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BRAINLIFE NEWSLETTER
Volume 5, Number 40 - 4 October 2006

Volume 5
 Archive
1: Br J Neurosurg. 2006 Apr;20(2):114.
 
Comment on:
Myxopapillary ependymoma with intracranial metastases by Higgins G, Smith C, Summers D, Statham P, Erridge S. Br J Neurosurg 2005; 19(4):356-8.

Davis CH.

Publication Types:
  • Comment
  • Letter

PMID: 16753632 [PubMed - indexed for MEDLINE]
 
2: Br J Neurosurg. 2006 Apr;20(2):111-3.
 
The next extreme sport? Subdural haematoma in a patient with arachnoid cyst after head shaking competition.

Hopkin J, Mamourian A, Lollis S, Duhaime T.

Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA. jeremy.hopkin@hitchcock.org

A young man, engaged in a head shaking competition presented with headache, nausea and vomiting. Imaging revealed a subdural haematoma and ipsilateral arachnoid cyst. This novel mechanism of trauma underscores the predisposition to haemorrhage in patients with arachnoid cysts, even with minor trauma. Aetiology, imaging and possible treatment options are discussed.

Publication Types:
  • Case Reports

PMID: 16753631 [PubMed - indexed for MEDLINE]
 
3: Br J Neurosurg. 2006 Apr;20(2):109-10.
 
An intramedullary vascular malformation mimicking intrinsic spinal cord tumour.

Peng EW, Kurian KM, Ironside JW, Macmullen-Price J, Fitzpatrick MO, Whittle IR.

Department of Clinical Neurosciences, Western General Hospital, Edinburgh, UK.

Publication Types:
  • Case Reports

PMID: 16753630 [PubMed - indexed for MEDLINE]
 
4: Br J Neurosurg. 2006 Apr;20(2):106-8.
 
An unusual progression of benign thoracic spinal cord teratoma in pregnancy: a hormonally-mediated pathway?

Kumar V, Peng EW, Kurian KM, Smith C, Fitzpatrick MO, Whittle IR.

Department of Clinical Neurosciences, Western General Hospital, Edinburgh, UK.

Intradural spinal cord teratoma is a very rare tumour that can be associated with dysraphism. The relationship of this lesion to pregnancy is unknown and its occurrence during pregnancy in the thoracic spine has not been previously reported. We report a 19-year-old pregnant woman with spinal dysraphism, who presented with a new onset thoracic myelopathy. The MRI scan showed an intradural, extramedullary lesion with solid and cystic component in the thoracic spine at the level of T5-T6. A thoracic laminectomy and excision of this lesion was followed by significant improvement of her lower limb function. Histopathology confirmed a benign mature teratoma. The rapid progression of this lesion during pregnancy suggests a hormonal mediated pathway for the tumour growth. Further analysis from the resected specimen confirmed that the tumour was oestrogen and progesterone receptors positive.

Publication Types:
  • Case Reports

PMID: 16753629 [PubMed - indexed for MEDLINE]
 
5: Br J Neurosurg. 2006 Apr;20(2):99-103.
 
Multiple synchronous spinal extra-osseous intradural chordomas: is it a distinct entity?

Badwal S, Pal L, Basu A, Saxena S.

Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, and Department of Pathology, Command Hospital, Central Command, Lucknow, India. deepsbadwal@hotmail.com

Chordomas are most commonly of extradural origin and are associated with bone destruction. Extra-osseous intradural chordomas are extremely rare and most of the cases described are located near the clivus. We report an extremely rare case of multiple extra-osseous intraspinal chordomas in a 36-year-old male patient with autopsy findings. This case highlights that behaviour of spinal intradural chordomas is not universally low grade, but is variable and aggressive.

Publication Types:
  • Case Reports

PMID: 16753627 [PubMed - indexed for MEDLINE]
 
6: Br J Neurosurg. 2006 Apr;20(2):94-6.
 
Diffusion tensor imaging in a symptomatic patient with an intra-axial arachnoid cyst.

Thorat JD, Sitoh YY, Chin CH, Ng I.

Department of Neurosurgery, National Neuroscience Institute, Singapore.

We present a case of an elderly lady with a symptomatic large intra-axial right frontoparietal arachnoid cyst displacing the corticospinal tract (CST) posteromedially on diffusion tensor imaging. This information assisted the surgeons in confirming the symptomatic nature of the lesion, in planning an appropriate surgical procedure, as well as in prognostication of recovery.

Publication Types:
  • Case Reports

PMID: 16753625 [PubMed - indexed for MEDLINE]
 
7: Br J Neurosurg. 2006 Apr;20(2):90-3.
 
Two cases of papillary glioneuronal tumours.

Epelbaum S, Kujas M, Van Effenterre R, Poirier J.

Services de Neuropathologie, Hopital de la Pitie-Salpetriere, Paris, France. steph6279@yahoo.fr

We report two cases of papillary glioneuronal tumour. Both patients underwent gross total resection of their tumour. One of them was also treated by radiotherapy. Neither tumour had recurred, 19 and 2 years after treatment, thus confirming the good prognosis commonly associated with this tumour.

Publication Types:
  • Case Reports

PMID: 16753624 [PubMed - indexed for MEDLINE]
 
8: Cancer. 2006 Sep 22; [Epub ahead of print]
 
Capillary physiology of human medulloblastoma: impact on chemotherapy.

Warnke PC, Kopitzki K, Timmer J, Ostertag CB.

Department of Neurological Science, Clinical Sciences Centre for Research and Education, University of Liverpool, Liverpool, Merseyside, United Kingdom.

BACKGROUND: Advances in the treatment of medulloblastoma have largely been attributed to the introduction of chemotherapy, although Phase III trials have shown advantages for chemotherapy only in subgroups. Because the efficacy of chemotherapy depends on tumor vascularization, the vascular physiology of human medulloblastomas was evaluated. METHODS: Seven patients with histologically proven medulloblastomas underwent measurements of capillary permeability and vascular plasma volume using contrast-enhanced dynamic computer tomography. Regional blood flow was measured in 5 patients using xenon computed tomography (CT). RESULTS: The capillary permeability-surface product for water-soluble compounds ranged from 1.7 +/- 5.5 to 17.6 +/- 12.3 muL/g/min with a mean of 10.5 +/- 6.3 muL/g/min. The vascular plasma volume ranged from 0.02 +/- 0.021 to 0.045 +/- 0.049 mL/g with a mean of 0.03 +/- 0.01 mL/g. The efflux rate ranged from 0.012 +/- 0.007 to 0.065 +/- 0.064 1/min with a mean of 0.039 +/- 0.020 1/min. Regional tumoral blood flow showed a mean of 19.86 +/- 6.8 mL/100g/min as compared with normal cerebellum with 45.4 +/- 12.03 mL/100g/min (P < .005). CONCLUSIONS: The current study demonstrated a low capillary permeability and blood flow in medulloblastomas that could explain the limited response rates of partially resected tumors even after aggressive high-dose chemotherapy, as recently reported. Cancer 2006. (c) 2006 American Cancer Society.

PMID: 16998941 [PubMed - as supplied by publisher]
 
9: Cancer Res. 2006 Aug 1;66(15):7793-800.
 
Genetic bases of estrogen-induced tumorigenesis in the rat: mapping of loci controlling susceptibility to mammary cancer in a Brown Norway x ACI intercross.

Schaffer BS, Lachel CM, Pennington KL, Murrin CR, Strecker TE, Tochacek M, Gould KA, Meza JL, McComb RD, Shull JD.

Department of Genetics, Eppley Institute for Research in Cancer, University of Nebraska Medical Center, 985805 Nebraska Medical Center, Omaha, NE 68198, USA.

