| 1: J Neurosurg. 2004 Dec;101(6):951-9. |
|
Surgical management of meningiomas involving the optic
nerve sheath.
Schick U, Dott U, Hassler W.
Department of Neurosurgery, Klinikum Duisburg, Duisburg, Germany.
Uta_Schick@web.de
OBJECT: The management of optic nerve sheath meningiomas (ONSMs) remains
controversial but includes surgery, radiotherapy, and plain observation.
Surgery is often thought to result in postoperative blindness. The authors
report on a large series of patients surgically treated for ONSM, with an
emphasis on the visual outcome. METHODS: Seventy-three patients with ONSMs
who had undergone surgery between 1991 and 2002 were retrospectively
analyzed. The standard surgical approach consisted of pterional craniotomy,
intradural (54 patients) or extradural (10 patients) unroofing of the optic
canal, or a combined procedure (seven patients). Thirty-two tumors
demonstrated extension through the optic canal. Twenty-nine tumors reached
the chiasm or contralateral side. Patients with intraorbital flat tumors
should undergo radiotherapy instead of surgery. Those with a large
intraorbital mass and no useful vision should undergo surgery. Tumors
extending intracranially through the optic canal are amenable to
decompression of the optic canal and resection of the intracranial portion.
The follow-up period was a mean 45.4 months (range 6-144 months). Ten
patients underwent postoperative radiotherapy. Visual acuity was not
significantly influenced by surgery but did become worse with a longer
duration of preoperative symptoms and a longer follow-up period. A tumor
location in the optic canal was another negative factor. Radiotherapy
preserved vision in five of 10 cases. CONCLUSIONS: The loss of vision in
patients with ONSM is only a matter of time. In patients with good vision
the role of radiotherapy becomes more important. Surgery is recommended for
intracranial tumors to prevent contralateral extension.
PMID: 15597756 [PubMed - in process]
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| 2: J Neurosurg. 2004 Dec;101(6):932-4. |
|
Gliomas following organ transplantation: analysis of the
contents of a tumor registry.
Schiff D.
Division of Neuro-Oncology, University of Virginia Health System,
Charlottesville, Virginia 22909-0432, USA. ds4jd@virginia.edu
OBJECT: The author and others have described a series of patients in whom
gliomas have developed following solid organ transplantation. Additionally,
patients infected with human immunodeficiency virus reportedly have an
increased incidence of gliomas. The author sought to examine the association
between the immunosuppressive state in organ transplant recipients and the
development of gliomas. METHODS: Reported cases of tumor in the transplant
population of the Israel Penn International Transplant Tumor Registry
(IPITTR) were examined. These cases were compared with predicted cases in
the 2001 American Cancer Society (ACS) estimates. Of the 7256 malignant
tumors listed in the IPITTR database, 19 (0.3%) were primary brain tumors,
including 14 gliomas. Tumors known to occur at an increased frequency in
transplant recipients accounted for a 1.6- to 2.9-fold increased percentage
of cases in the IPITTR compared with 2001 ACS estimates. Tumors not thought
to occur with an increased frequency in this population, such as
gastrointestinal malignancy and lung cancer, had ratios of 0.19 to 0.35. The
corresponding ratio for primary brain tumors was 0.19. None of the six cases
previously described by the author and his colleagues was reported to the
IPITTR. CONCLUSIONS: Primary brain tumors, including gliomas, do not appear
to be overrepresented in the IPITTR, indicating that they may not arise with
increased frequency in transplant recipients. Nevertheless, one cannot
exclude the possibility that neurooncologists may have underreported such
cases to this voluntary tumor registry.
PMID: 15597753 [PubMed - in process]
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| 3: J Neurosurg. 2004 Nov;101(5):874-7. |
|
Secretion of high-molecular-weight adrenocorticotropic
hormone from a pituitary adenoma in a patient without Cushing stigmata. Case
report.
Matsuno A, Okazaki R, Oki Y, Nagashima T.
