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Ultima Vez Modificado: 1 de septiembre del 2002
UI - 1511298
AU - Slack BE; Richardson UI; Nitsch RM; Wurtman RJ
TI - Dioctanoylglycerol stimulates accumulation of [methyl-14C]choline and its incorporation into acetylcholine and phosphatidylcholine in a human cholinergic neuroblastoma cell line.
SO - Brain Res 1992 Jul 10;585(1-2):169-76
AD - Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139.
Dioctanoylglycerol, a synthetic diacylglycerol, stimulated [14C]choline uptake in cultured human neuroblastoma (LA-N-2) cells. As this effect has not, to our knowledge, been reported before, it was of interest to characterize it in more detail. In the presence of 500 microM dioctanoylglycerol the levels of [14C]choline attained during a 2 hour labeling period were elevated by 78 +/- 12%, while [14C]acetylcholine and long fatty acyl chain [14C]phosphatidylcholine levels increased by 26 +/- 2% and 19 +/- 5%, respectively (mean +/- S.E.M.). Total (long chain plus dioctanoyl-) [14C]phosphatidylcholine was increased by 198 +/- 33%. Kinetic analysis showed that dioctanoylglycerol reduced the apparent Km for choline uptake to 56 +/- 9% of control (n = 4). The Vmax was not significantly altered. The stimulation of [14C]choline accumulation by dioctanoylglycerol was not dependent on protein kinase C activation; the effect was not mimicked by phorbol ester or by 1-oleoyl-2-acetylglycerol, and was not inhibited by the protein kinase C inhibitors H-7 or staurosporine, or by prolonged pretreatment with phorbol 12-myristate 13-acetate. The effect of dioctanoylglycerol was slightly (but not significantly) reduced by EGTA and strongly inhibited by the cell-permeant calcium chelator bis(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid, tetra(acetoxymethyl)ester. Although these results implicate elevated intracellular calcium in the response, dioctanoylglycerol did not increase phosphatidylinositol hydrolysis in LA-N-2 cells, and its effect was not inhibited by the diacylglycerol kinase inhibitor R 59 022 (which blocks the conversion of diacylglycerol to phosphatidic acid, a known stimulator of phosphatidylinositol hydrolysis).(ABSTRACT TRUNCATED AT 250 WORDS)
UI - 11830391
AU - Candito M; Billaud E; Chauffert M; Cottet-Emard JM; Desmoulin D; Garnier
TI - JP; Greffe J; Hirth C; Jacob N; Millot F; Nignan A; Patricot MC; Peyrin L; Plouin PF [Biochemical diagnosis of pheochromocytoma and neuroblastomas]
SO - Ann Biol Clin (Paris) 2002 Jan-Feb;60(1):15-36
AD - Laboratoire de biochimie, Hopital Pasteur, 30, avenue de la Voie-Romaine, BP 69, 06002 Nice cedex 1.
Pheochromocytoma and neuroblastoma are distinct tumours, but their biological diagnosis is based on secretion increase of one or several catecholamines. Assays have to be very sensible and specific for an early diagnosis. 24 hours urinary catecholamines and metabolites are currently measured, but technical improvements permit plasma metanephrine assay, an excellent indicator of pheochromocytoma. HPLC coupled to electrochemical detection represents the most efficient methodology. After a review of urinary and plasma assay methods, the authors show usual values of catecholamines, metanephrines, HVA and VMA, according to ages, and give examples of results encountered in classical or not tumours and in falsely positive cases. Urinary metanephrine assay is the most sensible and specific in biological diagnosis of pheochromocytoma, while catecholamines and VMA assays lack of sensibility. Results have to be given by 24 hours and by creatinine ratio. Metanephrine assay can be performed also in plasma and exhibits the same interest. However, in urine as in plasma, in case of renal failure, results cannot be interpreted. Neuroblastoma biological diagnosis is based classically on HVA, VMA, and dopamine assays, nowadays only in 24 hours urine (or in urinary micturition for screening), and results are also expressed as creatinine ratio. But even if several assays are advisable, 5% of the neuroblastoma cases do not produce increased catecholamine values. In some cases, metanephrine assay could be of interest. After the age of 12 months, clinical expression of neuroblastoma is dramatic in 70% of cases. So, a biological screening has been experimented in several countries including France. A French translation of the consensus conference report (1998) is appended, which shows the complexity of neuroblastoma screening. Now, there is no evidence that early tumour detection by screening lessens the mortality rate, but a weak benefit is not excluded.
UI - 12101494
AU - Haberle B; Hero B; Berthold F; von Schweinitz D
TI - Characteristics and outcome of thoracic neuroblastoma.
SO - Eur J Pediatr Surg 2002 Jun;12(3):145-50
AD - Department of Paediatric Surgery, University of Basel Childrens' Hospital, Basel, Switzerland.
