[Brainlife] Newsletter, Vol.4 No.8

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BRAINLIFE NEWSLETTER

Volume 4, Number 8 - 8 February 2005	Volume 4 Archive

1: AJNR Am J Neuroradiol. 2004 Oct;25(9):1549-52.

Atypical MR imaging perfusion in developmental venous anomalies.

Camacho DL, Smith JK, Grimme JD, Keyserling HF, Castillo M.

Department of Radiology, University of North Carolina, Chapel Hill, NC 27599, USA.

Developmental venous anomalies (DVAs) are common variants of cerebral venous drainage that are typically incidental findings on contrast-enhanced MR imaging studies. We present four cases of asymptomatic DVAs that demonstrate increased cerebral blood flow, cerebral blood volume, mean transit time, and time to peak on perfusion MR images. Our study indicates that alterations in perfusion MR imaging parameters can be seen with uncomplicated DVAs and do not necessarily imply a more ominous underlying etiologic factor, such as hypervascular tumor or stroke. Copyright American Society of Neuroradiology

Publication Types:

Case Reports

PMID: 15502136 [PubMed - indexed for MEDLINE]

2: AJNR Am J Neuroradiol. 2004 Oct;25(9):1538-40.

Pineal cystic germinoma with syncytiotrophoblastic giant cells mimicking MR imaging findings of a pineal cyst.

Hayashida Y, Hirai T, Korogi Y, Kochi M, Maruyama N, Yamura M, Yamashita Y.

Department of Radiology, Kumamoto University School of Medicine, Kumamoto, Japan.

We report a case of precocious puberty in a 4-year-old boy. Contrast-enhanced T1-weighted MR imaging suggested a pineal cyst with enhancement of the slightly thickened wall and focal wall irregularity. Three-dimensional constructive interference in a steady-state imaging revealed a focal lobulation and a nodule-like area in the lesion. The lesion mimicking a pineal cyst proved to be a germinoma with syncytiotrophoblastic giant cells, on the basis of biopsy and tumor marker results. Copyright American Society of Neuroradiology

Publication Types:

Case Reports

PMID: 15502133 [PubMed - indexed for MEDLINE]

3: Am J Clin Oncol. 2005 Feb;28(1):70-4.: Pushing the limits of radiotherapy for atypical and malignant meningioma.

Katz TS, Amdur RJ, Yachnis AT, Mendenhall WM, Morris CG.

Departments of Radiation Oncology, University of Florida College of Medicine, Gainesville, Florida, USA.

PURPOSE: The purpose of this study was to report the outcome of an extremely aggressive radiotherapy program in patients with atypical and malignant meningioma (60 Gy at 1.5 Gy per fraction twice daily +/- radiosurgery boost). METHODS AND MATERIALS: Thirty-six patients received radiotherapy with curative intent between 1984 and 1999 for atypical (27 patients) or malignant (9 patients) meningioma. All patients had a minimum of 2 years follow up. RESULTS: The overall 5-year local control, cause-specific survival, and absolute survival rates were 45%, 39%, and 36%, respectively. Accelerated hyperfractionated radiotherapy resulted in a local control rate of 45% compared with 50% for patients treated with less aggressive schedules (P = 0.99). A radiosurgery boost did not improve tumor control. The complication rate for those treated with accelerated hyperfractionated radiotherapy was dramatically higher (grade 3-5: 55% vs. 0%, grade 4-5: 27% vs. 0%. both P <0.05). CONCLUSION: Our data suggests that 50 to 60 Gy delivered with conventional, once-daily fractionation is probably the optimal schedule for atypical and malignant meningioma. More aggressive radiotherapy fractionation schedules and radiosurgery are unlikely to improve outcome.

PMID: 15685038 [PubMed - in process]

4: Cancer. 2005 Feb 2; [Epub ahead of print]: Cerebrospinal fluid-disseminated meningioma.

Chamberlain MC, Glantz MJ.

Department of Neurology, University of Southern California Norris Cancer Center, Lost Angeles, California.