Exposure to estrogens is associated with an increased risk of breast cancer. Our laboratory has shown that the ACI rat is uniquely susceptible to 17beta-estradiol (E2)-induced mammary cancer. We previously mapped two loci, Emca1 and Emca2 (estrogen-induced mammary cancer), that act independently to determine susceptibility to E2-induced mammary cancer in crosses between the susceptible ACI rat strain and the genetically related, but resistant, Copenhagen (COP) rat strain. In this study, we evaluate susceptibility to E2-induced mammary cancer in a cross between the ACI strain and the unrelated Brown Norway (BN) rat strain. Whereas nearly 100% of the ACI rats developed mammary cancer when treated continuously with E2, BN rats did not develop palpable mammary cancer during the 196-day course of E2 treatment. Susceptibility to E2-induced mammary cancer segregated as a dominant or incompletely dominant trait in a cross between BN females and ACI males. In a population of 251 female (BN x ACI)F(2) rats, we observed evidence for a total of five genetic determinants of susceptibility. Two loci, Emca4 and Emca5, were identified when mammary cancer status at sacrifice was evaluated as the phenotype, and three additional loci, Emca6, Emca7, and Emca8, were identified when mammary cancer number was evaluated as the phenotype. A total of three genetic interactions were identified. These data indicate that susceptibility to E2-induced mammary cancer in the BN x ACI cross behaves as a complex trait controlled by at least five loci and multiple gene-gene interactions.

PMID: 16885383 [PubMed - indexed for MEDLINE]
 
10: Clin Cancer Res. 2006 Sep 15;12(18):5550-6.
 
Human neural stem cells target experimental intracranial medulloblastoma and deliver a therapeutic gene leading to tumor regression.

Kim SK, Kim SU, Park IH, Bang JH, Aboody KS, Wang KC, Cho BK, Kim M, Menon LG, Black PM, Carroll RS.

Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.

PURPOSE: Medulloblastoma, a malignant pediatric brain tumor, is incurable in about one third of patients despite multimodal treatments. In addition, current therapies can lead to long-term disabilities. Based on studies of the extensive tropism of neural stem cells (NSC) toward malignant gliomas and the secretion of growth factors common to glioma and medulloblastoma, we hypothesized that NSCs could target medulloblastoma and be used as a cellular therapeutic delivery system. EXPERIMENTAL DESIGN: The migratory ability of HB1.F3 cells (an immortalized, clonal human NSC line) to medulloblastoma was studied both in vitro and in vivo. As proof-of-concept, we used HB1.F3 cells engineered to secrete the prodrug activating enzyme cytosine deaminase. We investigated the potential of human NSCs to deliver a therapeutic gene and reduce tumor growth. RESULTS: The migratory capacity of HB1.F3 cells was confirmed by an in vitro migration assay, and corroborated in vivo by injecting chloromethylbenzamido-Dil-labeled HB1.F3 cells into the hemisphere contralateral to established medulloblastoma in nude mice. In vitro studies showed the therapeutic efficacy of HB1.F3-CD on Daoy cells in coculture experiments. In vitro therapeutic studies were conducted in which animals bearing intracranial medulloblastoma were injected ipsilaterally with HB1.F3-CD cells followed by systemic 5-flourocytosine treatment. Histologic analyses showed that human NSCs migrate to the tumor bed and its boundary, resulting in a 76% reduction of tumor volume in the treatment group (P<0.01). CONCLUSION: These studies show for the first time the potential of human NSCs as an effective delivery system to target and disseminate therapeutic agents to medulloblastoma.

PMID: 17000692 [PubMed - in process]
 
11: Clin Cancer Res. 2006 Sep 15;12(18):5288-97.
 
Mouse models of brain tumors and their applications in preclinical trials.

Fomchenko EI, Holland EC.

Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA.

Primary brain tumors, including gliomas and medulloblastomas, often represent the most devastating and difficult-to-treat tumors, and are thought to arise from glial cells and/or their precursors or the external granule cell layer, respectively. The majority of genetic alterations characteristic of the human brain tumors are thought to occur in genes encoding proteins involved in signal transduction or cell cycle regulation. Accurate recapitulation of these genetic alterations using genetically engineered mouse models allows for in vivo modeling of brain tumors with similar histopathology, etiology, and biology. These mouse models, in turn, increase our understanding of brain tumor initiation, formation, progression, and metastasis, providing an experimental system to discover novel therapeutic targets and test various therapeutic agents.

PMID: 17000661 [PubMed - in process]
 
12: Eur J Cancer. 2006 Sep 21; [Epub ahead of print]
 
Histopathological prognostic factors in medulloblastoma: High expression of survivin is related to unfavourable outcome.

Haberler C, Slavc I, Czech T, Gelpi E, Heinzl H, Budka H, Urban C, Scarpatetti M, Ebetsberger-Dachs G, Schindler C, Jones N, Klein-Franke A, Maier H, Jauk B, Kiefer A, Hainfellner JA.

Institute of Neurology, Medical University of Vienna, Wahringer Gurtel 18-20, A-1097 Vienna, Austria.

Standard postoperative treatment of medulloblastoma consists of craniospinal irradiation and chemotherapy. Currently, only clinical factors are used for therapy stratification. To optimise treatment and patient outcome, biological prognostic markers are needed. In the present study we tested the prognostic influence of four histopathological parameters considered in recent publications as prognostic factors in medulloblastoma. We analysed a series of 82 Austrian medulloblastoma patients who were treated according to the consecutive HIT protocols for medulloblastoma conducted by the German Society of Paediatric Haematology and Oncology. Histological subtype and immunohistochemical expression of erbB-2, TRKC, and survivin were determined on paraffin embedded tumour tissue and correlated with patient outcome. Statistical analysis showed a significant correlation of high expression levels of survivin with decreased survival. None of the other investigated histopathological factors correlated significantly with patient outcome. Our data indicate that high survivin expression is related to unfavourable clinical outcome in medulloblastoma patients.

PMID: 16996732 [PubMed - as supplied by publisher]
 
13: J Clin Oncol. 2006 Sep 20;24(27):4517-20.
 
Response and resistance in a non-small-cell lung cancer patient with an epidermal growth factor receptor mutation and leptomeningeal metastases treated with high-dose gefitinib.

Jackman DM, Holmes AJ, Lindeman N, Wen PY, Kesari S, Borras AM, Bailey C, de Jong F, Janne PA, Johnson BE.

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Publication Types:
  • Case Reports

PMID: 16983123 [PubMed - indexed for MEDLINE]
 
14: J Neurooncol. 2006 Sep 27; [Epub ahead of print]
 
Expression of nine tumour antigens in a series of human glioblastoma multiforme: interest of EGFRvIII, IL-13Ralpha2, gp100 and TRP-2 for immunotherapy.

Saikali S, Avril T, Collet B, Hamlat A, Bansard JY, Drenou B, Guegan Y, Quillien V.

Departement d'Anatomie et cytologie pathologiques, Hopital Pontchaillou, Rennes, France.

In this study, we investigated the mRNA and protein expression of nine tumour antigens in human glioblastoma multiforme with a view to their possible use in dendritic cell-based immunotherapy. Expression of ALK, EGFRvIII, GALT3, gp100, IL-13Ralpha2, MAGE-A3, NA17-A, TRP-2 and tyrosinase were studied by real-time RT-PCR on frozen tissues using a series of 47 tumour samples from patients with glioblastoma. Results were compared with non-neoplastic brain expression or glioblastoma samples with very low levels of expression near the limits of detection for EGFRvIII and MAGE-A3, as these latter two antigens were not detected in non-neoplastic brain. Tumour antigens showing a 5-fold increase in mRNA expression were considered as positive, and only antigens displaying an mRNA over-expression in a significant number of cases were analysed by immunohistochemistry on paraffin-embedded sections. Using real time RT-PCR, we found EGFRvIII, gp100, IL-13Ralpha2 and TRP-2 to be positive in 64, 38, 32 and 21% of cases, respectively. While we observed no over-expression for ALK, GALT3 and tyrosinase, 3 samples out of 47 were positive for MAGE-3 and 1 sample for NA17-A. More than 25% of tumour cells showed strong protein expression in 13, 34, 85 and 96% of GBM samples for gp100, TRP-2, EGFRvIII and IL-13Ralpha2, respectively. Interestingly, protein expression of at least 3 antigens was observed in 38% of cases. These results point out the importance of EGFRvIII, IL-13Ralpha2 and, to a less extent gp100 and TRP-2, for developing an immunotherapy strategy against glioblastoma.

