Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Iodine ions exhibited the thyroxin-like effect on incorporation of 1-14C-leucine into proteins of isolated mitochondria and microsomes of thyroidectomized rats in vitro. Thyroxin, triiodothyronine (T3) and ICl increased the incorporation of 1-14C-leucine into proteins of isolated mitochondria of thyroidectomized rats, but did not affect the protein synthesis in microsomes in vitro. Rifampycin and olivomycin abolished completely the stimulating effect of T3 and ICl on incorporation of the label into mitochondrial proteins. The thyroid hormones and iodine ions stimulated protein synthesis in vitro in liver microsomes of thyroidectomized animals only after preincubation with mitochondria or nuclei. In these conditions preincubation with mitochondria elevated the rate of 1-14C-leucine incorporation into microsomal proteins 2--2.5-fold. In similar experiments with nuclei--4--4.8-fold stimulation was detected. Thyroid hormones and iodine ions stimulated synthesis of specific factors in mitochondria (MBS) and in nuclei (NBS) of thyroidectomized rat liver tissue, which increased the protein synthesis in isolated microsomes in vitro. Synthesis of MBS- and NBS-factor required the presence of all the four ribosetriphosphates (ATP, GTP, UTP, CTP) and was inhibited completely by olivomycin; rifampycin blocked only the MBS factor synthesis. NBS- and MBS-factors appear to be RNA (mRNA), synthesized in nuclei and mitochondria, which are transported into the incubation media and translated by ribosomes.
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PMID:[Effect of triiodothyronine and ICl on protein synthesis in cell-free systems]. 42 69

Iodine-labeled m-iodobenzylguanidine (MIBG) is a widely used radiopharmaceutical for both diagnosis and biologically targeted radiotherapy of neuroblastoma. However, resistance to the radiotherapeutic effects of MIBG is often encountered, mainly due to lack of MIBG accumulation by neoplastic cells. We have investigated whether the induction of neuroblastoma cell differentiation modifies MIBG incorporation and retention. LAN-5 cells were selected, due to their moderate ability to take up MIBG. Treatment of these cells with gamma-interferon (IFN-gamma) resulted in morphological changes accompanied by a significant increase in overall cell-associated MIBG. Desimipramine, but not reserpine, easily depleted IFN-gamma-treated LAN-5 cells of their MIBG content. This suggests that the mechanism involved is an uptake enhancement rather than an improved storage ability. Indeed, IFN-gamma induces de nov synthesis of MIBG receptor-transporters, as demonstrated by polymerase chain reaction amplification and semiquantitative analysis. Our results suggest that pretreating neuroblastoma patients with IFN-gamma before MIBG administration may enhance the efficacy of both biologically targeted radioimaging and therapy of this tumor.
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PMID:gamma-Interferon increases metaiodobenzylguanidine incorporation and retention in human neuroblastoma cells. 132 88

Whole-cell patch-clamp recordings were used to investigate nicotinic acetylcholine receptors (nAChRs) in the human neuroblastoma cell line, SH-SY5Y. Acetylcholine, nicotine and the neuronal nAChR agonist dimethylphenylpiperazinium iodide (DMPP), but not muscarine, all evoked inward currents in the cells (voltage-clamped at -60 mV). DMPP's actions were concentration- and voltage-dependent, and were antagonised by the neuronal nAChR antagonist mecamylamine (1-3 microM). Atropine was ineffective at 0.1 microM, but at 1 microM caused significant reductions in current amplitudes. Pre-incubation of cells with 2 microM alpha-cobratoxin had no effect on the actions of DMPP, and inward currents could also be induced when extracellular NaCl was replaced with CaCl2. DMPP also reversibly depolarized SH-SY5Y cells. These findings clearly identify nAChRs in SH-SY5Y cells, and provide two possible mechanisms by which receptor activation may lead to noradrenaline release, namely by triggering Ca2+ influx through the nAChR itself or by opening voltage-gated Ca2+ channels.
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PMID:Nicotinic acetylcholine receptors in human neuroblastoma (SH-SY5Y) cells. 146 17

