Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to evaluate the effect of carbogen breathing on the physiological profile of human glioma xenografts. Near infrared spectroscopy was used to investigate changes in oxy- and deoxyhemoglobin concentrations in tumor blood. Oxygen tension changes in tumor tissue were evaluated by (19)F-MR relaxometry, using perfluoro-15-crown-5-ether, and modifications of tumor blood perfusion (TBP) were analyzed by fast dynamic (1)H-MR imaging of Gd-DTPA uptake. Finally, changes of the bioenergetic status and pH of tumor cells were analyzed by (31)P-MRS. After 5 to 8 min of carbogen breathing, the average oxygen tension increase in tumor tissue was 4.6 +/- 1.3 mm Hg, which is in agreement with an increase of the oxyhemoglobin concentration in tumor blood (Delta[O(2)Hb] = 9. 2 +/- 3 microM). However, simultaneously the TBP was reduced, the bioenergetic status was diminished, and pH was decreased. As 100% O(2) breathing alone did not result in a detectable increase of oxyhemoglobin in tumor blood, the increase of the tumor oxygenation by carbogen appears to be mediated by its CO(2) content. This component may cause a nutrient-limited decrease of oxidative energy metabolism, indirectly via a steal-effect and/or by inhibition of the glycolytic rate resulting from tissue acidification. Magn Reson Med 42:490-499, 1999.
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PMID:Effect of carbogen breathing on the physiological profile of human glioma xenografts. 1046 93

Pathophysiologic parameters of the functional neovasculature and the blood-brain barrier of 9L-glioma in rat brain were measured noninvasively by dynamic 1H magnetic resonance imaging studies of gadolinium (Gd)-DTPA uptake. Changes of apparent [Gd-DTPA] uptake in time (CT[t]) were analyzed in a slice through the center of 10 9L-gliomas using fast T1 measurements. The distribution of the contrast agent was spatially correlated with the distribution of perfused microvessels as determined by immunohistochemical analysis. This method permits a distinction between perfused and nonperfused microvessels with a disrupted blood-brain barrier. In transverse slices of the whole tumor, a spatial correlation was observed between CT maps and the two-dimensional distribution of perfused microvessels. In the next step, Gd-DTPA uptake rates were spatially related to the perfused microvessel density (Np) or vascular surface area (Sp). In tumor voxels with perfused microvessels, a linear correlation was found between Gd-DTPA uptake rate constants (k values) and Np or Sp. No correlation was observed between k values and the total microvessel density. These are the first data that show a relation between Gd-DTPA uptake rates and parameters of the functional neovasculature in 9L-glioma growing in rat brain. Now that Gd-DTPA uptake studies can be related to parameters of the functional neovasculature, they may be used more efficiently as a prognostic tool before or during therapy.
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PMID:Noninvasive assessment of the functional neovasculature in 9L-glioma growing in rat brain by dynamic 1H magnetic resonance imaging of gadolinium uptake. 1082 37

Changes in [18F]-2-fluoro-2-deoxyglucose (FDG) uptake and gadopentetate dimeglumine (Gd-DTPA) enhancement before and after the first course of treatment with a cytostatic agent SU101 (N-[(4-trifluoromethyl)-phenyl]-5-methylisoxazole-4-carboxamide, SUGEN) were assessed using positron emission tomography (PET) and magnetic resonance imaging (MRI) in a pilot study of 8 patients with recurrent supratentorial malignant gliomas. The localization and the volume of Gd-DTPA enhancement and FDG hypermetabolism were analyzed. PET and MRI studies were performed one week before and 7.6+/-3.7 weeks after administration of SU101. The ratios of mean tumor activity to mean contralateral white matter and ipsilateral cerebellar activity were calculated for tumor regions, and SUV values corrected to the subjects' body surface area and glucose level (SUVbsa*glu) were calculated for nontumor regions. Five patients had a substantial increase of tumor volume on both PET and MRI during the first course of SU101. PET and MRI showed roughly equivalent volume changes. Large tumor volume increases were associated with a short time to clinical progression. The metabolic change in the tumor following the first course of SU101 varied from patient to patient, ranging from a 31% reduction to a 43% increase in FDG uptake ratio. Changes in FDG uptake were not predictive of time to progression or survival. In 2 patients with marked clinical deterioration and rapid tumor growth, there were differences in localization of Gd-DTPA enhancement and FDG hypermetabolism suggesting that hypermetabolism beyond the area of contrast enhancement may be of value in predicting rapid progression of high-grade glioma. SU101 did not induce any appreciable changes in SUVbsa*glu for non-tumor brain in 6 of 8 patients.
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PMID:Evaluation of early response to SU101 target-based therapy in patients with recurrent supratentorial malignant gliomas using FDG PET and Gd-DTPA MRI. 1090 56

