-
Oligodendroglioma metastatic to bone marrow.
Al-Ali
F, Hendon
AJ, Liepman
MK, Wisniewski
JL, Krinock
MJ, Beckman
K.
Neurointerventional and Diagnostic Services, Borgess Medical Center,
Kalamazoo, MI 49048, USA.
We report on a patient with oligodendroglioma metastatic to bone, presenting
with pancytopenia and fever 10 years after initial tumor resection. Our
review of the literature showed a total of 30 reported extraneural
metastases, with only 19 of these being similar cases of bone metastases.
These bony lesions have increased signal intensity in T2-weighted and low
signal intensity on T1-weighted images, with intense homogeneous
enhancement. However, on MR imaging, we were unable to find necrosis or
compression deformity of the vertebrae, despite extensive metastatic
disease.
Publication Types:
PMID: 16219856 [PubMed - indexed for MEDLINE]
-
-
Nonenhancing spinal subdural metastatic tumor.
Rumboldt
Z, Lambert
L, Talan-Hranilovic
J, Marjan
D, Sajko
T.
Department of Radiology, Medical University of South Carolina, Charleston,
SC 29425, USA.
We describe a case of a spinal subdural metastatic tumor that became rapidly
symptomatic after a minor trauma, as a result of severe cord compression and
cord hemorrhage. On MR imaging, the lesion was oval, hyperintense with a
dark rim on T2-weighted fast spin-echo images, isointense to the cord on
T1-weighted images, and had dark and bright areas on gradient-echo
T2*-weighted images, consistent with a hyperacute-to-acute hematoma. The
hemorrhagic tumor showed no evidence of contrast enhancement.
Publication Types:
PMID: 16219855 [PubMed - indexed for MEDLINE]
-
-
Spinal epidural synovial sarcoma: a case of homogeneous
enhancing large paravertebral mass on MR imaging.
Suh
SI, Seol
HY, Hong
SJ, Kim
JH, Kim
JH, Lee
JH, Kim
MG.
Medical Research Center, Guro Hospital, Korea.
We report the MR imaging findings in a 44-year-old man with a low-grade
synovial sarcoma. There was a right-sided epidural and paravertebral mass,
widening of the ipsilateral neural foramen at the L4-L5 level, and focal
erosion of the right superior articular process of the L5 vertebra. The mass
was relatively homogeneous, hyperintense to muscle and isointense to fat on
T2-weighted images, and isointense to muscle on T1-weighted images, and it
demonstrated moderate homogeneous enhancement.
Publication Types:
PMID: 16219854 [PubMed - indexed for MEDLINE]
-
-
An exploratory study of ferumoxtran-10 nanoparticles as a
blood-brain barrier imaging agent targeting phagocytic cells in CNS
inflammatory lesions.
Manninger
SP, Muldoon
LL, Nesbit
G, Murillo
T, Jacobs
PM, Neuwelt
EA.
Department of Radiology, Oregon Health & Science University, Portland,
OR, USA.
BACKGROUND AND PURPOSE: Iron oxide-based contrast agents have been
investigated as more specific MR imaging agents for central nervous system
(CNS) inflammation. Ferumoxtran-10 is a virus-size nanoparticle, taken up by
reactive cells, that allows visualization of the phagocytic components of
CNS lesions. Ferumoxtran-10 was compared with standard gadolinium-enhanced
MR images in this exploratory trial to assess its potential in evaluation of
CNS lesions with inflammatory aspects, including lymphoma, multiple
sclerosis (MS), acute disseminated encephalomyelitis (ADEM), and vascular
lesions. METHODS: Twenty-three patients with different types of intracranial
"inflammatory" lesions underwent standard brain MR with and
without gadolinium, followed an average of 10 days later by a ferumoxtran-10
scan. Patients were imaged 24 hours after infusion of 2.6 mg/kg
ferumoxtran-10. All MR images were evaluated subjectively by 4 investigators
for a difference in enhancement patterns, which could be useful in
differential diagnoses. RESULTS: In 5 cases, (one ADEM, 2 stroke, one
cavernous venous vascular malformation, one primary central nervous
lymphoma) the ferumoxtran-10 scan showed higher signal intensity, larger
area of enhancement, or new enhancing areas compared with gadolinium. Most
MS patients showed less enhancement with ferumoxtran-10 than with
gadolinium. CONCLUSION: Ferumoxtran-10 showed different enhancement patterns
in a variety of CNS lesions with inflammatory components in comparison to
gadolinium. The impact of timing and therapy need further evaluation to
better assess ferumoxtran-10 in addition to gadolinium as contrast agents
for use in diagnosis and monitoring therapy in patients with CNS
inflammatory lesions.
PMID: 16219835 [PubMed - indexed for MEDLINE]
-
-
Evaluation of treatment-induced cerebral white matter
injury by using diffusion-tensor MR imaging: initial experience.
Kitahara
S, Nakasu
S, Murata
K, Sho
K, Ito
R.
Departments of Radiology, Shiga University of Medical Science, Shiga, Japan.
BACKGROUND AND PURPOSE: Treatment with chemotherapy and radiation therapy
for brain tumors can cause white matter (WM) injury. Conventional MR
imaging, however, cannot always depict treatment-induced transient WM
abnormalities. We investigated the ability of diffusion-tensor (DT) MR
imaging and proton MR spectroscopy to detect the treatment-induced transient
changes within normal-appearing WM. METHODS: DT MR imaging and proton MR
spectroscopy were performed in 8 patients treated with a combination of
surgery, chemotherapy, and radiation therapy for brain tumors (17
examinations) and 11 age-matched controls. Apparent diffusion coefficient
(ADC) value, fractional anisotropy (FA) value, and N-acetylaspartate
(NAA)/creatine (Cr) ratio were obtained from 27 hemispheres with
normal-appearing WM in the patients. We divided the datasets of isotropic
ADC, FA, and NAA/Cr, on the basis of the time period after completion of
radiation therapy, into 4 groups: group 1 (0-2 months; n = 10), group 2 (3-5
months; n = 5), group 3 (6-9 months; n = 7), and group 4 (10-12 months; n =
5). We compared averages of mean isotropic ADC, mean FA, and NAA/Cr of each
patient group with those of the control group by using a t test. RESULTS: In
the group 2, averages of mean FA and NAA/Cr decreased and average of mean
isotopic ADC increased in comparison with those of the control group (P =
.004, .04, and .0085, respectively). There were no significant differences
in the averages between the control group and patient groups 1, 3, and 4.
CONCLUSION: DT MR imaging and proton MR spectroscopy can provide
quantitative indices that may reflect treatment-induced transient
derangement of normal-appearing WM.
PMID: 16219822 [PubMed - indexed for MEDLINE]
-
Comment in:
Assessing global invasion of newly diagnosed glial tumors
with whole-brain proton MR spectroscopy.
Cohen
BA, Knopp
EA, Rusinek
H, Babb
JS, Zagzag
D, Gonen
O.
Department of Radiology, New York University School of Medicine, New York,
NY 10016, USA.
BACKGROUND AND PURPOSE: Because of their invasive nature, high-grade glial
tumors are uniformly fatal. The purpose of this study was to quantify MR
imaging-occult, glial tumor infiltration beyond its radiologic margin
through its consequent neuronal cell damage, assessed by the global
concentration decline of the neuronal marker N-acetylaspartate (NAA).
