| 1: Am
J Clin Oncol. 2005 Aug;28(4):403-10. |
|
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Role of stereotactic radiosurgery in the treatment of
brain metastases.
Hazard
LJ, Jensen
RL, Shrieve
DC.
Department of Radiation Oncology, Huntsman Cancer Hospital, Salt Lake City,
Utah 84112, USA. lisa.hazard@hci.utah.edu
Stereotactic radiosurgery (SRS) is a highly conformal form of radiation
therapy designed to deliver a high dose in a single treatment to the target
volume while sparing adjacent normal tissues. Its role in the treatment of
brain metastases continues to be defined, but the recently reported RTOG
95-08 trial demonstrated a survival benefit with the addition of SRS to
whole-brain radiation therapy in select patients with a single brain
metastasis, as well as a local control and palliative benefit in select
patients with 1 to 3 brain metastases. The authors review the role of SRS in
the treatment of brain metastases and discuss the use of SRS with or without
whole-brain radiation therapy, optimal dose of SRS, SRS delivery methods,
and selection of appropriate patients for SRS.
PMID: 16062084 [PubMed - in process]
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| 2: Cancer. 2005 Aug 3; [Epub
ahead of print] |
|
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Caspase 8 is absent or low in many ex vivo gliomas.
Ashley
DM, Riffkin
CD, Muscat
AM, Knight
MJ, Kaye
AH, Novak
U, Hawkins
CJ.
Murdoch Children's Research Institute, Parkville, Australia.
BACKGROUND: Better treatments are required urgently for patients with
malignant glioma, which currently is incurable. Death ligands, such as tumor
necrosis factor-related apoptosis-inducing ligand (TRAIL), may offer promise
for the treatment high-grade glioma if such ligands induce apoptotic
signaling in vivo in glioma cells. Caspase 8 is required for death ligand
signaling, and its levels may influence the sensitivity of glioma cells to
death ligands. It also may act as a tumor suppressor protein. The authors
analyzed caspase 8 expression levels in ex vivo glioma specimens and
explored potential mechanisms of its regulation. METHODS: Eleven
glioblastomas, 5 anaplastic astrocytomas, and 3 low-grade astrocytomas were
studied. The levels of caspase 8, caspase 10, cellular FLICE inhibitory
protein (c-FLIP), and signal transducer and activator of transcription
(STAT)-1 were assayed using quantitative immunoblotting. Caspase 8 mRNA was
measured by Northern blot analysis. The methylation status of the caspase 8
gene was determined by bisulfate modification of genomic DNA, cloning, and
sequencing. Statistical analyses were performed using nonparametric
(Spearman) correlations. RESULTS: Some ex vivo glioma samples lacked
detectable caspase 8, with many expressing barely detectable levels. No
tumors expressed significant amounts of caspase 10 or c-FLIP. A strong
association was found between caspase 8 mRNA and protein levels. Neither
expression of the transcription factor STAT-1 nor caspase 8 gene methylation
correlated with caspase 8 levels. CONCLUSIONS: The absence of caspase 8
protein in many resected glioma samples implied that many patients with
glioma may not benefit from death ligand-based treatments, unless caspase 8
(or caspase 10) protein expression can be elevated. Demethylating agents are
unlikely to boost caspase 8 levels in glioma cells, but treatments that
increase caspase 8 mRNA levels may up-regulate expression of the protein.
Cancer 2005. (c) 2005 American Cancer Society.
PMID: 16080161 [PubMed - as supplied by publisher]
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| 3: Cancer. 2005 Aug 2; [Epub
ahead of print] |
|
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Phase 1 study of concurrent RMP-7 and carboplatin with
radiotherapy for children with newly diagnosed brainstem gliomas.
Packer
RJ, Krailo
M, Mehta
M, Warren
K, Allen
J, Jakacki
R, Villablanca
JG, Chiba
A, Reaman
G.
Division of Neurology, Children's National Medical Center, Washington, DC.
BACKGROUND: Ninety percent of children with diffuse intrinsic brainstem
tumors will die within 18 months of diagnosis. Radiotherapy is of transient
benefit, and one way to potentially improve its efficacy is to add
radiosensitizers. Carboplatin is antineoplastic and radiosensitizing.
However, delivery to the primary tumor site is problematic. RMP-7 is a
bradykinin analog that causes selective permeability of the
blood-brain-tumor interface. The goal of the current Phase I study was to
determine the toxicity and feasibility of delivering RMP-7 and carboplatin
for 5 successive days during radiotherapy. METHODS: RMP-7 was given before
the end of carboplatin infusion. Local radiotherapy (5940 centigrays) was
given within 4 hours of completion of drug delivery. Duration of treatment
was escalated in a stepwise, weekly fashion, in cohorts of 3, until there
was treatment-limiting toxicity or until radiotherapy was completed.