BACKGROUND: Intracranial meningiomas are common and comprise 20% of all primary brain tumors. Meningiomas infrequently metastasize; however, to the authors' knowledge there are limited data regarding the spread of disease through cerebrospinal fluid (CSF). METHODS: Eight of 200 consecutive patients (4%) with meningiomas manifested CSF dissemination. CSF cytology was positive in all patients, and neuroradiographic studies were consistent with CSF dissemination in eight patients. The patients (6 women and 2 men) ranged in age from 24-87 years (mean age, 52 years). All patients had undergone prior surgery (range, one to five surgeries; median, two surgeries), radiotherapy (involved-field radiotherapy in seven patients and stereotactic radiotherapy in six patients), and chemotherapy (hydroxyurea in eight patients). Multiple sites of metastases were seen in all patients and were both within the nervous system (subarachnoid or ventricular tumor: intracranial in eight patients, spinal cord in four patients) and extraneural (subcutaneous, cervical lymph nodes, orbit, or pulmonary in five patients). Treatment utilized both systemic chemotherapy (temozolomide in four patients, irinotecan in three patients, hydroxyurea in three patients, interferon-alpha in two patients, and doxorubicin plus ifosfamide in one patient) and intraventricular chemotherapy (liposomal cytosine arabinoside in seven patients, thiotepa in one patient, and busulfan in one patient). RESULTS: Treatment-related toxicity was seen in eight patients, including chemical meningitis in eight patients (Grade 2), neutropenia in five patients (Grade 2 in four patients and Grade 3 in one patient), fatigue in one patient (Grade 2), and gastrointestinal toxicity in one patient (Grade 2). The best response was stable disease in seven patients and progressive disease in one patient. The response duration ranged from 2-31 months (median, 3.5 months). The median survival was 5.5 months, and 3 patients were alive with disease at the time of last follow-up. CONCLUSIONS: The treatment of CSF-disseminated meningioma, although feasible and comparatively nontoxic, was associated with modest outcomes despite combined systemic and intraventricular chemotherapy. Cancer 2005. (c) 2005 American Cancer Society.

PMID: 15690330 [PubMed - as supplied by publisher]

5: Cancer. 2005 Feb 2; [Epub ahead of print]: Survival rates in patients with low-grade glioma after intraoperative magnetic resonance image guidance.

Claus EB, Horlacher A, Hsu L, Schwartz RB, Dello-Iacono D, Talos F, Jolesz FA, Black PM.

Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts.

BACKGROUND: No age-adjusted or histologic-adjusted assessments of the association between extent of resection and risk of either recurrence or death exist for neurosurgical patients who undergo resection of low-grade glioma using intraoperative magnetic resonance image (MRI) guidance. METHODS: The current data included 156 patients who underwent surgical resection of a unifocal, supratentorial, low-grade glioma in the MRI suite at Brigham and Women's Hospital between January 1, 1997, and January 31, 2003. Estimates of disease-free and overall survival probabilities were calculated using Kaplan-Meier methodology. The association between extent of resection and these probabilities was measured using a Cox proportional hazards model. Observed death rates were compared with the expected death rate using age-specific and histologic-specific survival rates obtained from the Surveillance, Epidemiology, and End Results Registry. RESULTS: Patients who underwent subtotal resection were at 1.4 times the risk of disease recurrence (95% confidence interval [95% CI], 0.7-3.1) and at 4.9 times the risk of death (95% CI, 0.61-40.0) relative to patients who underwent gross total resection. The 1-year, 2-year, and 5-year age-adjusted and histologic-adjusted death rates for patients who underwent surgical resection using intraoperative MRI guidance were 1.9% (95% CI, 0.3-4.2%), 3.6% (95% CI, 0.4-6.7%), and 17.6% (95% CI, 5.9-29.3%), respectively: significantly lower than the rates reported using national data bases. CONCLUSIONS: The data from the current study suggested a possible association between surgical resection and survival for neurosurgical patients who underwent surgery for low-grade glioma under intraoperative MRI guidance. Further study within the context of a large, prospective, population-based project will be needed to confirm these findings. Cancer 2005. (c) 2005 American Cancer Society.

PMID: 15690327 [PubMed - as supplied by publisher]

6: Cancer Res. 2004 Dec 15;64(24):9193-8.: Proliferation of transformed somatotroph cells related to low or absent expression of protein kinase a regulatory subunit 1A protein.

Lania AG, Mantovani G, Ferrero S, Pellegrini C, Bondioni S, Peverelli E, Braidotti P, Locatelli M, Zavanone ML, Ferrante E, Bosari S, Beck-Peccoz P, Spada A.

Institute of Endocrine Sciences, Ospedale Maggiore, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy.

