Determination of histopathological tumor grade in neuroepithelial brain tumors by using spectral pattern analysis of in vivo spectroscopic data

2003 ◽  
Vol 98 (1) ◽  
pp. 74-81 ◽  
Author(s):  
Sebastian Herminghaus ◽  
Thomas Dierks ◽  
Ulrich Pilatus ◽  
Walter Möller-Hartmann ◽  
Jörg Wittsack ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Success Rate ◽  
Mr Spectroscopy ◽  
Spectroscopic Data ◽  
Who Grade ◽  
Content Type ◽  
Grade Ii ◽  
Grade Iii ◽  
Fine Print

Object. In this study, 1H magnetic resonance (MR) spectroscopy was prospectively tested as a reliable method for presurgical grading of neuroepithelial brain tumors. Methods. Using a database of tumor spectra obtained in patients with histologically confirmed diagnoses, 94 consecutive untreated patients were studied using single-voxel 1H spectroscopy (point-resolved spectroscopy; TE 135 msec, TR 1500 msec). A total of 90 tumor spectra obtained in patients with diagnostic 1H MR spectroscopy examinations were analyzed using commercially available software (MRUI/VARPRO) and classified using linear discriminant analysis as World Health Organization (WHO) Grade I/II, WHO Grade III, or WHO Grade IV lesions. In all cases, the classification results were matched with histopathological diagnoses that were made according to the WHO classification criteria after serial stereotactic biopsy procedures or open surgery. Histopathological studies revealed 30 Grade I/II tumors, 29 Grade III tumors, and 31 Grade IV tumors. The reliability of the histological diagnoses was validated considering a minimum postsurgical follow-up period of 12 months (range 12–37 months). Classifications based on spectroscopic data yielded 31 tumors in Grade I/II, 32 in Grade III, and 27 in Grade IV. Incorrect classifications included two Grade II tumors, one of which was identified as Grade III and one as Grade IV; two Grade III tumors identified as Grade II; two Grade III lesions identified as Grade IV; and six Grade IV tumors identified as Grade III. Furthermore, one glioblastoma (WHO Grade IV) was classified as WHO Grade I/II. This represents an overall success rate of 86%, and a 95% success rate in differentiating low-grade from high-grade tumors. Conclusions. The authors conclude that in vivo 1H MR spectroscopy is a reliable technique for grading neuroepithelial brain tumors.

Treatment of progressive or recurrent pediatric malignant supratentorial brain tumors with herpes simplex virus thymidine kinase gene vector—producer cells followed by intravenous ganciclovir administration

2000 ◽  
Vol 92 (2) ◽  
pp. 249-254 ◽  
Author(s):  
Roger J. Packer ◽  
Cory Raffel ◽  
Judith G. Villablanca ◽  
Jörg-Christian Tonn ◽  
Stefan E. Burdach ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Herpes Simplex ◽  
Brain Tumors ◽  
Phase I Study ◽  
Retroviral Vector ◽  
Content Type ◽  
Supratentorial Brain Tumors ◽  
Simplex Virus ◽  
Fine Print

Object. The outcome for children with recurrent malignant brain tumors is poor. The majority of patients die of progressive disease within months of relapse, and other therapeutic options are needed. The goal of this Phase I study was to evaluate the safety of in vivo suicide gene therapy in 12 children with recurrent, malignant, supratentorial brain tumors.Methods. After optimal repeated tumor resection, multiple injections of murine vector—producing cells shedding murine replication—defective retroviral vectors coding the herpes simplex virus thymidine kinase type 1 (HSV-Tk1) gene were made into the rim of the resection cavity. Fourteen days after the vector-producing cells were injected, ganciclovir was administered for 14 days. The retroviral vector that was used only integrated and expressed HSV-Tk1 in proliferating cells, which are killed after a series of metabolic events lead to cell death. The median age of the patients was 11 years (range 2–15 years). Treated brain tumors included seven malignant gliomas, two ependymomas, and three primitive neuroectodermal tumors. The patients were treated with one of three escalating dose concentrations of vector-producer cells. Four transient central nervous system adverse effects were considered possibly related to the vector-producing cells. In no child did permanent neurological worsening or ventricular irritation develop, and tests for replication-competent retroviruses yielded negative findings.Conclusions. This Phase I study demonstrates that in vivo gene therapy in which a replication-defective retroviral vector in murine vector—producing cells is delivered by brain injections can be performed with satisfactory safety in a select group of children with localized supratentorial brain tumors.

