National Cancer Institute®
Last Modified: June 1, 2002
UI - 10980605
AU - Ohira M; Kageyama H; Mihara M; Furuta S; Machida T; Shishikura T;
TI - Takayasu H; Islam A; Nakamura Y; Takahashi M; Tomioka N; Sakiyama S; Kaneko Y; Toyoda A; Hattori M; Sakaki Y; Ohki M; Horii A; Soeda E; Inazawa J; Seki N; Kuma H; Nozawa I; Nakagawara A Identification and characterization of a 500-kb homozygously deleted region at 1p36.2-p36.3 in a neuroblastoma cell line.
SO - Oncogene 2000 Aug 31;19(37):4302-7
AD - Division of Biochemistry, Chiba Cancer Center Research Institute, Chiba 260-8717, Japan.
Loss of heterozygosity of the distal region of chromosome 1p where tumor suppressor gene(s) might harbor is frequently observed in many human cancers including neuroblastoma (NBL) with MYCN amplification and poor prognosis. We have identified for the first time a homozygously deleted region at the marker D1S244 within the smallest region of overlap at 1p36.2-p36.3 in two NBL cell lines, NB-1 and NB-C201 (MASS-NB-SCH1), although our genotyping has suggested the possibility that both lines are derived from the same origin. The 800-kb PAC contig covering the entire region of homozygous deletion was made and partially sequenced (about 60%). The estimated length of the deleted region was 500 kb. We have, thus far, identified six genes within the region which include three known genes (DFF45, PGD, and CORT) as well as three other genes which have been reported during processing our present project for the last 3(1/2) years (HDNB1/UFD2, KIAA0591F/KIF1B-beta, and PEX14). They include the genes related to apoptosis, glucose metabolism, ubiquitin-proteasome pathway, a neuronal microtubule-associated motor molecule and biogenesis of peroxisome. At least three genes (HDNB1/UFD2, KIAA0591F/KIF1B-beta, and PEX14) were differentially expressed at high levels in favorable and at low levels in unfavorable subsets of primary neuroblastoma. Since the 1p distal region is reported to be imprinted, those differentially expressed genes could be the new members of the candidate NBL suppressor, although RT-PCR-SSCP analysis has demonstrated infrequent mutation of the genes so far identified. Full-sequencing and gene prediction for the region of homozygous deletion would elucidate more detailed structure of this region and might lead to discovery of additional candidate genes. Oncogene (2000) 19, 4302 - 4307
UI - 11878777
AU - Anderson CP; Seeger RC; Satake N; Monforte-Munoz HL; Keshelava N; Bailey
TI - HH; Reynolds CP Buthionine sulfoximine and myeloablative concentrations of melphalan overcome resistance in a melphalan-resistant neuroblastoma cell line.
SO - J Pediatr Hematol Oncol 2001 Nov;23(8):500-5
AD - Division of Hematology-Oncology, Children's Hospital Los Angeles, California 90027, USA.
BACKGROUND: Alkylator resistance contributes to treatment failure in high-risk neuroblastoma. Buthionine sulfoximine (BSO) can deplete glutathione and synergistically enhance in vitro sensitivity to the alkylating agent melphalan (L-PAM) for many neuroblastoma cell lines, but optimal use of this combination needs to be defined because clinical responses have been less frequent and not durable. PATIENTS AND METHODS: The authors established and characterized a neuroblastoma cell line (CHLA-171) from a patient who died of progressive disease after treatment with BSO and low-dose L-PAM. RESULTS: CHLA-171 lacks MYCN amplification, expresses PGP (P-glycoprotein) 9.5 RNA, and shows cell surface antigen expression (human leukocyte antigen class I weakly positive, but HSAN 1.2 (hybridoma, SAN 1.2) and anti-GD2 (anti-ganglioside GD2 antibody) strongly positive) characteristic of neuroblastoma cell lines. Twenty-four hours of BSO treatment (0-1,000 micromol/L) maximally depleted CHLA-171 glutathione to 36% of baseline. The cytotoxic response of CHLA-171 to BSO and L-PAM, alone and in combination, was measured by digital image microscopy (DIMSCAN) over a range of drug concentrations and compared with drug levels obtained in the patient during BSO/L-PAM therapy. As single agents, CHLA-171 was highly resistant to L-PAM (LD90 = 42 micromol/L; peak plasma concentration in the patient equals 3.9 micromol/L) and moderately resistant to BSO (LD90 = 509 micromol/L; steady-state concentration in the patient equals 397 micromol/L). Treatment with a 10:1 (BSO:L-PAM) fixed ratio combination synergistically overcame resistance (3-4 logs of cell kill, combination index <1) at clinically achievable levels of BSO (100-400 micromol/L) and levels of L-PAM (10-40 micromol/L) clinically achievable only with hematopoietic stem cell support. CONCLUSIONS: The in vitro results obtained for CHLA-171 suggest that BSO/L-PAM therapy may be optimally effective for drug-resistant neuroblastoma using myeloablative doses of L-PAM.