Department of Neurosurgery, Teikyo University Ichihara Hospital, Ichihara
City, Chiba, Japan. akirakun@med.teikyo-u.ac.jp
The authors report a case in which a patient harbored a corticotroph
macroadenoma that secreted biologically inactive high-molecular-weight
adrenocorticotropic hormone (ACTH) as well as authentic ACTH 1-39. The
secretion of the high-molecular-weight ACTH was determined using gel
chromatography. The authors believe that these two molecules competed with
each other at the ACTH receptor and, thus, the bioactivity of ACTH 1-39 was
masked and Cushing features were not manifested in the patient. This type of
silent corticotroph adenoma may be categorized as a clinically
nonfunctioning adenoma. Plasmas from patients with silent corticotroph
adenomas, which are identified by positive immunohistochemical staining of
ACTH, should be frozen, stored, and analyzed using gel chromatography to
examine whether the tumors produce and secrete high-molecular-weight ACTH.
Publication Types:
PMID: 15540932 [PubMed - indexed for MEDLINE]
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| 4: J Neurosurg. 2004 Nov;101(5):787-98. |
|
Writing-specific sites in frontal areas: a cortical
stimulation study.
Lubrano V, Roux FE, Demonet JF.
Institut National de la Sante et de la Recherche Medicale (Unite 455),
Federation of Neurosurgery, University Hospitals, Toulouse, France.
OBJECT: The aim of this study was to determine whether cortical areas
involved in the writing process are associated with reading or naming areas
in patients undergoing surgery for brain tumors in frontal areas. This study
was undertaken to spare all language areas found in patients during surgery.
METHODS: Fourteen patients (eight women and six men [mean age 47 years] of
whom 12 were right handed, two left handed, 12 monolingual, and two
bilingual) who harbored brain tumors in the left (11 patients) or right
(three patients) frontal gyri or in rolandic areas, were tested by direct
stimulation by using the awake surgery technique for direct brain mapping.
Mapping of the frontal gyri was performed using naming, reading, and writing
under dictation tasks in the appropriate language(s). Considerable
individual variability in language organization among patients was observed.
Interferences in writing were found during direct stimulation in the frontal
gyri, in cortical sites common or not common to interferences in naming or
reading. In dominant regions, patterns of writing dysfunctions were variable
and included writing arrest, illegible script, letter omissions, and
paragraphia. These dysfunctions were nonspecific (stimulation-induced eye
movements) in nondominant frontal regions and in rolandic gyri (hand
contractions). In the same patient, different writing impairments could
sometimes be observed during stimulation of different sites. As is the case
for naming or reading interference sites, writing interference sites could
be extremely localized (1 cm2 in diameter). In this group of patients,
writing interference sites found in Broca areas were associated with other
sites of language interference, whereas writing-specific interference sites
were found twice in the dominant middle frontal gyrus. CONCLUSIONS: In this
series, we found that writing interference sites could be detected by direct
cortical stimulation in dominant inferior and middle frontal gyri regardless
of whether they were associated with naming or reading interference sites.
Writing disorders elicited by direct stimulation in the frontal lobes are
varied and probably depend on the functional status of the stimulated
cortical area.
PMID: 15540917 [PubMed - indexed for MEDLINE]
| 5: J Neurosurg. 2004 Nov;101(5):762-6. |
|
Continuous-flow shunt for treatment of hydrocephalus due
to lesions of the posterior fossa.
Arriada N, Sotelo J.
Research and Neurosurgical Divisions, National Institute of Neurology and
Neurosurgery of Mexico, Mexico City, Mexico.
