-
Expression of ADAMTS-8, a secreted protease with
antiangiogenic properties, is downregulated in brain tumours.
Dunn
JR, Reed
JE, du
Plessis DG, Shaw
EJ, Reeves
P, Gee
AL, Warnke
P, Walker
C.
1JK Douglas Cancer Research Laboratories, Clatterbridge Hospital, Bebington,
Wirral CH64 3JY, UK.
Angiogenesis and extracellular matrix degradation are key events in tumour
progression, and factors regulating stromal-epithelial interactions and
matrix composition are potential targets for the development of novel
anti-invasive/antiangiogenic therapies. Here, we examine the expression of
ADAMTS-8, a secreted protease with antiangiogenic properties, in brain
tissues. Using quantitative RT-polymerase chain reaction (PCR), high,
equivalent expression of ADAMTS-8 was found in normal whole brain, cerebral
cortex, frontal lobe, cerebellum and meninges. ADAMTS-8 expression in 34
brain tumours (including 22 high-grade gliomas) and four glioma cell lines
indicated at least two-fold reduction in mRNA compared to normal whole brain
in all neoplastic tissues, and no detectable expression in 14 out of 34
(41%) tumours or four out of four (100%) cell lines. In contrast,
differential expression of TSP1 and VEGF was seen in nine out of 15 (60%)
and seven out of 13 (54%) tumours, with no relationship in the expression of
these genes. Immunohistochemistry and Western analysis indicated
downregulation of ADAMTS-8 protein in >77% tumours. Methylation-specific
PCR analysis of ADAMTS-8 indicated promoter hypermethylation in one out of
24 brain tumours (a metastasis) and three out of four glioma cell lines
suggesting an alternative mechanism of downregulation. These data suggest a
role for ADAMTS-8 in brain tumorigenesis, warranting further investigation
into its role in regulation of tumour angiogenesis and local
invasion.British Journal of Cancer advance online publication, 28 March
2006; doi:10.1038/sj.bjc.6603006 www.bjcancer.com.
PMID: 16570050 [PubMed - as supplied by publisher]
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-
Mobile phone use and risk of glioma in adults:
case-control study.
Milham
S.
12318 Gravelly Beach Loop NW, Olympia, WA 98502, USA.
PMID: 16570042 [PubMed - as supplied by publisher]
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| 3: Cancer.
2006 Mar 27; [Epub ahead of print] |
|
-
Prognostic impact of molecular markers in a series of 220
primary glioblastomas.
Houillier
C, Lejeune
J, Benouaich-Amiel
A, Laigle-Donadey
F, Criniere
E, Mokhtari
K, Thillet
J, Delattre
JY, Hoang-Xuan
K, Sanson
M.
Mazarin Neurology Service and INSERM U711, Biology of Neuronal and Glial
Interactions, Paris, France.
BACKGROUND: In contrast to oligodendrogliomas, molecular predictors of
prognosis have not been consistently found in glioblastomas. However,
genetic studies show that glioblastomas consist of several genetic subtypes
and raise the possibility that molecular alterations could be predictive of
survival. METHODS: A search for loss of heterozygosity (LOH) on chromosome
1p, 9p, 10q, 19q, EGFR (epidermal growth factor receptor), CDK4, and MDM2
(mouse double minute) amplifications, CDKN2A (INK4A/ARF) homozygous
deletions, p53 expression, was performed in a series of 220 primary
glioblastomas. The molecular alterations were then correlated with each
other to identify distinct molecular pathways and with clinical parameters
and the course of the disease to identify prognostic markers. RESULTS:
Nonrandom associations were found between EGFR amplification and LOH10q,
LOH9p, and INK4A/ARF deletion, LOH1p and LOH19q, and MDM2 and CDK4
amplification, whereas mutual exclusions were found between p53 expression
and EGFR amplification, LOH 9p/INK4A/ARF homozygous deletion, and MDM2 and
CDK4 amplification. Age (P = 4.10(-5)) and performance status (P = .003)
were the main predictors of outcome. In contrast, molecular markers were of
limited impact: MDM2 amplification correlated with poor outcome on both
univariate and multivariate analysis (P = .01) and EGFR amplification with
good prognosis on multivariate analysis (P = .02). CONCLUSION: Despite their
limited prognostic impact, the genetic markers investigated here outline
distinct molecular pathways involved in glioblastoma tumorigenesis and
warrant broader molecular screening. Cancer 2006. (c) 2006 American Cancer
Society.
