• [Modulation of voltage-gated sodium channels by recombinant interferon-alpha2b in the human neuroblastoma cell line IMR-32]

• Complicated mechanisms of class II transactivator transcription deficiency in small cell lung cancer and neuroblastoma.

• Muscarinic receptor-mediated phosphorylation of cyclic AMP response element binding protein in human neuroblastoma cells.

• Isolation of streptonigrin and its novel derivative from Micromonospora as inducing agents of p53-dependent cell apoptosis.

• Circulating MYCN DNA as a tumor-specific marker in neuroblastoma patients.

• Role of the aspartyl-asparaginyl-beta-hydroxylase gene in neuroblastoma cell motility.

• Treatment of intracranial metastatic esthesioneuroblastoma.

• A brief commentary on "Chromosomal aberrations in neuroblastoma cell lines identified by cross species color banding and chromosome

• Expression of DeltaNp73 is a molecular marker for adverse outcome in neuroblastoma patients.

• Esthesioneuroblastoma: case report.

• Activation of the phosphatidylinositol 3-kinase/Akt signaling pathway by retinoic acid is required for neural differentiation of SH-SY5Y human

• Improved survival of children with advanced neuroblastoma treated by intensified therapy including myeloablative chemotherapy with stem cell

• Breakpoint position on 17q identifies the most aggressive neuroblastoma tumors.

• Establishment of cisplatin-resistant variants of human neuroblastoma cell lines, TGW and GOTO, and their drug cross-resistance profiles.

• Inhibition of insulin-like growth factor-1 receptor and IRS-2 signaling by ethanol in SH-SY5Y neuroblastoma cells.

• Two cases of pediatric neuroblastoma with tumor thrombus in the inferior vena cava.

• In vitro fertilization and childhood cancer.

• [A case of ganglioneuroblastoma occurring in the superior mediastinum in an adult]

• Stephen L. Gans overseas lecture. Mass screening for neuroblastoma in Japan: lessons learned and future directions.

• Analysis of cytogenetic aberrations in esthesioneuroblastomas by comparative genomic hybridization.

• Characterization of [3H]MK-801 binding in LA-N-2 neuroblastoma cells.

• [Diabetes mellitus with mixed neuroendocrine-neural tumor]

• Congenital heart disease and neuroblastoma: just coincidence?

• Doxorubicin resistant neuroblastoma cells secrete factors that activate AKT and attenuate cytotoxicity in drug-sensitive cells.

• TRAIL enhances thymidine kinase/ganciclovir gene therapy of neuroblastoma cells.

• Evolving significance of prognostic markers associated with treatment improvement in patients with stage 4 neuroblastoma.

1
UI - 12035540
AU - Kucher VV; Magura IS; Rozhmanova OM; Dolgaia EV; Pogorelaia NKh
TI - [Modulation of voltage-gated sodium channels by recombinant interferon-alpha2b in the human neuroblastoma cell line IMR-32]
SO - Ukr Biokhim Zh 2001 May-Jun;73(3):112-5
AD - Bogomolets Institute of Physiology, NAS of Ukraine, Kyiv.
Clonal human neuroblastoma cells imr-32 are a suitable model system for studies of neuronal excitability modulation. The ability interferon-alpha 2b "laferon" to modulate the mechanisms of electrical activity was studied in whole-cell patch-clamped undifferentiated human neuroblastoma cells IMR-32. It was shown that 1 h incubation of IMR-32 cells at 37 degrees C in medium with laferon (600 U/ml) exerted changes in voltage-dependent properties of Na(+)-channels. The results of the present study demonstrate that laferon decreased of Na(+)-channels sensitivity to changes of membrane potential leading of IMR-32 cells electrical excitability decrease.