It has been reported by several groups that thoracic neuroblastoma (NB) are associated with a better outcome than NB of other localisation. Concerning the reason for this phenomenon, however, the findings have diverged and therefore therapeutic recommendations are not uniform. We performed a retrospective analysis of the prognostic factors and surgical results of 113 thoracic NB and compared these to 556 NB of other sites, all treated according to the protocol of the German Cooperative Study NB90. Compared to non-thoracic NB, thoracic NB showed a female preponderance (P = 0.018), more often with localised disease stages 1 - 3 (P < 0.001), lower LDH serum levels (P = 0.027), and less often with MYCN amplification (P = 0.04), while there was no statistically significant difference in the patients' ages and histological grades. In a separate analysis of localised (stages 1 - 3), stage 4 and stage 4 S NB, there were no differences between thoracic and non-thoracic NB in LDH secretion. MYCN amplification was different only in localised NB (P = 0.037). In a multivariate analysis, tumour stage (P < 0.0001), MYCN-status (P < 0.001) and serum-LDH (P = 0.008), but not thoracic localisation, were independent prognostic factors. A complete resection was achieved in 73/104 (70 %) operated thoracic NB, while 25 (24 %) were partially resected and 6 (6 %) only biopsied. Patients with thoracic NB had a better outcome only in stage 4, but not in stages 1 - 3 and 4 S (EFS; P = 0.028). There was no difference for all stages in the event-free survival between completely and incompletely resected tumours. Surgical complications occurred in 34 (20 %) of all operations, some of them severe, although there were no surgical deaths. Our results suggest that although thoracic NB has a relatively favourable prognosis, it should be treated in the same way as NB with non-thoracic localisation, with stratification according to tumour stage and biological properties, such as MYCN status. Radical surgery is only indicated if mutilation and life-threatening complications can be avoided.
UI - 12153570
AU - Hatzi E; Murphy C; Zoephel A; Ahorn H; Tontsch U; Bamberger AM;
TI - Yamauchi-Takihara K; Schweigerer L; Fotsis T N-myc oncogene overexpression down-regulates leukemia inhibitory factor in neuroblastoma.
SO - Eur J Biochem 2002 Aug;269(15):3732-41
AD - Laboratory of Biological Chemistry, Medical School, University of Ioannina, Greece.
Amplification of N-myc oncogene is a frequent event in advanced stages of human neuroblastoma and correlates with poor prognosis and enhanced neovascularization. Angiogenesis is an indispensable prerequisite for the progression and metastasis of solid malignancies, which is modulated by tumor suppressors and oncogenes. We have addressed the possibility that N-myc oncogene might regulate angiogenesis in neuroblastoma. Here, we report that experimental N-Myc overexpression results in down-regulation of leukemia inhibitory factor (LIF), a modulator of endothelial cell proliferation. Reporter assays using the LIF promoter and a series of N-Myc mutants clearly demonstrated that down-regulation of the LIF promoter was independent of Myc/Max interaction and required a contiguous N-terminal N-Myc domain. STAT3, a downstream signal transducer, was essential for LIF activity as infection with adenoviruses expressing a phosphorylation-deficient STAT3 mutant rendered endothelial cells insensitive to the antiproliferative action of LIF. LIF did not influence neuroblastoma cell proliferation suggesting that, at least in the context of neuroblastoma, LIF is involved in paracrine rather than autocrine interactions. Our data shed light on the mechanisms by which N-myc oncogene amplification enhances the malignant phenotype in neuroblastoma.
UI - 12050681
AU - Melegh Z; Balint I; Nagy K; Magyarosy E; Galantai I; Szentirmay Z
TI - [Detection of n-myc gene amplification in neuroblastoma using polymerase chain reaction based methods]
SO - Magy Onkol 2002;46(1):43-8
AD - Molekularis Pathologiai Osztaly, Orszagos Onkologiai Intezet, Budapest, H1122, Hungary. email@example.com
We have used semiquantitative and real-time quantitative PCRs to detect n-myc gene-amplification in 21 frozen neuroblastoma biopsies and IMR 32 cell line in order to predict biological behaviour of the tumors. Two primer pairs were used in the semiquantitative method to co-amplify a 520-bp fragment of the beta -globin gene -used as a single copy reference standard -and a 258-bp fragment of the n-myc gene. After 30 cycles the PCR products were electrophoresed through an agarose gel and were compared to each other with use of a gel-densitometer. Real-time quantitative analysis was performed in a LightCycler instrument. A single primer pair was used to amplify a 120-bp fragment of the n-myc oncogene and a LC640-labelled fluorescent probe pair to detect the product. Calibration curve, which was set up from a serial dilution including samples with 1, 2, 10, 13, 25-fold n-myc oncogene amplification, was employed for quantitative analysis. Semiquantitative method did not show distinct difference between tumor groups with no amplification and less than 10-fold amplification, while quantitative LightCycler analysis was able to detect even 2-fold amplification. In situ PCRs were performed in two cases of differentiated tumor samples which contained n-myc amplification. We used biotinylated ATP labelling and the same primer pair as for the LightCycler analysis.In both cases differentiated cell forms did not show n-myc gene amplification, while considerable amplification was detected in the neuroblasts.
UI - 12087513
AU - Ohhashi G; Kamio M; Abe T; Otori N; Haruna S
TI - Endoscopic transnasal approach to the pituitary lesions using a navigation system (InstaTrak system): technical note.
SO - Minim Invasive Neurosurg 2002 Jun;45(2):120-3
AD - Department of Neurological Surgery, Jikei University, Tokyo, Japan. firstname.lastname@example.org
The endoscopic transnasal approach has become a procedure of choice for the surgical management of pituitary lesions. However, in conventional endoscopic transnasal surgery, the surgeon may become disorientated to the actual operating position. In our series, 31 patients have undergone an endoscopic transnasal approach to the pituitary lesions with the use of the navigation system InstaTrak for real-time imaging. This image guidance system proved valuable for anatomic localization during pituitary surgery. We have reduced the average surgical time, and improved patient outcome. As consequence, complications during surgery should decrease and safety should increase. Intraoperative image guidance is expected to have major advantageous effects on pituitary surgery by allowing the surgeon to remove pathology more efficiently. As this system is improved technically and surgeons become more proficient in its use, there should be better postoperative outcomes.
