| 1: Arch
Pathol Lab Med. 2005 Jan;129(1):e11-5. |
|
-
Intracranial peripheral primitive neuroectodermal tumors
of the cavernous sinus: a diagnostic peculiarity.
Idrees M, Gandhi C, Betchen S, Strauchen J, King W, Wolfe D.
The Lilian and Henry M. Stratton-Hans Popper Department of Pathology, Mount
Sinai Medical Center, New York, NY, USA. muhammad.idrees@msnyuhealth.org
<muhammad.idrees@msnyuhealth.org>
Peripheral primitive neuroectodermal tumors (pPNETs) are aggressive, poorly
differentiated neoplasms that occur in children and young adults. These
tumors are associated with a peak incidence in the second decade and a
slight male preponderance. Recently, Ewing sarcoma and pPNET tumors have
been proven to carry identical translocations, the most common being
t(11;22)(q24;q12). Intracranial Ewing sarcoma/pPNETs have rarely been
described in the literature. We studied a case of intracranial pPNET arising
in the right cavernous sinus of a 46-year-old man. On imaging, the tumor had
both sellar and suprasellar components and was centered within the right
parasellar region. Histologically, the tumor was composed of intermediate to
large cells with round to oval hyperchromatic nuclei with distinct nucleoli.
The cells contained a moderate amount of slightly basophilic cytoplasm. The
tumor was markedly fibrotic and had collagen bands surrounding both
individual and groups of cells. A large immunohistochemical panel was
positive only for CD99 and vimentin. Fluorescence in situ hybridization did
not show translocations associated with Ewing sarcoma/pPNET. However, a
small percentage of these tumors can be negative for this translocation. In
these cases, histology and immunohistochemical techniques in the absence of
an alternative diagnosis are the only tools available to establish the
diagnosis.
Publication Types:
PMID: 15628919 [PubMed - indexed for MEDLINE]
 
-
| 2: Childs
Nerv Syst. 2005 Jun 3; [Epub ahead of print] |
|
-
Cytotoxicity of rat marrow stromal cells against
malignant glioma cells.
Kang SG, Jeun SS, Lim JY, Yoo DS, Huh PW, Cho KS, Kim DS, Shin HJ, Kim
JH, Kim MC, Kang JK.
Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University
School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of
Korea.
OBJECTS: Marrow stromal cells (MSCs) have been shown to have the capacity of
orthodox and unorthodox plasticity. In this study, the authors tried to
access in vitro cytotoxicity of MSCs from rat and also to differentiate MSCs
into immune effector cell. METHODS: Rat MSCs (rMSCs) were isolated by
standard methodology and were activated by interleukin-2 (IL-2),
interleukin-15 (IL-15), granulocyte macrophage colony stimulating factor,
and combinations, which were effector cells. Cytotoxicity of rMSCs and
activated rMSCs against the target cells (9L rat glioma cell line) was
estimated using visual survival cell assay. Phenotypes of these various
activated cells were determined using flow cytometry. The secreted protein
from effector cells was estimated by enzyme-linked immunosorbent assay. The
expression of immune response-related genes in activated cells was measured.
RESULTS: There was a significant cytotoxicity of rMSCs activated with
various cytokine combinations. After various cytokine activations of rMSCs,
the population of immune effector cells (CD8, CD161a) and immune
reaction-related proteins (IL-4, gamma-INF) might increase. Apoptosis may be
one of the lysis mechanisms of target cells by activated rMSCs. The
contributing genes could be gamma-INF, FasL, and perforin. CONCLUSION: This
study suggests that rMSC may be used as adoptive transfer therapy in
patients suffering from malignant brain tumor, but we have to investigate
orthotopic animal study for the proper translation.
PMID: 15933882 [PubMed - as supplied by publisher]
-
| 3: Childs
Nerv Syst. 2005 Jun 2; [Epub ahead of print] |
|
-
Individualized treatment of pediatric craniopharyngiomas.
Albright AL, Hadjipanayis CG, Lunsford LD, Kondziolka D, Pollack IF,
Adelson PD.
Department of Neurosurgery, Children's Hospital of Pittsburgh, 3705 Fifth
Avenue, Pittsburgh, PA, 15213, USA.
OBJECTIVE: The treatment of children with craniopharyngiomas should be
individualized because of their heterogeneous clinical and radiographic
characteristics. We performed this study to correlate the clinical and
radiographic features at the time of presentation with the multimodality
treatments the children received. METHODS: Medical records were reviewed for
children with craniopharyngiomas who presented to the Children's Hospital of
Pittsburgh for their initial management between 1983 and 2004. Children were
treated with microsurgical tumor resections (27), intracavitary irradiation
with phosphorus 32 ((32)P) (12), and with gamma knife stereotactic
radiosurgery (GKSR) (5). CONCLUSIONS: There were no deaths in any treatment
group. Gross total resections were thought to be performed in 18 patients
and were confirmed by imaging in 13 of the 18 patients. The primary
operative morbidities were hormonal and visual. Every child needed at least
two replacement hormones and most had panhypopituitarism. Vision worsened
postoperatively in 5 of 27 children. There was no operative morbidity or
mortality from (32)P. After (32)P treatment, one child required a later cyst
aspiration and one required a craniotomy for progressive cyst enlargement.
There was no morbidity or mortality from GKSR, which achieved tumor
stabilization or shrinkage in 4 of 5 cases. Resections, (32)P, and GKSR are
complimentary treatment modalities for children with craniopharyngiomas.
Their indications and outcomes differ, but all should be available in the
treatment armamentarium.
PMID: 15931512 [PubMed - as supplied by publisher]
-
| 4: Childs
Nerv Syst. 2005 Jun 1; [Epub ahead of print] |
|
-
Long-term outcome and reconsideration of intracystic
chemotherapy with bleomycin for craniopharyngioma in children.
Takahashi H, Yamaguchi F, Teramoto A.
Department of Neurosurgery, Nippon Medical School Dai-ni Hospital, 1-396
Kosugi-cho, Nakahara-ku, Kawasaki City, Kanagawa, 211-8533, Japan,
hitaka84@nms.ac.jp.
OBJECT: We first reported postoperative intratumoral chemotherapy with
bleomycin for craniopharyngiomas in 1985. However, this local bleomycin
chemotherapy has not yet been used very frequently. It seems to be necessary
for us to report long-term outcome and reconsideration of this treatment.
METHODS AND RESULTS: Local bleomycin chemotherapy was performed on 7
children (to 1985) and 11 children (from 1988 to 2004). A total of 11
pediatric patients with recurrent cystic craniopharyngioma was treated by
intracystic injection of bleomycin after 1988 and followed up from 3 to 16
years. After 1985, 1 of 7 children whose clinical outcome was fair underwent
intracystic injection of bleomycin again. This patient has never had
recurrent tumor until now. The children whose clinical outcomes were
excellent have no recurrence during follow-up from 21 to 26 years. After
1988, the results showed that cystic recurrences of 7 children have almost
disappeared and the children have achieved a good school life, and 3
children are also achieving a good life after additional stereotactic
radiosurgery. CONCLUSION: Our results indicate that local bleomycin
chemotherapy is effective and that recurrence does not occur after
follow-up, which ranged in duration from 3 to 16 years.
