| 1: Cancer Res. 2005 Aug
15;65(16):7033-6. |
|
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The neurotrophic receptor TrkB in anoikis resistance and
metastasis: a perspective.
Geiger
TR, Peeper
DS.
Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam,
the Netherlands.
Resistance to anoikis ("detachment-induced apoptosis") has been
suggested to be a prerequisite for cancer cells to metastasize. In a
functional screen for suppressors of anoikis, we identified the neurotrophic
receptor TrkB. Upon s.c. inoculation in mice, TrkB-expressing cells formed
highly invasive and metastatic tumors. Here, we discuss our findings within
the context of the proposed role of TrkB in human malignancies and address
the question of its feasibility as a target for cancer therapy.
Publication Types:
PMID: 16103047 [PubMed - indexed for MEDLINE]
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| 2: Clin
Cancer Res. 2005 Oct 15;11(20):7499-507. |
|
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Schedule-Dependent Drug Effects of Oral
5-Iodo-2-Pyrimidinone-2'-Deoxyribose as an In vivo Radiosensitizer in U251
Human Glioblastoma Xenografts.
Seo
Y, Yan
T, Schupp
JE, Radivoyevitch
T, Kinsella
TJ.
Authors' Affiliations: Departments of Radiation Oncology and Epidemiology
and Biostatistics, Case Western Reserve University and University Hospitals
of Cleveland/Case Comprehensive Cancer Center, Cleveland, Ohio.
PURPOSE: 5-Iodo-2-pyrimidinone-2'-deoxyribose (IPdR) is an oral prodrug of
5-iodo-2'-deoxyuridine (IUdR), an in vitro/in vivo radiosensitizer. IPdR can
be rapidly converted to IUdR by a hepatic aldehyde oxidase. Previously, we
found that the enzymatic conversion of IPdR to IUdR could be transiently
reduced using a once daily (q.d.) treatment schedule and this may affect
IPdR-mediated tumor radiosensitization. The purpose of this study is to
measure the effect of different drug dosing schedules on tumor
radiosensitization and therapeutic index in human glioblastoma
xenografts.EXPERIMENTAL DESIGN: Three different IPdR treatment schedules
(thrice a day, t.i.d.; every other day, q.o.d.; every 3rd day, q.3.d.),
compared with a q.d. schedule, were analyzed using athymic nude mice with
human glioblastoma (U251) s.c. xenografts. Plasma pharmacokinetics, IUdR-DNA
incorporation in tumor and normal proliferating tissues, tumor growth delay
following irradiation, and body weight loss were used as end points.RESULTS:
The t.i.d. schedule with the same total daily doses as the q.d. schedule
(250, 500, or 1,000 mg/kg/d) improved the efficiency of IPdR conversion to
IUdR. As a result, the percentage of IUdR-DNA incorporation was higher using
the t.i.d. schedule in the tumor xenografts as well as in normal small
intestine and bone marrow. Using a fixed dose (500 mg/kg) per
administration, the q.o.d. and q.3.d. schedules also showed greater IPdR
conversion than the q.d. schedule, related to a greater recovery of hepatic
aldehyde oxidase activity prior to the next drug dosing. In the tumor
regrowth assay, all IPdR treatment schedules showed significant increases of
regrowth delays compared with the control without IPdR (q.o.d., 29.4 days;
q.d., 29.7 days; t.i.d., 34.7 days; radiotherapy alone, 15.7 days). The
t.i.d. schedule also showed a significantly enhanced tumor growth delay
compared with the q.d. schedule. Additionally, the q.o.d. schedule resulted
in a significant reduction in systemic toxicity.CONCLUSIONS: The t.i.d. and
q.o.d. dosing schedules improved the efficiency of enzymatic activation of
IPdR to IUdR during treatment and changed the extent of tumor
radiosensitization and/or systemic toxicity compared with a q.d. dosing
schedule. These dosing schedules will be considered for future clinical
trials of IPdR-mediated human tumor radiosensitization.
