Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroblastoma is the most common malignant solid tumor in infants less than 1 year old. A case of adrenal cystic neuroblastoma detected by ultrasound in the 37 th week of pregnancy, is reported. The sonographic features of fetal neuroblastoma range from solid to cystic or complex lesions. Early detection of the tumor by prenatal ultrasound permits prompt neonatal treatment and a better outcome.
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PMID:[Fetal cystic neuroblastoma]. 786 69

Neuroblastoma is the most common extracranial, solid tumor in children. Despite intensive chemotherapy and bone marrow transplantation, the 5-year projected survival rate is 20% to 25%. In vitro studies have shown enhanced natural killer cell (NK) lysis of tumor cells after exposure of NK cells to interleukin-2 (IL-2). In vivo studies have demonstrated similar immunologic effects but have also revealed severe toxicities associated with the use of IL-2. IL-12 is a newly described cytokine that has several properties, including the ability to act synergistically with IL-2 in generating lymphokine-activated killer cells (LAK) against known tumor targets. We investigated the role of IL-12 in the generation of peripheral blood mononuclear cell (PBMC) lysis of neuroblastoma cell lines. PBMC were activated with IL-12 alone and in combination with IL-2. Whereas IL-12 alone produced only modest enhancement of NK cell cytotoxicity, the combination of IL-2 and IL-12 was most effective in activating NK cell lysis of neuroblastoma cell lines. Further, we showed that large granular lymphocytes were the effector cells involved in target cell lysis. Finally, the CD18 molecule was shown to be critical in the lysis of neuroblastoma cells by activated PBMC.
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PMID:Lysis of neuroblastoma cell lines by human natural killer cells activated by interleukin-2 and interleukin-12. 790 63

A case control study was performed to investigate the potential advantage of allogeneic bone marrow transplantation in advanced or poorly responding neuroblastoma first remission patients using the European BMT Solid Tumor Registry. Seventeen allogeneic and 34 autologous bone marrow transplantation (BMT) cases were matched based on a number of prognostic factors including age, sex, prior treatment duration, pre-graft response status and bone and BM involvement before BMT. Only single BMT procedures are included. The median age at diagnosis was 47 months (range 18-113 months). The median follow-up time since BMT is 58 months (range 13-133 months). The only significant prognostic factor within the allogeneic BMT (p = 0.012) and autologous BMT groups (p = 0.025) was residual skeletal disease before BMT, detected by mIBG in 86% of the cases. However, the progression-free survival was not significantly different: 35% and 41% at 2 years, respectively. Only half of the allogeneic BMT patients had developed graft-versus-host disease (GVHD): 7 of 9 grade I-II and only 2 of 9 grade IV. The median donor age was very young with 74 months (range 20-240 months) and 10 of 17 were sex matched. Thus absence of GVHD risk factors in young children could be the major obstacle in achieving an anti-tumor effect with allogeneic BMT in neuroblastoma.
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PMID:Comparison of auto versus allografting as consolidation of primary treatments in advanced neuroblastoma over one year of age at diagnosis: report from the European Group for Bone Marrow Transplantation. 795 Nov 19

This review will summarize the rationale for pursuing investigations into the use of retinoids for pediatric patients with cancer, describe the phase I results of all-trans-retinoic acid (ATRA) in children, and discuss the results of a series of preclinical and clinical pharmacokinetic studies of ATRA. The prognosis for children with advanced stage neuroblastoma, the most common extracranial solid tumor of childhood, has remained poor despite significant increases in the intensity of multi-modality therapy. Observations that neuroblastoma has the potential in vivo to differentiate into the more mature neuronal phenotype of a ganglioneuroma or to spontaneously regress, combined with the ability of ATRA to induce differentiation of neuroblastoma cell lines in vitro, suggests that neuroblastoma may be a prime candidate for a retinoid-based approach to differentiation therapy. We previously performed a standard pediatric phase I trial of ATRA and defined the maximum tolerated dose (MTD) in children to be 60 mg/m2/day, significantly lower than the MTD in adult patients. Pharmacokinetic results revealed that the plasma half-life of ATRA was short (45 min) relative to 13-cis-RA (12-24 h), and that plasma drug exposure decreased significantly by day 28 of daily drug administration. Preclinical studies using an i.v. formulation of ATRA in a Rhesus monkey pharmacokinetic model then demonstrated that ATRA is eliminated by a capacity-limited (saturable) process. This elimination process was rapidly induced within the first week of daily i.v. ATRA administration, and suggested that an intermittent schedule of drug administration might allow for down-regulation of the elimination process. These pre-clinical studies formed the basis for investigating whether an intermittent schedule of ATRA administration would allow for repeated periods of relatively higher plasma drug concentrations. Preliminary results of two clinical trials using intermittent schedules of administration suggest that this approach may result in significantly higher plasma drug exposure over time. Plans to study the role of intermittent schedules of ATRA administration in pediatric phase II trials in patients with neuroblastoma are underway.
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PMID:Clinical and pharmacokinetic studies of all-trans-retinoic acid in pediatric patients with cancer. 796 27