PMID: 15928963 [PubMed - as supplied by publisher]
-
| 5: Clin
Cancer Res. 2005 Jun 1;11(11):4160-7. |
|
-
Clinical evaluation of dendritic cell vaccination for
patients with recurrent glioma: results of a clinical phase I/II trial.
Yamanaka R, Homma J, Yajima N, Tsuchiya N, Sano M, Kobayashi T, Yoshida
S, Abe T, Narita M, Takahashi M, Tanaka R.
Department of Neurosurgery, Brain Research Institute, Niigata University
School of Medicine, Niigata University, Niigata, Japan.
ryaman@bri-niigata-u.ac.jp
PURPOSE: To investigate the safety and the immunologic and clinical
responses of dendritic cell therapy for patients with recurrent malignant
glioma. EXPERIMENTAL DESIGN: Twenty-four patients with recurrent malignant
glioma (6 grade 3 and 18 grade 4 patients) were evaluated in a phase I/II
clinical study of dendritic cell therapy. All patients were resistant to the
standard maximum therapy. The patient's peripheral blood dendritic cells
were generated with granulocyte macrophage colony-stimulating factor, plus
interleukin 4 with or without OK-432, and pulsed with an autologous tumor
lysate. Dendritic cells were injected intradermally, or both intratumorally
and intradermally every 3 weeks. RESULTS: The protocols were well tolerated
with only local redness and swelling at the injection site in several cases.
Clinical responses were as follows: 1 patient with partial response, 3
patients with minor response, 10 patients with stable disease, and 10
patients with progressive disease. The patients whose dendritic cells were
matured with OK-432 had longer survival times than the dendritic cells from
patients without OK-432 maturation. The patients with both intratumoral and
intradermal administrations had a longer survival time than the patients
with intradermal administration only. Increased ELISPOT and delayed-type
hypersensitivity responses after vaccination could provide good laboratory
markers to predict the clinical outcome of patients receiving dendritic cell
vaccination. The overall survival of patients with grade 4 glioma was 480
days, which was significantly better than that in the control group.
CONCLUSIONS: This study showed the safety and clinical response of
autologous tumor lysate-pulsed dendritic cell therapy for patients with
malignant glioma. Dendritic cell therapy is recommended for further clinical
studies in malignant glioma patients.
PMID: 15930352 [PubMed - in process]
-
| 6: Clin
Cancer Res. 2005 Jun 1;11(11):4074-82. |
|
-
Different activation of mitogen-activated protein kinase
and Akt signaling is associated with aggressive phenotype of human
meningiomas.
Mawrin C, Sasse T, Kirches E, Kropf S, Schneider T, Grimm C, Pambor C,
Vorwerk CK, Firsching R, Lendeckel U, Dietzmann K.
Department of Neuropathology, Otto-von-Guericke University, Magdeburg,
Germany. Christian.mawrin@medizin.uni-magdeburg.de
PURPOSE: Activation of intracellular signaling cascades has been implicated
in the growth control of benign meningiomas, but their role for meningioma
progression and outcome is unknown. Here we determined the expression and
function of proteins involved in mitogen-activated protein kinase (MAPK) and
phosphinositol-3 kinase (PI3K)/Akt signaling in benign, atypical, and
malignant meningiomas and studied their association with clinicopathologic
data including meningioma recurrence. EXPERIMENTAL DESIGN: Expression of
various MAPK and PI3K signaling proteins was determined in 70 primary
meningiomas and, if present, in recurrent tumors by immunohistochemistry and
Western blotting. The expression patterns in primary and recurrent tumors
were related to clinical data. The effect of MAPK and PI3K pathway
inhibition on cell proliferation and apoptosis was determined using a
primary malignant meningioma cell culture. RESULTS: Atypical and malignant
meningiomas showed higher levels of phospho-Akt compared with benign tumors,
and their proliferation could be inhibited by PI3K blocking using
wortmannin. PI3K inhibition did not induce apoptosis in malignant meningioma
cells. In contrast, expression of phospho-Raf and phospho-MAPK was decreased
in aggressive meningiomas compared with benign tumors, but MAPK inhibition
by PD98059 resulted in tumor cell apoptosis and decreased proliferation.
Reduced MAPK activation was associated with meningioma recurrence, and PI3K
activation was associated with poor preclinical condition and brain invasion
of malignant meningiomas. CONCLUSIONS: Both MAPK and PI3K/Akt pathways are
activated at different levels in benign and malignant meningiomas.
Activation of PI3K/Akt signaling contributes to the aggressive behavior of
malignant meningiomas, whereas MAPK activation is involved in both
proliferation and apoptosis of malignant meningiomas.
PMID: 15930342 [PubMed - in process]
-
| 7: Int
J Radiat Oncol Biol Phys. 2005 May 28; [Epub ahead of print] |
|
-
Conformal radiotherapy, reduced boost volume,
hyperfractionated radiotherapy, and online quality control in standard-risk
medulloblastoma without chemotherapy: Results of the French M-SFOP 98
protocol.
Carrie C, Muracciole X, Gomez F, Habrand JL, Benhassel M, Mege M, Mahe M,
Quetin P, Maire JP, Soum F, Baron MH, Clavere P, Chapet S, Gaci Z, Kolodie
H, Maingon P, Vie B, Bernier V, Alapetite C, Hoffstetter S, Grill J, Lafay
F; French Society of Pediatric Oncology.
Department of Radiotherapy, Centre Leon Berard, Lyon, France.
PURPOSE: Between December 1998 and October 2001, patients <19 years old
were treated for standard-risk medulloblastoma according to the
Medulloblastome-Societe Francaise d'Oncologie Pediatrique 1998 (M-SFOP 98)
protocol. Patients received hyperfractionated radiotherapy (36 Gy in 36
fractions) to the craniospinal axis, a boost with conformal therapy
restricted to the tumor bed (to a total dose of 68 Gy in 68 fractions), and
no chemotherapy. Records of craniospinal irradiation were reviewed before
treatment start. RESULTS: A total of 48 patients were considered assessable.
With a median follow-up of 45.7 months, the overall survival and
progression-free survival rate at 3 years was 89% and 81%, respectively.
Fourteen major deviations were detected and eight were corrected. No
relapses occurred in the frontal region and none occurred in the posterior
fossa outside the boost volume. Nine patients were available for volume
calculation without reduction of the volume irradiated. We observed a
reduction in the subtentorial volume irradiated to >60 Gy, but a slight
increase in the volume irradiated to 40 Gy. No decrease in intelligence was
observed in the 22 children tested during the first 2 years. CONCLUSION:
This hyperfractionated radiotherapy protocol with a reduced boost volume and
without chemotherapy was not associated with early relapses in children.
Moreover, intellectual function seemed to be preserved. These results are
promising.
