-
CD155/PVR enhances glioma cell dispersal by regulating
adhesion signaling and focal adhesion dynamics.
Sloan
KE, Stewart
JK, Treloar
AF, Matthews
RT, Jay
DG.
Department of Physiology, Tufts University School of Medicine, Boston,
Massachusetts 02111, USA.
We recently identified the immunoglobulin-CAM CD155/PVR (the poliovirus
receptor) as a regulator of cancer invasiveness and glioma migration, but
the mechanism through which CD155/PVR controls these processes is unknown.
Here, we show that expression of CD155/PVR in rat glioma cells that normally
lack this protein enhances their dispersal both in vitro and on primary
brain tissue. CD155/PVR expression also reduced substrate adhesion, cell
spreading, focal adhesion density, and the number of actin stress fibers in
a substrate-dependent manner. Furthermore, we found that expression of
CD155/PVR increased Src/focal adhesion kinase signaling in a
substrate-dependent manner, enhancing the adhesion-induced activation of
paxillin and p130Cas in cells adhering to vitronectin. Conversely, depletion
of endogenous CD155/PVR from human glioma cells inhibited their migration,
increased cell spreading, and down-regulated the same signaling pathway.
These findings implicate CD155/PVR as a regulator of adhesion signaling and
suggest a pathway through which glioma and other cancer cells may acquire a
dispersive phenotype.
PMID: 16322240 [PubMed - in process]
-
"Conservative" surgical approach and early
postoperative radiotherapy in a patient with a huge cystic
craniopharyngioma.
Fraioli
MF, Santoni
R, Fraioli
C, Contratti
F.
Department of Neurosciences, Neurosurgery, Tor Vergata University of Rome,
Via Oxford 81, 00133, Rome, Italy, b.fraioli@libero.it.
OBJECTIVE: The treatment of huge craniopharyngiomas represents a therapeutic
challenge for neurosurgeons. Some authors prefer to run the high risks of
total removal at primary surgery, while others do not despise subtotal
removal in accordance with a multidisciplinary treatment. METHODS: We report
the case of a 17-year-old girl who underwent subtotal removal (tumour
remnant with maximum diameter of 2.5 cm) of a huge cystic craniopharyngioma
by frontotemporal approach, followed by early external fractionated
radiotherapy by linear accelerator. Serial magnetic resonance imaging during
a follow-up period of 5 years showed a progressive marked reduction of the
tumour remnant, accompanied by a complete recovery of visual deficits and an
almost complete regression of diencephalic disturbances. CONCLUSIONS:
Subtotal removal followed by early fractionated radiotherapy can be an
effective treatment for huge craniopharyngiomas. Such a multidisciplinary
treatment may favour tumour control and assure a satisfactory quality of
life as well.
PMID: 16320025 [PubMed - as supplied by publisher]
Lipidized giant-cell glioblastoma of cerebellum.
Queiroz
LS, Faria
AV, Zanardi
VA, Netto
JR.
Department of Pathology, School of Medical Sciences, Report State University
of Campinas (UNICAMP), Campinas, Brazil. gradanat@fcm.unicamp.br
Glioblastoma multiforme is recognized rarely in the cerebellum. We describe
a peculiar case with lipid accumulation in giant tumor cells, possibly the
second example so far reported in this unusual location. A 46-year-old man
with a 5-month history of headache, vomiting, dizziness and instability of
gait, was found to have on magnetic resonance imaging an expanding mass
situated deep in the left cerebellar hemisphere. The lesion was hypointense
in T 1- and hyperintense in T2-weighted images, had poorly defined borders,
peripheral edema and annular foci of contrast enhancement. Eight months
after subtotal removal and radiotherapy, control MRI showed tumor recurrence
with aggressive features. The patient was alive 15 months after operation
but follow-up was eventually lost. Histologically, the tumor showed marked
pleomorphism, with many giant cells characterized by finely vacuolated
cytoplasm strongly suggestive of lipid accumulation. There were few,
sometimes atypical mitotic figures and foci of endothelial proliferation.
The tumor cells were strongly positive for GFAP, vimentin and S100 protein,
all of which stressed the foamy appearance of the giant cells. About 15% of
nuclei were positive for Ki-67. We considered the case to be a so-called
lipidized glioblastoma, first recognized as a subtype by Kepes and
Rubinstein [1981]. Differential diagnosis with anaplastic pleomorphic
xanthoastrocytoma is discussed.
PMID: 16320820 [PubMed - in process]
-
Meningioma with the unique coexistence of secretory and
lipomatous components: a case report with immunohistochemical and
ultrastructural study.
Matyja
E, Naganska
E, Zabek
M, Jagielski
J.
Department of Experimental and Clinical Neuropathology, Medical Research
Centre, Polish Academy of Sciences, Brodnowski District Hospital, Warsaw,
Poland.
Meningiomas exhibit a broad spectrum of differentiation potency
corresponding to different histological subtypes. The separate secretory or
lipomatous transformation of meningothelial cells is uncommonly encountered
in meningiomas classified into distinct secretory or lipomatous variants.
The coexistence of these two different histological subtypes is extremely
rare. We report an exceptional case of secretory meningioma associated with
extensive lipomatous component in a 58-year-old woman. CT scan and MRI of
the brain showed a well-defined tumor mass in the right temporal lobe with
areas of adipose tissue and extensive surrounding brain edema.
Microscopically, the tumor was composed of two components: whorls of
meningothelial cells with numerous PAS-positive hyaline inclusions
(pseudopsammoma bodies) and numerous mature adipocyte-like cells. The
presence of neutral fat was confirmed by oil-red-O staining. The hyaline
inclusions and tumor cells surrounding them showed strong immunoreactivity
for EMA and CEA. Ultrastructural findings confirmed both secretory and
lipomatous differentiation of tumor cells. The majority of lipidized
neoplastic cells shared the features of meningothelial cells and adipocytes.
Our result supports the opinion that lipomatous component ought to be
considered as an advanced lipidization of neoplastic meningothelial cells
rather than true metaplastic transformation of meningothelial cells into
mature fat tissue. The present case of meningioma demonstrates a unique
coexistence of secretory and lipomatous meningothelial components,
reflecting the multipotency of phenotypic transformation of primary
meningothelial cells.
PMID: 16320819 [PubMed - in process]
-
Subcutaneous tumoral seeding from a glioblastoma
following stereotactic biopsy: case report and review of the literature.
Bouillot-Eimer
S, Loiseau
H, Vital
A.