To delineate the tumor margins of malignant gliomas laser-induced fluorescence detection technique was applied using 5-aminofluorescein-albumin as the fluorescent dye. The 5-aminofluorescein was linked to serum albumin (= AFlc-SA) as a cumulative protein label using residualizing markers. In a C6-glioma model the biodistribution and pharmacokinetics of the injected dye were investigated by labeling the protein conjugate with 111In-DTPA. Twenty-four hours after intravenous injection of the dye, fluorescence was activated by an argon laser and inspected in the C6-gliomas. Histological examinations were performed to compare the microscopic margins of the fluorescence-stained tumors with hematoxylin/eosin. The tumor uptake 24 h after dye injection was 23-fold higher than in the surrounding brain. Fluorescence inspection under laser activation demonstrated clearly stained and sharply demarcated tumors. The microscopic borders of the tumors corresponded exactly with the fluorescence, also demonstrating intracellular tumor uptake of the dye. In a preliminary study, three patients with malignant gliomas were operated using laser-induced fluorescence detection technique after injection of AFlc-SA. In all patients, the borders of the malignant gliomas were clearly stained by AFlc-SA during surgery. Laser-induced fluorescence imaging using the albumin conjugate AFlc-SA may be a promising method for delineating tumor margins which are hard to detect under the operating microscope alone.
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PMID:Laser-induced fluorescence detection of malignant gliomas using fluorescein-labeled serum albumin: experimental and preliminary clinical results. 1093 21

Dynamic contrast-enhanced magnetic resonance imaging (MRI) is widely used for measuring perfusion and blood volume, especially cerebral blood volume (CBV). In case of blood-brain barrier (BBB) disruption, the conventional techniques only partially determine the pharmacokinetic parameters of contrast medium (CM) exchange between different compartments. Here a modified pharmacokinetic model is applied, which is based on the bidirectional CM exchange between blood and two interstitial compartments in terms of the fractional volumes of the compartments and the vessel permeabilities between them. The evaluation technique using this model allows one to quantify the fractional volumes of the different compartments (blood, cells, slowly and fast enhancing interstitium) as well as the vessel permeabilities and cerebral blood flow (CBF) with a single T1-weighted dynamic MRI measurement. The method has been successfully applied in 25 glioma patients for generating maps of all of these parameters. The fractional volume maps allow for the differentiation of glioma vascularization types. The maps show a good correlation with the histological grading of these tumors. Furthermore, regions with enhanced interstitial volumes are found in high-grade gliomas. Differences in permeability maps of Gd-DTPA apart from BBB disruption do not exist between different tissue types. CBF measured in high-grade glioma is less pronounced than it would be expected from their blood volume. Therefore pharmacokinetic imaging provides an additional tool for glioma characterization.
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PMID:Pharmacokinetic analysis of glioma compartments with dynamic Gd-DTPA-enhanced magnetic resonance imaging. 1116 40

