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

Meta-iodobenzylguanidine (MIBG) is an effective imaging agent for neuroblastoma and pheochromocytoma in children, MIBG is concentrated by the neurosecretory granules of normal and neoplastic tissues of neural crest origin. The typical normal scintigraphic uptake pattern of MIBG includes the salivary glands, lung, myocardium, liver, gastrointestinal tract, and contents of the urinary bladder. When MIBG is labeled with iodine-123 (123I), the adrenal glands often are seen. The sensitivity and specificity of MIBG imaging is extremely high in both neuroblastoma and pheochromocytoma. MIBG may detect extensive bone and bone marrow involvement in neuroblastoma, in the absence of findings on bone marrow aspiration and biopsy, plain radiographs, and bone scintigraphy. MIBG labeled with 131I has been used with moderate success in the palliation of advanced neuroblastoma and pheochromocytoma. Early therapeutic intervention in advanced neuroblastoma is promising. Current controversies in the application of MIBG include (1)131I versus 123I as a label for imaging studies: Although improved image quality and reduced absorbed radiation dose are achieved with [123I]MIBG imaging, is it actually more efficacious in the detection of neuroblastoma? (2) Use of bone scintigraphy in neuroblastoma: Given the small number of false-negative MIBG scans for bone involvement, can the bone scan be dropped as a routine study in the follow-up of neuroblastoma? (3) Other new imaging agents: Is there a role for labeled monoclonal antibodies, somatostatin analogs, and magnetic resonance imaging of marrow in the routine follow-up of neuroblastoma? (4) Iodine-125 MIBG therapy in neuroblastoma: Is the improved energy deposition of 125I at extremely short range useful in the ablation of micrometastases? (5) Early therapy with MIBG in neuroblastoma: Is there a role for MIBG therapy in the initial therapeutic regimens of children with advanced neuroblastoma? Twelve years after the initial report of its use in humans, MIBG has become an important imaging agent in pediatric neural tumors, one that is used routinely and efficaciously in many centers. In the next few years we will continue to learn more about its use, particularly in the therapy of advanced neural crest tumors.
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PMID:Meta-iodobenzylguanidine in children. 837 96

Bone scintigraphy with 99mtechnetium-labelled polyphosphonates is the most sensitive test for early detection of skeletal metastases. Bone metastases are a major factor in prognosis and have a considerable influence on the therapy selected. In patients with prostate cancer, we recommend routine bone scintigraphy in the initial staging. Follow-up bone scans are indicated whenever a patient develops pain, an elevated level of acid phosphatase, or a rise in prostate specific antigen (PSA). Routine bone scans are not necessary for the initial staging of patients with renal cell carcinomas, bladder carcinomas and testicular tumours. Scans should be routinely performed, however, in patients with bone pain or elevated alkaline phosphatase or when radiological findings are inconclusive. Bone scanning is necessary in patients with neuroblastoma, both for the initial diagnosis and during follow-up in all cases with known skeletal involvement. In addition, bone scintigraphy should be performed in cases of recurrent or suspected malignant phaeochromocytoma as a complement to scintigraphy with iodine-123- or iodine-131-MIBG, respectively. Even though skeletal scintigraphy is a very sensitive test, it lacks specificity. This can be compensated, however, by careful interpretation of the scan in the light of the patient's history and the clinical findings. As a positive side-effect, bone scanning--especially in the form of multiphase scintigraphy--may detect renal abnormalities, concurrent diseases or complications in the upper or lower urinary tract. If scintigraphic findings are doubtful, plain film radiographs are required or, in selected cases, bone biopsy must be performed.
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PMID:[Nuclear medicine diagnosis and therapy in urology. Diagnosis of bone metastases]. 847 16

Growth factor-dependent neurons die when they are deprived of their specific growth factor. This "programmed" cell death (PCD) requires macromolecular synthesis and is distinct from necrotic cell death. To investigate the mechanisms involved in neuronal PCD, we have studied the sequence of events that occur when a neuronal cell line (F-11: mouse neuroblastoma X rat dorsal root ganglia) is deprived of serum in a manner analogous to growth factor deprivation from neurons. Protein synthesis was inhibited within the first 8 h of serum deprivation, while DNA cleavage into nucleosome ladders was prominent by 24 h. The DNA cleavage could be inhibited by cycloheximide, consistent with a requirement for protein synthesis. In contrast, mitochondrial function was not compromised by serum deprivation. Rather, the cells appeared to be metabolically activated after serum removal as shown by an increased reduction of MTT by mitochondrial dehydrogenases and an increase in cellular autofluorescence, which is thought to be due to elevated levels of NADH and flavoproteins. Assessment of cell viability by propidium iodide staining showed no indication of cell death within 24 h. After 48 h of serum deprivation, cells decreased in size and increased propidium iodide uptake. Thus, serum deprivation activates PCD in F-11 cells and may be a useful model to study the intracellular events responsible for PCD.
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PMID:Induction of programmed cell death in a dorsal root ganglia X neuroblastoma cell line. 851 49

