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 extra-cranial solid tumor of childhood. It originates in cells of the neural crest, and so can be found anywhere along the paravertebral sympathetic chain or in the adrenal gland. In the last 15 years, new developments in the genetics and biology of neuroblastoma, have led to a better understanding of the natural history and prognostic features of this cancer. The presence of identifying biochemical markers detectable in the urine of patients with neuroblastoma, as well as the remarkably inferior survival of children diagnosed at more than 12 months of age, have led some groups to screen infants for neuroblastoma, in the hope of decreasing both overall mortality, as well as the incidence of advanced stage disease. This article reviews some clinical aspects of neuroblastoma, but emphasizes the genetic and biologic features in relation to prognosis and treatment. Finally, we discuss the different screening experiences for this disease, in particular from the Quebec Neuroblastoma Screening Project.
 ...
PMID:Neuroblastoma: an enigmatic disease. 903 32

Human neuroblastoma is the most frequent solid tumor in children. Recent studies suggest that a multiplicity of genomic alterations contributes to neuroblastoma, the most frequent and well studied being deletion of the short arm of chromosome 1 and amplification of N-MYC. We here present and discuss different patterns of oncogene activation including, amplification of N-MYC, duplication of N-MYC and amplification of MDM2.
 ...
PMID:Patterns of oncogene activation in human neuroblastoma cells. 904 27

Neuroblastoma is the most common solid tumor in childhood and is the most frequent neural crest tumor (NCT). More than 90% of the patients excrete high levels of vanilmandelic acid (VMA) and homovanillic acid (HVA) in the urine. Original biochemical methods for measuring these two metabolites of catecholamines employed a collection of urine for 24 hours to avoid errors related to circadian cycle variations. More recently, attempts have been made to replace the 24-hour collections by random samples (RSs). This has practical advantages particularly for young children. The objective of this study is to assess whether urinary VMA related to urinary creatinine levels can be determined reliably by the method of Pisano et al. from RSs in patients with NCT. The determination of the consumption of VMA in urine stored for prolonged periods of time was also studied. We found a good correlation between the values of metabolites of catecholamines in RSs compared with 24-hour urine collections. There was consumption of VMA in urine samples after storage. We conclude that determination of VMA in RSs of urine by Pisano's method may identify NCT production of catecholamines and that the consumption of these catecholamines is an important factor to consider in the interpretation of values obtained with stored urine specimens.
 ...
PMID:Vanilmandelic acid and homovanillic acid levels in patients with neural crest tumor: 24-hour urine collection versus random sample. 918 10

The basic helix-loop-helix (bHLH) class of transcription factors plays a pivotal role in tissue-specific determination and differentiation. Moreover, dysregulated expression or loss of function of these factors contributes to leukemogenesis and solid tumor development. Neurogenesis is regulated by genes of the NEUROD/atonal and ACHAETE SCUTE families. We analyzed expression of human NEUROD1, NEUROD2, NEUROD3, and ACHAETE SCUTE 1 (HASH1) in cerebellar and cerebral primitive neuroectodermal tumors (PNETs), gliomas, and cell lines derived from a variety of neuroectodermal tumors by Northern analysis and in situ hybridization. NEUROD1 was expressed in each of the 12 medulloblastoma specimens, whereas NEUROD2 and NEUROD3/neurogenin were expressed in partly overlapping subsets of medulloblastomas. All of the tumors that presented with distant metastases expressed NEUROD3. The only other NEUROD3-positive tumor progressed early in treatment. Human ACHAETE SCUTE homologue (HASH1) was not expressed in medulloblastomas (infratentorial PNETs) but was expressed in three of five supratentorial PNETs. Neuroectodermal tumor cell lines derived from other sites (e.g., neuroblastoma and retinoblastoma) expressed NeuroD and ACHAETE SCUTE family members. No NEUROD message was detected in glial tumors or cell lines. Neurogenic bHLH transcription factor expression patterns suggest that specific family members may contribute to or reflect biological differences that arise during malignant transformation.
 ...
PMID:Expression of neurogenic basic helix-loop-helix genes in primitive neuroectodermal tumors. 927 24