UI - 11777275
AU - Brahmi U; Rajwanshi A; Joshi K; Dey P; Vohra H; Ganguly NK; Gupta SK
TI - Flow cytometric immunophenotyping and comparison with immunocytochemistry in small round cell tumors.
SO - Anal Quant Cytol Histol 2001 Dec;23(6):405-12
AD - Department of Cytopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
OBJECTIVE: To quantitate different antigens by flow cytometric immunophenotyping (FCI) in small round cell tumors (SRCTs) and to compare the FCI technique with immunocytochemistry (IC). STUDY DESIGN: IC and FCI were performed on 24 consecutive cases of SRCT on fine needle aspiration biopsy material using a panel of antibodies--e.g., cytokeratin (CK), leukocyte common antigen (LCA), desmin, epithelial membrane antigen, neuron-specific enolase, chromogranin, retinoblastoma gene product, neuroblastoma clone (NB84a (NB), vimentin and Mic-2 gene product. IC was done by indirect immunoperoxidase and FCI by indirect immunofluorescence onflow cytometry. RESULTS: In Ewing's sarcoma, with the help of FCI, positive results were obtained in an additional 4 samples in CK, 2 samples in actin and 3 samples in desmin. Similarly, one each sample was additional positive regarding Mic-2 and vimentin by IC. In cases of neuroblastoma with the help of FCI, additional positive results were obtained in one each sample of CK, LCA and NB and two in actin. Combined use of FCI and IC helped to show chromogranin positivity in an additional two cases. Divergent differentiation was noted in four cases of Ewing's sarcoma, one neuroblastoma and two peripheral neuroectodermal tumors. CONCLUSION: FCI technique is sensitive, more objective and quantitative in comparison with manual absorbance-based microscopic detection of enzyme immunohistochemistry products. FCI may determine divergent differentiation in SRCTs.
UI - 11990702
AU - Roberts S; Creamer K; Shoupe B; Flores Y; Robie D
TI - Unique management of stage 4S neuroblastoma complicated by massive hepatomegaly: case report and review of the literature.
SO - J Pediatr Hematol Oncol 2002 Feb;24(2):142-4
AD - Department of Pediatrics, Tripler Army Medical Center, Hawaii, USA. firstname.lastname@example.org
Stage 4S neuroblastoma is an unusual malignancy that has an excellent prognosis, except in young infants. A 2-month-old with 4S neuroblastoma complicated by massive hepatomegaly, managed by abdominal decompression surgery and a negative-pressure dressing system is presented. Diffuse alveolar hemorrhage also developed, which was treated with high-dose corticosteroids.
UI - 11990713
AU - Mugishima H; Matsunaga T; Yagi K; Asami K; Mimaya J; Suita S; Kishimoto
TI - T; Sawada T; Tsuchida Y; Kaneko M Phase I study of irinotecan in pediatric patients with malignant solid tumors.
SO - J Pediatr Hematol Oncol 2002 Feb;24(2):94-100
AD - Study Group of Japan for Treatment of Advanced Neuroblastoma, Gunma.
PURPOSE: To determine the dose-limiting toxicity, maximum tolerated dose, and potential efficacy of irinotecan in children with refractory malignant solid tumors. PATIENTS AND METHODS: In the present phase I clinical trial, 28 patients received irinotecan 50 to 200 mg/m2 per day by intravenous 2-hour infusion over the course of 3 days, repeated once after an interval of 25 days. Fifty-one treatment courses were administered to these patients. RESULTS: Dose-limiting toxicities were observed at the dose of 200 mg/m2 per day for 3 days. Diarrhea and hematopoietic toxicities were the dose-limiting factors, and the former required support with intravenous fluid administration. The occurrence of vomiting was variable. Decreases in clinical tumor marker levels were observed in the majority of patients who received two cycles of irinotecan 80 mg/m2 per day to 200 mg/m2 per day over the course of 3 days, and partial response was attained in four patients who received irinotecan in two cycles of 140 mg/m2 per day to 200 mg/m2 per day over the course of 3 days. Pharmacokinetic studies showed that the plasma concentration of irinotecan and its active metabolite SN-38 ranged from 93 to 2,820 ng/mL and 5.2 to 34.8 ng/mL, respectively, during 3-day infusions of irinotecan 200 mg/m2 per day. The mean clearance of irinotecan was 14.54 L/h per m2 (range 8.45-20.83 L/h per m2). CONCLUSION: The maximum tolerated dose was determined to be a dose of irinotecan between 160 mg/m2 per day and 180 mg/m2 per day administered over the course of 3 consecutive days on an inpatient basis, repeated once after 25 days off, and our results indicate that irinotecan is a promising anticancer agent that is worthy of phase II trials in pediatric solid tumors.