PMID: 16243824 [PubMed - in process]
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| 3: Clin
Cancer Res. 2005 Oct 15;11(20):7405-14. |
|
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Apurinic/Apyrimidinic endonuclease activity is associated
with response to radiation and chemotherapy in medulloblastoma and primitive
neuroectodermal tumors.
Bobola
MS, Finn
LS, Ellenbogen
RG, Geyer
JR, Berger
MS, Braga
JM, Meade
EH, Gross
ME, Silber
JR.
Authors' Affiliations: Division of Neurosurgery, Department of Surgery.
PURPOSE: Apurinic/apyrimidinic endonuclease (Ap endo) is a key DNA repair
activity that confers resistance to radiation- and alkylator-induced
cytotoxic abasic sites in human cells. We assayed apurinic/apyrimidinic
endonuclease activity in medulloblastomas and primitive neuroectodermal
tumors (PNET) to establish correlates with tumor and patient characteristics
and with response to adjuvant radiation plus multiagent
chemotherapy.EXPERIMENTAL DESIGN: Ap endo activity was assayed in 52
medulloblastomas and 10 PNETs from patients 0.4 to 21 years old. Ape1/Ref-1,
the predominant human Ap endo activity, was measured in 42 medulloblastomas
by immunostaining. Cox proportional hazards regression models were used to
analyze the association of activity with time to tumor progression
(TTP).RESULTS: Tumor Ap endo activity varied 180-fold and was significantly
associated with age and gender. Tumor Ape1/Ref-1 was detected almost
exclusively in nuclei. In a multivariate model, with Ap endo activity
entered as a continuous variable, the hazard ratio for progression after
adjuvant treatment in 46 medulloblastomas and four PNETs increased by a
factor of 1.073 for every 0.01 unit increase in activity (P </= 0.001)
and was independent of age and gender. Suppressing Ap endo activity in a
human medulloblastoma cell line significantly increased sensitivity to
1,3-bis(2-chlororethyl)-1-nitrosourea and temozolomide, suggesting that the
association of tumor activity with TTP reflected, at least in part, abasic
site repair.CONCLUSIONS: Our data (a) suggest that Ap endo activity promotes
resistance to radiation plus chemotherapy in medulloblastomas/PNETs, (b)
provide a potential marker of treatment outcome, and (c) suggest clinical
use of Ap endo inhibitors to overcome resistance.
PMID: 16243814 [PubMed - in process]
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| 4: Clin Neuropathol.
2005 Sep-Oct;24(5):236-8. |
|
Relationship between radiation injury and
Alzheimer-related neurodegenerative changes.
Riudavets,
Mena
H, Bouffard
JP, Sandberg
G, Rushing
EJ.
Department of Neuropathology and Ophthalmic Pathology, Armed Forces
Institute of Pathology, Washington, DC 20306-6000, USA.
The relationship between radiation injury and other neurodegenerative
changes such as the formation of neuritic or diffuse plaques and tangles
have received little attention in the literature. In the current study,
archival tissue was examined from 485 patients with the diagnosis of either
a primary or metastatic brain tumor, who had received radiation therapy
between the initial and subsequent pathological study (either surgical or
autopsy). Of those cases, 20 were identified that also contained cerebral
cortex in both specimens. Sections were stained with the modified
Bielschowsky technique and immunohistochemical preparations for
beta-amyloid. Contrary to previous reports, the present study did not
identify neurodegenerative changes typical of Alzheimer's disease as a
consequence of radiation therapy.
PMID: 16167548 [PubMed - indexed for MEDLINE]
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| 5: Clin Neuropathol.
2005 Sep-Oct;24(5):225-9. |
|
Challenging diagnosis: oligodendroglioma versus
extraventricular neurocytoma.
Mut
M, Guler-Tezel
G, Lopes
MB, Bilginer
B, Ziyal
I, Ozcan
OE.