Anti-disialoganglioside (GD2) monoclonal antibodies (MAbs) have been used in vivo for immunolocalization and in phase I and II trials to target disseminated neuroblastoma, the most common extracranial solid tumor in children. However, the efficacy of these first-generation MAbs is likely to be improved by using engineered anti-GD2 antibodies. The generation of single-chain antibody fragments (scFv) could be very helpful as these molecules can be further modified to produce recombinant molecules with pre-defined properties such as immunotoxins, chimeric, or bispecific antibodies. Thus, a scFv directed against GD2 (scFv 7A4) was cloned, sequenced, and expressed. Its binding properties were characterized and compared to that of the parental MAb 7A4. Nucleotide sequence analysis of the scFv 7A4 indicated that its VH region belongs to the V region IIID subgroup and the V kappa to the V region II subgroup. The scFv 7A4 bound to GD2+ neuroblastoma cell lines but not to GD2- cell lines or to GD2- cells isolated from peripheral blood. ELISA and thin-layer chromatography (TLC) indicated that it retained the anti-GD2 specificity, and exhibited a slight cross-reaction with GD3 as the parental MAb. This scFv makes it possible to develop new useful reagents through genetic engineering for adjuvant tumor therapy.
 ...
PMID:Generation and characterization of a mouse single-chain antibody fragment specific for disialoganglioside (GD2). 930 24

Neuroblastoma has been recognized as the most common solid tumor of infancy and childhood. The occurrence of bilateral adrenal neuroblastoma, however, is extremely rare and only a small number of cases have been previously reported. The authors herein report the clinical, histopathological and molecular biological features of two bilateral adrenal cases out of 125 neuroblastoma patients treated at Kyushu University Hospital over a 35-year period. The clinical and histopathological data of the two cases of bilateral adrenal neuroblastoma were reviewed. In Case 1, which had multiple liver metastases, a post-mortem examination revealed bilateral adrenal involvement. In Case 2, which had been detected by mass screening, CT showed masses in both adrenal glands. No big differences in size were recognized between the tumors in either of the cases. A histopathological examination revealed rosette fibrillary type neuroblastomas in both cases. The DNA of these tumor samples stored at -80 degrees C was extracted and the number of copies of the N-myc gene was determined by a Southern blot analysis. Fourteen copies of the gene were detected in Case 1, whereas neither of the tumors in Case 2 showed any amplification. The clinical outcome, histopathological findings and N-myc gene analysis of two cases might support the variety of biological features of this rare group of neuroblastoma.
 ...
PMID:Bilateral adrenal neuroblastoma. 940 93

Topotecan (Hycamtin; SmithKline Beecham Pharmaceuticals, Philadelphia, PA), a camptothecin analog, is a novel and specific inhibitor of the nuclear enzyme topoisomerase I. In preclinical studies, topotecan demonstrated significant in vitro activity in a variety of solid tumor explants derived from colorectal, breast, ovarian, renal cell, non-small cell lung cancer, and gastrointestinal sources. Notable activity was also demonstrated in vivo in a wide range of animal tumor models. A large number of phase I studies with topotecan have been conducted since 1992 in both adults and children with a broad range of refractory malignancies and as many as 14 different dosing schedules. Complete, partial, or minor responses were demonstrated in patients with recurrent or refractory neuroblastoma, non-small cell lung cancer, small cell lung cancer, ovarian cancer, breast cancer, colon cancer, esophageal cancer, renal cell carcinoma, and squamous cell carcinoma. The antitumor activity of topotecan in these phase I evaluations was associated more often with frequent or continuous dosing schedules compared with less frequent or short exposure schedules. Maximum tolerated doses were predominantly dependent on the dosing schedule used. Myelosuppression was the major dose-limiting toxicity across all schedules, and nonhematologic toxicities were generally mild. Data from phase I studies have provided valuable information about antitumor responses, maximum tolerated doses, and dose-limiting toxicities associated with different dosing schedules. Based on this information, there was substantial enthusiasm for further evaluating topotecan in a wide range of cancer patients in phase II studies.
 ...
PMID:Review of phase I clinical studies with topotecan. 942 56