Department of Neuropathology, Pellegrin Hospital, Bordeaux, France.
sandrine.bouillot@chu-bordeaux.fr
Extracranial metastases from glioblastoma are uncommon, likely because short
patient survival time prevent them to occur. Most of the few previously
reported cases occurred after invasive surgical procedures. We describe a
case of glioblastoma with concomitant seeding along the stereotactic biopsy
trajectory and subcutaneous metastasis. A 60-year-old woman presented with
severe headache. Neuroradiological work-up (including cranial computed
tomographic scan and magnetic resonance imaging) showed a heterogeneous
hyperdensity, suggestive of malignant glioma, in the left parietal region. A
computed tomographic-guided stereotactic biopsy was performed and
microscopic examination attested a diagnosis of glioblastoma. Radiotherapy
and chemotherapy were administered. Eight months later, the patient
presented with a subcutaneous tumor in the left occipital region. A cranial
computed tomographic scan revealed a large enhancement of the initial tumor,
intracranial tumor seeding along the stereotactic biopsy trajectory, and a
subcutaneous tumor. Partial resection of the subcutaneous lesion was
performed, and histological examination identified an extracranial
metastasis from the glioblastoma. Although uncommon, this observation points
to the risk of tumor seeding following stereotactic biopsy, and to the close
connection between this intracranial seeding and subcutaneous metastasis.
PMID: 16320817 [PubMed - in process]
-
-
Phase II Trial of Radiosurgery for One to Three Newly
Diagnosed Brain Metastases From Renal Cell Carcinoma, Melanoma, and Sarcoma:
An Eastern Cooperative Oncology Group Study (E 6397).
Manon
R, O'neill
A, Knisely
J, Werner-Wasik
M, Lazarus
HM, Wagner
H, Gilbert
M, Mehta
M.
K4/B3, 600 Highland Ave, Madison, WI 53792; e-mail: mehta@humonc.wisc.edu.
PURPOSE Long-term brain metastases survivors are at risk for neurologic
morbidity after whole-brain radiotherapy (WBRT). Retrospective radiosurgery
(RS) reports found no survival difference when compared with WBRT. Before RS
alone was evaluated with delayed WBRT in a phase III trial, the feasibility
of RS alone was tested prospectively. PATIENTS AND METHODS Patients with
renal cell carcinoma, melanoma, or sarcoma; one to three brain metastases;
and performance status of 0 to 2 were enrolled. Exclusion criteria were
leptomeningeal disease; metastases in medulla, pons, or midbrain; or liver
metastases. On the basis of tumor size, patients received 24, 18, or 15 Gy
RS. At recurrence, management was discretionary. The primary end point was
3- and 6-month intracranial progression. Results Between July 1998 and
August 2003, 36 patients were accrued; 31 were eligible. Median follow-up
was 32.7 months and the median survival was 8.3 months (95% CI, 7.4 to
12.2). Three- and 6-month intracranial failure with RS alone was 25.8% and
48.3%. Failure within and outside the RS volume, when in-field and distant
intracranial failures were scored independently, was 19.3% and 16.2% (3
months) and 32.2% and 32.2% (6 months), respectively. Approximately 38% of
patients experienced death attributable to neurologic cause. There were
three grade 3 toxicities related to RS. CONCLUSION Intracranial failure
rates without WBRT were 25.8% and 48.3% at 3 and 6 months, respectively.
Delaying WBRT may be appropriate for some subgroups of patients with
radioresistant tumors, but routine avoidance of WBRT should be approached
judiciously.
PMID: 16314647 [PubMed - in process]
-
-
Efficacy of fractionated stereotactic reirradiation in
recurrent gliomas: long-term results in 172 patients treated in a single
institution.
Combs
SE, Thilmann
C, Edler
L, Debus
J, Schulz-Ertner
D.
Department of Radiation Oncology, University of Heidelberg, INF 400, 69120
Heidelberg, Germany; e-mail: Stephanie.Combs@med.uni-heidelberg.de.
PURPOSE To evaluate the efficacy of fractionated stereotactic radiotherapy
(FSRT) performed as reirradiation in 172 patients with recurrent low- and
high-grade gliomas. PATIENTS AND METHODS Between 1990 and 2004, 172 patients
with recurrent gliomas were treated with FSRT as reirradiation in a single
institution. Seventy-one patients suffered from WHO grade 2 gliomas. WHO
grade 3 gliomas were diagnosed in 42 patients, and 59 patients were
diagnosed with glioblastoma multiforme (GBM). The median time between
primary radiotherapy and reirradiation was 10 months for GBM, 32 months for
WHO grade 3 tumors, and 48 months for grade 2 astrocytomas. FSRT was
performed with a median dose of 36 Gy in a median fractionation of 5 x 2
Gy/wk. Results Median overall survival after primary diagnosis was 21 months
for patients with GBM, 50 months for patients with WHO grade 3 gliomas, and
111 months for patients with WHO grade 2 gliomas. Histologic grading was the
strongest predictor for overall survival, together with the extent of
neurosurgical resection and age at primary diagnosis. Median survival after
reirradiation was 8 months for patients with GBM, 16 months for patients
with grade 3 tumors, and 22 months for patients with low-grade gliomas. Only
time to progression and histology were significant in influencing survival
after reirradiation. Progression-free survival after FSRT was 5 months for
GBM, 8 months for WHO grade 3 tumors, and 12 months for low-grade gliomas.
CONCLUSION FSRT is well tolerated and may be effective in patients with
recurrent gliomas. Prospective studies are warranted for further evaluation.
PMID: 16314646 [PubMed - in process]
-
-
Genomic and Protein Expression Profiling Identifies CDK6
As Novel Independent Prognostic Marker in Medulloblastoma.
Mendrzyk
F, Radlwimmer
B, Joos
S, Kokocinski
F, Benner
A, Stange
DE, Neben
K, Fiegler
H, Carter
NP, Reifenberger
G, Korshunov
A, Lichter
P.
German Cancer Research Center, Division of Molecular Genetics (B060), Im
Neuenheimer Feld 580, 69120 Heidelberg, Germany; e-mail: m.macleod@dkfz.de.
PURPOSE Medulloblastoma is the most common malignant brain tumor in
children. Despite multimodal aggressive treatment, nearly half of the
patients die as a result of this tumor. Identification of molecular markers
for prognosis and development of novel pathogenesis-based therapies depends
crucially on a better understanding of medulloblastoma pathomechanisms.