Thirteen patients were treated, whose median age was 7 years (range, 3-14
yrs). RESULTS: One child died early in treatment of progressive disease and
was not assessable for toxicity. Treatment for 3, 4, or 5 weeks was
tolerated well, with mild flushing, tachycardia, nausea, emesis, dizziness,
and abdominal pain. Of 3 children treated at the full duration of therapy
(33 doses over 7 wks), 1 developed dose-limiting hepatotoxicity and
neutropenia. The estimated median survival period was 328 days, and 1
patient remained disease progression free > 400 days from initiation of
treatment. CONCLUSIONS: The results of the current study confirmed the
feasibility of giving RMP-7 and carboplatin daily during radiotherapy.
Cancer 2005. (c) 2005 American Cancer Society.
PMID: 16078267 [PubMed - as supplied by publisher]
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| 4: Cancer Res. 2005 Aug
1;65(15):6850-7. |
|
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Brain tumor oncolysis with replication-conditional herpes
simplex virus type 1 expressing the prodrug-activating genes, CYP2B1 and
secreted human intestinal carboxylesterase, in combination with
cyclophosphamide and irinotecan.
Tyminski
E, Leroy
S, Terada
K, Finkelstein
DM, Hyatt
JL, Danks
MK, Potter
PM, Saeki
Y, Chiocca
EA.
Molecular Neuro-oncology Laboratories, Neurosurgery Service and
Biostatistics Center, Massachusetts General Hospital, Charlestown,
Massachusetts, USA.
The treatment of malignant glioma is currently ineffective. Oncolytic
viruses are being explored as a means to selectively lyse tumor cells in the
brain. We have engineered a mutant herpes simplex virus type 1 with
deletions in the viral UL39 and gamma(1)34.5 genes and an insertion of the
two prodrug activating genes, CYP2B1 and secreted human intestinal
carboxylesterase. Each of these can convert the inactive prodrugs,
cyclophosphamide and irinotecan (CPT-11), into their active metabolites,
respectively. This new oncolytic virus (MGH2) displays increased antitumor
efficacy against human glioma cells both in vitro and in vivo when combined
with cyclophosphamide and CPT-11. Importantly, cyclophosphamide, CPT-11, or
the combination of cyclophosphamide and CPT-11 does not significantly affect
oncolytic virus replication. Therefore, MGH2 provides effective multimodal
therapy for gliomas in preclinical models when combined with these
chemotherapy agents.
PMID: 16061668 [PubMed - in process]
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| 5: Cancer Res. 2005 Aug
1;65(15):6726-33. |
|
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Novel tumor-specific isoforms of BEHAB/brevican
identified in human malignant gliomas.
Viapiano
MS, Bi
WL, Piepmeier
J, Hockfield
S, Matthews
RT.
Department of Neurobiology and Neurosurgery, Yale University School of
Medicine, New Haven, Connecticut 06520, USA.
Malignant gliomas are deadly brain tumors characterized by diffuse invasion
into the surrounding brain tissue. Understanding the mechanisms involved in
glioma invasion could lead to new therapeutic strategies. We have previously
shown that BEHAB/brevican, an extracellular matrix protein in the central
nervous system, plays a role in the invasive ability of gliomas. The
mechanisms that underlie BEHAB/brevican function are not yet understood, due
in part to the existence of several isoforms that may have different
functions. Here we describe for the first time the expression of
BEHAB/brevican in human brain and characterize two novel glioma-specific
isoforms, B/b(sia) and B/b(Deltag), which are generated by differential
glycosylation and are absent from normal adult brain and other
neuropathologies. B/b(sia) is an oversialylated isoform expressed by about
half the high- and low-grade gliomas analyzed. B/b(Deltag) lacks most of the
carbohydrates typically present on BEHAB/brevican and is the major
up-regulated isoform of this protein in high-grade gliomas but is absent in
a specific subset of low-grade, indolent oligodendrogliomas. B/b(Deltag) is
detected on the extracellular surface, where it binds to the membrane by a
mechanism distinct from the other BEHAB/brevican isoforms. The
glioma-specific expression of B/b(Deltag), its restricted membrane
localization, and its expression in all high-grade gliomas tested to date
suggest that it may play a significant role in glioma progression and make
it an important new potential therapeutic target. In addition, its absence
from benign gliomas prompts its use as a diagnostic marker to distinguish
primary brain tumors of similar histology but different pathologic course.
PMID: 16061654 [PubMed - in process]
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| 6: Childs
Nerv Syst. 2005 Aug 3; [Epub ahead of print] |
|
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Craniopharyngioma: the pendulum of surgical management.
Sainte-Rose
C, Puget
S, Wray
A, Zerah
M, Grill
J, Brauner
R, Boddaert
N, Pierre-Kahn
A.
Service de Neurochirurgie Pediatrique, Hopital Necker Enfants Malades, 149
rue de Sevres, 75015, Paris, France,
christian.sainte-rose@nck.ap-hop-paris.fr.
BACKGROUND: For a long time, craniopharyngiomas have been considered
surgically attractive tumours. The fact that they are rare, histologically
benign, and located in a challenging (but considered accessible) area made
them worthy surgical prizes. METHODS: As we have saved vision and
"cured" many of these tumours, the insidious and devastating
effects on quality of life for these children has become evident.
