Volume 5
Archive

1: AJNR Am J Neuroradiol. 2006 Nov;27(10):2204-2209.

Imaging and Clinical Characteristics of Temporal Bone Meningioma.

Hamilton BE, Salzman KL, Patel N, Wiggins RH 3rd, Macdonald AJ, Shelton C, Wallace RC, Cure J, Harnsberger HR.

Department of Radiology, University of Utah, Salt Lake City, Utah.

BACKGROUND AND PURPOSE: Imaging characteristics of temporal bone meningioma have not been previously reported in the literature. CT and MR imaging findings in 13 cases of temporal bone meningioma are reviewed to define specific imaging features. METHODS: A retrospective review of our institutional case archive revealed 13 cases of histologically confirmed temporal bone meningioma. CT and MR imaging studies were reviewed to characterize mass location, vector of spread, bone changes, enhancement characteristics, and intracranial patterns of involvement. Clinical presenting signs and symptoms were correlated with imaging findings. RESULTS: Thirteen temporal bone meningiomas were reviewed in 8 women and 5 men, aged 18-65 years. Meningiomas were stratified into 3 groups on the basis of location and tumor vector of spread. There were 6 tegmen tympani, 5 jugular foramen (JF), and 2 internal auditory canal (IAC) meningiomas. Tegmen tympani and JF meningiomas were characterized by spread to the middle ear cavity. IAC meningiomas, by contrast, spread to the cochlea and vestibule. Hearing loss was the most common clinical presenting feature in all cases of temporal bone meningioma (10/13). The presence of tumor adjacent to the ossicles strongly correlated with conductive hearing loss (7/9). CONCLUSION: Meningioma involving the temporal bone is rare. Three subgroups of meningioma exist in this location: tegmen tympani, JF, and IAC meningioma. Tegmen tympani and JF meningiomas spread to the middle ear cavity. IAC meningiomas spread to intralabyrinthine structures. Conductive hearing loss is commonly seen in these patients and can be surgically correctable.

PMID: 17110695 [PubMed - as supplied by publisher]

 

2: AJNR Am J Neuroradiol. 2006 Nov;27(10):2137-2140.

Whole-Brain N-Acetylaspartate Spectroscopy and Diffusion Tensor Imaging in Patients with Newly Diagnosed Gliomas: A Preliminary Study.

Inglese M, Brown S, Johnson G, Law M, Knopp E, Gonen O.

Department of Radiology, New York University School of Medicine, NY.

BACKGROUND AND PURPOSE:Glial cancer cells can be found well beyond the MR imaging T2 signal-intensity hyperintensity. To quantify the extent of the diffuse microstructural tissue damage possibly due to the presence of these satellite tumor cells, we investigated the relationships between global metabolic and microstructural abnormalities in the normal-appearing brain regions of patients with newly diagnosed glioma. MATERIAL AND METHODS:Ten patients (6 men, 4 women) with radiologically suspected untreated supratentorial glial tumors and 9 healthy controls (5 men, 4 women) were studied with T1- and T2-weighted MR imaging, diffusion-weighted echo-planar MR imaging, and whole-brain N-acetylaspartate (WBNAA) proton MR spectroscopy. The relationship between the WBNAA concentration, the mean diffusivity (MD), and fractional anisotropy (FA) values in a large contralateral normal-appearing white matter (NAWM) brain region was investigated with the Spearman rank correlation test. RESULTS:WBNAA values were significantly lower (P < .001) in patients (9.7 +/- 1.7 mmol/L) than controls (13.1 +/- 1.1 mmol/L). MD values were higher (P = .0001) in patients (0.95 +/- 0.07 mm(2)s(-1)) than in controls (0.61 +/- 0.04 mm(2)s(-1)). FA values did not differ between patients (0.42 +/- 0.08) and controls (0.43 +/- 0.041). A strong inverse correlation between WBNAA and MD (r = -0.88, P = .0008) was found in the patients but not in controls (r = 0.012, P = .975). CONCLUSION:The correlation between the WBNAA and MD in the contralateral NAWM suggests that the microstructural damage possibly related to the presence of infiltrative tumor cells contributes to WBNAA decline in these patients.

PMID: 17110683 [PubMed - as supplied by publisher]

 

3: AJNR Am J Neuroradiol. 2006 Nov;27(10):2128-2134.

Low-Field MR Imaging of Meningiomas Including Dynamic Contrast Enhancement Study: Evaluation of Surgical and Histopathologic Characteristics.

Yrjana SK, Tuominen H, Karttunen A, Lahdesluoma N, Heikkinen E, Koivukangas J.

Department of Neurosurgery, Oulu University Hospital, Oulu, Finland.