For more than a decade radioiodinated metaiodobenzylguanidine (mIBG) has been commonly used for neuroblastoma imaging. The accuracy of this scintigraphic method in detecting both primary and secondary tumour sites is crucial when evaluating the extent of disease. The aim of our study was to assess the impact of high-activity mIBG scintigraphy on neuroblastoma staging. Eighteen scans (TS) were obtained in 15 children after a therapeutic dose of iodine-131 mIBG and compared to diagnostic mIBG scans (DS) (in eight cases with 131I-mIBG and in ten cases with 123I-mIBG). The superiority of TS over DS was confirmed by the overall results: a total of 220 lesions were disclosed with TS and 171 with DS. However, in only one case did the TS findings, namely skeletal involvement not evidenced on corresponding DS, have an impact on clinical staging. In contrast, neither TS nor DS detected proven bone involvement in four patients. The dose-related sensitivity of mIBG scintigraphy in detecting neuroblastoma tumour sites was confirmed. The ultimate impact of high-dose scans on neuroblastoma management, however, seems limited.
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PMID:Radioiodinated metaiodobenzylguanidine in neuroblastoma: influence of high dose on tumour site detection. 854 3

Rabbit muscle cytosolic creatine kinase (MM-CK) has been treated with N-bromosuccinimide, a reagent known to oxidize selectively the indole moiety of tryptophan residues of proteins in acidic conditions. Inactivation of the enzyme is achieved by modification of one residue per monomer. NBS treatment decreases the ultraviolet absorbance at 280 nm and the intrinsic fluorescence of the protein. From these data it can be deduced that the quantum yields of the four tryptophan residues of each monomer are different due to the more or less hydrophobic environment of each of them and that at least two of them are sufficiently close to Cys 282 to allow fluorescence energy transfer to an extrinsic fluorophore bound to this residue. The accessibility to iodide of the tryptophans has been evaluated during guanidinium chloride denaturation. These data allowed us to acquire a new insight into the environment, the contribution to intrinsic fluorescence and the role in enzymatic activity and fluorescence resonance energy transfer of the tryptophan residues of CK and to tentatively assign a position in the sequence to each of them.
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PMID:Discrimination between the four tryptophan residues of MM-creatine kinase on the basis of the effect of N-bromosuccinimide on activity and spectral properties. 861 41

To date, all reported measurements of multidrug resistance have been semiquantitative. The purpose of the present study is to establish and validate the self-competitive binding assay technique utilizing monoclonal antibody for quantitative estimation of multidrug resistance in tumor cells. This technique is used for P-glycoprotein concentration measurement in BE(2)-C human neuroblastoma cell line and its sublines with primary resistance to colchicine and actinomycin D. Monoclonal antibody MRK-16 was used in this study. It was labeled with iodine-125 (125I) to trace the concentration of antibody-antigen complexes. The binding data were obtained by varying the concentration of the unlabeled antibody. The results were fitted to a model equation to estimate the number of binding sites and antibody-antigen dissociation constant. The P-glycoprotein concentration was significantly higher in the resistant sublines than in the sensitive line. The highest levels were achieved in actinomycin D-resistant cells: 2.1 x 10(6) binding sites/cell versus 5.4 x 10(4) binding sites/cell in the sensitive cells. The consistency of the results was verified by repeating the study three times for each cell line. The binding assay results were confirmed by Western blot experiments performed on the same cell lines.
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PMID:Measurement of P-glycoprotein expression in multidrug-resistant human neuroblastoma cell lines using self-competitive binding assay. 866 May 14

