| 1: Cancer. 2004 Nov 24; [Epub ahead of print] |
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Role of temozolomide after radiotherapy for newly
diagnosed diffuse brainstem glioma in children.
Broniscer A, Iacono L, Chintagumpala M, Fouladi M, Wallace D, Bowers DC,
Stewart C, Krasin MJ, Gajjar A.
Department of Hematology-Oncology, St. Jude Children's Research Hospital,
Memphis, Tennessee.
BACKGROUND: The role of chemotherapy in the treatment of children with newly
diagnosed diffuse brainstem glioma is uncertain. In the current study, the
authors tested the efficacy of temozolomide treatment after radiotherapy
(RT) in this setting. METHODS: Patients ages 3-21 years were eligible for
the current multiinstitutional study. An optional window therapy regimen
consisting of 2 cycles of intravenous irinotecan (10 doses of 20 mg/m(2) per
day separated by 2 days of rest per cycle) was delivered over 6 weeks and
was followed by conventionally fractionated RT. The 5-day schedule of
temozolomide (200 mg/m(2) per day) was initiated 4 weeks after RT and was
continued for a total of 6 cycles. The pharmacokinetics of temozolomide and
its active metabolite, 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide
(MTIC), were analyzed during Cycles 1 and 3. RESULTS: Thirty-three patients
(median age at diagnosis, 6.4 years) were enrolled. Of the 16 patients who
received window therapy, 6 had irinotecan treatment discontinued due to
clinical progression (n = 5) or toxicity (n = 1); the remaining 10
experienced disease stabilization after 2 cycles. All patients completed RT
(median dose, 55.8 gray). Twenty-nine patients received a combined total of
125 cycles of temozolomide. Grade 3/4 neutropenia and thrombocytopenia
occurred in 33% and 29% of all temozolomide cycles, respectively. In
approximately one-third of the cycles, dose reduction was required due to
myelosuppression. No correlation was demonstrated between temozolomide/MTIC
exposure and myelosuppression at the conclusion of Cycle 1. All patients
died of disease progression (median survival, 12 months). The estimated
1-year survival rate was 48% (standard error, 8%). CONCLUSIONS: The
administration of temozolomide after RT did not alter the poor prognosis
associated with newly diagnosed diffuse brainstem glioma in children. Cancer
2005. (c) 2004 American Cancer Society.
PMID: 15565574 [PubMed - as supplied by publisher]
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| 2: Cancer. 2004 Nov 22; [Epub ahead of print] |
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Phase II trial of irinotecan plus celecoxib in adults
with recurrent malignant glioma.
Reardon DA, Quinn JA, Vredenburgh J, Rich JN, Gururangan S, Badruddoja M,
Herndon JE 2nd, Dowell JM, Friedman AH, Friedman HS.
Department of Surgery, Duke University Medical Center, Durham, North
Carolina.
BACKGROUND: In the current study, the authors report a Phase II trial of
irinotecan (CPT-11), a topoisomerase I inhibitor active against malignant
glioma (MG), with celecoxib, a selective COX-2 inhibitor, among MG patients
with recurrent disease. METHODS: Patients with MG at any type of recurrence
received CPT-11, administered as a 90-minute intravenous infusion on Weeks
1, 2, 4, and 5 of each 6-week cycle plus celecoxib, which was administered
continuously at a dose of 400 mg twice a day. CPT-11 was given at a dose of
350 mg/m(2) for patients receiving enzyme-inducing antiepileptic drugs
(EIAEDs) and at a dose of 125 mg/m(2) for those patients not receiving
EIAEDs. Assessments were performed after every cycle. The primary endpoint
was radiographic response and the secondary endpoints were progression-free
survival (PFS), overall survival (OS), and therapeutic safety. RESULTS:
Thirty-four of the 37 patients enrolled in the current study (92%) were
diagnosed with recurrent GBM and 3 patients (8%) were diagnosed with
recurrent anaplastic astrocytoma (AA). Twenty-one patients were receiving
EIAEDs and 16 patients were not. The median follow-up time was 76.9 weeks.
Concomitant CPT-11 plus celecoxib was found to be well tolerated and safe.
Hematologic toxicities of >/= Grade 3 (according the second version of
the Common Toxicity Criteria of the National Cancer Institute) reportedly
complicated 8.6% of treatment courses. Grade 3 diarrhea, the most commonly
reported nonhematologic toxicity, occurred with equal frequency (8%),
regardless of whether the patient was receiving EIAED. Six patients (16%),
all whom were diagnosed with recurrent GBM, achieved an objective
radiographic response whereas an additional 13 patients (35%) achieved
stable disease. The median PFS was 11.0 weeks and the 6-month PFS was
reported to be 25.1%. The median OS was 31.5 weeks. CONCLUSIONS: The results
of the current study confirm that CPT-11 plus celecoxib can be safely
administered concurrently at full dose levels, and that this regimen has
encouraging activity among heavily pretreated patients with recurrent MG.
Cancer 2005. (c) 2005 American Cancer Society.
