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

A series of diamines with the general structure NH2(CH2)xNH2, x=2-12, was tested for their potential effects on cell proliferation of cultured rat C6 glioma cells in comparison to natural polyamines. Long chain diamines reduced cell number after 48 h in culture with a sequence of 1,12-diaminododecane (1,12-DD) >1,10-diaminodecane >1,9-diaminononane. Polyamines (putrescine, spermidine and spermine) as well as diamines up to a CH2-chain length of x=8 were found to be ineffective. The spermine analogue 1,12-DD was the most effective molecule in reducing cell number in an irreversible, dose-dependent manner (EC50=3 microM under serum-free conditions). In further experiments we investigated the mechanisms of action of 1,12-DD. The compound had only a minor effect on cell cycle and did not affect free internal calcium concentration. Under physiological conditions 1,12-DD interacts with triplex DNA but not with duplex DNA. Ornithine decarboxylase activity as well as the concentration of internal polyamines were found to be reduced by 1,12-DD. Polyamine application, however, was not able to reverse the effect of 1,12-DD, indicating a polyamine-independent or non-competitive mechanism of action. 1,12-DD reduced cell number by induction of apoptosis as well as necrosis. In molecular modeling studies it was found that a minimal hydrophobic intersegment of at least 4 A was required to make a diamine an effective drug in respect to cellular growth. A hydrophobic gap of this size fits the minimum requirement expected from molecular modeling to provide space for hydrophobic interactions with parts of proteins like a CH3-group. Our results show that 1,12-DD acts as a potent drug, reducing the number of C6 glioma cells, and suggest that its spatial and hydrophobic properties are responsible for its mechanism of action.
 ...
PMID:Long chain diamines inhibit growth of C6 glioma cells according to their hydrophobicity. An in vitro and molecular modeling study. 1073 Oct 35

It is well established that, like glycine and D-alanine, D-serine potentiates glutamate neurotransmission via the N-methyl-D-aspartate (NMDA) receptor by selective stimulation of its strychnine-insensitive glycine site and acts as a co-agonist of the glutamate receptor. D-Serine has been found to modify behavioral changes associated with higher brain functions such as memory, convulsion, anxiety, psychotomimetic-induced abnormal behavior and cerebellar ataxia. Interestingly, a substantial amount of free D-serine has been demonstrated in mammalian brains, although it has long been presumed that D-amino acids are uncommon in mammals. Free D-serine is predominantly concentrated in the brain with a persistent high content throughout life. The patterns of the regional variations and the postnatal changes in brain D-serine are closely correlated with those of the R2B subunit of the N-methyl-D-aspartate (NMDA) type excitatory amino acid receptor. Moreover, D-serine is released to the extracellular space and taken up into the brain homogenates, C6 glioma cells and primary culture of astrocytes of the rat cerebral cortex. Recently, the conversion of L-serine to its D-form by serine racemase has been suggested by in vivo and in vitro experiments. These data are consistent with the view that D-serine might be an intrinsic positive modulator of the brain NMDA receptor containing the R2B subunit and play a pivotal role in controlling behavioral expression in mammals.
 ...
PMID:[Endogenous D-serine in mammalian brains]. 1089 22

The present study was aimed at elucidating the effect of cyclosporine on phenylephrine-evoked nitric oxide (NO) production in C6 glioma cells using direct electrochemical NO monitoring. Phenylephrine (0.1-10 microM) dose-dependently stimulated NO production (0.8-12.9 microM) and this was blocked by NO synthase inhibitor, prazosin, Ca2+-depletion and Xestospongin C (a blocker of the inositol 1,4,5-trisphosphate (IP3) receptor), suggesting that the alpha1-adrenoceptor signaling pathway mediates NO production in C6 cells. Cyclosporine (approximately 10 microM) failed to evoke NO production but increased phenylephrine-evoked NO production by 20-120% of phenylephrine alone in a dose-dependent manner (1-5 microM). Xestospongin C, at a concentration which showed no effect on phenylephrine-induced NO production, significantly inhibited the cyclosporine-enhanced phenylephrine response. This finding suggests that cyclosporine may increase phenylephrine-induced NO production by accelerating IP3 receptor function in the alpha1-adrenoceptor signaling pathway in C6 cells. This enhanced NO production in glial cells may be operative for the occurrence of cyclosporine neurotoxicity including convulsions and encephalopathy.
 ...
PMID:Cyclosporine enhances alpha1-adrenoceptor-mediated nitric oxide production in C6 glioma cells. 1106 17