BACKGROUND AND PURPOSE:Risks associated with surgery of meningiomas, especially those located in the skull base, are influenced by tumor consistency and vascularity. The purpose of this study was to find out if vascularity, consistency, and histologic characteristics of meningioma can be predicted preoperatively by using low-field MR imaging, including dynamic imaging of contrast enhancement. MATERIALS AND METHODS:Twenty-one patients (mean age, 56; range, 34-73 years; 16 women, 5 men) with meningioma requiring first surgery were imaged by a 0.23T scanner. Time to maximum enhancement, maximum enhancement, and maximum intensity increase were noted from the enhancement curve of dynamic imaging. Relative intensity of tumor in fluid-attenuated inversion recovery (FLAIR) and T2-weighted images was calculated. The neurosurgeon evaluated surgical bleeding and hardness of tumor on a visual analog scale. Histopathologic analysis included subtype, World Health Organization grade, mitotic activity, grades of progesterone receptor expression and collagen content, proliferation activity by Ki-67 (MIB-1), and microvessel density by CD34. Correlations were studied with Kendall tau statistics. RESULTS:The most powerful association was found between time to maximum enhancement and microvessel density (tau = -0.60, P < .001). Surgical bleeding (tau = 0.49, P = .002), blood loss during surgery (tau = 0.49, P = .002), progesterone receptor expression (tau = 0.59, P < .001), and collagen content (tau = -0.54, P < .001) were statistically best correlated with the relative intensity of meningioma on FLAIR images. Tissue hardness correlated best with relative intensity on T2-weighted images (tau = 0.40, P = .012). CONCLUSION:Assessment of microvessel density, collagen content, and progesterone receptor expression of meningioma may be clinically feasible by using low-field MR imaging.

PMID: 17110681 [PubMed - as supplied by publisher]

 

4: Br J Cancer. 2006 Oct 9;95(7):879-88. Epub 2006 Sep 12.

 
Antineoplastic effects of rosiglitazone and PPARgamma transactivation in neuroblastoma cells.

Cellai I, Benvenuti S, Luciani P, Galli A, Ceni E, Simi L, Baglioni S, Muratori M, Ottanelli B, Serio M, Thiele CJ, Peri A.

Endocrine Unit, Department of Clinical Physiopathology, Center for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders (DENOThe), University of Florence, Florence, Italy.

Neuroblastoma (NB) is the most common extracranial solid tumour in infants. Unfortunately, most children present with advanced disease and have a poor prognosis. In the present study, we evaluated the role of the peroxisome proliferator-activated receptor gamma (PPARgamma) agonist rosiglitazone (RGZ) in two NB cell lines (SK-N-AS and SH-SY5Y), which express PPARgamma. Rosiglitazone decreased cell proliferation and viability to a greater extent in SK-N-AS than in SH-SY5Y. Furthermore, 20 microM RGZ significantly inhibited cell adhesion, invasiveness and apoptosis in SK-N-AS, but not in SH-SY5Y. Because of the different response of SK-N-AS and SH-SY5Y cells to RGZ, the function of PPARgamma as a transcriptional activator was assessed. Noticeably, transient transcription experiments with a PPARgamma responsive element showed that RGZ induced a three-fold increase of the reporter activity in SK-N-AS, whereas no effect was observed in SH-SY5Y. The different PPARgamma activity may be likely due to the markedly lower amount of phopshorylated (i.e. inactive) protein observed in SK-N-AS. To our knowledge, this is the first demonstration that the differential response of NB cells to RGZ may be related to differences in PPARgamma transactivation. This finding indicates that PPARgamma activity may be useful to select those patients, for whom PPARgamma agonists may have a beneficial therapeutic effect.

PMID: 16969347 [PubMed - indexed for MEDLINE]

 

5: Br J Cancer. 2006 Oct 9;95(7):869-78. Epub 2006 Sep 12.

 
Fatty acid synthase: a novel target for antiglioma therapy.

Zhao W, Kridel S, Thorburn A, Kooshki M, Little J, Hebbar S, Robbins M.

Department of Radiation Oncology, Brain Tumor Center of Excellence, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. wzhao@wfubmc.edu

High levels of fatty acid synthase (FAS) expression have been observed in several cancers, including breast, prostate, colon and lung carcinoma, compared with their respective normal tissue. We present data that show high levels of FAS protein in human and rat glioma cell lines and human glioma tissue samples, as compared to normal rat astrocytes and normal human brain. Incubating glioma cells with the FAS inhibitor cerulenin decreased endogenous fatty acid synthesis by approximately 50%. Cell cycle analysis demonstrated a time- and dose-dependent increase in S-phase cell arrest following cerulenin treatment for 24 h. Further, treatment with cerulenin resulted in time- and dose-dependent decreases in glioma cell viability, as well as reduced clonogenic survival. Increased apoptotic cell death and PARP cleavage were observed in U251 and SNB-19 cells treated with cerulenin, which was independent of the death receptor pathway. Overexpressing Bcl-2 inhibited cerulenin-mediated cell death. In contrast, primary rat astrocytes appeared unaffected. Finally, RNAi-mediated knockdown of FAS leading to reduced FAS enzymatic activity was associated with decreased glioma cell viability. These findings suggest that FAS might be a novel target for antiglioma therapy.

