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)

Radiolabeled monoclonal antibodies have been used for radioimmunotherapy studies with human tumor spheroids and murine and human tumor xenografts in experimental animals. This paper reviews the work that has been performed in these models with different types of cancer, and highlights those papers that have presented dosimetry estimates and attempts to correlate the findings. Radioimmunotherapy studies in multicell spheroids, as a model for micrometastases, have been performed in human neuroblastoma, colon cancer, and melanoma cell lines using 131I-, 125I-, 186Re-, and 212Bi-labeled antibodies. The uniform geometry of the spheroid has allowed radiation dose estimates to be made. Up to three logs of cell kill have been achieved with 131I- and 186Re-specific antibody with minimal toxicity from labeled nonspecific antibody, but 212Bi-antibody had little effect because of its short half-life as shown by Langmuir. It appears that the two most important factors for therapeutic efficacy in this model are good penetration of the radiolabeled antibody and an adequate radionuclide half-life to allow penetration of the immunoconjugate prior to significant radionuclide decay. Radioimmunotherapy studies in animals bearing transplants of colon cancer, leukemia, lymphoma, hepatoma, renal cell carcinoma, neuroblastoma, glioma, mammary carcinoma, small cell lung carcinoma, cervical carcinoma, ovarian carcinoma, and bladder cancer have been performed with 131I, 90Y, 186Re, 153Sm, and 177Lu beta emitting, and 212Bi alpha emitting radionuclides conjugated to monoclonal antibodies. A few studies compared different radionuclides in the same model system. The approaches that have been used in these studies to estimate tumor dosimetry include the MIRD approach, thermoluminescent dosimetry, autoradiography, and comparison to external irradiation. The majority of investigators have estimated the dose to tumor and normal organs using MIRD-based calculations (time-activity curve and equilibrium dose constant method). The range of tumor doses has been between 17 and 11 171 mGy/MBq of administered radioactivity. The effectiveness of radiolabeled monoclonal antibody therapy depends on a number of factors relating to the antibody such as specificity, affinity, and immunoreactivity. The density, location, and heterogeneity of expression of tumor-associated antigen within tumors will affect the localization and therapeutic efficacy of radiolabeled antibodies, as will physiological factors such as the tumor vascularity, blood flow, and permeability. These factors are discussed and examples are presented.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Experimental radioimmunotherapy. 849 64

Human manganese-containing superoxide dismutase (MnSOD) is a nuclear encoded mitochondrial protein that scavenges potentially toxic superoxide radicals by dismuting O2- to O2 plus H2O2. To understand the molecular mechanism governing the transcriptional regulation of the human MnSOD gene, I have isolated and sequenced a genomic clone containing the 5' flanking region of the human MnSOD gene. One major transcription start site was mapped by primer extension to a guanine residue 67 base pairs upstream from the translation start site. Eight putative Sp1 binding elements and one AP1 consensus sequence, but no TATA or CAAT box, were found in the promoter region. Furthermore, a series of chimerical/CAT reporter gene constructs were used to transfect human hepatocellular carcinoma(HepG2) human neuroblastoma and human skin fibroblast cell lines to characterize the promoter and regulatory region of the human MnSOD gene. The results show that human MnSOD gene expression is governed by one promoter and that the basic promoter is located between nucleotides -34 and +38. The results also indicate that both positive and negative elements are involved in the regulation of the cell-type specific expression of the human MnSOD gene. The functional studies indicate that the Sp1 binding sites or G+C rich regions play an important role in regulation of expression of the human MnSOD gene in vivo.
 ...
PMID:Characterization of the 5' flanking region of the human MnSOD gene. 860 39

Endobronchial metastasis (EM) from nonpulmonary tumors is uncommon. A 9-year retrospective study at the University Hospital Vall d'Hebron (Barcelona, Spain) identified 32 patients with EM. All but four cases were diagnosed by fiberoptic bronchoscopy with bronchial biopsy. Primary tumors included the following types: breast cancer (20), colorectal cancer (3), melanoma (2), gastric cancer (1), neuroblastoma of the olfactory nerve (1), abdominal leiomyosarcoma (1), hypernephroma (1), endometrial carcinoma (1), papillary thyroid cancer (1), and hepatocarcinoma (1). Median age at diagnosis of EM was 58.7 years and median interval from the diagnosis of the primary tumor to the diagnosis of EM was 50.4 months. Seventeen patients (53%) had evidence of other metastatic sites at endobronchial relapse. The more common clinical manifestations included cough (37.5%), haemoptysis (28%), dyspnea (18.7%), and recurrent pulmonary infections (6.2%). Eight patients (25%) had no symptoms. There appears to be a predilection for metastatic involvement of the right and left upper lobe bronchus. Treatment was instituted in 20 patients, and their median survival was 11 months, in comparison with the 3 months found in 12 patients who received only palliative therapy because of advanced disseminated disease. Breast cancer is the most common tumor causing EM. The prognosis of patients with EM depends on the type of the primary tumor and the presence of other metastatic sites. Treatment must be individualized.
 ...
PMID:Endobronchial metastatic disease: analysis of 32 cases. 869 37

