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)

We investigated the effect of RU599 Arginine Vasopressin (AVP) inhibitor on peritumoral edema of Wistar rats implanted with C6 glioma. C6 glioma was implanted into the right caudoputamen of 3 week-old rat's brain. Five weeks after the implantation, the changes of the brain water contents were measured by the dry-weight method. RU599 (1 mg/ml/kg body weight) was administered into Wistar rats via the tail vein every one hour (total 4 times), and the same dose of saline was used as control. Rats were sacrificed 1 hour after the last administration, and the brain of each rat was divided into 3 parts such as the anterior part without a tumor, the middle part with a tumor and the posterior part without a tumor. After that each part was separated into the right and left parts. The tumor was removed from the brain. The water contents of the brain were increased in the area around the tumor and the contralateral cerebral hemisphere excluding the anterior part. RU599 could reduce the increased water contents significantly in all areas except in the tumor itself and the area surrounding the tumor. Tumor-origin brain edema includes not only localized one but also diffuse one in the brain, and this study suggests RU599 has an effect of inhibiting the diffuse brain edema.
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PMID:[Effect of arginine vasopressin (AVP) inhibitor in the inhibition of the peritumoral edema]. 939 31

Tissue acidosis occurring in cerebral ischemia and traumatic brain injury is a mediator of cytotoxic brain edema. In vitro, extracellular lactacidosis induces swelling of glial cells in a dose dependent manner. pH-regulatory membrane transporters and channels have been identified which are involved in the increase of the glial cell volume. Underlying mechanisms of their activation are poorly understood, however. We have, therefore, addressed the question, whether and how Ca(2+)-ions play a role in acidosis-induced glial swelling and intracellular acidification. For that purpose C6 glioma cells were suspended and the pH in the medium was lowered from 7.4 (baseline) to 6.2 by isotonic lactic acid. Cell volume and intracellular pH (pHi) were assessed by flow cytometry. In the presence of Ca(2+)-ions the cell volume reached a maximum of 125.1% from acidosis. In experiments using a calcium-free suspension medium, cell swelling from acidosis was inhibited by 74%. Additional buffering of intracellular calcium (Ca2+i) had no further inhibitory effect on acidosis-induced cell swelling, while buffering of Ca2+i by BAPTA-AM alone did not affect the glial volume increase secondary to administration of lactic acid. pHi which was decreasing from acidosis was not affected by the experimental modifications of the Ca(2+)-concentration in the medium or cytosol. The present data indicate that lactacidosis-induced glial swelling depends on the presence of extracellular Ca(2+)-ions, while release of Ca(2+)-ions from intracellular stores does not seem to be involved.
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PMID:Role of calcium ions in acidosis-induced glial swelling. 941 4

ATN-10, Mn-metalloporphyrin, has been developed as a tumor selective contrast agent for magnetic resonance (MR) imaging. To investigate the tumor specificity of ATN-10, we produced three experimental in vivo models; rat bran tumor (9L glioma) model, vasogenic (cold injury) and cytotoxic brain edema (24-hour MCA occlusion) models. The time course of contrast enhancement was compared after intravenous injection of ATN-10 or Gd-DTPA, measuring the signal intensity of the region of interest. After ATN-10 administration, the 9L glioma model showed early (5 min) and delayed (24 hr-) peak enhancement whereas the cold injury model showed only early enhancement and the 24-hour MCA occlusion model did not show significant enhancement. After Gd-DTPA administration, all three models showed similar pattern of only early enhancement. As a contrast agent for MR imaging, ATN-10 showed different behavior than Gd-DTPA in demonstrating the blood-brain barrier disruption and moreover ATN-10 showed selective enhancement in experimental brain tumors.
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PMID:Tumor specific contrast enhancement study of Mn-metalloporphyrin (ATN-10)--comparison of rat brain tumor model, cytotoxic and vasogenic edema models. 941 11

Tissue acidosis from trauma or ischemia induces cytotoxic brain edema, mainly affecting astrocytes. In vitro, lactacidosis induces a dose-dependent swelling of glial cells. Activation of membrane transporters and channels, also involved in regulation of intracellular pH (pHi), has been identified as underlying mechanism, although details are poorly understood. We have currently studied whether Ca(2+)-ions play a role in acidosis-induced glial swelling and the associated intracellular acidification. The medium pH of a cell suspension (C6 glioma) was lowered from control (7.4) to 6.2 by lactic acid. Cell volume (CV) and pHi were assessed by flow cytometry. During acidosis in normal medium (2.2 mM Ca2+) CV reached a maximum of 125.1%. In a calcium-free medium swelling from acidosis was inhibited by 74%, while additional buffering of intracellular calcium (Ca2+i) by BAPTA-AM had no further effect. Buffering of Ca2+i alone did not affect the CV increase from acidosis at all. pHi which is decreasing during acidosis was not influenced by the above modifications. The present experiments indicate that lactacidosis-induced glial swelling depends on the presence of extracellular Ca(2+)-ions, while alterations of Ca2+i do not seem to be involved.
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PMID:Relevance of calcium homeostasis in glial cell swelling from acidosis. 977 84