The biodistribution and pharmacokinetics of (111)In-DTPA-labeled pegylated liposomes (IDLPL) were studied in 17 patients with locally advanced cancers. The patients received 65-107 MBq of IDLPL, and nuclear medicine whole body gamma camera imaging was used to study liposome biodistribution. The t(1/2beta) of IDLPL was 76.1 h. Positive tumor images were obtained in 15 of 17 studies (4 of 5 breast, 5 of 5 head and neck, 3 of 4 bronchus, 2 of 2 glioma, and 1 of 1 cervix cancer). The levels of tumor liposome uptake estimated from regions of interest on gamma camera images were approximately 0.5-3.5% of the injected dose at 72 h. The greatest levels of uptake were seen in the patients with head and neck cancers [33.0 +/- 15.8% ID/kg (percentage of injected dose/kg)]. The uptake in the lung tumors was at an intermediate level (18.3 +/- 5.7% ID/kg), and the breast cancers showed relatively low levels of uptake (5.3 +/- 2.6% ID/kg). These liposome uptake values mirrored the estimated tumor volumes of the various tumor types (36.2 +/- 18.0 cm3 for squamous cell cancer of the head and neck, 114.5 +/- 42.0 cm3 for lung tumors, and 234.7 +/- 101.4 cm3 for breast tumors). In addition, significant localization of the liposomes was seen in the tissues of the reticuloendothelial system (liver, spleen, and bone marrow). One patient with extensive mucocutaneous AIDS-related Kaposi sarcoma was also studied according to a modified protocol, and prominent deposition of the radiolabeled liposomes was demonstrated in these lesions. An additional two patients with resectable head and neck cancer received 26 MBq of IDLPL 48 h before undergoing surgical excision of their tumors. Samples of the tumor, adjacent normal mucosa, muscle, fat, skin, and salivary tissue were obtained at operation. The levels of tumor uptake were 8.8 and 15.9% ID/kg, respectively, with tumor uptake exceeding that in normal mucosa by a mean ratio of 2.3:1, in skin by 3.6:1, in salivary gland by 5.6:1, in muscle by 8.3:1, and in fat by 10.8:1. These data strongly support the development of pegylated liposomal agents for the treatment of solid tumors, particularly those of the head and neck.
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PMID:Effective targeting of solid tumors in patients with locally advanced cancers by radiolabeled pegylated liposomes. 1123 71

MRI is increasingly being used as an interventional tool in neurosurgery. The field strength of "intraoperative" MR systems is usually lower than that of imagers commonly used for diagnostic purposes. However, lesion enhancement and apparent lesion extent depend on field strength. The aim of this study was to compare the contrast between intracranial, contrast-enhancing space-occupying lesions and the surrounding white matter obtained with low-field (0.2 T) and high-field (1.5 T) MR imaging and to find the contrast medium dosage for low-field MRI that produces the same lesion-to-white-matter contrast as the one obtained with high-field MRI after the administration of a standard dose of the contrast medium. A total of 38 patients with intracranial metastases or high-grade glioma were enrolled in this study. T1-weighted spin-echo sequences were acquired. High-field (1.5 T) studies were performed after the i.v. administration of 0.1 mmol gadolinium-DTPA/kg body weight. For low-field MRI (0.2 T) a dose escalation technique was used. T1-weighted sequences were repeated after each of three i. v. injections of 0.1 mmol gadolinium-DTPA/kg body weight. Thus, at the low-field examinations three T1-weighted sequences with a contrast medium dosage of 0.1, 0.2 and 0.3 mmol gadolinium-DTPA/kg body weight were obtained. Lesion-to-white-matter contrasts were calculated and compared. The average lesion-to-white-matter contrast obtained with high-field MR examinations was 1.63 (standard deviation 0.32). In the low-field MR examinations the average lesion-to-white-matter contrast was 1.34 (0.2) after a single dose, 1.57 (0.2) after a double dose, and 1.71 (.19) after a triple dose of contrast medium. The lesion-to-white-matter contrast of the high-field MR examination after a single dose of contrast medium was significantly higher than that of the low-field study after a single dose (P < 0.0001), but did not differ significantly from the low-field studies after a double (P = 0.28) or a triple dose (P = 0.17) of contrast medium. In a series of patients with contrast-enhancing space occupying brain lesions low-field MRI (0.2 T) after a double dose of contrast medium yielded the same lesion-to-white-matter contrasts as high-field MRI (1.5 T) after a standard dose. This is an important finding to avoid errors in intraoperative MRI due to the immanently lower degree of lesion enhancement in low-field MR imaging.
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PMID:Low-field interventional MRI in neurosurgery: finding the right dose of contrast medium. 1130 62