The two regulatory subunits (R1 and R2) of protein kinase A (PKA) are differentially expressed in cancer cell lines and exert diverse roles in growth control. Recently, mutations of the PKA regulatory subunit 1A gene (PRKAR1A) have been identified in patients with Carney complex. The aim of this study was to evaluate the expression of the PKA regulatory subunits R1A, R2A, and R2B in a series of 30 pituitary adenomas and the effects of subunit activation on cell proliferation. In these tumors, neither mutation of PRKAR1A nor loss of heterozygosity was identified. By real-time PCR, mRNA of the three subunits was detected in all of the tumors, R1A being the most represented in the majority of samples. By contrast, immunohistochemistry documented low or absent R1A levels in all tumors, whereas R2A and R2B were highly expressed, thus resulting in an unbalanced R1/R2 ratio. The low levels of R1A were, at least in part, due to proteasome-mediated degradation. The effect of the R1/R2 ratio on proliferation was assessed in GH3 cells, which showed a similar unbalanced pattern of R subunits expression, and in growth hormone-secreting adenomas. The R2-selective cAMP analog 8-Cl cAMP and R1A RNA silencing, stimulated cell proliferation and increased Cyclin D1 expression, respectively, in human and rat adenomatous somatotrophs. These data show that a low R1/R2 ratio promoted proliferation of transformed somatotrophs and are consistent with the Carney complex model in which R1A inactivating mutations further unbalance this ratio in favor of R2 subunits. These results suggest that low expression of R1A protein may favor cAMP-dependent proliferation of transformed somatotrophs.

PMID: 15604292 [PubMed - indexed for MEDLINE]

7: Childs Nerv Syst. 2004 Oct;20(10):770-3.

Bobble-head doll syndrome due to a suprasellar arachnoid cyst: endoscopic treatment in two cases.

Fioravanti A, Godano U, Consales A, Mascari C, Calbucci F.

Department of Neurosurgery, Bellaria Hospital, Via Altura n. 3, 40139 Bologna, Italy. antonio.fioravanti@ausl.bologna.it

OBJECT: We report two cases of bobble-head doll syndrome associated with a large suprasellar arachnoid cyst successfully treated with a minimally invasive endoscopic approach. METHODS: The clinical history, surgical treatment and results of two children, a 9-year-old boy and a 1-year-old girl, both presenting the clinical features of the bobble-head doll syndrome, are described. As a first procedure, a ventriculo-cystostomy was endoscopically performed in both patients, obtaining either resolution of the symptoms or notable cyst reduction. In the girl, a re-closure of the stoma, with cyst re-expansion, was observed after 18 months. She then underwent a second procedure, a ventriculo-cysto-cisternostomy, with a good result.After 3 years' follow-up, the neurological condition of both patients remains good with complete resolution of abnormal head movement. CONCLUSION: In our opinion, endoscopic treatment is the procedure of choice for this condition, as it involves few complications and gives good results.

Publication Types:

Case Reports

PMID: 15057560 [PubMed - indexed for MEDLINE]

8: Childs Nerv Syst. 2004 Oct;20(10):757-60.

Anterior cervical arachnoid cyst presenting with traumatic quadriplegia.

Muthukumar N.

Department of Neurosurgery, Madurai Medical College, Muruganagam, 138 Anna Nagar, 625-020 Madurai, India. prasan86@eth.net

Introduction: Intraduralspinal arachnoid cysts are rare.Rarer still are cysts located anteriorto the cervical spinal cord. To date,only 10 such cases have been re-ported in the English-language liter-ature. Case report: Two cases ofanterior cervical arachnoid cysts thatpresented as traumatic quadriplegiaare reported.

Publication Types:

Case Reports

PMID: 15007602 [PubMed - indexed for MEDLINE]

9: Clin Cancer Res. 2004 Jul 1;10(13):4303-6.: Imaging correlates of molecular signatures in oligodendrogliomas.

Megyesi JF, Kachur E, Lee DH, Zlatescu MC, Betensky RA, Forsyth PA, Okada Y, Sasaki H, Mizoguchi M, Louis DN, Cairncross JG.

Department of Clinical Neurological Sciences, University of Western Ontario and London Regional Cancer Centre, London, Ontario, Canada.

Molecular subsets of oligodendroglioma behave in biologically distinct ways. Their locations in the brain, rates of growth, and responses to therapy differ with their genotypes. Retrospectively, we inquired whether allelic loss of chromosomal arms 1p and 19q, an early molecular event and favorable prognostic marker in oligodendrogliomas, were reflected in their appearance on magnetic resonance imaging. Loss of 1p and 19q was associated with an indistinct border on T(1) images and mixed intensity signal on T(1) and T(2). Loss of 1p and 19q was also associated with paramagnetic susceptibility effect and with calcification, a common histopathological finding in oligodendrogliomas. These data encourage prospective evaluation of molecular alterations and magnetic resonance imaging characteristics of glial neoplasms.