PMID: 15927408 [PubMed - as supplied by publisher]
-
| 8: J
Clin Oncol. 2005 May 1;23(13):3030-7. |
|
-
Increased fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG)
uptake in childhood CNS tumors is correlated with malignancy grade: a study
with FDG positron emission tomography/magnetic resonance imaging
coregistration and image fusion.
Borgwardt L, Hojgaard L, Carstensen H, Laursen H, Nowak M, Thomsen C,
Schmiegelow K.
Positron Emission Tomography and Cyclotron Unit, Department of Clinical
Physiology, Nuclear Medicine and Positron Emission Tomography,
Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, 2100
Copenhagen, Denmark. borgwardtpet@rh.dk
PURPOSE Positron emission tomography (PET) has been used in grading of CNS
tumors in adults, whereas studies of children have been limited. PATIENTS
AND METHODS Nineteen boys and 19 girls (median age, 8 years) with primary
CNS tumors were studied prospectively by fluorine-18
2-fluoro-2-deoxy-D-glucose (FDG) PET with (n = 16) or without (n = 22)
H(2)(15)O-PET before therapy. Image processing included coregistration to
magnetic resonance imaging (MRI) in all patients. The FDG uptake in tumors
was semiquantitatively calculated by a region-of-interest-based tumor
hotspot/brain index. Eight tumors without histologic confirmation were
classified as WHO grade 1 based on location, MRI, and clinical course (22 to
42 months). Results Four grade 4 tumors had a mean index of 4.27 +/- 0.5,
four grade 3 tumors had a mean index of 2.47 +/- 1.07, 10 grade 2 tumors had
a mean index of 1.34 +/- 0.73, and eight of 12 grade 1 tumors had a mean
index of -0.31 +/- 0.59. Eight patients with no histologic confirmation had
a mean index of 1.04. For these 34 tumors, FDG uptake was positively
correlated with malignancy grading (n = 34; r = 0.72; P < .01), as for
the 26 histologically classified tumors (n = 26; r = 0.89; P < .01). The
choroid plexus papilloma (n = 1) and the pilocytic astrocytomas (n = 3) had
a mean index of 3.26 (n = 38; r = 0.57; P < .01). H(2)(15)O-uptake showed
no correlation with malignancy. Digitally performed PET/MRI coregistration
increased information on tumor characterization in 90% of cases. CONCLUSION
FDG PET of the brain with MRI coregistration can be used to obtain a more
specific diagnosis with respect to malignancy grading. Improved PET/MRI
imaging of the benign hypermetabolic tumors is needed to optimize clinical
use.
Publication Types:
PMID: 15860860 [PubMed - indexed for MEDLINE]
-
| 9: J
Natl Cancer Inst. 2005 Jun 1;97(11):823-35. |
|
-
Formylpeptide receptor FPR and the rapid growth of
malignant human gliomas.
Zhou Y, Bian X, Le Y, Gong W, Hu J, Zhang X, Wang L, Iribarren P, Salcedo
R, Howard OM, Farrar W, Wang JM.
Laboratory of Molecular Immunoregulation, CCR, NCI-Frederick, Building 560,
Room 31-40, Frederick, MD 21702-1201, USA.
BACKGROUND: The formylpeptide receptor (FPR) is a G-protein-coupled receptor
(GPCR) that mediates chemotaxis of phagocytic leukocytes induced by
bacterial peptide N-formyl-methionyl-leucyl-phenylalanine (fMLF). We
previously showed that selected human glioma cell lines also express
functional FPR. We therefore investigated the relationship between FPR
expression and the biologic behavior of glioma cells. METHODS: Expression
and function of FPR in the human glioblastoma cell line U-87 were examined
by reverse transcription-polymerase chain reaction (RT-PCR) and chemotaxis
assays, respectively. FPR protein expression was detected in specimens from
33 human primary gliomas by immunohistochemistry. FPR short interfering (si)
RNA was used to block FPR expression in U-87 cells. Cell proliferation was
assessed by measuring DNA synthesis. Xenograft tumor formation and growth
were measured in nude mice. Endogenous FPR agonist activity released by
necrotic tumor cells was assessed by measuring FPR activation in an
FPR-transfected basophil leukemia cell line and live U-87 cells. Vascular
endothelial growth factor (VEGF) mRNA was assessed by RT-PCR, and VEGF
protein was assessed by enzyme-linked immunosorbent assay. All statistical
tests were two-sided. RESULTS: FPR was selectively expressed by the highly
malignant human glioblastoma cell line U-87 and most primary grade IV
glioblastomas multiforme and grade III anaplastic astrocytomas. U-87 cells
responded to the FPR agonist fMLF by chemotaxis (i.e., increased motility),
increased cell proliferation, and increased production of VEGF protein. FPR
siRNA substantially reduced the tumorigenicity of U-87 cells in nude mice
(38 days after implantation, mean tumor volume from wild-type U-87 cells =
842 mm3, 95% confidence interval [CI] = 721 to 963 mm3; and from FPR-siRNA
transfected U-87 cells = 225 mm3, 95% CI = 194 to 256 mm3; P = .001).
Necrotic glioblastoma cells released a factor(s) that activated FPR in live
U-87 cells. CONCLUSIONS: FPR is expressed by highly malignant human glioma
cells and appears to mediate motility, growth, and angiogenesis of human
glioblastoma by interacting with host-derived agonists. Thus, FPR may
represent a molecular target for the development of novel antiglioma
therapeutics.
PMID: 15928303 [PubMed - in process]
-
| 10: J Neurooncol.
2005 May;73(1):89-90. |
|
-
Medulloblastoma in two successive pregnancies.
Razak AR, Nasser Q, Morris P, Alcutt D, Grogan L.
Department of Medical Oncology, Beaumont Hospital, Dublin, Ireland,
albiruni_ ryan@yahoo.co.uk.
A 24-year old primaparous female at 20 weeks gestation presented acutely
with cerebellar symptoms. Magnetic resonance imaging brain showed evidence
of a cerebellar vermis lesion. This was diagnosed as medulloblastoma on
histopathological analysis. She underwent surgical debulking and
radiotherapy. Interestingly, the lesion recurred 4 years later on her second
pregnancy. She underwent further surgical debulking and adjuvant
chemotherapy. We believe this is the first reported description of recurrent
medulloblastoma in successive pregnancies. A brief discussion on this
disease and its management in pregnancy setting is also presented.
PMID: 15933823 [PubMed - in process]
-
| 11: J Neurooncol.
2005 May;73(1):71-86. |
|
-
Brachytherapy for brain tumors.
Vitaz TW, Warnke PC, Tabar V, Gutin PH.
Neurosurgical Service Memorial Sloan-Kettering Cancer Center, New York, NY,
USA.