PMID: 17004103 [PubMed - as supplied by publisher]
 
15: J Neurooncol. 2006 Sep 26; [Epub ahead of print]
 
Disseminated medulloblastoma.

Amini A, Liu JK, Kestle JR.

Department of Neurosurgery, University of Utah, Health Sciences Center, Salt Lake City, UT, USA.

PMID: 17001520 [PubMed - as supplied by publisher]
 
16: J Neurooncol. 2006 Sep 26; [Epub ahead of print]
 
A lipoxygenase inhibitor in breast cancer brain metastases.

Flavin DF.

Foundation for Collaborative Medicine and Research, 24 Midwood Drive, Greenwich, CT, 06831, USA, Dana_FK@hotmail.com.

The complication of multiple brain metastases in breast cancer patients is a life threatening condition with limited success following standard therapies. The arachidonate lipoxygenase pathway appears to play a role in brain tumor growth as well as inhibition of apoptosis in in-vitro studies. The down regulation of these arachidonate lipoxygenase growth stimulating products therefore appeared to be a worthwile consideration for testing in brain metastases not responding to standard therapy. Boswellia serrata, a lipoxygenase inhibitor was applied for this inhibition. Multiple brain metastases were successfully reversed using this method in a breast cancer patient who had not shown improvement after standard therapy. The results suggest a potential new area of therapy for breast cancer patients with brain metastases that may be useful as an adjuvant to our standard therapy.

PMID: 17001517 [PubMed - as supplied by publisher]
 
17: J Neurooncol. 2006 Jul;78(3):217-25. Epub 2006 Jun 16.
 
Anti-apoptotic action by hypoxia inducible factor 1-alpha in human pituitary adenoma cell line, HP-75 in hypoxic condition.

Yoshida D, Kim K, Noha M, Teramoto A.

Department of Neurosurgery, Nippon Medical School, Tokyo, Japan.

Hypoxia-inducible factor-1 (HIF-1) alpha is the major transcription factor involved in the adaptive response to hypoxia. The purpose of this study was to investigate whether HIF 1-alpha protects HP75 cells, pituitary adenoma cell line from hypoxia induced apoptosis. HP75 was transfected with siRNA targeting HIF 1-alpha mRNA sequences or scrambled RNA duplexes, followed by subjected to hypoxia (1% oxygen) for 24 h, compared with normoxia (21%). The efficacy of RNAi was assessed via real-time RT-PCR and immunohistochemistry. Apoptosis was determined by Tdt-mediated dUTP nick end-labeling (TUNEL) assay and agarose gel electrophoresis. Membrane cDNA microarray was examined to detect gene profiling among the cell in normoxia, hypoxia, or hypoxia following the RNAi. A significantly greater proportion of HP75 cells transfected with specific siRNA duplexes and subsequently exposed to hypoxia demonstrated apoptosis to a large extent when compared with non-transfected cells. Transfection with specific siRNA duplexes knocked down HIF 1-alpha mRNA and protein expression in hypoxia-exposed cells by approximately 80%, whereas transfection with scrambled siRNA duplexes had no noticeable effect on HIF 1-alpha expression. Microarray analysis indicated that HIF1-alpha down-regulated caspase-10. These findings strongly suggest that HIF 1-alpha exerts an antiapoptotic role in HP75 in hypoxia.

PMID: 16779673 [PubMed - indexed for MEDLINE]
 
18: J Neurooncol. 2006 Jul;78(3):303-10. Epub 2006 Apr 6.
 
Intracranial tumors in adult population of the Varazdin County (Croatia) 1996-2004: a population-based retrospective incidence study.

Dobec-Meic B, Pikija S, Cvetko D, Trkulja V, Pazanin L, Kudelic N, Rotim K, Pavlicek I, Kostanjevec AR.

Department of Radiology, Jordanovac University Hospital for Pulmonary Diseases, Zagreb, Croatia.

AIM: To estimate the incidence of intracranial tumors in the adult population of the Varazdin County, Croatia, for the 1996-2004 period. METHODS: Setting: Varazdin County General Hospital and four university hospitals in Zagreb, the capital of Croatia. Study period: January 1, 1996 to December 31, 2004. Incident patients: county residents admitted for newly diagnosed intracranial tumors according to the WHO diagnostic criteria. Demographic data were extracted from the 2001 Croatian census. Incidence rates (IRs) per 100,000 person-years (p-y) and annual IRs (per 100,000 persons) were determined and compared as incidence rate ratios (IRRs) with 95% CI. RESULTS: For primary intracranial tumors (PITs), IR was 12.1/100,000 p-y (95% CI: 10.3-14.2), comparable in men and women. The highest incidence was recorded for glioblastoma (IR 4.8, 3.7-6.2) and meningioma (IR 3.1, 2.2-4.2). The incidence of PIT was somewhat greater than that of metastatic tumors (IRR 1.58, 95% CI: 1.22-2.05, P < 0.001). Metastatic tumors were more frequent in men than in women, especially metastatic lung tumors (IRR 6.08, 2.32-20.16, P < 0.001). IRs of all PIT taken together, neuroepithelial tumors cumulatively, nonepithelial tumors cumulatively, glioblastoma and meningioma were higher in the population aged > or = 40 vs. population aged < or = 39 (all IRRs with 95% CI greater than 1, P < 0.05 or < 0.001), comparable in men and women. Women were somewhat older than men at the time of diagnosis of PIT: median difference -6 years (95.1% CI: -10 to -1, P < 0.05). Annual IRs for all these tumor categories showed increasing trends over the study period. CONCLUSION: Overall, there was an increasing trend in the incidence of primary intracranial tumors in the Varazdin County. Data did not allow estimation for most of the specific tumor types.

PMID: 16598428 [PubMed - indexed for MEDLINE]
 
19: J Neurooncol. 2006 Jul;78(3):317-20. Epub 2006 Apr 6.
 
Embryonal tumor with abundant neuropil and true rosettes. A new entity or only variations of a parent neoplasms (PNETs)? This is the dilemma.

La Spina M, Pizzolitto S, Skrap M, Nocerino A, Russo G, Cataldo AD, Perilongo G.

Division of Hematology/Oncology, Department of Pediatrics, Catania University Hospital, Catania, Sicily, Italy. mlaspina@unict.it

A rare embryonal brain tumor has been diagnosed in a 4-year-old boy. The mass, located at the pons and mesencephalon, has been histologically classified as an embryonal tumor containing abundant neuropil and true rosettes.After surgical complete removal of the neoplasia, the child received intensive combined chemotherapy and radiotherapy. He is alive and free of disease at 34 months from surgery. Difficulties in histological definition, possible suggestions for treatment proposals are discussed.

Publication Types:
  • Case Reports

PMID: 16598427 [PubMed - indexed for MEDLINE]
 
20: J Neurooncol. 2006 Jul;78(3):321-6. Epub 2006 Apr 6.
 
High-grade astrocytoma treated concomitantly with estramustine and radiotherapy.

Henriksson R, Malmstrom A, Bergstrom P, Bergh G, Trojanowski T, Andreasson L, Blomquist E, Jonsborg S, Edekling T, Salander P, Brannstrom T, Bergenheim AT.