OBJECT: Management of hydrocephalus caused by expansive lesions of the
posterior fossa is complicated by two main drawbacks of shunt devices:
sudden decompression and overdrainage. The ventriculoperitoneal (VP)
continuous-flow (CF) shunt is characterized by a peritoneal catheter with an
internal diameter of 0.51 mm that promotes continuous drainage of
cerebrospinal fluid (CSF) at its production rate. The authors have
previously demonstrated in adult patients with hydrocephalus that sudden
decompression and overdrainage are absent when this shunt is used; here they
report the findings of a prospective study in which the goal was to test the
performance of this shunt in patients with severe hydrocephalus due to
lesions of the posterior fossa. METHODS: During a 5-year period, 103
patients with severe hydrocephalus caused by lesions of the posterior fossa
were treated by placement of a VP shunt. In 53 of these patients (control
group) a shunt and valve system was surgically implanted and in 50 patients
a CF shunt was implanted. All patients were followed up for a minimum of 2
years after surgery. Shunt revision or change was necessary in 21 patients
(40%) with conventional shunts and in four patients (8%) with the CF shunt
(p < 0.003). Signs of overdrainage were observed in 18 patients (34%) in
the control group, four of whom had ascending transtentorial herniation;
this complication was not seen in patients with the CF shunt. CONCLUSIONS:
The CF shunt had a low rate of dysfunction and an absence of complications
caused by overdrainage, which were frequently associated with the control
shunts. The hydrodynamic properties of the CF shunt make it effective, even
in severe cases of hydrocephalus caused by lesions of the posterior fossa.
Publication Types:
- Clinical Trial
- Controlled Clinical Trial
PMID: 15540913 [PubMed - indexed for MEDLINE]
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| 6: J Neurosurg. 2004 Nov;101 Suppl 3:435-40. |
|
Spinal lesions treated with Novalis shaped beam
intensity-modulated radiosurgery and stereotactic radiotherapy.
De Salles AA, Pedroso AG, Medin P, Agazaryan N, Solberg T, Cabatan-Awang
C, Espinosa DM, Ford J, Selch MT.
Division of Neurosurgery and Department of Radiation Oncology, David Geffen
School of Medicine, University of California, Los Angeles, California, USA.
adesalles@mednet.ucla.edu
OBJECT: Spinal radiosurgery was implemented to improve quality of life (QOL)
in patients with malignancies. It may also be applicable to the treatment of
benign lesions. METHODS: Between July 2002 and January 2004, 14 patients
harboring 22 lesions were treated; 13 received single-dose stereotactic
radiosurgery. Six were women. The mean age was 60.2 years (range 48-82
years). There were 11 metastases, two neurofibromas, and one meningioma. Six
lesions were cervical, 10 thoracic, and six lumbar. Ten patients suffered
pain, three paresthesias, two weakness, and three were asymptomatic. Seven
patients underwent spinal surgery, with four receiving instrumentation.
Twelve patients underwent conventional irradiation before stereotactic
radiosurgery/stereotactic radiotherapy. A mean dose of 12+/-2.7 Gy (range
8-21 Gy) was prescribed to the 91% isodose line (range 85-97%). The mean
tumor volume was 25+/-27.1 ml (range 0.75-91.8 ml). Treatment was planned
using intensity-modulated radiosurgery (IMRS) fields in 15 cases, dynamic
arcs in five, and conformal beams in two. The mean follow-up period was
6.1+/-3.9 months (range 1-16 months). Three patients became pain free and
four experienced considerable relief. Weakness improved in the two patients
with this preoperative symptom and the asymptomatic patients remained so.
Four lesions decreased in size, five remained stable, seven progressed, and
six were not followed up (two patients died before follow up). Four patients
in all died, three of systemic disease and one of thoracic lesion
progression. No complications due to shaped beam and
IMRS/intensity-modulated radiotherapy (IMRT) techniques were observed.
CONCLUSIONS: Shaped beam and IMRS/IMRT involving the Novalis system may
delay neurological deterioration, improving QOL. The lack of complication
suggests that higher doses can be delivered to improve the control rate in
patients with metastases.
Publication Types:
PMID: 15537201 [PubMed - indexed for MEDLINE]
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| 7: J Neurosurg. 2004 Nov;101 Suppl 3:381-9. |
|
A feasibility study of 18F-fluorodeoxyglucose positron
emission tomography targeting and simultaneous integrated boost for
intensity-modulated radiosurgery and radiotherapy.
Solberg TD, Agazaryan N, Goss BW, Dahlbom M, Lee SP.
