National Cancer Institute®
Last Modified: July 1, 2002
UI - 11912213
AU - Liang Y; Li XY; Rebar EJ; Li P; Zhou Y; Chen B; Wolffe AP; Case CC
TI - Activation of vascular endothelial growth factor A transcription in tumorigenic glioblastoma cell lines by an enhancer with cell type-specific DNase I accessibility.
SO - J Biol Chem 2002 May 31;277(22):20087-94
AD - Sangamo BioSciences Incorporated, Richmond, California 94804, USA.
Unregulated expression of vascular endothelial growth factor-A (VEGF-A) plays an important role in tumor growth. We have identified a cell type-specific enhancer, HS-1100, that contributes to VEGF-A transcriptional activation in tumorigenic glioblastoma cell lines. This enhancer exhibits increased accessibility to DNase I in glioblastoma cell lines that express high levels of VEGF-A but not in several other cell lines that express much lower levels of VEGF-A. HS-1100 contains a number of sequence elements that are highly conserved among human, mouse, and rat, including the hypoxia-response element (HRE). We show that the HRE contributes significantly to the cell type-specific enhancer activity of HS-1100 in U87MG glioblastoma cells. We use chromatin immunoprecipitation assays to show that endothelial PAS domain protein 1 (EPAS1) can efficiently bind to the endogenous HRE in U87MG cells but not in HEK293 cells in which the chromosomal HS-1100 is not accessible to DNase I. A dominant negative EPAS1 significantly reduces HS-1100 enhancer activity and VEGF-A levels in U87MG cells. Our results provide insight into the molecular mechanisms of VEGF-A up-regulation during cancer development.
UI - 11955607
AU - Wei JL; Scheithauer BW; Smith JS; Jenkins RB; Passe SM; Arndt CA; Strome
TI - SE Primary neuroblastoma of the maxillary sinus.
SO - Int J Pediatr Otorhinolaryngol 2002 Apr 25;63(2):155-62
AD - Department of Otorhinolaryngology, c/o Section of Scientific Publications, Mayo Clinic, Rochester, MN, USA.
Although neuroblastoma is the most common of extracranial solid tumors of childhood and infancy, we report the first case of an isolated neuroblastoma of a paranasal sinus. A 15-year-old girl with a right maxillary sinus mass was asymptomatic except for persistent epiphora. Computed tomography and magnetic resonance imaging scans showed that the mass extended into the nasal cavity, encroached on the lamina papyracea, and obstructed the nasofrontal duct. An extensive workup revealed no evidence of systemic disease. The patient underwent right craniofacial resection. Immunohistochemistry and electronmicroscopic findings were consistent with conventional neuroblastoma. Fluorescence in situ hybridization analysis was performed with probes selected to demonstrate genetic alterations associated with neuroblastoma. Studies revealed deletion of chromosome arm 1p, gain of chromosome 17, and normal N-myc gene copy number. In summary, the tumor exhibited morphologic features and genetic alterations more consistent with those of neuroblastoma than with those of esthesioneuroblastoma.
UI - 12028822
AU - Olivieri G; Otten U; Meier F; Baysang G; Dimitriades-Schmutz B;
TI - Muller-Spahn F; Savaskan E Oxidative stress modulates tyrosine kinase receptor A and p75 receptor (low-affinity nerve growth factor receptor) expression in SHSY5Y neuroblastoma cells.
SO - Neurol Clin Neurophysiol 2002;2002(2):2-10
AD - Neurobiology Laboratory, Psychiatric University Hospital, Basel, Switzerland. email@example.com
The interaction of neurotrophins and their tyrosine kinase receptors (trks) is essential for differentiation and survival of brain cells. In Alzheimer's disease (AD), the number of neurotrophins and receptors is markedly decreased. The cause of this reduction is unclear, but the role of beta-amyloid (Abeta) seems central in understanding the mechanisms controlling neurotrophin and trk expression. In the study reported here, we exposed SHSY5Y neuroblastoma cells to Abeta or hydrogen peroxide (H(2)O(2)) and measured the expression of trk-A and p75 at the protein and molecular levels. Both Abeta and H(2)O(2) induced oxidative stress (measured by a decrease in cellular glutathione), which decreased trk-A levels and increased p75 levels, decreased messenger RNA (mRNA) levels of both receptors, and increased nerve growth factor (NGF) secretion. Pretreatment of cells with the antioxidant melatonin returned levels of protein expression, mRNA, and NGF secretion to normal. These results are significant, as they can help in the planning and implementation of AD treatment strategies involving neurotrophins.
UI - 12086397
AU - Lee YS; Kwon EJ; Jin da Q; Park SH; Kang YS; Huh K; Kim JA
TI - Redox status-dependent regulation of cyclooxygenases mediates the capsaicin-induced apoptosis in human neuroblastoma cells.
SO - J Environ Pathol Toxicol Oncol 2002;21(2):113-20
AD - Department of Physiology, College of Medicine, Kwandong University, Kangnung, Korea.