Department of Radiation Sciences and Oncology, Umea University Hospital, Umea, Sweden. roger.henriksson@onkologi.umu.se

Experimental and early clinical investigations have demonstrated encouraging results for estramustine in the treatment of malignant glioma. The present study is an open randomized clinical trial comparing estramustine phosphate (Estracyt) in addition to radiotherapy with radiotherapy alone as first line treatment of astrocytoma grade III and IV. The 140 patients included were in a good clinical condition with a median age of 55 years (range 22-87). Estramustine was given orally, 280 mg twice daily, as soon as the diagnosis was established, during and after the radiotherapy for a period of in total 3 months. Radiotherapy was delivered on weekdays 2 Gy daily up to 56 Gy. Eighteen patients were excluded due to misclassification, leaving 122 patients eligible for evaluation. Overall the treatment was well tolerated. Mild or moderate nausea was the most common side effect of estramustine. The minimum follow-up time was 5.2 years for the surviving patients. For astrocytoma grade III the median survival time was 10.6 (1.3-92.7) months for the radiotherapy only group and 17.3 (0.4-96.9+) months for the estramustine + radiotherapy group. In grade IV the corresponding median survival time was 12.3 (2.1-89.2) and 10.3 (0.3-91.7+) months, respectively. Median time to progress for radiotherapy only and radiotherapy and estramustin group in grade III tumours was 6.5 and 10.1 months, respectively. In grade IV tumours the corresponding figures were 5.1 and 3.3 months, respectively. Although there was a tendency for improved survival in grade III, no statistical significant differences were found between the treatment groups. No differences between the two treatment groups were evident with respect to quality of life according to the EORTC QLQ-protocol. In conclusion, this first randomized study did not demonstrate any significant improvement of using estramustine in addition to conventional radiotherapy, however, a trend for a positive response for the estramustine group was found in patients with grade III glioma.

Publication Types:
  • Randomized Controlled Trial

PMID: 16598426 [PubMed - indexed for MEDLINE]
 
21: J Neurooncol. 2006 Jul;78(3):327. Epub 2006 Mar 31.
 
Addendum to "aggressive spinal germinoma with ascending metastases".

Tekkok IH.

Publication Types:
  • Case Reports
  • Letter

PMID: 16575533 [PubMed - indexed for MEDLINE]
 
22: J Neurooncol. 2006 Jul;78(3):227-32. Epub 2006 Mar 24.
 
Pharmacokinetic study of BSH and BPA in simultaneous use for BNCT.

Yokoyama K, Miyatake S, Kajimoto Y, Kawabata S, Doi A, Yoshida T, Asano T, Kirihata M, Ono K, Kuroiwa T.

Department of Neurosurgery, Osaka Medical College, Takatsuki Osaka, Japan.

In order to improve the effectiveness of boron neutron capture therapy (BNCT) for malignant gliomas, we examined the optimization of the administration of boron compounds in brain tumor animal model. We analyzed the concentration of boron atoms in intracranial C6 glioma -bearing rats using inductively coupled plasma atomic emission spectrometry. Each tumor-bearing rat received one of two different amounts of sodium borocaptate (BSH) and/or 500 mg/kg of boronophenylalanine (BPA) via intraperitoneal injection. We compared the boron concentrations of the tumor, the contralateral normal brain and the blood in rats of 3 different treatment groups (BSH alone, BPA alone and a combination of both BSH and BPA). Our results show that the tumor boron concentration increased much more than 30 microg/g by the coadministration of both compounds. Additionally, the blood boron concentration remained below 30 microg/g and the boron concentration in the normal brain was low (mean 4.7+/-1.1 microg/g). Even in comparison with the administration of BPA alone, coadministration of BPA and BSH shows an improved tumor/normal brain ratio of boron concentrations.

Publication Types:
  • Evaluation Studies

PMID: 16557351 [PubMed - indexed for MEDLINE]
 
23: J Neurooncol. 2006 Jul;78(3):255-60.
 
Erratum in:
  • J Neurooncol. 2006 Jul;78(3):261. Shah, Gaurav G [corrected to Shah, Gaurav D].

Systemic high-dose intravenous methotrexate for central nervous system metastases.

Lassman AB, Abrey LE, Shah GD, Panageas KS, Begemann M, Malkin MG, Raizer JJ.

Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. Lassmana@mskcc.org

BACKGROUND: Treatment options for patients with recurrent central nervous system (CNS) metastases are limited. Rapid infusion of high-dose intravenous methotrexate (HD IV MTX) penetrates the blood-brain barrier (BBB) and has reported activity in leptomeningeal metastases. METHODS: Medical records were reviewed for all patients treated with HD IV MTX (3.5 g/m2) for CNS parenchymal or leptomeningeal metastases. Radiographic response rate, survival, and toxicity were determined. RESULTS: Thirty-one women and one man with a median age of 52 years (range 33-76) were treated with a total of 141 cycles (median 4, range 1-13). Twenty-nine patients had breast cancer, and one each had cancer of unknown primary (CUP), squamous cell carcinoma of the head and neck, and non-small cell lung cancer (NSCLC). An objective radiographic response and stable disease were each observed in nine patients (28%), and 13 (44%) patients progressed. Prior treatment with low-dose MTX for systemic disease did not affect response (P = 0.8). The median overall survival (n = 32) was 19.9 weeks (range 2.9-135.4+) with one patient alive at 135.4 weeks. Myelosuppression and elevated serum hepatic transaminases were the most common acute toxicities (21% and 9% of HD IV MTX cycles, respectively). CONCLUSIONS: HD IV MTX is effective in the treatment of CNS metastases with disease control (response or stable) as a best response in 56% of assessable patients. Further study is warranted.

Publication Types:
  • Clinical Trial

PMID: 16344918 [PubMed - indexed for MEDLINE]
 
24: J Neurosurg. 2006 Sep;105(3):503; author reply 503-4.

Comment on:
Ependymoma.

Palma L.

Publication Types:
  • Comment
  • Letter

PMID: 16961153 [PubMed - indexed for MEDLINE]
 
25: J Neurosurg. 2006 Sep;105(3):465-7.

Tako-tsubo cardiomyopathy: reversible heart failure with favorable outcome in patients with intracerebral hemorrhage. Case report.

Deininger MH, Radicke D, Buttler J, Scheufler KM, Freiman T, Zentner JF.

Department of Neurosurgery, University of Freiburg Medical School, Freiburg, Germany. martin.deininger@uni-tuebingen.de

In patients with intracerebal hemorrhage, cardiac dysfunction is a common phenomenon. Tako-tsubo cardiomyopathy is characterized by complete reversibility and therefore may constitute an entity with a favorable outcome. In this case report the authors describe a previously healthy 23-year-old man with no history of cardiac disease who suffered a severe fourth ventricular hemorrhage due to an angioma of the vermis cerebelli. After emergency surgery, progressive tachycardia, fibrillation, and electromechanical decoupling developed in the patient. An echocardiogram revealed left ventricular apical akinesia and basal hyperkinesis characteristic of tako-tsubo cardiomyopathy. One week after admission, cardiac function was normal. Tako-tsubo cardiomyopathy differs from common cardiac dysfunction in its reversible nature. This characteristic must be taken into consideration when treating patients with intracerebral hemorrhage to avoid misclassification of the disease.

Publication Types:
  • Case Reports

PMID: 16961144 [PubMed - indexed for MEDLINE]
 
26: J Neurosurg. 2006 Sep;105(3):461-4.

Oligodendroglioma of the pineal region. Case report.

Das S, Chandler JP, Pollack A, Biggio EH, Diaz L, Raizer JJ, Batjer HH.

Department of Neurological Surgery, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611, USA. s-das@md.northwestern.edu

The authors describe an oligodendroglioma of the pineal region in a 59-year-old woman. The patient presented with intermittent confusion, memory disturbance, and headache associated with a cystic pineal region mass demonstrated on magnetic resonance imaging. Gross-total resection was performed via a suboccipital supratentorial approach. Pathological and genetic evaluation showed the tumor to be an anaplastic oligodendroglioma. Although the spectrum of tumors arising within the region of the pineal gland is broad, to the authors' knowledge this is the first report of an oligodendroglioma occurring in this area.

Publication Types:
  • Case Reports

PMID: 16961143 [PubMed - indexed for MEDLINE]
 
27: Neuroradiology. 2006 May;48(5):312-8. Epub 2006 Mar 22.
 
In vivo research in astrocytoma cell proliferation with 1H-magnetic resonance spectroscopy: correlation with histopathology and immunohistochemistry.

Chen J, Huang SL, Li T, Chen XL.

