Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Semipermeable silastic rubber membranes can be used to diffuse focally a variety of chemicals including antitumour drugs. Of the eight drugs tested, in vitro tests showed the best diffusion with dactinomycin, mithramycin, and oncovin, and the poorest diffusion with bleomycin, fluorouracil, and thiotepa. Biological testing was performed with mithramycin, dactinomycin, and oncovin using tissue cultures of human glioblastoma and subcutaneous implants of mouse ependymoblastoma. All three drugs caused rapid tissue culture cell death with direct injection, and impeded tumour growth when given intraperitoneally. Dactinomycin by silastic diffusion proved more effective than mithramycin against tissue cultures, but neither drug had a significant effect against local tumours treated with implanted drug capsules. Silastic diffusion of oncovin reduced tumour sizes significantly ipsilateral to the implant, compared to contralateral implants and to untreated controls.
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PMID:Focal chemotherapy of brain tumours using semipermeable membranes. 6 17

The TRAIL death receptor KILLER/DR5 is induced by DNA damaging agents in wild-type p53-expressing cells. Here we show that, unlike the p53-target CDK-inhibitor p21WAF1/CIP1, the TRAIL death receptor KILLER/DR5 is only induced in cells undergoing p53-dependent apoptosis and not cell cycle arrest. Thus GM glioblastoma cells carrying an inducible MMTV-driven p53 gene undergo cell cycle arrest and upregulate p21 but not KILLER/DR5 expression upon dexamethasone exposure. WI38 normal lung fibroblasts undergoing cell cycle arrest in response to ionizing irradiation also induce p21 but not KILLER/DR5 gene expression. KILLER/DR5 upregulation is also deficient in irradiated lymphoblastoid cells derived from patients with Ataxia Teleangiectasia suggesting a role for the ATM-p53 pathway in regulating KILLER/DR5 expression after DNA damage. Inhibition of transcription by Actinomycin D blocks both KILLER/DR5 and p21 induction in cells undergoing p53-dependent apoptosis. Our results suggest that the p53-dependent transcriptional induction of KILLER/DR5 death receptor is restricted to cells undergoing apoptosis and not cells undergoing exclusively p53-dependent G1 arrest.
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PMID:Induction of the TRAIL receptor KILLER/DR5 in p53-dependent apoptosis but not growth arrest. 1059 42

Vascular endothelial growth factor (VEGF) is a key mediator of tumor angiogenesis. Interferons (IFNs) have been widely used in the treatment of malignant or recurrent gliomas with only marginal benefit. The association between IFNs and VEGF expression remains unclear and should be an intensively investigated subject. The present study therefore examined the effects of different types of IFNs on VEGF expression in human T98G, A172 and U251 glioblastoma cells by quantitative RT-PCR and ELISA. Both type I (alpha, beta) and type II (gamma) IFNs upregulated VEGF expression in a cell-specific but p53-independent manner. Actinomycin D experiments demonstrated that IFNs did not alter VEGF mRNA stability. In contrast, induction of VEGF mRNA by IFNs was blocked by the protein synthesis inhibitor cycloheximide. Interestingly, cycloheximide also blocked IFN-induced activation of the p44/p42 mitogen-activated protein kinase, which was partially required for induction of VEGF by IFNs. These findings suggest that VEGF might be an indirect target gene of IFNs, and might provide insights into therapeutic applications of IFNs against angiogenesis-dependent tumors.
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PMID:Cell-specific but p53-independent regulation of vascular endothelial growth factor expression by interferons in human glioblastoma cells. 1628 38

Despite progress in conventional treatment for glioblastoma (GBM), the prognosis remains poor due to high tumor recurrence. Therefore, identification of new molecular mechanisms is a pressing need for betterment of GBM patient outcomes. qRT-PCR was used to determine BDNF-AS expression in GBM cells. CCK-8, EdU incorporation, and caspase-3 activity assays were employed to analyze biological functions of BDNF-AS. RIP and RNA pull-down were conducted to detect the interactions among BDNF-AS, ADAR, and p53. Actinomycin D was utilized to examine the stability of p53 mRNA. ChIP and luciferase reporter assays were performed to detect transcriptional activation of BDNF-AS by p53. We found that BDNF-AS was significantly downregulated in GBM cell lines, and its overexpression inhibited GBM cell growth, and promoted apoptosis. Importantly, we illustrated that BDNF-AS coupled with ADAR protein to potentiate stability of p53 mRNA and thus upregulate p53. Interestingly, we further identified p53 as a transcription factor of BDNF-AS, activating transcription of BNDF-AS. This study firstly demonstrated that BDNF-AS acted as a tumor suppressor in GBM and the positive feedback circuit of BDNF-AS/ADAR/p53 served an important mechanism to control GBM proliferation. Targeting this auto-regulatory loop may provide a potential therapeutic strategy for GBM patients.
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PMID:Activation of BDNF-AS/ADAR/p53 Positive Feedback Loop Inhibits Glioblastoma Cell Proliferation. 3193 89