The 5-hydroxytryptamine (5-HT)3 receptor blocking properties of YM060, [(R)-5-[(1-methyl-3-indolyl)carbonyl]-4,5,6,7-tetrahydro-1H- benzimidazole hydrochloride], were examined by electrophysiological and radioligand binding studies. Results were compared with those for ondansetron, granisetron and the enantiomer (S-form) of YM060. 5-HT and 2-methyl-5-HT, a selective 5-HT3 receptor agonist, induced dose-dependent depolarizations of rabbit nodose ganglion with ED50 values of 24.0 (19.9-29.1) and 40.1 (30.9-52.1) nmol, respectively (geometric mean, 95% CL). YM060, ondansetron, granisetron and the S-form dose-dependently inhibited 5-HT-induced depolarizations with IC50 values of 3.85 (2.47-5.98), 1.55 (1.26-1.91), 1.45 (1.18-1.79) and 13.5 (11.2-16.2) nM, respectively. Methysergide, a 5-HT1-like and 5-HT2 receptor antagonist, at a concentration of 10(-5) M had no effect on responses to 5-HT. YM060 up to 10(-5) M produced no significant depression of depolarizing responses to 1,1-dimethyl-4-phenylpiperazinium iodide and gamma-aminobutyric acid. YM060, ondansetron, granisetron and the S-form displaced specific binding of [3H]GR65630 to N1E-115 neuroblastoma cell membranes with Ki values of 0.091 (0.086-0.097), 7.03 (5.96-8.01), 2.02 (1.74-2.30) and 10.3 (9.96-10.6) nM, respectively. These results show that YM060, compared with ondansetron and granisetron, has considerably higher affinity for 5-HT3 receptors in N1E-115 cells and slightly less potent 5-HT3 receptor antagonistic activity in rabbit nodose ganglion. Moreover, the isomeric activity ratio (R-form/S-form) was approximately 112 in N1E-115 cells and no greater than 4 in the ganglion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of YM060, a potent and selective 5-hydroxytryptamine3 receptor antagonist, in rabbit nodose ganglion and N1E-115 neuroblastoma cells. 146 24

Iodine-131 metaiodobenzylguanidine (MIBG) has shown effectiveness as a systemic radiotherapeutic agent in neuroblastoma. The authors postulated a likely dose-related relationship of MIBG sensitivity when it was administered for neuroblastoma detection. They studied this relationship in neuroblastoma patients who underwent scanning after receiving diagnostic and therapeutic doses of MIBG in temporal proximity. Seven patients with stage IV disease received a total of 14 therapeutic administrations of I-131 MIBG (150-350 mCi [5,550-12,950 MBq]/m2 per treatment). Posttherapy scans were obtained at 3 and at 5-7 days. Diagnostic MIBG scans had been obtained no more than 4 weeks before the start of therapy. Use of diagnostic MIBG scanning led to underestimation of the tumor burden by 50% compared with use of posttherapy scanning. This difference may be an important consideration in selecting therapeutic strategies for individual patients. It further suggests that use of much larger diagnostic doses of MIBG is a rational strategy in histologically confirmed cases of advanced disease.
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PMID:Neuroblastoma: dose-related sensitivity of MIBG scanning in detection. 162 Aug 49

Thirty-one children with stage III and IV neuroblastoma were studied with iodine-131 metaiodobenzyl-guanidine (MIBG) scintigraphy, technetium-99m medronate scintigraphy, skeletal plain radiography, and computed tomography (CT) before and after bone marrow transplantation (BMT). Twenty-six pre-BMT and 90 post-BMT studies were reviewed. Fourteen patients were alive without tumor, and one patient died at 4 months while free of tumor. I-131 MIBG scans obtained before and after BMT were negative in eight of the 15 patients. Seven had positive I-131 MIBG scans obtained before BMT that became negative after BMT. Six of 15 patients had small, questionable lesions on CT scans of the chest or abdomen that never increased in size, and the I-131 MIBG scans remained negative. Sixteen children had progressive disease or relapse, including four in whom I-131 MIBG scans showed new abnormalities, four with persistently positive I-131 MIBG scans, and three who had negative I-131 MIBG scans at relapse. Two of the 16 patients initially had small lesions seen on abdominal CT scans that were not seen on I-131 MIBG scans; mass lesions were later seen at CT in these locations. Detectable I-131 MIBG uptake in abdominal and thoracic lesions was related to the diameter of the lesion. Both I-131 MIBG scintigraphy and CT should be used to evaluate patients with neuroblastoma who have undergone BMT.
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PMID:I-131 MIBG imaging after bone marrow transplantation for neuroblastoma. 173 72

Among children with advanced neuroblastoma, serum concentrations of the iron storage protein ferritin correlate inversely with prognosis. To determine whether ferritin stimulates tumor cell growth, the effects of graded concentrations on cell number were studied for each of three neuroblastoma cell lines (CHP-126, CHP-100, IMR-32) plated in serum-free tissue culture medium. Ferritin extracted from human liver, spleen, or CHP-126 cells (150 ng/ml, final concentration) but not from human heart (150-300 ng/ml) resulted in 1.4-fold +/- 0.2-fold increases in cell numbers over 72 hours as measured spectrophotometrically after reduction of a tetrazolium dye. Higher concentrations of isoferritins (up to 1000 ng/ml) did not further increase cell number, but stimulation was abrogated by rabbit immunoglobulin G antiferritin. Although specific receptors for iodine 125-labeled ferritin could not be demonstrated on the two cell lines tested, deoxyribonucleic acid (DNA) synthesis, measured by incorporation of 3H-thymidine, also increased after addition of ferritin, by approximately 25%. We conclude that ferritin has mitogenic activity for human neuroblastoma cells in vitro which may explain the clinical correlation between levels of that protein and prognosis. Possible implications for therapy are discussed.
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PMID:Stimulation of growth of neuroblastoma cells by ferritin in vitro. 174 Jun 26