Department of Radiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Hubei Province, Wuhan 430060, People's Republic of China. lily_chenjun82@yahoo.com.cn

INTRODUCTION: Assessment of brain tumor proliferative potential provides important prognostic information that supplements standard histopathologic grading. Proton magnetic resonance spectroscopy ((1)H-MRS) gives completely different information, relating to cell membrane proliferation, neuronal damage, energy metabolism and necrotic transformation of brain or tumor tissues. The aim of this study was to investigate the relationship between (1)H-MRS and tumor proliferative potential in astrocytomas. METHODS: We studied 34 patients with histologically verified astrocytomas using the (1)H-MRS protocol following routine MRI preoperatively. The tumor in 26 of these patients was classified as grade I/II (low grade), and the tumor in the remaining patients as grade III/IV (high grade) according to the World Health Organization classification criteria of nervous system tumors (2000). The tumor in 21 patients was homogeneous astrocytoma, and of these 17 were classified as low grade and 4 as high grade. Expression of proliferating cell nuclear antigen (PCNA) was determined immunohistochemically using streptavidin-biotin-peroxidase complex (SP) staining. RESULTS: The ratios of choline (Cho) to N-acetylaspartate (NAA) and Cho to creatine (Cr) in those with high-grade astrocytomas (n=4) were significantly higher than in those with low-grade astrocytomas (n=17) (t=2.899, P=0.009; t=3.96, P=0.001, respectively), and were found to be significantly correlated with the expression of PCNA in 21 patients with homogeneous astrocytomas (r=0.455, P=0.038; r=0.633, P=0.002, respectively). CONCLUSIONS: We conclude that (1)H-MRS may be a valuable method for predicting preoperatively the degree of malignancy of homogeneous astrocytomas by enabling the calculation of the Cho/NAA and Cho/Cr ratios in vivo, and indirect evaluation of the tumor proliferative potential and prognosis, which are not available using conventional magnetic resonance imaging (MRI).

PMID: 16552583 [PubMed - indexed for MEDLINE]
 
28: Neuroradiology. 2006 Jan;48(1):1-7. Epub 2005 Oct 20.
 
Intracranial lipomas: importance of localization.

Yildiz H, Hakyemez B, Koroglu M, Yesildag A, Baykal B.

Department of Radiology, School of Medicine, Suleyman Demirel University, 32200 Isparta, Turkey.

Intracranial lipomas are rare congenital malformations. They are usually pericallosal asymptomatic midline lesions. Other brain malformations are often seen in association with intracranial lipomas. We describe the findings of imaging studies, including computed tomography (CT), magnetic resonance (MR) imaging, and MR angiography, along with a brief review of the literature. The frequency and the spectrum of the associated brain malformations are also discussed. We retrospectively reviewed CT and MR findings of 24 patients (14 female, 10 male, mean age 38.6 years) diagnosed with intracranial lipoma between December 2000 and June 2004 in two different radiology departments. Seventeen of the patients were diagnosed using cranial MR and seven with cranial CT. The CT density of all lesions was measured. Imaging characteristics of lipomas, morphological findings and associated malformations were described. The intracranial locations of the lipomas were left-sided quadrigeminal cistern (n=3), right-sided quadrigeminal cistern (n=4), interpeduncular cistern (n=1), sylvian fissure (n=3), interhemispheric fissure (n=3), choroid plexus (n=2), intercerebellar fissure (n=3), corpus fornicis (n=1) and the periphery of the corpus callosum (n=4). Eighteen of the intracranial lipomas were tubulonodular; six were curvilinear. Associated anomalies were observed in six patients. All of the patients with sylvian fissure lipoma had seizures. The two preferential sites of intracranial lipomas were pericallosal and dorsal mesencephalic. Most intracranial lipomas are found incidentally during neuroradiological investigations. CT and MR examination usually lead to the diagnosis, because of the very low attenuation values of lipomas on CT and the short T1 and T2 on MR. Midline anomalies and other malformations such as aneurysms are frequently associated with intracranial lipomas. Careful radiologic evaluation is therefore necessary to evaluate associated pathologies. Sylvian fissure lipomas should be considered in the differential diagnosis of patients with epilepsy.

PMID: 16237548 [PubMed - indexed for MEDLINE]
 
29: Neurosurgery. 2006 Sep;59(3):660-70; discussion 660-70.
 
Absence of tight junctions between microvascular endothelial cells in human cerebellar hemangioblastomas.

Chen Y, Tachibana O, Hasegawa M, Xu R, Hamada J, Yamashita J, Hashimoto N, Takahashi JA.

Department of Neurosurgery, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan.

OBJECTIVE: Endothelial tight junctions form the main barrier of the blood-brain barrier (BBB). In human hemangioblastomas, cyst formation is a common and important clinical manifestation. Although most researchers consider that the cyst formation in hemangioblastomas may be caused by the breakdown of the BBB, the underlying molecular mechanisms for cyst formation remain unknown. At present, there are few reports about the change of tight junctions in microvessel endothelium of human hemangioblastomas. The purpose of this research is to investigate the change of tight junction and its major molecular components in microvessel endothelium of human hemangioblastomas. METHODS: Twenty-four consecutive patients with cerebellar hemangioblastomas were studied. Tight junctions in the microvessels of hemangioblastomas and the control brain were examined by electron microscopy. Immunohistochemistry and double immunofluorescent microscopy were used to analyze the expression of CLN5 and its relationship with astrocytic endfeet in the control brain and hemangioblastomas. Quantitative real-time reverse-transcriptase polymerase chain reaction and Western blots were used to investigate the expression level of CLN5 in hemangioblastomas. Triple immunofluorescent microscopy was used to analyze the coexpression of vascular endothelial growth factor, vascular endothelial growth factor-R1, and placenta growth factor on microvessels of hemangioblastomas. Clinical and experimental data were correlated and analyzed by the one-way analysis of variance, Kruskal-Wallis test, and Spearman rank correlation test. RESULTS: In the control brain, the paracellular cleft between adjacent endothelial cells is sealed by continuous strands of tight junctions. In cystic hemangioblastomas, a significant paracellular cleft could be found between adjacent endothelial cells. Some endothelial cells were connected with adherens junction and no tight junction was found between them. Compared with the control brain, expression of CLN5 was decreased in cystic hemangioblastomas (P < 0.05). Phosphorylated CLN5 was detected in most hemangioblastomas, but not in the control brain. Microvessels in hemangioblastomas showed a significant absence of astrocytic endfeet. Coexpression of vascular endothelial growth factor, vascular endothelial growth factor-R1, and placenta growth factor was detected in the endothelial cells. The Spearman rank correlation test showed a significant correlation between a greater degree of CLN5 expression and less morphological cystic formation in these patients studied (correlation coefficient = -0.520; P = 0.009). CONCLUSION: The continuity of tight junctions of the BBB is interrupted in human cerebellar hemangioblastomas. Significant absence of astrocytic endfeet and tight junctions can be found in microvessels of hemangioblastomas, which may lead to the breakdown of the BBB in these tumors. These findings suggest that the absence of tight junctions might play a role in cyst formation of hemangioblastomas.

PMID: 16955048 [PubMed - indexed for MEDLINE]
 
30: Neurosurgery. 2006 Sep;59(3):651-9; discussion 651-9.
 
Use of a volumetric target for image-guided surgery.

Gildenberg PL, Labuz J.

Department of Neurosurgery, Baylor Medical College, Houston, Texas, USA. hsc@stereotactic.net

A VIRTUAL REALITY system has been devised to superimpose a computer-generated rendering of a volumetric target to be surgically approached or resected on a real-time video image of the surgical field. A stereotactic frame is used to register the image from the video camera with the image of the target volume for accurate localization. The volumetric target is obtained from preoperative imaging studies and can be modified to adjust the intended line of resection or to avoid eloquent vascular or neural tissue. The computer-generated image is updated throughout surgery to visualize only that part of the tumor under resection so the surgeon may guide the resection along the border of the mass or intended preplanned line of resection. To date, 74 intracranial tumor resections have been performed under video virtual reality guidance. Postoperative scanning corresponds in every case with preoperative planning. This system is also designed to be adapted to frameless guidance, which can be further enhanced by the incorporation of an audible tone to signal the relationship of the tip of the resection instrument to the line of resection.

