Volume 5
Archive

1: AJNR Am J Neuroradiol. 2006 Sep;27(8):1639-42.

 
Pituicytoma: diagnostic features on selective carotid angiography and MR imaging.

Gibbs WN, Monuki ES, Linskey ME, Hasso AN.

School of Medicine, University of California, Irvine, CA, USA.

We report a case of pituicytoma, a rare primary tumor of the neurohypophysis. A 64-year-old man presented with progressive visual complaints, bitemporal hemianopsia, and headache. Imaging studies revealed distinctive features of a mass lesion that thickened the pituitary stalk with a bilobed protrusion extending into the hypothalamus. Angiography demonstrated tumor vascular supply from the superior hypophyseal arteries representing the diencephalic branches of the internal carotid arteries. We discuss the imaging and pathology of this unusual tumor.

Publication Types:

• Case Reports

PMID: 16971602 [PubMed - indexed for MEDLINE]

 

2: Cancer Res. 2006 Nov 6; [Epub ahead of print]

 
A Genome-Wide Screen Reveals Functional Gene Clusters in the Cancer Genome and Identifies EphA2 as a Mitogen in Glioblastoma.

Liu F, Park PJ, Lai W, Maher E, Chakravarti A, Durso L, Jiang X, Yu Y, Brosius A, Thomas M, Chin L, Brennan C, Depinho RA, Kohane I, Carroll RS, Black PM, Johnson MD.

Department of Neurological Surgery, Brigham and Women's Hospital and Harvard Medical School; Program in Neuro-Oncology, Brigham and Women's Hospital and Dana-Farber/Harvard Cancer Center; Harvard-Partners Center for Genetics and Genomics; Center for Applied Cancer Science, Belfer Foundation Institute for Innovative Cancer Science, Department of Medical Oncology, Dana-Farber Cancer Institute; Departments of Medicine and Genetics and Dermatology, Harvard Medical School; and Children's Hospital Informatics Program, Boston, Massachusetts.

A novel genome-wide screen that combines patient outcome analysis with array comparative genomic hybridization and mRNA expression profiling was developed to identify genes with copy number alterations, aberrant mRNA expression, and relevance to survival in glioblastoma. The method led to the discovery of physical gene clusters within the cancer genome with boundaries defined by physical proximity, correlated mRNA expression patterns, and survival relatedness. These boundaries delineate a novel genomic interval called the functional common region (FCR). Many FCRs contained genes of high biological relevance to cancer and were used to pinpoint functionally significant DNA alterations that were too small or infrequent to be reliably identified using standard algorithms. One such FCR contained the EphA2 receptor tyrosine kinase. Validation experiments showed that EphA2 mRNA overexpression correlated inversely with patient survival in a panel of 21 glioblastomas, and ligand-mediated EphA2 receptor activation increased glioblastoma proliferation and tumor growth via a mitogen-activated protein kinase-dependent pathway. This novel genome-wide approach greatly expanded the list of target genes in glioblastoma and represents a powerful new strategy to identify the upstream determinants of tumor phenotype in a range of human cancers. (Cancer Res 2006; 66(22): 10815-23).

PMID: 17090523 [PubMed - as supplied by publisher]

 

3: Clin Cancer Res. 2006 Nov 1;12(21):6557-6564.

 
Synthetic MicroRNA Designed to Target Glioma-Associated Antigen 1 Transcription Factor Inhibits Division and Induces Late Apoptosis in Pancreatic Tumor Cells.

Tsuda N, Ishiyama S, Li Y, Ioannides CG, Abbruzzese JL, Chang DZ.

Authors' Affiliations: Departments of Gynecologic Oncology, Surgical Oncology, Immunology, and Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, and The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas.

PURPOSE: To determine whether the synthetic microRNAs (miRNA) could effectively target tumor cells we designed several miRNA complementary to glioma-associated antigen-1 (Gli-1) mRNA and investigated their ability to inhibit tumor cell proliferation. The sonic hedgehog pathway is an early and late mediator of tumorigenesis in epithelial cancers. Activation of sonic hedgehog signaling seems to precede transformation of tissue stem cells to cancerous stem cells, with the Gli-1 transcription factor functioning as a mediator of environmental signals. Inhibiting cancer cell proliferation by targeting the Gli-1 effector pathway is difficult to achieve by chemotherapeutic agents or short interfering RNA. EXPERIMENTAL DESIGN: We hypothesized that targeting the 3'-untranslated region of Gli-1 mRNA would effectively inhibit tumor cell proliferation. To test this hypothesis, we used synthetic miRNAs of our own design and corresponding duplex/small temporal RNAs by introducing three-nucleotide loops in the 3'-untranslated region Gli-1 sequence of high GU content. RESULTS: We found that miRNA (Gli-1-miRNA-3548) and its corresponding duplex (Duplex-3548) significantly inhibited proliferation of Gli-1(+) ovarian (SK-OV-3) and pancreatic (MiaPaCa-2) tumor cells. The miRNAs mediated delayed cell division and activation of late apoptosis in MiaPaCa-2 cells. This is the first demonstration of inhibition of pancreatic tumor cell division by designed miRNA. CONCLUSIONS: Gli-1 miRNAs should significantly add to the general understanding of the mechanisms of metastasis and contribute toward the design of better treatments for epithelial cancers.