Cyclooxygenases (COX) appear to be involved in the mechanism of apoptosis in various cancer cells. In this study we investigated the role of COX in the capsaicin (Cap)-induced apoptosis in SK-N-SH human neuroblastoma cells. Cap induced decreased cell viability and apoptosis in a dose-dependent manner. Cap also significantly reduced the basal generation of reactive oxygen species (ROS) and lipid peroxidation in a time-dependent fashion. Cap markedly suppressed the expression of COX-1 and COX-2. Pretreatment with NS-398, a selective COX-2 inhibitor, or indomethacin, a nonselective COX inhibitor, significantly enhanced the Cap-induced decreased cell viability and apoptosis. Exogenous application of an oxidant, H2O2, significantly prevented the Cap-induced apoptosis and suppressed the expression of COX isoforms. These results suggest that redox status-dependent regulation of COX expression may mediate apoptosis induced by Cap in human neuroblastoma cells.
UI - 12019183
AU - Ambros IM; Amann G; Ambros PF
TI - Correspondence re: J. Mora et al., Neuroblastic and Schwannian stromal cells of neuroblastoma are derived from a tumoral progenitor cell. Cancer Res., 61: 6892-6898, 2001.
SO - Cancer Res 2002 May 15;62(10):2986-7; discussion 2988-9
UI - 12025836
AU - Shimada H
TI - Correspondence re: J. Mora et al., Neuroblastic and Schwannian stromal cells of neuroblastoma are derived from a tumoral progenitor cell. Cancer Res., 61: 6892-6898, 2001.
SO - Cancer Res 2002 May 15;62(10):2987-8; discussion 2988-9
UI - 12012219
AU - Swart JF; de Kraker J; van der Lely N
TI - Metaiodobenzylguanidine total-body scintigraphy required for revealing occult neuroblastoma in opsoclonus-myoclonus syndrome.
SO - Eur J Pediatr 2002 May;161(5):255-8
AD - Reiner de Graaf Gasthuis, Department of Paediactrics, Delft, The Netherlands. firstname.lastname@example.org
A girl aged 13 months presented with clinical features of subacute progressive ataxia leading to abasia, astasia, loss of unsupported sitting and apraxia. In addition, an opsoclonus, myoclonia and introvert behaviour developed. MRI of the brain, EEG, extensive tests of blood, urine and CSF showed no abnormalities. Based on clinical symptoms only, the diagnosis of opsoclonus-myoclonus syndrome (OMS) could be made. Under the suspicion of a neuroblastoma, further investigations were performed: a lateral and antero-posterior X-ray examination of the chest showed no tumour; neither did ultrasound of the abdomen. Concentrations of catecholamines and their metabolites in 24 h urine were normal and none of five tested anti-neuronal antibodies were found. However, a total-body scintigraphy with [I(123)] metaiodobenzylguanidine (MIBG) revealed a paravertebral hot spot on the left side compatible with a neural crest tumour. A MRI scan of the abdomen confirmed the supraphrenic lesion. [I(123)]MIBG uptake was sufficient for [I(131)]MIBG therapy. The response of the tumour to this therapy was favourable. The neurological symptoms of the patient slightly improved under steroid treatment. CONCLUSION: Opsoclonus-myoclonus syndrome is a serious disease in infants, sometimes associated with occult neuroblastoma for which a full oncological work-up, including metaiodobenzylguanidine total-body scintigraphy is required.
UI - 12065637
AU - Tucholski J; Johnson GV
TI - Tissue transglutaminase differentially modulates apoptosis in a stimuli-dependent manner.
SO - J Neurochem 2002 May;81(4):780-91
AD - Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, 1720 7th Avenue South, SC 1061, Birmingham, AL 35294-0017, USA.
Tissue transglutaminase is a unique member of the transglutaminase family as it not only catalyzes a transamidating reaction, but also binds and hydrolyzes GTP and ATP. Tissue transglutaminase has been reported to be pro-apoptotic, however, conclusive evidence is still lacking. To elucidate the role of tissue transglutaminase in the apoptotic process human neuroblastoma SH-SY5Y cells were stably transfected with vector only (SH/pcDNA), wild-type tissue transglutaminase (SH/tTG) and tissue transglutaminase that has no transamidating activity but retains its other functions (SH/C277S). In these studies three different apoptotic stimuli were used osmotic stress, staurosporine treatment and heat shock to delineate the role of tissue transglutaminase as a transamidating enzyme in the apoptotic process. In SH/tTG cells, osmotic stress and staurosporine treatments resulted in significantly greater caspase-3 activation and apoptotic nuclear changes then in SH/pcDNA or SH/C277S cells. This potentiation of apoptosis in SH/tTG cells was concomitant with a significant increase in the in situ transamidating activity of tissue transglutaminase. However, in the heat shock paradigm, which did not result in any increase in the transamidating activity in SH/tTG cells, there was a significant attenuation of caspase-3 activity, LDH release and apoptotic chromatin condensation in SH/tTG and SH/C277S cells compared with SH/pcDNA cells. These findings indicate for the first time that the effect of tissue transglutaminase on the apoptotic process is highly dependent on the type of the stimuli and how the transamidating activity of the enzyme is affected. Tissue transglutaminase facilitates apoptosis in response to stressors that result in an increase in the transamidating activity of the enzyme. However, when the stressors do not result in an increase in the transamidating activity of tissue transglutaminase, than tissue transglutaminase can ameliorate the apoptotic response through a mechanism that is independent of its transamidating function. Further, neither the phosphatidylinositol-3-kinase pathway nor the extracellular-regulated kinase pathway is downstream of the modulatory effects of wild-type tissue transglutaminase or C277S-tissue transglutaminase in the apoptotic cascade.
