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)

Infectious scrapie prions are composed largely, if not entirely, of an abnormal isoform of the prion protein (PrP) designated PrPSc. In scrapie-infected mouse neuroblastoma (ScN2a) and hamster brain (ScHaB) cells, PrPSc accumulates primarily within the cell cytoplasm, whereas cellular PrP (PrPC) is anchored to the external surface of the plasma membrane by a glycoinositol phospholipid moiety. To determine the subcellular localization of PrPSc, scrapie-infected cells were grown to approximately 75% confluency, fixed briefly, and then incubated with guanidine thiocyanate before antibody staining and examination by electron microscopy. PrPSc immunoreactivity was enhanced by denaturation with guanidine isothiocyanate which also permeabilized cells (Taraboulos et al., J Cell Biol 110:2117, 1990). As judged both by deposition of immunoperoxidase reaction product (diaminobenzidine) and by presence of immunogold particles, PrPSc was identified in discrete vesicular foci and some large bodies in the cytoplasm of scrapie-infected cells. Some vesicles with PrPSc staining also contained myelin figures resembling those found in autophagic vacuoles forming secondary lysosomes. The presence of PrPSc in secondary lysosomes is inferred from colocalization of guanidine isothiocyanate enhanced PrP immunoreactivity and acid phosphatase. Neither the diaminobenzidine reaction product nor immunogold particles were observed in association with the nucleus, endoplasmic reticulum, or Golgi stacks. Exposure of scrapie-infected cells to the brefeldin A dispersed the Golgi apparatus but did not alter the morphologic distribution of PrPSc, indicating that no detectable PrPSc was associated with Golgi stacks. It remains to be established whether secondary lysosomes are involved in the post-translational formation of PrPSc.
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PMID:Ultrastructural localization of scrapie prion proteins in cytoplasmic vesicles of infected cultured cells. 168 1

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

This study aims to select the radiopharmaceutical vehicle for targeted radiotherapy of neuroblastoma which is most likely to penetrate readily the centre of micrometastases in vivo. The human neuroblastoma cell line NB1-G, grown as multicellular spheroids, provided an in vitro model for micrometastases. The radiopharmaceuticals studied were the catecholamine analogue metaiodobenzyl guanidine (mIBG), a specific neuroectodermal monoclonal antibody (UJ13A) and beta nerve growth factor (beta NGF). Following incubation of each drug with neuroblastoma spheroids, autoradiographs of frozen sections were prepared to demonstrate their relative distributions. mIBG and beta NGF were found to penetrate the centre of spheroids readily although the concentration of mIBG greatly exceeded that of beta NGF. In contrast, UJ13A was only bound peripherally. We conclude that mIBG is the best available vehicle for targeted radiotherapy of neuroblastoma cells with active uptake mechanisms for catecholamines. It is suggested that radionuclides with a shorter range of emissions than 131I may be conjugated to benzyl guanidine to constitute more effective targeting agents with potentially less toxicity to adjacent normal tissues.
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PMID:The distribution of alternative agents for targeted radiotherapy within human neuroblastoma spheroids. 200 81

The targeted radiotherapy of neuroblastoma with 131l-labelled metaiodobenzyl guanidine (mIBG) is now the subject of several clinical studies. The precise intracellular localization of mIBG, necessary for nuclear microdosimetry, has not previously been described. We report the use of electron-energy-loss spectroscopy and electron spectroscopic imaging to establish the intracellular distribution of mIBG in cells from the human neuroblastoma line NBI-G which had been incubated with the drug by mapping iodine in ultra-thin sections of tumours. Most of the iodine is found within the mitochondria, with lesser amounts in the vesicles and on the nuclear membrane. The use of alternative radionuclides with different physical characteristics has been suggested to optimize the efficacy of this therapeutic strategy. The lack of penetration of mIBG into the nucleoplasm means that ultra-short-range Auger electron emitters such as 125I are not likely to prove more cytotoxic than 131I.
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PMID:Intracellular localization of metaiodobenzyl guanidine in human neuroblastoma cells by electron spectroscopic imaging. 201 Feb 30