UI - 12110498
AU - Godfried MB; Veenstra M; Valent A; Sluis P; Voute PA; Versteeg R; Caron
TI - HN Lack of interstitial chromosome 1p deletions in clinically-detected neuroblastoma.
SO - Eur J Cancer 2002 Jul;38(11):1513-9
AD - Department of Human Genetics, Academic Medical Center, University of Amsterdam, PO Box 22700 1100 DE, Amsterdam, The Netherlands.
Loss of heterozygosity (LOH) of the distal part of the short arm of chromosome 1 in neuroblastoma is a well characterised phenomenon. In addition, previous reports have described interstitial deletions outside the common region of loss on chromosome 1p36, suggesting additional tumour suppressor loci. In this study, we have searched extensively for interstitial 1p deletions in a panel of 67 neuroblastoma samples from clinically-detected cases. We used three VNTR probes and 10 dinucleotide markers from the 1p32-36 regions reported to show interstitial deletions. Fifteen (22%) tumours showed telomeric LOH without evidence for more proximal interstitial deletions. Forty-five tumours showed no LOH or allelic imbalance. Seven (10%) tumours demonstrated allelic imbalance for one or more markers. These tumours were subsequently analysed by fluorescent in situ hybridisation (FISH) and flow cytometry. The patterns found in all seven tumours were consistent with copy number changes of the entire chromosome 1, without evidence for interstitial deletions. This study indicates that interstitial deletions of chromosome 1p are rare in clinically-detected neuroblastoma when analysed by a combination of molecular and cytogenetic techniques.
UI - 12168819
AU - Tashiro F; Sugiyama A; Urano Y; Kochi M
TI - Sodium 5, 6-benzylidene-L-ascorbate induces in vitro neuronal cell differentiation accompanying apoptosis and necrosis.
SO - Anticancer Res 2002 May-Jun;22(3):1423-31
AD - Department of Biological Science and Technology, Science University of Tokyo, Noda, Chiba, Japan. email@example.com
Antiproliferative activity through induction of differentiation by chemotherapeutic agents is required for certain types of cancers. Here, we report that a potent antitumor agent, sodium 5, 6-benzylidene-L-ascorbate (SBA), could induce morphological change of human neuroblastoma IMR-32 cells into a ganglion-like cell aggregate (pseudoganglion) having many neurites and the property of cholinergic neurons. Simultaneously with neuronal differentiation, substantial apoptosis and necrosis/type 2 physiological cell death, which is independent of apoptosis and resistant to a broad-spectrum caspase inhibitor, Z-Asp-CH2-DCB, were also observed. These data indicated that SBA could suppress tumor cell growth through the induction of three different physiological pathways such as differentiation, apoptosis and necrosis by which tissues and organs regulate their own development and maintenance.
UI - 12196571
AU - D'Ascenzo M; Martinotti G; Azzena GB; Grassi C
TI - cGMP/protein kinase G-dependent inhibition of N-type Ca2+ channels induced by nitric oxide in human neuroblastoma IMR32 cells.
SO - J Neurosci 2002 Sep 1;22(17):7485-92
AD - Institute of Human Physiology, Medical School, Catholic University S. Cuore, I-00168 Rome, Italy.
Although data from our laboratory and others suggest that nitric oxide (NO) exerts an overall inhibitory action on high-voltage-activated Ca2+ channels, conflicting observations have been reported regarding its effects on N-type channels. We performed whole-cell and cell-attached patch-clamp recordings in IMR32 cells to clarify the functional role of NO in the modulation of N channels of human neuronal cells. During depolarizing steps to +10 mV from V(h) = -90 mV, the NO donor, sodium nitroprusside (SNP; 200 microm), reduced macroscopic N currents by 34% (p < 0.01). The magnitude of inhibition was similar at all voltages tested (range, -40 to +50 mV). No significant inhibition was observed when SNP was applied together with the NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide potassium salt (300 microm), or after cell treatment with the guanylate cyclase inhibitor, 1H-[1,2,4] oxadiazole [4,3-a] quinoxalin-1-one (10 microm). 8-bromoguanosine-cGMP (8-Br-cGMP) (400 microm) mimicked the effects of SNP, reducing Ba2+ currents by 37% (p < 0.001). Cell treatment with the protein kinase G (PKG) inhibitor KT5823 (1 microm) or guanosine 3',5'-cyclic monophosphorothioate, 8-(4-chloro-phenylthio)-Rp-isomer, triethylammonium salt (20 microm) virtually abolished the effects of 8-Br-cGMP. At the single-channel level, 8-Br-cGMP reduced the channel open probability by 59% and increased both the mean shut time and the null sweep probability, but it had no significant effects on channel conductance, mean open time, or latency of first openings. These data suggest that NO inhibits N-channel gating through cGMP and PKG. The consequent decrease in Ca2+ influx through these channels may affect different neuronal functions, including neurotransmitter release.
UI - 3361307
AU - Serra M; Mei L; Roeske WR; Lui GK; Watson M; Yamamura HI
TI - The intact human neuroblastoma cell (SH-SY5Y) exhibits high-affinity [3H]pirenzepine binding associated with hydrolysis of phosphatidylinositols.
SO - J Neurochem 1988 May;50(5):1513-21
AD - Department of Pharmacology, College of Medicine, University of Arizona, Tucson 85724.