PATIENTS AND METHODS We performed genome-wide analysis of DNA copy number
imbalances in 47 medulloblastomas using comparative genomic hybridization to
large insert DNA microarrays (matrix-CGH). The expression of selected
candidate genes identified by matrix-CGH was analyzed immunohistochemically
on tissue microarrays representing medulloblastomas from 189 clinically
well-documented patients. To identify novel prognostic markers, genomic
findings and protein expression data were correlated to patient survival.
Results Matrix-CGH analysis revealed frequent DNA copy number alterations of
several novel candidate regions. Among these, gains at 17q23.2-qter (P <
.01) and losses at 17p13.1 to 17p13.3 (P = .04) were significantly
correlated to poor prognosis. Within 17q23.2-qter and 7q21.2, two of the
most frequently gained chromosomal regions, confined amplicons were
identified that contained the PPM1D and CDK6 genes, respectively.
Immunohistochemistry revealed strong expression of PPM1D in 148 (88%) of 168
and CDK6 in 50 (30%) of 169 medulloblastomas. Overexpression of CDK6
correlated significantly with poor prognosis (P < .01) and represented an
independent prognostic marker of overall survival on multivariate analysis
(P = .02). CONCLUSION We identified CDK6 as a novel molecular marker that
can be determined by immunohistochemistry on routinely processed tissue
specimens and may facilitate the prognostic assessment of medulloblastoma
patients. Furthermore, increased protein-levels of PPM1D and CDK6 may link
the TP53 and RB1 tumor suppressor pathways to medulloblastoma
pathomechanisms.
PMID: 16314645 [PubMed - in process]
-
-
Phase III Study of Efaproxiral As an Adjunct to
Whole-Brain Radiation Therapy for Brain Metastases.
Suh
JH, Stea
B, Nabid
A, Kresl
JJ, Fortin
A, Mercier
JP, Senzer
N, Chang
EL, Boyd
AP, Cagnoni
PJ, Shaw
E.
Cleveland Clinic, Cleveland, OH; University of Arizona Health Sciences
Center, Tucson; Barrow Neurological Institute, Arizona Oncology Services,
Phoenix, AZ; US Oncology Research Inc, Dallas; The University of Texas M.D.
Anderson Cancer Center, Houston, TX; Allos Therapeutics Inc, Westminster,
CO; Wake Forest University School of Medicine, Winston-Salem, NC; Centre
Hospitalier Universitaire de Sherbrooke, Sherbrooke; Hotel-Dieu de Quebec du
Centre Hospitalier de Quebec CHUQ, Quebec City; and Hospital
Maisonneuve-Rosemont, Montreal, Quebec, Canada.
PURPOSE: To determine whether efaproxiral, an allosteric modifier of
hemoglobin, improves survival in patients with brain metastases when used as
an adjunct to whole-brain radiation therapy (WBRT). PATIENTS AND METHODS:
Patients with brain metastases from solid tumors and a Karnofsky performance
score of >/= 70 were randomly assigned to receive WBRT with supplemental
oxygen and either efaproxiral at 75 or 100 mg/kg (efaproxiral arm) or no
efaproxiral (control arm). The primary end point was survival. RESULTS: The
study consisted of 515 eligible patients (efaproxiral arm, n = 265; control
arm, n = 250). The median survival time (MST) was 5.4 months for the
efaproxiral arm versus 4.4 months for the control arm (hazard ratio [HR] =
0.87; P = .16). For the subgroup of patients with non-small-cell lung cancer
(NSCLC) or breast cancer, the MST was 6.0 and 4.4 months, respectively (HR =
0.82; P = .07). Cox multiple regression analysis demonstrated a significant
reduction in the risk of death for the efaproxiral arm in both primary
populations. Further analysis indicated that the benefit may be restricted
to the subgroup of patients with breast cancer. Response rates (radiographic
complete response plus partial response) improved by 7% (P = .10) and 13% (P
= .01) for all patients and for NSCLC and breast cancer patients in the
efaproxiral arm, respectively. The most common severe adverse event in
patients treated with efaproxiral was hypoxemia, which was reversible and
effectively managed with supplemental oxygen in most patients. CONCLUSION:
The addition of efaproxiral, a noncytotoxic radiation sensitizer, to WBRT
may improve response rates and survival in patients with brain metastases,
particularly metastases from breast cancer. A confirmatory trial for breast
cancer patients has been initiated.
PMID: 16314619 [PubMed - as supplied by publisher]
-
-
Novel targets for valproic acid: up-regulation of
melatonin receptors and neurotrophic factors in C6 glioma cells.
Rincon
Castro LM, Gallant
M, Niles
LP.
Department of Psychiatry and Behavioural Neurosciences, McMaster University,
Hamilton, Ontario, Canada.
Valproic acid (VPA) is a potent anti-epileptic and effective mood
stabilizer. It is known that VPA enhances central GABAergic activity and
activates the mitogen-activated protein kinase-extracellular
signal-regulated kinase (MAPK-ERK) pathway. It can also inhibit various
isoforms of the enzyme, histone deacetylase (HDAC), which is associated with
modulation of gene transcription. Recent in vivo studies indicate a
neuroprotective role for VPA, which has been found to up-regulate the
expression of brain-derived neurotrophic factor (BDNF) in the rat brain.
Given the interaction between the pineal hormone, melatonin, and GABAergic
systems in the central nervous system, the effects of VPA on the expression
of the mammalian melatonin receptor subtypes, MT(1) and MT(2), were examined
in rat C6 glioma cells. The effects of VPA on the expression of glial cell
line-derived neurotrophic factor (GDNF) and BDNF were also examined. RT-PCR
studies revealed a significant induction of melatonin MT(1) receptor mRNA in
C6 cells following treatment with 3 or 5 mm VPA for 24 h or 5 mm VPA for 48
h. Western analysis and immunocytochemical detection confirmed that the
VPA-induced increase in MT(1) mRNA results in up-regulation of MT(1) protein
expression. Blockade of the MAPK-ERK pathway by PD98059 enhanced the effect
of VPA on MT(1) expression, suggesting a negative role for this pathway in
MT(1) receptor regulation. In addition, significant increases in BDNF, GDNF
and HDAC mRNA expression were observed after treatment with VPA for 24 or 48
h. Taken together, the present findings suggest that the neuroprotective
properties of VPA involve modulation of neurotrophic factors and receptors
for melatonin, which is also thought to play a role in neuroprotection.
Moreover, the foregoing suggests that combinations of VPA and melatonin
could provide novel therapeutic strategies in neurological and psychiatric
disorders.
PMID: 16313512 [PubMed - in process]..
-
-
Tetrazolium violet induces G0/G1 arrest and apoptosis in
brain tumor cells.
Zhao
Y, Zhang
N, Kong
Q.