2
UI - 12107114
AU - Yazawa T; Ito T; Kamma H; Suzuki T; Okudela K; Hayashi H; Horiguchi H;
TI - Ogata T; Mitsui H; Ikeda M; Kitamura H Complicated mechanisms of class II transactivator transcription deficiency in small cell lung cancer and neuroblastoma.
SO - Am J Pathol 2002 Jul;161(1):291-300
AD - Department of Pathology, Yokohama City University School of Medicine, Kanagawa, Japan. tkyazawa@med.yokohama-cu.ac.jp
Small cell lung cancer (SCLC) and neuroblastoma (NB), the most aggressive adult and infant neuroendocrine cancers, respectively, are immunologically characterized by a severe reduction in major histocompatibility complex (MHC) that is indispensable for anti-tumor immunity. We had reported that the severe reduction of MHC in SCLC was caused by a deficient interferon (IFN)-gamma-inducible expression of class II transactivator (CIITA) that is known as a very important transcription factor for IFN-gamma-inducible class II and class I MHC expression (Yazawa T, Kamma H, Fujiwara M, Matsui M, Horiguchi H, Satoh H, Fujimoto M, Yokohama K, Ogata T: Lack of class II transactivator causes severe deficiency of HLA-DR expression in small cell lung cancer. J Pathol 1999, 187:191-199). Here, we demonstrate that the reduction of MHC in NB was also caused by a deficient IFN-gamma-inducible expression of CIITA and that the deficiency in SCLC and NB was caused by similar mechanisms. Human achaete-scute complex homologue (HASH)-1, L-myc, and N-myc, which are specifically overexpressed in SCLC and NB, bound to the E-box in CIITA promoter IV and reduced the transcriptional activity. Anti-sense oligonucleotide experiments revealed that overexpressed L-myc and N-myc lie upstream in the regulatory pathway of HASH-1 expression. The expression of HASH-1 was also up-regulated by IFN-gamma. Our results suggest that SCLC and NB have complicated mechanisms of IFN-gamma-inducible CIITA transcription deficiency through the overexpressed HASH-1, L-myc, and N-myc. These complicated mechanisms may play an important role in the escape from anti-tumor immunity.

3
UI - 12124440
AU - Greenwood JM; Dragunow M
TI - Muscarinic receptor-mediated phosphorylation of cyclic AMP response element binding protein in human neuroblastoma cells.
SO - J Neurochem 2002 Jul;82(2):389-97
AD - Department of Pharmacology, Faculty of Medicine and Health Science, University of Auckland, Auckland, New Zealand.
This study describes the effect of signalling through muscarinic acetylcholine receptors on two transcription factors implicated in long-term synaptic plasticity and memory formation, EGR1 and the cyclic AMP response element binding protein (CREB). In SK-N-SH neuroblastoma cells, treatment with the cholinergic agonist carbachol led to maximal induction of EGR1 1 h after stimulation. This was preceded by the phosphorylation of CREB, which peaked as early as 5 minutes after carbachol treatment. The levels of both EGR1 and phosphorylated CREB (pCREB) slowly decayed over 4-8 h. CREB phosphorylation and EGR1 induction showed similar sensitivity to carbachol concentration, with EC(50) values in the range of 1-10 microM, and the changes in both transcription factors were blocked by the muscarinic antagonist atropine. As has been described elsewhere, EGR1 induction was dependent on activation of p42/44 MAP kinase, as it was blocked by the MEK inhibitor U0126. However, CREB phosphorylation by carbachol was largely unaffected by MAP kinase blockade. As both CREB phosphorylation and EGR1 induction have been linked to long-term potentiation and some forms of memory consolidation, these results may implicate CREB and EGR1 in independent or partially independent cholinergic signalling pathways involved in memory processes.

4
UI - 12027749
AU - Wang H; Yeo SL; Xu J; Xu X; He H; Ronca F; Ting AE; Wang Y; Yu VC; Sim
TI - MM Isolation of streptonigrin and its novel derivative from Micromonospora as inducing agents of p53-dependent cell apoptosis.
SO - J Nat Prod 2002 May;65(5):721-4
AD - Medicinal and Combinatorial Chemistry Laboratory, Lead Discovery Group, Microbial Collection, Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore 117609, Singapore.
Streptonigrin (1) and its novel natural derivative 7-(1-methyl-2-oxopropyl)streptonigrin (2) were isolated from an actinomycete strain, Micromonospora sp. IM 2670. The inductions for 1 and 2 are more potent in the human neuroblastoma SH-SY5Y cells that contain wild-type p53 than in SH-SY5Y-5.6 cells that overexpress a dominant negative mutant of p53, thus suggesting that they induce apoptosis through a p53-dependent pathway.

5
UI - 12097268
AU - Combaret V; Audoynaud C; Iacono I; Favrot MC; Schell M; Bergeron C;
TI - Puisieux A Circulating MYCN DNA as a tumor-specific marker in neuroblastoma patients.
SO - Cancer Res 2002 Jul 1;62(13):3646-8
AD - Centre Leon Berard, 69008 Lyon, France.
MYCN oncogene amplification is an established indicator of the aggressiveness of neuroblastomas; it is used internationally for stratifying patients for therapy. The present study shows that high levels of MYCN DNA sequences are present in the peripheral blood of patients with MYCN-amplified neuroblastomas. Circulating MYCN DNA may be a powerful and noninvasive prognostic marker at the time of diagnosis. Furthermore, preliminary data strongly suggest that the release of MYCN sequences in the peripheral blood is an early process in disease progression, permitting us to propose this novel marker for the follow-up of patients after chemotherapy.

