| 1: Acta Cytol. 2005
Jul-Aug;49(4):452-6. |
|
Giant invasive pituitary adenoma extending into the
sphenoid sinus and nasopharynx: report of a case with intraoperative
cytologic diagnosis.
Inagawa
H, Ishizawa
K, Mitsuhashi
T, Shimizu
M, Adachi
J, Nishikawa
R, Matsutani
M, Hirose
T.
Department of Pathology, Saitama Medical School Morohongo, Moroyama,
Irumagun, Saitama, Japan.
BACKGROUND: Invasive pituitary adenomas involving the skull base are
difficult to distinguish from other, more aggressive tumors. Intraoperaive
diagnoses are crucial for deciding the course of treatment. CASE: A large
mass extending from the sella turcica to the sphenoid sinus and nasopharynx
was identified in a 42-year-old male. Because of the lack of endocrine
abnormalities and lack of an apparent rise in pituitary hormones,
preoperative diagnoses included chordoma, chondrosarcoma, meningioma and
pituitary adenoma. Tumor fragments were easily squeezed into a thin layer of
cells for cytologic specimens. Uniform, round tumor cells were arranged in
minimally cohesive cell sheets and possessed regular, ovoid nuclei with a
fine chromatin pattern and granular cytoplasm with prominent Golgi areas.
The cytologic features indicated a probable diagnosis of pituitary adenoma
and excluded other possibilities. Immunohistochemical demonstration of
prolactin and ultrastructural features established the final diagnosis of
prolactinoma. With the administration of bromocriptine, a large reduction in
tumor size occurred. As compared to frozen sections, cytologic preparations
are more effective for the intraoperative diagnosis of pituitary adenomas.
Such neoplasms should always be included in the differential diagnosis of
tumors involving the skull base.
Publication Types:
PMID: 16124180 [PubMed - indexed for MEDLINE]
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| 2: Br J
Neurosurg. 2005 Feb;19(1):53-5. |
|
Spontaneous decrease in the size of a residual thoracic
intradural lipoma.
Akyuz
M, Goksu
E, Tuncer
R.
Department of Neurosurgery, Akdeniz University of Medical School, Antalya,
Turkey. mahmutakyuz@superonline.com
Intradural spinal lipomas of thoracic cord are quite rare. It is known that
lipomas are hamartomas, which change their size with alterations of body
fat. An 18-year-old male patient, with a thoracic intradural lipoma showing
spontaneous decrease in the size of a residual lipoma and tethering of the
cord 4 years after surgery, is presented in this report.
Publication Types:
PMID: 16156032 [PubMed - indexed for MEDLINE]
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| 3: Br J
Neurosurg. 2005 Feb;19(1):38-42. |
|
A spectrum of behaviour in silent corticotroph pituitary
adenomas.
Baldeweg
SE, Pollock
JR, Powell
M, Ahlquist
J.
Department of Endocrinology, Middlesex Hospital, University College London
Hospitals, London. stephanie.baldeweg@uclh.org
Silent corticotroph adenomas (SCA) are pituitary tumours positive on
immunohistochemical staining for ACTH but without clinical evidence of
Cushing's disease in the patient. Previous reports suggest that these
tumours may behave in a more aggressive way then other pituitary adenomas.
We have followed the natural history of SCA and assessed whether
histopathological indices predict tumour behaviour. We identified 22
patients in whom trans-sphenoidal surgery was performed for a
non-functioning adenoma (NFA) with positive immunostaining for ACTH between
1990 and 2000 and examined the history of their disease. Patients were
followed up for a mean of 4.8 years. A total of 86.7% of patients had
documented visual deficits at presentation. In four cases hypercortisolaemia
was observed later in the course of the disease. Two patients died as a
result of their SCA and 33.3% of tumours recurred. Recurrence was more
frequent in patients treated with adjuvant radiotherapy. Pathological
indices (increased mitotic range and Ki-67) did not predict recurrence or
malignant transformation. We suggest that certain 'silent' corticotroph
tumours may have the potential for ACTH secretion leading to
hypercortisolaemia at a later stage in the disease. The possibility of
transformation to a more aggressive tumour needs to be considered in all
SCA.
PMID: 16147581 [PubMed - indexed for MEDLINE]
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| 4: Br J
Neurosurg. 2005 Feb;19(1):33-7. |
|
Suprabrow minicraniotomy for suprasellar tumours.
Joseph
V, Chacko
AG.
Department of Neurological Sciences, Christian Medical College and Hospital,
Vellore, India.
We present our experience with suprabow minicraniotomy in the excision of 18
suprasellar tumours between May 2001 and September 2003. There were 14
females and four males with ages ranging from 7 to 59 years. The tumours
included one epidermoid cyst, 10 meningiomas, five craniopharyngiomas and
two optico-chiasmatico-hypothalamic (OCHG) gliomas. The size of the
one-piece craniotomy was about 2.5 cm. Both OCHGs were biopsied; one
craniopharyngioma was totally excised, the remaining craniopharyngiomas and
epidermoid cyst were subtotally excised. Four meningiomas were radically
excised and six were subtotally removed. The patient with a
craniopharyngioma that had a radical excision died of hypothalamic
dysfunction. One patient developed a postoperative meningitis and subsequent
hydrocephalus requiring a shunt. The other patients did well and the
cosmetic result was excellent in all cases. This basal approach through a
small craniotomy provided good surgical access to suprasellar tumours with
minimal brain retraction.
PMID: 16147580 [PubMed - indexed for MEDLINE]
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| 5: Cancer. 2005 Oct 5; [Epub
ahead of print] |
|
-
Use of the Radiation Therapy Oncology Group recursive
partitioning analysis classification system and predictors of survival in 19
women with brain metastases from ovarian carcinoma.
Chen
PG, Lee
SY, Barnett
GH, Vogelbaum
MA, Saxton
JP, Fleming
PA, Suh
JH.
Department of Radiation Oncology, Cleveland Clinic Foundation, Cleveland,
Ohio.
