangiogenic lesions. Treatment with 25 mg/kg ZD6474 also resulted in
efficient blockade of vessel formation, but it did not fully inhibit
vascular leakage, thereby still allowing visualization in CE-MRI scans.
CONCLUSIONS: Our data show that, although angiogenesis can be effectively
blocked by ZD6474, in vessel-dense organs this may result in sustained tumor
progression via co-option, rather than in tumor dormancy. Importantly,
blocking VEGF-A may result in undetectability of tumors in CE-MRI scans,
leading to erroneous conclusions about therapeutic efficacy during magnetic
resonance imaging follow-up. The maintenance of VEGF-A-induced vessel
leakage in the absence of neovascularization at lower ZD6474 doses may be
exploited to improve delivery of chemotherapeutic agents in combined
treatment regimens of antiangiogenic and chemotherapeutic compounds.
PMID: 15448011 [PubMed - indexed for MEDLINE]
-
| 5: J Neuropathol Exp Neurol. 2004 Dec;63(12):1236-42. |
|
Pathogenesis of tuberous sclerosis subependymal giant
cell astrocytomas: biallelic inactivation of TSC1 or TSC2 leads to mTOR
activation.
Chan JA, Zhang H, Roberts PS, Jozwiak S, Wieslawa G, Lewin-Kowalik J,
Kotulska K, Kwiatkowski DJ.
Division of Neuropathology, Department of Pathology, Brigham and Women's
Hospital, Boston, Massachusetts 02115, USA.
In the central nervous system, tuberous sclerosis complex (TSC) is
characterized by a range of lesions including cortical tubers, white matter
heterotopias, subependymal nodules, and subependymal giant cell astrocytomas
(SEGAs). Recent studies have implicated an important role for the TSC genes
TSC1 and TSC2, in a signaling pathway involving the mammalian target of
rapamycin (mTOR) kinase. We performed immunohistochemical and genetic
analyses on SEGAs from 7 TSC patients, 4 with mutations in TSC1, and 3 with
mutations in TSC2. SEGA cells show high levels of phospho-S6K, phospho-S6,
and phospho-Stat3, all proteins downstream of and indicative of mTOR
activation. Such expression is not seen in histologically normal control
tissue. Five of 6 SEGAs also showed evidence of biallelic mutation of TSC1
or TSC2, suggesting that SEGAs develop due to complete loss of a functional
tuberin-hamartin complex. We conclude that TSC SEGAs likely arise through a
two-hit mechanism of biallelic inactivation of TSC1 or TSC2, leading to
activation of the mTOR kinase.
PMID: 15624760 [PubMed - indexed for MEDLINE]
-
| 6: J Neuropathol Exp Neurol. 2004 Dec;63(12):1211-24. |
|
Prognosis-related molecular markers in pediatric central
nervous system tumors.
Rickert CH.
Institute of Neuropathology, Department of Pediatric Hematology and
Oncology, Munster University Hospital, Germany. rickchr@uni-muenster.de
In the wake of recent progress in understanding the genetic pathways
involved in the development of brain tumors, a major goal is to correlate
molecular data with clinical outcome, survival, and response to treatment
modalities. This is of particular importance among the pediatric population.
Reliable prognostic factors could potentially permit a tailoring of therapy
in that only patients with the most aggressive tumors would receive the most
intense treatments. A survey of publications about prognosis-related
molecular features among pediatric brain tumors revealed 74 series, of which
46 presented statistically significant outcome-associated parameters as
defined by a p value <0.05. Most investigations revealing significant
prognosis-related features were performed on medulloblastomas (34
publications), followed by astrocytic tumors (6 publications) and
ependymomas (5 publications). Promising approaches and molecular markers
include gene expression profiles, DNA ploidy, loss of heterozygosity and
chromosomal aberrations as detected by CGH and FISH (1q, 17p, 17q), as well
as oncogenes/ tumor suppressor genes and their proteins (TP53, PTEN,
c-erbB2, N-myc, c-myc), growth factor and hormonal receptors (PDGFRA, VEGF,
EGFR, HER2, HER4, ErbB-2, hTERT, TrkC), cell cycle genes (p27) and cell
adhesion molecules, as well as factors potentially related to therapeutic
resistance (multi-drug resistance, DNA topoisomerase IIalpha,
metallothionein, P-glycoprotein, tenascin). This review discusses the
predictive potential of molecular markers for clinical outcome and their
influence on therapeutic decision-making among children with brain tumors.