PMID: 15558802 [PubMed - as supplied by publisher]
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| 3: Int J Cancer. 2004 Nov 18; [Epub ahead of print] |
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Biophysical measurement of brain tumor cohesion.
Winters BS, Shepard SR, Foty RA.
Department of Surgery, University of Medicine and Dentistry of New
Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
An advantage of using 3D multicellular spheres to study tumor biology is
that they better approximate the interactions encountered by cells in vivo.
Our previous studies have shown that the process of spheroid formation is
governed by the same thermodynamic principles driving the formation of
liquid droplets. This liquid-like behavior enables us to measure a key
property influencing tumor behavior, namely, intercellular cohesion. We have
developed a method, tissue surface tensiometry (TST), to measure the
cohesivity, expressible as surface tension (sigma), of tissue aggregates
under physiologic conditions. This study utilizes TST to measure the
cohesivity of 3 widely used malignant astrocytoma cell lines of different in
vitro invasive potentials. We compare invasiveness with aggregate cohesivity
and with the expression of N-cadherin, a key mediator of cell-cell cohesion
in neural tissues. We show that the cell lines exhibit liquid-like behavior
since they form spheroids whose surface tension is both force- and
volume-independent; that aggregates from each cell line have a distinct
surface tension that correlates with their in vitro invasive capacity; that
dexamethasone (Dex), a widely used therapeutic agent for the treatment of
tumor-related cerebral edema, increases aggregate cohesivity and decreases
invasiveness; that dexamethasone treatment decreases invasion in a
dose-dependent manner but only when cells are in direct contact with one
another; and that dex-mediated decreased invasiveness correlates with
increased aggregate cohesivity as measured by TST but not with N-cadherin
expression or function. Our results demonstrate that for these cell lines,
cohesivity is an excellent predictor of in vitro invasiveness. (c) 2004
Wiley-Liss, Inc.
PMID: 15551307 [PubMed - as supplied by publisher]
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| 4: Neurosurg Clin N Am. 2005 Jan;16(1):135-41. |
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A low-field intraoperative MRI system for glioma surgery:
is it worthwhile?
Oh DS, Black PM.
Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical
School, 75 Francis Street, Boston, MA 02115, USA.
PMID: 15561533 [PubMed - in process]
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| 5: Neurosurg Clin N Am. 2005 Jan;16(1):115-34. |
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Diffusion tensor magnetic resonance imaging of brain
tumors.
Cruz LC Jr, Sorensen AG.
Clinica de Diagnostico por Imagem, Multi-Imagem Ressonancia Magnetica, Av.
das Amerericas 4666, Centro Medico Barrashopping, Rio de Janeiro, Brazil.
PMID: 15561532 [PubMed - in process]
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| 6: Neurosurg Clin N Am. 2005 Jan;16(1):101-114. |
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Proton magnetic resonance spectroscopic imaging in brain
tumor diagnosis.
Gruber S, Stadlbauer A, Mlynarik V, Gatterbauer B, Roessler K, Moser E.
Magnetic Resonance Centre of Excellence, Medical University of Vienna,
Lazarettgasse 14, A-1090 Vienna, Austria; Department of Medical Physics,
Medical University of Vienna, Kompetenzzentrum Hochfeld-MR (MR-Holzhaus),
A-1090 Vienna, Lazarettgasse 14, Austria.
PMID: 15561531 [PubMed - as supplied by publisher]
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| 7: Oncogene. 2004 Nov 22; [Epub ahead of print] |
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Isolation of cancer stem cells from adult glioblastoma
multiforme.
Yuan X, Curtin J, Xiong Y, Liu G, Waschsmann-Hogiu S, Farkas DL, Black
KL, Yu JS.
1Maxine Dunitz Neurosurgical Institute, Suite 800 East, 8631 West 3rd
Street, Los Angeles, CA 90048, USA.
Glioblastoma multiforme (GBM) is the most common adult primary brain tumor
and is comprised of a heterogeneous population of cells. It is unclear which
cells within the tumor mass are responsible for tumor initiation and
maintenance. In this study, we report that brain tumor stem cells can be
identified from adult GBMs. These tumor stem cells form neurospheres,
possess the capacity for self-renewal, express genes associated with neural
stem cells (NSCs), generate daughter cells of different phenotypes from one
mother cell, and differentiate into the phenotypically diverse populations
of cells similar to those present in the initial GBM. Having a
distinguishing feature from normal NSCs, these tumor stem cells can reform
spheres even after the induction of differentiation. Furthermore, only these
tumor stem cells were able to form tumors and generate both neurons and
glial cells after in vivo implantation into nude mice. The identification of
tumor stem cells within adult GBM may represent a major step forward in
understanding the origin and maintenance of GBM and lead to the
identification and testing of new therapeutic targets.Oncogene advance
online publication, 22 November 2004; doi:10.1038/sj.onc.1208311.
PMID: 15558011 [PubMed - as supplied by publisher]
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Volume 3, Supplement 16 - 30 November 2004