Four different types of radiolabelled dextranated EGF were added to spheroids consisting of the human glioma cells U-343MGaCl2:6. Binding was analysed both in the peripheral well-nourished regions and in the deeper regions containing mainly quiescent cells. The substances had different molecular weights, and they were characterized regarding hydrophilic properties and isoelectric points. Two of the analysed conjugates, 125I-EGF-dextran (CDAP) and 125I-EGF-allyldextran-BSH, gave very low 125I binding in the deeper regions even after 24 h of incubation while better binding in these regions was found for 125I-EGF-dextran-DTPA, 125I-EGF-allyldextran and for the reference substance 125I-EGF. The molecular weight seemed not to be of major importance for the binding properties and there were no clear relationships between binding and the hydrophilic properties or the isoelectric point values. The obtained differences could not be explained by differences in molecular weight or easily measured physicochemical parameters such as hydrophilic properties or isoelectric point values. Thus, other explanations must be found.
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PMID:Effects of dextranation on the uptake of peptides in micrometastases: studies on binding of EGF in tumor spheroids. 1139 48

In a previous study, we demonstrated that the expression levels in tumor cells of emmprin (CD147) correlated with the grade of astrocytic tumors. Also, we found that emmprin was expressed in vascular endothelial cells of the non-neoplastic brain and hypothesized that emmprin expression could be associated with normal blood-brain-barrier (BBB) function of vascular endothelial cells. In this study, this possibility was examined in non-neoplastic brain, glioma and metastatic carcinoma tissues by comparing emmprin immunohistochemistry with gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) enhancement of magnetic resonance imaging (MRI), which is a clinical indicator of the BBB function. This study included 10 cases of non-neoplastic brain tissues, 7 of metastatic carcinoma, 7 of diffuse astrocytoma, 4 of anaplastic astrocytoma and 13 of glioblastoma multiforme. In all the cases, MRI with administration of Gd-DTPA was performed. The lesions were resected using the microdissection method with the help of ultrasonography and a neuronavigator. The tissues from Gd-DTPA-enhanced or non-enhanced areas were processed into frozen sections and subjected to immunohistochemistry with anti-emmprin antibody. The expression of emmprin in brain vascular endothelial cells inversely correlated with Gd-DTPA-enhancement of MRI: emmprin was positive in tissues not enhanced by Gd-DTPA and was negative in DTPA-enhanced tissues. Since BBB function presumably remains unimpaired in regions in which MR images are not Gd-DTPA-enhanced, emmprin expression appears to be associated with unimpaired BBB function. This is the first report to demonstrate a possible correlation between emmprin expression and BBB function in humans.
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PMID:Correlation of emmprin expression in vascular endothelial cells with blood-brain-barrier function: a study using magnetic resonance imaging enhanced by Gd-DTPA and immunohistochemistry in brain tumors. 1271 75

The potential clinical role of in vivo (1)H-MRS ((1)H-magnetic resonance spectroscopy) lipid methylene resonance measurements of human glioma has been assessed. 20 patients, 14 with low grade and 6 with high grade gliomas have been investigated using single voxel (1)H-MRS. Three of the low grade group had undergone transformation by clinical and imaging criteria. Short echo time (TE=20 ms, TR=2500 ms) single voxel Stimulated Echo Acquisition (STEAM) spectra with (acquisitions=64) and without (acquisitions=4) water suppression were acquired. Additionally, T(1) weighted (T(1)W) water spectra (TE=20 ms, TR=888 ms) were acquired pre- and post-injection of Gd-DTPA (0.2 mmol x kg(-1)). The T(1)W water spectra were used to determine the water proton enhancement occurring within the spectroscopic voxel. The enhancement expressed as a percentage was compared with the lipid methylene peak. All the high grade tumours had significantly higher levels of lipid than low grade tumours (p=0.002). Low grade tumours had significantly less water proton enhancement than transformers (p=0.04) and high grade tumours (p=0.001). The lipid methylene signal correlated strongly with the voxel water enhancement (r(2)=0.74, p<0.0001). The data support the view that the spectroscopically detected lipid methylene signal may be a useful criterion in grading glioma. The correlation of the lipid methylene signal with blood-brain barrier breakdown suggests that detection of a previously absent (1)H-MRS lipid methylene signal in low grade tumours might be an early indicator of transformation.
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PMID:Could assessment of glioma methylene lipid resonance by in vivo (1)H-MRS be of clinical value? 1285 5


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