METHODS: Seventeen patients (10 men; median age, 39 years; age range, 23-79
years) with radiologically suspected (later pathologically confirmed)
supratentorial glial neoplasms, and 17 age- and sex-matched controls were
studied. Their whole-brain NAA (WBNAA) amounts were obtained with proton MR
spectroscopy: for patients on the day of surgery (n = 17), 1 day postsurgery
(n = 15), and once for each control. To convert into concentrations,
suitable for intersubject comparison, patients' global NAA amounts were
divided by their brain volumes segmented from MR imaging. Least squares
regression was used to analyze the data. RESULTS: Pre- and postoperative
WBNAA (mean +/- SD) of 9.2 +/- 2.1 and 9.7 +/- 1.8 mmol/L, respectively, in
patients were indistinguishable (P = .369) but significantly lower than in
controls (12.5 +/- 1.4 mmol/L). Mean resected tumor size (n = 15) was
approximately 3% of total brain volume. CONCLUSION: The average 26% WBNAA
deficit in the patients, which persisted following surgical resection,
cannot be explained merely by depletion within the approximately 3% MR
imaging-visible tumor volume or an age-dependent effect. Although there
could be several possible causes of such widespread decline--perineuronal
satellitosis, neuronal deafferentation, Wallerian and retrograde
degeneration, vasogenic edema, functional diaschisis, secondary vascular
changes--most are a direct or indirect reflection of extensive, MR
imaging-occult, microscopic tumor cell infiltration, diffusely throughout
the otherwise "normal-appearing" brain.
PMID: 16219818 [PubMed - indexed for MEDLINE]
-
-
Pituitary cysts in childhood evaluated by MR imaging.
Takanashi
J, Tada
H, Barkovich
AJ, Saeki
N, Kohno
Y.
Department of Pediatrics , Graduate School of Medicine, Chiba University,
Chiba, Japan.
BACKGROUND AND PURPOSE: Pituitary cysts are common findings on pathologic
examination and imaging studies. They are generally considered to be rarer
in children than in adults; however, no good data exist to substantiate this
opinion. We reviewed MR imaging studies to evaluate the frequency and
imaging features of pituitary cysts in children. METHODS: We retrospectively
reviewed T1-weighted sagittal images in 341 patients <15 years of age to
evaluate for pituitary cysts. Paramagnetic contrast was administered in 86
of the 341 patients. Sagittal or coronal fast spin-echo T2-weighted images
were performed in 166 patients. For patients having pituitary cysts,
pituitary function was examined by assessing blood levels of pituitary
hormones. RESULTS: A cystic pituitary lesion was recognized in 4 patients
(1.2%) aged 1-4 years. None of the 4 manifested endocrinologic signs or
symptoms or were the results of their laboratory studies abnormal. All the
lesions were sharply demarcated and situated just posterior to the anterior
pituitary lobe. All were iso- or hypointense compared with the pons on
T1-weighted images without contrast enhancement, suggesting a Rathke cleft
cyst. MR imaging of a patient with probable low-grade gliomas in the left
hypothalamic region and optic chiasma showed complete resolution of a
pituitary cyst at a 1-year follow-up study. CONCLUSION: The frequency of
pituitary cysts on MR imaging in childhood is almost equal to that of Rathke
cleft cysts, as assessed in autopsy studies of subjects aged 10 to 29 years.
These cysts are common in children and should be considered, in the absence
of signs or symptoms of pituitary dysfunction, as incidental findings.
PMID: 16155173 [PubMed - indexed for MEDLINE]
-
-
Lesion size determines accuracy of thallium-201 brain
single-photon emission tomography in differentiating between intracranial
malignancy and infection in AIDS patients.
Young
RJ, Ghesani
MV, Kagetsu
NJ, Derogatis
AJ.
St. Luke's-Roosevelt Hospital Center, University Hospital of Columbia,
University College of Physicians and Surgeons, New York, NY 10019, USA.
BACKGROUND AND PURPOSE: Discrimination between enhancing mass lesions in
acquired immunodeficiency syndrome (AIDS) patients with conventional CT and
MR imaging remains difficult. We determined the effect of lesion size on
thallium-201 brain single-photon emission tomography (SPECT) imaging in
differentiating primary brain lymphoma from cerebral toxoplasmosis. METHODS:
We retrospectively identified 35 AIDS patients with a total of 48 focal
enhancing mass lesions on contrast-enhanced brain CT and/or MR images who
subsequently underwent thallium-201 brain SPECT imaging. The thallium index
of each lesion was evaluated on the basis of the ratio of mean uptake in the
lesion compared with the corresponding contralateral side. Receiver operator
curves were drawn to determine the optimal thallium index threshold. The
effect of lesion size on scan accuracy was evaluated. RESULTS: Malignant
lesions in 20 patients had a mean thallium index of 2.4 (range, 1-11).
Infectious lesions in 15 patients had a mean thallium index of 1.6 (range,
1-3.6). Twenty-five lesions were <2 cm (14 malignant, 11 nonmalignant)
and 23 lesions were > or =2 cm (14 malignant, 9 nonmalignant). Thallium
index was not a significant predictor of malignancy in the lesions <2 cm
by using the logistic regression (P = .27). Receiver operator curve analysis
by using thallium index of 2 in small lesions yielded 50% sensitivity and
82% specificity. In contrast, thallium index was a significant predictor of
malignancy in lesions > or =2 cm (P < .01), yielding 100% sensitivity
and 89% specificity. CONCLUSION: Lesion size is a significant determinant of
the accuracy of thallium-201 brain SPECT imaging, which should be the
initial diagnostic tool for lesions > or =2 cm.
Publication Types:
PMID: 16155145 [PubMed - indexed for MEDLINE]
-
Comment in:
Diffusion-weighted imaging of radiation-induced brain
injury for differentiation from tumor recurrence.
Asao
C, Korogi
Y, Kitajima
M, Hirai
T, Baba
Y, Makino
K, Kochi
M, Morishita
S, Yamashita
Y.
Department of Diagnostic Radiology, Graduate School of Medical Sciences,
Kumamoto University, Japan. casao@krmc.or.jp
BACKGROUND AND PURPOSE: Differentiation between tumor recurrence and
treatment-related brain injury is often difficult with conventional MRI. We
hypothesized that the diffusion-weighted imaging (DWI) could help
differentiate these 2 conditions, because water diffusion may be greater for
necrotic tissues in the treatment-related brain injury than for tumor
tissues in recurrence. Our aim was to analyze whether DWI findings of
recurrent tumor are distinct from those of radiation necrosis. METHODS:
Seventeen patients were examined prospectively. Two readers assessed the
images by consensus for homogeneity and signal intensity of the lesions.