PMID: 16568472 [PubMed - as supplied by publisher]
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| 4: Cancer.
2006 Mar 1;106(5):1140-3. |
|
-
Value of postoperative stereotactic radiosurgery and
conventional radiotherapy for incompletely resected typical neurocytomas.
Rades
D, Schild
SE.
Department of Radiation Oncology, University Medical Center Hamburg-Eppendorf,
Hamburg, Germany. Rades.Dirk@gmx.net
BACKGROUND: Two groups of central neurocytomas have been identified: typical
and atypical neurocytomas. The more benign typical neurocytomas have a
better prognosis. Complete resection of typical neurocytomas results in
significantly better outcome than incomplete resection. The current study
investigated whether the outcome after incomplete resection can be improved
by postoperative stereotactic radiosurgery (SRS) or by conventional
radiotherapy. METHODS: The data of all neurocytoma patients reported since
1997, when the first neurocytoma patient treated with SRS was described,
were reviewed. Patients who underwent complete resection or those with
atypical neurocytoma were excluded from the analysis. Three different
therapies were compared for overall survival (OS) and local control (LC):
incomplete resection alone (ITR), ITR followed by conventional radiotherapy
(ITR+cRT), and ITR followed by stereotactic radiosurgery (ITR+SRS). RESULTS:
Data were complete in 121 patients (59 ITR, 41 ITR+cRT, and 21 ITR+SRS). The
5-year-LC after ITR was 51%. LC was significantly better after ITR+cRT (87%,
P = 0.001) and after ITR+SRS (100%, P = 0.004). The difference between
ITR+cRT and ITR+SRS was not significant (P = 0.45). The 5-year-OS was 93%
after ITR, 100% after ITR+cRT, and 100% after ITR+SRS. The differences
between the various groups were not significant. The P-values were 0.13 for
ITR versus ITR+cRT, 0.29 for ITR versus ITR+SRS, and 1.0 for ITR+cRT versus
ITR+SRS. CONCLUSIONS: After ITR of typical neurocytomas, LC is significantly
improved by both conventional radiotherapy and SRS. The results of both
radiation treatments were similar. SRS is a reasonable alternative to
conventional radiotherapy in selected patients.
PMID: 16400638 [PubMed - indexed for MEDLINE]
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-
Metachronous secondary atypical meningioma and anaplastic
astrocytoma after postoperative craniospinal irradiation for medulloblastoma.
Hope
AJ, Mansur
DB, Tu
PH, Simpson
JR.
Department of Radiation Oncology, Washington University School of Medicine,
660 South Euclid Avenue, Campus Box 8224, St. Louis, MO, 63110, USA, ahope@radonc.wustl.edu.
INTRODUCTION: Malignant brain tumors have been reported to occur after
childhood irradiation more frequently than in the nonirradiated population.
DISCUSSION: In this study, we report the case of a 15-year-old boy treated
for medulloblastoma with surgery and craniospinal radiotherapy, who
developed a meningioma 18 years after initial treatment and subsequently an
anaplastic astrocytoma 23 years after primary treatment. The meningioma was
resected without complications. The patient is currently alive but with
recurrent astrocytoma after a complete remission on temozolomide monotherapy.
Second malignancies are a rare, potentially devastating risk in cancer
survivors, with risk continuing lifelong.
PMID: 16570196 [PubMed - as supplied by publisher]
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-
Role of temozolomide in pediatric brain tumors.
Barone
G, Maurizi
P, Tamburrini
G, Riccardi
R.