PMID: 15240515 [PubMed - indexed for MEDLINE]

10: Int J Cancer. 2005 Feb 1; [Epub ahead of print]: Residential and occupational exposure to 50-Hz magnetic fields and brain tumours in Norway: A population-based study.

Klaeboe L, Blaasaas KG, Haldorsen T, Tynes T.

The Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway.

Our case-control study was conducted to investigate whether residential and occupational exposure to magnetic fields increased the risk for brain tumours in adults. Data from an occupational exposure matrix was also evaluated. The study population in this nested case-control study was made up of subjects aged 16 years and older who had resided in a broad corridor around a high-voltage power line in 1980 or during one of the years from 1986-1996. The cases were incident cases diagnosed during 1980-96. Two controls were matched to each case by year of birth, sex, municipality and first year entering the cohort. The time-weighted average exposure to residential magnetic fields generated by the power lines was calculated for the exposure follow-up from 1 January 1967 to diagnosis. In addition, job titles and branches of industry were classified as categories of hours per week in a magnetic field above background level (0.1 muT). Exposures were cumulated over occupationally active years for the exposure follow-up from 1 January 1955 to diagnosis. When residential magnetic fields are evaluated, the 2 upper residential, time-weighted, average magnetic field categories showed elevated odds ratios (ORs) for all brain tumours (OR = 1.6; 95% confidence interval [95%CI] 0.9-2.7 and OR = 1.3; 95% CI 0.7-2.3). Occupational exposure showed no association to exposure for any site. We found an elevated risk for residential exposure to magnetic fields and brain tumours, although the risk was not significant, and no clear exposure-response pattern was found. The findings for the occupational exposure groups showed an inverse association. (c) 2005 Wiley-Liss, Inc.

PMID: 15688420 [PubMed - as supplied by publisher]

11: Int J Cancer. 2005 Feb 1; [Epub ahead of print]: Interleukin-6 induces transcriptional activation of vascular endothelial growth factor (VEGF) in astrocytes in vivo and regulates VEGF promoter activity in glioblastoma cells via direct interaction between STAT3 and Sp1.

Loeffler S, Fayard B, Weis J, Weissenberger J.

Division of Neuropathology, Institute of Pathology, University of Bern, Bern, Switzerland.

Interleukin-6 (IL-6) expression is strongly correlated with the degree of human glioma malignancy and necessary for tumor formation in a mouse model of spontaneous astrocytomas. Yet, exactly how IL-6 contributes to malignant progression of these brain tumors is still unclear. We have scrutinized the mechanism of transcriptional activation of vascular endothelial growth factor (VEGF) expression by IL-6 in the mouse brain and in glioblastoma cells. We demonstrate here that IL-6 drives transcriptional upregulation of VEGF in astrocytes in vivo using glial fibrillary acidic protein (GFAP)-IL-6/VEGF-green fluorescent protein (GFP) double transgenic mice. We further show that IL-6-induced VEGF transcription and VEGF secretion by human glioblastoma cells is dependent on signal transducer and activator of transcription 3 (STAT3). By progressive 5'-deletion analysis we defined the minimal VEGF promoter region for IL-6-responsiveness to nucleotides -88/-50. Surprisingly, this promoter region is rich in GC-boxes and does not contain STAT3 binding elements. Electrophoretic mobility shift and supershift assays revealed binding of Sp1 and Sp3 to the -88/-50 element upon IL-6 stimulation. Interestingly, preincubation with STAT3 antibody prevented the binding of Sp1 and Sp3 to the -88/-50 element, indicating that STAT3 is involved in IL-6-driven Sp1/Sp3 protein-DNA complex formation. Physical interaction of STAT3 and Sp1 was demonstrated by coimmunoprecipitation. The functional relevance of the STAT3/Sp1 association was corroborated by transient transfection experiments, which showed that overexpression of constitutively active STAT3 increased the minimal VEGF promoter activity. Taken together, our study suggests that IL-6 promotes tumor angiogenesis in gliomas and describes a novel transcriptional activation mechanism for STAT3 in the context of a STAT3 binding element (SBE)-free promoter. (c) 2005 Wiley-Liss, Inc.

PMID: 15688401 [PubMed - as supplied by publisher]

12: J Neurooncol. 2005 Jan;71(2):181-187.: A study of sequential high dose cyclophosphamide and high dose carboplatin with peripheral stem-cell rescue in resistant or recurrent pediatric brain tumors.