PMID: 16969344 [PubMed - indexed for MEDLINE]

 

6: Brain. 2006 Nov 14; [Epub ahead of print]

The invasion promoting effect of microglia on glioblastoma cells is inhibited by cyclosporin A.

Sliwa M, Markovic D, Gabrusiewicz K, Synowitz M, Glass R, Zawadzka M, Wesolowska A, Kettenmann H, Kaminska B.

Laboratory of Transcription Regulation, Department of Cell Biology, Nencki Institute of Experimental Biology, Warsaw, Poland.

The invasion of tumour cells into brain tissue is a pathologic hallmark of WHO grades II-IV gliomas and contributes significantly to the failure of current therapeutic treatments. Activated microglial cells are abundant in brain tumours and may support tumour invasiveness. We have previously demonstrated that cyclosporin A (CsA) can affect growth of glioma cells in vitro by inhibiting signalling pathways, which are essential for tumour proliferation and invasiveness. In this work, we demonstrate that migration of EGFP-transfected glioblastoma cells in organotypic brain slices was significantly inhibited by treatment with CsA. On average 77% of untreated cells migrated beyond 500 microm, while only 28-33% cells migrated as far in the brain slices treated with CsA (P < 0.001). This inhibitory effect on glioblastoma invasion was lost when glioblastoma cells were injected into microglia-depleted brain slices. Moreover, CsA significantly inhibits intracranial glioma growth in vivo. We demonstrate that microglia-derived factors increase glioma invasiveness in Matrigel assay in vitro and this is associated with activation of the PI-3K/Akt signalling pathway. The invasion promoting effect of microglia is abolished in the presence of CsA. Furthermore, glioma-derived soluble factors induce morphological transformation of microglia and activate MAPK signalling, although production of pro-inflammatory factors was not observed. Our findings that CsA interferes at clinically relevant concentrations with the tumour-promoting role of microglia and impairs invasive growth of glioma cells in vivo may provide a novel therapeutic strategy against gliomas.

PMID: 17107968 [PubMed - as supplied by publisher]

 

7: Childs Nerv Syst. 2006 Nov 15; [Epub ahead of print]

 
Short echo time 1 H magnetic resonance spectroscopy of childhood brain tumours.

Peet AC, Lateef S, Macpherson L, Natarajan K, Sgouros S, Grundy RG.

Institute of Child Health, University of Birmingham and Birmingham Children's Hospital, Birmingham, UK.

AIMS: To explore short echo time (30 ms) 1 H magnetic resonance spectroscopy (MRS) in children with brain tumours and determine the contributions to the characterization of these tumours of the metabolites inositol/myoinositol and glutamate/glutamine, which are not visible at long echo times (135 or 270 ms). METHODS: Over a 12-month period 86 single-voxel MRS investigations were performed on 59 children with various brain tumours on a Siemens Symphony 1.5-T Magnetom using point-resolved spectroscopy and echo time of 30 ms. RESULTS: The procedure was well tolerated, and good-quality data were obtained. N-Acetyl aspartate (NAA)/Choline (Cho) and creatine (Cr)/Cho concentration ratios were significantly (p<0.001) lower in tumour (0.95 and 1.63, respectively) compared with non-involved brain (3.68 and 3.98, respectively) in all histological types. Inositol/Myoinositol (Inos)/Cho ratios were significantly (p<0.05) lower in untreated tumours (1.91) than in treated tumours (3.93) and in non-involved brain (3.32). Inos/Cho ratios were high in diffuse pontine gliomas and low in medulloblastomas and supratentorial primitive neuroectodermal tumours (p<0.01). Glutamate/Glutamine (Glut)/Cho ratios were high in grade 1 astrocytomas (6.4) and unbiopsied optic gliomas (9.84) but low in diffuse pontine gliomas (2.44). Lipids and macromolecules were present in most tumours but in low quantities in non-involved brain. CONCLUSION: Good-quality short echo time MRS data can be collected routinely on children with brain tumours. Inos and Glut levels show greater variability between tumour types than NAA, Cho and Cr present at long echo times, providing improved tumour characterization. Inos/Cho levels differ between untreated and treated tumours and may be useful for treatment monitoring.