PMID: 17085671 [PubMed - as supplied by publisher]

 

4: Clin Cancer Res. 2006 Nov 1;12(21):6331-6336.

 
Attractin Is Elevated in the Cerebrospinal Fluid of Patients with Malignant Astrocytoma and Mediates Glioma Cell Migration.

Khwaja FW, Duke-Cohan JS, Brat DJ, Van Meir EG.

Authors' Affiliations: Laboratory of Molecular Neuro-Oncology, Departments of Neurosurgery and Hematology/Oncology, Winship Cancer Institute, and Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia; and Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, Massachusetts.

PURPOSE: There are a limited number of noninvasive methods available for the monitoring of neoplastic disease in the central nervous system. The goal of our study was to find reliable markers that could be used for disease monitoring as well as to identify new targets for the therapeutic intervention for malignant astrocytoma (WHO grades 3 and 4). EXPERIMENTAL DESIGN: We employed proteomic techniques to identify secreted proteins in the cerebrospinal fluid that were specific to patients with malignant astrocytoma. RESULTS: Among 60 cerebrospinal fluid samples of patients with various central nervous system diseases, attractin was consistently found to be elevated in the samples of patients with malignant astrocytoma. To independently validate these results, we examined attractin expression in a new set of 108 normal and tumoral brain tissue specimens and found elevated expression in 97% of malignant astrocytomas, with the highest levels in grade 4 tumors. Using immunohistochemistry, we further showed that attractin is produced and secreted by the tumor cells. Finally, we showed that cerebrospinal fluid from brain tumor patients induces glioma cell migration and that attractin is largely responsible for this promigratory activity. CONCLUSIONS: Our results find attractin to be a reliable secreted marker for high-grade gliomas. Additionally, our migration studies suggest that it may be an important mediator of tumor invasiveness, and thus, a potential target in future therapies.

PMID: 17085642 [PubMed - as supplied by publisher]

 

5: Int J Radiat Oncol Biol Phys. 2006 Nov 1; [Epub ahead of print]

 
Daoy medulloblastoma cells that express CD133 are radioresistant relative to CD133- cells, and the CD133+ sector is enlarged by hypoxia.

Blazek ER, Foutch JL, Maki G.

Radiation Oncology Department.

PURPOSE: Primary medulloblastoma and glioblastoma multiforme tumor cells that express the surface marker CD133 are believed to be enriched for brain tumor stem cells because of their unique ability to initiate or reconstitute tumors in immunodeficient mice. This study sought to characterize the radiobiological properties and marker expression changes of CD133+ vs. CD133- cells of an established medulloblastoma cell line. METHODS AND MATERIALS: Daoy and D283 Med cell lines were stained with fluorescently labeled anti-CD133 antibody and sorted into CD133+ and CD133- populations. The effect of oxygen (2% vs. 20%) on CD133 expression was measured. Both populations were analyzed for marker stability, cell cycle distribution, and radiosensitivity. RESULTS: CD133+ Daoy cells restored nearly native CD133+ and CD133- populations within 18 days, whereas CD133- cells remained overwhelmingly CD133-. Culturing Daoy cells in 2% oxygen rather than the standard 20% oxygen increased their CD133 expression 1.6-fold. CD133+ Daoy cells were radioresistant via the beta-parameter of the linear-quadratic model relative to CD133- Daoy cells, although their alpha-parameters and cell cycle distributions were identical. CONCLUSIONS: Restoration of the original CD133+ and CD133- populations from CD133+ Daoy cells in serum is further evidence that CD133+ cells are functionally distinct from CD133- cells. The radioresistance of CD133+ compared with CD133- Daoy cells is consistent with better repair of sublethal damage. Enlargement of the CD133+ sector is a new feature of the hypoxic response.