UI - 11930063
AU - Siegel MJ; Ishwaran H; Fletcher BD; Meyer JS; Hoffer FA; Jaramillo D;
TI - Hernandez RJ; Roubal SE; Siegel BA; Caudry DJ; McNeil BJ Staging of neuroblastoma at imaging: report of the radiology diagnostic oncology group.
SO - Radiology 2002 Apr;223(1):168-75
AD - Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S Kingshighway Blvd, St Louis, MO 63110, USA. email@example.com
PURPOSE: To compare the accuracies of computed tomography (CT), magnetic resonance (MR) imaging, and bone scintigraphy in staging disease in patients with neuroblastoma. MATERIALS AND METHODS: Ninety-six children with newly diagnosed neuroblastoma were enrolled in a multicenter prospective cohort study. CT, MR, and bone scintigraphy were used to evaluate tumor stage. Sensitivity and specificity values and receiver operating characteristic (ROC) curve analyses were used to compare the accuracy of CT, MR, and scintigraphy for tumor staging. RESULTS: Eighty-eight patients were eligible for staging analysis, and 45 patients who underwent surgery at initial diagnosis were eligible for analysis of local tumor extent. CT and MR had sensitivities of 43% and 83%, respectively (P <.01), and specificities of 97% and 88%, respectively (P >.05), for detection of stage 4 disease. Areas under the ROC curves for CT and MR were 0.81 and 0.85, respectively (P =.06); that for scintigraphy was 0.83. Addition of scintigraphy to both CT and MR increased the areas under the ROC curves to 0.90 and 0.88, respectively. Accuracy of CT and MR for staging disease confined to the chest or abdomen (stages 1, 2, and 3) was poor. CONCLUSION: MR alone and CT and MR combined with bone scintigraphy enable the accurate detection of stage 4 disease. Both CT and MR perform poorly for local tumor staging.
UI - 11997238
AU - Wasa M; Wang HS; Okada A
TI - Characterization of L-glutamine transport by a human neuroblastoma cell line.
SO - Am J Physiol Cell Physiol 2002 Jun;282(6):C1246-53
AD - Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan. firstname.lastname@example.org
This study characterized the Na+-dependent transport of L-glutamine by a human neuroblastoma cell line, SK-N-SH. The Na+-dependent component represented >95% of the total glutamine uptake. Kinetic studies showed a single saturable high-affinity carrier with a Michaelis constant (K(m)) of 163 +/- 23 microM and a maximum transport velocity (Vmax) of 13,713 +/- 803 pmol x mg protein(-1) x min(-1). Glutamine uptake was markedly inhibited in the presence of L-alanine, L-asparagine, and L-serine. Li+ did not substitute for Na+. These data show that L-glutamine is predominantly taken up through system ASC. Glutamine deprivation resulted in the decrease of glutamine transport by a mechanism that decreased Vmax without affecting K(m). The expression of the system ASC subtype ASCT2 decreased in the glutamine-deprived group, whereas glutamine deprivation did not induce changes in system ASC subtype ASCT1 mRNA expression. Adaptive increases in Na+-dependent glutamate, Na+-dependent 2-(methylamino)isobutyric acid, and Na+-independent leucine transport were observed under glutamine-deprived conditions, which were completely blocked by actinomycin D and cycloheximide. These mechanisms may allow cells to survive and even grow under nutrient-deprived conditions.
UI - 11777245
AU - Otori N; Haruna S; Kamio M; Ohashi G; Moriyama H
TI - Endoscopic transethmosphenoidal approach for pituitary tumors with image guidance.
SO - Am J Rhinol 2001 Nov-Dec;15(6):381-6
AD - Department of Otorhinolaryngology, Jikei University Hospital, Tokyo, Japan.
The advantages of endoscopic transethmosphenoidal surgery for pituitary tumors using a navigation system were reported. The surgical technique was as follows. First, sphenoidal sinuses were opened via the bilateral ethmoidal sinuses and the olfactory clefts. Then the septum of the sphenoidal sinuses was resected. Next, an endoscope was inserted via the left nasal cavity and fixed in place. The tumor was then removed via the right nasal cavity. Our approach for pituitary tumors provided sufficient working space and permitted the surgeon to carry out the procedure using both hands. In addition, use of the InstaTrak System made it possible to recognize the orientation of the surgical field in the sella turcica. Thus, the tumor could be resected more easily and safely. It is concluded that this approach will be particularly useful for patients with narrow nasal cavities or poor development of the paranasal sinuses.
