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 PTPN11 gene encodes SHP-2, a widely expressed cytoplasmic protein tyrosine phosphatase functioning as a signaling transducer. Germ-line PTPN11 mutations cause Noonan syndrome (NS), a developmental disorder characterized by an increased risk of malignancies. Recently, a novel class of activating mutations in PTPN11 has been documented as a somatic event in a heterogeneous group of leukemias. Because of the relatively higher prevalence of certain solid tumors in children with NS and the positive modulatory function of SHP-2 in RAS signaling, a wider role for activating PTPN11 mutations in cancer has been hypothesized. Here, we screened a number of solid tumors, including those documented in NS or in which deregulated RAS signaling occurs at significant frequency, for PTPN11 mutations. No disease-associated mutation was identified in rhabdomyosarcoma (n = 13), neuroblastoma (n = 32), melanoma (n = 50), thyroid (n = 85), and colon (n = 48) tumors; a novel missense change, promoting an increased basal phosphatase activity of SHP-2, was observed in one glioma specimen. Our data document that deregulated SHP-2 function does not represent a major molecular event in pediatric and adult tumors, further supporting our previous evidence indicating that the oncogenic role of PTPN11 mutations is cell-context specific.
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PMID:Activating PTPN11 mutations play a minor role in pediatric and adult solid tumors. 1663 68

Gefitinib (ZD1839, Iressa), a member of the 4-anilinoquinazoline class of compounds, has the chemical name 4-quinazolinamine, N-(3-chloro-4-flurophenyl)-7-methoxy-6-[3-(4-morpholinyl)propoxy]. Gefitinib often is referred to as a "specific" or "selective" inhibitor of epidermal growth factor receptor (EGFR). EGFR expression has been noted in neuroblastoma and rhabdomyosarcoma cell lines and in tumor specimens from children with Wilms tumor, osteosarcoma, and glioma. Thus, gefitinib, the first marketed EGFR tyrosine kinase inhibitor, was chosen for study in children with refractory solid tumors and central nervous system (CNS) malignancies. This review discusses findings from 3 clinical trials of gefitinib in children with refractory solid tumors and CNS malignancies, focusing on the clinical pharmacology of the compound. To date, gefitinib has been studied in children as a single agent and in combination with irinotecan. Overall, the compound has been well tolerated in children and has a safety profile similar to that observed in adults. The clinical pharmacokinetics of gefitinib in children are similar to those observed in adults. Finally, the future for the use of gefitinib in pediatrics is similar to that of other molecularly targeted agents and awaits definition of tumors and patient populations in which it will be most advantageous.
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PMID:Evaluation of gefitinib for treatment of refractory solid tumors and central nervous system malignancies in pediatric patients. 1680 60

Neurofibromatosis-1 (NF-1) is a multisystem disorder presenting with a variety of clinical and imaging manifestations. Neural and non-neural tumours, and unusual benign miscellaneous conditions, separately or combined, are encountered in variable locations. We present a 2(1/2)-year-old boy with NF-1 who demonstrated coexisting optic pathway glioma with involvement of the chiasm and optic nerve, orbital alveolar rhabdomyosarcoma and bilateral optic nerve sheath dural ectasia.
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PMID:Optic pathway glioma associated with orbital rhabdomyosarcoma and bilateral optic nerve sheath dural ectasia in a child with neurofibromatosis-1. 1694 Nov 84

Anticancer activity studies of 2-(4-fluorophenylamino)-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole (FABT), as one of the most promising derivatives from the N-substituted 2-amino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole set, have been continued. The tested compound inhibited proliferation of tumor cells derived from cancers of nervous system (medulloblastoma/rhabdosarcoma, neuroblastoma, and glioma) and peripheral cancers including colon adenocarcinoma and lung carcinoma. The anticancer effect of FABT was attributed to decreased cell division and inhibited cell migration. Furthermore, in anticancer concentrations it exerted a trophic effect in neuronal cell culture and had no influence on viability of normal cells including astrocytes, hepatocytes, and skin fibroblasts. Moreover, a prominent neuroprotective activity of FABT was observed in the neuronal cultures exposed to neurotoxic agents like serum deprivation and glutamate. To determine probability of tautomeric transition and indicate potential sites of interactions of FABT molecule with the receptor, quantum-chemical calculations with the ab initio Hartree-Fock model were made.
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PMID:Anticancer, neuroprotective activities and computational studies of 2-amino-1,3,4-thiadiazole based compound. 1735 Aug 46