Three water soluble copolymers based on N-(2-hydroxypropyl)methacrylamide were prepared. Copolymer I contains adriamycin, a chemotherapeutic agent, attached via enzymatically degradable oligopeptide (glycylphenylalanylleucylglycine; G-F-L-G) side chains. The other two copolymers contained the photosensitizer, meso-chlorin e6 monoethylene diamine disodium salt (Mce6). In Copolymer II, the chlorin is attached via the degradable G-F-L-G sequence, and it was bound by the nondegradable glycyl spacer in Copolymer III. Initially, the copolymers were characterized separately in vitro and in vivo. Combinations of the copolymer bound chemotherapeutic agent and each of the copolymer bound photosensitizers were then assessed for antitumor effect in vivo. Localization/retention studies (A/J mice; Neuro 2A neuroblastoma solid tumor) were performed with the two copolymers containing Mce6 as well as the free drug. Results of these experiments demonstrated a very different tumor uptake profile for the two copolymers. While the free drug was rapidly cleared from tumor tissue, the copolymer containing Mce6 attached via the non-degradable bond was retained for an extended period; drug concentrations in the tumor were high even after 5 days. On the other hand, a high concentration of the copolymer containing Mce6 bound via the degradable sequence was taken up by the tumor, yet its concentration in the tumor was substantially diminished at 48 h after administration. This shows indirect evidence of in vivo cleavage of Mce6 from the copolymer in the lysosomal compartment which is supported by direct evidence of cleavage by cathepsin B (a lysosomal enzyme) in vitro. Antitumor effects were assessed on Neuro 2A neuroblastoma induced in A/J mice for all three copolymers. Photodynamic therapy (PDT) proved the copolymer with Mce6 bound via the degradable oligopeptide sequence to be a more effective photosensitizer in vivo than the other chlorin containing copolymer. The difference in activity was consistent with the results obtained by photophysical analyses in which the free drug had a higher quantum yield of singlet oxygen generation than the polymer bound drug in buffer. The quantum yield of singlet oxygen generation increased with the enzymatic cleavage of the chlorin from the copolymer. Conditions were subsequently determined for which chemotherapy or PDT would show some antitumor effect, yet be incapable of curing tumors. Finally, combination therapy experiments were performed in which the copolymer bound adriamycin was mixed with either of the copolymer bound chlorin compounds and injected intravenously (i.v.) into the tail veins of mice.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A polymeric drug delivery system for the simultaneous delivery of drugs activatable by enzymes and/or light. 802 29

Patients with solid tumors are increasingly being treated by autologous bone marrow transplantation (BMT). Although response rates appear to be increased, disease recurrence is the commonest cause of treatment failure. Whether relapse is entirely due to residual disease in the patient or arises also from infiltrating malignant cells contained in the autologous marrow transplant has not been resolved. If the latter explanation is correct, then purging would be required as part of the transplantation procedure. We used retrovirally mediated transfer of the neomycin-resistance gene to mark BM harvested from eight patients with neuroblastoma in clinical remission. The marked marrow cells were subsequently reinfused as part of an autologous BMT. At relapse, we sought the marker gene in malignant cell populations. Three patients have relapsed, and in each the marker gene was detected by phenotypic and genetic analyses of resurgent malignant cells at medullary and extramedullary sites. Analysis of neuroblast DNA for discrete marker gene integration sites suggested that at least 200 malignant cells, each capable of tumor formation, were introduced with the autologous marrow transplant and contributed to relapse. Thus, autologous BMTs administered to patients with this solid tumor may contain a multiplicity of malignant cells that subsequently contribute to relapse. The marker-gene technique we describe should permit evaluation of the mechanisms of relapse and the efficacy of purging in patients receiving autologous marrow transplantation for other solid tumors that infiltrate the marrow.
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PMID:Direct demonstration that autologous bone marrow transplantation for solid tumors can return a multiplicity of tumorigenic cells. 802 66