Over the past several decades neurooncologists have attempted to find an
adjuvant treatment that prolongs survival for patients with malignant brain
tumors. Brachytherapy, radiotherapy delivered by placing radioactive sources
directly into the tumor, was initially thought to be the solution to this
problem. Initial single institution studies showed very promising results;
however, this technique has failed to show a significant survival advantage
in two randomized studies. Despite this, brachytherapy continues to be used
in a number of centers throughout the world for the treatment of various
types of brain tumors including low-grade gliomas, anaplastic astrocytomas,
glioblastomas, meningiomas and metastases. This article reviews
brachytherapy's rationale, radiobiology, complications, indications, and
results from numerous studies that have focused on its application for brain
tumors with emphasis on its application for glial tumors.
PMID: 15933821 [PubMed - in process]
-
| 12: J Neurooncol.
2005 May;73(1):57-69. |
|
-
Convection enhanced delivery for the treatment of
malignant gliomas: symposium review.
Vogelbaum MA.
Brain Tumor Institute, Department of Neurosurgery, Cleveland Clinic
Foundation/ND40, Cleveland, OH, USA, 44195, vogelbm@neus.ccf.org.
In January 2003 a symposium was held to discuss the current state of
progress and future challenges for the recently described technique of
convection enhanced delivery (CED). The focus of the CED symposium was on
the potential use of this novel drug delivery technology to enhance the
delivery of chemotherapy to malignant brain tumors. The international panel
of invited speakers included individuals who had a significant role in
pioneering the concept of CED, were actively pursuing new areas of
investigation into the uses of CED and/or who were directing the first
clinical trials using CED in patients with malignant brain tumors. Topics
covered included the physiology of the blood brain barrier, basic principles
of CED, application of CED to the treatment of brain tumors, and research
models that have been developed to further refine the technique of CED. Each
speaker's talk has been abstracted and a list of relevant references has
been compiled.
PMID: 15933820 [PubMed - in process]
-
| 13: J Neurooncol.
2005 May;73(1):53-6. |
|
-
Miliary brain metastases from primary gastric small cell
carcinoma: illustrating the seed and soil hypothesis.
Bugalho P, Chorao M, Fontoura P.
Department of Neurology, Hospital Sao Bernardo, Rua Camilo Castelo Branco,
2900, Setubal, Portugal, pfontoura@netcabo.pt.
Miliary metastases are a very rare condition usually found in the context of
primary lung tumor (small cell and adenocarcinoma), and refer to the
existence of numerous tumor nodules in widespread areas of the brain.
Besides pulmonary neoplasia, pancreatic adenocarcinoma and malignant
melanoma have also been implicated in some cases of miliary metastases. We
present the first case of miliary metastases originating in a primary small
cell gastric carcinoma (PSCGC), a rare type of neuroendocrine gastric tumor.
This location should therefore be investigated whenever other more frequent
tumors have been excluded as a cause for this particular type of metastases.
The pathological resemblance of PSCGC with small cell lung carcinoma may
correspond to an underlying similarity in biological behavior, which
accounts for this particular pattern of metastatic spreading, as proposed in
the seed and soil hypothesis.
PMID: 15933819 [PubMed - in process]
-
| 14: J Neurooncol.
2005 May;73(1):29-36. |
|
-
Tumor infiltration by myeloid suppressor cells in
response to T cell activation in rat gliomas.
Graf MR, Sauer JT, Merchant RE.
Department of Neurosurgery, Virginia Commonwealth University Medical Center,
1200 East Broad Street, P.O. Box 980631, Richmond, Virginia, 23298-0631,
mgraf@hsc.vcu.edu.
We have recently reported that activation of tumor-specific T cells by
subcutaneous vaccination with irradiated T9 glioma cells of syngeneic rats
with a pre-existing, intracranial (i.c.) T9 glioma (T9+vaccination) promotes
the mobilization of myeloid suppressor cells (MSC) which inhibit T cell
function resulting in unregulated tumor progression. The current study
investigated if this immunological paradigm could be recapitulated in T cell
deficient rats, in other rat glioma models or using a dendritic cell (DC)
vaccine. When nude rats were used in the T9+vaccination model, the level of
MSC tumor infiltration remained low in vaccinated and control groups and
there was no significant difference in tumor size between the groups.
Increased tumor infiltration by MSC after vaccination with respective
irradiated tumor cells was observed in the 9L, F98 and D74 gliomas. RT-2
tumors were markedly infiltrated with MSC regardless of vaccination.
Enhanced tumor progression in response to immunization and T cell activation
was observed in rats bearing F98 and D74 gliomas, although less pronounced
than in the T9 model, and there was a trend for increased tumor size in the
9L glioma model. Increased MSC infiltrate and augmented T9 glioma growth
were observed when DC pulsed with T9 cell lysate was used as a vaccine.
These results suggest that MSC infiltration and unregulated tumor growth in
response to vaccination is T cell-dependent; is not unique to the T9 glioma;
and can be recapitulated with an alternate immunization approach.
PMID: 15933813 [PubMed - in process]
-
| 15: J Neurooncol.
2005 May;73(1):9-18. |
|
-
The brain slice chamber, a novel variation of the Boyden
Chamber Assay, allows time-dependent quantification of glioma invasion into
mammalian brain in vitro.
Schichor C, Kerkau S, Visted T, Martini R, Bjerkvig R, Tonn JC,
Goldbrunner R.
Department of Neurosurgery, University of Munich, Germany,
roland.goldbrunner@med.uni-muenchen.de.
Glioma cell invasion occurs in a complex micromilieu consisting of neural
and glial cells, myelinated fiber tracts, blood vessels and extracellular
matrix proteins. The present work describes the brain slice chamber (BSC) as
a novel experimental model for assessing invasion of glioma cells into adult
mammalian white and gray matter on the basis of the well known Boyden
chamber system. As a matrix for invasive tumor cells we used freshly
prepared brain tissue from adult pigs. The tissue was sectioned into 40 mum
slices that were mechanically fixed to a millipore filter. The neural
structures and the three-dimensional architecture of the slice was preserved
as verified by immunohistochemistry, light- and electron microscopy. Human
U-373 and U87 astrocytoma cells stably transfected with green fluorescent
protein (GFP) were assessed for their invasiveness into the brain-slices
during a 24 h period. Invasion of U-87 GFP cells was quantified at different
time intervals by confocal laser scanning microscopy showing more intense
invasion into white compared to gray matter. Two cytostatics (vincristin and
paclitaxel) which both are known to affect the cytoskeleton, inhibited
glioma cell invasion in a dose dependent manner, which makes the presented
model system suitable for functional experiments. In conclusion, the BSC
represents a valid and rapid experimental model that may be used to describe
the invasive behavior of glioma cells within the preserved three-dimensional
structure of mammalian brain tissue in vitro.
PMID: 15933811 [PubMed - in process]
-
| 16: J Neurooncol.
2005 May;73(1):1-7. |
|
-
Scorpion venom induces glioma cell apoptosis in vivo and
inhibits glioma tumor growth in vitro.
Wang WX, Ji YH.
Institute of Physiology, Shanghai Institutes for Biological Sciences,
Chinese Academy of Sciences, China.