School of Life Science, Shandong University, Jinan, 250100, China.
Tetrazolium violet (TV), a potent anticancer agent, has been shown to induce
cell growth-inhibition in tumor cells. However, the related mechanism has
not been revealed yet. In this report we assessed the influence of TV on
cell growth and cell cycle in brain tumor cells. Treatment of C6 tumor cells
with TV (5-15 muM for 24-72 h) resulted in a growth inhibition in a dose and
time-dependent manner and G0/G1 phase arrest, determined by flow cytometry
analysis. These effects were accompanied by apoptosis other than necrosis,
evidenced by nuclear condensation, terminal deoxynucleotidyl
transferase-mediated nick end labeling (TUNEL) assay and trypan blue
exclusion assay plus lactate dehydrogenase (LDH) release assay. Treatment of
cells with TV at 15 muM for 24 h resulted in an increase in the activity of
caspase-3, evidenced by colorimetric assay, and a dramatic up-regulation of
p53, accompanied with a significant increase of Bax/Bcl-2 ratio, as
evidenced by immunofluorescence assay. These results suggest that TV induces
growth inhibition of C6 cells through p53-midiated apoptotic pathway and
G0/G1 checkpoint mechanism. Although detailed mechanisms remain to be
explored, selective blockage of tumor cells in G0/G1 phase accompanied by
p53-associated apoptosis makes tetrazolium violet a promising anticancer
agent, meriting further investigations.
PMID: 16314959 [PubMed - as supplied by publisher]
-
-
Sestamibi technetium-99m brain single-photon emission
computed tomography to identify recurrent glioma in adults: 201 studies.
Jeune
FP, Dubois
F, Blond
S, Steinling
M.
Service de Medecine Nucleaire, Unite fonctionnelle de neurologie, Hopital
Roger Salengro, Chru de Lille, France, prigent@rennes.fnclcc.fr.
OBJECT: In the follow-up of treated gliomas, CT and MRI can often not
differentiate radionecrosis from recurrent tumor. The aim of this study was
to assess the interest of functional imaging with (99m)Tc-MIBI SPECT in a
large series of 201 examinations. METHOD: MIBI SPECT were performed in 81
patients treated for brain gliomas. A MIBI uptake index was computed as the
ratio of counts in the lesion to counts in the controlateral region. SPECT
was compared to stereotactic biopsy in 14 cases, or in the others cases to
imaging evolution or clinical course at 6 months after the last
tomoscintigraphy Two hundred and one tomoscintigraphies were performed. One
hundred and two scans were true positive, 82 scans were true negative. Six
scans were false positive (corresponding to 3 patients): 2 patients with an
inflammatory reaction after radiosurgery, 1 with no explanation up to now.
Eleven scans were false negative (5 patients): 1 patient with a deep
peri-ventricular lesion, 2 patients with no contrast enhancement on MRI, 2
patients with a temporal tumor. The sensitivity for tumor recurrence was
90%, specificity 91.5% and accuracy 90.5%. We studied separately low and
high grade glioma: sensitivity for tumor recurrence was respectively 91% and
89%, specificity 100% and 83% and accuracy 95% and 87%. MIBI SPECT allowed
the diagnose of anaplasic degenerence of low grade sometimes earlier than
clinical (5 cases) or MRI signs (7 cases). CONCLUSIONS: Our results confirm
the usefullness of MIBI SPECT in the follow-up of treated gliomas for the
differential diagnosis between radiation necrosis and tumor recurrence.
PMID: 16314957 [PubMed - as supplied by publisher]
-
-
(123)I-metaiodobenzylguanidine single-photon emission
computerized tomography in brain tumors - a preliminary study.
Sasajima
T, Kinouchi
H, Naitoh
Y, Tomura
N, Watarai
J, Mizoi
K.
Department of Neurosurgery, Akita University School of Medicine, Akita,
Japan, sasajima@nsg.med.akita-u.ac.jp.
OBJECTIVE: (123)I-metaiodobenzylguanidine (MIBG) has been developed as a
functional analog of the neurotransmitter norepinephrine. The success of
MIBG as an imaging agent for neural crest tumors is derived from its
chemical similarities to norepinephrine. The present study aimed to explore
a potential of (123)I-MIBG to differentiate embryonal tumors from other
types of brain tumors. METHODS: Sixteen patients with brain tumors including
three medulloblastomas, one neuroblastoma, six gliomas, and six meningiomas
were examined with single-photon emission computerized tomography (SPECT)
using (123)I-MIBG. The (123)I-MIBG uptake of tumors was defined as the
ratios of tumor/nontumor (early and delayed T/NT) on SPECT images scanned 30
min and 6 h after intravenous injection of the tracer, respectively.
Retention index was calculated as (delayed T/NT - early T/NT)/early T/NT.
RESULTS: The T/NT ratios on the early images for embryonal tumors
(medulloblastomas and neuroblastoma), gliomas, and meningiomas were
3.2+/-1.7 (mean+/-SD), 1.4+/-0.3, and 1.6+/-0.5, respectively. The early
uptake was significantly higher in the embryonal tumors than in gliomas
(P<0.05). Delayed T/NT ratios for embryonal tumors were increased
compared to the early T/NT ratios, while in contrast delayed T/NT ratios for
the other tumors remained low (1.2-1.7). The high retention indices of the
embryonal tumors indicate specific uptake of (123)I-MIBG in the tumors.
CONCLUSION: Early high accumulation and high retention on delayed imaging
may indicate a possibility of (123)I-MIBG SPECT in differentiating embryonal
brain tumors from gliomas and meningiomas.
PMID: 16314956 [PubMed - as supplied by publisher]
-
-
A phase II window trial of procarbazine and topotecan in
children with high-grade glioma: a report from the children's oncology
group.
Chintagumpala
MM, Friedman
HS, Stewart
CF, Kepner
J, McLendon
RE, Modrich
PL, McCluggage
C, Burger
P, Holmes
E, Thompson
S, Rutka
J, Michalski
J, Woo
S, Blaney
SM, Kun
LE, Horowitz
AM; A
Pediatric Oncology Group Study.
Baylor College of Medicine, 6621 Fannin, CC 1510.00, Houston, TX, USA.
The role of chemotherapy in the treatment of high-grade gliomas in children
is unclear. Early reports were suggestive of improved outcome in children
with high-grade glioma with the addition of chemotherapy after surgery and
radiation therapy. Subsequent studies did not show similar favorable
contribution of chemotherapy to the outcome of these children. Further
efforts to identify active chemotherapy agents in children include use of
agents that have shown efficacy in adult patients with high-grade glioma and
agents that have shown promise in mice bearing human xenografts of brain
tumors. A Pediatric Oncology Group (POG 9431) trial tested the activity of
two such agents, procarbazine and topotecan in newly diagnosed patients with
high-grade glioma who had measurable disease after diagnostic surgery.