DISCUSSION: The state-of-the-art in the surgical management of
craniopharyngioma is now turning to multi-modality treatment strategies
(combination surgery and radiotherapy) aiming to limit morbidity. Questions
remain-what factors influence our surgical decision making? Do we understand
the long-term effects of the radiotherapy now being employed? We review a
series of craniopharyngiomas looking for variables that correlated with
outcome as perceived in terms of quality of life and we review briefly the
history of craniopharyngioma surgery and the relevant literature.
PMID: 16078079 [PubMed - as supplied by publisher]
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| 7: Childs
Nerv Syst. 2005 Aug 3; [Epub ahead of print] |
|
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Imaging of craniopharyngioma.
Curran
JG, O'connor
E.
Department of Medical Imaging, Children's Memorial Hospital, 2300 Children's
Plaza, Chicago, IL, 60614, USA, jcurran@childrensmemorial.org.
BACKGROUND: Craniopharyngiomas are present with a wide range of appearances,
but the existence of cysts, calcification, and enhancement in a suprasellar
tumor strongly favors the diagnosis. DISCUSSION: There is a significant
differential diagnosis that must be considered. The pre- and postoperative
imaging of craniopharyngioma is reviewed.
PMID: 16078078 [PubMed - as supplied by publisher]
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| 8: Childs
Nerv Syst. 2005 Jun 18; [Epub ahead of print] |
|
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Longitudinal study on quality of life in 102 survivors of
childhood craniopharyngioma.
Muller
HL, Bruhnken
G, Emser
A, Faldum
A, Etavard-Gorris
N, Gebhardt
U, Kolb
R, Sorensen
N.
Department of Paediatrics, Zentrum fur Kinder- und Jugendmedizin, Klinikum
Oldenburg GmbH, Oldenburg, Germany.
OBJECTS: We longitudinally analysed functional capacity and quality of life
(QoL) in 102 patients with a childhood craniopharyngioma during follow-up.
METHODS: The Fertigkeitenskala Munster-Heidelberg (FMH) ability scale was
used for QoL assessment. Multivariate analysis evaluated FMH scores at
various time points, examining hypothalamus involvement (HI), body mass
index (BMI), degree of resection, tumour progression, relapse and
irradiation. RESULTS AND CONCLUSION: Patients without HI (n=60)
self-assessed higher QoL at baseline (p=0.001) and follow-up (p<0.001)
than patients with HI (n=42). Only patients without HI evaluated at baseline
>12 months after diagnosis showed longitudinal improvement in FMH scores
(p=0.040). Rates of incomplete resection and irradiation were higher
(p=0.070 and p=0.002 respectively) in patients with HI. In multivariate
analysis, only HI, tumour relapse, progression, baseline FMH score, and time
between diagnosis and baseline evaluation had independent impact on QoL. HI,
tumour progression, and relapse had long-term QoL affects-most notably,
severe obesity.
PMID: 16075216 [PubMed - as supplied by publisher]
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| 9: Childs
Nerv Syst. 2005 Jun 17; [Epub ahead of print] |
|
-
Radiation therapy in the management of pediatric
craniopharyngiomas-a review.
Kalapurakal
JA.
Division of Radiation Oncology, Robert H. Lurie Comprehensive Cancer Center,
Children's Memorial Hospital, Northwestern University, Chicago, IL, USA.
Craniopharyngiomas are benign suprasellar tumors that arise from epithelial
remnants of the Rathke's pouch. The two standard treatment options are
primary total resection or limited surgery followed by external beam
radiation. The 10- and 20-year progression-free survival rates following
limited surgery and radiation therapy are superior to those achieved by
primary surgery alone. The side effect profiles for these two treatment
approaches are different. Following total resection there is a very high
incidence of panhypopituitarism requiring lifelong multiple hormone
replacement therapy. The other side effects include potential damage to
adjacent structures such as optic chiasm, vasculature and hypothalamus.
Following limited surgery and radiation therapy the incidence of endocrine
deficits is significantly lower compared to radical surgery, as is the risk
of neurovascular and hypothalamic injury. Optic neuropathy and brain
necrosis are rare in modern radiation therapy series. Second malignant
neoplasms, although rare, can occur. In children with recurrent
craniopharyngiomas following radical surgery, the recommended salvage
treatment is radiation therapy, as further surgical attempts at salvage are
associated with high relapse rates and increased morbidity and mortality.
There have been significant technological advances in the field of radiation
treatment planning and delivery that have great potential for reducing the
incidence of long-term irradiation sequelae in the developing brain. The
general availability of megavoltage linear accelerators and modern
radiotherapy innovations such as three-dimensional conformal radiation
treatment (3D CRT), stereotactic radiosurgery (SRS), stereotactic
radiotherapy (SRT), and intensity modulated radiation therapy (IMRT) should
further limit the rate of complications and improve cure rates in children
with primary or recurrent craniopharyngioma.
PMID: 16075214 [PubMed - as supplied by publisher]
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| 10: Childs
Nerv Syst. 2005 Jul 30; [Epub ahead of print] |
|
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Origin of craniopharyngiomas: implication on the growth
pattern.