Division of Pediatric Oncology, Catholic University of Rome, Largo A.
Gemelli, 8, Rome 00168, Italy, riccardi@rm.unicatt.it.
FEATURES OF TEMOZOLOMIDE: Temozolomide (TMZ) belongs to the imidazotetrazine
class and it is a DNA-methylating agent that has a good antitumor activity.
Despite of dacarbazine, TMZ is spontaneously converted into its active
metabolite 5-(3-methyltriazen-l-yl)imidazole-4-carboxamide at physiologic
pH, so it is not required in enzymatic demethylation in the liver. TMZ is
able to cross the blood brain barrier and is stable at gastric acid pH so it
has almost 100% oral bioavailability and is rapidly absorbed after it is
taken orally. TEMOZOLOMIDE IN CANCER PATIENTS: On the basis of the
relatively safe toxicity and the findings achieved in adult malignant
gliomas, phase I and II clinical trials were set up to evaluate the
opportunity of using this novel drug in pediatric cancer, too. In this
review, we evaluate the antitumor activity of TMZ against high-grade gliomas,
low-grade-gliomas, and medulloblastoma/primitive neuroectodermal tumors
analyzing several phases I and II clinical trials in children. CONCLUSIONS:
In spite of the poor activity of TMZ against pediatric brain tumors, the use
of the drug in combination with other compounds should be evaluated in
phases I and II clinical trials. Moreover, the evaluation of the methylation
status of the O6-methylguanine DNA methyltransferase promoter in
glioblastoma biopsy specimens could be assayed as a predictive factor of TMZ
efficacy.
PMID: 16565851 [PubMed - as supplied by publisher]
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-
Evaluation of imatinib mesylate effects on glioblastoma
aggressiveness with SPECT radiotracer (99m)Tc-(v)-DMSA.
Le
Jeune N, Dubois
F, Bin
V, Perek
N.
Department of Biophysics and Radiopharmaceuticals, Research group EA 3063
"Cellular Survival and Adhesion in tumours and grafts", Faculty of
Medicine Jacques Lisfranc, University of Saint-Etienne, France.
In vitro and in vivo studies have demonstrated inhibition of glioblastoma
growth by imatinib mesylate (Gleevec((R))). Imatinib is an inhibitor of the
tyrosine kinase activities of platelet-derived growth factor receptor (PDGF-r),
which is involved in glioblastoma agressiveness. In this study, we have
investigated the link between (99m)Tc-(V)-DMSA, an imaging agent used in
Single Photon Emission Computed Tomography, cellular accumulation and the
biological effects of imatinib mediated by PDGF-r in a human glioblastoma
cell line U87-MG. Cells treated with imatinib showed significant decreases
in proliferation, invasion, migration and PDGF-rbeta expression.
(99m)Tc-(V)-DMSA cellular uptake studies showed that the specific action of
imatinib on PDGF-r signal pathway, in the human glioblastoma cell line
U87-MG, could be followed by radioactive tracer. Furthermore, strong
correlations between cellular (99m)Tc-(V)-DMSA uptake and the effect of
imatinib therapy on U87-MG proliferation (r=0.896), invasion (r=0.621) and
migration (r=0.822) were obtained, likewise for (99m)Tc-(V)-DMSA uptake and
PDGF-r expression (r=0.958). Our results show that the biological effects of
imatinib therapy on tumour cells properties are linked to PDGF-r
phosphorylation and could be traced with (99m)Tc-(V)-DMSA, which also seems
to be a potential tracer to evaluate the response to imatinib therapy in
glioblastoma.
PMID: 16564690 [PubMed - as supplied by publisher]
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-
Association of meningioma with reproductive factors.
Lee
E, Grutsch
J, Persky
V, Glick
R, Mendes
J, Davis
F.
Division of Epidemiology and Biostatistics, School of Public Health,
University of Illinois at Chicago, IL, USA.