Neither agent showed efficacy within the confines of the statistical design
of the study. This study showed that children with high-grade glioma have an
innate resistance to alkylating agents based on mismatch repair deficiency
and high levels of alkyguanine transferase (AGT). Future trials should
consider strategies to overcome the resistance mechanisms in children with
high-grade glioma.
PMID: 16314955 [PubMed - as supplied by publisher]
-
-
Antisense oligonucleodes targeting the focal adhesion
kinase inhibit proliferation, induce apoptosis and cooperate with cytotoxic
drugs in human glioma cells.
Wu
ZM, Yuan
XH, Jiang
PC, Li
ZQ, Wu
T.
Department of Neurosurgery, Zhongnan Hospital, Wuhan University, 430071,
Wuhan, Hu Bei Province, People's Republic of China.
To examine the role of focal adhesion kinase in human glioma cells, we
studied its effects on proliferation and apoptosis using FAK antisense
oligonucleotide. U251 MG cells were transfected with ODNs, sense FAK,
mismatch FAK and antisense-FAK, respectively. Expression of FAK proteins
were detected by Western blots and Immnofluoressence. Cell apoptosis and
mitochondrial membrane potential were analyzed by flow cytometry. Caspase-3
activity was measured by spectrofluorometer. MTT assay was used to examine
changes in cell proliferation. The protein expression of FAK in U251 MG
cells decreased in antisense-FAK ODNs group significantly. Caspase-3
activity increased in cells treated with antisense-FAK and down-regulated
when treated with caspase-3 inhibitor. The level of cell apoptosis and loss
of mitochondrial membrane potential in antisense-FAK group was higher than
in the mismatch sense group. Cells proliferation was inhibited by
antisense-FAK, and the effects were clearly additive when antisense
oligonuceotides were added to cells treated with the anticancer agents. The
results suggest that antisense-FAK ODNs inhibit U251 MG cells proliferation
and induce their apoptosis. It is possible that FAK via mitochondrial and
caspase-3 inhibits U251 MG cells apoptosis. And antisense oligonucleotide
treatment enhances U251 MG cells sensitivity to chemotherapy.
PMID: 16314954 [PubMed - as supplied by publisher]
-
-
Concurrent chemoradiotherapy and adjuvant chemotherapy
with Topotecan for patients with glioblastoma multiforme.
Klautke
G, Schutze
M, Bombor
I, Benecke
R, Piek
J, Fietkau
R.
Department of Radiotherapy, University of Rostock, Sudring 75, 18059,
Rostock, Germany, gunther.klautke@med.uni-rostock.de.
PURPOSE: The prognosis for patients with glioblastoma multiforme remains
poor. Phase II studies, meta-analyses and a phase III study show that
concurrent chemoradiotherapy has an advantage over irradiation alone. In
this study the effectiveness of concurrent chemoradiotherapy with Topotecan
and an adjuvant chemotherapy with Topotecan was investigated. PATIENTS AND
METHOD: Forty-two patients with predominantly unfavourable prognosis factors
were included in the study and treated as follows: hyperfractionated
accelerated radiotherapy (2x1.75Gy to 45.5 + 12.25 Gy (RP)) with a
concurrent, continuous infusion of Topotecan (0.5 mg/m(2)/d, days 1-21). On
day 28 the adjuvant chemotherapy (three courses) was begun according to the
same scheme. RESULT: Haematological toxicities were 13/42 (30%) grade III
leucopenia, 2/42 (4%) grade IV, as well as 5/42 (10%) grade III
thrombopenias and 1/42 (2%) grade IV. 30/42 (71%) patients showed
improvement or stabilisation of an existing neurological symptomatic
complex. The median time to progression was 7.2 (+/- 0.8) months, the median
total survival was 10 (+/- 1.2) months, the 2 year survival rate 4.7 (+/-
0.3)%. Prognostic factors were age, surgical radicality, performance status
and the tumour volume before therapy. Concurrent chemoradiotherapy and an
adjuvant chemotherapy with Topotecan is feasible at acceptable toxicity
levels also for patients with a moderate performance status. The patients
benefit from the improvement of the clinical symptomatic complex and, even
with unfavourable prognosis factors, have a higher median survival in
comparison to data published on similar groups of patients given only
radiotherapy.
PMID: 16314953 [PubMed - as supplied by publisher]
-
-
Safety and efficacy of a novel cannabinoid
chemotherapeutic, KM-233, for the treatment of high-grade glioma.
Duntsch
C, Divi
MK, Jones
T, Zhou
Q, Krishnamurthy
M, Boehm
P, Wood
G, Sills
A, Ii
BM.
Departments of Neurosurgery, The University of Tennessee Health Science
Center, Memphis, TN, USA.
OBJECTIVE: To test in vitro and in vivo the safety and efficacy of a novel
chemotherapeutic agent, KM-233, for the treatment of glioma. METHODS: In
vitro cell cytotoxicity assays were used to measure and compare the
cytotoxic effects of KM-233, Delta(8)-tetrahydrocannabinol (THC), and
bis-chloroethyl-nitrosurea (BCNU) against human U87 glioma cells. An
organotypic brain slice culture model was used for safety and toxicity
studies. A human glioma-SCID mouse side-pocket tumor model was used to test
in vivo the safety and efficacy of KM-233 with intratumoral and
intra-peritoneal administration. RESULTS: KM-233 is a classical cannabinoid
with good blood brain barrier penetration that possesses a selective
affinity for the CB2 receptors relative to THC. KM-233 was as efficacious in
its cytotoxicity against human U87 glioma as Delta(8)-tetrahydrocannabinol,
and superior to the commonly used anti-glioma chemotherapeutic agent, BCNU.
The cytotoxic effects of KM-233 against human glioma cells in vitro occur as
early as two hours after administration, and dosing of KM-233 can be cycled
without compromising cytotoxic efficacy and while improving safety. Cyclical
dosing of KM-233 to treat U87 glioma in a SCID mouse xenograft side pocket
model was effective at reducing the tumor burden with both systemic and
intratumoral administration. CONCLUSION: These studies provide both in vitro
and in vivo evidence that KM-233 shows promising efficacy against human
glioma cell lines in both in vitro and in vivo studies, minimal toxicity to
healthy cultured brain tissue, and should be considered for definitive
preclinical development in animal models of glioma.