PMID: 17084552 [PubMed - as supplied by publisher]

 

6: Int J Radiat Oncol Biol Phys. 2006 Nov 1;66(3):825-32. Epub 2006 Sep 1.

 
Long-term normal-appearing brain tissue monitoring after irradiation using proton magnetic resonance spectroscopy in vivo: statistical analysis of a large group of patients.

Matulewicz L, Sokol M, Michnik A, Wydmanski J.

Department of Medical Physics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland. lukasz.matulewicz@io.gliwice.pl

PURPOSE: The aim of this study was to detect the non-neoplastic white-matter changes vs. time after irradiation using 1H nuclear magnetic resonance (NMR) spectroscopy in vivo. METHODS AND MATERIALS: A total of 394 1H MR spectra were acquired from 100 patients (age 19-74 years; mean and median age, 43 years) before and during 2 years after radiation therapy (the mean absorbed doses calculated for the averaged spectroscopy voxels are similar and close to 20 Gy). RESULTS: Oscillations were observed in choline-containing compounds (Cho)/creatine and phosphocreatine (Cr), Cho/N-acetylaspartate (NAA), and center of gravity (CG) of the lipid band in the range of 0.7-1.5 ppm changes over time reveal oscillations. The parameters have the same 8-month cycle period; however the CG changes precede the other by 2 months. CONCLUSIONS: The results indicate the oscillative nature of the brain response to irradiation, which may be caused by the blood-brain barrier disruption and repair processes. These oscillations may influence the NMR results, depending on the cycle phase in which the NMR measurements are performed in. The earliest manifestation of radiation injury detected by magnetic resonance spectroscopy is the CG shift.

PMID: 16949766 [PubMed - indexed for MEDLINE]

 

7: J Clin Oncol. 2006 Nov 6; [Epub ahead of print]

 
Late-Occurring Stroke Among Long-Term Survivors of Childhood Leukemia and Brain Tumors: A Report From the Childhood Cancer Survivor Study.

Bowers DC, Liu Y, Leisenring W, McNeil E, Stovall M, Gurney JG, Robison LL, Packer RJ, Oeffinger KC.

The University of Texas Southwestern Medical Center at Dallas, Dallas; The University of Texas M.D. Anderson Cancer Center, Houston, TX; Fred Hutchinson Cancer Research Center, Seattle, WA; US Food and Drug Administration, Rockville, MD; University of Michigan, Ann Arbor, MI; St Jude Children's Research Hospital, Memphis, TN; Children's National Medical Center, Washington, DC; and Memorial Sloan-Kettering Cancer Center, New York, NY.

PURPOSE: This report examines the incidence of and risk factors for strokes that occur in >/= 5-year survivors of childhood leukemia and brain tumors. PATIENTS AND METHODS: The rate of first occurrence of self-reported late-occurring strokes was determined for leukemia survivors (n = 4,828), brain tumor survivors (n = 1,871), and a comparison group of a random sample of cancer survivor siblings (n = 3,846). Relative risks (RRs) and 95% confidence intervals (CIs) of stroke by treatment exposures were examined by multivariate analyses. RESULTS: Thirty-seven leukemia survivors and 63 brain tumor survivors reported a late-occurring stroke. The rate of late-occurring stroke for leukemia survivors was 57.9 per 100,000 person-years (95% CI, 41.2 to 78.7). The RR of stroke for leukemia survivors compared with the sibling comparison group was 6.4 (95% CI, 3.0 to 13.8; P < .0001). The rate of late-occurring stroke for brain tumor survivors was 267.6 per 100,000 person-years (95% CI, 206.8 to 339.2). The RR of stroke for brain tumor survivors compared with the sibling comparison group was 29.0 (95% CI, 13.8 to 60.6; P < .0001). Mean cranial radiation therapy (CRT) dose of >/= 30 Gy was associated with an increased risk in both leukemia and brain tumor survivors in a dose-dependent fashion, with the highest risk after doses of >/= 50 Gy CRT. CONCLUSION: Survivors of childhood leukemia and brain tumors, particularly those with brain tumors treated with CRT at doses of greater than 30 Gy, are at an increased risk of stroke.

PMID: 17088567 [PubMed - as supplied by publisher]

 

8: J Neurochem. 2006 Sep;98(6):1973-84. Epub 2006 Aug 14.

 
Gene-linked shift in ganglioside distribution influences growth and vascularity in a mouse astrocytoma.

Abate LE, Mukherjee P, Seyfried TN.

Department of Biology, Boston College, Chestnut Hill, Massachusetts, USA.