Department of Radiation Oncology, David Geffen School of Medicine,
University of California, 90095-6951, USA. solberg@radonc.ucla.edu
OBJECT: The authors hypothesized that the efficacy of intensity-modulated
radiation therapy (IMRT) can be enhanced by selectively increasing the
radiation dose to the biologically active positron emission tomography
(PET)-documented positive tumor subregions while simultaneously maintaining
the overall clinically established target dose. METHODS: The authors
undertook a feasibility study to evaluate IMRT PET/computerized tomography
(CT) protocol for boost treatment in selected cancer patients. Prior to
treatment, FDG-PET and CT scans were acquired using an integrated PET/CT
scanner, ensuring accurate correlation between image sets. After
acquisition, tumor volume and objects-at-risk (OARs) were outlined on the CT
scans; any PET-positive tumor subregions were similarly outlined. Daily
dosages of 1.8 to 2 Gy were prescribed to tumor volume and the margin
whereas additional dosages of 10 to 20% were delivered to PET-positive
subregions. Dosage-volume histogram-derived constraints were used in inverse
planning to specify the desired dose to one or more PET-positive tumor
subregions, CT-delineated tumor volume, and OARs. The IMRT treatment was
delivered using a micromultileaf collimator. Simultaneous integrated boost
radiation was successfully delivered using IMRT with PET/CT planning.
Excellent dose conformality was achieved in the tumor volume and the dose to
PET-positive tumor subregions was increased while minimizing the dose to
OARs. CONCLUSIONS: When coupled with IMRT, PET/CT scanning allows dose
escalation to biologically active subregions within the tumor volume.
Further study is needed to determine if dose escalation to FDG-PET-active
sites correlates with improved treatment outcome. Finally, in extracranial
sites, PET scanning should only be performed with a dedicated PET/CT device
because present image fusion technologies are inadequate for accurately
registering deformable objects.
Publication Types:
PMID: 15537193 [PubMed - indexed for MEDLINE]
-
| 8: J Nucl Med. 2004 Oct;45(10):1766-75. |
|
-
Imaging endogenous gene expression in brain cancer in
vivo with 111In-peptide nucleic acid antisense radiopharmaceuticals and
brain drug-targeting technology.
Suzuki T, Wu D, Schlachetzki F, Li JY, Boado RJ, Pardridge WM.
College of Pharmacy, Nihon University, Chiba, Japan.
Imaging endogenous gene expression with sequence-specific antisense
radiopharmaceuticals is possible if the antisense agent is enabled to
traverse the biologic membrane barriers that separate the blood compartment
from messenger RNA (mRNA) molecules in the cytoplasm of the target cell. The
present studies were designed to image endogenous gene expression in brain
cancer using peptide nucleic acid (PNA) antisense agents that were modified
to allow for (a) chelation of the 111In radionuclide and (b) attachment to a
brain targeting system, which delivers the PNA across both the blood-brain
barrier (BBB) and the tumor cell membrane. METHODS: PNAs were designed that
were antisense to either the rat glial fibrillary acidic protein (GFAP) mRNA
or the rat caveolin-1alpha (CAV) mRNA. The PNA contained an amino-terminal
diethylenetriaminepentaacetic acid moiety to chelate 111In and a
carboxyl-terminal epsilon-biotinyl lysine residue, which enabled attachment
to the delivery system. The latter comprised streptavidin (SA) and the
murine OX26 monoclonal antibody to the rat transferrin receptor (TfR), which
were joined by a thiol-ether linker. Control PNAs were not conjugated to
SA-OX26. Brain tumors developed after the intracerebral injection of rat RG2
glial cells in adult Fischer CD344 rats. GFAP and CAV gene expression in the
tumor in vivo was monitored by confocal microscopy and Northern blotting
with GFAP and CAV complementary DNAs. RESULTS: If the PNA was not targeted
to the TfR, then no imaging of any brain structures was possible, owing to
the absence of PNA transport across the BBB. Conjugation of the
111In-GFAP-PNA to the SA-OX26 delivery system did not image brain cancer,
owing to the downregulation of the GFAP mRNA in brain glial tumors. In
contrast, brain cancer was selectively imaged with the 111In-CAV-PNA
conjugated to SA-OX26 owing to upregulation of CAV gene expression in brain
cancer. CONCLUSION: Imaging endogenous gene expression in vivo with PNA
antisense radiopharmaceuticals is possible if drug-targeting technology is
used. Attachment of the PNA antisense agent to the targeting ligand enables
the antisense radiopharmaceutical to traverse biologic membrane barriers and
access intracellular target mRNA molecules.