Five regions of interest were drawn within the lesions on trace DWI images
and apparent diffusion coefficient (ADC) maps. The minimal, maximal, and
mean values of each lesion were compared between the 2 groups. Findings in
12 of 17 patients were verified histologically by surgery or biopsy; the
diagnoses in the remaining 5 patients were made on the basis of follow-up
MRI findings and clinical follow-up. RESULTS: There were a total of 20
lesions; 12 lesions were due to radiation necrosis and 8 lesions to tumor
recurrence. In the radiation necrosis group, 8 lesions had marked
hypointensity. In the recurrence group, however, no marked hypointensity was
seen. The maximal ADC values within each lesion were significantly smaller
for the recurrence group than for the necrosis group (P = .039). CONCLUSION:
Radiation necrosis usually showed heterogeneity on DWI images and often
included spotty, marked hypointensity. Significant difference was found in
the maximal ADC values between radiation necrosis and tumor recurrence. DWI
was useful in differentiating recurrent neoplasm from radiation necrosis.
PMID: 15956515 [PubMed - indexed for MEDLINE]
-
-
Feasibility of using hyperosmolar mannitol as a liquid
tumor embolization agent.
Feng
L, Kienitz
BA, Matsumoto
C, Bruce
J, Sisti
M, Duong
H, Pile-Spellman
J.
Department of Radiology, Columbia University, New York, NY 10032, USA.
BACKGROUND AND PURPOSE: This study assesses the cytotoxicity of hyperosmolar
mannitol on human endothelial and meningioma cells in vitro and summarizes
the initial clinical experience of using mannitol as a liquid tumor
embolization agent. METHODS: Human umbilical vein endothelial cells and
primary meningioma cells from surgical specimens were treated with 300, 600,
900, and 1200 mOsm of mannitol, mannitol and iohexol mixture, saline, and
iohexol alone. Cell death was evaluated with a Live/Dead kit and quantified
with thymidine incorporation. From 1998 to 2004, 23 patients with meningioma
were treated with mannitol and 31 patients were treated with polyvinyl
alcohol (PVA) particles alone. Angiographic results, procedural
complications, intraoperative observation, and estimated blood loss during
surgical resection were retrospectively evaluated. RESULTS: Minimal
endothelial cell death was seen after incubation with 300 mOsm of mannitol
for 15 minutes, but 43 +/- 2% of endothelial cells were damaged by 1200 mOsm
of mannitol after 30 minutes. Five meningioma cell lines exhibited
significant cell death (22 +/- 2%; P < .05) after incubation with
mannitol. Satisfactory angiographic results were obtained in all 23
patients. Tumor necrosis was observed intraoperatively and confirmed
pathologically. There was no significant difference in estimated blood loss
between mannitol- and PVA-embolized patients (407 +/- 64 mL vs 381 +/- 50
mL; P > .75). CONCLUSION: High concentration of mannitol can injure
endothelial cells and meningioma cells in a short period of time. It is
feasible to use mannitol as a liquid embolic agent to treat meningioma.
PMID: 15956507 [PubMed - indexed for MEDLINE]
-
-
Neurotropic melanoma of the head and neck with clinical
perineural invasion.
Newlin
HE, Morris
CG, Amdur
RJ, Mendenhall
WM.
Department of Radiation Oncology, University of Florida College of Medicine,
Gainesville, Florida, USA.
OBJECTIVE: The purpose of this article is to report our experience with
neurotropic melanoma, a rare malignancy that sometimes produces neurologic
symptoms because of a direct extension of the primary tumor. METHODS: We
report 3 consecutive patients with neurotropic melanoma of the head and neck
who presented with clinical perineural invasion. RESULTS: Two patients had
incompletely resectable tumors and were treated with definitive radiotherapy
(RT), and 1 patient received surgery and postoperative RT. One patient
experienced recurrence in a regional lymph node 30 months after RT and
underwent salvage surgery; he is disease-free at 45 months after initial
treatment. The remaining 2 patients are disease-free 34 months and 14 months
after treatment. CONCLUSIONS: Radiotherapy alone or combined with surgery
may provide relatively long-term local control in patients who have
neurotropic melanoma with clinical perineural invasion.
Publication Types:
PMID: 16062083 [PubMed - indexed for MEDLINE]
-
-
Radiotherapy and radiosurgery for benign neurofibromas.
Chopra
R, Morris
CG, Friedman
WA, Mendenhall
WM.
Department of Radiation Oncology, University of Florida College of Medicine,
Gainesville, Florida 32610-0385, USA.
The purpose of this study was to evaluate the efficacy of radiotherapy (RT)
and stereotactic radiosurgery (SRS) for neurofibromas. We studied 4 patients
treated with RT (3 patients) or SRS (1 patient) and followed from 1.7 to
14.8 years. The tumor remained locally controlled in all patients. No
significant complications related to treatment were observed. RT and SRS are
likely to locally control neurofibromas in patients who require treatment
and are not good candidates for complete resection.
Publication Types:
PMID: 15923807 [PubMed - indexed for MEDLINE]
-
-
A suprasellar and intrasellar lesion.
Lara-Torres
HR, Aguirre-Quezada
DE, Chavez-Macias
LG, Olvera-Rabiela
JE.
Department of Neuropathology, Mexico City General Hospital, National
University of Mexico, Mexico City, Mexico.
Publication Types:
PMID: 16119997 [PubMed - indexed for MEDLINE]
  
-
-
Pseudoglandular elements in schwannomas.
Robinson
CA, Curry
B, Rewcastle
NB.
Department of Pathology, University of Calgary and Foothills Medical Center,
Calgary, Alberta, Canada. christopher.robinson@saskatoonhealthregion.ca
CONTEXT: Uncommon examples of schwannomas are seen in which a coexisting
glandular component is present. The pseudoglandular schwannoma is a
relatively recently described variant in which cystic spaces are lined by
pseudocolumnar or cuboidal-like neoplastic Schwann cells exhibiting an
epithelial-like appearance. OBJECTIVES: To determine the incidence of
pseudoglandular elements in schwannomas, to describe the variable morphology
of the schwannomas that may contain pseudoglandular elements, and to discuss
the potential mechanisms of development and biological significance of these
elements. DESIGN: We screened 202 schwannomas from any anatomic site for the
presence of pseudoglandular elements and examined these with light
microscopy, immunohistochemistry, and electron microscopy. RESULTS: Sixteen
(7.9%) of the schwannomas contained pseudoglandular elements, which ranged
from poorly to well organized in appearance and which were found in
schwannomas exhibiting a wide range of morphologic appearances. The Schwann
cell nature of the cells composing these elements was apparent both
immunohistochemically and ultrastructurally. The frequency of proliferative
activity within these elements was no greater than that observed throughout
the remainder of the respective schwannomas. CONCLUSIONS: Our observations
suggest that, rather than representing a distinct phenotypic schwannoma
variant, pseudoglandular elements likely arise as a response to a
degenerative phenomenon, perhaps reflecting the propensity that the Schwann
cell has to palisade formation. Such elements may be found within a variety
of schwannoma variants and do not appear to possess a unique growth
potential.
PMID: 16119981 [PubMed - indexed for MEDLINE]
-
-
A rare case of periosteal osteoblastoma located in the
frontal cranial bone.
Lin
YC, Commins
DL, Fedenko
AN, Pinsky
GS.
Department of Pathology, Keck School of Medicine, University of Southern
California, Los Angeles, CA 90033, USA.