The records of all children in Northern Israel under the age of 1 year in whom a malignant solid tumor was diagnosed were analyzed. Between 1973-1990 such tumors were found in 39 boys and 25 girls. The overall annual incidence was 137.1 per million, and the incidence was higher in boys (1.9/1.0), in Jews compared to non-Jews (1.3/1.0), and in Ashkenazic Jews compared to Sephardic Jews (1.2/1.0). Neuroblastoma was the most common (52% of all malignancies), followed by Wilms' tumor (13%), CNS neoplasm (11%), retinoblastoma (8%), soft tissue sarcoma (6%), lymphoma (5%) and all others (6%). The retinoblastomas were all in non-Jews, but Jews had a higher incidence of neuroblastomas. No differences in incidence were observed in other neoplasms.
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PMID:[Malignant solid tumors in the first year of life]. 803 44

Neuroblastoma is the most common extracranial solid tumor of children. Neuroblastoma tumors derive from the neural crest and synthesize neurotransmitters including the neuropeptide somatostatin. This study was designed to characterize somatostatin receptors both in primary neuroblastoma tumors and in two neuroblastoma cell lines, SKNSH and IMR32. Somatostatin receptors were identified in 6 of 7 Stage I and II compared to 7 of 19 Stage III and IV tumors. Down-regulation of somatostatin receptor binding was observed in five tumors during disease progression. A lack of high affinity binding of somatostatin was identified as a poor prognostic indicator; negative binding correlated with advanced disease and death. Somatostatin receptor binding was observed in the IMR32 cell line, but not in the SKNSH cell line. IMR32 cells demonstrated a single class of high affinity binding sites for both somatostatin and a synthetic analogue, octreotide (Kd 0.16 +/- 0.05 nM and 0.89 +/- 0.23 nM, respectively). Somatostatin and octreotide inhibited both vasoactive intestinal peptide-mediated and forskolin-mediated cyclic AMP accumulation in IMR32 cells. Somatostatin and octreotide inhibition of signal transduction was attenuated by pretreatment of the cells with pertussis toxin. Octreotide inhibited proliferation of IMR32 cells by 70% in a 6-day culture. In contrast, octreotide did not exhibit high affinity binding in SKNSH cells and had no effect on cyclic AMP accumulation or on proliferation in SKNSH cells. Together, these data indicate that octreotide interacts with high affinity somatostatin receptors to modulate signal transduction and regulate proliferation in neuroblastoma cell lines. These data also suggest that somatostatin receptor expression may be an independent prognostic factor in primary neuroblastoma tumors.
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PMID:Characterization of somatostatin receptors on human neuroblastoma tumors. 812 88

Neuroblastoma (NB) is a common malignant solid tumor in childhood, accounting for about 40% of the solid children's neoplasms on the Japanese registry in 1993. It is known that some cases of NB are hereditary, but their incidence is very low. We report two patients with adrenal familial NBs and review the literature on familial NB. Two hit theory was proposed to explain the occurrence of hereditary and non-hereditary NBs. This theory supports the fact that the median age at diagnosis is much younger and the incidence of multiple primaries is higher in the familial NB than in non-familial cases. As therapy for NB improves and more children survive to adulthood, there will be more opportunity to study their offspring.
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PMID:[Familial neuroblastoma]. 853 26

Neuroblastoma is the most frequent extracranial solid tumor of early childhood. Histologically and genetically, neuroblastoma represents a heterogeneous group of tumors with significant differences in clinical behavior. In the past, several different characteristic chromosomal aberrations of neuroblastoma have been described, of which a deletion on chromosome 1p and N-myc amplification have been shown to be of major prognostic significance. However, the role of various other nonrandom DNA imbalances in tumor development and progression needs to be clarified. Taking advantage of the recently established comparative genomic hybridization (CGH), we show that this method is able to accurately detect chromosomal imbalances of known prognostic impact. As CGH gives a comprehensive picture of genetic imbalances in just one experiment, it additionally sheds light on other abnormalities of possible prognostic relevance. We therefore recommend further use of this method not only in the field of research but also for the purpose of genetic routine diagnostics in neuroblastoma.
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PMID:[Synopsis of unbalanced chromosome aberrations in neuroblastoma by comparative genomic hybridization]. 899 79


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