Brain tumor growth and progression is dependent upon vascularity, and is associated with altered ganglioside composition and distribution. In this study, we examined the influence of gangliosides on growth and vascularity in a malignant mouse astrocytoma, CT-2A. Ganglioside distribution was altered in CT-2A tumor cells using an antisense construct to beta-1,4-N-acetylgalactosaminyltransferase (GalNAc-T), a key enzyme that uses the simple ganglioside GM3 as a substrate for the synthesis of the more complex gangliosides, GM2, GM1 and GD1a. GalNAc-T gene expression was significantly lower in CT-2A cells stably transfected with the antisense GalNAc-T plasmid, pcDNA3.1/TNG (CT-2A/TNG) than in either non-transfected CT-2A or mock-transfected (CT-2A/V) control tumor cells. GM3 was elevated from 16% to 58% of the total ganglioside distribution, whereas GM1 and GD1a were reduced from 17% and 49% to 10% and 17%, respectively, in CT-2A/TNG tumor cells. Growth, vascularity (blood vessel density and Matrigel assay) and vascular endothelial growth factor (VEGF) expression was significantly less in CT-2A/TNG tumors than in control CT-2A brain tumors. In addition, the expression of VEGF, hypoxia-inducible factor 1alpha (HIF-1alpha) and neuropilin-1 (NP-1) was significantly lower in CT-2A/TNG tumor cells than in control CT-2A tumor cells. These data suggest that gene-linked changes in ganglioside composition influence the growth and angiogenic properties of the CT-2A astrocytoma.

PMID: 16911584 [PubMed - indexed for MEDLINE]

 

9: Neurology. 2006 Oct 10;67(7):1303-4.

 
Metastases to the pineal gland.

Lassman AB, Bruce JN, Fetell MR.

Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. lassmana@mskcc.org

We identified 10 patients with symptomatic metastases to the pineal gland. We present the clinical and radiographic findings in this syndrome. Leptomeningeal metastases occur frequently and are a poor prognostic factor. In all cases, the primary cancer was clinically silent, either in remission (six cases) or previously undiagnosed (four cases). Hence, metastatic disease, albeit uncommon, should be considered in the differential diagnosis of pineal tumors.

PMID: 17030775 [PubMed - indexed for MEDLINE]

 

10: Neuroradiology. 2006 Nov 4; [Epub ahead of print]

 
Utilization of glutamate/creatine ratios for proton spectroscopic diagnosis of meningiomas.

Hazany S, Hesselink JR, Healy JF, Imbesi SG.

School of Medicine, University of California, San Diego, CA, USA.

INTRODUCTION: Our purpose was to determine the potential of metabolites other than alanine to diagnose intracranial meningiomas on proton magnetic resonance spectroscopy (MRS). METHODS: Using a 1.5-T MR system the lesions were initially identified on FLAIR, and T1- and T2-weighted images. Employing standard point-resolved spectroscopy (PRESS) for single voxel proton MRS (TR 1500 ms, TE 30 ms, 128 acquisitions, voxel size 2 x 2 x 2 cm, acquisition time 3.12 min), MR spectra were obtained from 5 patients with meningiomas, from 20 with other intracranial lesions, and from 4 normal controls. Peak heights of nine resonances, including lipid, lactate, alanine, NAA (N-acetylaspartate), beta/gamma-Glx (glutamate + glutamine), creatine, choline, myo-inositol, and alpha-Glx/glutathione, were measured in all spectra. The relative quantity of each metabolite was measured as the ratio of its peak height to the peak height of creatine. RESULTS: Relative quantities of alpha-Glx/glutathione, beta/gamma-Glx, and total Glx/glutathione were significantly elevated in meningiomas compared to the 20 other intracranial lesions and the normal control brains. Alanine was found in four of five meningiomas, but lactate partially masked the alanine in three meningiomas. None of the other lesions or control brains showed an alanine peak. The one meningioma with no alanine and the three others with lactate had elevated Glx. CONCLUSION: While alanine is a relatively unique marker for meningioma, our results support the hypothesis that the combination of glutamate/creatine ratios and alanine on proton MRS is more specific and reliable for the diagnosis of meningiomas than alanine alone.

PMID: 17086406 [PubMed - as supplied by publisher]

 

11: Surg Neurol. 2006 Nov;66(5):461-2.

 
Radiosurgery plus or minus whole brain radiation therapy for the treatment of brain metastases. An editorial comment.

Lunsford LD, Flickinger JC.

Department of Neurosurgery, Presbyterian University Hospital, Pittsburgh, PA 15213, USA.

Publication Types:

• Editorial

PMID: 17084185 [PubMed - in process]