PMID: 16955047 [PubMed - indexed for MEDLINE]
 
31: Neurosurgery. 2006 Sep;59(3):E703-4; discussion E703-4.
 
Follicular lymphoma of the dura: case report.

Hamilton DK, Bourne TD, Ahmed H, Cousar JB, Mandell JW, Sheehan JP.

Department of Neurological Surgery, University of Virginia, Charlottesville 22908, USA. dkh9e@virginia.edu

OBJECTIVE: We present an unusual dural-based follicular lymphoma with radiological and macroscopic features similar to a meningioma. The unusual location of this tumor and its distinction from meningioma, mucosa-associated lymphoid tissue-type marginal zone B-cell lymphoma of the dura, and intraparenchymal central nervous system lymphoma, dramatically alters the patient's postoperative treatment. The case illustrates the clinical, radiological, and histological relevance of this rare entity. CLINICAL PRESENTATION: A 41-year-old Caucasian man with chronic bifrontal headaches and a raised area over his left frontal cranium that persisted for 1 year presented to the emergency room with nausea and vomiting. His family reported that the patient demonstrated increased irritability and aggressive behavior. A computed tomographic scan revealed a large mass of the left frontal convexity with edema and mass effect. Magnetic resonance imaging scans showed a 5-cm homogeneously enhancing mass in the left posterior frontal lobe. INTERVENTION: Preoperatively, the patient underwent angiography and embolization of the tumor. The patient underwent gross total resection of tumor. The dural-based tumor invaded the cranium and scalp. Neuropathological findings were consistent with low-grade follicular lymphoma. The patient is currently undergoing radiation and chemotherapy. CONCLUSION: The current case represents the first report of extensive intracranial dural involvement by a follicular lymphoma that shows a classic immunophenotype by immunohistochemistry and flow cytometry. The case illustrates the clinical and radiographic similarities between dural-based lymphoma and meningioma. Distinguishing dural-based follicular lymphoma from mucosa-associated lymphoid tissue-type lymphoma and from intraparenchymal primary central nervous system lymphomas, which are more often large cell lymphomas with more aggressive biological behavior, is essential for proper clinical management.

Publication Types:
  • Case Reports

PMID: 16955025 [PubMed - indexed for MEDLINE]
 
32: Neurosurgery. 2005 Jan;56(1 Suppl):133-41; discussion 133-41.
 
Sequential visualization of brain and fiber tract deformation during intracranial surgery with three-dimensional ultrasound: an approach to evaluate the effect of brain shift.

Coenen VA, Krings T, Weidemann J, Hans FJ, Reinacher P, Gilsbach JM, Rohde V.

Department of Neurosurgery, University Hospital, Aachen University of Technology, Aachen, Germany. vacoenen@aol.com

OBJECTIVE: We present a technique that allows intraoperative display of brain shift and its effects on fiber tracts. METHODS: Three patients had intracranial lesions (one malignant glioma, one metastasis, and one cavernoma) in contact with either the corticospinal or the geniculostriate tract that were removed microneurosurgically. Preoperatively, magnetic resonance diffusion-weighted imaging (DWI) was performed to visualize the fiber tract at risk. DWI data were fused with those obtained from anatomic T1-weighted magnetic resonance imaging. A single-rack three-dimensional ultrasound neuronavigation system, which simultaneously displays the MRI scan and the corresponding ultrasound image, was used intraoperatively for 1) navigation; 2) definition of fixed and potentially shifting ultrasound landmarks near the fiber tract; and 3) sequential image updating at different steps of resection. The result was time-dependent brain deformation data. With a standard personal computer equipped with standard image software, the brain shift-associated fiber tract deformation was assessed by use of sequential landmark registration. After surgery, DWI was performed to confirm the predicted fiber tract deformation. RESULTS: The lesions were removed without morbidity. Comparison of three-dimensional ultrasound with DWI and T1-weighted magnetic resonance imaging data allowed us to define fixed and potentially shifting landmarks close to the respective fiber tract. Postoperative DWI confirmed that the actual fiber tract position at the conclusion of surgery corresponded to the sonographically predicted fiber tract position. CONCLUSION: By definition and sequential intraoperative registration of ultrasound landmarks near the fiber tract, brain shift-associated deformation of a tract that is not visible sonographically can be assessed correctly. This approach seems to help identify and avoid eloquent brain areas during intracranial surgery.

Publication Types:
  • Case Reports

PMID: 15799801 [PubMed - indexed for MEDLINE]
 
33: Neurosurgery. 2005 Jan;56(1 Suppl):125-32; discussion 125-32.
 
Microsurgical removal of intraventricular lesions using endoscopic visualization and stereotactic guidance.

Harris AE, Hadjipanayis CG, Lunsford LD, Lunsford AK, Kassam AB.

Center for Image-guided and Minimally Invasive Neurosurgery, Department of Neurosurgery, University of Pittsburgh Medical Center-Presbyterian, Pittsburgh, Pennsylvania 15213, USA.

OBJECTIVE: To demonstrate the technique of stereotactic microsurgical endoscopic removal of intraventricular tumors or colloid cysts assisted by intraoperative computed tomography. METHODS: We adapted a tubular "ventriculoport" for stereotactic insertion of an endoscope into the ventricle. This facilitated microsurgical resection of 14 intraventricular tumors or colloid cysts by use of intraoperative stereotactic microsurgical endoscopic removal of intraventricular tumors or colloid cysts assisted by intraoperative computed tomography. RESULTS: Gross total resection was achieved in 12 patients and confirmed by intraoperative computed tomographic scanning and postoperative magnetic resonance imaging. Patients with preoperative hydrocephalus had relief of their symptoms. Perioperative morbidity was limited to mild headache associated with postoperative pneumocephalus. The average length of stay was 3.6 days. Twelve patients had significant improvement in their symptoms. CONCLUSION: The combination of intraoperative computed tomography-guided stereotactic technique and rigid endoscopy facilitated an accurate, minimally invasive, microsurgical removal of these intraventricular masses. This approach minimized retraction and provided satisfactory visualization.

Publication Types:
  • Case Reports

PMID: 15799800 [PubMed - indexed for MEDLINE]
 
34: Neurosurgery. 2005 Jan;56(1 Suppl):98-109; discussion 98-109.
 
Functional identification of the primary motor area by corticospinal tractography.

Kamada K, Sawamura Y, Takeuchi F, Kawaguchi H, Kuriki S, Todo T, Morita A, Masutani Y, Aoki S, Kirino T.

Department of Neurosurgery, University of Tokyo, Hongo 7-3-1, Tokyo, Japan. kamady-k@umin.ac.jp

OBJECTIVE: For quick and stable identification of the primary motor area (PMA), diffusion tensor imaging (DTI) data were acquired and corticospinal tractography was mathematically visualized. METHODS: Data sets of DTI, anatomic magnetic resonance imaging, and functional magnetic resonance imaging with finger-tapping tasks were acquired during the same investigation in 30 patients with a brain lesion affecting the motor system. Off-line processing of DTI data was performed to visualize the corticospinal tract, placing a seed area in the cerebral peduncle of the midbrain, where the corticospinal tract is densely concentrated. Somatosensory evoked magnetic fields and intraoperative cortical somatosensory evoked potentials were recorded with electrical stimulation of the median nerve to confirm the results of the corticospinal tractography. RESULTS: Functional magnetic resonance imaging and somatosensory evoked magnetic fields failed to identify the PMA in eight patients (16.7%) and one patient (3.8%) investigated, respectively, because of cortical dysfunctions caused by brain lesions. DTI data were acquired within 3 minutes without patient tasks. Using the appropriate seed area and fractional anisotropy, corticospinal tractography successfully indicated the PMA location in all patients. The suspected PMA and central sulcus locations were confirmed by the cortical somatosensory evoked potentials. CONCLUSION: Corticospinal tractography enables identification of the PMA and is beneficial, particularly for patients who present with dysfunction of the PMA.

Publication Types:
  • Case Reports

PMID: 15799797 [PubMed - indexed for MEDLINE]
 
35: Neurosurgery. 2005 Jan;56(1 Suppl):36-45; discussion 36-45.
 