Most drugs have some efficacy so that improved methods to determine the relative intrinsic efficacy of partial agonists should be of benefit to preclinical and clinical investigators. We examined the effects of partial D(1) or partial D(2) dopamine agonists using a partial agonist interaction model. The dependent variable was the modulation of the dopamine-receptor-mediated cAMP response in C6 glioma cells selectively and stably expressing either D(1) or D(2) recombinant dopamine receptors. The dissociation constant (K(B)) and relative intrinsic efficacy (E(r)) for each partial agonist were calculated using a partial agonist interaction null model in which the effects of fixed concentrations of each partial agonist on the dopamine dose-response curve were evaluated. This model is an extension of the competitive antagonist null model to drugs with efficacy and assumes only that the log-dose--response curve is monotonic. Generally, the partial agonist interaction model fit the data, as well as fits of the independent logistic curves. Furthermore, the partial agonist K(B) values could be shared across partial agonist concentrations without worsening the model fit (by increasing the residual variance). K(B) values were also similar to drug affinities reported in the literature. The model was validated in three ways. First, we assumed a common tissue stimulus parameter (beta) and calculated the E(r) values. This provided a qualitative check on the interaction model results. Second, we calculated new relative efficacy values, E(r)(beta), using the beta estimate. Third, we calculated relative efficacy using relative maxima times midpoint shift ratios (J. Theor. Biol. 198 (1999) 347.). All three methods indicated that the present model yielded reasonable estimates of affinity and relative efficacy for the set of compounds studied. Our results provide a quick and convenient method of quantification of partial agonist efficacy. Special applications and limitations of the model are discussed. In addition, the present results are the first report of the relative intrinsic efficacy values for this set of D(2) ligands.
 ...
PMID:Nonlinear analysis of partial dopamine agonist effects on cAMP in C6 glioma cells. 1148 62