Department of Neurosurgery, Hacettepe University Institute of Neurological
and Psychiatric Sciences, Hacettepe University, Sihhiye Ankara, Turkey.
melikem@hacettepe.edu.tr
Diagnosis of oligodendroglioma from other clear cell neoplasms of central
nervous system (CNS) is still challenging despite advances in neuroradiology
and molecular diagnostic tools. Herein, we present a 44-year-old male
patient who had a diagnosis of right parietal oligodendroglioma grade II in
1994 which recurred in 2002. He presented with intratumoral hemorrhage and
he underwent radical resection of tumor in 2003. Histopathological
examination of the recurrent tumor showed anaplastic progression with
confusing immunohistochemical (IHC) results; the tumor was positive for NeuN
and synaptophysin staining. The question arisen was whether the recurrent
tumor was an oligodendroglioma with neuronal differentiation or an
extraventricular neurocytoma initially misdiagnosed as oligodendroglioma.
Repeated IHC staining showed negative results for NeuN and synaptophysin.
Chromosomal analysis revealed 1p/19q deletion, which led to the diagnosis
ofanaplastic oligodendroglioma grade III. Accurate diagnosis of
oligodendroglioma is crucial due to recent advances and promises in its
treatment. Current diagnostic methods of oligodendroglial tumors are
discussed in context of differentiating oligodendrogliomas from other clear
cell neoplasms of CNS, especially from extraventricular neurocytomas.
Publication Types:
PMID: 16167546 [PubMed - indexed for MEDLINE]
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| 6: Clin Neuropathol.
2005 Jul-Aug;24(4):184-90. |
|
Primary intracranial peripheral primitive neuroectodermal
tumor/Ewing's sarcoma presenting with acute intracerebral hemorrhage.
Bunyaratavej
K, Khaoroptham
S, Phonprasert
C, Tanboon
J, Shuangshoti
S.
Division of Neurosurgery, Department of Surgery, Faculty of Medicine,
Chulalongkorn University, Bangkok, Thailand. krbunya@yahoo.com
OBJECTIVE: To report two cases of intracerebral hemorrhage due to primary
intracranial peripheral primitive neuroectodermal tumor (pPNET)/Ewing's
sarcoma (ES) and review of related literatures. MATERIAL: Two cases of
17-year-old patients presented with acute increased intracranial pressure
one of which also had left hemiparesis. METHOD: On neuroimaging studies, the
first patient had an intraparenchymal hematoma with a size of 4 cm at the
right fronto-parietal junction adjacent to tumor infiltrating the superior
sagittal sinus. The second patient had a large left temporal tumor with
intraventricular hemorrhage. Both patients underwent craniotomy with
complete removal of tumor and hematoma. RESULTS: Pathological examination in
both cases revealed numerous small round tumor cells with stippled chromatin
pattern and scanty cytoplasm. Tumor cells strongly expressed CD99. Vimentin
immunoreactivity was observed. The final diagnosis of pPNET/ES was rendered.
There was no evidence of extracranial disease in both cases. Both patients
were doing well without evidence of recurrent disease at 12 and 24-month
follow-up respectively. CONCLUSIONS: Peripheral primitive neuroectodermal
tumor (pPNET)/Ewing's sarcoma (ES) is a malignant small round cell tumor,
commonly arising in soft tissue of the trunk and lower extremity. Those
occurring in the intracranium are rare, and most patients present with
progressively increased intracranial pressure and/or cranial nerve deficit.
The occurrence of intracerebral hemorrhage due to primary intracranial
pPNET/ES is exceedingly rare. The role of adjuvant therapy in this condition
is yet to be investigated.
Publication Types:
PMID: 16033135 [PubMed - indexed for MEDLINE]
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| 7: Clin Neuropathol.
2005 Jul-Aug;24(4):155-62. |
|
Fetal aqueductal glioneuronal hamartoma: a
clinicopathological and physiopathological study of three cases.
Marcorelles
P, Fallet-Bianco
C, Oury
JF, van
Wallenghem E, Parent
P, Labadie
G, Lagarde
N, Laquerriere
A.