Malignant gliomas are the main brain tumors notoriously resistant to
currently available therapies, since they fail to undergo apoptosis upon
anticancer treatment. Recent progress on enhanced studies of ion channels
involved in glioma cells shed new light on the investigation of glioma cell
growth and proliferation. Here we report BmK scorpion venom, a rich resource
of various ion channels blockers/modulators, induces cell death of cultured
malignant glioma U251-MG cells in vitro specifically at a dose of 10 mg/ml
while shows no effect on human hepatocellular carcinoma cells and Chinese
hamster ovary cells. The glioma cell death was then determined as apoptosis
using 4,6-diamidino-2-phenylindole staining and fluorescence-activated cell
sorting analysis. After incubation with BmK venom for 32 and 40 h, 36.20%
and 63.08% of U251-MG cells showed apoptosis. Furthermore, BmK venom could
significantly inhibit the tumor growth in vitro, which was assessed using
U251-MG tumor xenografts on severe combined immunodeficiency mice. The tumor
volume of the BmK venom treated mice is nearly 1/8 of that of control after
21 days, and the tumor weight is less than half of that of control. That BmK
venom induces apoptosis and inhibits growth of glioma may result from the
inhibition and/or modulation of various ion channels in glioma cells.
PMID: 15933810 [PubMed - in process]
-
| 17: J Neurooncol.
2005 Apr;72(2):179-83. |
|
-
Primary dissemination of high-grade gliomas in children:
experiences from four studies of the Pediatric Oncology and Hematology
Society of the German Language Group (GPOH).
Benesch M, Wagner S, Berthold F, Wolff JE.
Division of Pediatric Hematology and Oncology, Department of Pediatrics and
Adolescence Medicine, Medical University of Graz, Auenbruggerplatz 30,
A-8036, Graz, Austria, martin.benesch@klinikum-graz.at.
Purpose. Clinical data on central nervous system (CNS) dissemination of
high-grade gliomas (HGG) at initial presentation in children are
rare.Patients and methods. We conducted a retrospective data analysis of all
patients enrolled into four consecutive HGG protocols of the Pediatric
Oncology and Hematology Society of the German Language Group (GPOH) to
determine the incidence of primary CNS dissemination of HGG and to describe
clinical characteristics and outcome of children with HGG who were diagnosed
with CNS dissemination at initial presentation. 546 patients with newly
diagnosed HGG (n=348) or diffuse intrinsic pontine gliomas (n=198) were
enrolled in these four studies. Data concerning tumor dissemination are
available from 324 patients.Results. A total of 10 patients (3.1%)
(anaplastic astrocytoma: n=3, glioblastoma multiforme: n=6, diffuse
intrinsic pontine glioma: n=1) had primary tumor dissemination. Median age
at diagnosis was 9.3 years (range: 0.3-21.3 years). The most frequent
primary tumor sites were the cortex (n=4), followed by the ventricles (n=2),
cerebellum (n=1), spinal cord (n=1), and pons (n=1). One patient had diffuse
gliomatosis cerebri. Following surgery eight patients received local
radiotherapy and eight additional chemotherapy. At a median follow-up of 10
months (range: 0.05-3 years) four patients are alive. None is disease-free.
Median progression-free and overall survival was 0.8 years (95% CI 0.2-1.4)
and 1.5 years (95% CI 0.67-2.29) for patients with primary tumor
dissemination, respectively, with no statistically significant differences
between the group with and the group without primary tumor
dissemination.Conclusions. Initial diagnostic evaluation should include
complete CNS imaging as well as cerebrospinal fluid examination in all
patients with HGG. As prognosis of children with HGG and primary CNS
dissemination was not inferior to patients without dissemination in our
population, these patients should be treated in the same way as patients
without primary CNS dissemination.
PMID: 15925999 [PubMed - in process]
-
| 18: J Neurooncol.
2005 Apr;72(2):157-161. |
|
-
Bone marrow metastases from glioblastoma multiforme - A
case report and review of the literature.
Rajagopalan V, Kamar FG, Thayaparan R, Grossbard ML.
Hematology- Oncology Unit, St. Luke's- Roosevelt Hospital Center, New York,
USA.
Clinically detected extra-cranial metastases from glioblastoma multiforme
(GBM) are quite rare, with an incidence of <2% reported in the published
literature. Among the various reported sites of systemic metastases from
GBM, there are few cases of clinically symptomatic bone marrow metastasis.
The case of a patient developing systemic dissemination of a GBM is
described. A 60-year-old man with GBM who developed back pain,
thrombocytopenia and subsequently neurological deficits was found to have
extensive bony and bone marrow metastases. Previously reported cases of
extra-cranial systemic spread of GBM and attempts made in the literature to
explain the possible routes of extra-neural dissemination are reviewed.
PMID: 15925996 [PubMed - as supplied by publisher]
-
| 19: J Neurooncol.
2005 Apr;72(2):151-6. |
|
-
Apoptotic markers for primary brain tumor prognosis.
Konstantinidou AE, Korkolopoulou P, Patsouris E.
Department of Pathology, Faculty of Medicine, National Capodistrian
University of Athens, 28, Narkisson street, Halandri, Athens, 152 33,
Greece, ankon@med.uoa.gr.
Molecular studies of brain tumors have provided insights into pathogenesis,
yet it is unclear how important these markers are in predicting clinical
outcome and response to treatment. Quantitation of apoptosis by various
techniques and the expression of several apoptotic markers have been studied
in brain tumors, seeking to refine the information gained from established
prognostic variables, which traditionally dictate therapeutic approaches. In
the present review we discuss the role of the most extensively examined
molecules involved in the apoptotic procedure, such as bcl-2, bax, fas/fasL,
survivin and p53, as well as the incidence of baseline apoptosis in various
brain tumors, in relation to prognosis. Summarizing current evidence,
increased apoptosis and p53 genetic alterations have been advanced as
adverse prognosticators in various types of central nervous system
neoplasms, while bcl-2 expression appears to be deprived of any predictive
value in primary brain tumors. The prognostic significance of the remaining
apoptosis-related molecules remains controversial or too limited to draw any
firm conclusions. The lack of unanimity of results mostly based on
single-center retrospective studies underscores the necessity for large
prospective randomized clinical trials, to elucidate the role of these
molecular markers as determinants of clinical decision-making and as
potential correlates of a pathobiologically tailored and individualized
treatment strategy.
PMID: 15925995 [PubMed - in process]
-
| 20: J Neurooncol.
2005 Apr;72(2):133-47. |
|
-
Beauty product-related exposures and childhood brain
tumors in seven countries: results from the SEARCH International Brain Tumor
Study.
Efird JT, Holly EA, Cordier S, Mueller BA, Lubin F, Filippini G,
Peris-Bonet R, McCredie M, Arslan A, Bracci P, Preston-Martin S.
John A. Burns School of Medicine, University of Hawaii at Manoa, 1960
East-West Road, Room D-103, Honolulu, Hawaii, 96822-2319, USA.