PMID: 17106750 [PubMed - as supplied by publisher]

 

8: Childs Nerv Syst. 2006 Nov 15; [Epub ahead of print]

 
First report of occurrence of choroid plexus papilloma and medulloblastoma in the same patient.

Banka S, Walsh R, Brundler MA.

Department of Neurosurgery, Birmingham Children's Hospital, Steelhouse Lane, Birmingham, B4 6NH, UK, smbanka@yahoo.com.

INTRODUCTION: Choroid plexus papilloma is a benign epithelial brain tumour showing a striking predilection for infants and occurring most frequently in the lateral and fourth ventricles. Medulloblastoma, on the other hand, is a primitive neuroectodermal tumour and is the most frequent malignant brain tumour of the posterior fossa in children. In this study, we report a metachronous occurrence of choroid plexus papilloma and medulloblastoma in the same patient, which has not been reported before to the best of our knowledge. CASE REPORT: The authors describe the case of a girl who presented with an atypical choroid plexus papilloma on the posterior wall of the left lateral ventricle at 3 months of age that was resected completely. She was followed up regularly after surgery and made good progress with normal development. At 8 years of age, she presented with right cerebellar medulloblastoma. DISCUSSION: The authors review literature for incidence and aetiology of the two tumours.

PMID: 17106748 [PubMed - as supplied by publisher]

 

9: Int J Cancer. 2006 Nov 15;119(10):2330-8.

 
Identification of novel genes associated with astrocytoma progression using suppression subtractive hybridization and real-time reverse transcription-polymerase chain reaction.

van den Boom J, Wolter M, Blaschke B, Knobbe CB, Reifenberger G.

Department of Neuropathology, Heinrich-Heine-University, Dusseldorf, Germany.

To identify novel genes involved in glioma progression we performed suppression subtractive hybridization combined with cDNA array analysis on 4 patients with primary low-grade gliomas of World Health Organization (WHO) grade II that recurred as secondary glioblastomas (WHO grade IV). Eight genes showing differential expression between primary and recurrent tumors in 3 of the 4 patients were selected for further analysis using real-time reverse transcription-PCR on a series of 10 pairs of primary low-grade and recurrent high-grade gliomas as well as 42 astrocytic gliomas of different WHO grades. These analyses revealed that 5 genes, i.e., AMOG (ATP1B2, 17p13.1), APOD (3q26.2-qter), DMXL1 (5q23.1) DRR1 (TU3A, 3p14.2) and PSD3 (KIAA09428/HCA67/EFA6R, 8p22), were expressed at significantly lower levels in secondary glioblastomas as compared to diffuse astrocytomas of WHO grade II. In addition, AMOG, DRR1 and PSD3 transcript levels were significantly lower in primary glioblastomas than in diffuse astrocytomas. Treatment of glioma cell lines with 5-aza-2'-deoxycytidine and trichostatin A resulted in increased expression of AMOG and APOD transcripts. Sequencing of sodium bisulfite-modified DNA demonstrated AMOG promoter hypermethylation in the glioma cell lines and 1 primary anaplastic astrocytoma with low AMOG expression. Taken together, we identified interesting novel candidate genes that likely contribute to glioma progression and provide first evidence for a role of epigenetic silencing of AMOG in malignant glioma cells.

PMID: 16865689 [PubMed - indexed for MEDLINE]*

 

10: Int J Cancer. 2006 Nov 15;119(10):2487-91.

 
Epigenetic silencing of multiple genes in primary CNS lymphoma.

Chu LC, Eberhart CG, Grossman SA, Herman JG.

The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.

Epigenetic silencing of functionally important genes is important in the development of malignancies and is a source of potential markers for molecular detection. Primary central nervous system lymphoma (PCNSL) is an increasingly common tumor that has not been extensively examined for changes in promoter region methylation. We examined 14 tumor suppressor genes in 25 cases of PCNSL using methylation-specific PCR. Methylation was observed in DAPK (84%), TSP1 (68%), CRBP1 (67%), p16(INK) (4a) (64%), p14(ARF) (59%), MGMT (52%), RARbeta2 (50%), TIMP3 (44%), TIMP2 (42%), p15(INK) (4b) (40%), p73 (28%), hMLH1 (12%), RB1 (8%) and GSTP1 (8%). Promoter methylation of p14(ARF), p16(INK) (4a) and MGMT was correlated with loss of expression by immunohistochemical staining. The methylation of many of these genes in PCNSL is similar to that reported in other high-grade B-cell lymphomas. All 25 cases of PCNSL had methylation of at least 2 genes. Methylation of DAPK, p16(INK) (4a) or MGMT was found in 96% of the tumors, suggesting simple marker strategies to detect circulating methylated DNA in serum that might facilitate early tumor detection. Our study provides insight into the epigenetic alterations in PCNSL and provides potential biomarkers of disease.