Pathology Laboratory, University Hospital, Brest, France.
pascale.marcorelles@chu-brest.fr
Fetal hydrocephalus due to aqueductal stenosis is classified into two main
groups: congenital (X-linked, atresia, septa and forking) and acquired
(post-infectious or post-hemorrhagic, gliosis and tumors). MATERIAL AND
METHODS: We report three fetal cases presenting with severe hydrocephalus,
two of which being apparently sporadic, and the third possibly inherited. On
macroscopic examination, no associated malformations were identified, either
craniofacial dysmorphy, or visceral abnormalities. Neuropathological study
revealed massive hydrocephalus caused by narrowing of the Aqueduct of
Sylvius. Histological examination evidenced a nodular, well-demarcated mass
producing into the aqueductal lumen, and containing numerous immature
proliferating glioneuronal cells. Immunohistochemical analyses did not
suggest a developmental abnormality of the subcommissural organ but rather a
hamartomatous malformative process. RESULTS: Hamartoma of the posterior
fossa has been rarely reported. Post-natal cases have been described in the
cerebello-pontine angle or in the quadrigeminal plate, and have always been
diagnosed as pilocytic or low-grade astrocytomas. In our cases, the lesions
could be related to so-called pencil glioma, sometimes associated with type
1 neurofibromatosis and, to our knowledge, have never been described prior
to birth. The occurrence during fetal life and the progressive maturation of
the nodules are more likely in favor of a hamartomatous process. CONCLUSION:
Even though they could sporadically occur, an accurate genetic counseling
should be required in order to ensure that there is no familial history of
Recklinghausen disease, and to provide a more precise evaluation of
recurrence risk.
Publication Types:
PMID: 16033131 [PubMed - indexed for MEDLINE]
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| 8: Int
J Radiat Oncol Biol Phys. 2005 Oct 18; [Epub ahead of print] |
|
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[F-18]-fluorodeoxyglucose positron emission tomography
for targeting radiation dose escalation for patients with glioblastoma
multiforme: Clinical outcomes and patterns of failure.
Douglas
JG, Stelzer
KJ, Mankoff
DA, Tralins
KS, Krohn
KA, Muzi
M, Silbergeld
DL, Rostomily
RC, Scharnhorst
J, Spence
AM.
Department of Radiation Oncology, University of Washington Medical Center,
Seattle, WAUSA; Department of Neurological Surgery, University of Washington
Medical Center, Seattle, WAUSA.
PURPOSE: [F-18]-fluorodeoxyglucose positron emission tomography (FDG-PET)
imaging for brain tumors has been shown to identify areas of active disease.
Radiation dose escalation in the treatment of glioblastoma multiforme may
lead to improved disease control. Based on these premises, we initiated a
prospective study of FDG-PET for the treatment planning of radiation dose
escalation for the treatment of glioblastoma multiforme. METHODS AND
MATERIALS: Forty patients were enrolled. Patients were treated with standard
conformal fractionated radiotherapy with volumes defined by MRI imaging.
When patients reached a dose of 45-50.4 Gy, they underwent FDG-PET imaging
for boost target delineation, for an additional 20 Gy (2 Gy per fraction) to
a total dose of 79.4 Gy (n = 30). RESULTS: The estimated 1-year and 2-year
overall survival (OS) for the entire group was 70% and 17%, respectively,
with a median overall survival of 70 weeks. The estimated 1-year and 2-year
progression-free survival (PFS) was 18% and 3%, respectively, with a median
of 24 weeks. No significant improvements in OS or PFS were observed for the
study group in comparison to institutional historical controls. CONCLUSIONS:
Radiation dose escalation to 79.4 Gy based on FDG-PET imaging demonstrated
no improvement in OS or PFS. This study establishes the feasibility of
integrating PET metabolic imaging into radiotherapy treatment planning.
PMID: 16242251 [PubMed - as supplied by publisher]
| 9: J Neurooncol.
2005 May;73(1):39-42. |
|
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Diabetes insipidus caused by isolated intracranial
metatstases in patient with breast cancer.
Bobilev
D, Shelef
I, Lavrenkov
K, Tokar
M, Man
S, Baumgarten
A, Ariad
S.
Department of Oncology, Soroka University Medical Center, P.O. Box 151, Beer
Sheva, 84101, Israel.