UI - 11702143
AU - Hiorns MP; Owens CM
TI - Radiology of neuroblastoma in children.
SO - Eur Radiol 2001;11(10):2071-81
AD - Department of Diagnostic Imaging, Hospital for Sick Children, Great Ormond Street, London WC1N 3JH,UK.
The radiology of neuroblastoma reflects the diversity of the manifestations of this condition. The current radiological practice for imaging is outlined and illustrated with emphasis on cross-sectional and radionuclide imaging.
UI - 12004198
AU - Simpson PB; Woollacott AJ; Moneer Z; Rand V; Seabrook GR
TI - Estrogen receptor ligands affect mitochondrial activity in SH-SY5Y human neuroblastoma cells.
SO - Neuroreport 2002 May 24;13(7):957-60
AD - Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK.
We have studied the pharmacological regulation of mitochondrial activity in a human neuroblastoma cell line. Cyclosporin A was found to directly alter mitochondrial membrane potential and to decrease mitochondrial permeability as measured using calcein. The estrogen receptor ligands tamoxifen, nafoxidine and clomiphene were identified as agents which affect mitochondrial membrane potential in a cyclosporin A-like manner. Also when mitochondrial permeability was measured using calcein, tamoxifen, nafoxidine and clomiphene were effective in inhibiting dye loss from mitochondria. Nafoxidine and cyclosporin A inhibit effects of mastoparan on SH-SY5Y mitochondria. These studies indicate that estrogen receptor ligands appear to affect mitochondria in a cyclosporin A-like manner in human neuroblastoma cells.
UI - 12051711
AU - Andersson K; Olofsson A; Nielsen EH; Svehag SE; Lundgren E
TI - Only amyloidogenic intermediates of transthyretin induce apoptosis.
SO - Biochem Biophys Res Commun 2002 Jun 7;294(2):309-14
AD - Department of Cell and Molecular Biology, Umea University, S-901 87 Umea, Sweden.
In diseases like Alzheimer's disease and familial amyloidotic polyneuropathy (FAP) amyloid deposits co-localize with areas of neurodegeneration. FAP is associated with mutations of the plasma protein transthyretin (TTR). We can here show an apoptotic effect of amyloidogenic mutants of TTR on a human neuroblastoma cell line. Toxicity could be blocked by catalase indicating a free oxygen radical dependent mechanism. The toxic effect was dependent on the state of aggregation and unexpectedly mature fibrils from FAP-patients who failed to exert an apoptotic response. Morphological studies revealed a correlation between toxicity and the presence of immature amyloid. Thus, we can show that toxicity is associated with early stages of fibril formation and propose that mature full-length fibrils represent an inert end stage, which might serve as a rescue mechanism. (c) 2002 Elsevier Science (USA).
UI - 11829415
AU - Carlson K; Ehrich M
TI - Organophosphorus compounds alter intracellular F-actin content in SH-SY5Y human neuroblastoma cells.
SO - Neurotoxicology 2001 Dec;22(6):819-27
AD - Laboratory of Neurotoxicity Studies, Virginia-Maryland Regional College of Veterinary Medicine, Blacksburg, VA 24061, USA.
Cytoskeletal components, especially f-actin (filamentous actin), are responsible for neurite extension and maintenance. Alterations in neurite length and quality precede in vitro cell death induced by organophosphorus (OP) compounds and implicate f-actin proteins in this process. We, therefore, investigated changes in f-actin in SH-SY5Y human neuroblastoma cells exposed to 0.1 and 1 mM paraoxon, parathion, phenyl saligenin phosphate (PSP), tri-ortho-tolyl phosphate (TOTP), triphenyl phosphite (TPPi), and di-isopropyl phosphorofluoridate (DFP) for 0-48 h. The f-actin was measured by flow cytometry in cells labeled with Alexa 488 phalloidin. The relative amount off-actin was compared to total protein levels as determined by spectrophotometry. The cellular content of f-actin significantly decreasedfollowing exposure to PSP (0.1 mM, >30 min; 1 mM, >15 min), TOTP (0.1 mM, 16 h; 1 mM, >15 min), TPPi (1 mM, >4 h), paraoxon (1 mM, >24 h), and parathion (1 mM, 48 h). Exposure to DFP (0.1 and 1 mM) did not significantly alter f-actin content at any time point. Exposure to parathion (0.1 mM, 48 h) significantly increased the amount of cellular f-actin. Total protein was significantly decreased after exposure to PSP (0.1 and 1 mM, >8 h) and TPPi (1 mM, 48 h). Significant increases in total protein were observed following exposure to parathion (0.1 mM, >3 h). Consistent alterations in the protein content of DFP-exposed samples were not observed. These results suggest that the loss off-actin is an early event following OP compound exposure and that this loss significantly precedes a loss of protein content for some OP compounds (PSP, TPPi). Results also imply that under other exposure conditions (TOTP, paraoxon, parathion) alterations in the f-actin content are independent of protein content.