Publication Types:
- Evaluation Studies
- Validation Studies
PMID: 15471847 [PubMed - indexed for MEDLINE]
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| 9: Mayo Clin Proc. 2004 Dec;79(12):1489-94. |
|
Seizure prophylaxis in patients with brain tumors: a
meta-analysis.
Sirven JI, Wingerchuk DM, Drazkowski JF, Lyons MK, Zimmerman RS.
Department of Neurology Mayo Clinic College of Medicine, Scottsdale, Ariz,
USA. sirven.joseph@mayo.edu
OBJECTIVE: To assess whether antiepileptic drugs (AEDs) should be prescribed
to patients with brain tumors who have no history of seizures. METHODS: We
performed a meta-analysis of randomized controlled trials (1966-2004) that
evaluated the efficacy of AED prophylaxis vs no treatment or placebo to
prevent seizures in patients with brain tumors who had no history of
epilepsy. Summary odds ratios (ORs) were calculated using a random-effects
model. Three subanalyses were performed to assess pooled ORs of seizures in
patients with primary glial tumors, cerebral metastases, and meningiomas.
RESULTS: Of 474 articles found in the initial search, 17 were identified as
primary studies. Five trials met inclusion criteria: patients with a
neoplasm (primary glial tumors, cerebral metastases, and meningiomas) but no
history of epilepsy who were randomized to either an AED or placebo. The 3
AEDs studied were phenobarbital, phenytoin, and valproic acid. Of the 5
trials, 4 showed no statistical benefit of seizure prophylaxis with an AED.
Meta-analysis confirmed the lack of AED benefit at 1 week (OR, 0.91; 95%
confidence interval [CI], 0.45-1.83) and at 6 months (OR, 1.01; 95% CI,
0.51-1.98) of follow-up. The AEDs had no effect on seizure prevention for
specific tumor pathology, including primary glial tumors (OR, 3.46; 95% CI,
0.32-37.47), cerebral metastases (OR, 2.50; 95% CI, 0.25-24.72), and
meningiomas (OR, 0.62; 95% CI, 0.10-3.85). CONCLUSIONS: No evidence supports
AED prophylaxis with phenobarbital, phenytoin, or valproic acid in patients
with brain tumors and no history of seizures, regardless of neoplastic type.
Subspecialists who treat patients with brain tumors need more education on
this issue. Future randomized controlled trials should address whether any
of the newer AEDs are useful for seizure prophylaxis.
PMID: 15595331 [PubMed - in process]
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| 10: Neurology. 2004 Dec 14;63(11):2197; author reply 2197. |
|
-
Primary malignant brain tumor incidence and Medicaid
enrollment.
Greenberg H.
Publication Types:
PMID: 15596791 [PubMed - in process]
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| 11: Neurology. 2004 Jun 22;62(12):2336; author reply 2336. |
|
Comment on:
Progressive myoclonus in a child with a deep cerebellar
mass.
Gilbert GJ.
Publication Types:
PMID: 15216560 [PubMed - indexed for MEDLINE]
-
| 12: Neurology. 2004 Jun 22;62(12):2336; author reply 2336. |
|
Comment on:
Progressive myoclonus in a child with a deep cerebellar
mass.
Shetty T.
Publication Types:
PMID: 15210919 [PubMed - indexed for MEDLINE]
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| 13: Neurology. 2004 Jun 22;62(12):2330-1. |
|
-
Intracranial dural arteriovenous fistula mimicking
brainstem neoplasm.
Crum BA, Link M.
Departments of Neurology and Neurosurgery, Mayo Clinic, Rochester, MN 55905,
USA.
Publication Types:
PMID: 15210912 [PubMed - indexed for MEDLINE]
-
| 14: Neurology. 2004 Jun 22;62(12):2270-6. |
|
-
Dysembryoplastic neuroepithelial tumors in childhood:
long-term outcome and prognostic features.
Nolan MA, Sakuta R, Chuang N, Otsubo H, Rutka JT, Snead OC 3rd, Hawkins
CE, Weiss SK.