The binding of [3H]pirenzepine to a human neuroblastoma cell line (SH-SY5Y) and its correlation with hydrolysis of phosphatidylinositols were characterized. Specific [3H]pirenzepine binding to intact cells was rapid, reversible, saturable, and of high affinity. Kinetic studies yielded association (k+1) and dissociation (k-1) rate constants of 5.2 +/- 1.4 X 10(6) M-1 min-1 and 1.1 +/- 0.06 X 10(-1) min-1, respectively. Saturation experiments revealed a single class of binding sites (nH = 1.1) for the radioligand with a total binding capacity of 160 +/- 33 fmol/mg protein and an apparent dissociation constant of 13 nM. The specific [3H]pirenzepine binding was inhibited by the presence of selected muscarinic drugs. The order of antagonist potency was atropine sulfate greater than pirenzepine greater than AF-DX 116, with K0.5 of 0.53 nM, 2.2 nM, and 190 nM, respectively. The binding properties of [3H](-)-quinuclidinyl benzilate and its quaternary derivative [3H](-)-methylquinuclidinyl benzilate were also investigated. The muscarinic agonist carbachol stimulated formation of inositol phosphates which could be inhibited by muscarinic antagonists. The inhibition constants of pirenzepine and AF-DX 116 were 11 nM and 190 nM, respectively. In conclusion, we show that the nonclassical muscarinic receptor antagonist [3H]pirenzepine identifies a high-affinity population of muscarinic sites which is associated with hydrolysis of phosphatidylinositols in this human neuroblastoma cell line.
UI - 2767136
AU - Lambert DG; Ghataorre AS; Nahorski SR
TI - Muscarinic receptor binding characteristics of a human neuroblastoma SK-N-SH and its clones SH-SY5Y and SH-EP1.
SO - Eur J Pharmacol 1989 Jun 8;165(1):71-7
AD - Department of Pharmacology and Therapeutics, Leicester, U.K.
The present study examines the muscarinic receptor binding characteristics of parent human neuroblastoma (SK-N-SH) and its neuroblast (SH-SY5Y) and epithelial-like (SH-EP1) clones using [3H]methylscopolamine [( 3H]NMS). Specific [3H]NMS binding to intact SK-N-SH and SH-SY5Y cells was saturable with a Kd of 0.2 nM and Bmax of 100-150 fmol/mg protein. Specific [3H]NMS binding to whole cell preparations of SH-EP 1 could not be detected. Pharmacological analysis of the binding site both in whole cells and membranes of SK-N-SH are indicative of an homogeneous receptor population possessing low affinity for the M1-selective antagonist pirenzepine. The muscarinic receptors expressed by the neuroblast clone, SH-SY5Y were further characterized and shown to have the properties of an homogeneous M3 subtype with low affinity for the M1-selective antagonist pirenzepine and the M2-cardioselective AFDX-116 but high affinity for 4-diphenylacetoxy-N-methyl piperidine methiodide (4-DAMP). In conclusion the SH-SY5Y neuroblastoma should provide an important human neuronal cell model with which to define the regulation of post-receptor events driven by a single receptor population.
UI - 12210443
AU - Burkhardt-Hammer T; Spix C; Brenner H; Kaatsch P; Berthold F; Hero B;
TI - Michaelis J Long-term survival of children with neuroblastoma prior to the neuroblastoma screening project in Germany.
SO - Med Pediatr Oncol 2002 Sep;39(3):156-62
AD - Department of Epidemiology, University Ulm, Ulm, Germany.
BACKGROUND: In the last decades, prognosis of children with neuroblastoma has improved only slightly. Traditional estimates of survival reflect the survival experience of children diagnosed many years ago, and may thus not capture more recent progress in prognosis. We applied a new method of survival analysis, denoted period analysis, to provide more up-to-date estimates of long-term prognosis. We selected the cases diagnosed before the German neuroblastoma screening project in 1995, allowing to assess the method by comparing the 1994 projected survival estimates with the observations made today (2000). PROCEDURE: The data comes from the population based German Childhood Cancer Registry. We included all 1,353 children diagnosed with neuroblastoma below age 15 between 1980 and 1994. We derived 5-, 10-, and 15-year survival estimates using traditional analysis or period analysis as needed. Where possible we compared the period analysis estimates with the later obtained actual estimates. We showed trends in survival for the sample as a whole and for prognostic subgroups. RESULTS: Survival probabilities increased over time especially in the subgroups with poor prognosis. Short-term survival probabilities improved more than long-term survival probabilities. Evaluation of the period-analysis estimates showed them to provide accurate and timely projections of prognosis of newly diagnosed patients. CONCLUSIONS: The results suggest major improvements in prognosis of children with neuroblastoma, even prior to the start of the German neuroblastoma screening project, especially in advanced disease. This could have been disclosed with the application of the period analysis method in 1995 even then with considerable accuracy. We recommend a more widespread application of this method especially in population-based cancer registries. Copyright 2002 Wiley-Liss, Inc.
UI - 12210456
AU - Barbato M; Clerico A; Viola F; Dito L; Schiavetti A; Cucchiara S
TI - Coeliac disease and ganglioneuroblastoma: an unusual association.
SO - Med Pediatr Oncol 2002 Sep;39(3):215-6
AD - Pediatric Gastroenterology Unit, Istitute of Pediatrics, University of Rome La Sapienza, Italy. firstname.lastname@example.org
UI - 12210038
AU - Burekhovich S; Ghosh BC
TI - Computer graphic to design the approach for resection of esthesioneuroblastoma.
SO - J Surg Oncol 2002 Aug;80(4):222-3
AD - State University of New York Health Science Center at Brooklyn, New York Harbor Healthcare System, Brooklyn Campus, Brooklyn, New York 11209, USA.
UI - 11932470
AU - Woods WG; Gao RN; Shuster JJ; Robison LL; Bernstein M; Weitzman S; Bunin
TI - G; Levy I; Brossard J; Dougherty G; Tuchman M; Lemieux B Screening of infants and mortality due to neuroblastoma.