Wang
KC, Hong
SH, Kim
SK, Cho
BK.
Division of Pediatric Neurosurgery, Seoul National University Children's
Hospital, 28 Yongon-dong, Chongno-gu, Seoul 110-744, South Korea,
kcwang@snu.ac.kr.
BACKGROUND: The surgical management of craniopharyngiomas has been among the
most challenging neurosurgical procedures because of their complex
topographical relationship with surrounding structures and high recurrence
rate after subtotal resection. Craniopharyngiomas have been classified only
by their location to determine an appropriate surgical approach without due
regard to other factors that could affect the surgical results, such as the
extent of adhesion to surrounding structures or the nature of the tumor.
METHODS: We describe the role of the diaphragm sellae on the growth patterns
of craniopharyngiomas from surgical experiences and pathological evidences,
suggesting the classification of craniopharyngiomas into three categories by
the level of origin and the competence of the diaphragm sellae: a tumor of
subdiaphragmatic origin with competent diaphragm sellae, subdiaphragmatic
with incompetent diaphragm sellae, and supradiaphragmatic. DISCUSSION:
Tumors in each category have shown peculiar topographical relationship with
the optic chiasm, third ventricle, and also adhesion extents. The nature of
the tumor itself, e.g., the composition of cystic and solid parts, may bring
additional minor variations to the topographical features of a
craniopharyngioma, but will maintain the major characteristics determined by
its level of origin and competence of the diaphragm sellae. CONCLUSION: This
classification scheme, which considers the origin level, is clinically
relevant and useful because optimal surgical approaches could be designed by
considering multiple factors affecting surgical procedure and outcome,
including the expected extent of adhesion and preferred sites of recurrence,
as well as the topographical location of the tumor. In subdiaphragmatic
tumors, which correspond to intrasellar and prechiasmatic tumors, a
transsphenoidal approach could be reasonably attempted even with
considerable suprasellar extensions because they tend to adhere to the
intrasellar structures, and the superior surface of the tumor may be easily
separated from the brain structures by pulling. Supradiaphragmatic tumors,
however, may need a wider surgical approach that can provide direct vision
of the tumor because of possible extensive adhesion.
PMID: 16059733 [PubMed - as supplied by publisher]
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| 11: Clin
Cancer Res. 2005 Aug 1;11(15):5639-44. |
|
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Cooperative Antitumor Effect of Multitargeted Kinase
Inhibitor ZD6474 and Ionizing Radiation in Glioblastoma.
Damiano
V, Melisi
D, Bianco
C, Raben
D, Caputo
R, Fontanini
G, Bianco
R, Ryan
A, Bianco
AR, De
Placido S, Ciardiello
F, Tortora
G.
Authors' Affiliations: Cattedra di Oncologia Medica, Dipartimento di
Endocrinologia e Oncologia Molecolare e Clinica, Universita di Napoli
Federico II.
PURPOSE: Glioblastoma multiforme is an aggressive disease in which vascular
endothelial growth factor (VEGF) and the EGF receptor (EGFR) are implicated
in tumor growth, relapse, and resistance to radiotherapy and chemotherapy.
The VEGF receptors VEGFR-1 (flt-1) and VEGFR-2 (KDR), typically present on
endothelial cells, have also been identified in human glioblastoma tissues
and cell lines. In addition, EGFR is dysregulated in the majority of human
glioblastomas and EGFR overexpression correlates with shorter survival. We
have investigated the antitumor and antiangiogenic effect of ZD6474, an
inhibitor of both VEGFR and EGFR signaling as a single agent and in
combination with ionizing radiation.EXPERIMENTAL DESIGN: We have used ZD6474
and/or ionizing radiation in human glioblastoma cell lines D54 and U251 in
vitro and in nude mice bearing established xenografts. The effects of
treatment on tumor blood vessels and protein expression were evaluated by
Western blot and immunohistochemistry.RESULTS: As single agents, ionizing
radiation and ZD6474 caused a dose-dependent inhibition of soft agar growth
in D54 and U251 cell lines, whereas a cooperative effect was obtained in
combination. Treatment of mice bearing D54 xenografts with either ZD6474 or
radiotherapy alone caused tumor growth inhibition that was reversible upon
treatment cessation. A cooperative and long-lasting inhibition of tumor
growth was obtained with ZD6474 in combination with concomitant
radiotherapy. The antiproliferative effect was accompanied by inhibition of
VEGF protein expression and inhibition of angiogenesis as measured by vessel
counting.CONCLUSION: This study shows the antitumor activity of ZD6474 in
combination with ionizing radiation in glioblastoma both in vitro and in
vivo, and provides a scientific rationale to evaluate ZD6474 alone or in
combination with radiotherapy in patients affected by this disease.
PMID: 16061883 [PubMed - in process]
-
| 12: Clin
Cancer Res. 2005 Aug 1;11(15):5515-5525. |
|
-
Dendritic Cell Vaccination in Glioblastoma Patients
Induces Systemic and Intracranial T-cell Responses Modulated by the Local
Central Nervous System Tumor Microenvironment.