Layer hens (310 days old) affected with subcutaneous tumours were investigated pathologically. Basopholic intracytoplasmic viral matrix inclusions (MIs) were widely distributed in the chickens affected with subcutaneous myxoma rhabdomyosarcoma, perineuroma, glioma, intra-abdominal adenocarcinoma, and nephroblastoma. MIs were observed in the myocardial cells and the impulse-conducting-system cells. They were also present in the smooth muscle cells of the arteries in the spleen and lungs, in the smooth muscle of the digestive tract muscular layer (crop, oesophagus, proventriculus, gizzard, duodenum, jejunum, ileum, caecum, and large intestine), and in the smooth muscle of the capsule in the ovary and pancreas. They were also observed in the podocytes of glomeruli and renal epithelium in the kidneys, tumour cells of nephroblastoma, chondrocytes of the trachea, squamous-epithelial cells of the pharynx, and nerve cells of the cerebrum and tumour cells of the glioma in the cerebellum. Histochemically, MIs were stained with RNA, but not with DNA. MIs in the various tissues were strongly positive for the avian leukosis virus (ALV) antigen. Ultrastracturally, MIs were found in the cytoplasm of myocardial cells and podocytes of renal glomeruli. They consisted of electron-dense small granules and ring-shaped particles. Viral particles were observed in the vesicles of the cytoplasm of myocardial cells and glomerular podocytes. The gene product specific for subgroup A of ALV was detected in the livers or tumours by reverse transcription-polymerase chain reaction. This result suggests that MIs can be formed in organs rather than muscular systems in the chickens naturally affected with ALV-associated tumours.
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PMID:Basophilic intracytoplasmic viral matrix inclusions distributed widely in layer hens affected with avian-leukosis-virus-associated tumours. 1736 10

The effect of the potent and selective poly(ADP-ribose) (PAR) polymerase-1 [and PAR polymerase-2] inhibitor CEP-8983 on the ability to sensitize chemoresistant glioblastoma (RG2), rhabdomyosarcoma (RH18), neuroblastoma (NB1691), and colon carcinoma (HT29) tumor cells to temozolomide- and camptothecin-induced cytotoxicity, DNA damage, and G(2)-M arrest and on the potentiation of chemotherapy-induced myelotoxicity was evaluated using in vitro assays. In addition, the effect of the prodrug CEP-9722 in combination with temozolomide and/or irinotecan on PAR accumulation and tumor growth was also determined using glioblastoma and/or colon carcinoma xenografts relative to chemotherapy alone. CEP-8983 sensitized carcinoma cells to the growth-inhibitory effects of temozolomide and/or SN38 increased the fraction of and/or lengthened duration of time tumor cells accumulated in chemotherapy-induced G(2)-M arrest and sensitized tumor cells to chemotherapy-induced DNA damage and apoptosis. A granulocyte-macrophage colony-forming unit colony formation assay showed that coincubation of CEP-8983 with temozolomide or topotecan did not potentiate chemotherapy-associated myelotoxicity. CEP-9722 (136 mg/kg) administered with temozolomide (68 mg/kg for 5 days) or irinotecan (10 mg/kg for 5 days) inhibited significantly the growth of RG2 tumors (60%) or HT29 tumors (80%) compared with temozolomide or irinotecan monotherapy, respectively. In addition, CEP-9722 showed "stand alone" antitumor efficacy in these preclinical xenografts. In vivo biochemical efficacy studies showed that CEP-9722 attenuated PAR accumulation in glioma xenografts in a dose- and time-related manner. These data indicate that CEP-8983 and its prodrug are effective chemosensitizing agents when administered in combination with select chemotherapeutic agents against chemoresistant tumors.
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PMID:The selective poly(ADP-ribose) polymerase-1(2) inhibitor, CEP-8983, increases the sensitivity of chemoresistant tumor cells to temozolomide and irinotecan but does not potentiate myelotoxicity. 1769 24

Two 2-(monohalogenophenylamino)-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles were synthesized by reaction of sulfinyl bis(2,4-dihydroxythiobenzoyl) with 4-substituted 3-thiosemicarbazides and evaluated for their antiproliferative activity in tumor cells and for cytotoxicity in normal cells. Both derivatives in micromolar concentrations elicited a prominent antiproliferative effect in tumor cells derived from cancers of the nervous system (rhabdomyosarcoma/medulloblastoma, glioma) and peripheral cancers, including breast adenocarcinoma and lung carcinoma. The anticancer effect was attributed to decreased DNA synthesis and was not connected with apoptosis induction. Both compounds were not toxic to normal human skin fibroblasts.
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PMID:Evaluation of the antiproliferative activity of 2-(monohalogenophenylamino)-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles. 1875 2