UI - 11902539
AU - Dulguerov P; Allal AS; Calcaterra TC
TI - Esthesioneuroblastoma: a meta-analysis and review.
SO - Lancet Oncol 2001 Nov;2(11):683-90
AD - Division of Head and Neck Surgery, Geneva University Hospital, Switzerland. email@example.com
Our objective was to review recent developments in diagnosis, staging, and treatment of esthesioneuroblastoma (ENB). A meta-analysis of publications between 1990 and 2000 was carried out, and studies were classified according to their main subject: origin/aetiology of ENB, histopathological diagnosis, and treatment. Data so far point to the basal progenitor cells of the olfactory epithelium as the origin of ENB. Histopathological diagnosis remains difficult and is based on results of antigen expression detected through a panel of antibodies by immunohistochemistry. RT-PCR of HASH expression could be a specific marker of ENB. Overall and disease-free survival at 5 years averaged 45% (SD 22) and 41% (SD 21) in the studies included in the meta-analysis. Survival in Hyams' grades I-II was 56% (SD 20) compared with 25% (SD 20) in grades III-IV (odds ratio 6.2). In patients with metastases in cervical lymph nodes (on average 5% of the total) survival was 29%, compared with 64% for patients with N0 disease (odds ratio 5.1). Survival according to treatment modalities was 65% for surgery plus radiotherapy, 51% for radiotherapy and chemotherapy, 48% for surgery, 47% for surgery plus radiotherapy and chemotherapy, and 37% for radiotherapy alone. The histopathological grading according to Hyams and the presence of cervical lymph-node metastases emerged as prognostic factors. A combination of surgery and radiotherapy seems to be the optimum approach to treatment. The exact role of chemotherapy in treatment protocols is still unclear. The role of elective neck dissection is unclear.
UI - 12041619
AU - Tsuchida Y; Kaneko M
TI - Surgery in pediatric solid tumors with special reference to advanced neuroblastoma.
SO - Acta Paediatr Taiwan 2002 Mar-Apr;43(2):67-71
AD - Department of Surgery, Gunma Children's Medical Center, Seta-Gun, Japan. firstname.lastname@example.org
The role of surgery in Wilms' tumor and hepatoblastoma is well established, but that in advanced neuroblastoma is controversial. We analyzed factors contributing to the long-term survival of patients with MYCN-amplified neuroblastoma. METHOD: Patients with stage 3, 4, and 4S neuroblastoma with more than 10 copies of MYCN received induction 1993. Most of these patients underwent radical removal of the original tumor and metastatic lymph nodes plus supralethal preconditioning regimens followed by autologous bone marrow transplantation (ABMT) or peripheral blood stem cell transplantation (PBSCT). In assessing the radicality of surgery, three categories of "total", "subtotal", and 'partial" were used. RESULTS: During the study period, 66 patients with more than 10 copies of MYCN were treated, and 19 (29%) of the 66 patients survived disease-free for at least 69 months. All but one who survived, for more than 69 months disease-free underwent ABMT or PBSCT The radicality of surgery was total in 18 (95%), and subtotal in 1 (5%) of the 19 long-term survivors, while it was total in 38 (84%), and subtotal in 7 (16%) of the 45 patients who died (p > 0.05).CONCLUSIONS: Nineteen (29%) of the 66 patients with MYCN amplification were long-term disease-free survivors for more than 69 months. The prerequisites for survival in such patients appear to be intensive chemotherapy, total resection of the tumor plus metastases, and the use of ABMT/PBSCT, without any major delay in the time sequence.
UI - 12015773
AU - Sauvat F; Sarnacki S; Brisse H; Medioni J; Rubie H; Aigrain Y; Gauthier
TI - F; Audry G; Helardot P; Landais P; Michon J; Hartmann O; Nihoul-Fekete C Outcome of suprarenal localized masses diagnosed during the perinatal period: a retrospective multicenter study.
SO - Cancer 2002 May 1;94(9):2474-80
AD - Department of Pediatric Surgery, Hopital Necker Enfants-Malades, Paris, France.