Periosteal osteoblastoma is an extremely rare bone-forming neoplasm located
on the surface of cortical bone. Of the fewer than 30 cases of periosteal
osteoblastomas found in the literature, 2 have been reported to be located
in cranial bone, and these have not been documented in detail with clinical
history, radiographic findings, macroscopic features, and microscopic
findings. Although the differential diagnoses of periosteal lesions include
parosteal and periosteal osteosarcoma, periosteal chondroma and
chondrosarcoma, osteochondroma, osteoid osteoma, periostitis ossificans, and
myositis ossificans, an important differential diagnosis both radiologically
and pathologically of such a lesion in the cranium is meningioma. We report
an unusual case of periosteal osteoblastoma located in the frontal cranial
bone that was radiologically consistent with a meningioma. The differential
diagnosis of metaplastic meningioma with differentiation toward bone is
discussed.
Publication Types:
PMID: 15913430 [PubMed - indexed for MEDLINE]
-
-
Intracranial extension of acinic cell carcinoma of the
parotid gland.
Spencer
ML, Neto
AG, Fuller
GN, Luna
MA.
Department of Oral Pathology, College of Dentistry, University of
Concepcion, Concepcion, Chile.
We report the case of a 47-year-old woman who experienced multiple
recurrences of acinic cell carcinoma, lung metastasis, and intracranial
extension of the tumor during a 32-year period. In this report, the
clinical, microscopic, histochemical, and electron microscopy features of
this acinic cell carcinoma are described, and a review of published
information about this neoplasm is presented.
Publication Types:
PMID: 15913428 [PubMed - indexed for MEDLINE]
-
-
Proton beam therapy.
Levin
WP, Kooy
H, Loeffler
JS, DeLaney
TF.
Massachusetts General Hospital Northeast Proton Therapy Center, Boston, MA
02114, USA.
Conventional radiation therapy directs photons (X-rays) and electrons at
tumours with the intent of eradicating the neoplastic tissue while
preserving adjacent normal tissue. Radiation-induced damage to healthy
tissue and second malignancies are always a concern, however, when
administering radiation. Proton beam radiotherapy, one form of charged
particle therapy, allows for excellent dose distributions, with the added
benefit of no exit dose. These characteristics make this form of
radiotherapy an excellent choice for the treatment of tumours located next
to critical structures such as the spinal cord, eyes, and brain, as well as
for paediatric malignancies.
Publication Types:
PMID: 16189526 [PubMed - indexed for MEDLINE]
-
| 18: Cancer.
2005 Oct 1;104(7):1468-77. |
|
-
The prognostic impact of histology and 1p/19q status in
anaplastic oligodendroglial tumors.
McDonald
JM, See
SJ, Tremont
IW, Colman
H, Gilbert
MR, Groves
M, Burger
PC, Louis
DN, Giannini
C, Fuller
G, Passe
S, Blair
H, Jenkins
RB, Yang
H, Ledoux
A, Aaron
J, Tipnis
U, Zhang
W, Hess
K, Aldape
K.
Department of Pathology, The University of Texas M. D. Anderson Cancer
Center, Houston, Texas 77030, USA.
BACKGROUND: It has been reported previously that the combined loss of
chromosomal arms 1p and 19q is a significant predictor of outcome for
patients with anaplastic oligodendroglial (AO) tumors and that such
chromosomal loss correlates with classic histology in AO. The authors sought
to determine whether histology was an equivalent or superior predictor of
outcome compared with 1p/19q status in 131 patients with AO tumors. METHODS:
The status of 1p and 19q was determined using real-time, quantitative
polymerase chain reaction analysis and/or fluorescence in situ
hybridization. Clinical features (response to adjuvant therapy and tumor
location) and molecular genetic abnormalities (9p and 10q deletions,
overexpression of p53 and epidermal growth factor receptor) were determined
on available specimens. Histologic assessments for classic oligodendroglial
features were performed by five neuropathologists. RESULTS: Classic
histology was associated closely with 1p/19q loss, as reported previously.
Patients who had tumors that were considered classic by at least four of the
five neuropathologists showed significantly increased progression-free and
overall survival compared with the patients who had less classic tumors. The
authors also tested the correlation between 1p/19q status and outcome in
subsets of patients stratified according to classic tumor features. The
association of 1p/19q status with survival was related closely to the
presence of classic histology. Loss of 1p/19q was predictive of improved
outcome only among patients who had tumors with classic histologic features.
CONCLUSIONS: The current results suggested that, in addition to 1p/19q
status, histologic features contribute information to the prediction of
outcome in patients with AO. Loss of 1p and 19q appeared to be a prognostic
marker only in the subset of patients who had AO tumors with classic
histologic features.
PMID: 16088966 [PubMed - indexed for MEDLINE]
-
-
Inhibition of DNA methylation sensitizes glioblastoma for
tumor necrosis factor-related apoptosis-inducing ligand-mediated
destruction.
Eramo
A, Pallini
R, Lotti
F, Sette
G, Patti
M, Bartucci
M, Ricci-Vitiani
L, Signore
M, Stassi
G, Larocca
LM, Crino
L, Peschle
C, De
Maria R.
Department of Hematology, Oncology and Molecular Medicine, Istituto
Superiore di Sanita
Life expectancy of patients affected by glioblastoma multiforme is extremely
low. The therapeutic use of tumor necrosis factor-related apoptosis-inducing
ligand (TRAIL) has been proposed to treat this disease based on its ability
to kill glioma cell lines in vitro and in vivo. Here, we show that,
differently from glioma cell lines, glioblastoma multiforme tumors were
resistant to TRAIL stimulation because they expressed low levels of
caspase-8 and high levels of the death receptor inhibitor PED/PEA-15.
Inhibition of methyltransferases by decitabine resulted in considerable
up-regulation of TRAIL receptor-1 and caspase-8, down-regulation of
PED/PEA-15, inhibition of cell growth, and sensitization of primary
glioblastoma cells to TRAIL-induced apoptosis. Exogenous caspase-8
expression was the main event able to restore TRAIL sensitivity in primary
glioblastoma cells. The antitumor activity of decitabine and TRAIL was
confirmed in vivo in a mouse model of glioblastoma multiforme. Evaluation of
tumor size, apoptosis, and caspase activation in nude mouse glioblastoma
multiforme xenografts showed dramatic synergy of decitabine and TRAIL in the
treatment of glioblastoma, whereas the single agents were scarcely effective
in terms of reduction of tumor mass, apoptosis induction, and caspase
activation. Thus, the combination of TRAIL and demethylating agents may
provide a key tool to overcome glioblastoma resistance to therapeutic
treatments. (Cancer Res 2005; 65(24): 11469-77).
PMID: 16357155 [PubMed - in process]
-
-
ABCC Drug Efflux Pumps and Organic Anion Uptake
Transporters in Human Gliomas and the Blood-Tumor Barrier.
Bronger
H, Konig
J, Kopplow
K, Steiner
HH, Ahmadi
R, Herold-Mende
C, Keppler
D, Nies
AT.
Division of Tumor Biochemistry, German Cancer Research Center.
