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

Five radiotracers may be used for single-photon emission computed tomography (SPECT) imaging of brain tumors, namely technetium 99m pertechnetate, iodine-123 amphetamine derivatives, 99mTc-hexamethyl propylene amine oxime (HMPAO), thallium 201, and 123I alpha methyl tyrosine. Of these, pertechnetate may be considered as an "historical" procedure in brain tumors. However, there may be some equivocal cases in computed tomography or magnetic resonance imaging, where this procedure may still be used. In 1981, 123I isopropyl amphetamine was first used in brain tumors. Further studies showed, however, that IMP is not a useful tool for brain imaging in tumorous lesions. In 1986, 99mTc HMPAO appeared on the European market as a new tumor imaging agent. Some useful clinical results were obtained in patients before and after chemotherapy or radiotherapy. Thallium-201 was incidentally noted to accumulate in tumors. Using a threshold index, this agent can be used to distinguish low-versus high-grade lesions. The most promising agent for brain tumor SPECT is 123I-alpha methyl tyrosine, which shows potential to evaluate therapeutic procedures in brain tumors and may improve the differentiation between abscess and glioblastoma. The most promising aspect is the differentiation of tumor recurrences and scar tissue after brain surgery.
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PMID:Single photon emission computed tomography imaging of brain tumors. 199 25

The aim of this study was to identify targets for rational chemotherapy of glioblastoma. In order to elucidate differences in the biochemistry of tumor and normal human brain, in vivo pool sizes of purine nucleotides, nucleosides, and nucleobases and of purine metabolizing enzymes in biopsy material from 14 grade IV astrocytomas and 4 normal temporal lobe samples were analyzed. Specimens were collected during surgery using the freeze-clamp sampling technique and analyzed by high pressure liquid chromatography. Total purine nucleotides, adenylates, and guanylates in the tumors were 2186, 1865, and 310 nmol/g (wet weight), respectively, which corresponds to 61, 60, and 71% of normal brain tissue concentrations. Relative to normal brain the tumors had significantly lower ATP and GTP levels, essentially normal pool sizes of purine nucleosides and bases, unchanged activities of the salvage enzymes hypoxanthine-guanine phosphoribosyltransferase, adenine phosphoribosyltransferase, and adenosine kinase (659, 456, and 98 nmol/h/mg protein, respectively) and 4-fold higher activities of IMP dehydrogenase (11.6 nmol/h/mg protein); the latter is the rate limiting enzyme for guanylate de novo synthesis. IMP pools in the tumors were 64% of values in normal brain. Modulation of the guanylate pathway in glioblastoma by inhibition of IMP dehydrogenase with tumor specific agents such as tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide) appears to be a rational therapeutic approach. Preliminary in vitro experiments with normal and malignant tissue specimens from 2 additional patients revealed that significant amounts of the active metabolite thiazole-4-carboxamide adenine dinucleotide are formed from tiazofurin. At a concentration of 200 microM this drug was able to deplete guanylate pools in the tumors to a median of 54% of phosphate buffered saline treated controls. Flux studies with [14C]formate showed that tiazofurin strongly inhibited de novo synthesis of guanylates in glioblastoma to an average of 10% of controls. This effect was more pronounced in the tumors as compared to normal brain. No inhibition of salvage of [14C]guanine by tiazofurin could be observed in normal and malignant tissues. Supportive measures have to be considered to inhibit the highly active salvage enzyme hypoxanthine-guanine phosphoribosyltransferase that can partly antagonize a tiazofurin induced decrease in guanine nucleotides.
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PMID:Purine metabolism of human glioblastoma in vivo. 215 28

Ten patients with unusual uptake and retention of I-123 IMP in their brain tumors were studied. Of these ten patients, five had meningiomas and the remaining five had glioblastoma, malignant astrocytoma, malignant lymphoma, metastatic brain tumor, and cellular blue nevus. Six tumors (five meningiomas and the glioblastoma) showed short term retention of I-123 IMP. Three tumors (the malignant astrocytoma, the malignant lymphoma, and the metastatic brain tumor) showed a delayed increase of radioactivity and the cellular blue nevus showed a gradual increase and long term retention of the tracer.
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PMID:Unusual uptake and retention of I-123 IMP in brain tumors. 326 44

IMP preferring cytosolic 5'-nucleotidase (cN-II) is an ubiquitous nucleotide hydrolysing enzyme. The enzyme is widely distributed and its amino acid sequence is highly conserved among vertebrates. Fluctuations of cN-II activity have been associated with the pathogenesis of neurological disorders. The enzyme appears to be involved in the regulation of the intracellular availability of the purine precursor IMP and also of GMP and AMP, but the contribution of this activity and of its regulation to cell metabolism and to CNS cell functions remains uncertain. To address this issue, we used a vector based short hairpin RNA (shRNA) strategy to knockdown cN-II activity in human astrocytoma cells. Our results demonstrated that 53 h after transduction, cN-II mRNA was reduced to 17.9+/-0.03% of control cells. 19 h later enzyme activity was decreased from 0.7+/-0.026 mU/mg in control ADF cells to 0.45+/-0.046 mU/mg, while cell viability (evaluated by the MTT reduction assay) decreased up to 0.59+/-0.01 (fold vs control) and caspase 3 activity increased from 136+/-5.8 pmol min(-1) mg(-1) in control cells to 639+/-37.5 pmol min(-1) mg(-1) in silenced cells, thus demonstrating that cN-II is essential for cell survival. The decrease of enzyme activity causes apoptosis of the cultured cells without altering intracellular nucleotide and nucleoside concentration or energy charge. Since cN-II is highly expressed in tumour cells, our finding offers a new possible therapeutical approach especially against primary brain tumours such as glioblastoma, and to ameliorate chemotherapy against leukemia.
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PMID:Knockdown of cytosolic 5'-nucleotidase II (cN-II) reveals that its activity is essential for survival in astrocytoma cells. 1844 85