The p53/Mdm2/p14(ARF) cell cycle control pathway genes
may be inactivated by genetic and epigenetic mechanisms in gliomas.
Laboratorio de Oncogenetica Molecular, Unidad de Investigacion, Hospital
Universitario La Paz, Paseo Castellana 261, 28046 Madrid, Spain.
PMID: 16434325 [PubMed - in process]
Human leukocyte antigen and antigen processing machinery
component defects in astrocytic tumors.
Department of Animal Biology, University of Pavia and Center of Study for
Histochemistry, Consiglio Nazionale delle Ricerche, Italy.
PURPOSE: To determine the frequency of abnormalities in human leukocyte
antigen (HLA) and antigen processing machinery (APM) component expression in
malignant brain tumors. This information may contribute to our understanding
of the immune escape mechanisms used by malignant brain tumors because HLA
antigens mediate interactions of tumor cells with the host's immune system.
EXPERIMENTAL DESIGN: Eighty-eight surgically removed malignant astrocytic
tumors, classified according to the WHO criteria, were stained in
immunoperoxidase reactions with monoclonal antibody recognizing monomorphic,
locus-specific, and allospecific determinants of HLA class I antigens,
beta2-microglobulin, APM components (LMP2, LMP7, TAP1, TAP2, calnexin,
calreticulin, and tapasin), and HLA class II antigens. RESULTS: HLA class I
antigens were lost in approximately 50% of the 47 glioblastoma multiforme (GBM)
lesions and in approximately 20% of the 18 grade 2 astrocytoma lesions
stained. Selective HLA-A2 antigen loss was observed in approximately 80% of
the 24 GBM lesions and in approximately 50% of the 12 grade 2 astrocytoma
lesions stained. HLA class I antigen loss was significantly (P < 0.025)
correlated with tumor grade. Among the APM components investigated, tapasin
expression was down-regulated in approximately 20% of the GBM lesions
analyzed; it was associated, although not significantly, with HLA class I
antigen down-regulation and tumor grade. HLA class II antigen expression was
detected in approximately 30% of the 44 lesions analyzed. CONCLUSION: The
presence of HLA antigen defects in malignant brain tumors may provide an
explanation for the relatively poor clinical response rates observed in the
majority of the T cell-based immunotherapy clinical trials conducted to date
in patients with malignant brain tumors.
PMID: 16322289 [PubMed - indexed for MEDLINE]
Pathological changes after radiotherapy for primary
pituitary carcinoma: a case report.
Department of Radiology, University of Tokyo Hospital, 7-3-1, Hongo,
Bunnkyou-ku, Tokyo 113-8655, Japan. yamashitah-RAD@h.u-tokyo.ac.jp
Pituitary carcinomas are extremely rare. The definition, diagnosis, therapy,
and prognosis are controversial. So far, to our knowledge, there has been no
report regarding pathological changes after radiotherapy for primary
pituitary carcinoma. We reported a single case of a presumed prolactin
staining pituitary carcinoma. We defined carcinoma by premorbid intracranial
dissemination of the tumor. There were no proven extracranial metastases.
The tumor was silent on PET scanning. The patient received external beam
radiotherapy alone as primary therapy. Post-irradiation histology revealed
that necrotic tissue made up approximately more than half. Tumor had viable
cells. Probably approximately three-fifth of tumor cells were without
alteration and approximately two-fifth were with degeneration. We confirmed
that necrosis but no apoptosis were coexistent in the cells post irradiation
for pituitary carcinoma.
PMID: 16283444 [PubMed - indexed for MEDLINE]
Primary intradural myxoid chondrosarcoma: a case report
and review in the literature.