Meningiomas occur more commonly in females. The coincidence between
meningioma and breast cancer and case reports of tumor growth during
pregnancy support a hormonal hypothesis. A case control study was conducted
to investigate this. Female subjects treated between 1987 and 1992 were
identified from 3 hospitals in the Chicago area. Female spouses of male back
pain patients were recruited as controls. A self-administered mail
questionnaire focused on exogenous, endogenous and other hormonal factors,
personal and family medical history as well as radiation exposures. Odds
ratios and 95% confidence intervals were estimated using crude, stratified
and multivariable logistic models including 219 cases and 260 controls.
Participation rates were 86% among cases and 75% among controls. An
increased odds ratio (OR) was observed comparing African Americans to
Caucasians [OR = 2.4, 95% confidence interval (CI) = 1.0-6.1]. A protective
effect was observed for pregnancy, which increased with number and age at
first pregnancy. The odds ratio for 3 or more pregnancies compared to none
was 0.3 (95% CI = 0.2-0.6). Age at menarche or total period of hormonal
activity was not protective. Ever smokers showed a decreased odds ratio for
meningioma (OR = 0.6, 95% CI = 0.4-0.9). The increased odds ratios with
African Americans was retained in post-menopausal women, while the
protective odds ratios for pregnancy, smoking and oral contraceptives (OCs)
became stronger in pre-menopausal women. The pattern by duration and timing
of use does not suggest an etiologic role for OCs or hormone replacement
therapy. These data add to the evidence that factors known to influence
endogenous hormones (pregnancy and indirectly smoking) may have protective
effects for meningiomas primarily in premenopausal women. (c) 2006 Wiley-Liss,
Inc.
PMID: 16570277 [PubMed - as supplied by publisher]
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-
Optimization of combination therapy of arsenic trioxide
and fractionated radiotherapy for malignant glioma.
Ning
S, Knox
SJ.
Department of Radiation Oncology, Stanford University Medical Center,
Stanford, CA.
PURPOSE: The primary objective was to optimize the combined treatment
regimen using arsenic trioxide (ATO) and fractionated radiotherapy for the
treatment of malignant glioma. METHODS AND MATERIALS: Nude mice with human
glioma xenograft tumors were treated with fractionated local tumor radiation
of 250 cGy/fraction/day and 5 mg/kg ATO for 5-10 days. RESULTS: Time course
experiments demonstrated that maximal tumor growth delay occurred when ATO
was administered between 0 and 4 h after radiation. The combination
treatment of ATO and radiation synergistically inhibited tumor growth and
produced a tumor growth delay time of 13.2 days, compared with 1.4 days and
6.5 days for ATO and radiation alone (p < 0.01), respectively. The use of
concurrent therapy of radiation and ATO initially, followed by ATO as
maintenance therapy, was superior to the use of preloading with ATO before
combined therapy and produced a tumor growth delay time of 22.7 days as
compared with 11.7 days for the ATO preloading regimen (p < 0.01). The
maintenance dose of ATO after concurrent therapy was effective and important
for continued inhibition of tumor growth. CONCLUSIONS: The combined use of
fractionated radiation and ATO is effective for the treatment of glioma
xenograft tumors. ATO was most effective when administered 0-4 h after
radiation without pretreatment with ATO. These results have important
implications for the optimization of treatment regimen using ATO and
fractionated radiotherapy for the treatment of brain tumors.
PMID: 16563655 [PubMed - as supplied by publisher]
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-
X-ray volumetric imaging in image-guided radiotherapy:
the new standard in on-treatment imaging.
McBain
CA, Henry
AM, Sykes
J, Amer
A, Marchant
T, Moore
CM, Davies
J, Stratford
J, McCarthy
C, Porritt
B, Williams
P, Khoo
VS, Price
P.