PMID: 16314952 [PubMed - as supplied by publisher]..
-
-
Human leukocyte antigen distribution analysis in North
Italian brain Glioma patients: an association with HLA-DRB1*14.
Guerini
FR, Agliardi
C, Zanzottera
M, Delbue
S, Pagani
E, Tinelli
C, Boldorini
R, Car
PG, Veggiani
C, Ferrante
P.
Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi
Foundation IRCCS, S. Maria Nascente, Milan, Italy.
Human leukocyte antigens (HLA) are widely expressed cell surface molecules
that present antigenic peptides to T-lymphocytes and modulate the immune
response against inflammatory and malignant disease. Frequently, tumoral
cells express antigens that are recognized by the immune system. Ineffective
immune response could be the result of defects in antigen presentation in
those subjects with peculiar HLA alleles, which, owing to mechanisms that
are still unknown, are unable to carry out their function. Only a few
studies on glioma and HLA association have been performed to date. The aim
of our study was to characterize a group of Italian Caucasian patients with
glioma, to investigate a possible association between HLA antigens and
cerebral glioma tumorigenesis in Italian patients. HLA typing of class I and
class II loci was done by molecular typing performed on blood DNA from 36
glioma patients from northern Italy. The data obtained were compared with
HLA frequencies taken from the database of northern Italian organ donors.A
positive association between HLA-DRB1*14 and the presence of symptomatic
cerebral glioma was observed (p = 0.02, odds ratio = 2.48, 95% confidence
interval: 1.09-5.45).This is the first Italian report on a case-control data
study of HLA distribution conducted on a group of glioma patients and a
first step in defining a possible involvement of HLA in susceptibility to
brain glioma in the Italian population.
PMID: 16314951 [PubMed - as supplied by publisher]..
-
-
Pathological laughter and behavioural change in childhood
pontine glioma.
Hargrave
DR, Mabbott
DJ, Bouffet
E.
Paediatric Oncology Unit, Royal Marsden Hospital, Downs Road, SM2 5PT,
Sutton, Surrey, UK.
Children with pontine glioma usually present classically with ataxia, motor
deficits and cranial nerve palsies. The pons has generally not been regarded
as a structure that mediates complex affective behaviour. However, we report
nine children who either at the time of presentation or progression
demonstrated marked behavioural changes manifesting as either a8pathological
laughtera9 or separation anxiety in the form of school refusal. A mechanism
of how pontine lesions can cause such complex affective and cognitive
behaviour has been suggested to consist of the disruption of a network of
cerebro-ponto-cerebellar pathways and the evidence for this mechanism is
discussed.
PMID: 16314950 [PubMed - as supplied by publisher]
-
-
Osmotic blood-brain barrier disruption chemotherapy for
diffuse pontine gliomas.
Hall
WA, Doolittle
ND, Daman
M, Bruns
PK, Muldoon
L, Fortin
D, Neuwelt
EA.
Department of Neurosurgery, University of Minnesota Medical School,
Minneapolis, MN, USA, hallx003@umn.edu.
The prognosis for patients with diffuse pontine gliomas (DPG) remains poor.
New aggressive innovative treatments are necessary to treat this disease.
From 1984 to 1998, eight patients (4M/4F), median age 11 years, with DPG
were treated with monthly osmotic blood-brain barrier disruption (BBBD)
chemotherapy using intraarterial carboplatin or methotrexate and intravenous
cytoxan and etoposide. Patients presented for a median duration of 6 weeks
with increased intracranial pressure, long tract signs, diplopia, ataxia,
and nausea/vomiting. DPG was demonstrated on magnetic resonance (MR) imaging
in seven patients and on CT in one. Two patients had biopsies that showed an
astrocytoma and an anaplastic astrocytoma. Three tumors enhanced on MR
imaging after contrast administration. Three patients had radiation therapy
before BBBD chemotherapy and four afterwards. Two patients had chemotherapy
(tamoxifen, topotecan) before BBBD chemotherapy and two afterwards. In
general, patients were evaluated with MR imaging every 3 months to monitor
for a response to treatment. The median number of chemotherapy cycles that
were administered by BBBD was 10, mean 10. Three patients also received one,
two, or three cycles of intraarterial chemotherapy without BBBD. One patient
that was started on carboplatin was converted to methotrexate, and five that
were started on the methotrexate protocol were later converted over to
carboplatin. One patient received monthly methotrexate followed by 14 days
of procarbazine and one patient started on methotrexate was switched to
navelbine. MR imaging demonstrated two partial responses, five patients with
stable disease, and one with disease progression. The median time to tumor
progression was 15 months with the range from <1 to 40 months. The median
survival from the time of diagnosis was 27 months, ranging from 7 to 80
months. The median survival time from the first BBBD or intraarterial
treatment was 16.5 months, ranging from 5 to 69 months. One patient was lost
to follow-up with an unknown date of death. Although the sample size is
small, the TTP and survival times are longer than those previously reported
in other DPG series. In addition, the ability to demonstrate stable disease
or partial responses in DPG on MR imaging argues for the therapeutic benefit
of BBBD chemotherapy. The enhanced delivery of chemotherapy afforded by
osmotic BBBD supports the further examination of this treatment modality for
patients with DPG.
PMID: 16314949 [PubMed - as supplied by publisher]
-
-
Brain metastases from apocrine carcinoma of the scalp:
case report.
Shimato
S, Wakabayashi
T, Mizuno
M, Nakahara
N, Hatano
H, Natsume
A, Ishii
D, Hasegawa
Y, Hyodo
I, Nagasaka
T, Yoshida
J.
Department of Neurosurgery, Nagoya University Graduate School of Medicine,
Nagoya, Aichi, Japan.
Apocrine carcinoma is an extremely rare malignant neoplasm that occurs most
frequently in the axilla. Although it usually shows an indolent clinical
course, it often metastasizes to regional lymph nodes and sometimes to lungs
or bones. However, a literature search did not reveal any report describing
the detailed clinical course of brain metastases from apocrine carcinoma. We
report a case of a 54-year-old male who suffered from multiple brain
metastases from apocrine carcinoma that had originated in the scalp 6 years
before. The brain metastases appeared in spite of several regimens of
chemotherapy for lung metastases for two years. The tumor in the right
frontal lobe was successfully operated. However, the small tumor in the
right occipital lobe was not cured by gamma knife surgery, and eventually
required second operation. The operation had contributed to his
neurologically independent life for about one year until he died for gradual
progression of lung metastases. To our knowledge this is the first reported
case of metastatic brain tumor from apocrine carcinoma.