Liau
LM, Prins
RM, Kiertscher
SM, Odesa
SK, Kremen
TJ, Giovannone
AJ, Lin
JW, Chute
DJ, Mischel
PS, Cloughesy
TF, Roth
MD.
Authors' Affiliations: Division of Neurosurgery, Departments of Surgery,
Medicine, Pathology and Laboratory Medicine, and Neurology, The Brain
Research Institute, and The Jonsson Comprehensive Cancer Center, David
Geffen School of Medicine at University of California at Los Angeles,
University of California Los Angeles, Los Angeles, California.
PURPOSE: We previously reported that autologous dendritic cells pulsed with
acid-eluted tumor peptides can stimulate T cell-mediated antitumor immune
responses against brain tumors in animal models. As a next step in vaccine
development, a phase I clinical trial was established to evaluate this
strategy for its feasibility, safety, and induction of systemic and
intracranial T-cell responses in patients with glioblastoma
multiforme.EXPERIMENTAL DESIGN: Twelve patients were enrolled into a
multicohort dose-escalation study and treated with 1, 5, or 10 million
autologous dendritic cells pulsed with constant amounts (100 mug per
injection) of acid-eluted autologous tumor peptides. All patients had
histologically proven glioblastoma multiforme. Three biweekly intradermal
vaccinations were given; and patients were monitored for adverse events,
survival, and immune responses. The follow-up period for this trial was
almost 5 years.RESULTS: Dendritic cell vaccinations were not associated with
any evidence of dose-limiting toxicity or serious adverse effects. One
patient had an objective clinical response documented by magnetic resonance
imaging. Six patients developed measurable systemic antitumor CTL responses.
However, the induction of systemic effector cells did not necessarily
translate into objective clinical responses or increased survival,
particularly for patients with actively progressing tumors and/or those with
tumors expressing high levels of transforming growth factor beta(2)
(TGF-beta(2)). Increased intratumoral infiltration by cytotoxic T cells was
detected in four of eight patients who underwent reoperation after
vaccination. The magnitude of the T-cell infiltration was inversely
correlated with TGF-beta(2) expression within the tumors and positively
correlated with clinical survival (P = 0.047).CONCLUSIONS: Together, our
results suggest that the absence of bulky, actively progressing tumor,
coupled with low TGF-beta(2) expression, may identify a subgroup of glioma
patients to target as potential responders in future clinical investigations
of dendritic cell-based vaccines.
PMID: 16061868 [PubMed - as supplied by publisher]
-
| 13: Clin
Cancer Res. 2005 Aug 1;11(15):5370-80. |
|
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Vitamin D3 Metabolism in Human Glioblastoma Multiforme:
Functionality of CYP27B1 Splice Variants, Metabolism of Calcidiol, and
Effect of Calcitriol.
Diesel
B, Radermacher
J, Bureik
M, Bernhardt
R, Seifert
M, Reichrath
J, Fischer
U, Meese
E.
Authors' Affiliations: Institut fur Humangenetik, Theoretische Medizin.
PURPOSE: A better understanding of the vitamin D(3) metabolism is required
to evaluate its potential therapeutic value for cancers. Here, we set out to
contribute to the understanding of vitamin D(3) metabolism in glioblastoma
multiforme.EXPERIMENTAL DESIGN: We did nested touchdown reverse
transcription-PCR (RT-PCR) to identify CYP27B1 splice variants and real-time
RT-PCR to quantify the expression of CYP27B1. A cell line was treated with
calcitriol to determine the effect on the expression of CYP27B1,
1alpha,25-dihydroxyvitamin D(3)-24-hydroxylase (CYP24), and vitamin D(3)
receptor (VDR). We generated three antibodies for the specific detection of
CYP27B1 and splice variants. High-performance TLC was done to determine the
endogenous CYP27B1 activity and the functionality of CYP27B1 splice
variants. Using WST-1 assay, we determined the effect of vitamin D(3)
metabolites on proliferation.RESULTS: We report a total of 16 splice
variants of CYP27B1 in glioblastoma multiforme and a different expression of
CYP27B1 and variants between glioblastoma multiforme and normal tissues. We
found preliminary evidence for enzymatic activity of endogenous CYP27B1 in
glioblastoma multiforme cell cultures but not for the functionality of the
splice variants. By adding calcitriol, we found a proliferative effect for
some cell lines depending on the dose of calcitriol. The administration of
calcitriol led to an elevated expression of CYP27B1 and CYP24 but left the
expression of the VDR unaltered.CONCLUSIONS: Our findings show that
glioblastoma multiforme cell lines metabolize calcidiol. In addition, we
show various effects mediated by calcitriol. We found a special vitamin D(3)
metabolism and mode of action in glioblastoma multiforme that has to be
taken into account in future vitamin D(3)-related therapies.
PMID: 16061850 [PubMed - in process]
-
| 14: Int
J Cancer. 2005 Sep 1;116(3):479-86. |
|
-
Novel platinum(IV) complexes induce rapid tumor cell
death in vitro.