BACKGROUND: The growing use of abdominal ultrasonography during pregnancy and in the postnatal period is leading to the discovery of an increasing number of suprarenal masses. The optimal diagnosis and treatment of these masses has not yet been determined. METHODS: The authors reviewed the files of patients with suprarenal masses detected prenatally or during the first 3 months of life, between 1986 and 1999, in the pediatric surgery and oncology departments of Paris hospitals. RESULTS: Thirty masses were detected prenatally and 23 postnatally. In the latter group of patients, the diagnosis was based on ultrasound in 8 cases and on the palpation of a mass in 15 cases, 13 of which were neuroblastoma. At birth, the masses were cystic in 19 cases, solid in 17, and mixed in 13. Sensitivities of methyliodobenzylguanidine and urinary catecholamine assay were 70% and 52% respectively. Surgery was performed in 38 cases with a median age of 42 days. Histologic analysis showed 31 neuroblastomas, 1 adrenal hemorrhage, 2 necrotic masses, 1 bronchogenic cyst, and 3 sequestrations. All the patients were alive and disease free, at a follow-up ranging from 3 months to 13 years. CONCLUSIONS: In this series, 58% of the suprarenal masses diagnosed perinatally were localized neuroblastoma with a favorable outcome. All other cases either regressed spontaneously or turned out to be benign lesion. Thus, the management of these masses must strike a compromise between aggressive treatment and a wait-and-see attitude. This requires appropriate initial assessment and a close follow-up in a specialized center. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10502
UI - 12000695
AU - Zabel A; Thilmann C; Zuna I; Schlegel W; Wannenmacher M; Debus J
TI - Comparison of forward planned conformal radiation therapy and inverse planned intensity modulated radiation therapy for esthesioneuroblastoma.
SO - Br J Radiol 2002 Apr;75(892):356-61
AD - Department of Radiotherapy, German Cancer Research Center, INF280, 69120 Heidelberg, Germany.
The purpose of this study was to compare dose distribution of inverse planned intensity modulated radiation therapy (IMRT) with that of conformal radiation therapy (SCRT) in the treatment of esthesioneuroblastoma, and to report initial clinical results. 13 patients with esthesioneuroblastoma were planned both with IMRT and SCRT using complete three-dimensional data sets. A target dose of 60 Gy was prescribed. We performed a detailed dose volume histogram analysis. Dose coverage was equal in both plans while dose distribution was more conformal to the target volume with IMRT. Mean and maximum dose of the brain stem, chiasm, optic nerves and orbits were lower using IMRT than SCRT. The reduction was significant regarding orbit and optic nerve (p<0.05). IMRT was superior in sparing of organs at risk compared with SCRT. The additional sparing by IMRT was positively correlated to the size of the target volume, which was evident with target volumes above 200 cm3. Treatment time was approximately 20 minutes per fraction using IMRT compared with 15 minutes per fraction using SCRT. We conclude that IMRT is both feasible and a valuable tool for more conformal dose distribution in the treatment of esthesioneuroblastoma and to spare organs at risk that are in critical relationship to the tumour. This advantage could be seen especially well in complex shaped target volumes above 200 cm3. Thus, using IMRT, risk of complications may be minimized and local tumour control may be increased.
UI - 12040755
AU - Zabel A; Thilmann C; Milker-Zabel S; Schlegel W; Zuna I; Wannenmacher M;
TI - Debus J The role of stereotactically guided conformal radiotherapy for local tumor control of esthesioneuroblastoma.
SO - Strahlenther Onkol 2002 Apr;178(4):187-91
AD - Department of Radiotherapy, German Cancer Research Center, Heidelberg, Germany. A.Zabel@dkfz.de
BACKGROUND: In a retrospective analysis we compared conventional radiotherapy and stereotactically guided conformal radiotherapy (SCRT) in patients with esthesioneuroblastoma. PATIENTS AND METHODS: Between 1991 and 1999 14 patients with esthesioneuroblastoma underwent radiotherapy at our institution. Median follow-up was 30 months (range 12-107 months). Treatment included adjuvant radiotherapy (9), adjuvant radiochemotherapy (3) or radiotherapy alone (2). Eight patients received SCRT with 3-D treatment planning. For comparison a standard three-field plan for these patients and dose-volume histogram analyses were performed. Median total dose was 64 Gy using SCRT and 56 Gy with standard technique. RESULTS: Local tumor control rate was 50% with conventional radiotherapy and 75% with SCRT. Overall survival was 33.3% and 62.5%, respectively. Target coverage could be improved statistically significant (p < 0.05) and dose to critical structures was reduced using SCRT. Greatest differences were seen regarding volume above the 30%-isodose as well as mean dose of brain stem (p < 0.05). A reduction of maximum dose was seen using SCRT as consequence of a more homogeneous treatment. CONCLUSIONS: SCRT improves target coverage and sparing of organs at risk. Our clinical data although with low patient numbers suggest that the technical advantage translates into a clinical advantage. The use of SCRT appears to facilitate higher dose prescriptions without risking major acute and late side effects. Thus the risk of complications in this area is minimized. Adjuvant radiotherapy is a save and effective treatment modality for local control of esthesioneuroblastoma.
UI - 11910515
AU - Zambrano E; Reyes-Mugica M
TI - Hormonal activity may predict aggressive behavior in neuroblastoma.