PMID: 16314948 [PubMed - as supplied by publisher]
-
Immunotoxin pharmacokinetics: a comparison of the
anti-glioblastoma bi-specific fusion protein (DTAT13) to DTAT and DTIL13.
Rustamzadeh
E, Vallera
DA, Todhunter
DA, Low
WC, Panoskaltsis-Mortari
A, Hall
WA.
Departments of Neurosurgery, University of Minnesota Cancer Center,
Minneapolis, MN, USA.
DTAT13, a novel recombinant bispecific immunotoxin (IT) consisting of
truncated diphtheria toxin, an amino-terminal (AT) fragment of the
urokinase-type plasminogen activator (uPa), and a fragment of human IL-13
was assembled in order to target receptors on glioblastoma multiforme (GBM)
and its associated neovasculature. Previous in vitro studies confirmed the
efficacy of DTAT13 against various GBM cell lines expressing both IL-13
receptor or uPA receptor, and previous in vivo testing demonstrated the
efficacy of DTAT13 in significantly inhibiting a range of xenograft tumors
and showed that DTAT13 was 160- and 8-fold less toxic to the parental fusion
IT, DTAT and DTIL13, respectively.To further understand the properties of
DTAT13, pharmacokinetic/biodistribution experiments were performed. Binding
analysis revealed that the IL-13 domain functioned independently of the uPA
domain and that the K (d) for each binding domain was essentially the same
as that of DTIL13 and DTAT. Flow cytometry studies indicated that DTAT13
bound better than DTAT or DTIL13. Analysis of the rate of protein synthesis
inhibition in U87 MG cells by DTAT13 compared to DTAT revealed a faster rate
of inhibition with DTAT13 compared to DTAT. The rate of protein synthesis
inhibition of DTAT13 was identical to that of DTIL13 in U373 MG cells.
Intracranial biodistribution studies revealed that DTAT13 was able to cross
to the contralateral hemisphere unlike DTIL13 but similar to DTAT. These
studies show that DTAT13 has properties encompassing those of both DTIL13
and DTAT and warrants further consideration for clinical development.
PMID: 16314943 [PubMed - as supplied by publisher]
-
-
Response to chemotherapy of a radiation-induced
glioblastoma multiforme.
Nicolardi
L, Deangelis
LM.
School of Medicine, Padua University, Padua, Italy.
BACKGROUND: Radiation-induced glioblastoma multiforme (GBM) is particularly
resistant to treatment and therapeutic options are limited. We report a
patient with a radiation-induced GBM who had a complete response to
carmustine and survived for 44 months. PATIENTS AND METHODS: Case report of
a 38-year-old man with a radiation-induced GBM that responded to carmustine.
RESULTS: Our patient developed a left occipital GBM 35 years after a left
cerebellar astrocytoma was treated with surgery and radiation therapy (4500
rad). The GBM was treated with subtotal resection followed by four cycles of
carmustine; a complete response was achieved. He relapsed 34 months after
diagnosis and with further surgery survived 44 months from his diagnosis of
GBM. CONCLUSION: GBMs may be a late complication of radiation treatment for
pediatric brain tumors. If further radiotherapy is not a therapeutic option,
chemotherapy may result in prolonged survival.
PMID: 16314941 [PubMed - as supplied by publisher]..
-
-
The effect of thermotherapy using magnetic nanoparticles
on rat malignant glioma.
Jordan
A, Scholz
R, Maier-Hauff
K, van
Landeghem FK, Waldoefner
N, Teichgraeber
U, Pinkernelle
J, Bruhn
H, Neumann
F, Thiesen
B, von
Deimling A, Felix
R.
Center of Biomedical Nanotechnology (CBN), c/o Department of Radiology, CVK,
Charite - University Medicine, Berlin, Germany.
Thermotherapy using magnetic nanoparticles is a new technique for
interstitial hyperthermia and thermoablation based on magnetic field-induced
excitation of biocompatible superparamagnetic nanoparticles. To evaluate the
potential of this technique for minimally invasive treatment, we carried out
a systematic analysis of its effects on experimental glioblastoma multiforme
in a rat tumor model.Tumors were induced by implantation of RG-2-cells into
the brains of 120 male Fisher rats. Animals were randomly allocated to 10
groups of 12 rats each, including controls. Animals received two
thermotherapy treatments following a single intratumoral injection of two
different magnetic fluids (dextran- or aminosilane-coated iron-oxide
nanoparticles). Treatment was carried out on days four and six after tumor
induction using an alternating magnetic field applicator system operating at
a frequency of 100 kHz and variable field strength of 0-18 kA/m. The
effectiveness of treatment was determined by the survival time of the
animals and histopathological examinations of the brain and the
tumor.Thermotherapy with aminosilane-coated nanoparticles led up to 4.5-fold
prolongation of survival over controls, while the dextran-coated particles
did not indicate any advantage. Intratumoral deposition of the
aminosilane-coated particles was found to be stable, allowing for serial
thermotherapy treatments without repeated injection. Histological and
immunohistochemical examinations after treatment revealed large necrotic
areas close to particle deposits, a decreased proliferation rate and a
reactive astrogliosis adjacent to the tumor.Thus, localized interstitial
thermotherapy with magnetic nanoparticles has an antitumoral effect on
malignant brain tumors. This method is suitable for clinical use and may be
a novel strategy for treating malignant glioma, which cannot be treated
successfully today. The optimal treatment schedules and potential
combinations with other therapies need to be defined in further studies.
PMID: 16314937 [PubMed - as supplied by publisher]
-
-
Improvement of functional outcome after radical surgery
in glioblastoma patients: the efficacy of a navigation-guided fence-post
procedure and neurophysiological monitoring.
Yoshikawa
K, Kajiwara
K, Morioka
J, Fujii
M, Tanaka
N, Fujisawa
H, Kato
S, Nomura
And S, Suzuki
M.
Department of Neurosurgery, Yamaguchi University School of Medicine,
Yamaguchi, Japan.
This retrospective study investigated the functional outcomes of patient
with glioblastoma receiving radical surgery before and after the adoption of
the navigation-guided fence-post (NGFP) procedure and neurophysiological
monitoring. We investigated 42 glioblastoma patients receiving radical
surgery in our institute between 1980 and 2005. Of the 42 patients, 18
patients from 1980 to 1996 (1st term) underwent radical surgery without
navigation system guidance, NGFP, or neurophysiological monitoring; 11
patients from 1997 to 2002 (2nd term) underwent surgery with simple
navigation system guidance but without NGFP procedure or neurophysiological
monitoring, and 13 patients from 2003 to 2005 (3rd term) underwent surgery
with the NGFP procedure and neurophysiological monitoring as appropriate.