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.
 ...
PMID:The current status of targeted radiotherapy in clinical practice. 891 69

Eighteen patients (3 men and 15 women; mean age 63 years) with right-sided tumors were evaluated by both transthoracic and transesophageal echocardiography from 1989 to 1996. The indications for echocardiographic studies included evaluation for a presumed mass and further evaluation of ventricular function and valvular function. Fifteen patients had right atrial tumors. These included 5 hypernephromas, 4 myxomas, 2 angiosarcomas, 1 lipoma, 1 cavernous hemangioma, 1 hepatoma, and 1 chondrosarcoma. Three patients had right ventricular (RV) tumors: 1 metastatic olfactory neuroblastoma, a leiomyosarcoma, a chondrosarcoma, and a fourth patient had infiltration of the RV free wall of unknown etiology. Biopsy of either right atrial or RV masses was performed with transesophageal echocardiographic guidance in 2 patients, and allowed histologic diagnosis before surgical resection. These findings indicate that tumors are more often found in the right atrium than in the right ventricle, and females predominate. Most tumors arising within the right atrium are benign, whereas those extending into the right atrium from outside are malignant. RV tumors are rarely encountered; when present, they are likely to be malignant.
 ...
PMID:Right-sided cardiac tumors detected by transesophageal echocardiography and its usefulness in differentiating the benign from the malignant ones. 907 May 59

It is now clearly established that alpha-2 adrenergic receptors can be subdivided in three pharmacological subtypes (alpha-2A, alpha-2B and alpha-2C) encoded by distinct genes (alpha 2C10, alpha 2C2 and alpha 2C4, respectively, in humans). Whereas the study of the regulation of the human alpha-2A adrenergic receptor and of the promoter region of the alpha 2C10 gene has being greatly helped by the availability of the colon carcinoma cell line HT29, the study of the other human receptor subtypes has thus far been limited to homologous desensitization/down-regulation in transfected cells, because of the lack of human cellular models constitutively-expressing alpha-2B or alpha-2C adrenergic receptors. Several human cell lines were thus screened, in an attempt to find such models. Radioligand binding studies with [3H]RX821002 and [3H]MK912, reverse transcription-polymerase chain reactions and RNase mapping experiments with pairs of primers and riboprobes specific for each subtype demonstrated that the hepatoma cell line HepG2 and the neuroblastoma cell line SK-N-MC possess alpha-2 adrenergic receptors of the alpha-2C subtype. However, whereas HepG2 expresses exclusively alpha-2C receptors (55 +/- 7 fmol of [3H]MK912 binding sites/mg of protein), SK-N-MC expresses both alpha-2A and alpha-2C subtypes in fairly similar amounts (20 +/- 8 and 23 +/- 3 fmol of [3H]MK912 binding sites/mg of protein, respectively). The study of the inhibition of 3H-labeled antagonist binding by UK14304 demonstrated that a fraction of the receptor population was coupled to pertussis toxin-sensitive G-proteins, which were identified as Gi2 and Gi3 by immunoblotting. The alpha-2 agonist was, moreover, able to decrease forskolin-stimulated cAMP production by 47% in HepG2 and 23% in SK-N-MC, demonstrating that inhibition of adenylyl cyclase is one of the primary mechanisms of signal transduction in both cell lines. HepG2 and SK-N-MC are the first human cell lines unquestionably shown to natively express alpha-2C adrenergic receptors. The discovery of these two models may be useful for future study of the regulation of alpha 2C4 gene expression in cells of different origins and investigation of the reciprocal regulation of alpha-2A and alpha-2C subtype in single cells.
 ...
PMID:HepG2 and SK-N-MC: two human models to study alpha-2 adrenergic receptors of the alpha-2C subtype. 915 9

We have studied the biosynthesis of long chain polyunsaturated fatty acids (LC-PUFA) from their precursors in cultured cells undergoing physiological modifications, or under the influence of lipid-lowering drugs or ethanol. The formation of arachidonic acid (AA, 20:4 n-6) from the percursor linoleic acid (LA, 18:2 n-6) in the neuroblastoma cells SK-N-BE is enhanced at early stages of differentiation, and declines when differentiation is complete, in concomitance with maximal accumulation of AA in cell lipids. In the monocytic cells THP-1, the biosynthesis of LC-PUFA is also enhanced by treatment with the HMGCoA reductase inhibitor simvastatin (S), an effect which is reverted by mevalonate and other intermediates of cholesterol synthesis. Maximal activation of LC-PUFA synthesis by S occurs at concentrations lower than those required for maximal inhibition of cholesterol synthesis. In the hepatoma cells HepG2, ethanol decreases the biosynthesis of LC-PUFA while potentiating the incorporation of acetate into cholesterol. LC-PUFA synthesis appears thus to be modulated in the course of cell differentiation and complex interactions between LC-PUFA and cholesterol synthesis occur, as judged from data obtained through pharmacological manipulations.
 ...
PMID:Manipulation of the fate of long chain polyunsaturated fatty acids in cultured cells. 925 Jun 4

