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Abramson Cancer CenterNCI CANCERLIT® Search: Neuroblastoma - June 2002
National Cancer Institute®
Last Modified: June 1, 2002
- Identification and characterization of a 500-kb homozygously deleted region at 1p36.2-p36.3 in a neuroblastoma cell line.
- Buthionine sulfoximine and myeloablative concentrations of melphalan overcome resistance in a melphalan-resistant neuroblastoma cell line.
- RAS, the magician.
- Flow cytometric immunophenotyping and comparison with immunocytochemistry in small round cell tumors.
- Unique management of stage 4S neuroblastoma complicated by massive hepatomegaly: case report and review of the literature.
- Phase I study of irinotecan in pediatric patients with malignant solid tumors.
- Staging of neuroblastoma at imaging: report of the radiology diagnostic oncology group.
- Characterization of L-glutamine transport by a human neuroblastoma cell line.
- Endoscopic transethmosphenoidal approach for pituitary tumors with image guidance.
- Esthesioneuroblastoma: a meta-analysis and review.
- Challenge of therapy in advanced neuroblastoma.
- Surgery in pediatric solid tumors with special reference to advanced neuroblastoma.
- Outcome of suprarenal localized masses diagnosed during the perinatal period: a retrospective multicenter study.
- Comparison of forward planned conformal radiation therapy and inverse planned intensity modulated radiation therapy for esthesioneuroblastoma.
- The role of stereotactically guided conformal radiotherapy for local tumor control of esthesioneuroblastoma.
- Hormonal activity may predict aggressive behavior in neuroblastoma.
- Association of galectin-1- but not galectin-3-dependent parameters with proliferation activity in human neuroblastomas and small cell lung
- False-negative metaiodobenzylguanidine scintigraphy at diagnosis of neuroblastoma.
- Does a "false negative" MIBG scan predict a better outcome in neuroblastoma patients?
- Does a "false-negative" MIBG scan predict a better outcome in neuroblastoma patients?
- Angiogenesis and anti-angiogenesis in neuroblastoma.
- Prenylcysteine carboxymethyltransferase type III activity is decreased in retinoic acid-treated SH-SY5Y neuroblastoma cells.
- Fluorescence in situ hybridization analyses of chromosome band 1p36 in neuroblastoma detect two classes of alterations.
- Distinct cytogenetic pathways of advanced-stage neuroblastoma tumors, detected by spectral karyotyping.
- A case of growth failure caused by 13-CIS-retinoic acid administration after bone marrow transplantation for neuroblasoma.
Table of Contents
1
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
2
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.
3
UI - 12001986
AU - Brooksbank C
TI -
RAS, the magician.
SO - Nature Rev Cancer 2002 Apr;2(4):249
4
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.
5
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.
roberste@ohsu.edu
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.
6
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.
7
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.
siegelm@mir.wustl.edu
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.
8
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. wasa@pedsurg.med.osaka-u.ac.jp
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.
9
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.
10
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. pavel.dulguerov@hcuge.ch
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.
11
UI - 12041618
AU - Lai HS
TI -
Challenge of therapy in advanced neuroblastoma.
SO - Acta Paediatr Taiwan 2002 Mar-Apr;43(2):65-6
12
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.
tuchida@gcmc.pref.gunma.jp
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.
13
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
14
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.
15
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.
16
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.
17
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).
18
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.
19
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
20
UI - 11568913
AU - Garaventa A
TI -
Does a "false-negative" MIBG scan predict a better outcome in
neuroblastoma patients?
SO - Med Pediatr Oncol 2001 Oct;37(4):418
21
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. ribatti@anatomia.uniba.it
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.
22
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. guvades@ruca.ua.ac.be
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.
23
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.
24
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. dnaomi@clalit.org.il
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.
25
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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