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

Etoposide has demonstrated highly significant clinical activity against a wide variety of neoplasms, including germ-cell malignancies, small-cell lung cancer, non-Hodgkin's lymphomas, leukemias, Kaposi's sarcoma, neuroblastoma, and soft-tissue sarcomas. It is also one of the important agents in the preparatory regimens given prior to bone marrow and peripheral stem-cell rescue. Despite its high degree of efficacy in a number of malignancies, the optimal dose, schedule, and dosing form remain to be defined. It is possible that continuous or prolonged inhibition of the substrate, i. e., topoisomerase II, may be the key factor for the cytotoxic effects of etoposide. Clinical studies have shown the activity of etoposide to be schedule-dependent, with prolonged dosing, best accomplished by the oral dosing form, offering a therapeutic advantage. This benefit awaits validation by prospective randomized studies, some of which are in progress. Recent clinical investigations have focused on the use of etoposide in combination with (a) cytokines to ameliorate myelosuppression, the dose-limiting toxicity of etoposide; (b) agents such as cyclosporin A and verapamil to alter the p-glycoprotein (mdr1) function; and (c) topoisomerase I inhibitors to modulate the substrate upon which it acts. There is continued interest in the development of etoposide to its maximal clinical dimensions and in the examination of alternative biochemical and mechanistic approaches to further our understanding of this highly active agent.
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PMID:Etoposide: current status and future perspectives in the management of malignant neoplasms. 807 20

The neural cell adhesion molecule (N-CAM), a member of the immunoglobulin gene super-family mediating homophilic cell-cell adhesion in a neuroendocrine system, is preferentially expressed in human small cell lung cancer (SCLC). Immunoprecipitation of a panel of SCLC cell lines by monoclonal antibodies (mAbs) specific for N-CAM detects mainly the 145-kDa isoform. This result was correlated with Northern blotting where a single 6.2-kb mRNA was detected in nine SCLC cell lines. To determine cDNA sequence encoding the N-CAM isoform, we selected several cDNA clones encoding N-CAM isolated from OS2-R, a SCLC cell line established in our laboratory. Based on the analysis of the full-length cDNA obtained from two clones, the sequence of this 145-kDa isoform was shown to be essentially identical to that of the 140-kDa N-CAM isoform of neuroblastoma except for a single base pair changed at position 1620 without changing amino acid encoded.
Lung Cancer 1994 Mar
PMID:Complementary DNA sequence encoding the major neural cell adhesion molecule isoform in a human small cell lung cancer cell line. 807 73

Annamycin (Ann) is a highly lipophilic anthracycline antibiotic that has been shown to circumvent MDR-1 both in vitro and in vivo. A liposomal formulation of Ann is currently in phase I clinical trials. The multidrug resistance-associated protein (MRP) has been found to be over-expressed in some human leukemias at relapse and to be a poor prognostic factor in neuroblastoma. We studied the in vitro cytotoxicity and the cellular uptake and efflux of Ann and doxorubicin (Dox) in 2 pairs of human cell lines, breast carcinoma MCF7 and small-cell lung cancer UMCC-1, and their MRP-expressing counterparts, MCF-7/VP and UMCC-1/VP. Resistance indexes were 1.1 and 1.4 for Ann vs. 6.9 and 11.6 for Dox. Ann cellular accumulation was 3- to 5-fold higher than that of Dox in both sensitive and resistant cells. No changes in drug efflux between sensitive and resistant cells were observed in the case of Ann, while Dox efflux at 1 hr was 20-25% higher in resistant than in sensitive cells. By confocal microscopy, the subcellular distribution of Ann was identical in sensitive and resistant cells, localizing mostly in the perinuclear structures, while that of Dox was exclusively nuclear in sensitive cells and nuclear and in the cell membrane in resistant cells. There was a good correlation between the extent of DNA breaks induced by each drug in the different cell lines and cytotoxic effect. Our results indicate that Ann may be effective in the treatment of malignancies in which MRP is a relevant mechanism of clinical resistance.
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PMID:Annamycin circumvents resistance mediated by the multidrug resistance-associated protein (MRP) in breast MCF-7 and small-cell lung UMCC-1 cancer cell lines selected for resistance to etoposide. 909 63