6
UI - 12118090
AU - Sepe PS; Lahousse SA; Gemelli B; Chang H; Maeda T; Wands JR; de la Monte
TI - SM Role of the aspartyl-asparaginyl-beta-hydroxylase gene in neuroblastoma cell motility.
SO - Lab Invest 2002 Jul;82(7):881-91
AD - Department of Medicine, Rhode Island Hospital, Brown Medical School, Providence, Rhode Island 02903, USA.
Aspartyl (asparaginyl) beta-hydroxylase (AAH) is overexpressed in various malignant neoplasms, and high levels of immunoreactivity mainly occur in infiltrating or metastasized tumors. In addition, AAH is abundantly expressed in normally invasive placental trophoblastic cells. These observations led to the hypothesis that AAH may have a role in motility and aggressive behavior of tumor cells. The present study demonstrates that AAH is overexpressed in primary human malignant neuroectodermal tumors, including medulloblastomas and neuroblastomas, and that AAH expression is at a low level or undetectable in the normal mature brain. In the Sy5y neuroblastoma cell line, endogenous expression of the approximately 86-kd AAH protein was demonstrated by Western blot analysis, and immunoreactivity predominantly localized to the cell surface by immunocytochemical staining and FACS analysis. Sy5y cells that were stably transfected with the human AAH cDNA had increased levels of proliferating cell nuclear antigen and Bcl-2, and reduced levels of p21/Waf1 and p16. In addition, increased AAH expression enhanced Sy5y cell motility, whereas antisense oligodeoxynucleotide inhibition of AAH significantly reduced Sy5y cell motility and increased the levels of p21/Waf1 and p16. The findings suggest that AAH overexpression contributes to the malignant phenotype of neuroectodermal tumor cells by increasing motility and enhancing proliferation, survival, and cell cycle progression. Because AAH expression is at a low level or undetectable in normal brain, the AAH gene may be a target for treating primitive neuroectodermal tumors.

7
UI - 12124822
AU - Chamberlain MC
TI - Treatment of intracranial metastatic esthesioneuroblastoma.
SO - Cancer 2002 Jul 15;95(2):243-8
AD - Department of Neurology, University of Southern California, Norris Comprehensive Cancer Center and Hospital, Los Angeles, California 90033-0804, USA. chamberl@usc.edu
BACKGROUND: Esthesioneuroblastoma (ENB) is an uncommon tumor that may metastasize to the central nervous system (CNS). To the authors' knowledge there is no current consensus regarding treatment. The current study was conducted to determine the toxicity and response rate of combined modality therapy in the treatment of patients with ENB metastatic to the brain. METHODS: Six patients (2 men and 4 women) ranging in age from 47-61 years (median age, 53.5 years) with ENB had clinical and neuroradiographic evidence of CNS metastases (brain parenchyma in 6 patients and leptomeningeal metastases in 3 patients). CNS-directed therapy included radiotherapy (to the brain in three patients and to the spine in two patients) and chemotherapy (systemic in six patients and regional in three patients). Systemic chemotherapy was comprised of carboplatin, lomustine, and vincristine administered every 2 months. Patients were evaluated by neuroradiographic and neurologic examination every other month. RESULTS: Between 1-6 cycles of systemic chemotherapy were administered (median, 4.5 cycles). and 6-19 cycles of regional chemotherapy were administered (median, 17 cycles). Toxicity included aseptic meningitis (three patients), radiation enteritis (one patient), and > or = Grade 3 (according to the National Cancer Institute Common toxicity Criteria) myelosuppression (four patients). Two patients required hospitalization for neutropenic fever and two patients required a transfusion (platelets in two patients and red blood cells in one patient). No treatment-related deaths were reported. A partial response was achieved in four patients, and two patients demonstrated progressive disease. The median duration of response was 9 months (range, 2-12 months). Overall survival ranged from 3-13 months (median, 10.5 months). The cause of death was progressive parenchymal brain disease in three patients, systemic disease in two patients, and leptomeningeal disease in one patient. CONCLUSIONS: In the small cohort of patients in the current study, combined modality therapy was found to have modest toxicity and palliative efficacy. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10679

8
UI - 12127407
AU - Vandesompele J; Speleman F
TI - A brief commentary on "Chromosomal aberrations in neuroblastoma cell lines identified by cross species color banding and chromosome painting".
SO - Cancer Genet Cytogenet 2002 Jun;135(2):196

9
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.