Delivery of therapeutic agents to the brain and its neoplasms depends on the
presence of membrane transport proteins in the blood-brain barrier and in
the target cells. The cellular and subcellular localization of these
membrane transporters determines the drug accessibility to the brain and its
tumors. We therefore analyzed the expression and localization of six members
of the multidrug resistance protein family of ATP-dependent efflux pumps
(ABCC1-ABCC6, formerly MRP1-MRP6) and of six organic anion uptake
transporters (OATP1A2, OATP1B1, OATP1B3, OATP1C1, OATP2B1, and OATP4A1) in
61 human glioma specimens of different histologic subtypes. Real-time PCRs
indicated expressions of ABCC1, ABCC3, ABCC4, and ABCC5. In addition, we
detected expressions of the OATP uptake transporter genes SLCO1A2, SLCO1C1,
SLCO2B1, and SLCO4A1. At the protein level, however, only OATP1A2 and
OATP2B1 were detectable by immunofluorescence microscopy in the luminal
membrane of endothelial cells forming the blood-brain barrier and the
blood-tumor barrier, but not in the glioma cells. ABCC4 and ABCC5 proteins
were the major ABCC subfamily members in gliomas, localized both at the
luminal side of the endothelial cells and in the glioma cells of astrocytic
tumors and in the astrocytic portions of oligoastrocytomas. These results
indicate that expression of ABCC4 and ABCC5 is associated with an astrocytic
phenotype, in accordance with their expression in astrocytes and with the
higher chemoresistance of astrocytic tumors as compared with
oligodendrogliomas. Our data provide a basis for the assessment of the role
of uptake transporters and efflux pumps in the accessibility of human
gliomas for chemotherapeutic agents. (Cancer Res 2005; 65(24): 11419-28).
PMID: 16357150 [PubMed - in process]
-
-
Plexin D1 expression is induced on tumor vasculature and
tumor cells: a novel target for diagnosis and therapy?
Roodink
I, Raats
J, van
der Zwaag B, Verrijp
K, Kusters
B, van
Bokhoven H, Linkels
M, de
Waal RM, Leenders
WP.
Department of Pathology, Radboud University Nijmegen Medical Centre, The
Netherlands.
We previously reported that during mouse embryogenesis, plexin D1 (plxnD1)
is expressed on neuronal and endothelial cells. Endothelial cells gradually
loose plxnD1 expression during development. Here we describe, using in situ
hybridization, that endothelial plxnD1 expression is regained during tumor
angiogenesis in a mouse model of brain metastasis. Importantly, we found
PLXND1 expression also in a number of human brain tumors, both of primary
and metastatic origin. Apart from the tumor vasculature, abundant expression
was also found on tumor cells. Via panning of a phage display library, we
isolated two phages that carry single-domain antibodies with specific
affinity towards a PLXND1-specific peptide. Immunohistochemistry with these
single-domain antibodies on the same tumors that were used for in situ
hybridization confirmed PLXND1 expression on the protein level. Furthermore,
both these phages and the derived antibodies specifically homed to vessels
in brain lesions of angiogenic melanoma in mice after i.v. injection. These
results show that PLXND1 is a clinically relevant marker of tumor
vasculature that can be targeted via i.v. injections.
PMID: 16166308 [PubMed - indexed for MEDLINE]
-
-
Magnetic resonance angiography visualization of abnormal
tumor vasculature in genetically engineered mice.
Brubaker
LM, Bullitt
E, Yin
C, Van
Dyke T, Lin
W.
Department of Radiology, Lineberger Comprehensive Cancer Center, University
of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
lauren_brubaker@med.unc.edu
Previous research on the vasculature of tumor-bearing animals has focused
upon the microvasculature. Magnetic resonance angiography (MRA) offers a
noninvasive, complementary approach that provides information about larger
vessels. Quantitative analysis of MRA images of spontaneous preclinical
tumor models has not been previously reported. Eleven TgT121;p53+/- mice,
which invariably develop choroid plexus carcinoma (CPC), and nine
age-matched healthy controls were imaged using T1, T2, and a high-resolution
three-dimensional time-of-flight MRA sequences at 3 T. Tumors and vessels
were segmented to determine tumor volume and vascular attributes, including
number of terminal branches, vessel count, and the average vessel radii of
MRA-visible vessels within the tumor. Differences in the vasculature between
tumor-bearing animals and healthy controls were analyzed statistically.
Although the spatial resolution of MRA prohibits visualization of
capillaries, a high density of intratumor blood vessels was visualized in
CPC mice. A significant increase in terminal branch count and vessel count,
but not average vessel radius, was observed in CPCs when compared with
normal controls. Both terminal branch count and vessel count were highly
correlated with tumor volume. This study represents the first MRA analysis
of a spontaneous preclinical brain tumor model. Although the spatial
resolution of MRA is less than histologic analysis, MRA-obtained vascular
attributes provide useful information with full brain coverage. We show that
consistent tumor vasculature properties can be determined by MRA. Such
methods are critical for developing preclinical therapeutic testing and will
help guide the development of human brain tumor analyses.
PMID: 16166297 [PubMed - indexed for MEDLINE]
-
-
A homozygous mutation in MSH6 causes Turcot syndrome.
Hegde
MR, Chong
B, Blazo
ME, Chin
LH, Ward
PA, Chintagumpala
MM, Kim
JY, Plon
SE, Richards
CS.
Diagnostic Sequencing Laboratory, Department of Molecular and Human Genetics
and Texas Children's Cancer Center, Houston, Texas 77030, USA.
Heterozygous mutations in one of the DNA mismatch repair genes cause
hereditary nonpolyposis colorectal cancer (MIM114500). Turcot syndrome
(MIM276300) has been described as the association of central nervous system
malignant tumors and familial colorectal cancer and has been reported to be
both a dominant and recessive disorder. Homozygous and compound heterozygous
mutations in APC, MLH1, MSH2, and PMS2 genes have been reported in five
families. Here we describe a nonconsanguineous Pakistani family, including a
son with lymphoma and colorectal cancer diagnosed at ages 5 and 8,
respectively, and an 8-year-old daughter with glioblastoma multiforme. Both
children had features of neurofibromatosis type 1 including atypical cafe au
lait spots and axillary freckling without a family history consistent with
neurofibromatosis type 1, familial adenomatous polyposis, or hereditary
nonpolyposis colorectal cancer. Mutational analysis was done for MLH1, MSH2,
and MSH6 using denaturing high-performance liquid chromatography and
sequencing of a blood sample from the daughter. A novel homozygous single
base insertion mutation was identified (3634insT) resulting in a premature
stop at codon 1,223 in exon 7 of the MSH6 gene. Both parents were found to
be heterozygous for the 3634insT mutation. Microsatellite instability
testing showed instability in the glioblastoma sample. We report here the
first identification of a homozygous mutation in MSH6 in a family with
childhood-onset brain tumor, lymphoma, colorectal cancer, and
neurofibromatosis type 1 phenotype. Our findings support a role for MSH6 in
Turcot syndrome and are consistent with an autosomal recessive mode of
inheritance.
Publication Types:
PMID: 16000562 [PubMed - indexed for MEDLINE]
-
-
Intracranial therapy of glioblastoma with the fusion
protein DTIL13 in immunodeficient mice.
Rustamzadeh
E, Hall
WA, Todhunter
DA, Low
WC, Liu
H, Panoskaltsis-Mortari
A, Vallera
DA.
Department of Neurosurgery, University of Minnesota Cancer Research Center,
Minneapolis, MN, USA.