PMID: 16858686 [PubMed - indexed for MEDLINE]

 

11: J Clin Oncol. 2006 Nov 13; [Epub ahead of print]

 
Prognostic Significance of Human Epidermal Growth Factor Receptor Positivity for the Development of Brain Metastasis After Newly Diagnosed Breast Cancer.

Gabos Z, Sinha R, Hanson J, Chauhan N, Hugh J, Mackey JR, Abdulkarim B.

Department of Oncology, Cross Cancer Institute and University of Alberta; and the Departments of Radiation Oncology, Statistics and Epidemiology, Laboratory Medicine and Pathology, and Medical Oncology, University of Alberta, Edmonton, Alberta, Canada.

PURPOSE: As survival in breast cancer patients is improving, brain metastases are becoming increasingly prevalent. The risk of brain metastases in newly diagnosed human epidermal growth factor receptor 2 (HER-2) -overexpressing breast cancer patients is not yet fully defined. We aim to analyze the risk of brain metastasis in newly diagnosed HER-2-positive breast cancer patients in comparison with HER-2-negative patients. PATIENTS AND METHODS: To determine the incidence of brain metastases in HER-2-overexpressing patients, we analyzed a cohort of newly diagnosed 301 HER-2-positive and 363 HER-2-negative patients identified between January 1998 and December 2003. The association between histologic features and the occurrence of brain metastases was evaluated with univariate and multivariate Cox regression analysis. RESULTS: Median follow-up was 3.9 years. Brain metastases were identified in 9% (27 patients) with HER-2-overexpressing breast cancer compared with only 1.9% (7 patients) in the HER-2 negative patients (hazard ratio 4.23 [1.84-9.74], P = .0007). HER-2 overexpression, tumor size larger than 2 cm, at least one positive node, and grade 2/3 disease were predictors of brain metastases in univariate analysis. In multivariate analysis, HER-2 overexpression, tumor size larger than 2 cm, and hormone-receptor negativity were independent prognostic factors for the development of brain metastases, whereas hormone-receptor expression was protective. CONCLUSION: Our study shows that newly diagnosed HER-2-overexpressing breast cancer patients are at increased risk for brain metastases. Because most brain metastases occur after the development of systemic disease, these findings prompt consideration of brain prophylaxis strategies with HER-2-inhibiting small molecules able to cross the blood-brain barrier and/or radiologic screening to detect asymptomatic brain metastases.

PMID: 17102066 [PubMed - as supplied by publisher]

 

12: J Neurol Neurosurg Psychiatry. 2006 Dec;77(12):1305-1306.

Referral guidelines for suspected central nervous system or brain tumours.

Larner AJ.

Walton Centre for Neurology and Neurosurgery, Lower Lane, Fazakerley, Liverpool L9 7LJ, UK. a.larner@thewaltoncentre.nhs.uk.

PMID: 17110745 [PubMed - as supplied by publisher]

 

13: J Neurooncol. 2006 Nov 15; [Epub ahead of print]

 
Toll-like receptor triggered dendritic cell maturation and IL-12 secretion are necessary to overcome T-cell inhibition by glioma-associated TGF-beta2.

Grauer O, Poschl P, Lohmeier A, Adema GJ, Bogdahn U.

Department of Neurology, University of Regensburg, Universitatsstrasse 84, 93053, Regensburg, Germany.

Malignant gliomas are able to secrete large amounts of immunosuppressive cytokines like transforming growth factor beta 2 (TGF-beta2) and regularly escape from immune surveillance. Many strategies have been developed to induce potent anti-glioma responses, among those the use of dendritic cells (DC) as therapeutic vaccines. Here, we report that both mature DC and IL-12 secretion are necessary to overcome T-cell inhibition by TGF-beta2. Flow cytometric analyses showed that TGF-beta2 does not suppress the upregulation of MHC (major histocompatibility complex) class II molecules and the T cell stimulatory capacity of human DC that were stimulated with a strong cytokine cocktail containing tumor necrosis factor alpha (TNF-alpha), IL-1beta, IL-6 and prostaglandin E2 (PGE(2)). Moreover, TGF-beta2 signaling studies revealed that these cytokine-matured DC become unresponsive to TGF-beta2. Although both mature and immature DC expressed comparable amounts of the TGF-beta receptor type II, Smad2 phosphorylation and subsequent upregulation of Smad7 was inhibited in mature DC, but not immature DC. However, further analysis revealed that mature DC alone are not sufficient to mediate full T cell activation in the presence of TGF-beta2, unless IL-12 is added to the DC/T-cell coculture. Finally, we demonstrate that MHC class II expression and IL-12 secretion by DC are not disturbed by TGF-beta2 after DC stimulation with a modified maturation cocktail containing the Toll-like receptor (TLR)-ligands Poly I:C or R848, TNF-alpha, IL-1beta and INF-gamma. These data imply that mature DC retaining their capacity to produce IL-12 are of favorable use in glioma immunotherapy and suggest that TLR triggering of DC plays an important role to elicit a strong immune response in the immunosuppressive environment of malignant gliomas.