We present a case of late recurrence of breast cancer manifested with
diabetes insipidus caused by isolated intracranial metastases. A 57-year-old
postmenopausal woman was diagnosed with breast cancer and underwent radical
mastectomy, without any adjuvant therapy. Seventeen years later, she
presented with polyuria, polydipsia, weight loss, weakness, diffuse bone
pain, hoarseness and mild dyspnoea. Cranial CT revealed several dural masses
in the frontal, parietal and occipital lobes and along the falx cerebri. The
diagnosis of central diabetes insipidus without impairment of anterior
pituitary function was based on the clinical symptoms, laboratory tests and
imaging findings. The patient was successfully treated with desmopressin
acetate and letrozole, and remained alive and ambulating 22 months after
initial presentation with diabetes insipidus.
Publication Types:
PMID: 15933815 [PubMed - indexed for MEDLINE]
| 10: J Neurooncol.
2005 May;73(1):19-27. |
|
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HUlip, a human homologue of unc-33-like phosphoprotein of
Caenorhabditis elegans; Immunohistochemical localization in the developing
human brain and patterns of expression in nervous system tumors.
Choi
YL, Kim
CJ, Matsuo
T, Gaetano
C, Falconi
R, Suh
YL, Kim
SH, Shin
YK, Park
SH, Chi
JG, Thiele
CJ.
Department of Diagnostic Pathology, Samsung Medical Center, Sungkyunkwan
University School of Medicine, Korea.
HUlip is a human homologue of a C. elegans gene, unc-33, that is
developmentally regulated during maturation of the nervous system. HUlip is
highly expressed only in the fetal brain and spinal cord, and is undetected
in the adult brain. The purpose of this study was to investigate the pattern
of hUlip expression in the developing human brain and nervous system tumors.
Ten human brains at different developmental stages and 118 cases of nervous
system tumor tissues were examined by immunohistochemistry. Twelve related
tumor cell lines were also analyzed by northern blotting and immunoblotting.
HUlip was expressed in late fetal and early postnatal brains; strongly in
the neurons of the brain stem, basal ganglia/thalamus, and dentate gyrus of
the hippocampus, and relatively weakly in the cerebral and cerebellar
cortex. Among tumors, hUlip expression was easily detected in tumor cells
undergoing neuronal differentiation such as ganglioneuroblastomas and
ganglioneuromas. Furthermore, hUlip immunoreactivity was also found in
various brain tumors showing neuronal differentiation: central neurocytomas
(6 of 6 cases were positive), medulloblastomas (5/11), atypical teratoid
rhabdoid tumor (1/1) and gangliogliomas (4/7). Some astrocytic tumors also
showed weak positivity: astrocytomas (1 of 5 cases), anaplastic astrocytomas
(2/5), and glioblastomas (3/11). Subependymal giant cell astrocytomas and
subependymomas, which are of controversial histogenetic origin, showed
strong hUlip immunoreactivity. The results of this study indicate that the
expression of hUlip protein is distinctly restricted to the late fetal and
early postnatal periods of human nervous system development and to certain
subsets of nervous system tumors. The exact function of hUlip needs to be
further clarified; yet the results of our study strongly imply that hUlip
function is important in human nervous system development and its aberrant
expression in various types of nervous system tumors suggests a role of
hUlip as an oncofetal neural antigen.
PMID: 15933812 [PubMed - indexed for MEDLINE]
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| 11: J Neurooncol.
2005 Apr;72(2):191-3. |
|
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Necrotizing vasculopathy of the CNS: case report.
Begemann
M, Krol
G, Rosenblum
MK, Deangelis
LM.
Department of Neurology, Memorial Sloan Kettering Cancer Center, New York
City, NY, USA. begemann@molgen.mpg.de
A 62-year-old man with progressive cerebellar and brainstem dysfunction had
gadolinium-enhancing lesions in basal ganglia and occipital lobe on MRI
suggestive of primary CNS lymphoma (PCNSL). The patient, who had been
treated with high-dose steroid hormones for several months, developed
respiratory failure and expired before a histological diagnosis could be
obtained. The postmortem examination showed Pneumocystis cariniiwas the
cause of death. Pathology of the brain showed a necrotizing vasculopathy
affecting the white matter of the cerebrum and cerebellum with involvement
of the basal ganglia and the periventricular gray matter. Other organs such
as liver, lung, and kidneys were spared. Necrotizing vasculopathy is a novel
entity that should be considered in the differential diagnosis of PCNSL.