CuZn superoxide dismutase (SOD) secretion was detected in media of [35S]cysteine-labeled human neuroblastoma SK-N-BE cells precipitated with antihuman CuZn SOD antibodies. The ability of Fe2+/ascorbate oxidative stress to induce CuZn SOD in SK-N-BE cells was evaluated by Western blot analysis. The results showed that, like human hepatocarcinoma cells and human fibroblasts, SK-N-BE cells secrete CuZn SOD. In addition, the CuZn SOD concentration was higher in cells subjected to oxidative stress than in unstressed cells. The secretion of CuZn SOD and the ability of Fe2+/ascorbate to increase its protein content in SK-N-BE cells indicates that this enzyme protects the brain from damage induced by oxidative stress.
 ...
PMID:Secretion and increase of intracellular CuZn superoxide dismutase content in human neuroblastoma SK-N-BE cells subjected to oxidative stress. 957 Jul 22

The neuronal promoter of human aromatic l-amino acid decarboxylase gene has been analysed to elucidate the mechanisms of neuron type-specific expression. The (-560/+92) promoter segment was sufficient to direct luciferase expression at a higher level in SK-N-BE neuroblastoma cells, than in CHP126 neuroepithelia, HepG2 hepatoma or SK-Hep1 epithelioma cells. Deletions experiments showed that this segment contained a neuronal-specific (element T1) and a SK-N-BE-specific (element N1) cis-activating sequences. Element T1 (-72/-36) bound Sp1 and NF-Y proteins, and unidentified neuronal-specific factors. Element N1 (-102/-72) bound cell-specific factors, identified as HNF-3, N-Oct-3/Brn-2 and N-Oct-2. HNF-3 proteins recognized the sequence TCAGTAAATA that matches the consensus motif. Oct-1, N-Oct-2 and N-Oct-3 bound the AAATAATGC sequence that overlaps the HNF-3 binding site. In addition, we show that the HNF-3 binding sites from aldolase C and HNF-3beta gene promoters also bind N-Oct-2 and N-Oct-3 proteins. These data suggest a functional interplay of winged helix/forkhead and POU-domain transcription factors on a variety of neuronal gene promoters.
 ...
PMID:Winged helix hepatocyte nuclear factor 3 and POU-domain protein brn-2/N-oct-3 bind overlapping sites on the neuronal promoter of human aromatic L-amino acid decarboxylase gene. 960 35

p73 has been recently identified as a new structural and functional homologue of the transcription factor p53. It is expressed in either a full-length form, alpha, or a shorter beta mRNA variant, with exon 13 spliced out. Here we report the identification and functional characterization of two new p73 splicing variants, gamma (splicing out exon 11) and delta (splicing out exons 11, 12, and 13). Both gamma and delta p73 variants are expressed in human peripheral blood lymphocytes, primary keratinocytes, and different tumor cell lines, including neuroblastoma, glioblastoma, melanoma, hepatoma, and leukemia. The expression pattern of the four p73 splicing variants differs in both primary cells of different lineage and established cell lines even within the same type of tumor. A two-hybrid assay was used to characterize the homodimeric and heterodimeric interactions between the p73 variants, and showed that neither p73gamma nor p73delta interact with p53, whereas p73gamma showed strong interactions with all p73 isoforms, and p73delta binds efficiently p73alpha and p73gamma but only weakly p73beta. At the functional level, p73gamma is significantly less efficient in activating transcription of the p21(Waf1/Cip1) promoter than p53 or p73beta, whereas the effect of p73delta is intermediate and comparable to that of p73alpha. The ability of the different p73 variants to affect cell growth in p53 null osteosarcoma SAOS-2 cells correlates with their transcriptional activity on the p21(Waf1/Cip1) promoter: p73beta is the most efficient in inhibiting colony formation, whereas p73gamma is almost ineffective. Our results suggest that p73 isoforms may be differentially regulated, with four different isoforms capable of interacting among themselves and with p53. The relative expression level of each splice variant may modulate p73 transcriptional and growth suppression activities by affecting heterodimer formation.
 ...
PMID:Two new p73 splice variants, gamma and delta, with different transcriptional activity. 980 88


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>