Foreman NK, Schissel D, Le T, Strain J, Fleitz J, Quinones R, Giller R.

The Children's Hospital, Denver, The University of Colorado, Health Sciences Center, Denver, Colorado, USA.

Purpose: To determine the maximum tolerated dose (MTD) of carboplatin with autologous hematopoietic stem-cell rescue, in children with poor-prognosis brain tumors.Patients and methods: A previously determined dose of cyclophosphamide with stem-cell rescue was used as a first course. In a second course, carboplatin was given for 3days with stem-cell rescue to 20 children. The starting dose of carboplatin was 400mg/m(2)/day with increments of 75mg/m(2)/day in subsequent cohorts. Toxicity and tumor response were recorded.Results: There were two grade IV toxicities at the dose level of 775mg/m(2)/day. There were no toxic deaths. Thus, the MTD of carboplatin was 700mg/m(2)/day for 3days. There were six complete responses (33%, 95% confidence interval [CI], 13-59%), two partial responses (11%; 95% CI, 1-35%), four with stable diseases (22%; 95% CI, 6-48%) and six progressed (33%; 95% CI, 13-59%) out of 18 assessable. Seven of the eight responses were in primitive neuroectodermal tumors (PNETs) or Germinomas. One child with a metastatic anaplastic astrocytoma had a CR. The median duration of tumor response was 10 months (range: 1.5-87months) with two children disease free at 66 and 87months. Actuarial survival is 21%. Median follow-up of survivors is 35months (range: 15-87months).Conclusion: The MTD of carboplatin with stem-cell rescue is 700mg/m(2)/day for 3days. Sequential stem-cell supported cyclophosphamide and carboplatin was tolerable in children with brain tumors and produced responses in PNETs and Germinomas.

PMID: 15690136 [PubMed - as supplied by publisher]

13: J Neurooncol. 2005 Jan;71(2):135-40.: Increased resistance of glioma cell lines to extracellular ATP cytotoxicity.

Morrone FB, Horn AP, Stella J, Spiller F, Sarkis JJ, Salbego CG, Lenz G, Battastini AM.

Departamento de Bioquimica, Instituto de Ciencias Basicas de Saude, UFRGS, Rua Ramiro Barcelos 2600-Anexo, 90.035.003, Porto Alegre, RS, Brazil.

Glioblastomas are the most common form of primary tumors of the central nervous system (CNS) and despite treatment, patients with these tumors have a very poor prognosis. ATP and other nucleotides and nucleosides are very important signaling molecule in physiological and pathological conditions in the CNS. ATP is degraded very slowly by gliomas when compared to astrocytes, potentially resulting in the accumulation of extracellular ATP around gliomas. Cell lysis caused by excitotoxic death or by tumor resection may liberate intracellular ATP, a known mitotic factor for glioma cells. The aim of this study is to examine the effects on cytotoxicity induced by extracellular ATP in U138-MG human glioma cell line and C6 rat glioma cell line compared to hippocampal organotypic cell cultures. The cytotoxicity of ATP (0.1, 0.5, 5 mM) was measured using propidium iodide and LDH assays. Caspases assay was performed to identify apoptotic cell death. Results showed that the glioma cells present resistance to death induced by ATP when compared with a normal tissue. High ATP concentrations (5 mM) induced cell death after 24 h in organotypic cell cultures but not in glioma cell lines. Our data indicate that ATP released in these situations can induce cell death of the normal tissue surrounding the tumor, potentially opening space to the fast growth and invasion of the tumor.

PMID: 15690128 [PubMed - in process]

14: J Neurooncol. 2005 Jan;71(2):127-34.: Protein delivery of caspase-3 induces cell death in malignant C6 glioma, primary astrocytes and immortalized and primary brain capillary endothelial cells.

Zassler B, Blasig IE, Humpel C.

Laboratory of Psychiatry, University Clinic of Psychiatry, Innsbruck, Austria.

Most brain tumors consist of transformed glia cells and are highly vascularized by capillary endothelial cells. The aim of the present study therefore was to deliver pro-apoptotic caspase-3 into malignant C6 glioma and immortalized rBCEC4 brain endothelial cells to induce cell death. Both cell lines were transfected with a reporter protein (beta-galactosidase) using lipid-mediated gene transfer (FuGENE6(TM)) or using the novel protein delivery reagent BioPORTER(TM). beta-Galactosidase protein was successfully delivered into both cells, the protein expression peaked around day 2 and was transient. Delivery of caspase-3 induced TUNEL-positive cell death of both cell types. As a control, caspase-3 was also delivered to non-neoplastic primary astrocytes and endothelial cells and induced cell death. In conclusion BioPORTER(TM)-protein delivery of pro-apoptotic molecules may provide a potent tool to cause death of the cells in brain tumors, however, this method is limited due to its toxicity to non-malignant cells.