Previously, we induced vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) secretion in glioma cell lines by using physiologic concentrations of epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), or platelet-derived growth factor-BB (PDGF-BB). We hypothesized that VEGF/VPF might enhance the blood supply required for the unregulated growth of tumors, and that it acts as the central mediator of tumor angiogenesis. The objective of this study was to determine whether the expression of VEGF/VPF by meningiomas is regulated by growth factors or sex hormones. By means of an enzyme-linked immunosorbent assay of CH-157MN meningioma cell supernatants, we demonstrated that EGF and bFGF similarly induce VEGF secretion by CH-157MN meningioma cells. At the maximum concentrations of EGF (50 ng/mL) and bFGF (50 ng/mL) used in this study, VEGF secretion was induced to 140% to 160% above baseline constitutive secretion. PDGF-BB homodimer did not enhance VEGF secretion significantly. Estradiol (up to 10(-7) mol/L), progesterone (up to 10(-5) mol/L), or testosterone (up to 10(-5) mol/L) did not stimulate or inhibit VEGF secretion in CH-157MN meningioma cells (p > 0.05). Furthermore, we demonstrated that dexamethasone decreased VEGF secretion to 32% of baseline constitutive secretion. This might explain the effect of corticosteroids in alleviating peritumoral brain edema in meningiomas. These results suggest that VEGF secretion in CH-157MN meningioma cells is mainly regulated by growth factors and corticosteroids, but not by sex hormones. Understanding the regulation of VEGF/VPF secretion in meningiomas might contribute to the development of a new therapeutic strategy.
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PMID:Regulation of vascular endothelial growth factor secretion in human meningioma cells. 1008 66

This study examines the contribution of anion transporters to the swelling and intracellular acidification of glial cells from an extracellular lactacidosis, a condition well-known to accompany cerebral ischemia and traumatic brain injury. Suspended C6 glioma cells were exposed to lactacidosis in physiological or anion-depleted media, and different anion transport inhibitors were applied. Changes in cell volume and intracellular pH (pH(i)) were simultaneously quantified by flow cytometry. Extracellular lactacidosis (pH 6.2) led to an increase in cell volume to 125.1 +/- 2.5% of baseline within 60 min, whereas the pH(i) dropped from the physiological value of 7.13 +/- 0.05 to 6.32 +/- 0.03. Suspension in Cl(-)-free or HCO(3)(-)/CO(2)-free media or application of anion transport inhibitors [0.1 mM bumetanide or 0.5 mM 4, 4'-diisothio-cyanatostilbene-2,2'-disulfonic acid (DIDS)] did not affect cell volume during baseline conditions but significantly reduced cell swelling from lactacidosis. In addition, the Cl(-)-free or HCO(3)(-)/CO(2)-free media and DIDS attenuated intracellular acidosis on extracellular acidification. From these findings it is concluded that besides the known activation of the Na(+)/H(+) exchanger, activation of the Na(+)-independent Cl(-)/HCO(3)(-) exchanger and the Na(+)-K(+)-Cl(-) cotransporter contributes to acidosis-induced glial swelling and the intracellular acidification. Inhibition of these processes may be of interest for future strategies in the treatment of cytotoxic brain edema from cerebral ischemia or traumatic brain injury.
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PMID:Contribution of anion transporters to the acidosis-induced swelling and intracellular acidification of glial cells. 1085 55

The potential antitumor effect of MX2, a new lipophilic morpholino anthracycline, was compared with those of ACNU or doxorubicin (DOX) using two different rodent glioma models. A mouse subcutaneous glioma model (203 glioma) was used to measure the effect of each drug on reducing the glioma size and a rat 9L intracerebral glioma model (9L glioma) was used to assess the antitumor effect on survival rate in a clinically similar fashion. Treatment with ACNU inhibited tumor growth by 94.6% (p < 0.0001) and complete regression of the tumor was observed in 3 of 25 (12.0%) of the ACNU-treated cases. Tumor growth was inhibited by 32.4% with DOX despite a tendency (p < 0.16) and by 59.4% with MX-2 (p < 0.001); neither of these drugs resulted in complete tumor regression. In the intracerebral glioma rats, only ACNU tended to ameliorate survival rate, but there was no statistical significance. These results suggest that ACNU has the most potent effect but MX2 can be an option for chemotherapy of malignant gliomas. Interestingly, all three drugs significantly elevated the brain water content on both the ipsilateral and contralateral sides of the tumor, although they did not induce brain edema in the normal rat brains. Careful management of brain edema might be required regardless of the drug used during chemotherapy to maximize the prognosis of glioma patients.
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PMID:Antitumor effect and peritumoral brain edema formation in relation to MX2, ACNU, and doxorubicin therapy: a comparative analysis using rodent models of gliomas. 1114 45