Anatomical data on the craniocervical junction and their correlation with degenerative changes in 30 cadaveric specimens

2005 ◽  
Vol 3 (5) ◽  
pp. 379-385 ◽  
Author(s):  
Stefan A. König ◽  
Axel Goldammer ◽  
Hans-Ekkehart Vitzthum
Keyword(s):  
Articular Cartilage ◽  
Articular Surface ◽  
Craniocervical Junction ◽  
Degenerative Changes ◽  
Content Type ◽  
Articular Surfaces ◽  
Anatomical Data ◽  
Grade Ii ◽  
Grade Iii ◽  
Fine Print

>Object. The goal of this project was to measure vertebral dimensions at the craniocervical junction and to investigate degenerative changes in this region and their correlations with the anatomical data. These studies will assist in an understanding of biomechanical conditions in this region, which are clinically relevant in cases of cervicogenic headaches and vertigo. Methods. The authors examined 30 cadaveric specimens obtained from patients ranging in age from 24 to 88 years at death. Measurements of angles of the vertebrae were conducted using an imprint method. Microsections of osseous endplates and articular cartilage were graded according to their degrees of degeneration by using the Petersson classification (0, no sign of degeneration; I, superficial degeneration with several fragmentations; II, deeper degeneration with cartilaginous disintegration and penetrating ulceration; or III, complete cartilaginous degeneration with the appearance of subchondral bone in > 50% of the articular surface). The authors found Grade I changes in 100% of the occiput specimens. In the superior articular cartilage of C-1 no changes (Grade 0) were found in two specimens, whereas 6% of the specimens exhibited Grade II changes and 89% exhibited Grade I changes. In the inferior articular cartilage of C-1, 57% of the specimens displayed Grade I changes, 14% Grade II, and 20% Grade III changes. In the superior articular cartilage of C-2, 62.5% of the specimens displayed Grade I changes and 25% Grade II changes. At the occiput—C1 level the authors found a higher frequency of degeneration at the upper left articular surface of the atlas (Quadrants 1 and 3), and at the C1–2 level they found a higher frequency of degeneration at the upper left and upper right articular surfaces of the axis (Quadrants 2 and 3, respectively). Using the McNemar test, the authors investigated the frequency of affection of single quadrants in a left—right side comparison (lateral reversal). Significant differences were identified for Quadrant 2 of the upper left articular surface of C-2 and Quadrant 3 of the upper right articular surface of C-2. These results correlate with the analysis of single articular surfaces of the axis, but contradict the results for the atlas, in which no significant difference in the left—right side comparison was found. Conclusions. Severe degeneration in the atlantooccipital joints appears to be a rare condition, with no Grade II or III degeneration found in the occipital condyles and 6% Grade I, 89% Grade II, but no Grade III changes in the superior articular cartilage of the atlas. Degeneration of the inferior articular cartilage of C-1 and the superior articular cartilage of C-2 indicates that the atlantoaxial joint faces more intense mechanical exposure, which is increased at the upper joint surfaces.

Thoracic pedicle screws: postoperative computerized tomography scanning assessment

2004 ◽  
Vol 100 (4) ◽  
pp. 325-331 ◽  
Author(s):  
Robert F. Heary ◽  
Christopher M. Bono ◽  
Margaret Black
Keyword(s):  
Computerized Tomography ◽  
Pedicle Screws ◽  
Ct Scanning ◽  
Screw Placement ◽  
Grading System ◽  
Content Type ◽  
Thoracic Pedicle Screws ◽  
Grade Ii ◽  
Grade Iii ◽  
Fine Print

Object. The authors evaluated the accuracy of placement of thoracic pedicle screws by performing postoperative computerized tomography (CT) scanning. A grading system is presented by which screw placement is classified in relation to neurological, bone, and intrathoracic landmarks. Methods. One hundred eighty-five thoracic pedicle screws were implanted in 27 patients with the assistance of computer image guidance or fluoroscopy. Postoperative CT scanning was conducted to determine a grade for each screw: Grade I, entirely contained within pedicle; Grade II, violates lateral pedicle but screw tip entirely contained within the vertebral body (VB); Grade III, tip penetrates anterior or lateral VB; Grade IV, breaches medial or inferior pedicle; and Grade V, violates pedicle or VB and endangers spinal cord, nerve root, or great vessels and requires immediate revision. Based on anatomical morphometry, the spine was subdivided into upper (T1–2), middle (T3–6), and lower (T7–12) regions. Statistical analyses were performed to compare regions. The mean follow-up period was 37.6 months. The following postoperative CT scanning—documented grades were determined: Grade I, 160 screws (86.5%); Grade II, 15 (8.1%); Grade III, six (3.2%); Grade IV, three (1.6%); and Grade V, one (0.5%). Among cases involving screw misplacements, Grade II placement was most common, and this occurred most frequently in the middle thoracic region. Conclusions. The authors' grading system has advantages over those previously described; however, further study to determine its reliability, reproducibility, and predictive value of clinical sequelae is warranted. Postoperative CT scanning should be considered the gold standard for evaluating thoracic pedicle screw placement.