10
UI - 12068366
AU - Gondim J; Ramos F Jr; Azevedo J; Carrero FP Jr; Tella OI Jr
TI - Esthesioneuroblastoma: case report.
SO - Arq Neuropsiquiatr 2002 Jun;60(2-A):303-7
AD - Hospital Geral de Fortaleza, Fortaleza, CE, Brazil. jagondim@secrel.com.br
Esthesioneuroblatoma (ENB) is a rare tumor arising from the olfactory epithelium of the nasal vault which frequently invades the cranial base, cranial vault and orbit. ENB has a bimodal age distribution between 11 and 20 years and between 51 and 60 years. ENB accounts for approximately 1 to 5% of intranasal cancers and no consensus has been reached regarding treatment of this tumor. We report on a 66 year old female patient with a Kadish stage C tumor with frontal lobe invasion submitted a total craniofacial resection with a combined head neck and neurosurgeon team. The purpose of this study is to analyze the natural history, treatment and prognosis of this tumor, based on the literature review.

11
UI - 12000752
AU - Lopez-Carballo G; Moreno L; Masia S; Perez P; Barettino D
TI - Activation of the phosphatidylinositol 3-kinase/Akt signaling pathway by retinoic acid is required for neural differentiation of SH-SY5Y human neuroblastoma cells.
SO - J Biol Chem 2002 Jul 12;277(28):25297-304
AD - Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Cientificas, Spain.
Retinoic acid (RA) induces neural differentiation of SH-SY5Y neuroblastoma cells. We show that the mRNA levels of the differentiation-inhibiting basic helix-loop-helix transcription factors ID1, ID2, and ID3 are down-regulated during RA-induced differentiation of SH-SY5Y cells. The levels of ID proteins decreased in parallel to the observed transcriptional repression. The expression of other basic helix-loop-helix genes changed during RA-induced differentiation: expression of neuroblast-specific ASCL1 (HASH-1) gene was promptly reduced after RA treatment, whereas expression of differentiation-promoting genes NEUROD6 (NEX-1, HATH-2) and NEUROD1 was increased. Treatments with 12-O-tetradecanoylphorbol-13-acetate, another inducer of neuroblastoma cell differentiation, also resulted in coordinated down-regulation of ID gene expression, underscoring the role of ID genes in differentiation. Down-regulation of ID gene expression by RA involves a complex mechanism because full transcriptional repression required newly synthesized proteins and signaling by phosphatidylinositol 3-kinase (PI3K). RA treatment activates the PI3K/Akt signaling pathway, resulting in increased PI3K activity in extracts from RA-treated cells and a rapid increase in phosphorylation of Akt in Ser-473. Inhibition of PI3K by LY294002 impaired RA-induced differentiation, as assessed by morphological and biochemical criteria. We propose that RA, by activating the PI3K/Akt signaling pathway, plays an important role in the regulation of neuronal cell survival.

12
UI - 11846211
AU - Imaizumi M; Watanabe A; Kikuta A; Takano T; Ito E; Shimizu T; Tsuchiya
TI - S; Iinuma K; Konno T; Ohi R; Hayashi Y; Tohoku Neuroblastoma Study Group Improved survival of children with advanced neuroblastoma treated by intensified therapy including myeloablative chemotherapy with stem cell transplantation: a retrospective analysis from the Tohoku Neuroblastoma Study Group.
SO - Tohoku J Exp Med 2001 Oct;195(2):73-83
AD - Department of Pediatric Hematology and Oncology, Tohoku University School of Medicine, Sendai, Japan. mimaizumi@ped.med.tohoku.ac.jp
In the hospitals of the Tohoku Neuroblastoma Study Group (TNBSG), treatment for children with advanced neuroblastoma (NB) was intensified in the mid-1990's with the introduction of myeloablative therapy (MT) with stem cell transplantation (SCT) including the use of autologous peripheral blood stem cells (PBSC) and bone marrow transplantation (BMT). In this report, we examined whether the intensified therapy improved the outcome of children with advanced NB (age> 12 months) who were diagnosed between 1991 and 1997. Patients were 36 children (23 boys and 13 girls) with an average age of 3.4 years (range; 1 to 14 years). Six of them had stage III disease, and the other 30 had stage IV. They were treated initially with induction chemotherapy, surgery, and post-operative chemoradiotherapy, after which 17 of them continued further chemotherapy and the other 19 received MT/SCT (18 with PBSCT and 1 with BMT). Progression-free survival (PFS) rate at seven years from diagnosis was 43.5% for all patients, 66.7% for stage III patients and 38.2% for stage IV patients. The difference between stage III and IV patients was not significant. Among the 30 patients with stage IV disease, PFS at seven years was significantly higher in the 19 patients who received MT/SCT (55.6%) than in the 11 patients who did not receive it (12.5%). There was no difference in clinical and biological risk factors between these two groups, except for the proportion of patients with favorable response to initial therapy (36% and 80% for patients without and with MT/SCT, respectively). Furthermore, the proportion of patients with N-myc amplification was significantly higher in patients with progressive disease (PD) after MT/SCT than in those in CR after MT/SCT. The results of this retrospective study of children with advanced NB suggest that therapy intensification involving MT/SCT might result in lengthened survival time for patients with stage IV disease, and that post-transplant PD remains a risk for patients with high levels of N-myc amplification.