Computed tomography (CT) and 123I- or 131I-meta-iodo-benzyl-guanidine (MIBG) scintigraphy were compared for accuracy in tumor detection in 47 patients with neuroectodermal neoplasms. MIBG concentration was found in 12 of 13 pheochromocytomas, 12 of 12 neuroblastomas, 5 of 9 carcinoids, and 1 of 4 glomus tumors. MIBG uptake was not observed in medullary thyroid carcinomas, oat-cell carcinomas, Merkel tumors, 1 gastrinoma, and 2 unclassified neuroectodermal neoplasms. With regard to the different tumor manifestations, the sensitivity in detecting pheochromocytomas, neuroblastomas, and carcinoids was 87%, 77%, and 100% for CT, and 83%, 100% and 71% for MIBG scintigraphy, MIBG scintiscan was superior in the detection of small adrenal pheochromocytomas (less than 1 cm diameter) and in the depiction of small bone metastases and bone marrow infiltration from neuroblastoma. In all, 25 cycles of high-dose MIBG therapy were performed in eight patients with surgically incurable tumors (4 malignant pheochromocytomas, 1 neuroblastoma, 3 carcinoids). The total therapeutic activity applied was 3.55-43.29 GBq 131I-MIBG. Tumor kinetics of MIBG were investigated before and during treatment. One patient with metastatic pheochromocytoma has been in complete remission for a follow-up period of 36 months since completion of treatment, and another patient is in partial remission. Tumor reduction or no change was observed in four patients. Two patients died of non-concentrating recurrence and metastases.
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PMID:[Diagnosis and therapy of neuroectodermal tumors]. 253 1

While 131I-meta-iodobenzyl guanidine (131I-MIBG) scanning has made possible the scintigraphic visualization of pheochromocytoma and neuroblastoma, an accumulation of this agent has recently been reported in medullary thyroid cancer. We present the case of a patient with Sipple's syndrome (multiple endocrine neoplasia type IIa), in whom we were able to identify distant metastases and local invasion of medullary thyroid cancer as well as primary thyroid tumour and right adrenal pheochromocytoma, using 131I-MIBG scans. This case highlights the usefulness of 131I-MIBG in the detection of metastatic medullary thyroid cancer and suggests that this agent may also be of therapeutic use in the treatment of tumours.
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PMID:Detection of metastatic medullary thyroid cancer with 131I-MIBG scans in Sipple's syndrome. 287 28

Tissue culture substratum adhesion sites from EGTA-detached Platt human neuroblastoma cells were extracted with a buffer containing ocytlglucoside, NaCl, guanidine hydrochloride, and a variety of protease inhibitors, an extraction which resulted in quantitative solubilization of the 35SO4 = -radiolabeled proteoglycans and 3H-leucine-radiolabeled proteins. Of the sulfate-radiolabeled material, the vast majority was heparan sulfate proteoglycan (Kav = 0.15 on Sepharose C14B columns) and the remainder was chondroitin sulfate chains (no single chains of heparan sulfate were observed). This extract was then fractionated on DEAE-Sephadex columns under two different buffer elution conditions. Under DEAE-I conditions in low ionic strength acetate buffer, two major peaks of 35SO4 = -radiolabeled material (A,B) and a minor peak (C) could be resolved in the NaCl gradient; however, three-fourths of the material required 4 M guanidine hydrochloride to elute it from the column (peak D). Under DEAE-II conditions in acetate buffer supplemented with 8 M urea, the vast majority of the proteoglycan material could be eluted in the NaCl gradient as peak AB. Peak D material was shown to contain aggregated proteoglycan, along with nonproteoglycan protein, which high concentrations of urea or guanidine could dissociate, but not nonionic or zwitterionic detergents. Three different affinity chromatography systems were used to further characterize these components. Approximately 60% of peak A heparan sulfate proteoglycan from DEAE-I binds to the hydrophobic matrix, octyl-Sepharose, while 80% of the proteoglycan in DEAE-I peak D binds to this hydrophobic column. A sizable fraction of peak A proteoglycan fails to bind to plasma fibronectin but does bind to platelet factor-4 affinity columns. In contrast, peak AB proteoglycan from DEAE-II columns yields a much higher proportion of molecules which do bind to fibronectin. To examine the basis for these differences in affinity binding, nonproteoglycan protein from these adhesion sites was mixed with peak AB proteoglycan prior to affinity chromatography; proteoglycan binding to fibronectin decreased markedly while binding to platelet factor-4 was unaffected. This modulating activity involves the binding of nonproteoglycan protein in adhesion site extracts to both fibronectin on the column, as well as to heparan sulfate proteoglycan itself, and it could not be mimicked by a number of known proteins in adhesion site extracts or several other proteins. These results demonstrate selectivity and specificity in this modulation and indicate that a previously unidentified protein(s) is responsible.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Heparan sulfate proteoglycans in the substratum adhesion sites of human neuroblastoma cells: modulation of affinity binding to fibronectin. 296 1