There were no significance differences between any of the three term groups
in age, gender, preoperative KPS score, or 'surgical staging for glioma'
according to the difficulty of surgery. The rates of 95% or greater volume
reduction in each term were 38.9%, 54.5% and 76.9%. The rates of morbidity
were 38.9%, 18.1% and 0%. The change in KPS scores (delta KPS) before and
after the perioperative period in each term were -16.1 +/- 6.6SEM, -9.0 +/-
5.8SEM and +8.5 +/- 3.7SEM, respectively. The delta KPS in the 3rd term was
significantly better than those of 1st and 2nd terms (P < 0.01,
Kruskal-Wallis rank test). The rate of patients who were discharged to home
and who resumed daily useful life without assistance was 38.9%, 63.6% and
84.6% in each term, respectively. The mean survival times in each term were
9.9, 14.0 and 16.8 months. The introduction of the NGFP procedure and
neurophysiological monitoring in glioblastoma radical surgery improved the
functional outcome of patients.
PMID: 16314936 [PubMed - as supplied by publisher]
-
-
Topotecan can compensate for protracted radiation
treatment time effects in high grade glioma xenografts( bigstar).
Pinel
S, Chastagner
P, Merlin
JL, Marchal
C, Taghian
A, Barberi-Heyob
M.
Laboratoire de Recherche en Oncologie, Centre A. Vautrin,
Vandoeuvre-les-Nancy, France, pinel.sophie@tiscali.fr.
Purpose: Several studies reported that prolongation of overall treatment
time of fractionated radiotherapy reduces the chance of tumor control. In
the present study, we hypothesize that combining topotecan with irradiation
could compensate for this detrimental time effect on the radioresponse.
Therefore, we investigated the efficiency of different schedules of
topotecan (TPT), radiotherapy (RT) or concomitant combination TPT +
RT.Methods and Materials: Experiments were performed in two human high-grade
glioma xenograft models (U87 and GBM Nan1). TPT and RT were delivered at a
total dose of 3 mg/kg and 40 Gy, respectively. For the TPT + RT groups, TPT
was injected 5 min before radiation. Total radiation doses were delivered in
5, 10, 20, or 30 fractions over 1, 2, 4, or 6 weeks, respectively. The
efficiency of TPT, RT, and TPT + RT was evaluated by tumor growth delay
(TGD).Results: At this low total dose, and independent of the schedule, no
efficacy was found in TPT-treated glioma xenografts. Conversely,
radiotherapy-induced antitumor effect decreased with prolongation of
treatment time. For TPT + RT combination, antitumor activity was not
influenced by schedule, and tumor response was always comparable to those
measured for the shortest and the most efficient irradiation schedule (i.e.
1 week). When treatment was delivered over 4 or 6 weeks in U87 glioma
xenografts, therapeutic enhancement ratios reached 2.6 and 3.7,
respectively. This indicated that the interaction between ionizing radiation
and topotecan was synergistic.Conclusion: The present study demonstrated
that concomitant topotecan can compensate for the detrimental effect of
treatment time protraction on radiotherapy efficacy in two malignant glioma
xenografts.
PMID: 16311843 [PubMed - as supplied by publisher]..
-
-
Mitogenic signal transduction pathways in meningiomas:
novel targets for meningioma chemotherapy?
Johnson
M, Toms
S.
From the Department of Pathology (MJ), University of Tennessee, Graduate
School of Medicine, Knoxville, Tennessee; Brain Tumor Institute (ST), The
Cleveland Clinic Foundation, Cleveland, Ohio.
ABSTRACT: The roles of growth factor receptors and numerous downstream
growth regulatory pathways are of increasing interest in neuro-oncology.
These pathways have been extensively studied in gliomas but only recently
analyzed in meningiomas. This article reviews current research on the growth
factor receptor-Ras-Raf-1-MEK-1-MAPK, PI3K-Akt/PKB, PLC-gamma1-PKC,
phospholipase A2-cyclooxygenase, and TGF-beta receptor-Smad pathways that
appear to regulate meningioma growth and inhibit apoptosis. Sites along
these receptor/kinase cascades that might be targeted by novel therapies are
also discussed.
PMID: 16319713 [PubMed - in process]
-
| 28: Oncogene.
2005 Dec 12; [Epub ahead of print] |
|
-
Identification of genes differentially expressed in
glioblastoma versus pilocytic astrocytoma using Suppression Subtractive
Hybridization.
Colin
C, Baeza
N, Bartoli
C, Fina
F, Eudes
N, Nanni
I, Martin
PM, Ouafik
L, Figarella-Branger
D.
1Laboratoire de Biopathologie de l'Adhesion et de la Signalisation, EA3281,
IPHM, Faculte de Medecine Timone, 13005, Marseille, France.
Glioblastoma (GBM) is a highly malignant glioma, which has the propensity to
infiltrate throughout the brain in contrast to pilocytic astrocytoma (PA) of
the posterior fossa, which does not spread and can be cured by surgery. We
have used Suppression Subtractive Hybridization to define markers that
better delineate the molecular basis of brain invasion and distinguish these
tumor groups. We have identified 106 genes expressed in PA versus GBM and 80
genes expressed in GBM versus PA. Subsequent analysis identified a subset of
20 transcripts showing a common differential expression pattern for the two
groups. GBM differs from PA by the expression of five genes involved in
invasion and angiogenesis: fibronectin, osteopontin, chitinase-3-like-1
(YKL-40), keratoepithelin and fibromodulin. PA differs from GBM by the
expression of genes related to metabolism (apolipoprotein D), proteolysis
(protease-serine-11), receptor and signal transduction (PLEKHB1 for
Pleckstrin-Homology-domain-containing-protein-family-B-member-1),
transcription/translation
(eukaryotic-translation-elongation-factor-1-alpha1) processes and cell
adhesion (SPOCK1 for
SPARC/Osteonectin-CWCV-kazal-like-domains-proteoglycan). The expression of
these genes was confirmed by real-time quantitative RT-PCR and
immunohistochemistry. This study highlights the crucial role of brain
invasion in GBM and identifies specific molecules involved in this process.
In addition, it offers a restricted list of markers that accurately
distinguish PA from GBM.Oncogene advance online publication, 12 December
2005; doi:10.1038/sj.onc.1209305.
PMID: 16314830 [PubMed - as supplied by publisher]
-
|
Volume 4, Number
50 - 6 December 2005