SO - Pediatr Dev Pathol 2002 Mar-Apr;5(2):190-9
AD - Department of Pathology, Yale University School of Medicine, 310 Cedar Street, Lauder Hall, CB20, P.O. Box 208023, New Haven, CT 06520-8023, USA.
Overproduction of catecholamines (dopamine [DA], norepinephrine [NE]) and their metabolites (homovanillic [HVA] and vanillylmandelic [VMA] acids) characterizes neuroblastoma (NB). In previous studies, increased urinary DA/NE, and DA/VMA ratios have been associated with poor prognosis, whereas low DA/NE ratios have been associated with longer disease-free survival. Higher urinary VMA, HVA, and NE levels have been found in association with low MYCN amplification, in contrast to cases with high MYCN amplification in which normal levels have been found. It is then believed that an "immature" catecholamine pattern indicates poor prognosis. We correlated urinary DA, NE, VMA, and HVA levels with age, clinical tumor stage, histological features (favorable [FH]/unfavorable [UH]) and MYCN status of 33 patients with NB. DA/VMA and DA/HVA ratios were also calculated. Wilcoxon rank sum and chi-squared tests were performed to determine statistical significance. Eighty-eight percent (15/17) of stage 3-4 cases had DA levels >2 times the upper limit of normal, but only 8% (1/12) of stage 1-2 cases had DA levels twice the upper limit of normal. In 61% (11/18) of stage 3-4 cases, the VMA level was >10 times the upper limit of normal, in contrast to stage 1-2 cases, in which only one patient (1/15) had a VMA level >10 times the upper limit of normal. Similar findings were obtained with urinary HVA and NE. Patients older than 12 months of age at diagnosis also had higher urinary levels of DA, VMA, HVA, and NE than those of patients younger than 12 months of age at diagnosis. Eighty-two percent (14/17) of stage 3-4 cases had DA/VMA ratios <0.78, with the other 18% (3/17) showing ratios between 1.4 and 8.82 (all stage 4 and >12 months of age). In contrast, all stage 1-2 cases ((12)) had ratios <1.4. All (12/12) non- MYCN-amplified cases had DA/VMA ratios <1.4 (0.06-0.84), while one MYCN-amplified case (1/3) had a ratio of 8.82; the other two MYCN-amplified cases had DA/VMA ratios of 0.09-0.11. Twenty-nine percent (2/7) of cases with UH had a DA/VMA ratio >1.4, but in all FH cases (14/14) the DA/VMA ratio was <1.4 (0.08-0.084). Similar to previous studies, we found that aggressive NB is associated with higher urinary levels of DA, VMA, HVA, and NE. We also confirmed the previous observation that there appears to be a subset of NB in which a possible blockade in DA metabolism is associated with poor prognostic features (>12 months, stage 4, UH, and MYCN amplification). A seemingly novel observation in our study is that all high DA/HVA and DA/VMA ratios were obtained in stage 4 tumors, suggesting an association between the inability to metabolize DA and the acquisition of metastatic potential. On the basis of our results, we would like to emphasize the importance of determining not only DA, HVA, and VMA urinary levels, to support the diagnosis of NB, but also DA/HVA and DA/VMA ratios as a rapid initial assessment of prognosis in these patients.
UI - 12017323
AU - Gabius HJ; Andre S; Gunsenhauser I; Kaltner H; Kayser G; Kopitz J; Lahm
TI - H; Harms D; Szymas J; Kayser K Association of galectin-1- but not galectin-3-dependent parameters with proliferation activity in human neuroblastomas and small cell lung carcinomas.
SO - Anticancer Res 2002 Jan-Feb;22(1A):405-10
AD - Institut fur Physiologische Chemie, Tierarztliche Fakultat, Ludwig-Maximilians-Universitat, Munich, Germany.
BACKGROUND: Galectins, a family of animal lectins binding beta-galactosides, are involved in growth regulation of diverse cell types in vitro, even harboring the potential to act as biphasic modulators with cell type selectivity. Owing to this capacity they might affect tumor growth when expression is adapted adequately. MATERIALS AND METHODS: To determine galectin-1-/-3- related features in routinely-fixed sections of two tumor types with poor prognosis (neuroblastoma and small cell lung carcinoma), immuno- and lectin histochemistry with specific antibodies and labeled galectins was performed. RESULTS: In comparison to previously studied tissue culture models, galectin-3 was frequently present, documenting occurrence of discrepancies between tumor models and clinical material for this protein. Cytoplasmic staining with galectin-1 and its antibody coincides with the proliferative activity of positive tumor cells determined by the MIB-1 monoclonal antibody. No statistical correlation was seen for galectin-3. CONCLUSION: These results encourage further cell biological studies to assess a regulatory role of galectin-1 on cell growth in vitro as a model for interfering with tumor proliferation by modulating expression of this type of endogenous effector(s).