Brain and Behavior Program, Division of Neurology, Department of Pediatrics,
The Hospital for Sick Children, Toronto, Canada.
BACKGROUND: Dysembryoplastic neuroepithelial tumors (DNTs) are associated
with medically intractable epilepsy and a favorable prognosis after surgical
resection. The authors describe the clinical, radiologic, and pathologic
characteristics and outcomes in children after surgical resection of
pathologically confirmed DNT to ascertain prognostic features for seizure
recurrence following surgery. METHODS: Neurology, neurosurgery, and
pathology databases from 1993 to 2002 at the Hospital for Sick Children were
searched to retrospectively identify children with confirmed DNT and
presentation with seizures. Risk factors for postoperative seizure
recurrence were examined with respect to seizure outcome at 12 months and
long-term follow-up. RESULTS: Of the 26 children identified (mean age at
surgery 10.0 years) seizure outcome was good in 22 children (85%) at 12
months (Class 1). At longer follow-up (mean 4.3, range 1.0 to 11.0 years)
only 16 (62%) remained seizure-free. Residual DNT was evident in 15 of the
24 children with available postoperative MRI. Three children demonstrated
recurrence of tumor. At 12 months follow-up, older age (>10 years) and
longer duration of epilepsy (>2 years) were associated with seizure
recurrence. The presence of residual tumor was a risk factor for seizure
recurrence at long-term follow-up (p = 0.02). CONCLUSIONS: Children with DNT
and epilepsy may benefit from surgical management; however, seizure outcome
is not always favorable. Although the majority of children remain seizure
free after surgical excision of DNT, a considerable number have recurrent
seizures. Short-term outcome is influenced by older age at surgery and
longer duration of epilepsy. Residual tumor is a significant risk factor for
poor seizure outcome. Recurrent tumor can occur.
PMID: 15210893 [PubMed - indexed for MEDLINE]
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| 15: Neuroradiology. 2004 Aug;46(8):692-5. Epub 2004 Jul 03. |
|
-
Posterior pericallosal lipoma extending through the
interhemispheric fissure into the scalp via the anterior fontanelle.
Chen CF, Lee YC, Lui CC, Lee RJ.
Department of Diagnostic Radiology, Chang Gung Memorial Hospital, Kaohsiung
Medical Centre, 123 Ta Pei Road, Niao Sung Hsiang, Kaohsiung Hsien, Taiwan.
xfroggykimo@yahoo.com.tw
We report an unusual pericallosal lipoma presenting as scalp mass at birth.
The patient had no obvious neurological deficit, but CT and MRI revealed a
striking lipoma extending extracranially into the scalp from the
interhemispheric fissure via the anterior fontanelle. The corpus callosum
was distorted but not dysplastic.
Publication Types:
PMID: 15235757 [PubMed - indexed for MEDLINE]
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| 16: Neuroradiology. 2004 Aug;46(8):655-65. Epub 2004 Jun 15. |
|
-
A comparison of Gd-BOPTA and Gd-DOTA for
contrast-enhanced MRI of intracranial tumours.
Colosimo C, Knopp MV, Barreau X, Gerardin E, Kirchin MA, Guezenoc F,
Lodemann KP.
Section of Radiology, Department of Clinical Sciences and Bioimaging,
University G. d'Annunzio, via Colle dell'Ara, 66100 Chieti, Italy.
A two-centre intra-individual crossover study was performed in 23 patients
with suspected high-grade glioma or metastases to assess and compare the
safety and enhancement characteristics of two different MRI contrast media
(gadobenate dimeglumine, Gd-BOPTA and gadoterate meglumine, Gd-DOTA) at
equivalent doses of 0.1 mmol/kg body weight. T1-weighted spin-echo (SE) and
T2-weighted fast SE images were obtained before and T1-weighted images 0, 2,
4, 6, 8 and 15 min after injection. T1-weighted images with magnetisation
transfer contrast were acquired 12 min after injection. Qualitative
assessment by blinded, off-site readers (reader 1:19 patients; reader 2:21)
and on-site investigators (23) revealed significant (P< or =0.005)
overall preference for Gd-BOPTA over Gd-DOTA for contrast enhancement
(Gd-BOPTA preferred in 18, 15 and 18 cases; Gd-DOTA in 0, 1 and 1 and no
preference in 1, 5 and 4; off-site readers 1 and 2, and on-site
investigators, respectively). A similar significant preference for Gd-BOPTA
was expressed by off-site readers and on-site investigators for
lesion-to-brain contrast, lesion delineation, internal lesion structure, and
overall image preference. Quantitative assessment by off-site readers
revealed significantly (p<0.05) greater lesion enhancement with Gd-BOPTA
than with Gd-DOTA at all times from 2 min after injection.