13
UI - 12112532
AU - Lastowska M; Cotterill S; Bown N; Cullinane C; Variend S; Lunec J;
TI - Strachan T; Pearson AD; Jackson MS Breakpoint position on 17q identifies the most aggressive neuroblastoma tumors.
SO - Genes Chromosomes Cancer 2002 Aug;34(4):428-36
AD - Institute of Human Genetics, International Centre for Life, University of Newcastle upon Tyne, Central Parkway, Newcastle upon Tyne NE1 3BZ, UK. m.a.lastowska@ncl.ac.uk
Gain of chromosome arm 17q is a powerful prognostic factor in neuroblastoma, and the distribution of 17q breakpoints suggests that the dosage of one or more genes in 17q22-23 to 17qter is critical for tumor progression. To identify the smallest region of 17q gain, we used eight probes to map translocation breakpoints in 48 primary neuroblastoma tumors. We identified at least five different breakpoints, all localized within the proximal part of 17q (from D17Z1 to MPO). The shortest region of gain identified by these probes extends from MPO (17q23.1) to 17qter. Surprisingly, we found that breakpoints localized proximal to ERBB2 (17q12) were associated with significantly better patient survival than breakpoints localized distal to ERBB2. Breakpoints localized distal to ERBB2 identified patients with a particularly poor prognosis, higher mitotic karyorrhectic index, and stage 4 disease. This implies that breakpoint position on 17q is a discriminative factor within this prognostically poor group of patients. This result also suggests that the biological effect of 17q gain during neuroblastoma progression has a complex basis. We propose that this involves dosage alterations of genes localized on both sides of the 17q breakpoints, with a gene or genes mapping between 17cen and 17q12 acting to suppress progression, and a gene or genes mapping between 17q23.1 and 17qter acting to promote tumor progression. Copyright 2002 Wiley-Liss, Inc.

14
UI - 12107547
AU - Iwasaki I; Sugiyama H; Kanazawa S; Hemmi H
TI - Establishment of cisplatin-resistant variants of human neuroblastoma cell lines, TGW and GOTO, and their drug cross-resistance profiles.
SO - Cancer Chemother Pharmacol 2002 Jun;49(6):438-44
AD - Department of Molecular Biology, Toho University School of Medicine, 5-21-16 Ohmori-Nishi, Ohta-Ku, Tokyo 143-8540, Japan.
PURPOSE: The emergence of multidrug resistance (MDR) in neuroblastoma is a critical issue for chemotherapy. In order to study low-level MDR, we developed variants derived from two neuroblastoma cell lines, TGW and GOTO, by exposure to low doses of cisplatin (CDDP). The cross-resistance to other cytotoxic agents and expression of MDR-related proteins in the variants and their clones were examined. MATERIALS AND METHODS: Cells were exposed to 3 or 10 micro M CDDP and three variants were obtained from each cell line, TGW and GOTO. Clones TR1 and TR2, derived from the TGW variants, were also established. Cytotoxicity was determined using a dye-staining method. Expression of MDR-related proteins was detected by immunoblotting. RESULTS: Resistant variants exhibited 1.1- to 2.5-fold increased resistance to CDDP, N-methyl- N'-nitro- N-nitrosoguanidine (MNNG), doxorubicin and vincristine. The cytotoxicity of these agents varied between clones of resistant variants. The microsatellite profiles of the TR1 clones differed, indicating that the TR1 variant comprised a heterogeneous cell population. The cytotoxicities of cytosine beta- D-arabinofuranoside (Ara-C) and chlorambucil in these variants and clones were similar to those in the parent cells. No significant changes in the cellular levels of MDR1, MRP, hMLH1 and hMSH2 were detected in the TGW variants. Cyclosporin A increased the sensitivity of both parental cell lines and the variants to doxorubicin and vincristine, but not to CDDP or MNNG. CONCLUSIONS: Ara-C and chlorambucil may be useful for the treatment of neuroblastoma exhibiting an MDR phenotype. These CDDP-resistant variants and clones may be useful for studying the mechanisms of low-level drug resistance in neuroblastoma.