Lateral ventricle tumors: surgical strategies according to tumor origin and development--a series of 72 cases.

D'Angelo VA, Galarza M, Catapano D, Monte V, Bisceglia M, Carosi I.

Department of Neurosciences, Division of Neurosurgery, Hospital Casa Sollievo della Sofferenza, Istituto di Ricovero e Cura a Carattere Scientifico, San Giovanni Rotondo, Foggia, Italy. v.dangelo@operapadrepio.it

OBJECTIVE: Optimal surgical management in lateral ventricle tumors remains controversial. We conducted a retrospective study of patients with these lesions treated with a surgical strategy on the basis of tumor origin: primary or secondary ventricular and associated transependymal development. METHODS: A total of 72 patients underwent surgery for lateral ventricle tumors. The mean patient age was 39 years (range, 6 mo to 78 yr). Raised intracranial pressure occurred in 53% of patients, followed by mental disturbances or psychiatric symptoms (32%) and motor deficits (21%). The transcortical approach was used in 44 patients, and an interhemispheric approach was used in 28 patients; a transcallosal approach was used in 16 patients, and a parasplenial approach was used in 12 patients. Neuropsychological tests were performed in selected patients. RESULTS: Total resection was performed in 82% of patients. Sixty-five percent of tumors were benign and low-grade tumors. There was no surgical mortality, and the morbidity rate was 11%. Postoperative epilepsy (5.9%) was significantly increased in the transcortical group. The mean follow-up period was 55 months; 59% of patients achieved good recovery and moderate disability. In postoperative neuropsychological testing sessions, deficits in verbal memory were observed in six patients (8%). Final morbidity correlated well with preoperative clinical condition and pathological diagnosis. CONCLUSION: Lateral ventricle tumors can be treated best by careful selection of the approach according to tumor origin and development. Overall, the transcallosal approach is preferred, but in patients with transependymal growth or large primary or secondary ventricular tumors, the transcortical is a better option.

PMID: 15799791 [PubMed - indexed for MEDLINE]
 
36: Oncogene. 2006 Sep 25; [Epub ahead of print]
 
Silencing mammalian target of rapamycin signaling by small interfering RNA enhances rapamycin-induced autophagy in malignant glioma cells.

Iwamaru A, Kondo Y, Iwado E, Aoki H, Fujiwara K, Yokoyama T, Mills GB, Kondo S.

1Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

The mammalian target of rapamycin (mTOR) plays a central role in regulating the proliferation of malignant glioma cells, and mTOR-specific inhibitors such as rapamycin analogs are considered as promising therapy for malignant gliomas. However, the efficacy of mTOR inhibitors alone in the treatment of patients with malignant gliomas is only modest, potentially because these agents rather than acting as mTOR kinase inhibitors instead interfere with the function of only mTOR/raptor (regulatory-associated protein of mTOR) complex and thus do not perturb all mTOR functions. The purpose of this study was to determine whether global inhibition of the mTOR molecule enhances the antitumor effect of rapamycin on malignant glioma cells. We showed that rapamycin induced autophagy and that inhibition of autophagy by small interfering RNA (siRNA) directed against autophagy-related gene Beclin 1 attenuated the cytotoxicity of rapamycin in rapamycin-sensitive tumor cells, indicating that the autophagy was a primary mediator of rapamycin's antitumor effect rather than a protective response. Exogenous expression of an mTOR mutant interfering with its kinase activity markedly enhanced the incidence of rapamycin-induced autophagy. Moreover, silencing of mTOR with siRNA augmented the inhibitory effect of rapamycin on tumor cell viability by stimulating autophagy. Importantly, not only rapamycin-sensitive malignant glioma cells with PTEN mutations but also rapamycin-resistant malignant glioma cells with wild-type PTEN were sensitized to rapamycin by mTOR siRNA. These results indicate that rapamycin-induced autophagy is one of the agent's antitumor effects and that silencing or inhibiting mTOR kinase activity could enhance the effectiveness of rapamycin.Oncogene advance online publication, 25 September 2006; doi:10.1038/sj.onc.1209992.

PMID: 17001313 [PubMed - as supplied by publisher]
 
37: Oncogene. 2006 Aug 28;25(38):5294-301.
 
Role of the interaction between large T antigen and Rb family members in the oncogenicity of JC virus.

Caracciolo V, Reiss K, Khalili K, De Falco G, Giordano A.

Department of Biology, Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA 19122, USA.

Human polyomaviruses (JC virus, BK virus and simian virus 40) are causative agents of some human diseases and, interestingly, are involved in processes of cell transformation and oncogenesis. These viruses need the cell cycle machinery of the host cell to complete their replication; so they evolved mechanisms that can interfere with the growth control of infected cells and force them into DNA replication. The retinoblastoma family of proteins (pRb), which includes pRb/p105, p107 and pRb2/p130, acts as one of the most important regulators of the G1/S transition of the cell cycle. Rb proteins represent an important target for viral oncoproteins. Early viral T antigens can bind all members of the pRb family, promoting the activation of the E2F family of transcription factors, thus inducing the expression of genes required for the entry to the S phase.The interaction between early viral antigens and cell cycle regulators represents an important mechanism through which viruses deregulate cell cycle and lead to cell transformation. In this review, we will discuss the effects of the interaction between large T antigen and Rb proteins in JC virus-mediated oncogenesis.

Publication Types:
  • Review

PMID: 16936750 [PubMed - indexed for MEDLINE]
 
38: Oncogene. 2006 Aug 28;25(38):5286-93.
 
Interaction of retinoblastoma protein family members with large T-antigen of primate polyomaviruses.

White MK, Khalili K.

Center for Neurovirology, Department of Neuroscience, Temple University School of Medicine, Philadelphia, PA 19122, USA.

The retinoblastoma gene product pRb and other members of the Rb family of pocket proteins have a central role in the regulation of cell cycle progression. Soon after its discovery, pRb was found to interact with the transforming oncoproteins of DNA tumor viruses and this led to rapid advances in our understanding of the mechanisms of viral transformation and cell cycle progression. DNA viruses of the polyomavirus family have small, circular, double-stranded DNA genomes contained within non-enveloped icosahedral capsids and are highly tumorigenic in experimental animals. At least three types of polyomavirus infect humans: JC virus (JCV), BK virus (BKV) and Simian Vacuolating virus-40. The early region of these viruses encodes the transforming proteins large T-antigen and small t-antigen, which are involved in viral replication and also promote transformation of cells in culture and oncogenesis in vivo. Binding of T-antigen to pRb promotes the activation of the E2F family of transcription factors, which induce the expression of cellular genes required for S phase. In the context of lytic infection, this cell cycle progression is necessary for viral replication because polyomaviruses rely on S phase-specific host factors for their DNA synthesis. In the context of cellular transformation and tumorigenesis, T-antigen/pRB interaction is an indispensable event.

Publication Types:
  • Review

PMID: 16936749 [PubMed - indexed for MEDLINE]
 
39: Oncogene. 2006 Aug 24;25(37):5125-33. Epub 2006 Apr 10.
 
5-Aza-2'-deoxycytidine and IFN-gamma cooperate to sensitize for TRAIL-induced apoptosis by upregulating caspase-8.

Fulda S, Debatin KM.