During apoptosis, one of the first membrane changes that can be detected is exposure of phosphatidylserine residues at the outer plasma membrane leaflet, while early apoptosis is also accompanied by changes in the cytoskeletal organization. In this study we investigated the relationship between these two phenomena during olomoucine- and roscovitin-induced apoptosis in human lung cancer and neuroblastoma cell lines. Loss of membrane asymmetry was detected by biotin-labeled or FITC-labeled annexin V binding to negatively charged phosphatidylserine, while cytoskeletal components were visualized by immunocytochemistry. The apoptotic, annexin V-positive, cells were analyzed by flow cytometry, confocal scanning laser microscopy, and Western blotting. We report that cytokeratin and vimentin aggregation in early apoptosis occurs simultaneously with phosphatidylserine exposure and chromatin condensation. In contrast to these intermediate filament proteins, which were disassembled and proteolytically cleaved in early apoptosis, microfilaments and microtubuli were not proteolytically degraded but were found to be present as aggregated filaments in the apoptotic bodies. We also show that loss of membrane asymmetry and cytokeratin aggregation are independent processes, since N-ethylmaleimide-induced phosphatidylserine exposure does not cause cytokeratin disassembly. Vice versa, phorbol 12-myristate 13-acetate-induced cytokeratin filament aggregation does not result in phosphatidylserine exposure.
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PMID:Plasma membrane alterations and cytoskeletal changes in apoptosis. 929 67

Topotecan (Hycamtin) is a promising new topoisomerase I-targeting anticancer agent that first entered clinical trials in 1989 under National Cancer Institute sponsorship in collaboration with SmithKline Beecham. In 1996, it was approved for use by the United States Food and Drug Administration (FDA) for previously treated patients with advanced ovarian cancer. For these patients, topotecan provides another therapeutic option upon disease progression after initial platinum-based chemotherapy. Topotecan also has activity in other tumor types, including small-cell lung cancer, hematologic malignancies and pediatric neuroblastoma and rhabdomyosarcoma. Topotecan combination regimens with paclitaxel (Taxol), etoposide (VePesid), cisplatin (Platinol), and cytarabine and with other treatment modalities, such as radiation therapy, are in development. Studies evaluating topotecan combinations as initial treatment in such diseases as ovarian and small-cell lung carcinoma are also underway. It is hoped that earlier use of topotecan, with its novel mechanism of action, will prolong survival and increase cure rates in patients with these chemoresponsive tumors. Whether or not such hopes are realized, these important studies will help define the role of topotecan in cancer chemotherapy.
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PMID:Clinical status and optimal use of topotecan. 939 64

To investigate neuron-specific antigens, hybridoma cells were produced between mouse spleen cells immunized with human neuroblastoma cells (IMR-32) and mouse myeloma cells. 247 hybridoma clones were harvested and one of them was further cultured for recloning. Eventually, one hybridoma clone was obtained and its antibody was designated N-A8. The characteristics of this antibody were determined by immunostaining and flow cytometry. First, the antibody recognized the surface antigens of IMR-32 cells. Second, unexpectedly, N-A8 was reactive not only with human neuroblastoma cell lines but also with human lung cancer cell lines. As analyzed by immunoprecipitation method and SDS-PAGE, the molecular size of the antigen recognized by N-A8 was 210 kDa. The antigen was then purified by affinity chromatography and identified as neural adhesion molecule L1 by amino acid sequence analysis. By the present investigation, it was clearly demonstrated that L1 is expressed in human lung cancer cells.
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PMID:Expression of neural cell adhesion molecule L1 in human lung cancer cell lines. 943 55

The retinoblastoma protein-interacting zinc finger gene RIZ maps to the distal short arm of human chromosome 1 (1p36), a region thought to harbor tumor suppressor genes for a variety of human cancers including breast cancer. The RIZ gene normally produces two protein products of different length, RIZ1 and RIZ2. RIZ2 is generated by an internal promoter and lacks an NH2-terminal motif of RIZ1, the PR domain conserved in a subfamily of zinc finger genes that function as negative regulators of tumorigenesis. We have here studied whether the RIZ gene may play a role in human neoplasia. We found that expression of RIZ1 is commonly decreased or at undetectable levels in breast cancer tissues and cell lines. Decreased RIZ1 expression was also found in other tumor types including neuroblastoma and lung cancer. Remarkably, RIZ2 is normally expressed in all cases examined, suggesting that the abnormality observed for RIZ1 is specific. Forced RIZ1 expression in breast cancer cells caused cell cycle arrest in G2-M and/or programmed cell death. These observations suggest an exclusive negative selection for RIZ1 but not RIZ2 in breast cancer and a role for RIZ1 in tumor suppression.
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PMID:RIZ1, but not the alternative RIZ2 product of the same gene, is underexpressed in breast cancer, and forced RIZ1 expression causes G2-M cell cycle arrest and/or apoptosis. 976 44