UI - 11992472
AU - Amoroso S; D'Alessio A; Sirabella R; Di Renzo G; Annunziato L
TI - Ca(2+)-independent caspase-3 but not Ca(2+)-dependent caspase-2 activation induced by oxidative stress leads to SH-SY5Y human neuroblastoma cell apoptosis.
SO - J Neurosci Res 2002 May 15;68(4):454-62
AD - Department of Pharmacology, School of Medicine, University of Ancona, Ancona, Italy. email@example.com
Continuous and long-lasting exposure to tert-butylhydroperoxide (t-BOOH) increased the number of apoptotic SH-SY5Y human neuroblastoma cells both in the presence and in the absence of the intracellular Ca(2+) ion chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). In addition, t-BOOH exposure induced activation of CPP32, as demonstrated by poly-(ADP-ribose) polymerase (PARP) cleavage, and of ICH-1L caspases. Exposure to t-BOOH also induced a time-dependent release of cytochrome c. Interestingly, in the presence of BAPTA, CPP32 activation still occurred, whereas ICH-1L activation was blocked. Ac-DEVD-CHO, an inhibitor of CPP32 activity, prevented the appearance of apoptotic cells, whereas the inhibitor of ICH-1L activity Z-VDVAD-FMK did not. Collectively, these findings demonstrate that in SH-SY5Y neuroblastoma cells exposure to continuous and long-lasting oxidative stress induced activation of caspase-3 that was independent of intracellular Ca(2+) ion concentration ([Ca(2+)](i)) elevation but led to cell apoptosis. In contrast, caspase-2 activation was dependent on [Ca(2+)](i) increase but did not result in apoptosis. Copyright 2002 Wiley-Liss, Inc.
UI - 12095929
AU - Massimo L
TI - Neuroblastoma: a challenge for pediatric oncology of the third millennium.
SO - Ann N Y Acad Sci 2002 Jun;963():59-62
AD - Director Emeritus, Department of Pediatric Hematology and Oncology, G. Gaslini Scientific Children's Hospital, Genoa, Italy. firstname.lastname@example.org
Neuroblastoma is the only cancer of childhood considered in this conference on hormone-related tumors, because the percentage of deaths in children with this rare type of cancer is still very high. Pediatricians feel the need for help from basic researchers to better understand the biological nature of this disease and to improve protocols and the challenge of cure.
UI - 12095930
AU - Schwab M
TI - Amplified MYCN in human neuroblastoma: paradigm for the translation of molecular genetics to clinical oncology.
SO - Ann N Y Acad Sci 2002 Jun;963():63-73
AD - Division of Cytogenetics, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. email@example.com
Increase in the dosage of cellular oncogenes by DNA amplification is a frequent genetic alteration of cancer cells. In neuroblastoma, amplification of the gene MYCN has been associated with aggressively growing cancers and is an indicator for poor prognosis. MYCN amplification is of predictive value in identifying patients with neuroblastoma who require specific therapeutic regimens and those who do not benefit from chemotherapy.
UI - 12095931
AU - Perri P; Longo L; McConville C; Cusano R; Rees SA; Seri M; Conte M;
TI - Romeo G; Devoto M; Tonini GP Linkage analysis in families with recurrent neuroblastoma.
SO - Ann N Y Acad Sci 2002 Jun;963():74-84
AD - Laboratory of Neuroblastoma Research, Advanced Biotechnology Center, Genoa, Italy. firstname.lastname@example.org
Neuroblastoma is a neural crest-derived tumor of childhood with a serious prognosis; only 20% of patients with stage 4 disease survive 5 years from diagnosis. Mechanisms involved in neuroblastoma development are unclear, but the engagement of many neuroblastoma-related gene(s) is suggested by specific chromosomal alterations. Most prominent among these is the amplification of the MYCN oncogene and the deletion of the 1p36 region. Other genetic aberrations have been discovered over the years such as deletions of 11q and 14q and gain of 17q. Although tumor aggressiveness greatly depends on the most frequent genetic abnormalities, to date no neuroblastoma-related gene has been discovered. Neuroblastoma usually occurs sporadically, but 1.5% of all diagnosed cases show familial recurrence with an autosomal dominant inheritance and incomplete penetrance. A comparison between hereditary and sporadic neuroblastomas led Knudson and Strong to gather that the two-hit hypothesis, proposed for retinoblastoma, could be applied to neuroblastoma. To determine if the 1p36 region harbors a predisposition gene for familial neuroblastoma, we carried out linkage analysis at 1p36 loci in two families with recurrent neuroblastoma. Similarly, we analyzed loci of chromosome 16, where a predisposition locus was recently mapped. We also analyzed markers located close to several candidate genes (RET, NF1, GDNF, GFRA1, EDNRB, and EDN3) involved to a different extent in other neurocristopathies. Our findings indicate that the candidate chromosomal regions and genes analyzed are not in linkage with neuroblastoma.
UI - 11867941
AU - Berger A; Tuechler C; Almer D; Kogner P; Ratschek M; Kerbl R; Iismaa TP;
TI - Jones N; Sperl W; Kofler B Elevated expression of galanin receptors in childhood neuroblastic tumors.
SO - Neuroendocrinology 2002 Feb;75(2):130-8
AD - Department of Pediatrics, General Hospital Salzburg, Salzburg, Austria.