Data from 1218 cases of childhood brain tumors (CBT) diagnosed between 1976
and 1994 and 2223 matched controls from the general population were included
in an analysis of maternal beauty product exposure and beauty-related
employment in 9 centers in 7 countries. A 50% increased odds ratio (OR) [95%
confidence interval (CI) = 1.0-2.1] for CBT was observed among children of
mothers who were exposed via personal use of and/or possible ambient contact
with beauty products during the 5 years preceding the index child's birth
compared with children of mothers never exposed to beauty products during
this time period. Overall maternal personal use of hair-coloring agents in
the month before or during the pregnancy of the index child's birth was not
associated with CBT (OR = 1.0, CI = 0.83-1.3) or with astroglial (OR = 1.1,
CI = 0.85-1.4), PNET (OR = 1.0, CI = 0.71-1.5) and other glial subtypes (OR
= 1.0, CI = 0.62-1.0). Similarly, no statistically increased ORs or
discernable pattern of risk estimates were observed for period of use or for
number of applications per year for maternal personal use of hair-coloring
agents overall or by histologic type. Among children born on or after 1980,
increased ORs for CBT were associated with maternal non-work-related
exposure to any beauty products (OR = 2.6, CI = 1.2-5.9), hair-dyes (OR =
11, CI = 1.2-90), and hair sprays (OR = 3.4, CI = 1.0-11). No overall
increased OR for CBT was observed among children of mothers employed in
beauty-related jobs during the 5 years preceding the index child's birth
compared with those who reported no beauty-related employment. In general,
other specific beauty product-related exposures were not associated with
increased ORs for CBT. Data from our study provide little evidence of an
increased risk for CBT with mothers' exposures to beauty products.
PMID: 15925993 [PubMed - in process]
-
| 21: J Neurooncol.
2005 Apr;72(2):125-31. |
|
-
Intratumoral delivery of mitoxantrone in association with
90-Y radioimmunotherapy (RIT) in recurrent glioblastoma.
Boiardi A, Bartolomei M, Silvani A, Eoli M, Salmaggi A, Lamperti E,
Milanesi I, Botturi A, Rocca P, Bodei L, Broggi G, Paganelli G.
Department of Neuro-oncology, Istituto Nazionale Neurologico, "C.
Besta", Via Celoria 11, 20133, Milan, Italy, boiardi@istituto-besta.it.
Twenty-six recurrent Glioblastoma (rGBM) patients sequentially treated at
the National Neurological Institute 'C Besta' were enrolled for a second
surgery in order to remove recurrent tumor and to place an Ommaya reservoire
to allow local delivery of chemotherapy and local pre-targeted
radio-immunotherapy (RIT). All patients had partial tumor resection and 75%
of them had a residual tumor mass after exeresis larger than 2 cm. After
surgery all patients were managed with a second line systemic chemotherapy
(PCV). Moreover the protocol scheduled two cycles of local RIT (90 Yttrium
5- 25 mCi per cycle) with a 10 week interval. Locoregional mitoxantrone
chemotherapy was locally delivered as a single dose of 4 mg every 20 days.
Responses to treatment were assessed by monthly neurological examination and
by MRI or contrast-enhanced CT scan performed every 2 months.For the whole
group of patients the PFS after second surgery at 6 and 12 months was 61%
and 22%, respectively and survival after recurrence at 6, 12 and 18 months
was 80%, 53% and 42%, respectively. Neither major side effects occurred
systemically nor related on the place of local injections. The percentage of
long-term survivors was very high: 42% of patients were still alive at 18
months. We stress the concept that the combined treatments could be more
effective if delivered into a smaller residual tumor mass and probably in an
adjuvant setting, before tumour recurrence.
PMID: 15925992 [PubMed - in process]
-
| 22: J Neurooncol.
2005 Apr;72(2):115-22. |
|
-
Alterations of cell cycle regulators in gliomatosis
cerebri.
Mawrin C, Kirches E, Schneider-Stock R, Boltze C, Vorwerk CK, von Mawrin
A, Kirches E, Schneider-Stock R, Boltze C, Vorwerk CK, von Mawrin A, Kirches
E, Schneider-Stock R, Boltze C, Vorwerk CK, von Mawrin A, Kirches E,
Schneider-Stock R, Boltze C, Vorwerk CK, Deimling A, Stoltenburg-Didinge G,
Bornemann A, Romeike B, Sellhaus B, Dietzmann K.
Institut fur Neuropathologie, Otto-von-Guericke-Universitat, Leipziger
Strasse 44, D-39120, Magdeburg, Germany.
Gliomatosis cerebri (GC) is regarded as a rare glial neoplasm of unknown
origin, and a detailed analysis of molecular alterations underlying this
disease has started only recently. However, because GC characteristically
affects large parts of the brain and spinal cord, the distribution of
genetic alterations may be highly variable between different tumor areas.
Additionally, tumor areas with varying degrees of differentiation may be
present, raising the possibility to model the genetic events associated with
astrocytoma progression. Here we analyzed various tumor regions with
features of low-grade and high-grade astrocytomas from 9 autopsy-proven GC
cases for the immunoexpression of the cell cycle-controlling proteins mdm2,
p21, p27/kip1, p16, and Rb. The samples were also screened for EGFR
expression, and for amplification of the EGFR and MDM2 genes. Furthermore,
allelic losses of the CDKN2A gene and of a PTEN flanking region of
chromosome 10 were determined. We detected tumor regions with
immunoexpression of p21 only rarely in our series, without association to
the tumor grade. No MDM2 gene amplification was detected. In contrast, three
cases demonstrated maintained Rb expression. The expression of p27(kip1)
showed a clear reduction with increasing astrocytoma malignancy in 7 cases.
Allelic loss of the CDKN2A gene occurred in 5 patients but was not related
to the tumor grading, nor to the intensity of p16 immunoexpression. No
homozygous CDKN2Adeletions were detected. EGFR amplification was also absent
in our series, but one case demonstrated EGFR expression only in the
high-grade tumor area. Allelic losses on chromosome 10 were found in one out
of six informative cases. However, marked differences in the
immunoexpression, as well as in the distribution of genetic aberrations were
seen between different tumor samples within a given case. The distribution
of the alterations suggests that these molecular genetic changes represent
secondary events, which may develop within tumor clones derived from a
common founder tumor clone characterized by extraordinary spreading through
the brain. Moreover, the detected aberrations in gliomatosis cerebri can
reflect the tumor progression associated with secondary malignant
astrocytoma formation even within a single case.
PMID: 15925990 [PubMed - in process]
-
| 23: J Neurooncol.
2005 Apr;72(2):107-13. |
|
-
Tumor lysate and IL-18 loaded dendritic cells elicits Th1
response, tumor-specific CD8+ cytotoxic T cells in patients with malignant
glioma.
Yamanaka R, Honma J, Tsuchiya N, Yajima N, Kobayashi T, Tanaka R.
Department of Neurosurgery, Brain Research Institute, Niigata University,
Asahimachi-dori 1-757, Niigata City, 951-8585, Japan,
ryaman@bri.niigata-u.ac.jp.