BACKGROUND: Brain metastases are an uncommon complication in women with
primary ovarian carcinoma; thus, little is known about whether the Radiation
Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA)
prognostic classification system is valid in this patient population.
METHODS: From September 1985 to June 2002, 19 patients with brain metastases
resulting from primary ovarian carcinoma underwent treatment at the
Cleveland Clinic Foundation. The medical records of these patients were
retrospectively reviewed. RESULTS: At the time of data analysis, all 19
women had died. The median age at diagnosis of primary ovarian carcinoma and
brain metastasis was 51 and 54 years of age, respectively. Fifteen patients
presented with a Karnofsky performance status (KPS) of 70 or higher. Seven
patients had a single brain lesion and 12 had multiple lesions. All RTOG RPA
prognostic classes were represented, with median survivals of 24.7, 8.9, and
2.6 months for Classes I, II, and III, respectively (P = 0.31). Patients who
underwent surgical resection survived longer than those who did not (33.7
vs. 7.4 mos). The presence of multiple lesions was adversely related to
survival on multivariate analysis (P = 0.03). Primary control was an
important predictor of survival on multivariate analysis as well (P = 0.01)
and was achieved in 15 of the 19 women. CONCLUSIONS: This is the first study
to support the prognostic usefulness of the RTOG RPA classification for
ovarian carcinoma patients with metastasis to the brain. The number of
metastatic intracranial lesions should be included when determining the
prognosis. Cancer 2005. (c) 2005 American Cancer Society.
PMID: 16208705 [PubMed - as supplied by publisher]
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| 6: Cancer Res. 2005 Oct
1;65(19):8936-43. |
|
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Decreased replication ability of E1-deleted adenoviruses
correlates with increased brain tumor malignancy.
Ghosh
S, Duigou
GJ.
Department of Neurological Surgery, College of Physicians and Surgeons,
Columbia University, New York, New York 10032, USA.
E1 region replacement adenoviruses are replication defective and are
propagated in cells providing adenovirus E1A and E1B proteins. Although they
are being developed for antitumor therapies, the proliferative behaviors of
these viruses in normal brain tissues or in brain tumors are unknown. To
address this, freshly cultured cells from normal human brain and common
brain tumors (astrocytomas and meningiomas) were infected using wild-type
species C adenoviruses and adenoviruses missing E1A (H5dl312) or E1A plus
E1B (H5dl434). Viral DNA replication, late viral protein expression, and
production of infectious progeny were characterized. Wild-type adenoviruses
grew efficiently in normal brain and brain tumor cells. In comparison,
E1-deleted adenovirus DNA replication was delayed and lower in cells derived
from normal brain tissues, meningiomas, and low-grade astrocytomas. However,
in contrast, E1-deleted adenovirus DNA replication did not occur or was
extremely low in cells derived from malignancy grade III and IV astrocytic
tumors. Because wild-type adenoviruses infected and replicated in all cells,
the malignancy grade-based differential E1-deleted adenovirus DNA
replication was not explained by differential virus uptake. Infectious
H5dl312 and H5dl434 production correlated with viral DNA replication.
Compared with a 5-day average for wild-type infections, advanced
cytopathology was noted approximately 4 weeks after H5dl312 or H5dl434
infection of meningioma, astrocytoma, and normal brain cells. Cytopathology
was not observed after H5dl312 or H5dl434 infection of glioblastoma,
anaplastic astrocytoma, and gliosarcoma cells. Because of this tumor
grade-based differential growth, the E1-deleted adenoviruses may represent
novel tools for studies of brain tumor malignancy.
PMID: 16204066 [PubMed - in process]
-
| 7: Cancer Res. 2005 Oct
1;65(19):8679-89. |
|
-
Functional network analysis reveals extended
gliomagenesis pathway maps and three novel MYC-interacting genes in human
gliomas.
Bredel
M, Bredel
C, Juric
D, Harsh
GR, Vogel
H, Recht
LD, Sikic
BI.
Division of Oncology, Center for Clinical Sciences Research, Stanford
University School of Medicine, Stanford, California 94305-5151, USA.
mbredel@stanford.edu
Gene expression profiling has proven useful in subclassification and outcome
prognostication for human glial brain tumors. The analysis of biological
significance of the hundreds or thousands of alterations in gene expression
found in genomic profiling remains a major challenge. Moreover, it is
increasingly evident that genes do not act as individual units but
collaborate in overlapping networks, the deregulation of which is a hallmark
of cancer. Thus, we have here applied refined network knowledge to the
analysis of key functions and pathways associated with gliomagenesis in a
set of 50 human gliomas of various histogenesis, using cDNA microarrays,
inferential and descriptive statistics, and dynamic mapping of gene
expression data into a functional annotation database. Highest-significance
networks were assembled around the myc oncogene in gliomagenesis and around
the integrin signaling pathway in the glioblastoma subtype, which is
paradigmatic for its strong migratory and invasive behavior. Three novel
MYC-interacting genes (UBE2C, EMP1, and FBXW7) with cancer-related functions
were identified as network constituents differentially expressed in gliomas,
as was CD151 as a new component of a network that mediates glioblastoma cell
invasion. Complementary, unsupervised relevance network analysis showed a
conserved self-organization of modules of interconnected genes with
functions in cell cycle regulation in human gliomas. This approach has
extended existing knowledge about the organizational pattern of gene
expression in human gliomas and identified potential novel targets for
future therapeutic development.
PMID: 16204036 [PubMed - in process]
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| 8: Clin
Cancer Res. 2005 Oct 1;11(19 Pt 1):6767-71. |
|
-
Food and Drug Administration Drug approval summary:
temozolomide plus radiation therapy for the treatment of newly diagnosed
glioblastoma multiforme.
Cohen
MH, Johnson
JR, Pazdur
R.