Academic Department of Radiation Oncology, Christie Hospital NHS Trust,
Manchester, England, United Kingdom. catherine.mcbain@christie-tr.nwest.nhs.uk
PURPOSE: X-ray volumetric imaging (XVI) for the first time allows for the
on-treatment acquisition of three-dimensional (3D) kV cone beam computed
tomography (CT) images. Clinical imaging using the Synergy System (Elekta,
Crawley, UK) commenced in July 2003. This study evaluated image quality and
dose delivered and assessed clinical utility for treatment verification at a
range of anatomic sites. METHODS AND MATERIALS: Single XVIs were acquired
from 30 patients undergoing radiotherapy for tumors at 10 different anatomic
sites. Patients were imaged in their setup position. Radiation doses
received were measured using TLDs on the skin surface. The utility of XVI in
verifying target volume coverage was qualitatively assessed by experienced
clinicians. RESULTS: X-ray volumetric imaging acquisition was completed in
the treatment position at all anatomic sites. At sites where a full gantry
rotation was not possible, XVIs were reconstructed from projection images
acquired from partial rotations. Soft-tissue definition of organ boundaries
allowed direct assessment of 3D target volume coverage at all sites.
Individual image quality depended on both imaging parameters and patient
characteristics. Radiation dose ranged from 0.003 Gy in the head to 0.03 Gy
in the pelvis. CONCLUSIONS: On-treatment XVI provided 3D verification images
with soft-tissue definition at all anatomic sites at acceptably low
radiation doses. This technology sets a new standard in treatment
verification and will facilitate novel adaptive radiotherapy techniques.
Publication Types:
PMID: 16343802 [PubMed - indexed for MEDLINE]
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-
Fractionated proton beam irradiation of pituitary
adenomas.
Ronson
BB, Schulte
RW, Han
KP, Loredo
LN, Slater
JM, Slater
JD.
Department of Radiation Medicine, Loma Linda University Medical Center, Loma
Linda, CA 92354, USA.
PURPOSE: Various radiation techniques and modalities have been used to treat
pituitary adenomas. This report details our experience with proton treatment
of these tumors. METHODS AND MATERIALS: Forty-seven patients with pituitary
adenomas treated with protons, who had at least 6 months of follow-up, were
included in this analysis. Forty-two patients underwent a prior surgical
resection; 5 were treated with primary radiation. Approximately half the
tumors were functional. The median dose was 54 cobalt-gray equivalent.
RESULTS: Tumor stabilization occurred in all 41 patients available for
follow-up imaging; 10 patients had no residual tumor, and 3 had greater than
50% reduction in tumor size. Seventeen patients with functional adenomas had
normalized or decreased hormone levels; progression occurred in 3 patients.
Six patients have died; 2 deaths were attributed to functional progression.
Complications included temporal lobe necrosis in 1 patient, new significant
visual deficits in 3 patients, and incident hypopituitarism in 11 patients.
CONCLUSION: Fractionated conformal proton-beam irradiation achieved
effective radiologic, endocrinological, and symptomatic control of pituitary
adenomas. Significant morbidity was uncommon, with the exception of
postradiation hypopituitarism, which we attribute in part to concomitant
risk factors for hypopituitarism present in our patient population.
PMID: 16257131 [PubMed - indexed for MEDLINE]
-
-
12 Gy gamma knife radiosurgical volume is a predictor for
radiation necrosis in non-AVM intracranial tumors.
Korytko
T, Radivoyevitch
T, Colussi
V, Wessels
BW, Pillai
K, Maciunas
RJ, Einstein
DB.
Department of Radiation Oncology, University Hospitals of Cleveland and Case
Western Reserve University, Cleveland, OH 44106, USA.