Publication Types:
- Clinical Trial
- Randomized Controlled Trial
PMID: 15205859 [PubMed - indexed for MEDLINE]
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| 17: Oncogene. 2004 Dec 13; [Epub ahead of print] |
|
-
Arsenic trioxide induces autophagic cell death in
malignant glioma cells by upregulation of mitochondrial cell death protein
BNIP3.
Kanzawa T, Zhang L, Xiao L, Germano IM, Kondo Y, Kondo S.
[1] 1Department of Neurosurgery, The University of Texas MD Anderson Cancer
Center, Houston, TX 77030, USA [2] 3Department of Neurosurgery, Mount Sinai
School of Medicine, New York, NY 10510, USA.
Arsenic trioxide (As(2)O(3)) has shown considerable efficacy in treating
hematological malignancies with induction of programmed cell death (PCD)
type I, apoptosis. However, the mechanisms underlying the antitumor effect
of As(2)O(3) on solid tumors are poorly defined. Previously, we reported
that As(2)O(3) induced autophagic cell death (PCD type II) but not apoptosis
in human malignant glioma cell lines. The purpose of this study was to
elucidate the molecular pathway leading to autophagic cell death. In this
study, we demonstrated that the cell death was accompanied by involvement of
autophagy-specific marker, microtubule-associated protein light chain 3
(LC3), and damage of mitochondrial membrane integrity, but not by caspase
activation. Analysis by cDNA microarray, RT-PCR, and Western blot showed
that cell death members of Bcl-2 family, Bcl-2/adenovirus E1B
19-kDa-interacting protein 3 (BNIP3) and its homologue BNIP3-like (BNIP3L),
were upregulated in As(2)O(3)-induced autophagic cell death. Exogenous
expression of BNIP3, but not BNIP3L, induced autophagic cell death in
malignant glioma cells without As(2)O(3) treatment. When upregulation of
BNIP3 induced by As(2)O(3) was suppressed by a dominant-negative effect of
the transmembrane-deleted BNIP3 (BNIP3DeltaTM), autophagic cell death was
inhibited. In contrast, BNIP3 transfection augmented As(2)O(3)-induced
autophagic cell death. These results suggest that BNIP3 plays a central role
in As(2)O(3)-induced autophagic cell death in malignant glioma cells. This
study adds a new concept to characterize the pathways by which As(2)O(3)
acts to induce autophagic cell death in malignant glioma cells.Oncogene
advance online publication, 13 December 2004; doi:10.1038/sj.onc.1208095.
PMID: 15592527 [PubMed - as supplied by publisher]
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| 18: Oncogene. 2004 Dec 13; [Epub ahead of print] |
|
-
Mechanisms of thymidine kinase/ganciclovir and cytosine
deaminase/ 5-fluorocytosine suicide gene therapy-induced cell death in
glioma cells.
Fischer U, Steffens S, Frank S, Rainov NG, Schulze-Osthoff K, Kramm CM.
[1] 1Institute of Molecular Medicine, Heinrich-Heine-University, Dusseldorf,
Germany [2] 2Department of Pediatric Hematology, Oncology, and Immunology,
Heinrich-Heine-University, Dusseldorf, Germany.
Suicide gene transfer using thymidine kinase (TK) and ganciclovir (GCV)
treatment or the cytosine deaminase (CD)/5-fluorocytosine (5-FC) system
represents the most widely used approach for gene therapy of cancer.