The modalities of uptake and storage of iodine-labeled m-iodobenzylguanidine (MIBG) by four human neuroblastoma cell lines have been studied. SK-N-BE(2)C cell line has been shown to possess the specific (type 1) MIBG uptake, as well as an efficient extravesicular storage mechanism. Conversely, LAN-5 cells, which show a nonsaturation kinetic of MIBG incorporation, lack only the ability to efficiently store the MIBG taken up by a mechanism that can be pharmacologically defined as uptake 1. The two other neuroblastoma cell lines tested, GI-LI-N and GI-CA-N, lack both uptake and storage capacity. In view of the fact that the only detailed study on specific MIBG uptake by a human neuroblastoma cell line has been carried out on SK-N-SH, a highly heterogeneous cell line, our report provides new insights on the molecular and cellular pharmacology of radiolabeled MIBG.
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PMID:Accumulation of m-iodobenzylguanidine by neuroblastoma cells results from independent uptake and storage mechanisms. 186 58

Positron emission tomography (PET) is potentially useful for the quantitative imaging of radiolabeled antibodies, leading in turn to improved dosimetry in radioimmunotherapy. Iodine-124 is a positron-emitting nuclide with appropriate chemical properties and half-life (4.2 days) for such studies since the radiolabeling of antibodies with iodine is well understood and the half-life permits measurements over several days. Unfortunately, I-124 has a complex decay scheme with many high-energy gamma rays and a positron abundance of only 25%. It has therefore been largely ignored as a PET-imaging nuclide. However, measurements made with phantoms and animals under realistic conditions using a BGO-based PET scanner have shown that satisfactory imaging and quantitation can be achieved. Investigations of spatial resolution, the linearity of regional observed count rate versus activity in the presence of other activity, and the visualization and quantitation of activity in spheres with different surrounding background activities were carried out with phantoms up to 22 cm in diameter. Compared with F-18, spatial resolution was only slightly degraded (13.5 mm FWHM vs 12 mm FWHM) while linearity was the same over a 10:1 activity range (0.015 to 0.15 MBq/ml for I-124). The visualization and quantitation of spheres was also slightly degraded when using similar imaging times. Increasing the imaging time for I-124 reduced the difference. To verify that the technique would work in vivo, measurements were made of human neuroblastoma tumors in rats which had been injected with I-124 labeled 3F8 antibody. Although the number of samples was small, good agreement was achieved between image-based measurements and direct measurements of excised 4-g tumors. Thus quantitative imaging of I-124 labeled antibodies appears to be possible under realistic conditions.
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PMID:Quantitative imaging of I-124 using positron emission tomography with applications to radioimmunodiagnosis and radioimmunotherapy. 187 Apr 76

A method was developed for the determination of tin in human serum by radiochemical neutron activation analysis, using the long-lived radioisotope Sn(T1/2 = 115.09 days). This radioisotope decays to a daughter isotope 113mIn, the most suitable nuclide for counting (T1/2 = 1.658 h, gamma-ray of 391.7 keV). Experience showed that, with the exception of the serum samples with the lowest tin levels, in the experimental conditions of the present study tin could mostly also be determined by using its radioisotope 117mSn(T1/2 = 13.61 days, gamma-ray of 158.5 keV). Samples were collected and prepared by using the procedure elaborated by the authors, which proved its effectiveness in preventing significant sample contamination on several occasions. Because samples had to be irradiated at 10(14) n.cm-2.s-1, dry ashing was necessary. After irradiation, tin was separated by solvent extraction of tin(IV) iodide from a sulfuric acid-ammonium iodide solution with toluene. The dry ashing and solvent extraction steps were exhaustively tested by means of radioactive tracer experiments whereas the accuracy and precision of the analytical method were thoroughly checked by analyzing biological reference materials (Bowen's kale powder, the NBS' bovine liver, the NBS' nonfat milk powder, and the "second-generation" biological reference material--freeze-dried human serum--for trace element determinations, developed by the authors).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Determination of tin in human blood serum by radiochemical neutron activation analysis. 188 71


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