Division of Oncology Drug Products, Center for Drug Evaluation and Research,
US Food and Drug Administration, Rockville, Maryland 20857, USA.
cohenma@cder.fda.gov
On March 15, 2005, the U.S. Food and Drug Administration approved
temozolomide (Temodar capsules, Schering-Plough Research Institute) for the
treatment of adult patients with newly diagnosed glioblastoma multiforme
concomitantly with radiotherapy and then as maintenance treatment. Five
hundred seventy-three glioblastoma multiforme patients were randomized to
receive either temozolomide + radiotherapy (n = 287) or radiotherapy alone
(n = 286). Patients in the temozolomide + radiotherapy arm received
concomitant temozolomide (75 mg/m2) once daily for the duration of radiation
therapy (42-49 days). This was followed, 4 weeks later, by six cycles of
temozolomide, 150 or 200 mg/m2 daily for 5 days, every 4 weeks. Patients in
the control arm received radiotherapy only. In both arms, radiotherapy was
delivered as 60 Gy/30 fractions to the tumor site with a 2 to 3 cm margin.
Pneumocystis carinii pneumonia prophylaxis was required during temozolomide
+ radiotherapy treatment and was continued until recovery of lymphocytopenia
(Common Toxicity Criteria grade <1). At disease progression, temozolomide
salvage treatment was given to 161 of 282 patients (57%) in the radiotherapy
alone arm, and to 62 of 277 patients (22%) in the temozolomide +
radiotherapy arm. Patients receiving concomitant and maintenance
temozolomide + radiotherapy had significantly improved overall survival. The
hazard ratio was 0.63 (95% confidence interval, 0.52-0.75; log-rank, P <
0.0001). Median survival was 14.6 months (temozolomide + radiotherapy)
versus 12.1 months (radiotherapy alone). Adverse events during temozolomide
treatment included thrombocytopenia, nausea, vomiting, anorexia,
constipation, alopecia, headache, fatigue, and convulsions.
PMID: 16203762 [PubMed - in process]
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| 9: Int
J Radiat Oncol Biol Phys. 2005 Sep 27; [Epub ahead of print] |
|
-
Distinctive clinical course and pattern of relapse in
adolescents with medulloblastoma.
Tabori
U, Sung
L, Hukin
J, Laperriere
N, Crooks
B, Carret
AS, Silva
M, Odame
I, Mpofu
C, Strother
D, Wilson
B, Samson
Y, Bouffet
E; Canadian
Pediatric Brain Tumor Consortium.
Pediatric Brain Tumor Program, The Hospital for Sick Children, Toronto,
Ontario, Canada.
PURPOSE: To report the clinical course of adolescents with medulloblastoma,
with specific emphasis on prognosis and pattern of relapse. METHODS AND
MATERIALS: We retrospectively studied the clinical course and outcomes of
children aged 10-20 years with medulloblastoma, treated at centers
throughout Canada between 1986 and 2003. To better assess time to relapse, a
cohort of patients aged 3-20 years at diagnosis was generated. RESULTS: A
total of 72 adolescents were analyzed. Five-year overall survival and
event-free survival rates were 78.3% +/- 5.4% and 68.0% +/- 6.2%,
respectively. Late relapses occurred at a median of 3.0 years (range,
0.3-6.8 years). In univariate analysis, conventional risk stratification and
the addition of chemotherapy to craniospinal radiation did not have
prognostic significance. Female patients had improved overall survival (p =
0.007). Time to relapse increased with age in a linear fashion. After
relapse, patients faired poorly regardless of treatment modality. Patients
who did not receive chemotherapy initially had improved progression-free
survival at relapse (p = 0.05). CONCLUSIONS: Our study suggests that
adolescents with medulloblastoma might have a unique prognosis and pattern
of relapse, dissimilar to those in younger children. They might benefit from
different risk stratifications and prolonged follow-up. These issues should
be addressed in future prospective trials.
PMID: 16198067 [PubMed - as supplied by publisher]
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| 10: J Neurooncol.
2005 Sep 15; [Epub ahead of print] |
|
-
Immunohistochemical Analysis of Platelet-derived Growth
Factor Receptor-alpha, -beta, c-kit, c-abl, and arg Proteins in
Glioblastoma: Possible Implications for Patient Selection for Imatinib
Mesylate Therapy.
Haberler
C, Gelpi
E, Marosi
C, Rossler
K, Birner
P, Budka
H, Hainfellner
JA.
Institute of Neurology, Medical University of Vienna, Austria,
hainfellner@kin.at.
Inhibition of tyrosine kinase (TK) receptors by synthetic small molecules
has become a promising new therapy option in oncology. The TK inhibitor
imatinib mesylate selectively targets PDGFR-alpha, -beta, c-kit, c-abl and
arg and has proven successful in the treatment of chronic myeloid leukaemia.
In recurrent glioblastoma, phase II therapy trials using imatinib mesylate
have been initiated. As only a fraction of patients seems to benefit from
imatinib mesylate therapy and due to potential side effects and high costs
of imatinib mesylate therapy, selection of the right patients is important.
The goal of our study was to assess systematically immunohistochemical
expression of the major TKs targeted by imatinib mesylate in glioblastoma,
as expression of these factors could be used to select patients for imatinib
mesylate therapy. In a cohort of 101 glioblastoma patients,
anti-PDGFR-alpha, -beta, c-kit, c-abl and arg protein immunohistochemistry
was performed. Expression of these proteins was assessed semi-quantitatively
and correlated with patient survival. PDGFR-alpha and arg expression in
tumor cells was widespread in 1/101 cases, respectively. Focal PDGFR-alpha,
-beta, c-kit, c-abl and arg immunolabeling was detected in 25/101, 19/101,
4/101, 7/101 and 31/101 cases, respectively. Statistical analysis did not
reveal any correlation between expression of the TKs and patient survival.
We show here for the first time in a large series of glioblastomas that
PDGFR-alpha, -beta, c-kit, c-abl and arg expression is immunohistochemically
detectable in a fraction of cases. The value of anti-tyrosine kinase
immunolabeling as predictive factor for patient selection remains to be
clarified by comparative analysis of tumor tissue of therapy-responders
versus non-responders.