PMID: 15690127 [PubMed - in process]

15: J Neurooncol. 2005 Jan;71(2):121-5.: Tamoxifen-induced cell death and expression of neurotrophic factors in cultured C6 glioma cells.

Kim YJ, Lee CJ, Lee U, Yoo YM.

Department of Biological Sciences, College of Natural Sciences, Inha University, South Korea.

The effects of ( Z)-2[ p -(1,2-diphenyl-1-butenyl)phenoxy]-N ,N -dimethylamine citrate (tamoxifen) on cell survival and the expression of neurotrophic factors (NTF) were investigated in rat C6 glioma cells (C6). C6 cells do not express the estrogen receptor. Cytotoxic effect was detected from 24 h after the treatment with 10 muM tamoxifen and increased with time in a dose-dependent manner. C6 cells treated with tamoxifen also displayed various morphological types such as elliptical, round and aggregated form. As the treatment time increased, the proliferation of C6 cells was reduced remarkably and most of them became the round or aggregated form.To examine the relationship of the expression of NTF and the cytotoxicity of tamoxifen, the mRNA level of brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), and basic fibroblast growth factor (bFGF) was measured after 24 h treatment with tamoxifen by RT-PCR. The expression of mRNA of BDNF or GDNF in C6 cells treated with various concentrations of tamoxifen was comparable to controls. The expression of bFGF mRNA was significantly reduced in C6 cells treated with 10 or 15 muM tamoxifen. The results suggest that tamoxifen exerts cytotoxic effect on estrogen receptor-negative C6 cells through the inhibition of the transcription of bFGF.

PMID: 15690126 [PubMed - in process]

16: J Neurooncol. 2005 Jan;71(2):113-9.: Radiation dosimetry of (131)I-chlorotoxin for targeted radiotherapy in glioma-bearing mice.

Shen S, Khazaeli MB, Gillespie GY, Alvarez VL.

Department of Radiation Oncology, Birmingham, AL.

Chlorotoxin, or TM-601, is a peptide derived from the venom of the scorpionLeiurus Quinquestriatus that specifically binds to malignant brain tumors, but not to normal tissues. Targeted radiotherapy using (131)I-Chlorotoxin is promising for post-surgery treatment of brain tumors. This study reports dosimetry results of (131)I-Chlorotoxin in athymic nude mice with intracranially implanted human glioma xenografts and projected radiation doses in patients receiving 370 MBq of (131)I-Chlorotoxin. (125)I/(131)I-Chlorotoxin were injected into the right brain where D54 MG xenografts were implanted. Mice were sacrificed 24-96 h later. The blood, normal organs, and tumors were weighed and counted to determine (131)I-Chlorotoxin concentration. The radiation dose from (131)I was calculated based on non-penetrating radiation in the mouse model. Assuming similar tissue uptake in mice and patients, radiation doses for patients were extrapolated. Distributions of (125)I/(131)I-Chlorotoxin were only significant in tumor, stomach, kidneys, and brain (injection site), reflecting non-specific uptake of Chlorotoxin in normal tissues. Mean radiation dose (cGy/37 kBq) was 58.2 for tumor, 17.9 for brains, 1.8 for marrow, 27.1 for stomach, 16.0 for kidneys in mice. For intracranial injection of 370 MBq (131)I-Chlorotoxin in patients, extrapolated patient dose (cGy) was 70 for brains, 6 for marrow, 35 for stomach, 60 to kidneys, 227 to tumor, suggesting that 3.7 GBq of (131)I-Chlorotoxin can be safely administrated to patients. These promising results demonstrated potential in improving patient survival using this novel targeting agent.

PMID: 15690125 [PubMed - in process]

17: J Neurooncol. 2005 Jan;71(2):107-11.: Specific intensity imaging for glioblastoma and neural cell cultures with.

Duffner F, Ritz R, Freudenstein D, Weller M, Dietz K, Wessels J.

Department of Neurosurgery, Eberhard-Karls University of Tuebingen, Germany.