15
UI - 11208920
AU - Seiler AE; Ross BN; Rubin R
TI - Inhibition of insulin-like growth factor-1 receptor and IRS-2 signaling by ethanol in SH-SY5Y neuroblastoma cells.
SO - J Neurochem 2001 Jan;76(2):573-81
AD - Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia 19107, USA.
The effect of ethanol on insulin-like growth factor-1 (IGF-I)-mediated signal transduction and functional activation in neuronal cells was examined. In human SH-SY5Y neuroblastoma cells, ethanol inhibited tyrosine autophosphorylation of the IGF-I receptor. This corresponded to the inhibition of IGF-I-induced phosphorylation of p42/p44 mitogen-activated/extracellular signal-regulated protein kinase (MAPK) by ethanol. Insulin-related substrate-2 (IRS-2) and focal adhesion kinase phosphorylation were reduced in the presence of ethanol, which corresponded to the prevention of lamellipodia formation (30 min). By contrast, ethanol had no effect on Shc phosphorylation when measured up to 1 h, and did not affect the association of Grb-2 with Shc. Neurite formation at 24 h was similarly unaffected by ethanol. The data indicate that the IGF-I receptor is a target for ethanol in SH-SY5Y cells However, there is diversity in the sensitivity of signaling elements within the IGF-I receptor tyrosine kinase signaling cascades to ethanol, which can be related to the inhibition of specific functional events in neuronal activation.

16
UI - 12142791
AU - Bagatell R; Morgan E; Cosentino C; Whitesell L
TI - Two cases of pediatric neuroblastoma with tumor thrombus in the inferior vena cava.
SO - J Pediatr Hematol Oncol 2002 Jun-Jul;24(5):397-400
AD - Department of Pediatrics and Steele Memorial Children's Research Center, Tucson, Arizona, USA. bagatell@peds.arizona.edu
The authors describe two children with abdominal neuroblastoma with radiographic evidence of tumor extension into the inferior vena cava. Imaging studies were suggestive of Wilms tumor, but histologic analysis revealed neuroblastoma. In one patient a pulmonary embolus developed after initiation of cytotoxic therapy; the second patient was prophylactically anticoagulated and had no embolic event.

17
UI - 12142799
AU - Odone-Filho V; Cristofani LM; Bonassa EA; Braga PE; Eluf-Neto J
TI - In vitro fertilization and childhood cancer.
SO - J Pediatr Hematol Oncol 2002 Jun-Jul;24(5):421-2

18
UI - 12166258
AU - Tanaka N; Yoshida K; Imada A; Kojima H; Nakamura N; Yoshida Y; Hasegawa
TI - N; Abe S [A case of ganglioneuroblastoma occurring in the superior mediastinum in an adult]
SO - Nihon Kokyuki Gakkai Zasshi 2002 May;40(5):378-82
AD - Department of Respiratory Medicine, Kushiro City General Hospital, Shunkodai 1-12, Kushiro, Japan.
We report a case of ganglioneuroblastoma occurring in the superior mediastinum in adult. A 63-year-old man was admitted to our hospital for detailed investigation of an abnormal shadow on his chest radiograph. Chest radiography and CT imaging showed a left superior mediastinal tumor. Histopathologically, the tumor was identified as a ganglioneuroblastoma. Although ganglioneuroblastomas occur predominantly in children, 3 cases have been reported in adults in Japan. Incidentally, this is the first reported case of ganglioneuroblastoma occurring in the superior mediastinum in Japan.

19
UI - 12077747
AU - Suita S
TI - Stephen L. Gans overseas lecture. Mass screening for neuroblastoma in Japan: lessons learned and future directions.
SO - J Pediatr Surg 2002 Jul;37(7):949-54
AD - Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
BACKGROUND/PURPOSE: Since 1985, a nationwide mass screening program (MS) for neuroblastoma has been conducted for 6-month-old infants throughout Japan, resulting in the detection of more than 1,900 cases of neuroblastoma. The outcome of these patients has been excellent: more than 97% of them are alive. Yet, several reports suggest that the number of advanced-stage neuroblastoma patients over 1 year of age has not changed substantially. The current report focuses on the 15-year experience with MS of the Kyushu Pediatric Oncology Study Group. METHODS: The clinical and biological features of neuroblastoms detected (n = 320) and not detected by MS (n = 245) were compared. Regional and national statistics for neuroblastoma before and after 1985 were analyzed using standard epidemiologic measures for the occurrence of disease. RESULTS: The majority of the MS-positive cases were biologically favorable and had an excellent outcome. In contrast, the majority of non-MS patients in whom neuroblastoma later developed had advanced-stage, unfavorable-prognosis tumors. The overall mortality rate of neuroblastoma in the Kyushu area was not improved by MS. CONCLUSIONS: The optimal time for screening is the point at which neuroblastomas regressing spontaneously can no longer be detected, but more aggressive disease can be found. A birth cohort study could determine the optimal timing for a second screening. Identification of other new prognostic factors may be required. Copyright 2002, Elsevier Science (USA). All rights reserved.