PMID: 16205964 [PubMed - as supplied by publisher]
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| 11: J Neurooncol.
2005 Sep 15; [Epub ahead of print] |
|
-
Oligodendroglial-specific Transcriptional Factor SOX10 is
Ubiquitously Expressed in Human Gliomas.
Bannykh
SI, Stolt
CC, Kim
J, Perry
A, Wegner
M.
Department of Pathology, Yale University School of Medicine, New Haven, CT,
USA, Serguei.Bannykh@yale.edu.
The two most common types of gliomas: astrocytoma and oligodendroglioma are
distinguished based on their morphologic similarities to mature astrocytes
and oligodendroglia. Whereas prototypical examples of the tumors have
distinct pathogenetic and prognostic differences, the majority of the
gliomas falls in the intermediate category and their distinction is
problematic. The transcriptional factor SOX10 is one of the key determinants
of oligodendroglial differentiation. We applied immunohistochemistry to
analyze whether the expression of SOX10 can differentiate astrocytoma and
oligodendroglioma. The majority of oligodendrogliomas, but also a large
fraction of astrocytomas, including the least differentiated glioblastomas,
expressed SOX10, albeit at lower levels. Comparison with 1p and 19q deletion
status by FISH analysis also revealed no obvious associations. High levels
of expression were also found in pilocytic astrocytoma, consistent with
recent studies suggesting that pilocytic astrocytomas have greater overlap
with oligodendroglial than astrocytic tumors. Our data raise a possibility
that histogenesis of gliomas have more common features than previously
anticipated.
PMID: 16205963 [PubMed - as supplied by publisher]
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| 12: J Neurooncol.
2005 Sep 10; [Epub ahead of print] |
|
-
Gliomatosis cerebri: a review of 296 cases from the
ANOCEF database and the literature.
Taillibert
S, Chodkiewicz
C, Laigle-Donadey
F, Napolitano
M, Cartalat-Carel
S, Sanson
M.
Federation de Neurologie, Groupe hospitalier Pitie-Salpetriere, 47-83 bd de
l'hopital, 75651, Paris, cedex 13, France, m.sanson@psl.ap-hop-paris.fr.
Gliomatosis cerebri (GC) is a rare disease, defined as a diffuse neoplastic
glial cell infiltration of the brain. Diagnosis and management of GC are
difficult. This study analyzed 296 individual cases (90 patients followed
through the ANOCEF network, and 206 cases from the literature), aged 1 month
to 85 years (median 42), sex ratio = 1.31. Median survival was 14.5 months.
It was higher for patients younger than 42 years (17 months vs. 13 months),
with performance status >/=80 (27 months vs. 9 months), low grade
gliomatosis (grade 2 = 20 months, grade 3 = 11.5 months, grade 4 = 8.5
months), oligodendroglial subtype (36 months compared to 14 months for mixed
GC and 11 months for astrocytic GC). Male population was younger (median 39
years vs. 45), had a higher incidence of oligodendroglial GC (22% vs. 13%),
which may explain their better prognosis (median survival 17 months vs. 11.5
months) than female population. Despite a high rate of stabilization, the
impact on survival of whole brain radiotherapy, which carries the risk of
severe toxicity, is still unclear. Up-front chemotherapy benefit to some
patients and may be prefered to whole brain radiotherapy. However, the many
bias of such retrospective heterogeneous data claim for multicentric
clinical trials in this rare disease.
PMID: 16200347 [PubMed - as supplied by publisher]
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| 13: J Neurooncol.
2005 Sep 12; [Epub ahead of print] |
|
-
Radiation enhances the invasive potential of primary
glioblastoma cells via activation of the Rho signaling pathway.
Zhai
GG, Malhotra
R, Delaney
M, Latham
D, Nestler
U, Zhang
M, Mukherjee
N, Song
Q, Robe
P, Chakravarti
A.
Department of Radiation Oncology, Massachusetts General Hospital/Harvard
Medical School, 100 Blossom Street,Founders House, Room 536, Boston, MA,
02114, USA.
Glioblastoma multiforme (GBM) is among the most treatment-refractory of all
human tumors. Radiation is effective at prolonging survival of GBM patients;
however, the vast majority of GBM patients demonstrate progression at or
near the site of original treatment. We have identified primary GBM cell
lines that demonstrate increased invasive potential upon radiation exposure.
As this represents a novel mechanism by which radiation-treated GBMs can
fail therapy, we further investigated the identity of downstream signaling
molecules that enhance the invasive phenotype of irradiated GBMs. Matrigel
matrices were used to compare the extent of invasion of irradiated vs.
non-irradiated GBM cell lines UN3 and GM2. The in vitro invasive potential
of these irradiated cells were characterized in the presence of both
pharmacologic and dominant negative inhibitors of extracellular matrix and
cell signaling molecules including MMP, uPA, IGFR, EGFR, PI-3K, AKT, and Rho
kinase. The effect of radiation on the expression of these signaling
molecules was determined with Western blot assays. Ultimately, the in vitro
tumor invasion results were confirmed using an in vivo 9L GBM model in rats.
Using the primary GBM cell lines UN3 and GM2, we found that radiation
enhances the invasive potential of these cells via activation of EGFR and
IGFR1. Our findings suggest that activation of Rho signaling via PI-3K is
required for radiation-induced invasion, although not required for invasion
under physiologic conditions. This report clearly demonstrates that
radiation-mediated invasion is fundamentally distinct from invasion under
normal cellular physiology and identifies potential therapeutic targets to
overcome this phenomenon.
PMID: 16200346 [PubMed - as supplied by publisher]
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| 14: J Neurooncol.
2005 Sep 12; [Epub ahead of print] |
|
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Increasing of HER2 membranar density in human
glioblastoma U251MG cell line established in a new Nude mice model.
Mineo Jean-François, Bordron Anne, Quintin-Roué Isabelle,
Maurage Claude-Alain, Buhé Virginie, Loisel Séverine,
Dubois François, Blond Serge and Berthou Christian
Department of Neurosurgery, Hospital Roger Salengro, University Hospital of
Lille, 59037, Lille, France, j-mineo@chru-lille.fr.