The neuropeptide galanin (GAL) has been shown to be present in certain brain tumors. In order to learn more about GAL and its receptors in human tumors of the peripheral nervous system, we investigated the expression of the GAL peptide and the GAL receptors in tumor tissue from childhood neuroblastic tumors. GAL peptide concentrations up to 674 +/- 166 fmol/mg of tissue were detected by radioimmunoassay, but no significant correlation with standard tumor markers or the prognosis of the 14 patients investigated was observed. Ligand binding experiments showed different levels of GAL binding in all 28 primary neuroblastomas and 7 ganglioneuromas investigated. All three human GAL receptor subtypes cloned to date could be detected, with the GALR1 receptor subtype being expressed most prominently. GAL binding did not significantly correlate with genetic markers such as unfavorable DNA ploidy, amplification of the oncogene MYCN and allelic loss of chromosome 1p. However, low galanin binding was significantly correlated with survival (p = 0.021) in this limited analysis of neuroblastic tumor samples. These results raise the possibility that the expression of GAL binding sites may play a role in neuroblastic tumor biology and behavior. Copyright 2002 S. Karger AG, Basel
UI - 12085233
AU - Noujaim D; van Golen CM; van Golen KL; Grauman A; Feldman EL
TI - N-Myc and Bcl-2 coexpression induces MMP-2 secretion and activation in human neuroblastoma cells.
SO - Oncogene 2002 Jul 4;21(29):4549-57
AD - Department of Neurology, University of Michigan, Ann Arbor 48109, USA.
Neuroblastoma is a peripheral nervous system tumor that accounts for 8-10% of all solid childhood tumors. N-Myc is the most reliable prognostic indicator for neuroblastoma. Bcl-2 is detected in 40-60% of primary neuroblastoma tumors and demonstrates anti-apoptotic action by conferring resistance to chemotherapy and radiation treatment. In neuroblastoma cell lines, the coexpression of N-Myc and Bcl-2 leads to increased tumorigenic properties. Matrix metalloproteinases (MMPs) are endopeptidases that degrade a wide range of basement membrane components, a process important for tumor invasion. This study investigates the effect of N-Myc and Bcl-2 on MMP expression and activation. MMP-2 expression and secretion are increased in SHEP neuroblastoma cells expressing Bcl-2 alone (SHEP/Bcl-2 cells) or both N-Myc and Bcl-2 (SHEP/N-Myc/Bcl-2 cells). MMP-2 activity is increased in the SHEP/N-Myc/Bcl-2 cells yet remains unchanged in SHEP/Bcl-2 cells. TIMP-2 expression is high in SHEP/Bcl-2 cells, which likely inhibits MMP-2 activity, and absent in SHEP/N-Myc/Bcl-2 cells, allowing MMP-2 activity. Invasion is increased in SHEP/N-Myc/Bcl-2 cells and prevented by the use of a pharmacologic MMP-2 inhibitor. These data imply that N-Myc and Bcl-2 cooperate to increase the expression, secretion, and activation of MMP-2, which likely leads to a more tumorigenic phenotype due to increased MMP-2 mediated invasion.
UI - 11829154
AU - Jang MH; Shin MC; Kim YJ; Chung JH; Yim SV; Kim EH; Kim Y; Kim CJ
TI - Protective effects of puerariaeflos against ethanol-induced apoptosis on human neuroblastoma cell line SK-N-MC.
SO - Jpn J Pharmacol 2001 Dec;87(4):338-42
AD - Departments of Physiology, College of Medicine, Kyung Hee University, Dongdaemun-gu, Seoul, Korea.
Puerariaeflos (PF) is an oriental medical herb for alcohol abuse. To investigate whether PF possesses protective effects against ethanol (EtOH)-induced cytotoxicity in the central nervous system, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometric analysis, DNA fragmentation assay, and reverse transcription-polymerase chain reaction were performed on SK-N-MC human neuroblastoma cells. Cells treated with EtOH exhibited several apoptotic features, while those pre-treated with PF prior to EtOH exposure showed a decreased occurrence of apoptotic features. In addition, PF pre-treatment inhibited the EtOH-induced increase in caspase-3 mRNA expression. These results suggest that PF may exert protective effects against EtOH-induced apoptosis in human neuroblastoma cells.
UI - 11822704
AU - Seven M; Karaman B; Hacihanefioglu S; Deviren A; Yuksel A; Basaran S
TI - Neuroblastoma in a dysmorphic girl with a partial duplication of 2p caused by an unbalanced translocation.
SO - Clin Dysmorphol 2002 Jan;11(1):39-42
AD - Genetic and Teratology Research Center (GETAM), Cerrahpas Medical Faculty, Istanbul University, Turkey. email@example.com
A 1-year-old female child with multiple dysmorphic features including microcephaly, hypertelorism, a short philtrum, low set ears, a narrow high arched palate, micrognathia and growth retardation was found to have a de novo chromosome abnormality including a partial duplication of the short arm of chromosome 2 and a partial deletion of the long arm of chromosome 17. The clinical features of the case shared many similarities to previous reports of trisomy 2p. Three years later, ecchymotic spots appeared around the left ocular region. Further clinical and pathological examination confirmed the diagnosis of a neuroblastoma. This is the first case of an unbalanced translocation, 46, XX, der (17), t (2; 17) (p23; q25), showing the development of a neuroblastoma in addition to the dysmorphic features. We suggest that trisomy 2p including the N-myc proto-oncogene may have predisposed the patient to the development of a neuroblastoma.