The aim of the present study is to develop a mathematical model for evaluating therapeutic response of combined treatment modalities. The study was performed in rats of the Fischer-344 strain with rat glioma N32 or N29 tumors implanted subcutaneously on the thigh of the hind leg. Pulsed electric fields, PEF, with 16 exponentially decaying pulses with a maximum electric field strength of 140 V/mm and t(1/e)= 1 ms were first applied to the tumors. Then within 5 min radiation therapy with (60)Co-gamma radiation, RT, was given in daily fractions of 5 Gy. The animals were arranged into one group of controls and 3 groups of different kind of treatments: PEF only, RT only or combination of PEF + RT. At about 4 weeks after inoculation, the tumors were given the treatment sessions during one week. In 2 experimental series with totally 52 rats with N32 tumors, of which 16 were controls, were given 4 sessions of PEF treatments and RT (totally 20 Gy). In a special experimental series with totally 56 rats with N32 tumors, of which 10 were controls, the different groups were given 1, 2, 3 or 4 treatment sessions respectively. Another strain of glioma tumor, N29 with 62 tumors of which 14 were controls was studied in 2 series given 4PEF + 4RT and 2PEF + 4RT respectively. Fitting the data obtained from consecutive measurements of tumor volume (TV) of each individual tumor to an exponential model TV = TV(0). exp[TGR.t] estimated the tumor growth rate (TGR % per day) after the first day of treatment (t = 0). The TGR of N32 tumors treated with the combination of 4PEF + 4RT are significantly decreased compared to the controls (p < 0.0001), compared to RT alone (p < 0.0001) and compared to PEF alone (p < 0.001). The combined treatment of N32 gives significant effect on the tumor growth rate after 2, 3 and 4 treatment session while RT alone seems to be most efficient after one treatment of 5 Gy and PEF alone is most efficient after 2 treatments at 2 consecutive days. The TGR of N29 tumors treated with the combination of 4PEF + 4RT are significantly decreased compared to the controls (p < 0.05) but the combination of 2PEF + 4RT was more effective (p < 0.005). The specific therapeutic effect STE is defined as the difference between the average tumor growth rates of controls and exposed tumors divided by the average tumor growth rate of the controls. With 4PEF treatments alone the average STE value was 0.32 for N32 tumors and 0 for N29; for 4RT alone the STE values were 0.29 and 0.42 respectively, and for combined treatments 4PEF + 4RT 0.67 and 0.17 respectively. For the N29 tumors treated with 2PEF + 4RT the STE value was 0.53. The therapeutic enhancement ratio, TER, value increase with the number of treatment sessions and the TER of the combined treatments is above 1 in two of the N32 series, which indicates a synergistic effect of 4PEF + 4RT. This work demonstrate the use of our model for analyzing the combination PEF + RT, but it can also be used for evaluation the therapeutic effects of combining RT with chemotherapy or immunogenetic therapy.
 ...
PMID:A model for evaluating therapeutic response of combined cancer treatment modalities: applied to treatment of subcutaneously implanted brain tumors (N32 and N29) in Fischer rats with pulsed electric fields (PEF) and 60Co-gamma radiation (RT). 1452 12

The purpose of this study was to clarify the radiation injury in acute or delayed stage after boron neutron capture therapy (BNCT) using mixed epithermal- and thermal neutron beams in patients with malignant glioma. Eighteen patients with malignant glioma underwent mixed epithermal- and thermal neutron beam and sodium borocaptate between 1998 and 2004. The radiation dose (i.e. physical dose of boron n-alpha reaction) in the protocol used between 1998 and 2000 (Protocol A, n = 8) prescribed a maximum tumor volume dose of 15 Gy. In 2001, a new dose-escalated protocol was introduced (Protocol B, n = 4); it prescribes a minimum tumor volume dose of 18 Gy or, alternatively, a minimum target volume dose of 15 Gy. Since 2002, the radiation dose was reduced to 80-90% dose of Protocol B because of acute radiation injury. A new Protocol was applied to 6 glioblastoma patients (Protocol C, n = 6). The average values of the maximum vascular dose of brain surface in Protocol A, B and C were 11.4+/-4.2 Gy, 15.7+/-1.2 and 13.9+/-3.6 Gy, respectively. Acute radiation injury such as a generalized convulsion within 1 week after BNCT was recognized in three patients of Protocol B. Delayed radiation injury such as a neurological deterioration appeared 3-6 months after BNCT, and it was recognized in 1 patient in Protocol A, 5 patients in Protocol B. According to acute radiation injury, the maximum vascular dose was 15.8+/-1.3 Gy in positive and was 12.6+/-4.3 Gy in negative. There was no significant difference between them. According to the delayed radiation injury, the maximum vascular dose was 13.8+/-3.8 Gy in positive and was 13.6+/-4.9 Gy in negative. There was no significant difference between them. The dose escalation is limited because most patients in Protocol B suffered from acute radiation injury. We conclude that the maximum vascular dose does not exceed over 12 Gy to avoid the delayed radiation injury, especially, it should be limited under 10 Gy in the case that tumor exists in speech center.
 ...
PMID:Radiation injury of boron neutron capture therapy using mixed epithermal- and thermal neutron beams in patients with malignant glioma. 1530 93