PURPOSE: To determine whether the 12-Gy radiosurgical volume (12-GyV)
correlates with the development of postradiosurgical imaging changes
suggestive of radiation necrosis in patients treated for non-arteriovenous
malformation (non-AVM) intracranial tumors with gamma knife stereotactic
radiosurgery (GKSRS). METHODS AND MATERIALS: A retrospective
single-institution review of 129 patients with 198 separate non-AVM tumors
was performed. Patients were followed with magnetic resonance imaging (MRI)
and physical examinations at 3- to 6-month intervals. Patients who developed
postradiosurgical MRI changes suggestive of radiation necrosis were labeled
as having either symptomatic radiation necrosis (S-NEC) if they experienced
any decline in neurologic examination associated with the imaging changes,
or asymptomatic radiation necrosis (A-NEC) if they had a stable or improving
neurologic examination. RESULTS: 12-GyV correlated with risk of S-NEC, which
was 23% (for 12-GyV of 0-5 cc), 20% (5-10 cc), 54% (10-15 cc), and 57%
(>15 cc). The risk of A-NEC did not significantly change with 12-GyV.
Logistic regression analyses showed that the following factors were
associated with the development of S-NEC: 12-GyV (p<0.01), occipital and
temporal lesions (p<0.01), previous whole-brain radiotherapy (p=0.03),
and male sex (p=0.03). Radiosurgical plan conformality did not correlate
with the development of S-NEC. CONCLUSION: The risk of S-NEC, but not A-NEC
after GKSRS for non-AVM tumors correlates with 12-GyV, and increases
significantly for 12-GyV>0 cc.
PMID: 16226848 [PubMed - indexed for MEDLINE]
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-
Combined-modality therapy for primary central nervous
system lymphoma: long-term data from a Phase II multicenter study (Trans-Tasman
Radiation Oncology Group).
O'Brien
PC, Roos
DE, Pratt
G, Liew
KH, Barton
MB, Poulsen
MG, Olver
IN, Trotter
GE; Trans-Tasman
Radiation Oncology Group.
Radiation Oncology Department, Newcastle Mater Hospital, New South Wales,
Australia. Peter.OBrien@mater.health.nsw.gov.au
PURPOSE: To assess, in a multicenter setting, the long-term outcomes of a
brief course of high-dose methotrexate followed by radiotherapy for patients
with primary central nervous system lymphoma (PCNSL). METHODS AND MATERIALS:
Forty-six patients were entered in a Phase II protocol consisting of
methotrexate (1 g/m(2) on Days 1 and 8), followed by whole-brain irradiation
(45-50.4 Gy). The median follow-up time was 7 years, with a minimum
follow-up of 5 years. RESULTS: The 5-year survival estimate was 37% (+/-14%,
95% confidence interval [CI]), with progression-free survival being 36%
(+/-15%, 95% CI), and median survival 36 months. Of the original 46
patients, 10 were alive, all without evidence of disease recurrence. A total
of 11 patients have developed neurotoxicity, with the actuarial risk being
30% (+/-18%, 95% CI) at 5 years but continuing to increase. For patients
aged>60 years the risk of neurotoxicity at 7 years was 58% (+/-30%, 95%
CI). CONCLUSION: Combined-modality therapy, based on high-dose methotrexate,
results in improved survival outcomes in PCNSL. The risk of neurotoxicity
for patients aged>60 years is unacceptable with this regimen, although
survival outcomes for patients aged>60 years were higher than in many
other series.
Publication Types:
PMID: 16198065 [PubMed - indexed for MEDLINE]
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-
Genomics Identifies Medulloblastoma Subgroups That Are
Enriched for Specific Genetic Alterations.
Thompson
MC, Fuller
C, Hogg
TL, Dalton
J, Finkelstein
D, Lau
CC, Chintagumpala
M, Adesina
A, Ashley
DM, Kellie
SJ, Taylor
MD, Curran
T, Gajjar
A, Gilbertson
RJ.
St Jude Children's Research Hospital, Memphis, TN; Texas Children's
Hospital, Houston, TX; Royal Children's Hospital, Melbourne; The Children's
Hospital at Westmead and University of Sydney, Sydney, Australia; and
Hospital for Sick Children, Toronto, Ontario, Canada.