In view of the increasing significance of mild hypothermia (32 degrees C) as an efficient procedure of neuroprotection, the present study was performed to examine the influence of this level of hypothermia on the volume of glial cells under physiological as well as under pathological conditions. The influence of mild (32 degrees C) and moderate (27 degrees C) hypothermia on cell volume and cell viability of C6 glioma cells was studied for 60 minutes in vitro. Cells were suspended in an incubation chamber under continuous control of temperature, pH and pO2. Cell volume was measured by an advanced Coulter system. Hypothermia itself was causing significant cell swelling in a dose-dependent manner, which could be prevented by omission of Na(+)-ions from the suspension medium, while the replacement of Cl(-)-ions failed to prevent cell swelling from hypothermia. Inhibition of the Na+/H(+)-antiporter with EIPA (5N-ethyl-n-isopropyl-amiloride, 50 microM) was significantly reducing the hypothermia induced cell swelling, indicating activation of the Na+/H(+)-antiporter. Conversely, mild or moderate hypothermia failed to prevent cell swelling from lactic acid, arachidonic acid or glutamate, i.e. agents which are mediating the development of cytotoxic brain edema in vivo in cerebral trauma, ischemia and other acute insults. The findings indicate that cerebral protection by hypothermia in vivo is most likely not attributable to an inhibition of cytotoxic brain edema. Further investigations, however, are required in vivo and in vitro to elucidate the hypothermia-induced swelling of glial cells in more detail, e.g. as to the role of the Na+/H(+)-antiporter.
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PMID:Influence of hypothermia on cell volume and cytotoxic swelling of glial cells in vitro. 1145 89

We report a case with double primary intracranial tumors of different cell types without phacomatosis. The patient was hospitalized due to progressive memory impairment, headaches, dysarthria and right hemiparesis. Initial computed tomographic (CT) examinations revealed a large hyperdense tumor over the right frontal lobe, suggestive of an extra-axial meningioma. Additionally, there was unusual brain edema in the contralateral hemisphere that subsequently proved to originate from an intrinsic tumor. Staged craniotomies were used to treat the patient. Pathological examinations confirmed the two tumors to be a meningioma and a glioblastoma multiforme, respectively. The patient made an uneventful recovery after treatment. Although meningioma and glioma represent two common primary intracranial tumors, the simultaneous development of the two tumors is rare. A randomly occurring event most likely accounted for this linkage in the patient. We suggest that extraordinary brain edema far remote from the primary brain lesion warrants special attention for identifying other potentially undetected lesions.
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PMID:Two primary brain tumors, meningioma and glioblastoma multiforme, in opposite hemispheres of the same patient. 1238 24

By flow cytometry, a panel of 18 primary glioma cell explants exhibited high expression of class I HLA-A, B, C, but class II HLA-DR expression was absent. Freshly isolated normal brain cells displayed little or no HLA antigens. Alloreactive cytotoxic T lymphocytes (aCTL), sensitized to the HLA of the patient, were generated in a one-way mixed lymphocyte response (MLR). The specificity of aCTL was confirmed to be to target cells (patient glioma cells or lymphoblasts) expressing the relevant HLA antigens. However, nontumor patient-specific aCTL did not lyse normal brain cells. Titration of antibodies to HLA class I into cytotoxicity assays blocked lysis of gliomas by aCTL, confirming aCTL T cell receptor (TCR) interactions with the class I antigen on gliomas. Furthermore, aCTL interactions with glioma cells caused their apoptosis. Coincubations of aCTL with gliomas resulted in upregulated cytokine secretion. Importantly, dexamethasone, an immunosuppressive steroid used for brain edema, did not affect aCTL lytic function against tumor, indicating that steroid-dependent patients may benefit from the immunotherapy. We also explored the use of interferon-gamma (IFN-gamma) to increase aCTL tumor recognition. Coincubation of gliomas with exogenous IFN-gamma (500 U/ml, 48 h) caused a 3-fold upregulation of HLA class I and a slight induction of class II antigen expression. Gene-modified glioma cells producing IFN-gamma similarly displayed upregulated HLA expression. Glioma cells incubated with exogenous IFN-gamma or IFN-gamma-transduced glioma cells were more susceptible to lysis by aCTL than their parental counterparts, thus supporting the concept of combining IFN-gamma cytokine gene therapy with adoptive aCTL immunotherapy for brain tumor treatment.
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PMID:Human alloreactive CTL interactions with gliomas and with those having upregulated HLA expression from exogenous IFN-gamma or IFN-gamma gene modification. 1451 64


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