PMID: 17106649 [PubMed - as supplied by publisher]

 

14: J Neurooncol. 2006 Nov 11; [Epub ahead of print]

 
Exogenous wt-p53 enhances the antitumor effect of HSV-TK/GCV on C6 glioma cells.

Huang Q, Pu P, Xia Z, You Y.

Department of Neurosurgery, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin, 300052, People's Republic of China.

OBJECTIVE: To study on the antitumor effect of combining wt-p53 gene with suicide gene therapy (HSV-tk+GCV) for malignant gliomas. METHODS: AdCMV-p53 was transfected into C6 glioma cells at MOI of (Multiplicity of infection) 0(G100), 10(TPG1), 100(TPG2), then AdCMV-tk was transducted to C6 glioma cells of G100, TPG1 and TPG2, respectively, at MOI of 100. The C6 glioma cells tranfected with both AdCMV-p53 and AdCMV-tk were exposed to various concentration of GCV. The cell survival rate was measured by MTT assay in vitro. Rat glioma model was established by injecting 5 x 10(5) C6 glioma cells into right caudate nucleus of SD rats. AdCMV-p53 and AdCMV-tk were injected into glioma on day 5 and 6, respectively. On day 7, ganciclovir (GCV) was administrated intraperitoneally at 15 mg/kg/day for 14 days. The survival time of all rats was observed. The growth of intracerebral tumors was monitored dynamically by enhanced MRI. Cell apoptosis was evaluated by TUNEL method. Expression of HSV-tk gene was identified by in situ hybridization and expression of exogenous p53 gene was detected with Western blotting. RESULTS: In vitro, wt-p53 significantly enhanced antitumor effect of HSV-tk/GCV. The concentration of GCV for ID50 of TPG2 cells (0.001 mug/ml GCV) was 10 times lower than that for the cells of tk-GCV group (MOI = 100), while the concentration of GCV for ID100 of TPG2 (0.01 mug/ml GCV) and TPG1(0.1 mug/ml GCV) was 100 and 10 times lower than that for the cells of tk-GCV group (MOI = 100), respectively. Apoptosis of C6 glioma cells also could be induced by transfection with wt-p53 gene slightly. For in vivo study, the survival time of tumor-bearing rats treated with HSV-TK/GCV or wt-p53 combined with HSV-TK/GCV was significantly prolonged and the intracerebral tumors were regressed and disappeared earlier in the combined gene therapy group than those in the HSV-TK/GCV therapy group as shown in enhanced MRI. However, only half dose of GCV for the rats treated with both wt-p53 and HSV-TK/GCV was needed to obtain the same efficacy as those rats treated with HSV-TK/GCV alone. These results indicate that the transfection of wt-p53 potentiates the effect of HSV-TK/GCV therapy. CONCLUSIONS: The combination of HSV-tk/GCV system with wt-p53 gene transduction is optimal for clinical therapeutic trials of suicide gene therapy for malignant gliomas.

PMID: 17102907 [PubMed - as supplied by publisher]

 

15: J Neuropathol Exp Neurol. 2006 Oct;65(10):1004-11.

 
Prognosis and histopathologic features in papillary tumors of the pineal region: a retrospective multicenter study of 31 cases.

Fevre-Montange M, Hasselblatt M, Figarella-Branger D, Chauveinc L, Champier J, Saint-Pierre G, Taillandier L, Coulon A, Paulus W, Fauchon F, Jouvet A.