Kaludjerovic
GN, Miljkovic
D, Momcilovic
M, Djinovic
VM, Stojkovic
MM, Sabo
TJ, Trajkovic
V.
Faculty of Chemistry, University of Belgrade, Belgrade, Serbia and
Montenegro.
The anticancer activity of platinum complexes has been known since the
discovery of classical Pt(II)-based drug cisplatin. However, Pt(IV)
complexes have greater inertness than corresponding Pt(II) complexes, thus
allowing the oral administration and reducing the toxicity associated with
platinum-based chemotherapy. Here, we describe the in vitro antitumor
activity of some novel Pt(IV)-based agents against mouse fibrosarcoma L929
cells and human astrocytoma U251 cells. The cytotoxicity of 2 Pt(IV)
complexes with bidentate ethylenediamine-N,N'-di-3-propanoato esters was
found to be markedly higher than that of their Pt(II) counterparts and
comparable to the antitumor action of cisplatin. In contrast to cisplatin,
which caused oxidative stress-independent apoptotic cell death of tumor
cells, these Pt(IV) complexes induced oxygen radical-mediated tumor cell
necrosis. Importantly, the cytotoxic action of novel Pt(IV) complexes was
markedly more rapid than that of cisplatin, indicating their potential
usefulness in anticancer therapy.
PMID: 15818622 [PubMed - indexed for MEDLINE]
-
| 15: J
Clin Oncol. 2005 Jun 20;23(18):4225-6. |
|
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CNS manifestations of malignancies: case 1. Conjunctival
relapse of acute lymphoblastic leukemia heralding pituitary and CNS disease.
Hon
C, Law
RW, Shek
TW, Au
WY.
Department of Opthalmology, Prince of Wales Hospital, Hong Kong.
Publication Types:
PMID: 15961769 [PubMed - indexed for MEDLINE]
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| 16: J Neurooncol.
2005 Aug;74(1):93-5. |
|
-
CHEK2 mutations in primary glioblastomas.
Sallinen
SL, Konen
T, Haapasalo
H, Schleutker
J.
Department of Pediatrics, Genetics Clinic, Tampere University Hospital, P.O.
Box 2000, FIN-33521, Tampere, Finland, satu.sallinen@uta.fi.
PMID: 16078115 [PubMed - in process]
-
| 17: J Neurooncol.
2005 Aug;74(1):87-90. |
|
-
Instability of mitochondrial DNA and MRI and clinical
correlations in malignant gliomas.
Montanini
L, Regna-Gladin
C, Eoli
M, Albarosa
R, Carrara
F, Zeviani
M, Bruzzone
MG, Broggi
G, Boiardi
A, Finocchiaro
G.
Unit of Biochemistry and Genetics, Istituto Nazionale Neurologico Besta
Milan, Italy, finocchiaro@istituto-besta.it.
Mutations and instability of mitochondrial DNA (mtDNA) are frequent in
tumors but their pathogenic relevance is not established. To assess their
role in the clinical management of malignant gliomas we have studied the D
loop of mtDNA in 42 such tumors. Alterations were found in 36 of the cases.
The MRI and the clinical follow-up of these patients suggest that these
mutations are not associated with increased aggressiveness. mtDNA could be
amplified from post-surgical tumor cavities in patients undergoing a
loco-regional treatment. These results imply that mtDNA mutations are
unlikely to play a role in diagnostic or prognostic evaluations of
gliomas:their detection, however, could be of use for the clinical follow-up
of malignant gliomas.
PMID: 16078113 [PubMed - in process]
-
| 18: J Neurooncol.
2005 Aug;74(1):77-86. |
|
-
HER1/EGFR tyrosine kinase inhibitors for the treatment of
glioblastoma multiforme.
Study
JJ.
Feinberg School of Medicine, Northwestern University, Abbott Hall, Room
1123, 710 North Lake Shore Drive, Chicago, IL, 60611, USA, Jraizer@nmff.org.
Glioblastoma multiforme (GBM) is a highly malignant brain tumor with limited
therapeutic options, a high recurrence rate and mortality. Standard therapy
is maximal surgical resection and radiotherapy (RT). Recent data suggest
combining temozolomide with RT is better than RT alone. Adjuvant
chemotherapy has a modest impact on survival. For relapsed patients there is
no standard therapy, but options include chemotherapeutic agents or new
agents in development. One approach to improve outcome is using targeted
agents that interfere with cell-surface receptors or intracellular signaling
pathways. Between 40% and 50% of GBM tumors show HER1/EGFR dysregulation,
and almost half co-express the constitutively active mutant receptor subtype
EGFRvIII, which may contribute to the aggressive and refractory course of
GBM. Numerous studies show a relationship between aberrant HER1/EGFR biology
and tumorigenicity in GBM cells. Two available HER1/EGFR tyrosine kinase
inhibitors (TKIs) are gefitinib (Iressa(R)) and erlotinib (Tarcevatrade
mark); both show antitumor and radiosensitization effects in vitro and in
animal models of GBM. Clinical trials in patients with GBM and other gliomas
are ongoing. Preliminary and published results from trials of gefitinib in
recurrent GBM show no increased time to progression or overall survival (OS)
compared with historical controls. Studies with erlotinib show greater
antitumor activity in patients with GBM than with gefitinib, although the
impact of both agents on OS remains unclear. GBM treatment with HER1/EGFR
TKIs alone or combined with other targeted therapies and conventional
modalities deserve further investigation and refinement, as does our
understanding of their mechanisms of action and the role of genetics.