Publication Types:
PMID: 15624758 [PubMed - indexed for MEDLINE]
-
| 7: J Nucl Med. 2004 Nov;45(11):1931-8. |
|
-
Uptake of 18F-fluorocholine, 18F-fluoroethyl-L-tyrosine,
and 18F-FDG in acute cerebral radiation injury in the rat: implications for
separation of radiation necrosis from tumor recurrence.
Spaeth N, Wyss MT, Weber B, Scheidegger S, Lutz A, Verwey J, Radovanovic
I, Pahnke J, Wild D, Westera G, Weishaupt D, Hermann DM, Kaser-Hotz B,
Aguzzi A, Buck A.
PET Center, Division of Nuclear Medicine, University Hospital Zurich,
Zurich, Switzerland.
Differentiation between posttherapy radiation necrosis and recurrent tumor
in humans with brain tumor is still a difficult diagnostic task. The new PET
tracers (18)F-fluoro-ethyl-l-tyrosine (FET) and (18)F-fluorocholine
(N,N-dimethyl-N-(18)F-fluoromethyl-2-hydroxyethylammonium [FCH]) have shown
promise for improving diagnostic accuracy. This study assessed uptake of
these tracers in experimental radiation injury. METHODS: In a first model,
circumscribed lesions were induced in the cortex of 35 rats using proton
irradiation of 150 or 250 Gy. After radiation injury developed, uptake of
(18)F-FET, (18)F-FCH, and (18)F-FDG was measured using autoradiography and
correlated with histology and disruption of the blood-brain barrier as
determined with Evans blue. In a second model, uptake of the tracers was
assessed in acute cryolesions, which are characterized by the absence of
inflammatory cells. RESULTS: Mean (18)F-FET, (18)F-FCH, and (18)F-FDG
standardized uptake values in the most active part of the radiation lesion
and the contralateral normal cortex (in parentheses) were 2.27 +/- 0.46
(1.42 +/- 0.23), 2.52 +/- 0.42 (0.61 +/- 0.12), and 6.21 +/- 1.19 (4.35 +/-
0.47). The degree of uptake of (18)F-FCH and (18)F-FDG correlated with the
density of macrophages. In cryolesions, (18)F-FET uptake was similar to that
in radiation lesions, and (18)F-FCH uptake was significantly reduced.
CONCLUSION: Comparison of tracer accumulation in cryolesions and radiation
injuries demonstrates that (18)F-FET uptake is most likely due to a
disruption of the blood-brain barrier alone, whereas (18)F-FCH is
additionally trapped by macrophages. Uptake of both tracers in the radiation
injuries is generally lower than the published uptake in tumors, suggesting
that (18)F-FET and (18)F-FCH are promising tracers for separating radiation
necrosis from tumor recurrence. However, the comparability of our data with
the literature is limited by factors such as different species and
acquisition protocols and modalities. Thus, more studies are needed to
settle this issue. Nevertheless, (18)F-FCH and (18)F-FET seem superior to
(18)F-FDG for this purpose.
Publication Types:
PMID: 15534065 [PubMed - indexed for MEDLINE]
-
| 8: Neurology. 2005 Jan 11;64(1):166-7. |
|
-
Central neurogenic hyperventilation and lactate
production in brainstem glioma.
Gaviani P, Gonzalez RG, Zhu JJ, Batchelor TT, Henson JW.