UI - 10918246
AU - Biasotti S; Garaventa A; Villavecchia GP; Cabria M; Nantron M; De
TI - Bernardi B False-negative metaiodobenzylguanidine scintigraphy at diagnosis of neuroblastoma.
SO - Med Pediatr Oncol 2000 Aug;35(2):153-5
AD - Department of Pediatric Hematology-Oncology, Giannina Gaslini Institute, Genova, Italy.
UI - 11496360
AU - Chan GC; Leung YL; Shing MM; Luk CW; Ling SC; Lee AC
TI - Does a "false negative" MIBG scan predict a better outcome in neuroblastoma patients?
SO - Med Pediatr Oncol 2001 Aug;37(2):155
UI - 11937307
AU - Ribatti D; Vacca A; Nico B; De Falco G; Giuseppe Montaldo P; Ponzoni M
TI - Angiogenesis and anti-angiogenesis in neuroblastoma.
SO - Eur J Cancer 2002 Apr;38(6):750-7
AD - Department of Human Anatomy and Histology, University of Bari Medical School, Italy. email@example.com
Angiogenesis is a biological process by which new capillaries are formed from pre-existing vessels. It occurs in physiological and pathological conditions, such as tumours, where a specific critical turning point is the transition from the avascular to the vascular phase. Tumour angiogenesis depends mainly on the release by neoplastic cells of growth factors specific for endothelial cells that able to stimulate the growth of the host's blood vessels. This review summarises the literature concerning the relationship between angiogenesis and progression in human neuroblastoma, the most common extracranial solid tumour of infancy and childhood. It is becoming increasingly evident that agents which interfere with blood vessel formation also block tumour progression. Accordingly, anti-angiogenic tumour therapy has gained much interest in preclinical and clinical assessments. The recent applications of anti-angiogenic agents which interfere or block neuroblastoma progression are reviewed.
UI - 11906819
AU - Van Dessel GA; De Busser HM; Lagrou AR
TI - Prenylcysteine carboxymethyltransferase type III activity is decreased in retinoic acid-treated SH-SY5Y neuroblastoma cells.
SO - Int J Biochem Cell Biol 2002 May;34(5):477-86
AD - RUCA-Laboratory for Human Biochemistry, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium. firstname.lastname@example.org
Prenylcysteine carboxymethyltransferase (pcCMT) is an enzyme that catalyzes the post-translational carboxymethylation of isoprenylated proteins ensuring a more efficient membrane attachment and proper guiding to a specific target membrane. In this paper, we report on modulation of pcCMT activity in retinoic acid (RA)-treated SH-SY5Y neuroblastoma cells using N-acetyl-S-farnesyl-L-cysteine (AFC) as artificial methyl acceptor. In addition, the methylation of endogenous proteins was followed by the vapor phase equilibrium assay and the storage phosphor screen (P-screen) technique with S-adenosyl-[3H-methyl] methionine (AdoMet) as methyl donor. Methylation of AFC was reduced to 75% of that of the control, the most prominent decrease being observed with the post-nuclear membrane fraction as enzyme source. With regard to protein methylation both screening methods yielded analogous results showing the [3H]-labeling of endogenous proteins in the 21-25kDa molecular mass (MM) range to be diminished by nearly 50%. This questions the role of protein carboxymethylation as an essential component of the differentiation process in SH-SY5Y neuroblastoma cells. The P-screen technique revealed that the methylation of other molecular mass proteins was also affected. Both S-adenosylhomocysteine (AdoHcy) and AFC (AdoHcy being the most effective) inhibited endogenous methylation. An interesting feature was that AFC inhibited the protein methylation proportionally more effective in RA-treated cells. Finally, the levels of three small guanosine-5'-triphosphate (GTP) binding proteins were screened upon differentiation showing rab3A to be increased while rhoA and H-ras were decreased.
UI - 12007190
AU - Spitz R; Hero B; Westermann F; Ernestus K; Schwab M; Berthold F
TI - Fluorescence in situ hybridization analyses of chromosome band 1p36 in neuroblastoma detect two classes of alterations.