PMID: 16078112 [PubMed - in process]
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| 19: J Neurooncol.
2005 Aug;74(1):43-5. |
|
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Sylvian meningioma without dural attachment in an adult.
Chang
JH, Kim
JA, Chang
JW, Park
YG, Kim
TS.
Department of Neurosurgery, Brain Research Institute, and BK21 Project for
Medical Sciences, Yonsei University College of Medicine, 134 Shinchon-dong,
Seodaemun-gu, Seoul, Korea, ygpark@yumc.yonsei.ac.kr.
This paper presents a rare case of a sylvian meningioma in a 35-year-old
male. The patient visited our hospital because of a 10-year history of
simple partial seizures. Magnetic resonance imaging revealed a 3.5-cm,
well-circumscribed, homogenously enhanced, circular mass without dural
attachments in the left insular region. The tumor was not stained on
angiogram. The tumor was located in the extra-axial space of the sylvian
fissure without any dural attachment, and was strongly attached to the
middle cerebral artery. The tumor was excised, and a histological diagnosis
of a transitional meningioma without a malignancy was made. A Sylvian
meningioma without dural attachment is quite rare, and a preoperative
differentiation of this lesion is generally difficult. This paper discusses
the characteristics and possible pathogenesis of meningiomas without a dural
detachment.
PMID: 16078106 [PubMed - in process]
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| 20: J Neurooncol.
2005 Aug;74(1):31-40. |
|
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Cannabinoids selectively inhibit proliferation and induce
death of cultured human glioblastoma multiforme cells.
Allister
SD, Chan
C, Taft
RJ, Luu
T, Abood
ME, Moore
DH, Aldape
K, Yount
G.
California Pacific Medical Center Research Institute, 475 Brannan St., Suite
220, San Francisco, CA, 94107, USA, mcallis@sutterhealth.org.
Normal tissue toxicity limits the efficacy of current treatment modalities
for glioblastoma multiforme (GBM). We evaluated the influence of
cannabinoids on cell proliferation, death, and morphology of human GBM cell
lines and in primary human glial cultures, the normal cells from which GBM
tumors arise. The influence of a plant derived cannabinoid agonist,
Delta(9)-tetrahydrocannabinol Delta(9)-THC), and a potent synthetic
cannabinoid agonist, WIN 55,212-2, were compared using time lapse
microscopy. We discovered that Delta(9)-THC decreases cell proliferation and
increases cell death of human GBM cells more rapidly than WIN 55,212-2.
Delta(9)-THC was also more potent at inhibiting the proliferation of GBM
cells compared to WIN 55,212-2. The effects of Delta(9)-THC and WIN 55,212-2
on the GBM cells were partially the result of cannabinoid receptor
activation. The same concentration of Delta(9)-THC that significantly
inhibits proliferation and increases death of human GBM cells has no
significant impact on human primary glial cultures. Evidence of selective
efficacy with WIN 55,212-2 was also observed but the selectivity was less
profound, and the synthetic agonist produced a greater disruption of normal
cell morphology compared to Delta(9)-THC.
PMID: 16078104 [PubMed - in process]
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| 21: J Neurooncol.
2005 Aug;74(1):19-30. |
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Techniques to assess the proliferative potential of brain
tumors.
Quinones-Hinojosa
A, Sanai
N, Smith
JS, McDermott
MW.
Department of Neurological Surgery, University of California, San Francisco,
505 Parnassus Avenue, Moffitt Hospital Room M779, Box 0112, San Francisco,
CA, 94143-0112, USA, quinones@post.harvard.edu.
Assessment of brain tumor proliferative potential provides important
prognostic information that supplements standard histopathologic grading.
Many laboratories rely on mitotic figures to quantify the proliferative
potential of brain tumors, but this conventional cellular proliferative
index is subject to inter-observer variability and not consistently
predictive for low-and high-grade tumors. Recent advancements in technology
have made it possible to use proliferative indices as a standard supplement
in pathology laboratories. Non-invasive tumor tissue measurements of cell
proliferation can be performed using- bromodeoxyuridine labeling index (BrdU
LI), flow cytometry (FCM), MIB-1 antibody to the Ki-67 antigen (MIB-1),
proliferating cell nuclear antigen (PCNA), and argyrophilic nucleolar
organizing regions (AgNOR). Each of these assays has been described in the
literature with respect to its ability to predict tumor grade or outcome. At
the present time MIB-1 and AgNOR are the simplest and most reliable of these
techniques. In addition, advances in our understanding of the genetic
alterations associated with proliferation promise to provide more specific
markers of proliferative potential. Beyond the pathology laboratory,
radiographic studies such as positron emission tomography (PET), single
photon emission computed tomography (SPECT), and most recently magnetic
resonance spectroscopy (MRS) have been used as follow-up measures, assessing
response to treatment and tumor recurrence, rather than as predictors of
response to treatment. These radiographic tools, however, have the potential
to provide an assessment of tumor proliferation without the need for
invasive measures. In this article, we present a review of the current
techniques utilized to understand the proliferative potential of brain
tumors.