INSERM, U433, Fac Med RTH Laennec, Lyon, France. montange@lyon.inserm.fr

Papillary tumor of the pineal region (PTPR) is a recently described tumor entity thought to arise from the specialized ependyma of the subcommissural organ. Whereas histologic features of PTPR are well defined, data on the prognostic value of PTPR remain scarce. We therefore investigated clinicopathologic features, including data on progression-free survival and overall survival, in a retrospective series of 31 PTPR. The age of the 14 males and 17 females ranged from 5 to 66 years (median age, 29 years). Histologically, all tumors were characterized by an epithelial-like growth pattern in which the vessels were covered by layers of columnar or cuboidal tumor cells forming perivascular pseudorosettes. Most of the tumor cells showed strong expression of neuron-specific enolase, cytokeratins (particularly CK18), S-100 protein, and vimentin. Most PTPRs examined also expressed microtubule-associated protein-2. Expression of synaptophysin, epithelial membrane antigen, transthyretin, neural cell adhesion molecule, and nestin was encountered in some tumors. Gross total resection could be achieved in 21 of 31 cases; 15 patients received radiotherapy on resection of the primary tumor. Nevertheless, the majority of patients experienced recurrences; 5-year estimates for overall survival and progression-free survival were 73% and 27%, respectively. To conclude, the clinical course of PTPR is characterized by frequent local recurrence, and the value of radiotherapy on disease progression will need to be investigated in future prospective trials.

Publication Types:

• Multicenter Study

PMID: 17021405 [PubMed - indexed for MEDLINE]

 

16: J Neuropathol Exp Neurol. 2006 Oct;65(10):988-94.

 
Identification of der(1;19)(q10;p10) in five oligodendrogliomas suggests mechanism of concurrent 1p and 19q loss.

Griffin CA, Burger P, Morsberger L, Yonescu R, Swierczynski S, Weingart JD, Murphy KM.

Department of Pathology, Johns Hopkins University, Baltimore, Maryland 21287, USA. cgriffin@jhmi.edu

Deletions of portions of chromosomes 1p and 19q are closely associated with the oligodendroglioma histologic phenotype. In most cases, 1p and 19q are codeleted, yet the mechanism of dual loss is unexplained. We report 5 cases (World Health Organization grade III) in which metaphase cytogenetics identified a derivative chromosome consisting of what appears to be the whole arms of 1q and 19p forming a der(1;19)(q10;p10). Metaphase fluorescent in situ hybridization (FISH) confirmed the derivative chromosome was composed of 1q and 19p material in 3 cases; in 2 cases with few metaphases, FISH confirmed 19p material on the derivative chromosome. In all cases, interphase FISH showed net loss of 1p and 19q in 77% to 92% of cells, and microsatellite studies were consistent with 1p and 19q loss. We hypothesize the following: occurrence of a balanced whole-arm translocation between chromosomes 1 and 19 forming 2 derivative chromosomes, one composed of 1q and 19p, the other of 1p and 19q. Subsequent loss of the der(1;19)(p10;q10) then results in the simultaneous 1p and 19q loss observed in oligodendroglioma with retention of the der(1;19)(q10;p10) seen in these cases.

Publication Types:

• Case Reports

PMID: 17021403 [PubMed - indexed for MEDLINE]

 

17: J Neuropathol Exp Neurol. 2006 Oct;65(10):935-44.

 
Immunohistochemical analysis of metastatic neoplasms of the central nervous system.

Becher MW, Abel TW, Thompson RC, Weaver KD, Davis LE.

Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2561, USA. mark.becher@vanderbilt.edu

Metastatic neoplasms to the central nervous system are often encountered in the practice of surgical neuropathology. It is not uncommon for patients with systemic malignancies to present to medical attention because of symptoms from a brain metastasis and for the tissue samples procured from these lesions to represent the first tissue available to study a malignancy from an unknown primary. In general surgical pathology, the evaluation of a metastatic neoplasm of unknown primary is a very complicated process, requiring knowledge of numerous different tumor types, reagents, and staining patterns. The past few years, however, have seen a remarkable refinement in the immunohistochemical tools at our disposal that now empower neuropathologists to take an active role in defining the relatively limited subset of neoplasms that commonly metastasize to the central nervous system. This information can direct imaging studies to find the primary tumor in a patient with an unknown primary, clarify the likely primary site of origin in patients who have small tumors in multiple sites without an obvious primary lesion, or establish lesions as late metastases of remote malignancies. Furthermore, specific treatments can begin and additional invasive procedures may be prevented if the neuropathologic evaluation of metastatic neoplasms provides information beyond the traditional diagnosis of "metastatic neoplasm." In this review, differential cytokeratins, adjuvant markers, and organ-specific antibodies are described and the immunohistochemical signatures of metastatic neoplasms that are commonly seen by neuropathologists are discussed.

Publication Types:

• Review

PMID: 17021398 [PubMed - indexed for MEDLINE]

 

18: Neurology. 2006 Nov 14;67(9):1668-70.

 
Clinical and radiographic features of peritumoral infarction following resection of glioblastoma.

Ulmer S, Braga TA, Barker FG 2nd, Lev MH, Gonzalez RG, Henson JW.