SO - N Engl J Med 2002 Apr 4;346(14):1041-6
AD - AFLAC Cancer Center, Emory University and Children's Healthcare of Atlanta, GA 30322, USA. email@example.com
BACKGROUND: Neuroblastoma, the most common extracranial solid tumor that occurs in early childhood, can be identified in the preclinical stages by the detection of catecholamines in the urine. However, it is unknown whether routine screening for neuroblastoma reduces mortality due to this disease. METHODS: Through their parents, we offered screening for neuroblastoma at three weeks and six months of age to all 476,654 children born in the province of Quebec, Canada, during a five-year period (May 1, 1989, through April 30, 1994). The participation rate was 92 percent. The rate of death due to neuroblastoma was determined and compared with the rates in several unscreened control populations born during the same period. RESULTS: Among children younger than eight years of age in the Quebec cohort, there were 22 deaths due to neuroblastoma; the cumulative (+/-SE) mortality rate due to neuroblastoma was 4.78+/-1.14 per 100,000 children over a period of nine years. The standardized incidence ratios for death due to neuroblastoma for the Quebec cohort were 1.11 (95 percent confidence interval, 0.64 to 1.92) as compared with a control group in Ontario, Canada; 0.90 (95 percent confidence interval, 0.48 to 1.70) as compared with a control group in Minnesota; 1.40 (95 percent confidence interval, 0.81 to 2.41) as compared with a control group in Florida; and 0.96 (95 percent confidence interval, 0.56 to 1.66) as compared with a control group in the Greater Delaware Valley. The standardized mortality ratio for the Quebec cohort as compared with the rest of Canada was 1.39 (95 percent confidence interval, 0.85 to 2.30); the odds ratio for the comparison with a cohort born in Quebec before the screening program began was 0.98 (95 percent confidence interval, 0.54 to 1.77). CONCLUSIONS: Screening infants for neuroblastoma does not appear to reduce mortality due to this disease.
UI - 11932471
AU - Schilling FH; Spix C; Berthold F; Erttmann R; Fehse N; Hero B; Klein G;
TI - Sander J; Schwarz K; Treuner J; Zorn U; Michaelis J Neuroblastoma screening at one year of age.
SO - N Engl J Med 2002 Apr 4;346(14):1047-53
AD - Klinikum Stuttgart, Olgahospital, Child and Adolescent Health, Pediatrics 5, Stuttgart, Germany. firstname.lastname@example.org
BACKGROUND: Neuroblastoma is the second most common type of childhood tumor. It is not known whether screening for neuroblastoma at one year of age reduces the incidence of metastatic disease or mortality due to neuroblastoma. METHODS: We offered urine screening for neuroblastoma at approximately one year of age to 2,581,188 children in 6 of 16 German states from 1995 to 2000. A total of 2,117,600 eligible children in the remaining states served as controls. We compared the two groups in terms of the incidence of disseminated disease and mortality from neuroblastoma. RESULTS: A total of 1,475,773 children (61.2 percent of those who were born between July 1, 1994, and October 31, 1999) underwent screening. In this group, neuroblastoma was detected by screening in 149 children, of whom 3 have died. Fifty-five children who had negative screening tests were subsequently given a diagnosis of neuroblastoma; 14 of these children have died. The screened group and children in the control area had a similar incidence of stage 4 neuroblastoma (3.7 cases per 100,000 screened children [95 percent confidence interval, 2.7 to 4.7] and 3.8 per 100,000 controls [95 percent confidence interval, 2.9 to 4.6]) and a similar rate of death among children with neuroblastoma (1.3 deaths per 100,000 screened children [95 percent confidence interval, 0.7 to 1.8] and 1.2 per 100,000 controls [95 percent confidence interval, 0.7 to 1.7]). Comparison of the screened group and the children in the control area revealed substantial overdiagnosis in the former group (an estimated rate of 7 cases per 100,000 children [95 percent confidence interval, 4.6 to 9.2]); the overdiagnosis rate represents children who had neuroblastoma that was diagnosed by screening but who would not benefit from earlier diagnosis and treatment. CONCLUSIONS: The present findings do not support the usefulness of general screening for neuroblastoma at one year of age.
UI - 12226161
AU - Suita S
TI - Neuroblastoma screening in early life.
SO - N Engl J Med 2002 Sep 12;347(11):852-4; discussion 852-4
UI - 12227369
AU - Kerbl R; Urban CE; Ambros PF
TI - Neuroblastoma screening in early life.
SO - N Engl J Med 2002 Sep 12;347(11):852-4; discussion 852-4
UI - 12227370
AU - Collins MH
TI - Neuroblastoma screening in early life.
SO - N Engl J Med 2002 Sep 12;347(11):852-4; discussion 852-4
UI - 7920654
AU - Lahti JM; Valentine M; Xiang J; Jones B; Amann J; Grenet J; Richmond G;
TI - Look AT; Kidd VJ Alterations in the PITSLRE protein kinase gene complex on chromosome 1p36 in childhood neuroblastoma.
SO - Nat Genet 1994 Jul;7(3):370-5
AD - Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
p58cdc2L1, a protein kinase implicated in apoptotic signaling, is one of eight separate kinases encoded by three tandemly duplicated and linked genes, which we have termed PITSLRE A, B and C. One allele of this complex on chromosome 1 was either deleted or translocated in each of 18 neuroblastoma cell lines with cytogenetically apparent 1p alterations. A protein encoded by this locus, PITSLRE gamma 1, was absent in three of the lines and a smaller, apparently truncated, PITSLRE polypeptide was found in another line. These findings identify a novel gene complex on chromosome 1 that encodes a protein kinase subfamily. We suggest that the PITSLRE locus may harbour one or more tumour suppressor genes affected by chromosome 1p36 modifications in neuroblastoma.