PMID: 16078103 [PubMed - in process]
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| 22: J Neurooncol.
2005 Aug;74(1):9-17. |
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An experimental study of dendritic cells-mediated
immunotherapy against intracranial gliomas in rats.
Zhu
X, Lu
C, Xiao
B, Qiao
J, Sun
Y.
Institute of Neurology, Huashan Hospital, Fudan University, Shanghai,
200040, China, zhu_xinmei@yahoo.com.cn.
Object: To investigate the effect of dendritic cells(DC) pulsed with
apoptotic tumor cells for treatment of intracranial gliomas in rats.
Methods: C6 glioma cells were injected into brain of Wistar rats under
stereotactic monitor to establish an animal model of glioma. The precursors
of DCs were isolated from bone marrow of rats, stimulated in vitro with
recombinent rat granulocyte-macrophage colony-stimulating factor (rrGM-CSF)
and interleukin-4 (rrIL-4). These DCs were then pulsed ex vivo with
apoptotic C6 glioma cells induced by heating and subsequently injected
subcutaneously into rats harboring intracranial C6 glioma. Rats were treated
with five weekly subcutaneous injections of either control media, unpulsed
DCs, or DCs pulsed with apoptotic tumor cells. The animals were followed for
survival, volume of tumor by MRI, CD8 + T cells, cytotoxicity assay in vitro
and proliferational function of lymphocytes in peripheral blood were
determined by flow cytometry(FCM). The concentration of cytokines
interferon-gamma (IFN-gamma) and interleukin-10(IL-10) were monitored
through enzyme-linked immunosorbent assay(ELISA) using ELISAkit. Results:
Our results indicated that C6 glioma model rats treated with apoptotic tumor
cells pulsed DCs prolonged survival, inhibited the tumor growth and
increased the level of CD8 + T lymphocytes in peripheral blood comparing
with control group. Cytotoxicity assay suggested that vaccination with these
apoptotic cells pulsed DCs can induce cytotoxic T lymphocytes response
against C6 tumor cells compared with control group. Furthermore,
significantly enhanced IFN-gamma and reduced IL-10(even undetectable) were
observed in peripheral blood of rats treated with pulsed-DCs. No evident
autoimmune response were detected. Conclusions: Our data demonstrated that
systemic vaccination with DCs pulsed with apoptotic cells is a safe and
effective immunotherapy for intracranial glioma.
PMID: 16078102 [PubMed - in process]
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| 23: Neurology. 2004 Nov
23;63(10):1813-7. |
|
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Epileptic activity influences the lateralization of
mesiotemporal fMRI activity.
Janszky
J, Ollech
I, Jokeit
H, Kontopoulou
K, Mertens
M, Pohlmann-Eden
B, Ebner
A, Woermann
FG.
Bethel Epilepsy Center, Mara Hospital, Bielefeld, Germany.
OBJECTIVE: To identify clinical factors contributing to the lateralization
of mesiotemporal memory functions in epilepsy by using memory-activated
fMRI. METHODS: Sixty patients aged 16 to 63 years with mesial temporal lobe
epilepsy (MTLE) and 20 patients aged 16 to 60 years with extratemporal
epilepsy (ETE) due to circumscribed epileptogenic lesions who consecutively
underwent presurgical evaluation including continuous video-EEG monitoring
and structural MRI examinations were examined. During memory fMRI, the
activation condition consisted of retrieval from long-term memory induced by
self-paced performance of an imaginative walk through the patient's
hometown. On the basis of a previous study, memory lateralization was
defined as typical if larger fMRI activation was in the mesiotemporal
structures contralateral to the epileptic focus. RESULTS: There were 45
patients with MTLE who had typical memory lateralization (75%), whereas only
9 patients (45%) with ETE exhibited typical memory lateralization (p =
0.013). In MTLE patients, bilateral independent epileptiform discharges
occurred more often in the atypical group than in patients with typical
memory lateralization (p = 0.015). CONCLUSIONS: The fMRI lateralization of
mesiotemporal visuospatial memory functions in patients with mesiotemporal
lobe epilepsy (MTLE) is asymmetric: The larger activation usually appears
contralateral to the side of the epileptogenic region. These findings occur
more often in MTLE; in patients with extratemporal epilepsy, such type of
asymmetry is not characteristic. In MTLE patients with bilateral independent
epileptiform discharges, this type of asymmetry is also less frequent.
PMID: 15557495 [PubMed - indexed for MEDLINE]
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Volume 4, Number 33 - 9 August 2005