Stephen E. Catherine Pappas Center for Neuro-oncology and Division of Neuroradiology, Massachusetts General Hospital, Boston, MA 02114, USA.

Focal areas of restricted diffusion adjacent to high-grade glioma resection cavities were detected in 70% of patients on immediate postoperative MRI studies. Follow-up studies demonstrated cystic encephalomalacia in 91% of these foci, suggesting the presence of infarction, and the infarcted tissue demonstrated enhancement in 43% of cases. New postoperative deficits correlated well with the anatomic region of infarction in six patients. Enhancement in perioperative infarcts can mimic tumor progression on follow-up imaging studies.

PMID: 17101902 [PubMed - in process]*

 

19: Neurology. 2006 Nov 14;67(9):1540-1.

 
Glioblastoma: what's ischemia got to do with it?

Wick W, Kaufmann A.

Publication Types:

• Comment
• Editorial

PMID: 17101883 [PubMed - in process]

 

20: Neuroradiology. 2006 Nov 14; [Epub ahead of print]

 
Miliary brain metastases from adenocarcinoma of the lung: MR imaging findings with clinical and post-mortem histopathologic correlation.

Iguchi Y, Mano K, Goto Y, Nakano T, Nomura F, Shimokata T, Iwamizu-Watanabe S, Hashizume Y.

Department of Neurology Medicine, Japanese Red Cross Nagoya First Hospital, 3-35 Michishitacho, Nakamuraku, Nagoya, Aichi, 453-8511, Japan, iguyo@hotmail.co.jp.

INTRODUCTION: Miliary dissemination is a rare form of brain metastasis. The clinical and pathologic features of this form are unclear. METHODS: We report a 66-year-old man with miliary brain metastases from adenocarcinoma of the lung, describing MRI and neuropathologic findings in the context of previously reported cases. RESULTS: Initial disorientation progressed to an apallic state within 6 months. Although, CT with administration of contrast agent failed to demonstrate any lesions, MRI with Gd-DTPA administration showed multiple enhancing miliary nodules in the cerebral cortex, basal ganglia, thalamus, cerebellum, and brainstem. Some of those nodules also could be seen on T2-weighted imaging without Gd-DTPA, but were difficult to identify conclusively. A histopathologic examination at autopsy disclosed diffusely distributed miliary tumor nodules in a perivascular distribution without surrounding focal edema or reactive gliosis. Notably, this patient with miliary brain metastases developed disorientation followed by unconsciousness, which overshadowed other focal neurologic signs at that time. CONCLUSION: We should consider this pattern of brain dissemination when a cancer is associated with unexplained disturbance of consciousness.

PMID: 17103154 [PubMed - as supplied by publisher]

 

21: Oncogene. 2006 Nov 13; [Epub ahead of print]

 
Transglutaminase 2 inhibitor, KCC009, disrupts fibronectin assembly in the extracellular matrix and sensitizes orthotopic glioblastomas to chemotherapy.

Yuan L, Siegel M, Choi K, Khosla C, Miller CR, Jackson EN, Piwnica-Worms D, Rich KM.

1Department of Neurological Surgery, Washington University School of Medicine, St Louis, MO, USA.

Transglutaminase 2 (TG2, a.k.a. tissue transglutaminase) belongs to a family of transglutaminase enzymes that stabilize proteins by affecting covalent crosslinking via formation of amide bonds. Cell surface TG2 is directly involved as an adhesive receptor in cell-extracellular matrix (ECM) interactions. Here, we show that TG2 activity is elevated in glioblastomas compared with non-neoplastic brain. Immunofluorescent studies showed increased staining of fibronectin colocalized with TG2 in the ECM in glioblastomas. In addition, small clusters of invading human glioblastoma cells present in non-neoplastic brain parenchyma secrete high levels of TG2 and fibronectin that distinguish them from normal brain stroma. Downregulation of TG2 in U87MG glioblastoma cells with RNAi demonstrated decreased assembly of fibronectin in the ECM. Treatment with KCC009 blocked the remodeling of fibronectin in the ECM in glioblastomas in both in vitro and in vivo studies. KCC009 treatment in mice harboring orthotopic glioblastomas (DBT-FG) sensitized the tumors to N,N'-bis(2-chloroethyl)-N-nitrosourea chemotherapy, as measured by reduced bioluminescence, increased apoptosis and prolonged survival. The ability of KCC009 to interfere with the permissive remodeling of fibronectin in the ECM in glioblastomas suggests a novel target to enhance sensitivity to chemotherapy directed not only at the tumor mass, but also invading glioblastoma cells.Oncogene advance online publication, 13 November 2006; doi:10.1038/sj.onc.1210048.

PMID: 17099729 [PubMed - as supplied by publisher]