Glioblastoma multiform (GBM) remains the most devastating primary tumour in
neuro-oncology. Human Epithelial Receptor Type 2 (HER2) is a transmembrane
tyrosine/kinase receptor that is important for cancer growth. HER2 is not
expressed in adult glial cells, but its expression increases with the degree
of astrocytomas anaplasia. We have recently demonstrated the ability of
anti-HER2 antibodies to induce in vitro apoptosis GBM cell lines; this
ability is correlated to HER2 density. A decreasing of tyrosine/kinase
receptors density during in vitro culture was reported. No information
exists about the variation of HER2 expression after in vivo implantation.
For that, the two cell lines in vitro tested (U251MG, A172) were in vivo
implanted. We established a U251MG in vivo model in balb/c nude mice showing
an important increasing of HER2 density. The HER2 density is correlated to
anti-HER2 antibody efficiency so this model will be useful for the
evaluation of in vivo anti-HER2 antibody treatment.
PMID: 16200345 [PubMed - as supplied by publisher]
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| 15: J Neurooncol.
2005 Sep 10; [Epub ahead of print] |
|
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Temozolomide after radiotherapy for newly diagnosed
high-grade glioma and unfavorable low-grade glioma in children.
Broniscer
A, Chintagumpala
M, Fouladi
M, Krasin
MJ, Kocak
M, Bowers
DC, Iacono
LC, Merchant
TE, Stewart
CF, Houghton
PJ, Kun
LE, Ledet
D, Gajjar
A.
Department of Hematology-Oncology, St. Jude Children's Research Hospital,
Memphis, TN, USA, alberto. broniscer@stjude.org.
Chemotherapy is commonly used in the treatment of children with high-grade
glioma, although its usefulness is uncertain. We conducted a
multi-institutional study to evaluate the efficacy of temozolomide given
after radiotherapy in children with newly diagnosed high-grade glioma and
unfavorable low-grade glioma (gliomatosis cerebri or bithalamic
involvement). Optional window therapy of intravenous irinotecan (10 doses of
20 mg/m(2) per cycle x 2) was given over 6 weeks. The 5-day schedule of
temozolomide (200 mg/m(2) per day) started 4 weeks after the completion of
radiotherapy and continued for a total of 6 cycles. Thirty-one eligible
patients (median age: 12.3 years) participated. Tumors most commonly
involved cerebral hemispheres (n=13, 42%) and thalamus (n=14, 45%). Whereas
six patients underwent radical resection, the remainder had limited surgery,
including biopsy (n=14, 45%). The predominant histologic diagnoses were
glioblastoma multiforme (n=15, 48%) and anaplastic astrocytoma (n=10, 32%).
Two patients had bithalamic grade II astrocytoma. Twenty-seven patients
received radiotherapy (median dose: 59.4 Gy), including craniospinal
irradiation in 3 because of leptomeningeal spread. Four patients did not
receive radiotherapy in this study because of consent withdrawn (n=2),
toxicity during window therapy (n=1), or at the physician's discretion
(n=1). Twenty-three patients received 112 cycles of temozolomide therapy.
The 2-year progression-free and overall survival estimates were 11+/-5% and
21+/-7%, respectively. Although the heterogeneity of prognostic factors in
our patients made assessment of treatment outcome more difficult, the
addition of 6 cycles of temozolomide after radiotherapy did not seem to
alter the poor outcome of these patients.
PMID: 16200343 [PubMed - as supplied by publisher]
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| 16: J Neurooncol.
2005 Sep 8; [Epub ahead of print] |
|
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Planning for Intracavitary Anti-EGFR Radionuclide Therapy
of Gliomas. Literature Review and Data on EGFR Expression.
Carlsson J, Ren Z.P, Wester K, Sundberg Å.L, Heldin N.E,
Hesselager G, Persson M, Gedda L, Tolmachev V, Lundqvist H,
Blomquist E and Nistér M
Unit of Biomedical Radiation Sciences, Department of Oncology, Radiology and
Clinical Immunology, Rudbeck Laboratory, Uppsala University, Uppsala,
Sweden, Jorgen.Carlsson@ bms.uu.se.
Targeting with radionuclide labelled substances that bind specifically to
the epidermal growth factor receptor, EGFR, is considered for intracavitary
therapy of EGFR-positive glioblastoma multiforme, GBM. Relevant literature
is reviewed and examples of EGFR expression in GBM are given. The
therapeutical efforts made so far using intracavitary anti-tenascin
radionuclide therapy of GBM have given limited effects, probably due to low
radiation doses to the migrating glioma cells in the brain. Low radiation
doses might be due to limited penetration of the targeting agents or
heterogeneity in the expression of the target structure. In this article we
focus on the possibilities to target EGFR on the tumour cells instead of an
extracellular matrix component. There seems to be a lack of knowledge on the
degree of intratumoral variation of EGFR expression in GBM, although the
expression seemed rather homogeneous over large areas in most of the
examples (n=16) presented from our laboratory. The observed homogeneity was
surprising considering the genomic instability and heterogeneity that
generally characterises highly malignant tumours. However, overexpression of
EGFR is, at least in primary GBMs, one of the steps in the development of
malignancy, and tumour cells that lose or downregulate EGFR will probably be
outgrown in an expanding tumour cell population. Thus, loss of EGFR
expression might not be the critical factor for successful intracavitary
radionuclide therapy. Instead, it is likely that the penetration properties
of the targeting agents are critical, and detailed studies on this are
urgent.
PMID: 16200342 [PubMed - as supplied by publisher]
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| 17: J Neurosurg.
2005 Jan;102(1 Suppl):72-7. |
|
The transformation of pediatric gliomatosis cerebri to
cerebellar glioblastoma multiforme presenting as supra- and infratentorial
acute disseminated encephalomyelitis. Case report.
Senatus
PB, McClelland
S 3rd, Tanji
K, Khandji
A, Huang
J, Feldstein
N.