PURPOSE: Traditional genetic approaches to identify gene mutations in cancer
are expensive and laborious. Nonetheless, if we are to avoid rejecting
effective molecular targeted therapies, we must test these drugs in patients
whose tumors harbor mutations in the drug target. We hypothesized that gene
expression profiling might be a more rapid and cost-effective method of
identifying tumors that contain specific genetic abnormalities. Materials
and METHODS: Gene expression profiles of 46 samples of medulloblastoma were
generated using the U133av2 Affymetrix oligonucleotide array and validated
using real-time reverse transcriptase polymerase chain reaction (RT-PCR) and
immunohistochemistry. Genetic abnormalities were confirmed using
fluorescence in situ hybridization (FISH) and direct sequencing. RESULTS:
Unsupervised analysis of gene expression profiles partitioned
medulloblastomas into five distinct subgroups (subgroups A to E). Gene
expression signatures that distinguished these subgroups predicted the
presence of key molecular alterations that we subsequently confirmed by gene
sequence analysis and FISH. Subgroup-specific abnormalities included
mutations in the Wingless (WNT) pathway and deletion of chromosome 6
(subgroup B) and mutations in the Sonic Hedgehog (SHH) pathway (subgroup D).
Real-time RT-PCR analysis of gene expression profiles was then used to
predict accurately the presence of mutations in the WNT and SHH pathways in
a separate group of 31 medulloblastomas. CONCLUSION: Genome-wide expression
profiles can partition large tumor cohorts into subgroups that are enriched
for specific genetic alterations. This approach may assist ultimately in the
selection of patients for future clinical trials of molecular targeted
therapies.
PMID: 16567768 [PubMed - as supplied by publisher]
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-
Chordoid glioma of the third ventricle.
Baehring
JM, Bannykh
S.
Departments of Pathology, Neurosurgery and Neurology, Yale University School
of Medicine, New Haven, CT.
PMID: 16568345 [PubMed - in process]
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-
Incidence and patterns of neuraxis metastases in children
with diffuse pontine glioma( bigstar).
Gururangan
S, McLaughlin
CA, Brashears
J, Watral
MA, Provenzale
J, Coleman
RE, Halperin
EC, Quinn
J, Reardon
D, Vredenburgh
J, Friedman
A, Friedman
HS.
The Brain Tumor Center at Duke, Duke University Medical Center, Durham, NC
27710, USA.
PURPOSE: We performed a retrospective study of patients with diffuse pontine
glioma (DPG) who suffered neuraxis metastasis (NM) and characterized the
incidence, clinical features, radiologic findings, and patterns of disease
dissemination. METHODS: Magnetic resonance imaging (MRI) of brain and spine
was used to assess NM. Some patients also underwent magnetic resonance
spectroscopy (MRS) (6 patients) and fluorodeoxyglucose positron emission
tomography (FDG-PET) scans (13 patients) to further evaluate areas of
metastatic disease. Three patients had histologic confirmation of disease at
the site of NM. RESULTS: Between 1986 and 2003, 18 of 96 patients (17.3%)
with DPG developed NM. The median age at diagnosis was 8 years (range,
4-17). All patients had adjuvant chemotherapy and/or focal radiotherapy at
diagnosis. The NM occurred at a median of 15 months from diagnosis of DPG
(range, 3-96). Three patterns of NM were seen on MRI of brain and spine in
these patients; 8 (39%) had parenchymal (PM), 4 (22%) leptomeningeal (PM), 2
(11%) subependymal, and in 5 a combination of two or more patterns. The MRS
and FDG-PET scan of suspected areas of metastatic disease was consistent
with tumor in 6 of 6 and 12 of 13 patients who underwent these procedures
respectively. Three patients also had histologic confirmation of malignant
glioma at the site of NM. Despite salvage therapy, all 18 patients have died
of disease at a median of 5 months (range, 0.5-20) from diagnosis of
neuraxis spread. CONCLUSION: Our study emphasizes the need for screening
patients with DPG for NM at the time of recurrence.
PMID: 16568209 [PubMed - as supplied by publisher]
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-
Small regions of overlapping deletions on 6q26 in human
astrocytic tumours identified using chromosome 6 tile path array-CGH.
