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)

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

Glioblastoma multiforme (GBM) is the most common form of malignant glioma, characterized by genetic instability, intratumoral histopathological variability, and unpredictable clinical behavior. Malignant gliomas express preferentially a number of surface markers that may be exploited as therapeutic targets, such as tenascin-C, an extracellular matrix glycoprotein contributes to tumor cell adhesion, invasion, migration and proliferation. Disappointing results in the treatment of gliomas with surgery, radiation and chemotherapy have fuelled a search for new treatment modalities. Here we present the data for 46 patients suffering from brain tumor. They were resected and treated with dsRNA (ATN-RNA) complementary to the sequence of tenascin-C mRNA. MRI and CT follow up studies showed growth tumor delay or lack of its recurrence symptoms, due to inhibition of TN-C synthesis. A significant improvement in overall survival (OS) was observed without loosing of the quality of life (QOL) of patients. This novel therapy based on RNA interference shows a big therapeutical potential. To our knowledge intervention with RNAi (iRNAi) is the first protocol of application of RNAi in human disease treatment.
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PMID:A multivariate analysis of patients with brain tumors treated with ATN-RNA. 1917 48

Malignant gliomas are the deadliest brain tumors, which are characterized by highly invasive growth, a rampant genetic instability and intense resistance to apoptosis. Such an aggressive behavior of malignant gliomas is reflected in the resistance to chemo- and radiotherapy and weak prognosis in spite of cytoreduction through surgery. Brain tumors preferentially express a number of specific protein and RNA markers, that may be exploited as potential therapeutic targets in design of the new treatment modalities based on nucleic acids. For almost three decades, a possibility to apply DNA and RNA molecules as anticancer therapeutics have been studied. A variety of antisense oligonucleotides, ribozymes, DNAzymes, and aptamers can be designed to trigger the sequence-specific inhibition of particular mRNA of interest. RNA interference (RNAi) is the latest and the most promising technique in the long line of nucleic acid-based therapeutic technologies. Recently, we designed and implemented the experimental therapy of patients suffering from malignant brain tumors based on application of double-stranded RNA (dsRNA) specific for tenascin-C (TN-C) mRNA. That therapeutic agent, called ATN-RNA, induces RNAi pathway to inhibit the synthesis of TN-C, the extracellular matrix protein which is highly overexpressed in brain tumor tissue. In the chapter specific problems of application of nucleic acid-based technologies in glioma tumors treatment will be discussed.
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PMID:Nucleic acid-based technologies in therapy of malignant gliomas. 2190 32