The fluorescence of protophorphyrin IX (PpIX) synthesized after incubation with 5-aminolevulinic acid (5-Ala) is used for the intraoperative visualisation of glioma cells in vivo. Such fluorescence may also be useful for the photodynamic therapy (PTD) of gliomas. A significant difference of fluorescence intensity in tumor cells compared to neurons is required for this application. To explore this, eight human glioma cell lines (LN-18, LN-428, U87MG, U373MG, D247MG, U251MG, LN-308, T98G) were compared with human astrocytes (SV-FHAS) and rat neurons after incubation for different periods of timein vitro with 5-Ala (1mg/ml). Fluorescence intensity profiles were measured by a digital camera comparing glioma cell lines with control cells. All glioma cell lines could be discriminated from neural cells by their intensity of fluorescence by post-hoc tests for pairwise comparisons using Tukey's honestly significant difference test, at the global significance level of 5%. The glioma cell lines showed significant variation in this possibly limiting clinical use of fluorescence as a guide for resection.

PMID: 15690124 [PubMed - in process]

18: J Neurooncol. 2005 Jan;71(2):99-106.: Ganglioside GM3 inhibits proliferation and invasion of glioma.

Fujimoto Y, Izumoto S, Suzuki T, Kinoshita M, Kagawa N, Wada K, Hashimoto N, Maruno M, Nakatsuji Y, Yoshimine T.

Department of Neurosurgery, Osaka University Medical School, Suita, Osaka, Japan.

GM3, the simplest ganglioside, modulates cell adhesion, proliferation and differentiation in the central nervous system and exogenously added GM3 regulates cell-cell and cell-extracellular matrix adhesion and induces apoptosis. To assess the anti-tumor action of exogenous GM3, we examined its effect on the proliferation and invasion of glioma cells. Its inhibitory effect on cell proliferation was demonstrated in vitro by 3-(4,5-dimethyl-2-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay and in vitro in rats with meningeal gliomatosis whose survival was significantly prolonged by the intrathecal injection of GM3. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay revealed that GM3 induced glioma cell apoptosis in vitro and in vitro. In rat brain slice cultures, GM3 suppressed the invasion of glioma cells; this effect manifested earlier than the inhibition of cell proliferation and before apoptosis induction. Our results suggest exogenous GM3 as a potential therapeutic agent in patients with glioma requiring adjuvant therapy.

PMID: 15690123 [PubMed - in process]

19: Neurol Res. 2004 Oct;26(7):774-7.

Primary primitive neuroectodermal tumor within the spinal epidural space: report of a case and review of the literature.

Aydin MV, Sen O, Ozel S, Kayaselcuk F, Caner H, Altinors N.

Department of Neurosurgery, Medical Faculty, Baskent University, Adana, Turkey. volkan8@hotmail.com

Primary intraspinal primitive neuroectodermal tumors (PNETs) are rare tumors and a have poor prognosis. In reviews of the literature, it is seen that primary intraspinal PNETs may arise at all levels of the spine and may be intramedullary, intradural-extramedullary, or epidural. Spinal epidural location of PNET is extremely rare and out of 22 cases of primary spinal PNETs reported to date, only two were epidural. Tumors within the epidural space of the spinal canal are most often metastatic neoplasms from different primary sites. Here we report a case of primary extradural PNET located in the thoracic spine in a 16-year-old boy and review the relevant literature.

Publication Types:

Case Reports

PMID: 15494121 [PubMed - indexed for MEDLINE]

20: Oncogene. 2005 Feb 3;24(6):1128.: INK4a/Arf is required for suppression of EGFR/DeltaEGFR(2-7)-dependent ERK activation in mouse astrocytes and glioma.

Lachat Y, Diserens AC, Nozaki M, Kobayashi H, Hamou MF, Godard S, Tribolet N, Hegi ME.

PMID: 15690058 [PubMed - in process]

21: Oncogene. 2005 Jan 31; [Epub ahead of print]: Membrane localization of the U2 domain of Protein 4.1B is necessary and sufficient for meningioma growth suppression.

Robb VA, Gerber MA, Hart-Mahon EK, Gutmann DH.

1Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA.