Ichimura
K, Mungall
AJ, Fiegler
H, Pearson
DM, Dunham
I, Carter
NP, Collins
VP.
Department of Pathology, Division of Molecular Histopathology, University of
Cambridge, Addenbrooke's Hospital, Cambridge, UK. ki212@cam.ac.uk
Deletions of chromosome 6 are a common abnormality in diverse human
malignancies including astrocytic tumours, suggesting the presence of tumour
suppressor genes (TSG). In order to help identify candidate TSGs, we have
constructed a chromosome 6 tile path microarray. The array contains 1,780
clones (778 P1-derived artificial chromosome and 1,002 bacterial artificial
chromosome) that cover 98.3% of the published chromosome 6 sequences. A
total of 104 adult astrocytic tumours (10 diffuse astrocytomas, 30
anaplastic astrocytomas (AA), 64 glioblastomas (GB)) were analysed using
this array. Single copy number change was successfully detected and the
result was in general concordant with a microsatellite analysis. The pattern
of copy number change was complex with multiple interstitial
deletions/gains. However, a predominance of telomeric 6q deletions was seen.
Two small common and overlapping regions of deletion at 6q26 were
identified. One was 1,002 kb in size and contained PACRG and QKI, while the
second was 199 kb and harbours a single gene, ARID1B. The data show that the
chromosome 6 tile path array is useful in mapping copy number changes with
high resolution and accuracy. We confirmed the high frequency of chromosome
6 deletions in AA and GB, and identified two novel commonly deleted regions
that may harbour TSGs. Oncogene (2006) 25, 1261-1271.
doi:10.1038/sj.onc.1209156; published online 3 October 2005.
PMID: 16205629 [PubMed - indexed for MEDLINE]
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-
Epigenetic repression of RASSF1A but not CASP8 in
supratentorial PNET (sPNET) and atypical teratoid/rhabdoid tumors (AT/RT) of
childhood.
Muhlisch
J, Schwering
A, Grotzer
M, Vince
GH, Roggendorf
W, Hagemann
C, Sorensen
N, Rickert
CH, Osada
N, Jurgens
H, Fruhwald
MC.
Department of Pediatric Hematology and Oncology, University Children's
Hospital Muenster, Germany.
Supratentorial primitive neuroectodermal tumors (sPNET) and atypical
teratoid/rhabdoid tumors (AT/RT) of the CNS represent a biological and
clinical enigma, despite advances in both molecular techniques and clinical
management for these two rare embryonal brain tumors of childhood.
Epigenetic changes hold great potential as possible disease mechanisms and
may be manipulated therapeutically. We thus studied aberrant methylation of
the genes RASSF1A and CASP8 and its consequence on expression in cell lines
and primary tumors using a combination of semiquantitative methylation
specific PCR (MSP), bisulfite sequencing and RT-PCR. In all, 17 samples of
autopsy-derived normal appearing brain served as controls. Opposed to
control tissues 19/24 sPNET and 4/6 AT/RT demonstrated aberrant methylation
for the RASSF1A promoter region. Treatment of cell lines using
5-Aza-2'-deoxycytidine (5AZA) alone or in combination with trichostatin A (TSA)
succeeded in re-establishing expression of RASSF1A in cell lines derived
from a renal rhabdoid, an AT/RT and a medulloblastoma. A 5' CpG-rich region
of CASP8 was methylated in normal tissues and in tumors. However, CASP8
showed inconsistent expression patterns in normal and tumor tissues. Our
results indicate that aberrant methylation of the RASSF1A promoter region
may be of importance in the origin and progression of sPNET and AT/RT while
the analysed 5'-CpG rich region of the CASP8 gene does not seem to play an
important role in these tumors. Further studies of epigenetic changes in
these rare tumors are warranted as their biology remains obscure and
treatment efforts have been rather unsuccessfull.
PMID: 16186793 [PubMed - indexed for MEDLINE]
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Volume 5, Number 14 - 3 April
2006