Department of Neurosurgery, Haseki Educational and Research Hospital,
Istanbul, Turkey. firstname.lastname@example.org
OBJECTIVE AND IMPORTANCE: Chondrosarcomas are extremely rare cartilaginous
tumours that typically usually are associated with bone. Therapeutic
experience with primary spinal mesenchymal chondrosarcomas is also extremely
limited. The exact origin of rare intradural spinal chondrosarcomas remains
obscure. We report the first case in the literature of a primary intradural
myxoid chondrosarcoma.CLINICAL PRESENTATION: This 40-year-old man
experienced a 3 month history with back pain. The results of his
neurological examination were normal. Magnetic resonance imaging (MRI)demonstrated
at the T12 level intradural tumour. We could not identify this lesion as
chondrosarcoma in preoperative period.INTERVENTION: At surgery, a mass found
attached solely to pia mater, with a normal arachnoid and dura mater
overlying was seen. The mass was excised completely and microscopic
examination identified a myxomatous chondrosarcoma. The postoperative course
was unremarkable. But a histological examination revealed primary myxoid
chondrosarcoma. Experience with primary spinal mesenchymal chondrosarcomas
is also extremely limited. We especially discussed to the histological
examination.CONCLUSION: The differential diagnosis considered in the present
case included meningioma, plasmacytoma, and non-neoplastic intradural spinal
cord lesion. We emphasize the benefit of surgical resection without
radiotherapy and/or chemotherapy. This case presents the first case in the
literature of an primary spinal intradural myxoid chondrosarcoma.
PMID: 16283441 [PubMed - indexed for MEDLINE]
Aggressive spinal germinoma with ascending metastases.
Mersin University School of Medicine, Mersin, Turkey. email@example.com
We report the case of a 28-year-old young man who presented with progressive
paraparesis and urinary incontinence. Initial spinal MR scans showed a
sausage-like lesion that extended between L1 and S2. At surgery, an
encapsulated intradural extramedullary tumor was removed en bloc. The
initial histopathological diagnosis was ependymoma. The tumor recurred
locally to double its original size only 4 months later. After second
surgery, 5,100 cGy of local spinal radiation was given since the pathologist
believed that the new tumor exhibited anaplastic features. Subsequently
tumor recurred at T6-10 levels and later in the right parasellar region.
Surgery was undertaken for both recurrences and radiation to whole spine and
to whole brain respectively followed surgery. At 11 months after the initial
presentation, a new tumor was diagnosed at T11-T12 levels. After fifth
surgery, chemotherapy with cisplatin, doxorubicin and vincristine was
started. At this stage, review of all five surgical specimens by an outside
neuropathologist was considered crucial. The new and correct histological
diagnosis was germinoma. A new chemotherapy regimen targeted for germinoma
was then started. The patient remains alive with no evidence of disease at
22 months after initial presentation. Primary spinal germinomas are
exceedingly rare. A review of the literature revealed only 14 biopsy-proven
spinal germinoma cases. Our case is clearly unique in aggressivity of the
tumor, a feature often unexpected for germinomas. This case proves that the
dissemination risk may be very serious for germinomas and that the
craniospinal radiation may be a more secure treatment mode.
PMID: 16132516 [PubMed - indexed for MEDLINE]
Cerebral involvement of metastatic thymic carcinoma.
do H, Park
Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University
School of Medicine, 50 Ilwon-dong Kangnam-gu, Seoul 135-710, Korea. firstname.lastname@example.org
The authors report the clinical presentations, radiological findings, and
treatment outcome of thymic carcinoma patients with cerebral metastasis. The
authors retrospectively reviewed the medical records of 49 patients with
thymic carcinoma and 6 of them (12.2%) developed brain metastasis. There
were 4 men and 2 women with a mean age of 48 years (ranging from 33 to 56
years). The pathological types of thymic carcinoma which developed brain
metastasis were thymic carcinoma type C of the WHO classification in three
patients, type B3 in one and carcinoid tumor in two patients. Surgical
resection was performed as an initial treatment for brain lesions in three
patients. Five patients received whole brain radiation therapy (WBRT) and
radiosurgery was performed in one of them. The survival time was from 2
months in a patient with no treatment for brain lesions to 9 months in a
patient who is still alive after surgical resection combined with WBRT and
radiosurgery. There is high probability of metastasis particularly in thymic
carcinoma type C or carcinoid tumor. Frequent surveillance and aggressive
therapeutic approach are necessary to improve survival in these patients
with cerebral involvement.