Department of Hematology/Oncology, University Children's Hospital, Ulm, Germany. simone.fulda@uniklinik-ulm.de

Resistance of tumors to cytotoxic therapy remains a major obstacle in cancer treatment and is often caused by defects in apoptosis programs. Caspase-8, a key mediator of death receptor-induced apoptosis, has previously been reported to be frequently inactivated by epigenetic silencing in many tumors, for example in neuroblastoma or medulloblastoma. Here, we provide for the first time evidence that combined treatment with suboptimal concentrations of the demethylating agent 5-Aza-2'-deoxycytidine (5-dAzaC) and interferon-gamma (IFN-gamma) cooperated to upregulate caspase-8 expression in neuroblastoma and medulloblastoma cells lacking caspase-8. Consequently, activation of caspase-8 and downstream caspases upon addition of TNF-related apoptosis-inducing ligand (TRAIL) was restored by pretreatment with 5-dAzaC and IFN-gamma. Importantly, pretreatment with 5-dAzaC and IFN-gamma acted in concert to significantly enhance TRAIL-induced apoptosis in neuroblastoma and medulloblastoma cells. Inhibition of caspase-8 by dominant-negative caspase-8 or by the relatively specific caspase-8 inhibitior zIETD.fmk inhibited the increase in apoptosis provided by 5-dAzaC and IFN-gamma, indicating that caspase-8 is a key mediator of this sensitization effect. Thus, by demonstrating that 5-dAzaC and IFN-gamma at relatively low individual concentrations cooperate to restore caspase-8 expression and sensitize resistant neuroblastoma and medulloblastoma cells to TRAIL-induced apoptosis, our findings have important implications for novel strategies targeting defective apoptosis pathways in neuroectodermal tumors.

PMID: 16607283 [PubMed - indexed for MEDLINE]
 
40: Pediatr Neurol. 2006 Oct;35(4):287-8.
 
Ataxia-telangiectasia complicated by craniopharyngioma - a new observation.

Masri AT, Bakri FG, Al-Hadidy AM, Musharbash AF, Al-Hussaini M.

Department of Pediatrics, Division of Child Neurology, Jordan University Hospital, Amman, Jordan.

Ataxia-telangiectasia is a rare autosomal recessive neurodegenerative disorder with high incidence of malignancy including leukemias, lymphomas, and solid tumors. Central nervous system tumors in ataxia telangiectasia include medulloblastomas and gliomas. We describe a 13-year-old girl with ataxia telangiectasia who developed craniopharyngioma and non-Hodgkin's lymphoma. To our knowledge, this is the first case of ataxia telangiectasia complicated by craniopharyngioma in the English literature.

PMID: 16996406 [PubMed - in process]
 
41: Pediatr Neurol. 2006 Oct;35(4):280-283.
 
Idiopathic Granulomatous Encephalitis Mimicking Malignant Brain Tumor.

Shuper A, Michovitz S, Amir J, Kornreich L, Boikov O, Yaniv Y, Rorke-Adams LB.

Department of Hematology-Oncology, Schneider Children's Medical Center of Israel, Petah Tiqva, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Idiopathic granulomatous encephalitis is a rare disorder of unknown etiology, undetermined treatment, and often grave prognosis. This article describes a 4-year-old female who presented with a single focal febrile convulsion followed a few weeks later by right-sided hemiparesis. A huge infiltrative cerebral mass tumor was found which proved to be a granuloma on histologic study. Despite a thorough evaluation, including tissue studies and search for an infectious agent, no etiology could be identified, and the final diagnosis was idiopathic granulomatous encephalitis. Recurrent resections and high-dose steroid treatment failed to control the process, and the patient died of disease 6 months after presentation. Evaluation and treatment of idiopathic granulomatous encephalitis should be aggressive, and the possibility of chemotherapy and perhaps even radiotherapy should be considered if there is no response to steroids.

PMID: 16996404 [PubMed - as supplied by publisher]
 
42: Surg Neurol. 2006 Aug;66(2):212-4.
 
Spinal intradural capillary hemangioma.

Kim KJ, Lee JY, Lee SH.

Department of Neurosurgery, Wooridul Spine Hospital, Kangnam-Gu, Seoul 135-100, Korea. kkj723@hanmail.net

BACKGROUND: Capillary hemangiomas are typically superficial lesions found in the skin or mucosa of the head and neck, but intradural locations are rare. We report a case of the spinal intradural capillary hemangioma of the lumbar spine with a review of the pertinent literature. CASE DESCRIPTION: A 59-year-old man presented with a 3-month history of low back pain and left leg pain. On examinations, the patient was shown to have paresthesia in the left L4, L5, and S1 dermatome and a diminution of the left knee jerk. Magnetic resonance imaging revealed an approximately 2-cm intradural enhancing lesion at the level of the L1-2 disk space. Laminectomy of L1-2 was performed for tumor removal. A reddish mass was covered by matted adherent nerve roots and derived its blood supply from radicular vessels. Complete excision was accomplished. Histologic diagnosis was capillary hemangioma. After operation, the patient's symptoms were improved. CONCLUSION: We experienced a rare spinal intradural vascular tumor of the lumbar spine. Histologic diagnosis was capillary hemangioma. We report a rare case of spinal intradural capillary hemangioma of the lumbar spine.

Publication Types:
  • Case Reports

PMID: 16876637 [PubMed - indexed for MEDLINE]
 
43: Surg Neurol. 2006 Aug;66(2):203-6; discussion 206.
 
Klippel-Trenaunay-Weber syndrome and intramedullary cervical cavernoma: a very rare association. Case report.

Pichierri A, Piccirilli M, Passacantilli E, Frati A, Santoro A.

Department of Neurological Sciences--Neurosurgery, University of Rome "La Sapienza," Rome, Italy. angelopichierri@fastwebnet.it

BACKGROUND: Klippel-Trenaunay-Weber syndrome is a rare mesodermal phakomatosis characterized by cutaneous hemangiomata, venous varicosities, and osseous-soft tissue hypertrophy of the affected limb. As the pathologic aspect of KTWS arises from the site in which malformations occur, the clinical picture varies widely from patients who complain for cosmetic reasons to patients with life-threatening lesions. CASE DESCRIPTION: We describe a very rare case in which KTWS was associated with a cervical intramedullary cavernous angioma surgically treated. CONCLUSION: This report confirms the wide range of expression of vascular abnormalities in neurocutaneous developmental diseases and the need of a careful multisystemic evaluation of these patients.

Publication Types:
  • Case Reports

PMID: 16876633 [PubMed - indexed for MEDLINE]
 
44: BMC Cancer. 2006 Sep 23;6(1):226 [Epub ahead of print]
 
In vivo glioblastoma growth is reduced by apyrase activity in a rat glioma model.

Morrone FB, Oliveira DL, Gammermann P, Stella J, Wofchuk S, Wink MR, Meurer L, Edelweiss MI, Lenz G, Battastini AM.

ABSTRACT: BACKGROUND: ATP is an important signalling molecule in the peripheral and central nervous system. Both glioma growth and tumor resection induces cell death, thus liberating nucleotides to the extracellular medium. Nucleotides are hydrolyzed very slowly by gliomas when compared with astrocytes and induce neuronal cell death and glioma proliferation. The objective of the present study was to test the involvement of extracellular ATP in glioblastoma growth in a rat glioma model. METHODS: To deplete the extracellular ATP, the enzyme apyrase was tested on the treatment of gliomas implanted in the rats CNS. One million glioma C6 cells in 3 microliters of DMEM/FCS were injected in the right striata of male Wistar rats, 250-270g. After 20 days, the rats were decapitated and the brain sectioning and stained with hematoxylin and eosine. We performed immunohistochemical experiments with Ki67, CD31 and VEGF. Total RNA was isolated from cultured glioma C6 cells and the cDNA was analyzed by Real Time-PCR with primers for the NTPDase family. RESULTS: C6 glioma cells effectively have a low expression of all NTPDases investigated, in comparison with normal astrocytes. The implanted glioma co-injected with apyrase had a significant reduction in the tumor size (p<0.05) when compared with the rats injected only with gliomas or with gliomas plus inactivated apyrase. According to the pathological analysis, the malignant gliomas induced by C6 injection and co-injected with apyrase presented a significant reduction in the mitotic index and other histological characteristics that indicate a less invasive/proliferative tumor. Reduction of proliferation induced by apyrase co-injection was confirmed by counting the percentage of Ki67 positive glioma cell nuclei. According to counts with CD31, vessel density and neoformation was higher in the C6 group 20 days after implantation. Confirming this observation, rats treated with apyrase presented less VEGF staining in comparison to the control group. CONCLUSION: These results indicate that the participation of extracellular ATP and the ecto-nucleotidases may be associated with the development of this type of brain tumor in an in vivo glioma model.

PMID: 16995949 [PubMed - as supplied by publisher]