In this study, we demonstrate that tumor lysate-loaded dendritic cells can
elicit a specific CD8+ cytotoxic T lymphocyte response against autologous
tumor cells in patients with malignant glioma. CTL from three of five
patients expressed strong cytolytic activity against autologous glioma
cells, did not lyse autologous lymphoblasts and were variably cytotoxic
against the LAK-sensitive cell line Daudi. Also, DCs pulsed normal brain
lysate failed to induce cytolytic activity against autologous glioma cells,
suggesting the lack of autoimmune response. Two of five patients CD8+ T
cells expressed a modest cytotoxicity against autologous glioma cells. CD8+
T cells isolated during these ineffective primings secreted large amounts of
IL-10, less amounts of IFN-gamma as detected by ELISA, Type 2 bias in the
CD8+ T cell response accounts for the lack of cytotoxic effector function
from these patients. Cytotoxicity against autologous glioma cells could be
significantly inhibited by anti-HLA class I antibody. These data demonstrate
that tumor lysate-loaded DC can be an effective tool in inducing
glioma-specific CD8+ CTL able to kill autologous glioma cells in vitro.
However, high levels of tumor specific tolerance in some patients may
account for a significant barrier to therapeutic vaccination. Moreover,
cytotoxic responses were augmented by transfecting DC with the gene for
IL-18. For all five patients, CD8+T cells treated with IL18 transfected DC
produced Th1 response. These results may have important implications for the
treatment of malignant glioma patients with immunotherapy. DCs loaded with
total tumor lysate and IL-18 may represent a method for inducing Th1
immunoresponses against the entire repertoire of glioma antigens.
PMID: 15925989 [PubMed - in process]
-
| 24: J Neurosurg.
2005 May;102(4 Suppl):417-22. |
|
Radiation-induced cerebellar glioblastoma at the site of
a treated medulloblastoma: case report.
Yang SY, Wang KC, Cho BK, Kim YY, Lim SY, Park SH, Kim IH, Kim SK.
Departments of Pathology and Therapeutic Radiology, Seoul National
University College of Medicine, Seoul, Korea.
Radiation-induced glioblastoma multiforme (GBM) is a rare complication of
radiotherapy. The authors report such a case occurring 10 years after
treatment of cerebellar medulloblastoma. The patient was a 15-year-old boy
who had undergone a gross-total removal of a medulloblastoma and received
radiation therapy at the age of 5 years. He had experienced no tumor
recurrences for 10 years until a new enhancing mass was found at the
original site of the medulloblastoma. Following its resection the new lesion
was found to be a GBM and there was no evidence of a medulloblastoma. The
second tumor developed at the same site as the previous one after a
sufficient latent period and fulfilled the criteria for a radiation-induced
neoplasm. The original tumor cells expressed synaptophysin without p53
overexpression, a characteristic feature of medulloblastomas. In contrast,
cells from the later tumor expressed glial fibrillary acidic protein and p53
but not synaptophysin. A sequence analysis of the p53 gene showed deletion
at codon 233 and a C to G transition at codon 278 in the GBM but no mutation
in the medulloblastoma. A GBM specimen revealed no amplification of the
epidermal growth factor receptor compared with a normal control specimen. In
conclusion, the clinical features of a radiation-induced GBM are similar to
that of the primary GBM, whereas its genetic alterations render it a
secondary GBM. These findings indicate that radiation-induced GBM should be
considered a distinct clinical entity.
PMID: 15926395 [PubMed - in process]
-
| 25: Neurol Res.
2005 Jan;27(1):53-6. |
|
-
Congenital intracranial immature teratoma of the lateral
ventricle: a case report and review of the literature.
Erman T, Gocer IA, Erdogan S, Gunes Y, Tuna M, Zorludemir S.
Department of Neurosurgery, Cukurova University, School of Medicine,
Balcali-Adana/01330, Turkey. ermant@cu.edu.tr
OBJECTIVE: Congenital intracranial tumors are very rare and only account for
0.5-1.5% of all childhood brain tumors. The most common type of these tumors
present at birth is teratomas, which represent 0.5% of all intracranial
tumors. Most teratomas are midline tumors located predominantly in the
sellar and pineal regions. In this study, we report a neonatal intracranial
immature teratoma at the lateral ventricle because of its rare location.
CASE REPORT: A 3-day-old female neonate presented with a history of
irritability, vomiting, and recurrent generalized clonic seizures since
birth. A head computed tomographic scan and magnetic resonance imaging
disclosed a large tumor filling the right lateral ventricle and extending
into the ipsilateral posterior fossa. With right parieto-occipital
craniotomy, large grayish-white lobulated vascular mass was encountered and
total removal of tumor was performed. Histological examination revealed the
diagnosis of immature teratoma. CONCLUSION: The prognosis of congenital
intracranial immature teratoma is usually poor because the lesions are
extensive when they are identified. Prenatal ultrasonography is necessary
for the prenatal diagnosis. Fetal magnetic resonance imaging should be made
for the evaluation of intracranial tumor. If the tumor is detected before
the 24 week of gestation, termination of the pregnancy should be considered.
Publication Types:
PMID: 15829159 [PubMed - indexed for MEDLINE]
-
| 26: Neurol Res.
2005 Jan;27(1):11-5. |
|
-
Diagnostic value of super-selective bilateral cavernous
sinus sampling with hypothalamic stimulating hormone loading in patients
with ACTH-producing pituitary adenoma.
Fujimura M, Ikeda H, Takahashi A, Ezura M, Yoshimoto T, Tominaga T.
Department of Neurosurgery, Tohoku University Graduate School of Medicine,
1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
fujimur@nsg.med.tohoku.ac.jp
AIMS: Early diagnosis and early treatment by transsphenoidal surgery is
desirable for ACTH-producing pituitary microadenoma, but accurate
localization of the functional lesion is not always possible before surgery
because magnetic resonance (MR) imaging may provide false negative and/or
positive findings. The diagnostic value of super-selective bilateral
cavernous sinus sampling with the administration of corticotropin-releasing
hormone (CRH) was assessed in patients with functioning ACTH-producing
pituitary adenoma. METHODS: Fifteen patients with pituitary adenoma (14 with
microadenoma) aged from 23 to 74 years (mean 46.7 years) underwent cavernous
sinus sampling with or without the CRH loading test and subsequent
transsphenoidal surgery in our institute from October 1997 through to
November 2002. MR imaging including dynamic scan failed to detect the
adenomatous lesion in all patients. To eliminate the bias due to uneven
blood flow in the cavernous sinuses and the multi-hormonal response to CRH
administration, the ACTH/FSH ratios were evaluated. The inter-cavernous
gradient (ICG) was calculated as the higher/lower ACTH venous blood levels
in the right and left cavernous sinuses with or without CRH loading. The
adjusted ICG was calculated using the ACTH/FSH ratios. The results were
compared with the surgical findings. An ICG of 1.4 or greater was considered
to indicate the localization of the responsible lesion. RESULTS:
Transsphenoidal surgery revealed the functioning lesion on the right in five
cases, the left in six, the midline in three and the bilateral lateral wings
(double adenoma) in one. Adjusted ICG with CRH loading had a localization
accuracy of 93.3% (14/15), which was significantly higher than that of 73.3%
(11/15) using ICG without hypothalamic stimulating hormone loading (p =
0.0402). CONCLUSIONS: Super-selective cavernous sinus sampling with
hypothalamic stimulating hormone administration can provide accurate
localization of the responsible lesion in patients with ACTH-producing
pituitary adenoma.