Gene transfer is a potentially powerful tool for the treatment of a wide variety of diseases. The transfer of these genes is achieved by utilizing a variety of vectors, including retroviral, adenoviral, adeno-associated virus (AAV) and a number of non-viral mechanisms. Numerous studies have successfully demonstrated transduction of genes into target cells with a variety of vectors, and have provided 'proof-in-principle' that gene transfer can result in prolonged in vivo expression of transduced genes, albeit at low quantities. Furthermore, gene marking studies in acute myeloblastic leukemia (AML), chronic myeloid leukemia (CML) and neuroblastoma have elegantly demonstrated that gene-marked tumor cells contribute to relapse following autologous transplantation. However none of the studies examining the therapeutic benefit of gene therapy has definitively demonstrated a clinically meaningful benefit. Nonetheless, the results of studies involving gene transfer for severe combined immunodeficiency (SCID), chronic granulomatous disease (CGD), melanoma and lung cancer highlight the potential benefit of this strategy. This review will discuss mechanisms of achieving gene transfer into target cells. It will examine some of the pre-clinical and clinical results to date and will discuss some of the potential uses of gene transfer for therapeutic purposes.
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PMID:Gene transfer: a review of methods and applications. 983 7

Perillyl alcohol is a monoterpene isolated from the essential oils of lavendin, peppermint, spearmint, cherries, celery seeds, and several other plants. In animal studies it has been shown to regress pancreatic, mammary, and liver tumors, to exhibit possible application as a chemopreventative agent for colon, skin, and lung cancer, and as a chemotherapeutic agent for neuroblastoma, and prostate and colon cancer. Perillyl alcohol is active in inducing apoptosis in tumor cells without affecting normal cells and can revert tumor cells back to a differentiated state. Its mechanism of action is unclear, but it has actions on various cellular substances which control cell growth and differentiation. It has been shown to increase mannose-6-phosphate/insulin-like growth factor II receptors, increase tissue growth factor beta receptors, increase Bak, decrease ras protein prenylation, decrease ubiquinone synthesis, and induce Phase I and Phase II detoxification systems. Preliminary human trials have not demonstrated tumor regression at a four times daily dosage schedule. In addition, significant side-effects, mainly gastrointestinal, have been experienced.
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PMID:Perillyl alcohol: applications in oncology. 985 69

The objective of the present work is to critically summarize published studies and reassess the state of knowledge on a highly controversial topic: the potential association between prenatal exposure to passive smoking as well as maternal active smoking and postnatal exposure to environmental tobacco smoke (ETS) and enhanced incidence of childhood cancer. Elements to be considered include the substantial proportion of pregnant women who remain smokers, the widespread nature of exposure to ETS during pregnancy as well as during childhood, the known toxicology of tobacco smoke, and in particular sidestream smoke, characterized by a rich carcinogen content, the specific metabolism of foetuses and new-borns and finally the amount of epidemiologic data already available. We conducted a thorough review of the literature to identify studies either exclusively dealing with the effects of passive smoking on the occurrence of childhood cancers or more generally etiologic studies of cancer, be it overall or site-specific. We identified close to 50 publications presenting pertinent results from epidemiological investigations and about 50 more on mechanisms and metabolism, smoking in pregnancy and exposure to ETS as well as selected reviews and commentaries. Collaborative epidemiological studies were conducted in the United Kingdom (UK), USA, Sweden, Netherlands and internationally (France, Italy). In addition, other studies were also available from the USA, UK, Canada, Australia, Sweden, Italy, Denmark and People's Republic of China. The vast majority were case-control studies dealing with all cancers, leukaemia and lymphomas, central nervous system (CNS) tumours, Wilms' tumour, retinoblastoma, neuroblastoma, hepatoblastoma, rhabdomyosarcoma, bone and soft tissues tumours, germ cell tumours, as well as specific histological types of leukaemias, lymphomas or CNS tumours. No strong association between maternal smoking in pregnancy and/or exposure to ETS and childhood cancer is found. Yet, several studies found slightly increased relative risks, generally smaller than 1.5, i.e. the order of magnitude associated with some recognized hazards of exposure to ETS (1.2 to 1.3 for adult lung cancer and cardiovascular diseases). Tumours most often found associated with maternal smoking in pregnancy or ETS exposure are childhood brain tumours and leukaemia-lymphoma, with risks up to two or greater in selected studies. In a few studies, risks associated with paternal smoking are higher than the maternal ones. This evidence from human studies coupled with demonstration of genotoxic effects on the foetus of exposure to metabolites of tobacco smoke, and demonstrable presence of adducts should lead to strong recommendations aiming at fully protecting foetuses, new-borns and infants from tobacco smoke.
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PMID:From in utero and childhood exposure to parental smoking to childhood cancer: a possible link and the need for action. 1033 1


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