Interstitial radiosurgery of low-grade gliomas

1995 ◽  
Vol 82 (3) ◽  
pp. 418-429 ◽  
Author(s):  
Friedrich W. Kreth ◽  
Michael Faist ◽  
Peter C. Warnke ◽  
Reinhard Roβner ◽  
Benedikt Volk ◽  
...  
Keyword(s):  
Ct Scan ◽  
Tumor Recurrence ◽  
Survival Rates ◽  
Low Grade ◽  
Who Grade ◽  
Content Type ◽  
Low Grade Gliomas ◽  
Interstitial Radiosurgery ◽  
Grade Ii ◽  
Fine Print

✓ The treatment of patients with low-grade gliomas remains a subject of controversy, especially with respect to new treatment modalities such as interstitial radiosurgery (brachytherapy), radiosurgery, and stereotactic radiotherapy. In a retrospective analysis conducted between 1979 and 1991, the authors studied the results of interstitial radiosurgery in 455 patients with low-grade gliomas (World Health Organization (WHO) Grade I + WHO Grade II) with regard to survival time, quality of life, the risk of malignant transformation, and the risk profile of the treatment concept. Interstitial radiosurgery with iodine-125 was performed using permanent (1979–1985) or temporary implants (after 1985) with low-dose rates (≤ 10 cGy/hr) and a reference dose of 60 to 100 Gy calculated to the outer rim of the tumor. The 5- and 10-year survival rates in patients with pilocytic astrocytomas (97 patients) were 84.9% and 83%, and in patients with WHO Grade II astrocytomas (250 patients) 61% and 51%, respectively. Five-year survival rates for patients with oligoastrocytomas (60 patients), oligodendrogliomas (27 patients), and gemistocytic astrocytomas (21 patients) were 49%, 50%, and 32%, respectively. In the group with WHO Grade II gliomas, young age and a good performance status were associated with a better prognosis. Unfavorable factors were midline shift, enhancement on computerized tomography (CT) scan, and tumor recurrence after previous radiotherapy or surgery. Tumor location had no influence on the prognosis (247 patients in this series had deep-seated tumors). Malignant transformation was the major cause of death. Important risk factors for malignancy were the patient's age, tumor enhancement in CT scan, and tumor recurrence after previous surgery or radiotherapy. Perioperative mortality was 0.9% and perioperative morbidity was 1.7%. Radiogenic complications were observed in 2.7% of all patients, most often in larger tumors and after using permanent implants. The authors conclude that interstitial radiosurgery represents a specific treatment modality for selected patients with unifocal circumscribed low-grade gliomas with a diameter of less than 4 cm in any location. The efficacy of this treatment lies in the same range as the best results after surgery and radiotherapy.

Surgery for cerebral arteriovenous malformation: risks related to lenticulostriate arterial supply

1997 ◽  
Vol 86 (5) ◽  
pp. 801-805 ◽  
Author(s):  
Michael K. Morgan ◽  
Katharine J. Drummond ◽  
Verity Grinnell ◽  
William Sorby
Keyword(s):  
Cerebral Arteriovenous Malformation ◽  
Arterial Supply ◽  
Content Type ◽  
Increased Risk ◽  
Complications Of Surgery ◽  
Grade Ii ◽  
Martin Grade ◽  
Grade Iii ◽  
Fine Print