PMID: 16132513 [PubMed - indexed for MEDLINE]
C-kit expression in germinoma: an immunohistochemistry-based
Department of Neurosurgery, Graduate School of Medical Science, Kumamoto
University, 1-1-1 Honjo, 860-8556 Kumamoto, Japan. email@example.com
In our immunohistochemical study of 25 human primary intracranial germinomas
and germinomas with syncytiotrophoblastic giant cells (STGC), we stained the
same sections for c-kit and placental alkaline phosphatase (PLAP).
Immunohistochemical expression was graded using a semi-quantitative scoring
system where 3+ =51-75%, and 4+ =76-100%. Of the 25 cases, 7 (28%) were
graded 3+ and 18 (72%) 4+ for c-kit; 8 (32%) were 3+ or 4+ for PLAP. All 3
cases negative for PLAP-staining were strongly positive and all embryonal
carcinomas, immature teratomas, and yolk sac tumors were negative for c-kit
staining. The soluble isoform of c-kit (s-kit) is reportedly detectable in
cerebral spinal fluid of patients with germinomas and germinomas with STGC.
C-kit and s-kit may be powerful tumor markers for germinomas with or without
PMID: 16132509 [PubMed - indexed for MEDLINE]
Postoperative radiotherapy and chemotherapy in the
management of oligodendroglioma: single institutional review of 88 patients.
Department of Radiation Oncology, Faculty of Medicine, Hacettepe University,
06100 Ankara, Turkey. gozyigit @hacettepe.edu.tr
We retrospectively evaluate the prognostic factors affecting the local
control, survival and the potential role of chemotherapy in the management
of patients with oligodendroglioma. The medical records of 88 patients
treated by postoperative external beam radiotherapy +/- chemotherapy at our
institution between December 1993 and December 2002 were analyzed. Nine
patients (10%) were treated with an accelerated fractionation scheme, while
79 patients were treated with conventional doses. The median RT dose was
54.8 +/- 2.58 Gy for low-grade tumors, and 58.7 +/- 2.46 Gy for high-grade
tumors. PCV chemotherapy regimen was given to 18 patients; temozolamide was
administered in three patients. Chemotherapy was not given concomitantly in
any patients. The median follow-up was 56 months (range 7-134 months). The
5-year overall and progression-free survival rates for entire group were 86%
and 79%, respectively. Patients with epilepsy at presentation had better
5-year overall survival (93% vs. 74%, P=0.04). High grade tumors had
significantly lower overall survival rate. Age, presence of motor deficit at
diagnosis and histological grade were found have a significant impact on
progression-free survival. The 5-year overall and progression free survival
rates of patients with high-grade tumors were 69%, 51% and 74%, 68% for
chemotherapy and no-chemotherapy group, respectively (P=0.9 for OS, P=0.3
for PFS). In multivariate analysis no significant factor affecting the
overall survival and progression-free survival was found. Chemotherapy given
after postoperative radiotherapy in patients with oligodendroglioma did not
improve survival in this retrospective study.
PMID: 16132506 [PubMed - indexed for MEDLINE]
CD117 expression in glial tumors.
Department of Pathology, University of Arkansas for Medical Sciences, 4301
W. Markham St., Little Rock, AR 72205, USA.
C-kit is a proto-oncogene involved in normal growth and development and
neoplastic processes, and its product, CD117, is a highly specific
immunohistochemical diagnostic marker for gastrointestinal stromal tumors (GISTs).