UI - 11831613
AU - Anderson BD; Mason S; Cheson BD
TI - Clinical trials referral resource. Current clinical trials in neuroblastoma.
SO - Oncology (Huntingt) 2002 Jan;16(1):82-4, 86, 89
AD - National Cancer Institute, USA.
UI - 12072202
AU - Giordani L; Iolascon A; Servedio V; Mazzocco K; Longo L; Tonini GP
TI - Two regions of deletion in 9p22- p24 in neuroblastoma are frequently observed in favorable tumors.
SO - Cancer Genet Cytogenet 2002 May;135(1):42-7
AD - Department of Biomedicina dell'Eta Evolutiva, University of Bari, Bari, Italy.
Neuroblastoma is a tumor of infancy that presents several chromosomal abnormalities. Nonrandom deletion of chromosome arm 9p has been identified in primary neuroblastoma suggesting the presence of a tumor suppressor gene located on this chromosome. In previous work, we showed that CDKN2A and CDKN2B genes, mapped at 9p21, were not deleted in neuroblastoma cells. In the present article, we refine the deleted region of 9p using polymerase chain reaction-based analysis of highly polymorphic simple sequence repeats and a two color fluorescence in situ hybridization technique on interphase nuclei. We analyzed 71 primary tumors of patients at the onset of the disease. We found loss of heterozygosity (LOH) in 16 of 71 (23%) cases; the frequency of LOH for 9p was higher (28%) in favorable stages 1, 2, and 4s than in unfavorable stages 3 and 4 (14%). Our results identify two regions of frequent allelic loss: the first at the locus D9S1849 and the second at the locus D9S157. These regions appear to be distant from CDKN2A and CDKN2B loci suggesting that other genes may be involved in 9p deletion. Finally, our data show that 9p deletion is more frequent in tumors of patients with a favorable prognosis, indicating that deleted genes may not be crucial for tumor progression.
UI - 12094652
AU - Popko E; Popko M; Famulski W
TI - [Esthesioneuroblastoma of nasal cavity and ethmoid sinus]
SO - Otolaryngol Pol 2002;56(2):235-7
AD - Katedra i Klinika Otolaryngologii AM w Bialymstoku.
This paper presents a rarely occurring tumor of nasal cavity and ethmoid sinus (esthesioneuroblastoma--2nd grade of the pathological grading system proposed by Hyams). It was observed in a woman aged 68. Moreover, there were described surgical therapy and repair of cerebral spinal fluid leaks using composite bone/mucosal graft of the lower turbinate as a donor material. The treatment was successful.
UI - 11820738
AU - Akudugu JM; Bohm L
TI - Micronuclei and apoptosis in glioma and neuroblastoma cell lines and role of other lesions in the reconstruction of cellular radiosensitivity.
SO - Radiat Environ Biophys 2001 Dec;40(4):295-300
AD - Department of Radiation Oncology, Faculty of Medical Sciences and Tygerberg Hospital, University of Stellenbosch, South Africa.
It is now well established that micronuclei frequency does not always rank cell lines according to radiosensitivity. There is, however, a growing interest in reconstructing cellular radiosensitivity (measured by colony assay) from concurrent micronucleus and apoptosis data. Using a variety of radiosensitive and radioresistant cell lines, we have derived a missing parameter--Poe, the probability of cell death by other events such as small deletions, chromosome aberrations, late apoptosis and necrosis which are undetectable by micronucleus and apoptosis assays performed at a single time point. In the radioresistant glioma cell lines G120, G60, G28, G44 and G62 (SF2 > or =0.59), a characteristic threshold dose exists above which cell loss due to undetectable lesions occurs. In the radiosensitive SK-N-SH and KELLY cell lines (SF2 < or =0.43), the Poe parameter is positive at very low doses, reaches a maximum and declines at higher doses. In the radiation resistant G28 cells, Poe was found to be below zero for doses up to 6 Gy. In the G62, G44 and G120 cell lines, the threshold doses to induce Poe events were 0.87, 3.04 and 3.85 Gy, respectively. Cell death by undetectable lesions is a cell-specific and time-dependent variable. Micronucleus and apoptosis assays performed concurrently and at a specific time point miss cell death due to other events and this may be the reason why reconstruction of cellular radiosensitivity from micronucleus and apoptosis data fails.
UI - 12115498
AU - Rapella A; Negrioli A; Melillo G; Pastorino S; Varesio L; Bosco MC
TI - Flavopiridol inhibits vascular endothelial growth factor production induced by hypoxia or picolinic acid in human neuroblastoma.
SO - Int J Cancer 2002 Jun 10;99(5):658-64
AD - Laboratory of Molecular Biology, G. Gaslini Institute, Genoa, Italy.