However, molecular pathways and resistance mechanisms remain controversial
for GCV-mediated cytotoxicity, and are virtually unknown for the CD/5-FC
system. Here, we elucidated some of the cellular pathways in glioma cell
lines that were transduced to express the TK or CD gene. In wild-type
p53-expressing U87 cells, exposure to GCV and 5-FC resulted in a weak p53
response, although apoptosis was efficiently induced. Cell death triggered
by GCV and 5-FC was independent of death receptors, but accompanied by
mitochondrial alterations. Whereas expression of Bax remained unaffected, in
particular, GCV and also 5-FC caused a decline in the level of Bcl-2.
Similar findings were obtained in 9L and T98G glioma cells that express
mutant p53, and also underwent mitochondrial apoptosis in both the TK/GCV
and CD/5-FC system. Upon treatment of 9L cells with 5-FC, Bcl-x(L)
expression slowly declined, whereas exposure to GCV resulted in the rapid
proapoptotic phosphorylation of Bcl-x(L). These data suggest that TK/GCV-
and CD/5-FC-induced apoptosis does neither require p53 nor death receptors,
but converges at a mitochondrial pathway triggered by different mechanisms
of modulation of Bcl-2 proteins.Oncogene advance online publication, 13
December 2004; doi:10.1038/sj.onc.1208290.
PMID: 15592511 [PubMed - as supplied by publisher]
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| 19: Pediatr Neurosurg. 2004 May-Jun;40(3):153-4. |
|
-
Choroid plexus angioma in a newborn presenting with
hydrocephalus.
Labeodan OA.
F.C.S. Neurosurgery, Department of Neurosurgery, Johannesburg General
Hospital, Witwatersrand University, Johannesburg, South Africa.
sheunlab@yahoo.com
Publication Types:
PMID: 15367812 [PubMed - indexed for MEDLINE]
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| 20: Pediatr Neurosurg. 2004 May-Jun;40(3):151-2. |
|
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Giant posterior fossa arachnoid cyst.
Lancon JA, Ellis AL.
Department of Neurosurgery, The Blair E. Batson Hospital for Children, The
University of Mississippi Medical Center, Jackson, Miss., USA.
jlancon@neurosurgery.umsmed.edu
Publication Types:
PMID: 15367811 [PubMed - indexed for MEDLINE]
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| 21: Pediatr Neurosurg. 2004 May-Jun;40(3):149-50. |
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High-grade spinal cord tumor with cerebellar and
retroperitoneal extension.
Morimoto K, Wakayama A, Yoshimine T, Nakayama M.
Osaka Medical Center and Research Institute for Maternal and Child Health,
Izumi, Osaka 594-1101, Japan. fr8kmrmt@mch.pref.osaka.jp
Publication Types:
PMID: 15367810 [PubMed - indexed for MEDLINE]
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| 22: Pediatr Neurosurg. 2004 May-Jun;40(3):145-6. |
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Brainstem astroblastoma.
Kim BS, Kothbauer K, Jallo G.
Division of Pediatric Neurosurgery, Institute for Neurology and
Neurosurgery, Beth Israel Medical Center, New York, NY 10028, USA.
Publication Types:
PMID: 15367808 [PubMed - indexed for MEDLINE]
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| 23: Pediatr Neurosurg. 2004 May-Jun;40(3):124-7. |
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Congenital cystic hemangioblastomas of the cerebral
hemisphere in a neonate without alteration in the VHL gene.
Johnson MD, Mitchell AR, Troup EC, Bhowmick DA, Wait SD, Aulino J, Zhuang
Z, Weil RJ.
Department of Pathology, Vanderbilt University School of Medicine,
Nashville, Tenn., USA.
A 4-week-old child presented with lethargy, emesis, decreased spontaneous
movements, and a bulging fontanelle. Neuroimaging demonstrated a large,
hemispheric, multicystic lesion with multiple enhancing nodules, which, on
pathological examination, proved to be multiple, distinct hemangioblastomas.
Careful molecular analysis failed to reveal alterations of the VHL gene.
This represents an uncommon presentation for these tumors and suggests that
genes other than VHL may be important in the genesis of these tumors.
Publication Types:
PMID: 15367802 [PubMed - indexed for MEDLINE]
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Volume 3, Supplement 24 - 31 December 2004