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)

In the present study, the P2Y receptor(s) mediating the effects of the pyrimidines UTP and UDP on phospholipase C activation in the mouse neuroblastoma x rat glioma hybrid cell line NG108-15 was investigated. Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) analysis detected transcripts for the P2Y(6) and P2Y(2) receptors, but not for P2Y(1) and P2Y(4.) UTP and UDP were equipotent agonists and their effects were partially additive. Suramin, reactive blue 2 and pyridoxal phosphate-6-azophenyl-2',4'disulfonic acid (PPADS) antagonised the phospholipase C response to both UTP and UDP. High micromolar concentrations of adenosine, 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS-21680), 2',3'-O-isopropylideneadenosine (iPAdo) and adenosine 3':5'-cyclic monophosphate (3',5'-cAMP) were able to antagonise the effect of UTP on phospholipase C but not that of UDP. The additivity of the UTP and UDP responses, novel P2 receptor antagonist profile and the distinguishing action of adenosine may indicate the expression of a pyrimidine selective P2Y receptor in addition to the P2Y(6) type in these cells.
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PMID:Pharmacological characterisation of pyrimidinoceptor responses in NG108-15 cells. 1127 90

Suramin is a polysulfonated naphthylurea that inhibits the function of growth factors and growth factor receptors implicated in glioma progression, angiogenesis, and radioresistance. The safety and benefits of combining inhibitors of angiogenesis and growth factors with cytotoxic therapies in patients with neoplasms of the central nervous system remain unclear. The objectives of this phase 2 study were to determine the safety of administering suramin with standard cranial radiotherapy (RT) and to estimate survival using this approach in patients with newly diagnosed glioblastoma multiforme (GBM). Fifty-five patients with newly diagnosed GBM (Karnofsky performance status >or= 60) were enrolled in this multicenter phase 2 study. Patients received suramin by a conventional intermittent fixed-dosing regimen for 1 week prior to and during cranial RT (60 Gy in 30 fractions, weeks 2-7). Patients with stable or responsive disease at week 18 received an additional 4 weeks of suramin (weeks 19-22). The median survival for suramin-treated patients was 11.6 months, with 1-year and 18-month survival rates of 49% (95% confidence interval [CI], 36%-62%) and 18% (95% CI, 8%-28%), respectively. Overall, 55% of the patients (30/55) had greater than grade 2 toxicity at least possibly related to suramin therapy. Two patients died of possibly related neurologic events (i.e., stroke, elevated intracranial pressure). Otherwise, toxicities were generally transient and self-limited. Administration of suramin using an intermittent fixed-dosing regimen during cranial RT was generally well tolerated. However, overall survival is not significantly improved when compared with the New Approaches to Brain Tumor Therapy GBM database or other comparable patient populations.
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PMID:Suramin and radiotherapy in newly diagnosed glioblastoma: phase 2 NABTT CNS Consortium study. 1476 35

Glioblastoma multiforme (GBM) is the most treatment-resistant glioma variant. Significant roles for telomerase in etiology, recurrence and drug resistance of GBM have been highlighted. Suramin (Bayer, Leverkusen, Germany) is an antineoplastic agent that affects many cellular mechanisms including growth factor, purinergic receptor, cytokine and key cellular enzymes signaling. The aim of this study was to investigate whether suramin, 40 mg/kg, i.p., inhibits telomerase activity in a subcutaneous C6 glioma/Wistar experimental brain tumor model using PCR based telomeric repeat amplification assay. In comparison to the control group, suramin increased tumor volume and telomerase activity. We also used transmission electron microscopy to evaluate the alterations of cell morphology. Apoptosis was seen markedly in electron micrographs of the control group and anti-apoptotic activity of telomerase was verified in the electron micrographs of suramin-applied group. The in vitro inhibitory effects of suramin on telomerase activity in several cell lines except for brain tumors have been reported. Contrary to in vitro reports, our results were the first to demonstrate that suramin increased telomerase activity in a C6 glioma/Wistar experimental brain tumor. Large numbers of drugs exhibited apparent hormetic effects on cultured cancer cells and in vivo cancer growth. Several drug examples for their hormetic effects in vivo were listed as resveratrol, suramin, and tamoxifen. The action of suramin in the present study could be evaluated as one of the hormetic examples of suramin in vivo.
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PMID:Suramin increased telomerase activity in the c6 glioma/wistar experimental brain tumor model. 2367 31


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