✓ The aim of this study was to compare complications of surgery in arteriovenous malformations (AVMs) supplied by the middle cerebral artery (MCA) with and without a lenticulostriate arterial contribution. Ninety-two consecutive surgical resections of AVMs with an angiographically demonstrated MCA supply were performed between January 1989 and July 1996. Ten of these cases had a significant lenticulostriate arterial contribution. The cases were graded according to the Spetzler—Martin classification. There were no deaths and 4.3% of cases developed new major neurological deficit by the 3-month follow-up examination. All cases had angiographically confirmed obliteration of the AVM. There were no complications in 16 patients with Spetzler—Martin Grade I AVMs, one case of complications in 40 patients with Grade II AVMs, eight cases of complications in 26 patients with Grade III AVMs, and seven cases of complications in 10 patients with Grade IV and V AVMs. The supply of blood from lenticulostriate branches was associated with complications in eight of the 10 cases. The effect of the presence of a lenticulostriate arterial supply was most apparent in cases of Grade III AVMs: complications were experienced in three of 20 patients whose AVMs were not supplied by the arteries and in five of six patients whose AVMs were fed by the lenticulostriate arteries. This difference is significant (p < 0.0001). The conclusions drawn from this study are that for Grade III AVMs, the presence of a lenticulostriate arterial supply can be considered a factor predictive of an increased risk of surgical complications.

Cerebral metabolism in experimental hydrocephalus: an in vivo 1H and 31P magnetic resonance spectroscopy study

1999 ◽  
Vol 91 (4) ◽  
pp. 660-668 ◽  
Author(s):  
Kees P. J. Braun ◽  
Pieter van Eijsden ◽  
W. Peter Vandertop ◽  
Robin A. de Graaf ◽  
Rob H. J. M. Gooskens ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Magnetic Resonance ◽  
Mr Spectroscopy ◽  
Neuronal Damage ◽  
Lactate Production ◽  
Cerebral Damage ◽  
Adult Rats ◽  
Content Type ◽  
Fine Print

Object. Brain damage in patients with hydrocephalus is caused by mechanical forces and cerebral ischemia. The severity and localization of impaired cerebral blood flow and metabolism are still largely unknown. Magnetic resonance (MR) spectroscopy offers the opportunity to investigate cerebral energy metabolism and neuronal damage noninvasively and longitudinally. Previous 1H MR spectroscopy studies have shown an increased lactate resonance that is suggestive of anaerobic glycolysis. The aim of this study was to assess cerebral damage and energy metabolism in kaolin-induced hydrocephalus in adult rats by using in vivo 1H and 31P MR spectroscopy. The presence of lactate was correlated with high-energy phosphate metabolism and intracellular pH. The measurement of relative concentrations of N-acetyl aspartate (NAA), choline (Cho), and total creatine (tCr) served to assess neuronal damage.Methods. Hydrocephalus was induced in adult rats by surgical injection of kaolin into the cisterna magna. Magnetic resonance studies, using a 4.7-tesla magnet, were performed longitudinally in hydrocephalic animals at 1 (10 rats), 8 (six rats), and 16 weeks (six rats) thereafter, as well as in eight control animals. To evaluate ventricular size and white matter edema T2-weighted MR imaging was performed. The 1H MR spectra were acquired from a 240-µl voxel, positioned centrally in the brain, followed by localized 31P MR spectroscopy on a two-dimensional column that contained the entire brain but virtually no extracranial muscles. The 1H and 31P MR spectroscopy peak ratios were calculated after fitting the spectra in the time domain, intracellular pH was estimated from the inorganic phosphate (Pi) chemical shift, and T2 relaxation times of 1H metabolites were determined from the signal decay at increasing echo times.Conclusions. In hydrocephalic rats, ventricular expansion stabilized after 8 weeks. White matter edema was most pronounced during acute hydrocephalus. Lactate peaks were increased at all time points, without a decrease in phosphocreatine (PCr)/Pi and PCr/adenosine triphosphate (ATP) peak ratios, or pH. Possibly lactate production is restricted to periventricular brain tissue, followed by its accumulation in cerebrospinal fluid, which is supported by the long lactate T2 relaxation time. Alternatively, lactate production may precede impairment of ATP homeostasis. The NAA/Cho and tCr/Cho ratios significantly decreased during the acute and chronic stages of hydrocephalus. These changes were not caused by alterations in metabolite T2 relaxation time. The decreases in the NAA/Cho and tCr/Cho ratios implicate neuronal loss/dysfunction or changes in membrane phospholipid metabolism, as in myelin damage or gliosis. It is suggested that 1H MR spectroscopy can be of additional value in the assessment of energy metabolism and cerebral damage in clinical hydrocephalus.