Department of Neurological Surgery, Columbia College of Physicians and
Surgeons, Neurological Institute of New York, New York 10032, USA.
pps19@columbia.edu
Cerebellar glioblastoma multiforme (GBM) is a rare entity in adults and an
extremely rare entity in children. Approximately 30 cases have been reported
in the literature. The authors report the case of a histologically confirmed
cerebellar GBM presenting initially as supra- and infratentorial gliomatosis
cerebri. Acute disseminated encephalomyelitis had been diagnosed in the
patient and that diagnosis remained until near the end of his treatment.
This case underscores the need for recognizing the clinical presentation of
gliomatosis cerebri and multifocal GBM in the pediatric subpopulation
thought to harbor demyelinating disease.
PMID: 16206737 [PubMed - in process]
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| 18: J Neurosurg.
2005 Jan;102(1 Suppl):53-8. |
|
Infusion rates and drug distribution in brain tumor
models in rats.
Khan
A, Jallo
GI, Liu
YJ, Carson
BS Sr, Guarnieri
M.
Division of Pediatric Neurosurgery, The Johns Hopkins Hospital, Baltimore,
Maryland 21287-8811, USA.
OBJECT: The aim of this study was to investigate the optimal delivery rates
of chemotherapy for the treatment of central nervous system tumors and to
determine whether local delivery can lower toxicity profiles and increase
target concentrations of chemotherapy. METHODS: The authors used two brain
tumor models in rats. Slow (1 microl/hour) and fast (10 microl/hour) pumps
were used to deliver chemotherapy--carboplatin, doxorubicin, and a
high-molecular-weight transferrin-doxorubicin conjugate to the brains of
normal rats and rats previously injected with F98 or 9L rat brain tumor
cells. Brains were cut in 1-mm sections rostral and caudal from the infusion
point. Slices were analyzed for doxorubicin and platinum by fluorescence and
atomic absorption, respectively. In the normal tissues, the volume of drug
distribution is generally greater at the faster flow rate. In abnormal
tissues, distribution is similar at slow and fast infusion rates for
low-molecular-weight drugs and greater at slow rates for a
high-molecular-weight targeted toxin. CONCLUSIONS: After local
administration the distribution of chemotherapy appears to be significantly
influenced by tumor metabolism. Additional studies are needed to determine
the optimal delivery rates for the interaction of the drug with the targeted
tumor.
PMID: 16206734 [PubMed - in process]
-
| 19: J Neurosurg.
2005 Jan;102(1 Suppl):44-52. |
|
Treatment strategies for high-risk medulloblastoma and
supratentorial primitive neuroectodermal tumors. Review of the literature.
Jakacki
RI.
Division of Pediatric Hematology/Oncology, Children's Hospital of
Pittsburgh, Pennsylvania 15213, USA. regina.jakacki@chp.edu
Primitive neuroectodermal tumors (PNETs) are malignant tumors with a high
propensity to disseminate throughout the cerebrospinal fluid. Current
treatment guidelines are largely determined by clinically based prognostic
factors, the most important of which are tumor location and the extent of
tumor spread. Although the cure rate for high-risk PNETs has improved, the
irreversible sequelae of craniospinal axis radiation treatment in patients
who survive have motivated researchers to investigate more fully which
patients can safely receive less treatment. The author reviews the
literature, describes currently available treatment options for patients
with high-risk PNETs, and discusses strategies aimed at improving outcome
and refining prognosis that are currently being explored.
PMID: 16206733 [PubMed - in process]
| 20: J Neurosurg.
2005 Aug;103(2):372-7. |
|
The evolution of Harvey Cushing's surgical approach to
pituitary tumors from transsphenoidal to transfrontal.
Cohen-Gadol
AA, Laws
ER, Spencer
DD, De
Salles AA.
Department of Neurologic Surgery, Mayo Clinic and Mayo Foundation,
Rochester, Minnesota 55902, USA. cohengadol.aaron@mayo.edu
The evolution of transsphenoidal surgery represents a special chapter in the
progress of neurosurgery. Although Cushing initially advocated a
transsphenoidal approach to pituitary tumors, he became disenchanted with
this approach, ultimately favoring the subfrontal or
"transfrontal" route late in his career. Other neurosurgeons
followed Cushing's example, and the fate of transsphenoidal surgery entered
a dark era in 1929. A review of Cushing's patients' records reveals that his
abandonment of the transsphenoidal route was primarily related to the
limitations of this approach in providing effective resection of large
pituitary lesions-the symptomatic tumor recurrence rate after this procedure
was substantial. Furthermore, given the preoperative uncertainty about the
suprasellar extension of pituitary tumors prior to modern neuroimaging, the
transfrontal route assured Cushing an adequate decompression of the optic
chiasm. By 1927, Cushing's mastery of intracranial surgery was accompanied
by the use of electrosurgical methods that enabled him to remove sellar
lesions through the transfrontal route safely and with timely and effective
restoration of visual loss. Transsphenoidal surgery remained relatively
dormant, awaiting the efforts and enthusiasm of Norman Dott who bridged the
gap between Cushing and Gerard Guiot, the surgeon who revitalized
transsphenoidal adenomectomy for future generations of pituitary surgeons.
Publication Types:
Personal Name as Subject:
PMID: 16175871 [PubMed - indexed for MEDLINE]
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| 21: J Neurosurg.
2005 Aug;103(2):218-23. |
|
Gamma knife surgery for the treatment of intracranial
metastases from breast cancer.
Goyal
S, Prasad
D, Harrell
F Jr, Matsumoto
J, Rich
T, Steiner
L.
Department of Radiation Oncology, Howard University Hospital, Washington,
DC, USA.