Rhabdoid tumor cells are typically observed in atypical teratoid/rhabdoid tumor (AT/RT) but may also be seen in meningioma,glioma, melanoma, rhabdomyosarcoma and metastatic carcinoma.We present an astroblastoma with unusual rhabdoid features which is rarely described in the English literature. Apart from the rhabdoid tumor cells, all the histopathological features typical for astroblastoma are present in this case. These features include pseudopapillary arrangement, astroblastic pseudorosettes, perivascular hyalinization and calcifications, absence of fibrillary background and a pushing tumor border. The tumor cells display a multilineage immunohistochemical profile. In addition, diffuse and strong membranous and cytoplasmic dot-like pattern is appreciated with epithelial membrane antigen (EMA). The diagnosis of astroblastoma is also well supported by the age of presentation, anatomical location and radiological features of the tumor.We believe that on top of the above-mentioned unusual tumors with rhabdoid cells, astroblastoma should also be considered in the list of differential diagnosis.
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PMID:A 33-year-old Chinese woman with a left frontal tumor. 1929 Oct 1

Gene expression profiling has revealed that the gene coding for cannabinoid receptor 1 (CB1) is highly up-regulated in rhabdomyosarcoma biopsies bearing the typical chromosomal translocations PAX3/FKHR or PAX7/FKHR. Because cannabinoid receptor agonists are capable of reducing proliferation and inducing apoptosis in diverse cancer cells such as glioma, breast cancer, and melanoma, we evaluated whether CB1 is a potential drug target in rhabdomyosarcoma. Our study shows that treatment with the cannabinoid receptor agonists HU210 and Delta(9)-tetrahydrocannabinol lowers the viability of translocation-positive rhabdomyosarcoma cells through the induction of apoptosis. This effect relies on inhibition of AKT signaling and induction of the stress-associated transcription factor p8 because small interfering RNA-mediated down-regulation of p8 rescued cell viability upon cannabinoid treatment. Finally, treatment of xenografts with HU210 led to a significant suppression of tumor growth in vivo. These results support the notion that cannabinoid receptor agonists could represent a novel targeted approach for treatment of translocation-positive rhabdomyosarcoma.
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PMID:Cannabinoid receptor 1 is a potential drug target for treatment of translocation-positive rhabdomyosarcoma. 1950 71

Emerging evidence suggests a role for glutamate and its receptors in the biology of cancer. This study was designed to systematically analyze the expression of ionotropic and metabotropic glutamate receptor subunits in various human cancer cell lines, compare expression levels to those in human brain tissue and, using electrophysiological techniques, explore whether cancer cells respond to glutamate receptor agonists and antagonists. Expression analysis of glutamate receptor subunits NR1-NR3B, GluR1-GluR7, KA1, KA2 and mGluR1-mGluR8 was performed by means of RT-PCR in human rhabdomyosarcoma/medulloblastoma (TE671), neuroblastoma (SK-NA-S), thyroid carcinoma (FTC 238), lung carcinoma (SK-LU-1), astrocytoma (MOGGCCM), multiple myeloma (RPMI 8226), glioma (U87-MG and U343), lung carcinoma (A549), colon adenocarcinoma (HT 29), T cell leukemia cells (Jurkat E6.1), breast carcinoma (T47D) and colon adenocarcinoma (LS180). Analysis revealed that all glutamate receptor subunits were differentially expressed in the tumor cell lines. For the majority of tumors, expression levels of NR2B, GluR4, GluR6 and KA2 were lower compared to human brain tissue. Confocal imaging revealed that selected glutamate receptor subunit proteins were expressed in tumor cells. By means of patch-clamp analysis, it was shown that A549 and TE671 cells depolarized in response to application of glutamate agonists and that this effect was reversed by glutamate receptor antagonists. This study reveals that glutamate receptor subunits are differentially expressed in human tumor cell lines at the mRNA and the protein level, and that their expression is associated with the formation of functional channels. The potential role of glutamate receptor antagonists in cancer therapy is a feasible goal to be explored in clinical trials.
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PMID:Expression of glutamate receptor subunits in human cancers. 1952 64


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