UI - 7972224
AU - White PS; Fujimori M; Marshall HN; Kaufman BA; Brodeur GM
TI - Characterization of the region of consistent deletion within 1p36 in neuroblastomas.
SO - Prog Clin Biol Res 1994;385():3-9
AD - Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110.
UI - 10830907
AU - Judson H; van Roy N; Strain L; Vandesompele J; Van Gele M; Speleman F;
TI - Bonthron DT Structure and mutation analysis of the gene encoding DNA fragmentation factor 40 (caspase-activated nuclease), a candidate neuroblastoma tumour suppressor gene.
SO - Hum Genet 2000 Apr;106(4):406-13
AD - Molecular Medicine Unit, University of Leeds, St James's University Hospital, UK.
We have characterised the DFFB gene, encoding the active subunit of the apoptotic nuclease DNA fragmentation factor (DFF40). DFFB maps to 1p36, near the imprinted putative tumour suppressor gene TP73. The DFFA gene (encoding the inhibitory DFF45 subunit) also maps to 1p36.2-36.3, and we show by FISH that DFFB lies distal to DFFA. We have also mapped a processed DFFB pseudogene to chromosome 9. DFFB itself has seven coding exons spanning 10 kb. Exhaustive mutation screening of 41 neuroblastomas and other tumours in which a 1p36 tumour suppressor gene is implicated showed no tumour-specific mutations. A coding region polymorphism was used to demonstrate uniformly biallelic expression in human fetal DFFB transcripts. Since the putative neuroblastoma tumour suppressor gene in distal 1p36 is predicted to be maternally expressed, the lack of imprinting and absence of somatic mutations in DFFB indicate that it is probably not the neuroblastoma tumour suppressor gene.
UI - 11420752
AU - Yang HW; Chen YZ; Piao HY; Takita J; Soeda E; Hayashi Y
TI - DNA fragmentation factor 45 (DFF45) gene at 1p36.2 is homozygously deleted and encodes variant transcripts in neuroblastoma cell line.
SO - Neoplasia 2001 Mar-Apr;3(2):165-9
AD - Department of Pediatrics, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 13-8655, Japan.
Recently, loss of heterozygosity (LOH) studies suggest that more than two tumor suppressor genes lie on the short arm of chromosome 1 (1p) in neuroblastoma (NB). To identify candidate tumor suppressor genes in NB, we searched for homozygous deletions in 20 NB cell lines using a high-density STS map spanning chromosome 1p36, a common LOH region in NB. We found that the 45-kDa subunit of the DNA fragmentation factor (DFF45) gene was homozygously deleted in an NB cell line, NB-1. DFF45 is the chaperon of DFF40, and both molecules are necessary for caspase 3 to induce apoptosis. DFF35, a splicing variant of DFF45, is an inhibitor of DFF40. We examined 20 NB cell lines for expression and mutation of DFF45 gene by reverse transcription (RT)-polymerase chain reaction (PCR) and RT-PCR-single-strand conformation polymorphism. Some novel variant transcripts of the DFF45 gene were found in NB cell lines, but not in normal adrenal gland and peripheral blood. These variants may not serve as chaperons of DFF40, but as inhibitors like DFF35, thus disrupting the balance between DFF45 and DFF40. No mutations of the DFF45 gene were found in any NB cell line, suggesting that the DFF45 is not a tumor suppressor gene for NB. However, homozygous deletion of the DFF45 gene in the NB-1 cell line may imply the presence of unknown tumor suppressor genes in this region.
UI - 11870543
AU - Abel F; Sjoberg RM; Ejeskar K; Krona C; Martinsson T
TI - Analyses of apoptotic regulators CASP9 and DFFA at 1P36.2, reveal rare allele variants in human neuroblastoma tumours.
SO - Br J Cancer 2002 Feb 12;86(4):596-604
AD - Department of Clinical Genetics, Gothenburg University, Sahlgrenska University Hospital/East, S-416 85 Gothenburg, Sweden.
The genes encoding Caspase-9 and DFF45 have both recently been mapped to chromosome region 1p36.2, that is a region alleged to involve one or several tumour suppressor genes in neuroblastoma tumours. This study presents an update contig of the 'Smallest Region of Overlap of deletions' in Scandinavian neuroblastoma tumours and suggests that DFF45 is localized in the region. The genomic organization of the human DFF45 gene, deduced by in-silico comparisons of DNA sequences, is described for the first time in this paper. In the present study 44 primary tumours were screened for mutation by analysis of the genomic sequences of the genes. In two out of the 44 tumours this detected in the DFFA gene one rare allele variant that caused a non-polar to a polar amino acid exchange in a preserved hydrophobic patch of DFF45. One case was hemizygous due to deletion of the more common allele of this polymorphism. Out of 194 normal control alleles only one was found to carry this variant allele, so in respect of it, no healthy control individual out of 97 was homozygous. Moreover, our RT-PCR expression studies showed that DFF45 is preferably expressed in low-stage neuroblastoma tumours and to a lesser degree in high-stage neuroblastomas. We conclude that although coding mutations of Caspase-9 and DFF45 are infrequent in neuroblastoma tumours, our discovery of a rare allele in two neuroblastoma cases should be taken to warrant further studies of the role of DFF45 in neuroblastoma genetics.