OBJECT: The goal of this study was to evaluate the effectiveness and
limitations of gamma knife surgery (GKS) in the treatment of intracranial
breast carcinoma lesions. METHODS: A retrospective analysis of the GKS
database at the University of Virginia Health System identified 43 patients
with a total of 84 lesions who were treated between 1989 and 2000. All
patients who received treatment were included in this study. Imaging studies
were available in 35 patients with 67 treated lesions. The overall duration
of median survival was 13 months (95% confidence interval [CI] 7-16 months)
after radiosurgery. A univariable Cox regression analysis revealed that a
single lesion (p = 0.035), a high Karnofsky Performance Scale (KPS) score (p
= 0.019), and a high Score Index for Radiosurgery (SIR) in Brain Metastases
(p = 0.036) were associated with a significantly lengthened time to local
treatment failure. The median duration of survival for patients grouped
according to the SIR as low, middle, and high was 3, 8, and 21 months,
respectively (p = 0.00033). A multivariable analysis showed that a high KPS
score (p = 0.006), a high SIR (p = 0.014), and advanced age (0.038) were
predictive of survival. The 1-, 2-, 3-, and 5-year survival rates were 49,
23, 12, and 2%, respectively. The overall median time to local treatment
failure was 10 months (95% CI 6-14 months) after GKS. A univariable analysis
demonstrated that a single lesion, higher KPS score, and a higher SIR were
associated with a significantly longer time until local treatment failure. A
multivariable analysis showed that a higher KPS score and SIR and patients
who had received chemotherapy were associated with a significantly longer
time to local treatment failure. Neuroimaging scores given for the
enhancement pattern (ring-enhancing, heterogeneous, and homogeneous signal),
amount of necrosis (none, < 50%, and > 50%), and mass effect (none,
mild, moderate, and severe) of each treated lesion did not correlate with
survival or local treatment failure. CONCLUSIONS: The SIR and the KPS score
are prognostic factors in patients whose intracranial breast cancer
metastases are treated with GKS. The SIR, which includes the KPS score,
patient age, systemic disease status, largest lesion volume, and number of
lesions, can be used to identify those patients with breast cancer
metastasis who would benefit from GKS better than KPS score alone. The
contribution of whole-brain radiation therapy to GKS with regard to local
tumor control or survival could not be identified.
PMID: 16175849 [PubMed - indexed for MEDLINE]
| 22: J Neurosurg.
2005 Jul;103(1 Suppl):54-60. |
|
Neuroendoscopic transventricular ventriculocystostomy in
treatment for intracranial cysts.
Di
Rocco F, Yoshino
M, Oi
S.
Division of Pediatric Neurosurgery, Department of Neurosurgery, Jikei
University School of Medicine, Tokyo, Japan.
OBJECT: Although in recent years endoscopic procedures have been used for
intracranial arachnoid cysts with favorable preliminary results in certain
locations, optimal surgical treatment is still controversial. The purpose of
this study was to evaluate the efficacy and safety of endoscopic
transventricular ventriculocystostomy in the treatment of intracranial cysts
based on the concept of normalizing cerebrospinal fluid (CSF) dynamics.
METHODS: Twelve symptomatic pediatric patients with congenital intracranial
cysts underwent surgery at Jikei University in Tokyo. A neuroendoscopic
transventricular ventriculocystostomy was performed in nine patients and an
endoscope-assisted craniotomy in the remaining three. Endoscopy was
performed using a freehand maneuver with a newly designed rigid-rod
neuroendoscope that is frameless and has a small diameter. Clinical results
were good in all patients, although cysts in three were not prominently
reduced in size when follow-up imaging studies were performed. Neither death
nor symptomatic morbidity occurred, and no patient required shunt placement.
In three cases the endoscopic fenestration was associated with an endoscopic
third ventriculostomy (ETV). Postoperative CSF dynamics studies consisting
of computerized tomography ventriculocysternography, and pre- and
postoperative cine-mode magnetic resonance imaging demonstrated free
communication between fenestrated cysts and ventricular/ cistern CSF
pathways consistent with normalization of CSF dynamics. CONCLUSIONS:
Neuroendoscopic transventricular ventriculocystostomy constitutes a valid
alternative to microsurgery for intracranial cysts located within or
adjacent to the ventricles. It creates an effective CSF flow within the cyst
with minimal alteration of subarachnoid spaces. It may be combined with an
ETV procedure in case of obstruction of CSF pathways and should be preferred
to the insertion of shunts.
PMID: 16122006 [PubMed - indexed for MEDLINE]
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| 23: J Neurosurg.
2005 Jul;103(1 Suppl):40-2. |
|
Hydrocephalus in children with posterior fossa tumors:
role of endoscopic third ventriculostomy.
Fritsch
MJ, Doerner
L, Kienke
S, Mehdorn
HM.
Department of Neurosurgery, Universitatsklinikum Schleswig-Holstein, Campus
Kiel, Kiel, Germany. fritschm@nch.uni-kiel.de
OBJECT: Controversy exists regarding the indication for endoscopic third
ventriculostomy (ETV) in children with hydrocephalus caused by posterior
fossa tumors. The authors present their treatment modalities and discuss the
role of ETV in the management of hydrocephalus. METHODS: The authors
retrospectively reviewed the cases of 58 children who were admitted to their
clinic consecutively with posterior fossa tumors between January 1999 and
December 2003. Fifty-two patients presented with hydrocephalus. The mean age
at the time of admission was 6 years and 3 months. The mean follow-up period
was 25 months. The authors evaluated how many children required a
cerebrospinal fluid (CSF) draining procedure (external ventricular drain
[EVD], ventriculoperitoneal [VP] shunt, or ETV) prior to or following tumor
removal. Only six patients (11.5%) required permanent treatment for
hydrocephalus. Four patients received a VP shunt and two patients underwent
ETV. A temporary EVD was placed in five patients (two required a shunt).
Forty-six patients (88.5%) did not require a permanent CSF draining
procedure. CONCLUSIONS: For children with posterior fossa tumors, ETV is not
indicated as a standard operation either prior to or following tumor
removal. Only six of 52 children presenting with hydrocephalus required a
permanent CSF draining procedure. Endoscopic third ventriculostomy may be
suitable for patients with fourth ventricle outflow obstruction and
persisting or progressive hydrocephalus following tumor removal.