Publication Types:
PMID: 15926001 [PubMed - indexed for MEDLINE]
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| 12: J Neurooncol.
2005 Apr;72(2):185-9. |
|
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Neoplastic meningitis-related encephalopathy.
Chamberlain
MC, Tsao-Wei
D, Groshen
S.
Department of Neurology, University of Southern California, Norris
Comprehensive Cancer and Hospital, 1441 Eastlake Avenue, Los Angeles, CA
90033-0804, USA. chamberl@usc.edu
BACKGROUND: A retrospective comparison evaluating survival in two
well-matched cohorts of patients with cytologically positive neoplastic
meningitis (NM) presenting with or without encephalopathy. METHODS: Two
cohorts were studied: 20 with and 20 without of NM-related encephalopathy
defined as a confusional syndrome. Cohorts were matched with respect to age,
primary tumor, performance status, absence of CSF compartmentalization and
absence of neuroradiographic bulky CNS disease. Primary tumor histology
included the following: breast(10 patients); non-small cell lung cancer (8);
non-Hodgkin's lymphoma (8); colorectal cancer (6); melanoma (4); small cell
lung cancer (2); prostate cancer (2). NM at presentation revealed:
encephalopathy (20 patients); spinal cord dysfunction (18); and cranial
neuropathy (15). Radiotherapy was administered to 31 patients (whole brain
only in 17 patients; restricted spine only in 8 patients; whole brain and
restricted spine in 6 patients). All patients received intraventricular
chemotherapy and 16 patients received concurrent tumor-specific systemic
chemotherapy. RESULTS: Median survival was 2.5 months (range 1.5-5 months)
in the cohort with NM-related encephalopathy compared to 6 months (range:
2-10 months) in the cohort without NM-related encephalopathy (p < 0.001).
No treatment-related deaths were observed. All patients demonstrated
progressive disease and died of either NM or systemic cancer. CONCLUSIONS:
NM-related encephalopathy is a clinical variable that predicts for poor
survival in patients with NM. As a consequence, patients with NM-related
encephalopathy may be best served by offering supportive care.
Publication Types:
PMID: 15926000 [PubMed - indexed for MEDLINE]
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| 13: J Neurooncol.
2005 Apr;72(2):169-77. |
|
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Primary central nervous system lymphomas (PCNSL): MRI
features at presentation in 100 patients.
Kuker
W, Nagele
T, Korfel
A, Heckl
S, Thiel
E, Bamberg
M, Weller
M, Herrlinger
U.
Department of Neuroradiology, Medical School, University of Tubingen,
Tubingen, Germany. wilhelm. kueker@orh.nhs.uk
To avoid an unnecessary extend of surgery in primary central nervous system
lymphoma (PCNSL), the diagnosis should be suspected after MRI. Pre-treatment
MRI examinations of 100 immunologically competent patients with
biopsy-proven PCNSL were evaluated. All patients had T2- and T1-weighted
images with contrast enhancement. Diffusion-weighted MRI (DW-MRI) was
available in 15, proton-MR-spectroscopy (1H-MRS) in four patients.The number
of lesions ranged from one (n=65 patients) to eight (n=1) with a mean of
1.7. The most frequent locations were the cerebral hemispheres (n=66), the
basal ganglia (n=27) and the corpus callosum (n=24). In the 65 patients with
a solitary lesion, hemispheric lesions were most frequent (n=23) followed by
corpus callosum (n=18). Contrast enhancement was found in all but one
patient. 1H-MRS revealed a uniformly pathologic pattern of metabolite
concentrations in all patients. Characteristic imaging features of PCNSL are
contrast-enhancing lesions with a diameter of at least 15 mm in contact with
the subarachnoid space. DW-MRI and proton spectroscopy may aid in
differential diagnosis.