A fusion protein consisting of human interleukin-13 and the first 389 amino
acids of diphtheria toxin was assembled in order to target human
glioblastoma cell lines in a murine intracranial model. In vitro studies to
determine specificity indicated that the protein called DTIL13 was highly
selective for human glioblastoma. In vivo, the maximum tolerated dose of
DTIL13 was 1 mug/injection given every other day and repeated for 3 days.
Doses that exceeded this amount resulted in weight loss and liver damage as
determined by histology and enzyme assay. Experiments in IL-4 receptor
knockout mice revealed that liver toxicity was receptor-related. This same
dose given to nude mice with established U373 MG brain tumors resulted in
significant reductions in tumor volume and significantly prolonged survival
(p < 0.0001). Magnetic resonance imaging (MRI) proved to be extremely
useful in (i) determining the ability of DTIL13 to reduce tumor size and
(ii) for studying toxicity since diffusion-weighted and gradient
echo-weighted MRI revealed that vascular leak syndrome was not a limiting
toxicity at this dose. These results suggest that DTIL13 is as effective in
an intracranial rodent model as it was in a flank model in previous studies
and that DTIL13 might be an effective treatment for glioblastoma multiforme.
(c) 2005 Wiley-Liss, Inc.
PMID: 16358262 [PubMed - as supplied by publisher]
-
-
Prolonged survival of Fischer rats bearing F98 glioma
after iodine-enhanced synchrotron stereotactic radiotherapy.
Adam
JF, Joubert
A, Biston
MC, Charvet
AM, Peoc'h
M, Le
Bas JF, Balosso
J, Esteve
F, Elleaume
H.
INSERM U647, Grenoble, France; Universite Joseph Fourier, Grenoble, France;
European Synchrotron Radiation Facility, Medical Beamline ID17, Grenoble,
France.
PURPOSE: Heavy-atom-enhanced synchrotron stereotactic radiotherapy (SSR) is
a treatment that involves selective accumulation of high-Z elements in
tumors followed by stereotactic irradiation with X-rays from a synchrotron
source. The purpose of this study was to determine whether the efficacy of
iodine-enhanced SSR could be further improved in the F98 rodent glioma
model, by using a concomitant injection of an iodinated contrast agent and a
transient blood-brain barrier opener (mannitol) during irradiation. METHODS
AND MATERIALS: Fourteen days after intracerebral inoculations of F98 cells,
the rats were irradiated with 50-keV X-rays while receiving an infusion of
hyperosmotic mannitol with iodine, either intravenously or via the carotid
(9 to 15 rats per group, 117 rats total). RESULTS: For doses </=15 Gy,
the intracarotid infusion of mannitol and iodine improved the rats' survival
compared with intravenous injection or irradiation alone. The
percentage-increased life spans (ILS) were 91%, 116%, and 169% without
iodine, after infusion of iodine and mannitol intravenously, and
intracarotid, respectively (15 Gy). At 25 Gy, the rats irradiated without
iodine had the longest survival (ILS = 607%), but no additional benefit was
obtained with iodine and mannitol. CONCLUSIONS: Iodine-enhanced SSR is
significantly improved with concomitant intracarotid infusion of iodine and
mannitol for radiation doses </=15 Gy.
PMID: 16338098 [PubMed - as supplied by publisher]
-
-
Dose distribution outside of a sphere of P-32 chromic
phosphorous colloid.
Hechtman
CD, Li
Z, Mansur
DB, Perez
CA, Myerson
RJ, Simpson
JR, Anders
JC, Wu
C, Palucci
CA.
Department of Radiation Oncology, Washington University School of Medicine,
and the Alvin J. Siteman Cancer Center, St. Louis, MO 63110, USA.
ckhechtman@aol.com
PURPOSE: To evaluate the dose distribution outside of a cyst instilled with
phosphorous-32 (P-32, an electron emitter with a short effective range of
2-8 mm and average energy of 0.69 MeV, used to treat cystic
craniopharyngioma) as a function of cyst size with and without plating
(migration and adhesion of P-32 to the cyst surface). METHODS AND MATERIALS:
A cystic craniopharyngioma treated with instillation of P-32 was
approximated by a sphere of uniformly distributed and plated chromic P-32
colloid. The percent depth dose was calculated along a radial position
vector exterior to the sphere with a three-dimensional convolution integral
and a dose point kernel. RESULTS: The percent depth dose variation of
surface or volume source external to a family of spheres was plotted.
Complex cyst geometry is amenable to evaluation by approximation with simple
spheres. Error estimates are calculated for the dose outside of truncated
sphere segments. Plating might occur and raise the dose outside the cyst by
more than a factor of 5.0. This has the potential to cause damage to
adjacent tissues, including the optic chiasm. CONCLUSION: Clinicians are
faced with a number of treatment options for cystic craniopharyngioma,
including intracystic instillation of colloid P-32. Unfortunately, plating
might occur and potentially damage adjacent normal tissues. It is
recommended that the propensity for a craniopharyngioma to plate be
evaluated before full treatment, especially after previous treatment.
PMID: 16199325 [PubMed - indexed for MEDLINE]
-
-
Spinal reirradiation after short-course RT for metastatic
spinal cord compression.
Rades
D, Stalpers
LJ, Veninga
T, Hoskin
PJ.
Department of Radiation Oncology, University Hospital Hamburg-Eppendorf,
Hamburg, Germany. Rades.Dirk@gmx.net
PURPOSE: To investigate the feasibility and effectiveness of reirradiation
(re-RT) for in-field recurrence of metastatic spinal cord compression after
primary RT with 1 x 8 Gy or 5 x 4 Gy. METHODS AND MATERIALS: A total of 62
patients, treated with 1 x 8 Gy (n = 34) or 5 x 4 Gy (n = 28) between
January 1995 and August 2003, received re-RT for in-field recurrence of
metastatic spinal cord compression. The median time to recurrence was 6
months (range, 2-40 months). Re-RT was performed with 1 x 8 Gy (after 1 x 8
Gy or 5 x 4 Gy, n = 34), 5 x 3 Gy (after 1 x 8 Gy or 5 x 4 Gy, n = 15), or 5
x 4 Gy (after 1 x 8 Gy, n = 13). The cumulative biologically effective dose
(primary RT plus re-RT) was 80-100 Gy2. The median follow-up after re-RT was
8 months (range, 2-42 months). Motor function was evaluated up to 6 months
after re-RT. RESULTS: After re-RT, 25 patients (40%) showed improvement of
motor function, 28 (45%) had no change, and 9 (15%) had deterioration. Of
the 16 previously nonambulatory patients, 6 (38%) regained the ability to
walk. No second in-field recurrence in the same spinal region was observed
after re-RT. The outcome was not significantly influenced by the radiation
schedule. Radiation myelopathy was not observed. CONCLUSIONS: Spinal re-RT
with 1 x 8 Gy, 5 x 3 Gy, or 5 x 4 Gy for in-field recurrence of metastatic
spinal cord compression appears safe and effective. Myelopathy seems
unlikely, if the cumulative biologically effective dose is < or = 100
Gy2.