Because GISTs that express immunohistochemically-detectable CD117 respond
dramatically to treatment with tyrosine kinase inhibitors, identification of
central nervous system tumors that express CD117 might open new therapeutic
approaches for treatment of brain tumors. Specimens from 52 glial tumors of
various histologic types and grades were assayed for CD117 immunoreactivity,
and about 75% of the tumors were positive for CD117 expression; all except a
few exhibited strong cytoplasmic and membranous staining. The proportion of
high grade tumors of all tumor types with detectable CD117 immunoreactivity
was statistically significantly greater than low grade tumors, and
glioblastoma and anaplastic oligodendroglioma showed the highest staining
grade. These findings support further investigation into the possibility
that CD117 has an important role in growth of glial tumors and that patients
with brain tumors expressing CD117 might benefit from treatment with
receptor tyrosine kinase inhibitors.
PMID: 16132504 [PubMed - indexed for MEDLINE]
Surviving glioblastoma for more than 5 years: the
Department of General Neurology, Hertie Institute for Clinical Brain
Research, Tubingen, Germany. firstname.lastname@example.org
The authors performed a comprehensive analysis of the functional outcome of
10 patients who had survived 5 years from a diagnosis of glioblastoma.
Neurologic deficits were mild in most patients, but neuropsychological
testing demonstrated cognitive deficits in all patients. Depression and
anxiety were common. Although most patients thought that their social
functioning and work ability were impaired, little reduction in overall
quality of life was perceived.
PMID: 16434662 [PubMed - in process]
Recent advances in the molecular genetics of malignant
gliomas disclose targets for antitumor agent perillyl alcohol.
Fonseca CO, Landeiro
Costa Carvalho Mda G, Gattass
Servico de Neurocirurgia, Hospital Universitario Antonio Pedro, UFF, Niteroi,
Tumors of glial origin such as glioblastoma multiforme (GBM) comprise the
majority of human brain tumors. Despite advances in surgery, radiation, and
chemotherapy, the prognosis for patients with malignant glioma has not
improved, emphasizing the need for a search for new chemotherapeutic drugs.
Deregulated p21-Ras function, as a result of mutation, overexpression, or
growth factor-induced overactivation, contributes to the growth of GBM. The
monoterpene perillyl alcohol (POH) has preventive and therapeutic effects in
a wide variety of preclinical tumor models and is currently under phase I
and phase II clinical trials. As inhibition of posttranslational
isoprenylation of Ras, a family of proteins that are involved in signal
transduction is among the drug-related activities observed in this compound;
POH may be a potential chemotherapeutic agent for GBM. Intranasal delivery
is a practical and noninvasive approach that allows therapeutic agents that
do not cross the blood-brain barrier to enter the central nervous system,
reducing unwanted systemic side effects. This article describes the effect
of intranasal delivery of POH in a patient with relapsed GBM.
PMID: 16427438 [PubMed - in process]
Transient memory disturbance after removal of an
intraventricular trigonal meningioma by a parieto-occipital interhemispheric
precuneus approach: Case report.
Department of Neurological Surgery, Okayama University Graduate School of
Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
BACKGROUND: Pitfalls in a parieto-occipital interhemispheric precuneus
approach for the ventricular trigonal region of a dominant hemisphere have
been rarely reported. We described a case with memory disturbance after
surgery using this approach. CASE DESCRIPTION: A 57-year-old, right-handed
woman complained of numbness of the lower extremities and underwent magnetic
resonance imaging, which incidentally demonstrated a trigonal meningioma in
the left lateral ventricle with a maximal diameter of 4 cm. The patient's
preoperative neurologic examination was normal. The tumor was successfully
removed by a parieto-occipital interhemispheric approach with an incision of
the left precuneus cortex. Postoperative motor, sensory, and visual
functions were normal; however, recent memory disturbance developed, which
gradually resolved in the following 3 months. CONCLUSIONS: An
interhemispheric precuneus approach is a useful alternative to trigonal
tumors with few surgical complications, but postoperative memory disturbance
can be one pitfall of this procedure.
PMID: 16427415 [PubMed - in process]