In vitro studies of tumor tissue have shown that 131I-IBG is specifically bound to the plasma membrane-enriched fraction of two neuroblastoma cell lines (NA-2 and C-1300). NB C-1300 showed a slightly higher binding capacity than NB NA-2. It may be inferred from experiments performed with activators of the adrenergic and dopaminergic systems that binding of IBG to proteins on the plasma membrane which is physiologically important for binding of this guanidine derivative, is probable.
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PMID:[Detection of the binding of 131I-meta-iodobenzylguanidine to structures of the plasma membranes of neuroblastoma cell lines]. 340 81

It was recently reported (Endoh et al. 1981, Exp Cell Biol 49:272-277) that conditioned medium of neonatal mouse brain (CM-NB) inhibited the growth of mouse neuroblastoma cells. In this work we fractionated CM-NB by size exclusion high performance liquid chromatography, and separated two active principles (28,000 and 62,000 daltons) Each or a combination of the 28,000 and 62,000 dalton fractions showed a differential inhibitory effect on DNA synthesis or clonal growth of the three human lung cell lines: the normal diploid fibroblast WI38 cells were less susceptible than their simian virus 40-transformed VA13 cells and carcinoma A549 cells. This preferential growth-inhibition of malignant cells was also observed for rat fibroblast 3Y1 and its simian virus 40-transformed W3Y cells, and for two other normal and five other malignant cell lines. The growth-inhibitory activity of CM-NB or the 28,000 and 62,000 dalton fractions was lost by pronase, trypsin, tetrahydrofuran, acetonitrile, or dithiothreitol in the presence of guanidine, and also labile to heat, vigorous agitation, or freeze-thawing. The activity was also found in the conditioned medium of prenatal mouse brain, but not in either the conditioned medium of the adult brain and of the secondary culture of the neonatal brain, or in the homogenate and rinsing fluid of the neonatal brain. Thus the mouse brain at the terminal stage of ontogenesis liberates proteinaceous factors, which exhibit a preferential growth-inhibition of tumor or transformed cells and act on malignant cells of human and rodent origin.
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PMID:Inhibition of tumor cell growth by protein factors derived from the developing mouse brain. 407 18

Adrenal scintigraphy using 131I-6-beta-iodomethyl-19-norcholesterol or 6-methyl-75Se-methyl-19-norcholesterol is a function-dependent imaging method which, in association with high-resolution spatial imaging techniques, plays an essential role in the study of adrenocortical hyperfunction. It can distinguish between bilateral cortical hyperplasia and monolateral adenoma or carcinoma and can lateralise the adenoma. In patients with Cushing syndrome, in addition to allowing a distinction to be made between ACTH-dependent forms and independent forms, adrenocortical scintigraphy is particularly appropriate to identify non-common forms of adenomatous hyperplasia. Adrenocortical scintigraphy, performed during dexamethasone administration, is an accurate mean of differentiating bilateral adrenal hyperplasia from monolateral forms (adenoma or carcinoma) in patients with Conn's syndrome. Owing to the gradual spread of high-resolution spatial imaging techniques, the problem of the diagnostic classification of so-called "incidentalomas" (clinically silent masses discovered by chance) is a subject of considerable interest. Adreno-cortical scintigraphy appears to be able to provide an important contribution to identifying the functional behaviour of these tumours. Since the early 80s meta-iodobenzyl-guanidine (MIBG), marked with 131I or 123I, with a structure similar to norepinephrine and characterized by selective tropism for sympathetic and chromaffin tissue, has been used for the scintigraphic study of adrenal medulla. MIBG scintigraphy has been found to be particularly appropriate for the study of intra- and extra-adrenal, single and multiple, benign and malignant pheochromocytomas. This method has a high overall sensitivity and specificity. Lastly, MIBG scintigraphy is useful in the study of neuroblastoma.
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PMID:[Nuclear medicine methods for the diagnosis of adrenal tumors]. 765 Dec 80


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