Publication Types:
PMID: 15925998 [PubMed - indexed for MEDLINE]
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| 14: J Neurooncol.
2005 Apr;72(2):103-6. |
|
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Aberrant TP53 protein accumulation in the neuronal
component of ganglioglioma.
Fukushima
T, Katayama
Y, Watanabe
T, Yoshino
A, Komine
C, Yokoyama
T.
Department of Neurological Surgery, Nihon University School of Medicine,
30-1 Oyaguchi-kamimachi, Itabashi-ku, Tokyo, 173-8610, Japan.
cco51080@syd.odn.ne.jp
Gangliogliomas are characterized by their different phenotypic composition
of ganglion cells and glial cells. In contrast to the glial cells that are
capable of mitotic activity, the ganglion cells are generally considered to
lack a neoplastic nature. The authors report here the first unequivocal case
of a ganglioglioma harboring aberrant TP53 product that was expressed
predominantly in the neuronal component. GeneChip TP53 assay revealed a
point mutation resulting in an exchange of amino acid. This case suggests
that ganglion cells can participate in the neoplastic process of
gangliogliomas.
Publication Types:
PMID: 15925988 [PubMed - indexed for MEDLINE]
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| 15: J Neurooncol.
2005 Apr;72(2):95-102. |
|
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Comparative genetic analysis of metachronous anaplastic
oligoastrocytomas with extended recurrence-free interval.
Martinez
R, Schackert
HK, Kirsch
M, Paulus
W, Joos
S, Schackert
G.
Department of Neurosurgery, University of Dresden, Fetscherstr. 74, D-01307,
Dresden, Germany. voelter.martinez@t-online.de
Two metachronous anaplastic oligoastrocytomas with different cerebral
locations were analyzed in a 51-year-old patient with an extended
recurrence-free interval of 6 years and an a long survival of 9 years.
Remarkably, the patient had not undergone adjuvant chemotherapy. Different
cytogenetic and molecular techniques were performed including comparative
genomic hybridization (CGH), fluorescence in situ hybridization (FISH),
allelic loss analysis, sequencing of p53, p16(INK4a)/CDKN2A and p14(ARF),
EGFRamplification studies, investigation of the DNA mismatch repair system
as well as tumor clonality. Using CGH and FISH a profile of low accumulation
of cytogenetic aberrations was found in the second tumor, with no
significant increase in the percentage of hyperdiploid nuclei.
Microsatellite analysis showed a common pattern of allelic losses at 1p36,
19q13 and 9p21. Both specimens were also similar in that they retained
heterozygosity at 10q23-q24 and 13q14 and that they harbor neither EGFR
amplification nor mutations of p53, p16(INK4a)/CDKN2A or p14(ARF). The only
further alteration in the second tumor was an allelic loss at p53. The
X-chromosome inactivation (HUMARA) analysis revealed a polyclonal pattern in
both samples. Our data strongly suggest that the second anaplastic
oligoastrocytoma developed as a distant relapse of the first tumor. Whether
the paucity of accumulation of the observed genetic alterations might be
associated with the unusually extended relapse-free time of the patient
remains to be elucidated.
Publication Types:
PMID: 15925987 [PubMed - indexed for MEDLINE]
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| 16: J
Neuropathol Exp Neurol. 2005 Nov;64(11):948-955. |
|
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Histology-Based Expression Profiling Yields Novel
Prognostic Markers in Human Glioblastoma.
Dong
S, Nutt
CL, Betensky
RA, Stemmer-Rachamimov
AO, Denko
NC, Ligon
KL, Rowitch
DH, Louis
DN.
From Department of Pathology, Cancer Center and Neurosurgical Service (SD,
CLN, AOS-R, DNL), Massachusetts General Hospital and Harvard Medical School,
Boston, Massachusetts; Department of Biostatistics (RAB), Harvard School of
Public Health, Boston, Massachusetts; Division of Radiation and Cancer
Biology (NCD), Department of Radiation Oncology, Stanford, California; and
Department of Pediatric Oncology (KLL, DHR), Dana-Farber Cancer Institute,
Boston, Massachusetts.