Stephen E. and Catherine Pappas Center for Neuro-oncology, Massachusetts
General Hospital, Boston, MA 02114, USA.
PMID: 15642931 [PubMed - in process]
-
| 9: Neurology. 2004 Feb 10;62(3):451-6. |
|
Comment in:
Treatment-induced leukoencephalopathy in primary CNS
lymphoma: a clinical and autopsy study.
Lai R, Abrey LE, Rosenblum MK, DeAngelis LM.
Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York,
NY 10021, USA.
BACKGROUND: Treatment-related leukoencephalopathy is the leading toxicity
after successful treatment of primary CNS lymphoma (PCNSL). Its mechanism is
poorly understood and there are no autopsy data available on such patients.
METHODS: From a database of immunocompetent patients with PCNSL diagnosed
between 1985 and 2001, the authors identified five autopsied patients who
died of leukoencephalopathy. The authors reviewed their clinical records,
MRI, and autopsy findings. RESULTS: The median age was 74 years (range 41 to
79) at PCNSL diagnosis. Symptoms of neurotoxicity developed a median of 1
month after treatment completion, and median survival was 30 months (range
22 to 68 months) after neurotoxicity onset. All had white matter
hyperintensity on T2-weighted MRI, and two developed enhancing lesions 5 and
14 months following completion of treatment. At autopsy no PCNSL was
identified. Myelin and axonal loss, gliosis, pallor, spongiosis, and
rarefaction of the white matter were found in all; two patients had tissue
necrosis that correlated with the enhancement on MRI, and one had fibrinoid
necrosis of vessels. Four of the five patients had atherosclerosis of large
cerebral vessels in the circle of Willis and all had small vessel disease;
two had recent strokes at autopsy. CONCLUSIONS: Treatment-induced
leukoencephalopathy is not a late delayed consequence of neurotoxic
treatment but can be seen very early in some patients. Vascular disease may
be a component of this white matter injury.
Publication Types:
- Case Reports
- Review
- Review, Multicase
PMID: 14872029 [PubMed - indexed for MEDLINE]
-
| 10: Surg Neurol. 2005 Jan;63(1):56-61. |
|
-
Fractional anisotropy value by diffusion tensor magnetic
resonance imaging as a predictor of cell density and proliferation activity
of glioblastomas.
Beppu T, Inoue T, Shibata Y, Yamada N, Kurose A, Ogasawara K, Ogawa A,
Kabasawa H.
Departments of Neurosurgery.
BACKGROUND: In vivo, water diffusion displays directionality due to presence
of complex microstructural barriers in tissue. The extent of directionality
of water diffusion can be expressed as a fractional anisotropy (FA) value
using diffusion tensor magnetic resonance imaging (DTI). The FA value has
been suggested as an indicator of the cell density of astrocytic tumors. The
aim of the present study was to confirm beyond doubt that FA values indicate
cell density even when limited in glioblastomas and to determine whether the
FA value of a given patient predicts proliferation activity in the
individual glioblastoma. METHODS: We performed DTI in 19 patients with
glioblastoma and measured the FA values of tumor and normal brain regions
prior to computed tomography-guided stereotactic biopsy. Differences in mean
FA value between normal brain regions and glioblastoma lesion were compared.
Cell density and MIB-1 indices were examined using tumor specimens obtained
from biopsies. Correlation among FA values, cell density, and MIB-1 indices
was also evaluated. RESULTS: The mean FA value significantly differed
between normal brain regions and glioblastoma lesions. Positive correlation
was observed between FA value and cell density (r = 0.73, P < 0.05) and
between FA value and MIB-1 index (r = 0.80, P < 0.05). CONCLUSIONS: Our
results suggest that the FA value of glioblastoma as determined by DTI prior
to surgery is a good predictor of cell density and, consequently,
proliferation activity.
PMID: 15639528 [PubMed - in process]
|
Volume 4, Number 4 - 18 January 2005