Publication Types:
PMID: 15829152 [PubMed - indexed for MEDLINE]
-
| 27: Neurosurgery. 2005
Jun;56(6):1243-52; discussion 1252-3. |
|
-
Safety and feasibility of convection-enhanced delivery of
Cotara for the treatment of malignant glioma: initial experience in 51
patients.
Patel SJ, Shapiro WR, Laske DW, Jensen RL, Asher AL, Wessels BW,
Carpenter SP, Shan JS.
Department of Neurological Surgery, Medical University of South Carolina,
Charleston, South Carolina, USA.
OBJECTIVE: We report the safety and feasibility of using convection-enhanced
delivery to administer Cotara (Peregrine Pharmaceuticals, Inc., Tustin, CA),
a novel radioimmunotherapeutic agent, to patients with malignant glioma.
METHODS: Between April 1998 and November 2002, 51 patients with
histologically confirmed malignant glioma received Cotara by
convection-enhanced delivery. Most patients (88%) were treated with Cotara
targeting tumor volume-dependent, single or multiple administrations of
activity ranging from 0.5 to 3.0 mCi/cm3 of baseline clinical target volume.
Two weeks after infusion, single-photon emission computed tomographic
imaging determined the spatial distribution of Cotara. Patients were
followed for as long as 41 months (average follow-up, 5 mo). Safety was
evaluated on the basis of incidence of procedure-related, neurological, and
systemic adverse events. Feasibility was evaluated in a subset of patients
on the basis of the correlation between the prescribed activity and the
actual activity administered to the targeted region. RESULTS: Fifty-one
patients, 37 with recurrent glioblastoma multiforme, 8 with newly diagnosed
glioblastoma multiforme, and 6 with recurrent anaplastic astrocytomas, were
treated. Average tumor volume was 36 +/- 27.6 cm3 (range, 5-168 cm3). Of the
67 infusions, 13 (19%), 52 (78%), and 2 (3%) delivered less than 90%, 100
+/- 10%, and more than 110%, respectively, of the prescribed administered
activity to the targeted region. Treatment-emergent, drug-related central
nervous system adverse events included brain edema (16%), hemiparesis (14%),
and headache (14%). Systemic adverse events were mild. Several patients had
objective responses to Cotara. CONCLUSION: The majority of Cotara infusions
delivered between 90 and 110% of the prescribed administered activity to the
targeted region. This method of administration has an acceptable safety
profile compared with literature reports of other therapeutics delivered by
convection-enhanced delivery.
PMID: 15918940 [PubMed - in process]
-
| 28: Neurosurgery. 2005
Jun;56(6):1234-41; discussion 1241-2. |
|
-
Depression in relation to survival among neurosurgical
patients with a primary brain tumor: a 5-year follow-up study.
Mainio A, Hakko H, Timonen M, Niemela A, Koivukangas J, Rasanen P.
Department of Psychiatry, University of Oulu, and Oulu University Hospital,
Oulu, Finland. arja.mainio@oulu.fi
OBJECTIVE: The adverse impact of depression in relation to survival among
cancer patients is currently a subject of great interest in research. In a
5-year follow-up study, we investigated the association of depression with
survival of patients with a primary brain tumor. METHODS: The study
population consisted of 75 patients with a solitary primary brain tumor
treated surgically at the Oulu Clinic for Neurosurgery, Oulu University
Hospital, in Northern Finland. The patients were interviewed during
admission to the hospital for the tumor surgery. Assessment of depression
was made using the Beck Depression Inventory and the Crown-Crisp
Experiential Index. Information on all deaths within 60 months after tumor
operation was collected from the Cause of Death Register, provided by
Statistics Finland. RESULTS: The patients with a high-grade glioma had a
survival time of 22.5 months (standard deviation, 21.4 mo), whereas the
corresponding time was 50.2 months (standard deviation, 19.9 mo) for
patients with a low-grade glioma and 58.2 months (standard deviation, 9.4
mo) for the patients with a histologically benign tumor (P < 0.001,
difference between groups, Kruskal-Wallis test). In the subgroup of patients
with low-grade gliomas, depressive patients had a significantly shorter
survival time compared with nondepressive subjects (P = 0.031, Kaplan-Meier
survival analysis). A corresponding difference was not found in patients
with high-grade gliomas or benign tumors. Tumor location in one hemisphere
compared with bilateral location and wider extent of tumor surgery was
associated with better survival in patients with low-grade gliomas and
benign tumors but not in patients with high-grade gliomas. CONCLUSION:
Preoperative depression seemed to be a significant prognostic factor for
worse survival in low-grade glioma patients. In clinical practice, an
evaluation of depression among brain tumor patients by structured and
standardized diagnostic methods is needed to distinguish the patients whose
depression actually needs treatment. The effective treatment of clinical
depression among brain tumor patients and the impact of treatment on the
patients' chances of survival should be a focus of future research.
PMID: 15918939 [PubMed - in process]
-
| 29: Oncogene. 2005 May
12;24(21):3427-35. |
|
-
Transgenic mice overexpressing the wild-type form of the
HMGA1 gene develop mixed growth hormone/prolactin cell pituitary adenomas
and natural killer cell lymphomas.
Fedele M, Pentimalli F, Baldassarre G, Battista S, Klein-Szanto AJ,
Kenyon L, Visone R, De Martino I, Ciarmiello A, Arra C, Viglietto G, Croce
CM, Fusco A.
Istituto di Endocrinologia ed Oncologia Sperimentale del CNR c/o
Dipartimento di Biologia e Patologia Cellulare e Molecolare, Universita di
Napoli Federico II, 80131 Naples, Italy.
Overexpression of HMGA1 proteins is a constant feature of human carcinomas.
Moreover, rearrangements of this gene have been detected in several human
benign tumors of mesenchymal origin. To define the role of these proteins in
cell transformation in vivo, we have generated transgenic mice
overexpressing ubiquitously the HMGA1 gene. These mice developed mixed
growth hormone/prolactin cell pituitary adenomas and natural killer
(NK)-T/NK cell lymphomas. The HMGA1-induced expression of IL-2 and IL-15
proteins and their receptors may account for the onset of these lymphomas.
At odds with mice overexpressing a wild-type or a truncated HMGA2 protein,
adrenal medullar hyperplasia and pancreatic islet cell hyperplasia
frequently occurred and no increase in body size and weight was observed in
HMGA1 mice. Taken together, these data indicate an oncogenic role of the
HMGA1 gene also in vivo.
PMID: 15735694 [PubMed - indexed for MEDLINE]
|
Volume 4, Number
24 - 8 June 2005