PMID: 15939549 [PubMed - indexed for MEDLINE]
-
-
Long-term outcome in children with relapsed ALL by
risk-stratified salvage therapy: results of trial acute lymphoblastic
leukemia-relapse study of the Berlin-Frankfurt-Munster Group 87.
Einsiedel
HG, von
Stackelberg A, Hartmann
R, Fengler
R, Schrappe
M, Janka-Schaub
G, Mann
G, Hahlen
K, Gobel
U, Klingebiel
T, Ludwig
WD, Henze
G.
Department of Pediatric Oncology/Hematology, Charite Universitatsmedizin
Berlin, Germany.
PURPOSE: Approximately 20% of children with acute lymphoblastic leukemia
(ALL) suffer a relapse, and their prognosis is unfavorable. Between 1987 and
1990, the multicenter trial Acute Lymphoblastic Leukemia-Relapse Study of
the Berlin-Frankfurt-Munster Group (ALL-REZ BFM) 87 was conducted to
establish a uniform treatment for these children in Germany and Austria.
PATIENTS AND METHODS: Of 207 registered patients, 183 patients were
stratified into three groups according to the protocol: A, early bone marrow
(BM) relapse (n = 56); B, late BM relapse (n = 101); C, isolated
extramedullary relapse (n = 26). Treatment consisted of risk-adapted
alternating short-course multiagent systemic and intrathecal chemotherapy,
cranial irradiation, if indicated, and conventional maintenance therapy.
Additionally, 24 patients with an exceptionally poor prognosis (early BM or
any relapse of T-cell ALL) were treated with individual regimens. In 35
patients, stem-cell transplantation was performed. RESULTS: The probability
of event-free survival (EFS) and overall survival of all registered patients
at 15 years was 0.30 +/- 0.03 and 0.37 +/- 0.03, respectively, with
significant differences between the strategic groups (A, 0.18 +/- 0.05 and
0.20 +/- 0.05; B, 0.44 +/- 0.05 and 0.52 +/- 0.05; C, 0.35 +/- 0.09 and 0.42
+/- 0.10). Despite risk-adapted treatment, an early time point of relapse
and T-lineage immunophenotype were significant predictors of inferior EFS in
uni- and multivariate analyses. CONCLUSION: With the ALL-REZ BFM 87
protocol, more than one-third of patients may be regarded as cured from
recurrent ALL with second complete remissions lasting more than 10 years.
Immunophenotype and time point of relapse are important prognostic factors
that allow us to adapt more precisely treatment intensity to individual
prognosis in future trials.
Publication Types:
PMID: 16258094 [PubMed - indexed for MEDLINE]
-
-
[11C]-Methionine PET: dysembryoplastic neuroepithelial
tumours compared with other epileptogenic brain neoplasms.
Rosenberg
DS, Demarquay
G, Jouvet
A, Le
Bars D, Streichenberger
N, Sindou
M, Kopp
N, Mauguiere
F, Ryvlin
P.
Cermep, Hopital Neurologique, 59 Bd Pinel, Lyon 69003, France.
BACKGROUND AND OBJECTIVES: Brain tumours responsible for longstanding
partial epilepsy are characterised by a high prevalence of dysembryoplastic
neuroepithelial tumour (DNT), whose natural evolution is much more benign
than that of gliomas. The preoperative diagnosis of DNT, which is not yet
feasible on the basis of available clinical and imaging data, would help
optimise the therapeutic strategy for this type of tumour. This study tested
whether [(11)C]-methionine positron emission tomography (MET-PET) could help
to distinguish DNTs from other epileptogenic brain tumours. METHODS:
Prospective study of 27 patients with partial epilepsy of at least six
months duration related to a non-rapidly progressing brain tumour on
magnetic resonance imaging (MRI). A structured visual analysis, which
distinguished between normal, moderately abnormal, or markedly abnormal
tumour methionine uptake, as well as various regions of interest and
semiquantitative measurements were conducted. RESULTS: Pathological results
showed 11 DNTs (41%), 5 gangliogliomas (18%), and 11 gliomas (41%). MET-PET
visual findings significantly differed between the various tumour types
(p<0.0002), regardless of gadolinium enhancement on MRI, and were
confirmed by semiquantitative analysis (p<0.001 for all calculated
ratios). All gliomas and gangliogliomas were associated with moderately or
markedly increased tumour methionine uptake, whereas 7/11 DNTs had a normal
methionine uptake, including all six located in the mesiotemporal
structures. No DNT presented with a marked MET-PET abnormality. CONCLUSION:
Normal MET-PET findings in patient with an epileptogenic and non-rapidly
progressing brain tumour are suggestive of DNT, whereas a markedly increased
tumour methionine uptake makes this diagnosis unlikely.
PMID: 16291894 [PubMed - indexed for MEDLINE]
-
-
Intra-parenchymal mesenchymal chondrosarcoma of the
cerebellum: case report and review of the literature.
Yassa
M, Bahary
JP, Bourguoin
P, Belair
M, Berthelet
F, Bouthillier
A.
A 44-year-old male presented with a 3-week history of clumsiness and
numbness of the left hemibody. CT scan and MRI revealed a 2 cm mass in the
right hemisphere of the cerebellum. The patient underwent a sub-occipital
craniotomy with gross total resection of the intra-parenchymal lesion. On
pathology, the lesion was found to be compatible with a mesenchymal
chondrosarcoma. The patient received adjuvant radiation treatment and
remains free of disease 60 months after completion of treatment. Mesenchymal
chondrosarcomas are neoplasms that rarely arise intra-cranially. Thirty
cases have been found in the literature. Our case resembles more closely six
of these cases because the tumour had no dural attachment. We describe our
case in more detail and review similar cases found in the English
literature.
Publication Types:
PMID: 16187026 [PubMed - indexed for MEDLINE]
-
-
Cyclin D1 genotype and expression in sporadic
hemangioblastomas.
Gijtenbeek
JM, Boots-Sprenger
SH, Franke
B, Wesseling
P, Jeuken
JW.
Department of Neurology, Radboud University, Nijmegen Medical Center, P.O.
Box 9101, 6500 HB Nijmegen, The Netherlands. j.gijtenbeek@neuro.umcn.nl
Central nervous system (CNS) hemangioblastomas are highly-vascularized
tumors occurring in sporadic form or as a manifestation of von Hippel-Lindau
disease (VHL). The VHL protein (pVHL) regulates various target genes, one of
which is the CCND1 gene, encoding cyclin D1, a protein that plays a critical
role in the control of the cell cycle. Overexpression of cyclin D1 is found
in many cancers. The CCND1 gene contains a common G --> A polymorphism
(870G > A) that enhances alternative splicing of the gene. CCND1 genotype
is associated with clinical outcome in a number of cancers although
prognostic significance varies with tumor type. In VHL disease, CCND1
genotype has been suggested as a genetic modifier that influences
susceptibility to hemangioblastomas.In order to analyze whether CCND1
genotype plays a role in sporadic CNS hemangioblastomas, we investigated
CCND1 genotype in tumor tissue of 17 sporadic and also in five VHL-related
CNS hemangioblastomas. In addition, in these tumors the extent and
localization of cyclin D1 expression was investigated by
immunohistochemistry. We found no deviation in CCND1 genotype distribution
and allele frequencies from expected values. Also, there was no correlation
between age at onset and CCND1 genotype. The expression of cyclin D1 as
detected by immunohistochemistry was highly variable within and between
tumors, without a clear correlation with CCND1 genotype. We conclude that,
whereas variable but sometimes high cyclin D1 expression is a feature of
sporadic hemangioblastomas, CCND1 genotype is unlikely to be an important
genetic modifier in the oncogenesis of these tumors.