UI - 12203125
AU - Hopkins-Donaldson S; Yan P; Bourloud KB; Muhlethaler A; Bodmer JL; Gross
TI - N Doxorubicin-induced death in neuroblastoma does not involve death receptors in S-type cells and is caspase-independent in N-type cells.
SO - Oncogene 2002 Sep 5;21(39):6132-7
AD - Department of Pediatric Onco-Hematology, Centre Hospitalier Universitaire Vaudois, CH1011 Lausanne, Switzerland.
Death induced by doxorubicin (dox) in neuroblastoma (NB) cells was originally thought to occur via the Fas pathway, however since studies suggest that caspase-8 expression is silenced in most high stage NB tumors, it is more probable that dox-induced death occurs via a different mechanism. Caspase-8 silenced N-type invasive NB cell lines LAN-1 and IMR-32 were investigated for their sensitivity to dox, and compared to S-type noninvasive SH-EP NB cells expressing caspase-8. All cell lines had similar sensitivities to dox, independently of caspase-8 expression. Dox induced caspase-3, -7, -8 and -9 and Bid cleavage in S-type cells and death was blocked by caspase inhibitors but not by oxygen radical scavenger BHA. In contrast, dox-induced death in N-type cells was caspase-independent and was inhibited by BHA. Dox induced a drop in mitochondrial membrane permeability in all cell lines. Dox-induced death in S-type cells gave rise to apoptotic nuclei, whereas in N-type cells nuclei were non-apoptotic in morphology. Transfection of SH-EP cells with a dominant negative FADD mutant inhibited TRAIL-induced death, but had no effect on dox-induced apoptosis. These results suggest that S-type cells undergo apoptosis after dox treatment independently of death receptors, whereas N-type cells are killed by a caspase-independent mechanism.
UI - 12209604
AU - Behrends U; Jandl T; Golbeck A; Lechner B; Muller-Weihrich S; Schmid I;
TI - Till H; Berthold F; Voltz R; Mautner JM Novel products of the HUD, HUC, NNP-1 and alpha-internexin genes identified by autologous antibody screening of a pediatric neuroblastoma library.
SO - Int J Cancer 2002 Aug 20;100(6):669-77
AD - Hamatologie-Onkologie, Kinderklinik der Technische Universitat Munchen, Kolner Platz 1, 80804 Munich, Germany. email@example.com
Autologous serological screening of a cDNA expression library (SEREX) derived from childhood neuroblastoma led to the identification of 10 different antigens, including 6 novel gene products. The novel antigen 018INX was derived from a small open reading frame in a region of alpha-internexin mRNA that was previously described as 3' untranslated region. 018INX thus represents a novel type of tumor antigen. Five novel gene products were derived from NNP-1 (NNP3) and Hu genes (HuC-L, HuD3, HuDY, HuD1pro(c)). As indicated by sequence analysis, these antigens were generated by alternative splicing and/or alternative promoter usage or allelic polymorphism. mRNA expression analyses revealed different tissue restrictions of novel compared to known HuD and NNP-1 transcripts in normal and malignant tissues. The expressions patterns of distinct transcripts indicated potential clinical meanings as diagnostic and/or prognostic tissue markers. When kinetics of serum antibody titres against SEREX-defined antigens were compared to tumor load over time in our patient with neuroblastoma, we found 100-fold increases of anti-Hu and anti-018INX antibody titres preceding the clinical diagnosis of recurrent tumor growth after 2 years. When sera of pediatric patients with cancer (30) and healthy controls (30) were tested for humoral responses to SEREX-defined neuroblastoma antigens, we detected antibodies against all known antigens and NNP3 with low frequencies and titres in control sera, while anti-018INX and anti-Hu antibodies were found in cancer patients only. Our findings indicate that SEREX-defined tumor antigens might provide novel tools for understanding and treatment of this aggressive childhood malignancy. Copyright 2002 Wiley-Liss, Inc.
UI - 12097996
AU - Sterba J
TI - Contemporary therapeutic options for children with high risk neuroblastoma.
SO - Neoplasma 2002;49(3):133-40
AD - Pediatric Oncology Department; University Hospital, Brno, 662 63 Czech Republic. firstname.lastname@example.org
Despite the use of aggressive chemotherapy, stage 4 high risk neuroblastoma still has a very poor prognosis, which is estimated at 25%. Therefore, novel treatment approaches are needed. Increasing number of reports has been concerned with the use of novel treatment modalities. Literature regarding intensive induction, local therapy, myeloablative therapy and immunotherapy and biotherapy was reviewed in order to draw conclusions and recommendations for the management of children with high risk neuroblastic tumors.
UI - 12175342
AU - Zhao SP; Zhou XF
TI - Co-expression of trkA and p75 neurotrophin receptor in extracranial olfactory neuroblastoma cells.
SO - Neuropathol Appl Neurobiol 2002 Aug;28(4):301-7
AD - Department of ENT, Xiang-Ya Hospital, Central South University, Changsha, PR China.
Olfactory neuroblastoma (ON, esthesioneuroblastoma) is a high-grade malignant tumour of neuronal origin. Little is known about the neurobiological behaviour of this tumour. Ten cases of ON and five cases of nasopharyngeal carcinoma were examined for expression of trkA and p75 neurotrophin receptor (p75NTR) using immunohistochemistry and double labelling fluorescence. We found that all ON tissues from 10 cases expressed both trkA and p75NTR at different levels. Double staining revealed that almost all trkA-immunoreactive ON cells also contained p75NTR immunoreactivity. By contrast, no trkA or p75NTR immunoreactivity was detected in nasopharyngeal carcinoma cells from five patients. These results suggest that nerve growth factor may play a role in the generation of ON and staining of trkA and p75NTR may assist in the diagnosis of ON.