Neuroblastoma is the most common extracranial solid tumor of childhood, accounting for 15% of cancer-related deaths. These tumors have a predilection for young children; 60% of cases occur before age 2 years and 97% before age 10. Neuroblastomas derive from embryonic neural crest cells of the peripheral sympathetic nervous system. The behavior of this malignancy is characterized by marked clinical heterogeneity, ranging from spontaneous maturation in some patients to inexorable rapid metastatic progression in others. This article will discuss some of the molecular and biological features of neuroblastoma that are associated with these differences in behavior, and how these features have been used to develop a risk-based approach to therapy.
 ...
PMID:Neuroblastoma: biology and therapy. 943 90

The increase in the number of patients treated with high-dose chemotherapy/autologous stem cell transplantation (HDC/ASCT) for solid tumor malignancies has generated concern about the infusion of tumor cell contamination in the graft. In an effort to study so-called minimal residual disease (MRD) in the HDC/ASCT setting, a variety of assay methods have been used. Although these assays vary in terms of sensitivity and specificity of tumor detection, they are in agreement as to the presence and viability of tumor cells in ASCT grafts. A growing body of evidence indicates that MRD is present in ASCT grafts from neuroblastoma, breast cancer, and ovarian cancer patients. More importantly, several retrospective studies have determined that the infusion of tumor cells with the ASCT graft is strongly associated with post-ASCT relapse. Gene-marking studies have directly demonstrated that infused tumor cells are present at sites of disease relapse. Thus, the issue of tumor contamination of autologous grafts is an area of growing concern. This review article details the current status of MRD in solid tumor malignancies, with emphasis on assay methodology, clinical utility, and clinical relevance in transplantation medicine.
 ...
PMID:Minimal residual disease in solid tumor malignancies: a review. 950 77

We have identified the CD95 system as a key mediator of chemotherapy-induced apoptosis in leukemia and neuroblastoma cells. Here, we report that sensitivity of various solid tumor cell lines for drug-induced cell death corresponds to activation of the CD95 system. Upon drug treatment, strong induction of CD95 ligand (CD95-L) and caspase activity were found in chemosensitive tumor cells (Hodgkin, Ewing's sarcoma, colon carcinoma and small cell lung carcinoma) but not in tumor cells which responded poorly to drug treatment (breast carcinoma and renal cell carcinoma). Blockade of CD95 using F(ab')2 anti-CD95 antibody fragments markedly reduced drug-induced apoptosis, suggesting that drug-triggered apoptosis depended on CD95-L/receptor interaction. Moreover, drug treatment induced CD95 expression, thereby increasing sensitivity for CD95-induced apoptosis. Drug-induced apoptosis critically depended on activation of caspases (ICE/Ced-3-like proteases) since the broad-spectrum inhibitor of caspases zVAD-fmk strongly reduced drug-mediated apoptosis. The prototype substrate of caspases, poly(ADP-ribose) polymerase, was cleaved upon drug treatment, suggesting that CD95-L triggered autocrine/paracrine death via activation of caspases. Our data suggest that chemosensitivity of solid tumor cells depends on intact apoptosis pathways involving activation of the CD95 system and processing of caspases. Our findings may have important implications for new treatment approaches to increase sensitivity and to overcome resistance of solid tumors.
 ...
PMID:Chemosensitivity of solid tumor cells in vitro is related to activation of the CD95 system. 953 69


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>