Human neuroblastoma (NB) tumors elaborate angiogenic peptides, and enhanced angiogenesis correlates with their aggressive behavior, metastatic spread and poor clinical outcome. Hence, inhibition of angiogenic factor production may represent a potential therapeutic target for NB treatment. There is currently little information regarding the stimuli that control NB production of angiogenic mediators. In this study, we analyzed the effects of hypoxia, a common feature of solid tumors and a major drive to tumor angiogenesis, and of PA, a tryptophan catabolite produced under inflammatory conditions and endowed with several biologic properties, on the production of the angiogenic activator VEGF by advanced-stage human NB cell lines. We demonstrate that both stimuli are potent inducers of VEGF expression and secretion. VEGF upregulation by PA involved iron chelation because iron sulfate prevented this effect whereas the iron-chelating agent DFX induced VEGF production. Conversely, the CDK inhibitor Flp completely blocked VEGF induction by hypoxia. This effect occurred as early as 3 hr after stimulation and did not require de novo protein synthesis. Moreover, Flp exerted similar inhibitory activity on VEGF induction by PA or DFX, suggesting that this compound targets an essential step in the signaling pathway that leads to VEGF expression. Our findings demonstrate that PA can modulate angiogenic factor production by tumor cells and establish the importance of Flp as an inhibitor of VEGF production by human NB. Copyright 2002 Wiley-Liss, Inc.
UI - 12108315
AU - Chauty A; Raimondo G; Vergeron H; Branchereau S; Dessemme P; Devictor D;
TI - Hartmann O [Discovery of a neuroblastoma producing cardiogenic shock in a 2-month-old child]
SO - Arch Pediatr 2002 Jun;9(6):602-5
AD - Departement de pediatrie, institut Gustave-Roussy, 94805 Villejuif, France.
CASE REPORT: A two-month-old male child presented a severe heart failure associated with a malignant hypertension. Abdominal ultrasound revealed a mass connected to the left adrenal gland. CT scan showed a tumor of 7 x 6 x 8 cm, forcing back both the left kidney and the aorta. A biopsy allowed the diagnosis of neuroblastoma without MYCN oncogene amplification. Intensive care stabilized the hemodynamic situation. Under chemotherapy the tumor volume decreased significantly and complete surgical excision became possible. Three years after diagnosis, the patient remained in complete remission. CONCLUSION: Clinical presentation of this neuroblastoma was extremely uncommon. The catecholamines produced by the tumoral cells could induce an increase of the myocardiac work following the left ventricule post charge increase. Theses mechanisms could be synergistic for a myocardial exhaustion.
UI - 11859407
AU - Casciano I; Mazzocco K; Boni L; Pagnan G; Banelli B; Allemanni G;
TI - Ponzoni M; Tonini GP; Romani M Expression of DeltaNp73 is a molecular marker for adverse outcome in neuroblastoma patients.
SO - Cell Death Differ 2002 Mar;9(3):246-51
AD - Laboratory of Population Genetics, Istituto Nazionale per la Ricerca sul Cancro (IST), Largo Rosanna Benzi 10, 16132 Genova, Italy.
The p73 gene is a p53 homologue which induces apoptosis and inhibits cell proliferation. Although p73 maps at 1p36.3 and is frequently deleted in neuroblastoma (NB), it does not act as a classic oncosuppressor gene. In developing sympathetic neurons of mice, p73 is predominantly expressed as a truncated anti-apoptotic isoform (DeltaNp73), which antagonizes both p53 and the full-length p73 protein (TAp73). This suggests that p73 may be part of a complex tumor-control mechanism. To determine the role of DeltaNp73 in NB we analyzed the pattern of expression of this gene in vivo and evaluated the prognostic significance of its expression. Our results indicate that DeltaNp73 expression is associated with reduced apoptosis in a NB tumor tissue. Expression of this variant in NB patients significantly correlates with age at diagnosis and VMA urinary excretion. Moreover it is strongly associated with reduced survival (HR=7.93; P<0.001) and progression-free survival (HR=5.3; P<0.001) and its role in predicting a poorer outcome is independent from age, primary tumor site, stage and MYCN amplification (OS: HR=5.24, P=0.012; PFS: HR=4.36, P=0.005). In conclusion our data seem to indicate that DeltaNp73 is a crucial gene in neuroblastoma pathogenesis.
UI - 12027962
AU - Paice JA
TI - Pain and suffering in an adolescent with neuroblastoma.
SO - Cancer Pract 2002 May-Jun;10 Suppl 1():S4-8
AD - Northwestern University, Medical School, Division of Hematology-Oncology, Northwestern Memorial Hospital, Chicago, Illinois, USA.
UI - 11607767
AU - Kushner BH; Cheung NK; Kramer K; Dunkel IJ; Calleja E; Boulad F
TI - Topotecan combined with myeloablative doses of thiotepa and carboplatin for neuroblastoma, brain tumors, and other poor-risk solid tumors in children and young adults.