PMID: 16187023 [PubMed - indexed for MEDLINE]
-
-
FAS associated phosphatase (FAP-1) blocks apoptosis of
astrocytomas through dephosphorylation of FAS.
Foehr
ED, Lorente
G, Vincent
V, Nikolich
K, Urfer
R.
AGY Therapeutics Inc., Drug Discovery, 270 East Grand Avenue, South San
Francisco, CA 94080, USA. efoehr@agyinc.com
Astrocytomas are the most common primary tumor of the adult human central
nervous system. Despite efforts to develop more effective clinical treatment
strategies, median survival time for patients with the most severe form of
astrocytoma, glioblastoma multiforme (GBM), remains about one year.
Astrocytomas are resistant to cytotoxic therapy in general and radiation
therapy in particular, greatly limiting treatment options. One reason for
this seems to be defects in the pathways controlling apoptosis. We have
characterized the role of the tyrosine phosphatase FAP-1 (FAS-associated
phosphatase 1) in astrocytomas. Our studies demonstrate that FAP-1 is
overexpressed in astrocytomas and this contributes to the resistance of the
tumor cells to FAS-mediated apoptosis. We demonstrate that knockdown of
FAP-1 by RNA interference leads to increased apoptosis and increased
sensitivity of astrocytoma cells to FAS-induced cell death. FAP-1 binds to
FAS in a ligand-dependent manner and forms a signaling complex that
modulates the ability of astrocytoma cells to undergo FAS ligand
(FASL)-mediated cell death. In astrocytoma cells, FASL treatment induces
tyrosine phosphorylation of FAS. FAP-1 dephosphorylates phospho-tyrosine 275
in the carboxyl terminus of FAS. This is the first direct evidence that FAS
activity can be regulated by reversible phosphorylation and suggests a
mechanism for astrocytoma resistance to apoptosis.
PMID: 16187021 [PubMed - indexed for MEDLINE]
-
-
Malignant rhabdoid tumor in a pregnant adult female:
literature review of central nervous system rhabdoid tumors.
Erickson
ML, Johnson
R, Bannykh
SI, de
Lotbiniere A, Kim
JH.
Department of Pathology, Yale University School of Medicine, New Haven, CT
06520-8023, USA.
Rhabdoid tumors of the central nervous system are uncommon, aggressive
childhood malignancies. The 13 described adult cases comprise both primary
CNS tumors and malignant transformation of previously existing gliomas,
meningiomas, and astrocytomas. Central nervous system rhabdoid lesions of
adults have been diagnosed as primary malignant rhabdoid tumors, atypical
teratoid/rhabdoid tumors, and more recently, rhabdoid glioblastomas. We
report a case of a 20-year-old woman in her 30th week of pregnancy who
presented with headache, nausea and blurry vision. MRI revealed a large
rim-enhancing mass of the right occipital lobe. Gross total resection was
achieved via a right parietal-occipital craniotomy. Pathologic evaluation
revealed histology, electron microscopy and immunohistochemistry consistent
with the diagnosis of malignant rhabdoid tumor. FISH studies were negative
for the INI-1 genetic mutations and chromosome 22q deletion associated with
childhood atypical rhabdoid/rhabdoid tumor in 75% of cases. The patient
delivered her infant via caesarian section prior to initiating further
therapy. We briefly describe the characteristics and current understanding
of rhabdoid tumors, and review the literature comparing the 12 other cases
of central nervous system rhabdoid tumors in adults. Furthermore, we
consider and discuss the implications of this case being the second
presentation of MRT during pregnancy in only six adult female patients.
Publication Types:
PMID: 16132523 [PubMed - indexed for MEDLINE]
-
-
Report of GBM metastasis to the parotid gland.
Ogungbo
BI, Perry
RH, Bozzino
J, Mahadeva
D.
Glioblastoma Multiforme frequently metastasises from their original location
by for example infiltration along white matter tracts [1]. GBM metastasis
outside the central nervous system is distinctly rare though there are
previous reports of spread to various organs [2-5]. We add an unusual case
of a patient with aggressive cerebral GBM metastasis to the parotid gland
and the lungs.
Publication Types:
PMID: 16132510 [PubMed - indexed for MEDLINE]
-
-
Multi-focal gliosarcoma: a case report and review of the
literature.
Pakos
EE, Goussia
AC, Zina
VP, Pitouli
EJ, Tsekeris
PG.
Department of Radiation Therapy, University Hospital of Ioannina, University
of Ioannina, Greece. epakos@yahoo.gr
Gliosarcoma (GS) is an uncommon malignant brain tumor with biphasic tissue
pattern consisted of both glial and sarcomatous components. It usually
occurs in adult population of middle age. We report a rare case of
multi-focal GS that was initially interpreted as metastases of extra-cranial
tumor. The histological examination revealed the biphasic pattern of a GS.
The patient was treated with postoperative external radiation therapy and
had poor prognosis. To our knowledge this is the second published case of GS
with multi-focal presentation. In this study we also review the literature
on clinicopathological aspects of GS.
Publication Types:
PMID: 16086111 [PubMed - indexed for MEDLINE]
-
Pediatric orbital multifocal cavernous hemangiomas
associated with bilateral arachnoid cysts of the middle cranial fossa. Case
report and review of the literature.
Tatli
M, Guzel
A, Keklikci
U, Guzel
E.
Department of Neurosurgery, University of Dicle Diyarbakir, Turkey.
mtatli@dicle.edu.tr
Cavernous hemangiomas of the orbit are benign vascular growths that commonly
occur in adults and account for 6% of all intraorbital tumors. Multifocal
intraorbital cavernous hemangiomas are quite rare. The reported incidence of
arachnoid cysts accounts for only 1% of lesions that occupy intracranial
space, and they are nearly always sporadic and single. So far, the authors
have not encountered any study reporting the coexistence of bilateral
arachnoid cysts of the middle cranial fossa and orbital multifocal cavernous
hemangiomas. In this report, they describe a 10-year-old boy with such a
hemangioma that included the eyelid, conjunctiva, and retrobulbar space. His
was the first case of a surgically treated pediatric orbital multifocal
cavernous hemangioma associated with bilateral arachnoid cysts of the middle
cranial fossa. An association between arachnoid cysts, intracranial
cavernous malformations, and bilateral arachnoid cysts and metabolic
disorders has been reported. The authors report on the coexistence of
orbital multifocal cavernous hemangiomas and bilateral arachnoid cysts of
the middle cranial fossa. Based on these observations, they believe that all
patients with bilateral temporal arachnoid cysts should be screened for
genetic disorders. In addition, the possibility of orbital cavernous
malformations should be kept in mind for the follow-up period, and patients
should be evaluated for possible symptoms of this condition.
Publication Types:
PMID: 16302620 [PubMed - indexed for MEDLINE]
-
|
Volume 4, Number 52 - 20 December 2005