UI - 12216106
AU - Kushner BH; Kramer K; Cheung NK
TI - Chronic neuroblastoma.
SO - Cancer 2002 Sep 15;95(6):1366-75
AD - Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. email@example.com
BACKGROUND: An indolent course is associated with neuroblastoma (NB) in adolescents and adults. In the current study, the authors analyzed this phenomenon in a large series of children with metastatic NB. METHODS: The authors studied 38 patients who were diagnosed with NB in the first decade of life and had metastatic disease 5 years or more from diagnosis. RESULTS: The median age at diagnosis was 3 years 10 months. MYCN was amplified in 2 of 28 patients tested. Of 30 patients with classic Stage 4 NB, 9 had a late first recurrence of disease (4.3-13 years from diagnosis). Of eight patients who had atypical cases at diagnosis (one isolated mandibular lesion, two Stage 4-N, five non-Stage 4), six had a late first distant recurrence of disease (4 years 11 months-38 years 8 months). Nineteen patients were off therapy continuously for 3 years or more before disease recurred a first or second time. Myeloablative therapy was used to consolidate a first or second response in 27 patients. High-dose conventional therapy helped to achieve a second remission of disease in 9 of 20 patients assessable for response of first recurrence but achieved no major responses of second or third relapse in 10 of 11 patients. The combination of anti-G(D2) immunotherapy and/or cis-retinoic acid, targeted radiotherapy, and multiple cycles of chemotherapy with modest toxicity helped prolong survival. Twelve patients survive at 5 years 6 months+ to 19 years 4 months+ from diagnosis (median, 6 years 10 months+), including four with complete remission of disease; 10 received anti-G(D2) immunotherapy after recurrence. The other 26 patients died of disease (n = 22) or toxicity (n = 4) at 5 years-41 years 5 months from diagnosis (median, 6 years 5 months). CONCLUSIONS: The concept of indolent or smoldering NB should not be limited to adolescents/adults. The expanding repertoire of anti-NB treatments, including biologic therapies and chemotherapy regimens of modest toxicity, can convert childhood NB into a chronic disease with prolonged survival after recurrence. Copyright 2002 American Cancer Society.
UI - 10415288
AU - Koyama T; Kanadani T; Tanaka M; Nakahara S; Yamadori I
TI - A case of Down's syndrome associated with progressive extradural neuroblastoma.
SO - Pediatr Surg Int 1999 Jul;15(5-6):373-5
AD - Department of Pediatrics, National Okayama Hospital, 2-13-1 Minamigata, Okayama-City, 700-8566, Japan.
We describe a case of Down's syndrome associated with progressive extradural neuroblastoma. Postmortem aspiration of the bone marrow revealed diffuse infiltration by tumor cells, in which trisomy 21 was found by fluorescence in hybridization in situ.
UI - 10472332
AU - Soling A; Schurr P; Berthold F
TI - Expression and clinical relevance of NY-ESO-1, MAGE-1 and MAGE-3 in neuroblastoma.
SO - Anticancer Res 1999 May-Jun;19(3B):2205-9
AD - Department of Pediatric Hematology and Oncology, University of Cologne, Germany. firstname.lastname@example.org
Human genes NY-ESO-1, MAGE-1 and MAGE-3 code for antigens which are expressed in malignancies of various histological types but not in normal tissues except testis. These antigens might therefore represent potential targets for specific immunotherapy. We studied the expression of genes NY-ESO-1, MAGE-1 and MAGE-3 in 98 neuroblastoma tumors by reverse transcription-polymerase chain reaction (RT-PCR). MAGE-1 was expressed in 66%, NY-ESO-1 in 36% and MAGE-3 in 33% of the tumors. NY-ESO-1 gene expression was associated with age older than one year (p = 0.017), more differentiated tumor histology (p = 0.044), elevated urinary vanillylmandelic acid (VMA, p = 0.018) and normal serum ferritin levels (p = 0.023). MAGE-1 expression correlated significantly with normal serum ferritin levels (p = 0.009) and absence of MycN amplification (p = 0.007) while MAGE-3 expression was associated with absence of metastasis (p = 0.027). We conclude that approximately 70% of the neuroblastoma tumors express at least one of the genes coding for NY-ESO-1, MAGE-1 or -3, respectively.
UI - 11958898
AU - Paulino AC; Mayr NA; Simon JH; Buatti JM
TI - Locoregional control in infants with neuroblastoma: role of radiation therapy and late toxicity.
SO - Int J Radiat Oncol Biol Phys 2002 Mar 15;52(4):1025-31
AD - Department ofRadiation Oncology, The University of Iowa College of Medicine and Children's Hospital of Iowa, Iowa City, IA 52242, USA. email@example.com
PURPOSE: To review patterns of failure in infants with neuroblastoma and determine late toxicity and efficacy of radiotherapy (RT) on locoregional control. MATERIALS AND METHODS: From 1955 to 1998, 53 children (35 males and 18 females) <1 year old with neuroblastoma were seen at our institution. Twenty-one (40%) were =1 month of age (neonates). Seven congenital anomalies were seen in 4 children (atrial septal defect, pulmonary valve stenosis, and absent corpus callosum were seen in 1 patient each; the other child had atrial and ventricular septal defect, aortic arch hypoplasia, and mitral valve stenosis). Primary tumor was located in the adrenal gland in 26 (49%), abdomen/nonadrenal in 14 (26%), thorax in 9 (17%), neck in 2 (4%), and pelvis in 2 (4%). All infants were retrospectively staged acco
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