SO - Genes Chromosomes Cancer 2002 Jul;34(3):299-305
AD - University Children's Hospital, Department of Pediatric Oncology, Cologne, Germany. Ruediger.Spitz@medizin.uni-koeln.de
Chromosomal alterations in 1p36 were investigated in 196 neuroblastoma tumors using fluorescence in situ hybridization. Additionally, by using the same technique, it was determined whether MYCN was amplified in 149 of these. The most frequent finding was a deletion in 1p36, leading to monosomy of this region (29 cases, 15%). Furthermore, we found tumors with at least two intact copies of chromosome 1 and additional 1p36-deleted copies. Altogether, 21 tumors (11%) displayed this imbalance of 1p36. Similar to the cases with deletion, imbalances were predominantly found in stage 4 tumors (81%), and they were significantly associated with an increased patient age (P = 0.01). Nearly all 1p-deleted tumors showed amplification of MYCN (24/27 analyzed samples, 89%), whereas only 8 of 21 (38%) with imbalance did. Eight cases with imbalance were investigated for loss of heterozygosity (LOH) using microsatellite markers in 1p35-36. Only 4 displayed 1p36 LOH, whereas the remaining 4 were heterozygous. Both patients with deletion of 1p and with imbalance had a poor outcome [3-year rate of event-free-survival (EFS): 33 +/- 15% and 41 +/- 15%], which was significantly worse compared to the outcome of patients without 1p alterations (3-year EFS: 70 +/- 5%; P = 0.01 and P = 0.0059). We conclude that besides monosomic short arm deletions, imbalance of 1p36 is a strong marker of a poor prognosis in neuroblastoma and not necessarily associated with MYCN amplification and LOH. Copyright 2002 Wiley-Liss, Inc.
UI - 12007192
AU - Stark B; Jeison M; Bar-Am I; Glaser-Gabay L; Mardoukh J; Luria D;
TI - Feinmesser M; Goshen Y; Stein J; Abramov A; Zaizov R; Yaniv I Distinct cytogenetic pathways of advanced-stage neuroblastoma tumors, detected by spectral karyotyping.
SO - Genes Chromosomes Cancer 2002 Jul;34(3):313-24
AD - Cancer Cytogenetic Laboratory, Schneider Children's Medical Center of Israel, Petah Tiqva, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. email@example.com
Molecular studies of advanced-stage neuroblastoma (NBL) have revealed a marked genetic heterogeneity. In addition to MYCN amplification and chromosome 1 short-arm deletions/translocations detected by conventional cytogenetics, application of fluorescence in situ hybridization has disclosed a high prevalence of 17q gain, whereas allelotyping and comparative genomic hybridization techniques also have revealed loss of 11q and of other chromosomal material. Using the recently developed technique of spectral karyotyping (SKY), we sought to refine the cytogenetic information, identify hidden recurrent structural chromosomal abnormalities, and compare them to the molecular findings. Thirteen samples of metaphase spreads from 11 patients with advanced-stage NBL were analyzed by SKY. Most of them were found to have complex karyotypes (more than three changes per metaphase) and complex unbalanced rearrangements. Recurrent aberrations leading to 17q gain, deletion of 1p, MYCN amplification, and loss of 11q appeared in 7, 4, 4, and 5 patients, respectively, in simple and complex karyotypes. Chromosome 3 changes and gain of 1q and 7q appeared in 6, 5, and 4 patients, respectively, in complex karyotypes only, reflecting later changes. A strikingly high prevalence of the unbalanced translocation der(11)t(11;17), leading to concomitant 11q loss and 17q gain in 4 patients, delineated a distinct cytogenetic group, none having 1p deletion and/or MYCN amplification. der(11)t(11;17) was associated with complex karyotypes with changes in chromosomes 3 and 7q. The 17q translocations with partners other than 11q were associated with 1p deletion and/or MYCN amplification. The distinct cytogenetic subgroups identified by SKY confirm and extend the recent molecular observations, and suggest that different genes may interact in the der(11)t(11;17) pathway of NBL development and progression. Copyright 2002 Wiley-Liss, Inc.
UI - 12054112
AU - Inamo Y; Suzuki T; Mugishima H
TI - A case of growth failure caused by 13-CIS-retinoic acid administration after bone marrow transplantation for neuroblasoma.
SO - Endocr J 1999 Mar;46 Suppl():S113-5
AD - Department of General Pediatrics, Nihon University Nerima-Hikarigaoka Hospital, Tokyo, Japan.
We report an 11-year-old girl with growth failure caused by long-term administration of 13-cis-retinoic acid after bone marrow transplantation for neuroblastoma. Her growth velocity was 1-2 cm/year after 13-cis-retinoic acid administration. Her endocrinological findings were normal except for peak growth hormone levels of 6.4 ng/ml (clonidine) and 9.7 ng/ml (arginine). IGF-1 and IGFBP-3 were normal. It is not possible to conclude that her severe growth failure was caused by partial growth hormone deficiency, but premature epiphyseal closure was seen on radiographic examination. We concluded that the growth failure was caused by pediatric cancer therapy for the musculoskeletal system but not by endocrinological disturbance.
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