The Ki-67 labeling index as a prognostic factor in Grade II oligoastrocytomas

2005 ◽  
Vol 102 (6) ◽  
pp. 1033-1039 ◽  
Author(s):  
Mark E. Shaffrey ◽  
Elana Farace ◽  
David Schiff ◽  
James M. Larner ◽  
Melike Mut ◽  
...  
Keyword(s):  
Labeling Index ◽  
World Health ◽  
Ki 67 ◽  
Content Type ◽  
Prognostic Utility ◽  
Grade Ii ◽  
Health Organization ◽  
The University ◽  
Grade Iii ◽  
Fine Print

Object. This study was conducted to determine whether proliferative tumor activity, as assessed using the Ki-67 immunohistochemical labeling index (LI), has prognostic utility for patients with Grade II oligoastrocytomas. Methods. The study period spans the years 1988 to 2000. In a retrospective analysis, the authors selected cases with biopsy-proven diagnoses of Grade II oligoastrocytomas on initial presentation. The authors added new patients to this group and followed all patients prospectively at the University of Virginia Neuro-Oncology Center. Twenty-three adult patients were followed for at least 1 year (median 40.3 months). Eleven patients with Grade II tumors and initial Ki-67 LIs less than 10% had a significantly longer median time to tumor progression (TTP, 51.8 months compared with 9.9 months) and a longer median survival (93.1 months compared with 16.1 months) than 12 patients with initial Ki-67 LIs of 10% or greater. Twelve patients with Grade III oligoastrocytomas had a mean TTP that was similar to the TTP of patients with Grade II tumors and high Ki-67 LIs (mean 4 months compared with 9.9 months) and duration of survival (13.3 months compared with 16.1 months). Conclusions. Patients with a Grade II oligoastrocytoma and a Ki-67 LI of 10% or greater have a much shorter TTP and potentially a poorer disease prognosis than expected—more similar to patients with a Grade III oligoastrocytoma. These results indicate that in the future a measure of proliferative activity should be taken into consideration along with the World Health Organization grading criteria for oligoastrocytomas.

Increased pedicle screw pullout strength with vertebroplasty augmentation in osteoporotic spines

2002 ◽  
Vol 96 (3) ◽  
pp. 309-312 ◽  
Author(s):  
John S. Sarzier ◽  
Avery J. Evans ◽  
David W. Cahill
Keyword(s):  
Pedicle Screw ◽  
Pedicle Screws ◽  
Pullout Strength ◽  
Mineral Density ◽  
Content Type ◽  
Pullout Force ◽  
Grade Ii ◽  
The Mean ◽  
Grade Iii ◽  
Fine Print

Object. The authors conducted a biomechanical study to evaluate pedicle screw pullout strength in osteoporotic cadaveric spines. Nonaugmented hemivertebrae were compared with pressurized polymethylmethacrylate (PMMA)—augmented hemivertebrae. Methods. Six formalin-fixed cadaveric thoracolumbar spines at least two standard deviations below the mean bone mineral density (BMD) for age were obtained. Radiographic and BMD studies were correlated to grades I, II, and III osteoporosis according to the Jekei scale. Each of the 21 vertebrae underwent fluoroscopic placement of 6-mm transpedicular screws with each hemivertebra serving as the control for the contralateral PMMA-augmented hemivertebra. Pedicle screws were then evaluated for biomechanical axial pullout resistance. Augmented hemivertebrae axial pullout forces were increased (p = 0.0005). The mean increase in pullout force was 181% for Grade I, 206% for Grade II, and 213% for Grade III osteoporotic spines. Augmented Grade I osteoporotic spines demonstrated axial pullout forces near those levels reported in the literature for nonosteoporotic specimens. Augmented Grade II osteoporotic specimens demonstrated increases to levels found in nonaugmented vertebrae with low-normal BMD. Augmented Grade III osteoporotic specimens had increases to levels equal to those found in nonaugmented Grade I vertebrae. Conclusions. Augmentation of osteoporotic vertebrae in PMMA-assisted vertebroplasty can significantly increase pedicle screw pullout forces to levels exceeding the strength of cortical bone. The maximum attainable force appears to be twice the pullout force of the nonaugmented pedicle screw for each osteoporotic grade.