Iodine-labelled metaiodobenzylguanidine (MIBG) is a radiopharmaceutical used for diagnostic imaging and targeted radiotherapy of neuroendocrine tumors. We previously reported that the ability of a neuroblastoma (NB) cell line, LAN-5, to accumulate MIBG was powerfully stimulated by interferon-gamma (IFN-gamma), a well-known NB differentiation-promoting agent. To extend the above findings, we have investigated 5 NB cell lines for their ability to accumulate 125I-MIBG in basal conditions or after various combinations of differentiative stimuli. Our results show that association of IFN-gamma and tumor necrosis factor-alpha boosts MIBG uptake in the early times of incubation in LAN-5 and GI-LI-N cells, while both SK-N-SH and SK-N-BE(2)c cells are strongly stimulated by co-treatment with IFN-gamma and all-trans retinoic acid. Moreover, although only LAN-5 and GI-LI-N cells are sensitive to IFN-gamma alone, the combination of IFN-gamma and IFN-alpha causes a synergistic increase in MIBG uptake in all the NB cell lines tested. From experiments on MIBG release we conclude that no intracellular storage within specialized structures took place during differentiation. The observed enhancement in MIBG accumulation results from an increased uptake of the drug only. This conclusion was confirmed by analyzing MIBG-transporter gene expression, which was increased in cells subjected differentiative regimens. According to these findings, inducing differentiation of NB cells in vitro appears to improve their MIBG incorporation ability powerfully.
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PMID:Increase of metaiodobenzylguanidine uptake and intracellular half-life during differentiation of human neuroblastoma cells. 869 May 31

Biologically targeted radiotherapy in clinical practice requires a molecule which has a relative specificity for tumour tissue--the missile--coupled to a radionuclide with appropriate physical characteristics--the warhead. When administered to a patient this combination should result in selective irradiation of the target tumour cells with relative sparing of normal tissues. Simple ions and small molecules which follow physiological pathways as either the natural substrates or analogues form the best examples of biological targeting. Clinically valuable results are seen with, for instance, iodine uptake by normal and malignant thyroid cells, incorporation of the calci-mimetic element strontium in areas of increased bone metabolism and accumulation of the catecholamine analogue meta-iodobenzylguanidine in neuroblastoma. The use of monoclonal antibodies as targeting vehicles has not proved to be a panacea, yet some patients with lymphoma, hepatoma and ovarian carcinoma have obtained benefit. Current clinical studies in targeted radiotherapy focus on the integration of radionuclide treatment with conventional treatments, and the optimization of such combined approaches. The development of modifications to offset the limitations inherent in the use of crude antibodies also offers an opportunity for improved clinical outcomes.
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PMID:The current status of targeted radiotherapy in clinical practice. 891 69

A novel cytotoxic mechanism against neuroblastoma (NB) cells based on natural immunoglobulin M serum antibodies is described. The occurrence of these antibodies, which are able to induce complement-mediated cytolysis of NB cells, has been investigated in several age groups of healthy persons and in patients with NB. The cytotoxicity of serum samples has been measured in terms of propidium iodide DNA incorporation using a FACScan. The prevalence of anti-NB 1gM antibodies shows a strong age dependence characterized by a nearly complete lack in the first year of life and a steep rise up to 82% beginning with the second year of life. In the sera of 11 NB-bearing patients no cytotoxicity has been found, despite the fact that 8 of these patients were older than 1 year. These findings lead to the hypothesis that natural 1gM antibodies could play a role as an immunological control mechanism against NB.
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PMID:Naturally occurring humoral cytotoxicity against neuroblastoma (NB) cells in healthy persons and NB patients. 894 Jul 38

N-(4-Hydroxyphenyl)retinamide (4-HPR, Fenretinide) is a retinoid derivative with antineoplastic activity in various tumor types including prostate carcinoma. The mechanism of action of 4-HPR toxicity is unknown. 4-HPR induces apoptosis in leukemia- and lymphoma-derived cells, neuroblastoma, and small cell lung cancers. The present study was designed to investigate: (a) the mechanism of 4-HPR cytotoxicity in prostate cancer cells; and (b) correlate increased expression of transforming growth factor beta 1 (TGF beta 1) with induction of apoptosis. 4-HPR exposure to PC-3 cells in vitro was associated with apoptosis as evidenced by increased incidence of hypodiploid nuclei in propidium iodide fluorescence histograms and DNA fragmentation. An increase in the percentage of nuclei in the G1 phase of the cell cycle preceded induction of apoptosis. TGF beta 1-increased expression was noted in mRNA levels and in secretion of active TGF beta 1 into culture media. TGF beta 1 and TGF-beta receptor type II detected immunohistochemically were increased in 4-HPR-treated PC-3 cells. Furthermore, 4-HPR-induced cytotoxicity in PC-3 cells was abrogated by the addition of anti-TGF beta 1 antibody. In BT-20 cells, a 4-HPR-resistant breast carcinoma cell line, apoptosis was not observed after exposure to 4-HPR nor was TGF beta 1 expression enhanced in stained cells or in conditioned media. It is concluded that 4-HPR induces the expression of TGF beta 1 in association with the induction of apoptosis.
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PMID:Fenretinide: induction of apoptosis and endogenous transforming growth factor beta in PC-3 prostate cancer cells. 899 39


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