PMID: 16122003 [PubMed - indexed for MEDLINE]
-
| 24: J
Nucl Med. 2005 Oct;46(10):1707-18. |
|
-
microPET Imaging of Glioma Integrin {alpha}v{beta}3
Expression Using 64Cu-Labeled Tetrameric RGD Peptide.
Wu
Y, Zhang
X, Xiong
Z, Cheng
Z, Fisher
DR, Liu
S, Gambhir
SS, Chen
X.
Molecular Imaging Program at Stanford (MIPS), Department of Radiology and
Bio-X Program, Stanford University, Stanford, California.
Integrin alpha(v)beta(3) plays a critical role in tumor-induced angiogenesis
and metastasis and has become a promising diagnostic indicator and
therapeutic target for various solid tumors. Radiolabeled RGD peptides that
are integrin specific can be used for noninvasive imaging of integrin
expression level as well as for integrin-targeted radionuclide therapy.
METHODS: In this study we developed a tetrameric RGD peptide tracer
(64)Cu-DOTA-E{E[c(RGDfK)](2)}(2) (DOTA is
1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid) for PET
imaging of integrin alpha(v)beta(3) expression in female athymic nude mice
bearing the subcutaneous UG87MG glioma xenografts. RESULTS: The RGD tetramer
showed significantly higher integrin binding affinity than the corresponding
monomeric and dimeric RGD analogs, most likely due to a polyvalency effect.
The radiolabeled peptide showed rapid blood clearance (0.61 +/- 0.01 %ID/g
at 30 min and 0.21 +/- 0.01 %ID/g at 4 h after injection, respectively
[%ID/g is percentage injected dose per gram]) and predominantly renal
excretion. Tumor uptake was rapid and high, and the tumor washout was slow
(9.93 +/- 1.05 %ID/g at 30 min after injection and 4.56 +/- 0.51 %ID/g at 24
h after injection). The metabolic stability of
(64)Cu-DOTA-E{E[c(RGDfK)](2)}(2) was determined in mouse blood, urine, and
liver and kidney homogenates at different times after tracer injection. The
average fractions of intact tracer in these organs at 1 h were approximately
70%, 58%, 51%, and 26%, respectively. Noninvasive microPET studies showed
significant tumor uptake and good contrast in the subcutaneous tumor-bearing
mice, which agreed well with the biodistribution results. Integrin
alpha(v)beta(3) specificity was demonstrated by successful blocking of tumor
uptake of (64)Cu-DOTA-E{E[c(RGDfK)](2)}(2) in the presence of excess
c(RGDyK) at 1 h after injection. The highest absorbed radiation doses
determined for the human reference adult were received by the urinary
bladder wall (0.262 mGy/MBq), kidneys (0.0296 mGy/MBq), and liver (0.0242
mGy/MBq). The average effective dose resulting from a single
(64)Cu-DOTA-E{E[c(RGDfK)](2)}(2) injection was estimated to be 0.0164
mSv/MBq. CONCLUSION: The high integrin and avidity and favorable biokinetics
make (64)Cu-DOTA-E{E[c(RGDfK)](2)}(2) a promising agent for peptide receptor
radionuclide imaging and therapy of integrin-positive tumors.
PMID: 16204722 [PubMed - in process]
-
| 25: Neurol Res.
2005 Oct;27(7):747-54. |
|
-
Chromosomal and genetic abnormalities in benign and
malignant meningiomas using DNA microarray.
Wada
K, Maruno
M, Suzuki
T, Kagawa
N, Hashiba
T, Fujimoto
Y, Hashimoto
N, Izumoto
S, Yoshimine
T.
Department of Neurosurgery, Osaka University Graduate School of Medicine,
Suita, Osaka 565-0871, Japan.
BACKGROUND: Meningioma is the commonest brain tumor and many genetic
abnormalities, such as the loss of chromosome 22q and the mutation of NF2,
have been reported.METHODS: These classical abnormalities were detected
using Southern blot, PCR, fluorescence in situ hybridization and comparative
genomic hybridization, but these methods examine only very limited regions
or limited mapping resolution of the tumor genome. In this study, we used
DNA microarray assay, which detects numerous genetic abnormalities
simultaneously and analyses a global assessment of molecular events in
meningioma cells. We studied 31 meningiomas by GenoSensor Array 300 in order
to detect the chromosomal aberrations and genetic abnormalities in the whole
genome.RESULTS: This study demonstrated not only classical chromosomal
aberration, such as loss of chromosome 22q in 19 meningiomas (61.3%), but
also new genetic characteristics of meningiomas, such as amplification of
MSH2 in 16 meningiomas (51.6%), deletion of GSCL in 13 meningiomas (41.9%)
and deletion of HIRA in seven meningiomas (22.6%).CONCLUSIONS: These results
suggest that DNA microarray assay is useful in research for the genetic
characters of meningiomas and understanding tumorigenesis.
PMID: 16197812 [PubMed - in process]
-
| 26: Neurol Res.
2005 Oct;27(7):703-16. |
|
-
Immunotherapy for malignant glioma: current approaches
and future directions.
Sikorski
CW, Lesniak
MS.
Division of Neurosurgery, The University of Chicago Pritzker School of
Medicine, 5841 South Maryland Avenue, MC 3026, Chicago, Illinois 60637, USA.
Traditional therapies for the treatment of malignant glioma have failed to
make appreciable gains regarding patient outcome in the last decade.
Therefore, immunotherapeutic approaches have become increasingly popular in
the treatment of this cancer. This article reviews general immunology of the
central nervous system and the immunobiology of malignant glioma to provide
a foundation for understanding the rationale behind current glioma
immunotherapies. A review of currently implemented immunological treatments
is then provided with special attention paid to the use of vaccines, gene
therapy, cytokines, dendritic cells and viruses. Insights into future and
developing avenues of glioma immunotherapy, such as novel delivery systems,
are also discussed.
PMID: 16197807 [PubMed - in process]
|
Volume 4, Number 42 - 13 October 2005