Although the prognosis for patients with glioblastoma is poor, survival is
variable, with some patients surviving longer than others. For this reason,
there has been longstanding interest in the identification of prognostic
markers for glioblastoma. We hypothesized that specific histologic features
known to correlate with malignancy most likely express molecules that are
directly related to the aggressive behavior of these tumors. We further
hypothesized that such molecules could be used as biomarkers to predict
behavior in a manner that might add prognostic power to sole histologic
observation of the feature. We reasoned that perinecrotic tumor cell
palisading, which denotes the most aggressive forms of malignant gliomas,
would be a striking histologic feature on which to test this hypothesis. We
therefore used laser capture microdissection and oligonucleotide arrays to
detect molecules differentially expressed in perinecrotic palisades. A set
of RNAs (including POFUT2, PTDSR, PLOD2, ATF5, and HK2) that were
differentially expressed in 3 initially studied, microdissected
glioblastomas also provided prognostic information in an independent set of
28 glioblastomas that did not all have perinecrotic palisades. On validation
in a second, larger independent series, this approach could be applied to
other human glioma types to derive tissue biomarkers that could offer
ancillary prognostic and predictive information alongside standard
histopathologic examination.
PMID: 16254489 [PubMed - as supplied by publisher]
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| 17: Oncogene. 2005 Oct 24;
[Epub ahead of print] |
|
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Identification of novel genomic markers related to
progression to glioblastoma through genomic profiling of 25 primary glioma
cell lines.
Roversi
G, Pfundt
R, Moroni
RF, Magnani
I, van
Reijmersdal S, Pollo
B, Straatman
H, Larizza
L, Schoenmakers
EF.
1Department of Biology and Genetics, University of Milan, Milan, Italy.
Identification of genetic copy number changes in glial tumors is of
importance in the context of improved/refined diagnostic, prognostic
procedures and therapeutic decision-making. In order to detect recurrent
genomic copy number changes that might play a role in glioma pathogenesis
and/or progression, we characterized 25 primary glioma cell lines including
15 non glioblastoma (non GBM) (I-III WHO grade) and 10 GBM (IV WHO grade),
by array comparative genomic hybridization, using a DNA microarray
comprising approx. 3500 BACs covering the entire genome with a 1 Mb
resolution and additional 800 BACs covering chromosome 19 at tiling path
resolution. Combined evaluation by single clone and whole chromosome
analysis plus 'moving average (MA) approach' enabled us to confirm most of
the genetic abnormalities previously identified to be associated with glioma
progression, including +1q32, +7, -10, -22q, PTEN and p16 loss, and to
disclose new small genomic regions, some correlating with grade malignancy.
Grade I-III gliomas exclusively showed losses at 3p26 (53%), 4q13-21 (33%)
and 7p15-p21 (26%), whereas only GBMs exhibited 4p16.1 losses (40%). Other
recurrent imbalances, such as losses at 4p15, 5q22-q23, 6p23-25, 12p13 and
gains at 11p11-q13, were shared by different glioma grades. Three intervals
with peak of loss could be further refined for chromosome 10 by our MA
approach. Data analysis of full-coverage chromosome 19 highlighted two main
regions of copy number gain, never described before in gliomas, at 19p13.11
and 19q13.13-13.2. The well-known 19q13.3 loss of heterozygosity area in
gliomas was not frequently affected in our cell lines. Genomic hotspot
detection facilitated the identification of small intervals resulting in
positional candidate genes such as PRDM2 (1p36.21), LRP1B (2q22.3), ADARB2
(10p15.3), BCCIP (10q26.2) and ING1 (13q34) for losses and ECT2 (3q26.3),
MDK, DDB2, IG20 (11p11.2) for gains. These data increase our current
knowledge about cryptic genetic changes in gliomas and may facilitate the
further identification of novel genetic elements, which may provide us with
molecular tools for the improved diagnostics and therapeutic decision-making
in these tumors.Oncogene advance online publication, 24 October 2005;
doi:10.1038/sj.onc.1209177.
PMID: 16247447 [PubMed - as supplied by publisher]
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Volume 4, Number
45 - 1 November 2005