20
UI - 12165452
AU - Riazimand SH; Brieger J; Jacob R; Welkoborsky HJ; Mann WJ
TI - Analysis of cytogenetic aberrations in esthesioneuroblastomas by comparative genomic hybridization.
SO - Cancer Genet Cytogenet 2002 Jul 1;136(1):53-7
AD - Department of Otorhinolaryngology, University Hospital School of Medicine, Mainz, Germany.
Esthesioneuroblastoma (ENB) are rare tumors originating from the olfactory epithelium of the superior nasal cavity. This lesion is morphologically closely related to Ewing sarcoma and other peripheral primitive neuroectodermal tumors (pPNET). The affiliation of ENB to the pPNET family is still under discussion. Only very limited and contradictory cytogenetic data are available on ENB and only one patient has been analyzed by comparative genomic hybridization (CGH), so far. In the present study, genomic imbalances of three ENB were analyzed by CGH to evaluate (1) a recurrent pattern of imbalances, and (2) its relation to the pPNET family. The CGH analysis of three ENB revealed multiple recurrent aberrations including DNA overrepresentations of chromosomal material of the entire chromosome 19, partial gains of the long arms of chromosomes 8, 15, and 22, and deletions of the entire long arm of chromosome 4. Beside these common aberrations, several single gains and losses occurred, that is, gains on 6p, 10q, 1p, 9q, and 13q. We confirmed the former observation of amplified genetic material on chromosome 8 and found several new, currently not described recurrent genetic aberrations distinct from those described for pPNET. Our findings give evidence that ENB is not part of the pPNET family. We suggest that the combined gain of genetic material on 15q, 22q, and chromosome 8 might be indicative for ENB. To verify our findings and to define prognosis-related aberrations, a larger number of cases needs to be studied.

21
UI - 1637063
AU - Richardson UI; Wurtman RJ
TI - Characterization of [3H]MK-801 binding in LA-N-2 neuroblastoma cells.
SO - Ann N Y Acad Sci 1992 May 11;648():328-9
AD - Laboratory of Neuroendocrine Regulation, Massachusetts Institute of Technology, Cambridge 02139.

22
UI - 12056028
AU - Ichikawa H; Sugano H; Tanada S; Sawada T; Nakayama K; Yorimitsu S;
TI - Takahashi I; Iwata J [Diabetes mellitus with mixed neuroendocrine-neural tumor]
SO - Nippon Naika Gakkai Zasshi 2002 Apr 10;91(4):1309-12
AD - Department of Internal Medicine, Kochi Municipal Central Hospital, Kochi.

23
UI - 12089127
AU - Holzer R; Franklin RC
TI - Congenital heart disease and neuroblastoma: just coincidence?
SO - Arch Dis Child 2002 Jul;87(1):61-4
AD - Paediatric Unit, Harefield Hospital, Royal Brompton and Harefield NHS Trust, Harefield, UK.
The clinical history of a neonate with simple transposition of the great arteries in whom a metastatic neuroblastoma was diagnosed incidentally at autopsy is described, and the literature containing all 66 previously reported cases of neuroblastoma associated with congenital cardiac malformations is reviewed. One third of the described cases were classified as in situ neuroblastoma; neural crest derived cardiac lesions were present in 31%. Several possible aetiological mechanisms are discussed, and we conclude that the association of neuroblastoma with congenital cardiac malformations is multifactorial in origin. The described case represents the first reported example in which catecholamine release may have contributed to the fatal outcome of definitive congenital cardiac surgery.

24
UI - 12175523
AU - Emran MA; Rebbaa A; Mirkin BL
TI - Doxorubicin resistant neuroblastoma cells secrete factors that activate AKT and attenuate cytotoxicity in drug-sensitive cells.
SO - Cancer Lett 2002 Aug 8;182(1):53-9
AD - Department of Surgery, Illinois Masonic Medical Center, Children's Memorial Institute for Education and Research (CMIER), Cancer Biology and Chemotherapy Program, Northwestern University Medical School, Chicago, IL 60614, USA.
The present study aims to verify the hypothesis that tumor cells with acquired resistance to chemotherapy may secrete survival factors and thus, participate in the protection of drug-sensitive cells against drug toxicity. A human neuroblastoma cell line, SK-N-SH, and its doxorubicin resistant derivative, RDOX6, have been used. Conditioned medium from RDOX6 cells attenuated the cytotoxic response of SK-N-SH cells to doxorubicin. This protective effect was associated with activation of the Akt survival pathway and inhibition of caspase-3. These data indicate that secretion, by drug-resistant cells, of factors that activate anti-apoptotic pathways in drug-sensitive cells, may constitute a novel mechanism of drug resistance.