Meningiomas are common central nervous system tumors; however, the molecular mechanisms underlying their pathogenesis are largely undefined. Previous work has implicated Protein 4.1B as an important tumor suppressor involved in the development of these neoplasms. In this report, we demonstrate that the U2 domain is necessary and sufficient for the ability of Protein 4.1B to function as a meningioma growth suppressor. Using a series of truncation and deletion constructs of DAL-1 (a fragment of Protein 4.1B that retains all the growth suppressive properties), we narrowed the domain required for 4.1B growth suppression to a fragment containing a portion of the FERM domain and the U2 domain using clonogenic assays on meningioma cells. Deletion of the U2 domain in the context of the full-length DAL-1 molecule eliminated growth suppressor function, as measured by thymidine incorporation and caspase-3 activation. Moreover, targeting the U2 domain to the plasma membrane using a membrane localization signal (MLS) reduced cell proliferation, similar to wild-type DAL-1. Collectively, the data suggest that the U2 domain, when properly targeted to the plasma membrane, contains all the residues necessary for mediating Protein 4.1B growth suppression.Oncogene advance online publication, 31 January 2005; doi:10.1038/sj.onc.1208335.

PMID: 15688033 [PubMed - as supplied by publisher]

22: Pediatr Neurol. 2004 Oct;31(4):261-6.: The clinical and surgical aspects of spinal tumors in children.

Baysefer A, Akay KM, Izci Y, Kayali H, Timurkaynak E.

Department of Neurosurgery, School of Medicine, Gulhane Military Medical Academy, Ankara, Turkey.

A series of 20 pediatric patients underwent surgery for spinal tumor at the Department of Neurosurgery, Gulhane Military Medical Academy between 1995 and 2003. Motor weakness and reflex changes were the main initial signs in these patients. Epidural tumors and intradural-extramedullary tumors were in equal number, and total tumor removal was achieved in most of the patients without adjuvant treatment. Laminotomy was the main surgical method in 60% of the patients with spinal tumor, especially in children younger than 3 years of age.

PMID: 15464638 [PubMed - indexed for MEDLINE]

23: Surg Neurol. 2005 Feb;63(2):162-9.: Glioblastoma multiforme-report of 267 cases treated at a single institution.

Stark AM, Nabavi A, Mehdorn HM, Blomer U.

Department of Neurosurgery, University of Schleswig-Holstein Medical Center, 24105 Kiel, Germany.

OBJECTIVE: Glioblastoma multiforme (GBM) is the most common and most malignant primary brain tumor in adults. We present 267 cases treated at a single institution and discuss clinical characteristics and prognostic factors with regard to the neurosurgical literature. METHODS: Included in this study were 267 patients who underwent craniotomy for newly diagnosed GBM between 1990 and 2001 at our department. Clinical charts and radiographic images were reviewed. Association to patient survival was estimated using log-rank test. RESULTS: Median patient age was 61 years (mean, 59.5; range, 22-86 years), the male-female ratio was 1.2:1. In 35 cases (13.1%) the tumor was multicentric. Most of the tumors were classified as primary GBM (87.6%). During follow-up,72 patients (26.4%) underwent recraniotomy for GBM recurrence and 3 patients (1.1%) developed spinal drop metastases. Overall median survival was 47 weeks (range, 5-305 weeks). The following parameters were significantly associated with prolonged survival: (1) age 61 years or younger, P < .001; (2) Karnofsky performance scale score of 70 or more, P < .001; (3) radiotherapy with a total dose of at least 54 Gy, P < .001; (4) chemotherapy, P < .001; (5) total tumor resection, P = .014; (6) recraniotomy for GBM recurrence, P = .012. CONCLUSIONS: Glioblastoma multiforme remains an important cause of morbidity and mortality from intracranial tumors. The overall prognosis is dismal, although interdisciplinary therapy can significantly prolong survival and allows a small subgroup of patients to survive 3 years or more.

PMID: 15680662 [PubMed - in process]

24: Pediatr Neurosurg. 2004 Sep-Oct;40(5):230-3.: Intracranial ectopic recurrence of craniopharyngioma after ommaya reservoir implantation.

Ishii K, Sugita K, Kobayashi H, Kamida T, Fujiki M, Izumi T, Mori T.

Department of Neurosurgery, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Oita 879-5593, Japan. keisuke@med.oita-u.ac.jp

We present a very rare case of a craniopharyngioma showing intracranial ectopic recurrence after the total removal of recurrent craniopharyngioma arising at the primary site accompanied by Ommaya reservoir implantation. A 2-year-old boy underwent a bifrontal craniotomy and total removal of the adamantinomatous craniopharyngioma via the interhemispheric translamina terminalis approach. Four months later, he underwent total removal of recurrent craniopharyngioma and implantation of an Ommaya reservoir via the same approach. Ten months later, total removal of the ectopic recurrent craniopharyngioma following the placement of the Ommaya reservoir cannula, which was placed within the surgical route, was performed via the same craniotomy. Copyright (c) 2004 S. Karger AG, Basel.

PMID: 15687737 [PubMed - in process]