SO - Bone Marrow Transplant 2001 Sep;28(6):551-6
AD - Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Topotecan appears to be relatively unaffected by the most common multidrug resistance mechanisms, may potentiate cytotoxicity of alkylators, has good penetration into the central nervous system, is active against a variety of neoplasms, and has myelosuppression as its paramount toxicity. We present our experience with a myeloablative regimen that includes topotecan. Twenty-one patients with poor-prognosis tumors and intact function of key organs received topotecan 2 mg/m2 by 30-min intravenous (i.v.) infusion on days -8, -7, -6, -5, -4; thiotepa 300 mg/m2 by 3 h i.v. infusion on days -8, -7, -6; and carboplatin by 4 h i.v. infusion on days -5, -4, -3 with a daily dose derived from the pediatric Calvert formula, using a targeted area under the curve of seven mg/ml* min ( approximately 500 mg/m2/day). Stem cell rescue was on day 0. The patients were 1 to 29 (median 4) years old; 18 were in complete remission (CR) and three in partial remission (PR). Early toxicities were severe mucositis and erythema with superficial peeling in all patients and a seizure, hypertension, and renal insufficiency followed by veno-occlusive disease in one patient each. Post-transplant treatment included radiotherapy alone (four patients) or plus biological agents (11 patients with neuroblastoma). With a follow-up of 6+ to 32+ (median 11+) months, event-free survivors include 10/11 neuroblastoma patients (first CR), 4/5 brain tumor patients (second PR or CR), 1/3 patients with metastatic Ewing's sarcoma (first or second CR), and a patient transplanted for multiply recurrent immature ovarian teratoma; a patient with desmoplastic small round-cell tumor (second PR) had progressive disease at 8 months. Favorable results for disease control, manageable toxicity, and the antitumor profiles of topotecan, thiotepa, and carboplatin, support use of this three-drug regimen in the treatment of neuroblastoma and brain tumors; applicability to other tumors is still uncertain.
UI - 11506485
AU - Anderson J; Kempski H; Hill L; Rampling D; Gordon T; Michalski A
TI - Neuroblastoma in monozygotic twins--a case of probable twin-to-twin metastasis.
SO - Br J Cancer 2001 Aug 17;85(4):493-6
AD - Unit of Molecular Haematology, Institute of Child Health, Great Ormond Street Hospital for Children NHS Trust, London, UK.
Concordance for neuroblastoma in monozygotic twins has been reported only rarely, and the cause of the shared pathology has not been established. We describe a case of infant monozygotic twins developing tumours that were morphologically, clinically and molecularly indistinguishable, but with a delay of 6 months between times of presentation. Both tumours were metastatic and had amplification of MYCN and deletion at 1p36. Twin 1, who developed neuroblastoma first, had constitutional karyotype abnormalities in at least 5% of peripheral blood mononuclear cells involving 1p and 3p, and a deletion of 1q44 in 21% of cells. Twin 2 had a normal constitutional karyotype and lacked rearrangement or deletion of these regions. We propose an acquired neuroblastoma predisposition specific for twin 1, and in utero metastatic spread of tumour cells to twin 2 via the shared placental circulation. Copyright 2001 Cancer Research Campaign.
UI - 12115395
AU - Cheung IY; Lo Piccolo MS; Collins N; Kushner BH; Cheung NK
TI - Quantitation of GD2 synthase mRNA by real-time reverse transcription-polymerase chain reaction: utility in bone marrow purging of neuroblastoma by anti-GD2 antibody 3F8.
SO - Cancer 2002 Jun 1;94(11):3042-8
AD - Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. firstname.lastname@example.org
BACKGROUND: Antigen ganglioside GD2 is expressed abundantly on neuroblastoma (NB) cells. Anti-GD2 monoclonal antibody (MoAb) 3F8 kills NB cells by complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity. Its utility in bone marrow (BM) purging is evaluated by a real-time reverse transcription-polymerase chain reaction (RT-PCR) assay to quantify the mRNA of GD2 synthase, the key enzyme in GD2 synthesis. METHODS: From 1990 to 1993, 10 patients with relapsed/refractory Stage 4 NB participated in a pilot study. In these patients, MoAb 3F8 was used to purge tumor cells from harvested BM that had 5% or less tumor content by immunofluorescence (IF). Subsequently, 31 Stage 4 NB patients who underwent treatment on the N7 protocol (1994-1999) had their BM, which was in remission, purged by 3F8 before (131)I-3F8 myeloablative radioimmunotherapy. GD2-positive tumor cells before and after purging were quantified by real-time quantitative RT-PCR of GD2 synthase. RESULTS: GD2 positivity by IF was found before purging in six of eight patients in the pilot study. Five of six patients became negative postpurging. Of 31 patients on the N7 protocol, the more sensitive real-time quantitative RT-PCR detected GD2 synthase mRNA in the BM samples of 7 patients even though the prepurge BM samples were negative by histology and IF. Six of the seven BM samples became negative after 3F8 purging. Marker positivity before purging was statistically significant in predicting overall survival (P = 0.04), but not progression-free survival (P = 0.1). In vitro hematopoietic stem cell recovery and the median time to engraftment were acceptable. CONCLUSION: Tumor cell depletion quantified by real-time RT-PCR demonstrated efficacy of MoAb 3F8 in BM purging. Copyright 2002 American Cancer Society.
UI - 12116069
AU - Crazzolara R; Abrederis K; Kreczy A; Meister B
TI - Reply to Langer et al. Expression of vascular endothelial growth factor (VEGF) and VEGF receptors in human neuroblastomas.
SO - Med Pediatr Oncol 2002 Aug;39(2):146
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