25
UI - 11960288
AU - Beltinger C; Fulda S; Walczak H; Debatin KM
TI - TRAIL enhances thymidine kinase/ganciclovir gene therapy of neuroblastoma cells.
SO - Cancer Gene Ther 2002 Apr;9(4):372-81
AD - University Children's Hospital, Ulm 89075, Germany. christian.beltinger@medizin.uni-ulm.de
The clinical benefit of suicide gene therapy of tumors has been marginal, mostly due to the low gene transfer efficiency in vivo. The death-inducing ligand, TRAIL, effectively kills many tumor cell types, while sparing most normal tissues. We hypothesized that TRAIL may enhance HSV thymidine kinase/ganciclovir (TK/GCV) gene therapy of tumor cells by augmenting both target and bystander cell kill. Human SH-EP neuroblastoma cells expressing TK as well as bystander cells were effectively killed by apoptosis, and their clonogenicity was ablated following GCV. Human TRAIL enhanced TK/GCV-induced cell death and decreased clonogenicity of TK-expressing cells and also of bystander cells. Cooperation between TRAIL and TK/GCV depended both on caspase activation and on mitochondrial apoptogenic function because both the broad-spectrum caspase inhibitor zVAD.fmk and overexpression of Bcl-2 decreased enhancement of cell kill by TRAIL. Facilitation of TRAIL signalling by up-regulation of TRAIL receptors did not contribute to enhancement because cell surface expression of the agonistic TRAIL receptors 1 and 2 was not increased by TK/GCV. In conclusion, the concerted activation of caspases and the mitochondrial amplification of caspase activation by TK/GCV may explain the cooperative effect of TK/GCV and TRAIL on the kill of neuroblastoma cells. Because combined treatment also augmented the bystander cell kill, the addition of TRAIL may increase the efficacy of TK/GCV gene therapy of neuroblastoma.

26
UI - 12173347
AU - Mora J; Gerald WL; Qin J; Cheung NK
TI - Evolving significance of prognostic markers associated with treatment improvement in patients with stage 4 neuroblastoma.
SO - Cancer 2002 May 15;94(10):2756-65
AD - Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. jmora@hsjdbcn.org
BACKGROUND: With recent improvements in the treatment and outcome of patients with neuroblastoma (NB), the authors reassessed the prognostic importance of clinical and biologic markers in patients with Stage 4 NB who were treated at the Memorial Sloan-Kettering Cancer Center (MSKCC). METHODS: The authors analyzed 84 patients with Stage 4 NB who were treated on the N5, N6, or N7 protocols at MSKCC from 1987 to 1999. The impact on survival of clinical factors (age, serum ferritin, and lactate dehydrogenase [LDH] levels), histopathology (International Neuroblastoma Pathology Classification [INPC]), and tumor biologic markers (MYCN; ploidy; loss of heterozygosity [LOH] at 1p36, 1p22, 11q23, 14q12-q32, 9p21, and 19q13; and gain at 17q) were analyzed in univariate and multivariate models. RESULTS: Forty-six of 84 patients were alive at the time of this report (55%), with a median follow-up of 41 months from the time of diagnosis. In the univariate analysis, there was no prognostic impact on survival by age, serum ferritin and LDH levels, MYCN, 1p36 LOH, 14q32 LOH, or 17q gain. LOH at 11q23 was associated significantly with superior progression free survival (P = 0.04) and survival (P = 0.04) in the univariate analysis. In the multivariate analysis, it was found that 11q23 status was the most significant variable associated with overall survival (hazard ratio, 0.50; 95% confidence interval, 0.26-0.99). LOH at 11q23 and LOH at 1p22 were highly correlated (P = 0.02). It was found that 11q23 status and INPC score were the most significant variables associated with progression free survival. CONCLUSIONS: Because patient survival improves with more effective therapy, traditional prognostic markers, such as age, MYCN amplification, and elevated serum LDH levels, have become less important for patients with Stage 4 NB. In the current study, less common chromosomal abnormalities (LOH at 1p22 and 11q23) appeared to assume new importance.

The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.

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