Biochemical characterization of pediatric brain tumors by using in vivo and ex vivo magnetic resonance spectroscopy

2002 ◽  
Vol 96 (6) ◽  
pp. 1023-1031 ◽  
Author(s):  
A. Aria Tzika ◽  
Leo Ling Cheng ◽  
Liliana Goumnerova ◽  
Joseph R. Madsen ◽  
David Zurakowski ◽  
...  
Keyword(s):  
Mr Spectroscopy ◽  
Biochemical Characterization ◽  
Ex Vivo ◽  
Pediatric Brain Tumors ◽  
Tumor Biopsy ◽  
Content Type ◽  
Pediatric Brain ◽  
Fine Print

Object. Magnetic resonance (MR) spectroscopy provides biochemical information about tumors. The authors sought to determine the relationship between in vivo and ex vivo biochemical characterization of pediatric brain tumors by using MR spectroscopy. Their hypothesis was that ex vivo MR spectroscopy provides a link between in vivo MR spectroscopy and neuropathological analysis. Methods. In vivo proton MR spectroscopy was performed before surgery in 11 patients with neuroepithelial tumors. During resection, a total of 40 tumor biopsy samples were obtained from within the volume of interest identified on in vivo MR spectroscopy and were frozen immediately in liquid nitrogen. High-Resolution Magic Angle Spinning (HRMAS) was used to perform ex vivo MR spectroscopy in these 40 tumor biopsy samples. Neuropathological analysis was performed using the same biopsy samples, and the tumors were classified as ependymoma, choroid plexus carcinoma, pineoblastoma (one each), and pilocytic astrocytoma, medullobastoma, low-grade glioma, and glioblastoma multiforme (two each). Ex vivo HRMAS MR spectroscopy improved line widths and line shapes in the spectra, compared with in vivo MR spectroscopy. Choline (Cho) detected in vivo corresponded to three different peaks ex vivo (glycerophosphocholine, phosphocholine [PCho], and Cho). Metabolite ratios from in vivo spectra correlated with ratios from ex vivo spectra (Pearson correlation coefficient range r = 0.72–0.91; p ≤ 0.01). Metabolite ratios from ex vivo spectra, such as PCho/total creatine (tCr) and lipid/tCr, correlated with the percentage of cancerous tissue and percentage of tumor necrosis, respectively (r = 0.84; p ≤ 0.001). Conclusions. Agreement between in vivo and ex vivo MR spectroscopy indicates that ex vivo HRMAS MR spectroscopy can improve resolution of this modality and provide a link between in vivo MR spectroscopy and neuropathological analysis.

Decreased expression of heparanase in glioblastoma multiforme

2005 ◽  
Vol 102 (3) ◽  
pp. 513-521 ◽  
Author(s):  
Yushi Ueno ◽  
Masaaki Yamamoto ◽  
Israel Vlodavsky ◽  
Iris Pecker ◽  
Kohichi Ohshima ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Brain Tumors ◽  
Brain Tissue ◽  
Cell Lines ◽  
Immunohistochemical Analysis ◽  
Metastatic Brain Tumors ◽  
Content Type ◽  
Fine Print

Object. The authors investigated the presence of endoglycosidase heparanase in human glioblastoma multiforme (GBM) and metastatic brain tumors as well as in healthy brain tissue to explore the relationship between the biological characteristics of GBM and the role of heparanase. Methods. Heparanase messenger (m)RNA was almost undetectable in GBMs in vivo, whereas it was frequently seen in metastatic brain tumors according to results of reverse transcription—polymerase chain reaction (RT-PCR). Immunohistochemical analysis of paraffin-embedded tissue sections showed that neoplastic cells in metastatic brain tumors, especially in cells that invaded blood vessels, exhibit intense heparanase immunoreactivity. Heparanase was present in two highly invasive glioma cell lines, U87MG and U251MG, in vitro. These cell lines did not have metastatic capability, which was tested in an experimental pulmonary metastases model in mice. The activity of heparanase in these cell lines was almost the same as that in the highly metastatic melanoma cell line B16-F1. After nude mice were inoculated with U87MG cells, however, heparanase was no longer detected in subcutaneous or intracerebral experimental glioma in vivo based on results of immunohistochemical analysis. According to results of real-time quantitative PCR, there was a 10-fold increase in heparanase mRNA in U87MG glioma cells in vitro compared with that in experimental U87MG glioma tissue in vivo in nude mice. Conclusions. These results indicate that the expression of heparanase was downregulated in GBM in vivo, which rarely metastasizes to distant organs outside the central nervous system. Heparanase is not implicated in the invasiveness of GBM to surrounding healthy brain tissue in vivo.

Sign in / Sign up

Export Citation Format

Share Document