Pleomorphic xanthoastrocytoma has been generally conceived to be in a benign nature, showing a relatively favorable prognosis. Apoplectic attack attributable by massive hemorrhage in this distinct form of the supratentorial glioma is an exceedingly rare event. A 61-year-old female presented with a sudden onset of generalized tonic--clonic convulsion. CT and MRI disclosed the presence of a tumor composing of massive intra-tumoral hemorrhage filling the cyst associated with mural nodule in the left frontotemporal lobe. At surgery, the subpial mass involving hematoma was well marginated and slightly adherent to the dura mater. It could be removed totally and proved to be a pleomorphic xanthoastrocytoma. The unusual hemorrhagic presentation of this typically benign entity is extremely rare and is thought to be intra-tumoral bleeding in this case, since subarachnoid hemorrhage was absent.
 ...
PMID:A case of pleomorphic xanthoastrocytoma presenting with massive tumoral hemorrhage. 1629 92

A total of 45 cases were studied to elucidate the variation between CT scan findings and histological diagnosis of intracranial glioma. They were operated and histopathological examination of all cases was studied. The mean age of the patients were 35+/-2.37 years and ranged from 01 to 65 years. The highest incidence of glioma was found in age group between 40-50 years. The incidence of glioma was more in male 36(80%) in comparison to female 9(20%). The main presenting complaints were headache in 42(93.3%), vomiting in 34(75%), limb weakness in 28(62.2%) and blurring of vision were in 26(57.8%) patients. Other symptoms were convulsion in 29(64.4%) patients and altered consciousness 24(53.3%) patients. By CT scan, diagnosis was made as informed gliomas in all cases. Histopathological examination showed 41(91.1%) cases were gliomas and 3(6.7%) were meningiomas and 1(2.2%) was brain abscess. So there were little variations between CT scan findings and histopathological diagnosis.
 ...
PMID:Variation between CT scan findings and histological diagnosis of intracranial glioma. 1862 52

For nearly a century, glial neoplasms have been classified by microscopic features alone with treatment prescribed based on histology using a "one-size-fits-all" formula. However, recent advances in our understanding of the molecular events underlying gliomagenesis are beginning to change the way we think about the diagnostic classification of gliomas. Indeed, several recurring molecular derangements are now being viewed as cornerstones of a new diagnostic framework because these alterations appear to be superior to traditional microscopic classification schemes as guideposts for treatment selection and prognosis. Moreover, molecular analysis of tumor tissue is identifying aberrant growth signaling pathways in glioma which can now be blocked selectively by a new generation of targeted therapies, including small molecule inhibitors and monoclonal antibodies. Time will tell whether these new agents can be successfully introduced into the clinical arena. In the meantime, the molecular characteristics of gliomas are being used to select patients for both randomized trials and phase II studies.
 ...
PMID:Invited article: the expanding impact of molecular biology on the diagnosis and treatment of gliomas. 1866 82

The authors report a case of glioma nasopalatine Multifoil in wallet, location-intra nasal and palatal left. The nasal glioma is a rare congenital malformation presenting as a nasal mass composed of neuroglial tissue heteropias resulting from an abnormality in embryonic development. It is a benign tumor that fits into the nosology of the masses of the midline. This abnormality arises primarily a diagnostic problem because often mistaken for a meningo-encephalocele or a nasal dermoid cyst. Localization nose and palate, an hourglass, is extremely rare if not exceptional; The computed tomography (CT) has enabled the accurate assessment of injury and has guided the choice of surgical technique. The resection was done successfully without recurrence. Histology examination of the surgical specimen confirmed the nature of astrocytic neuroglial tumor. The location of the tumor pedide palate to that of the left nostril is special and especially histological diagnosis of this congenital malformation.
 ...
PMID:[Diagnostic and surgical approach to an hourglass-shaped nasopalatine glioma in an infant]. 2132 23


<< Previous 1 2 3 4 5 Next >>