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)

Most neonatal abdominal masses will be due to benign retroperitoneal lesions such as hydronephrosis and multicystic dysplastic kidney. Although history and physical examination, plain radiographs and ultrasonography will confirm most diagnoses, severe unilateral hydronephrosis, hemorrhagic neuroblastoma, and intraperitoneal cysts may provide diagnostic difficulties. Masses identified by prenatal ultrasound need careful evaluation as they may represent normal structures, nonsignificant variants, or physiologically significant anomalies. Many lesions will require operative intervention, which can be safely performed in small infants by trained personnel at facilities with appropriate support services. Genuine controversy exists in the management of some of these lesions including MDK, renal vein thrombosis, and acalculous cholecystitis.
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PMID:Abdominal mass lesions in the newborn: diagnosis and treatment. 265 56

Pleiotrophin (PTN) and midkine (MK) are members of a new family of neurotrophic factors whose expression is developmentally regulated. PTN also transforms NIH 3T3 cells, and MK is mitogenic to certain cell lines. Neuroblastomas are tumors derived from neural crest cells, and recent studies have revealed that the biology of these tumors is at least partly regulated by neurotrophic factors and their receptors. To examine the expression of PTN and MK in neuroblastoma, we analyzed their mRNA expression in 72 primary neuroblastomas and 11 neuroblastoma cell lines as well as other tissues and cell lines. PTN is highly expressed in favorable neuroblastomas (stages I, II, and IV-S, n = 44), whereas it is expressed at a significantly lower level in advanced tumors (stages III and IV, n = 28, P = 0.003). PTN is not expressed in either aggressive neuroblastomas with N-myc amplification or in neuroblastoma cell lines. Moreover, the expression pattern of PTN was similar to that of TRK-A, the high affinity receptor for nerve growth factor, in that it is correlated with a favorable prognosis (P < 0.004). In contrast, MK is highly expressed in almost all primary neuroblastomas and cell lines and showed no correlation with disease stage or N-myc amplification. These results suggest that differential expression of PTN and MK may have an important role in regulating growth and differentiation of neuroblastomas.
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PMID:Differential expression of pleiotrophin and midkine in advanced neuroblastomas. 771 89

The treatment of advanced neuroblastoma (NB) or Ewing's sarcoma (ES) is one of the major challenges in pediatric oncology. Both malignancies are refractory to conventional therapies and have an extremely poor prognosis. High-dose myeloablative radiochemotherapy with autologous bone marrow or peripheral blood stem cell rescue is one of the most aggressive treatments attempted for these diseases but is often undermined by residual tumor cells contaminating the graft. Thus, in this approach, purging of tumor cells from the graft is key to the prevention of relapse after transplantation. We investigated a novel approach to eliminate tumor cells from the bone marrow or peripheral blood stem cell graft without causing stem cell damage through the use of a conditionally replicative adenovirus (Ad). ES and NB are sensitive to Ad infection, and advanced NBs express a high level of the growth/differentiation factor midkine (MK). We confirmed in this study that ES cell lines (SK-ES-1 and RD-ES) are also sensitive to Ad infection and express high levels of MK. In contrast, CD34+ stem cells are refractory to Ad infection and express very little MK. A conditionally replicative Ad in which the expression of E1 is controlled by the MK promoter achieved good levels of viral replication in NB or ES and induced remarkable tumor cell killing. On the other hand, this virus caused no damage to CD34+ cells even after 3 h of infection at a dose of 1000 multiplicity of infection. We concluded that application of this replication-competent Ad to hematopoietic grafts could be a simple but effective procedure to achieve complete tumor cell purging.
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PMID:A midkine promoter-based conditionally replicative adenovirus for treatment of pediatric solid tumors and bone marrow tumor purging. 1169 8

Cell-surface heparan sulfate proteoglycans participate in molecular events that regulate cell adhesion, migration, and proliferation. The present study was performed to elucidate whether glypican-2 plays a role in interactions of neurons with midkine (MK), a heparin-binding neuroregulatory factor. MK bound to heparan sulfate chains of glypican-2 in a manner similar to syndecan-3. Microbeads coated with MK or poly-L-lysine induced clustering of glypican-2 as well as syndecan-3. Substratum-bound MK or poly-L-lysine induced cell adhesion of N2a neuroblastoma cells, while only MK promoted neurite outgrowth of these cells. Ligation of cell-surface glypican-2 with MK or an antibody against epitope-tagged glypican-2 induced cell adhesion and promoted neurite outgrowth. These results verified that cell-surface glypican-2 bound to MK and suggested that MK-glypican-2 interactions participate in neuronal cell migration and neurite outgrowth. In addition, we observed different localization of epitope-tagged glypican-2 and syndecan-3 on the surface of N2a cells; the result suggested that they may play different roles in MK-mediated neural function.
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PMID:Glypican-2 binds to midkine: the role of glypican-2 in neuronal cell adhesion and neurite outgrowth. 1208 85

The heparin-binding growth factor midkine (MK) is the product of a retinoic acid-responsive gene, and is implicated in neuronal survival and differentiation, and carcinogenesis. We previously reported that MK mRNA expression is elevated in neuroblastoma specimens at all stages, whereas pleiotrophin, the other member of the MK family, is expressed at high levels in favourable neuroblastomas. As MK is a secretory protein, it can be detected in the blood. Here, we show a significant correlation of the plasma MK level with prognostic factors of neuroblastomas. The plasma MK level was determined in 220 patients with neuroblastomas, and compared with that in children without malignant tumors (n=17, <500 pg ml(-1)). The plasma MK level became significantly elevated with advancing stages (stage 1: 445 pg ml(-1) (median), n=73; stage 2: 589, n=39; stage 3: 864, n=40; stage 4: 1445, n=56; and stage 4S: 2439, n=12). More importantly, a higher MK level was strongly correlated with poor prognostic factors: over 1 year of age (P=0.0299), MYCN amplification (P<0.0001), low TrkA expression (P=0.0005), nonmass screening, sporadic neuroblastomas (P<0.0001), and diploidy/tetraploidy (P=0.0007). Thus, these results demonstrate that the plasma MK level is a good marker for evaluating the progression of neuroblastomas. Moreover, considering the ability of antisense MK oligodeoxyribonucleotide to suppress tumour growth of colorectal carcinoma cells in nude mice, as recently reported, the present study suggests that MK is a possible candidate molecular target for therapy for neuroblastomas.
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PMID:Correlation of elevated level of blood midkine with poor prognostic factors of human neuroblastomas. 1277 16

Appican produced by rat C6 glioma cells, the chondroitin sulfate (CS) proteoglycan form of the amyloid precursor protein, contains an E disaccharide, -GlcUA-GalNAc(4,6-O-disulfate)-, in its CS chain. In this study, the appican CS chain from rat C6 glioma cells was shown to specifically bind several growth/differentiation factors including midkine (MK) and pleiotrophin (PTN). In contrast, the appican CS from SH-SY5Y neuroblastoma cells contained no E disaccharide and showed no binding to either MK or PTN. These findings indicate that the E motif is essential in the interaction of the appican CS chain with growth/differentiation factors, and suggest that glial appican may mediate the regulation of neuronal cell adhesion and migration and/or neurite outgrowth.
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PMID:Chondroitin sulfate of appican, the proteoglycan form of amyloid precursor protein, produced by C6 glioma cells interacts with heparin-binding neuroregulatory factors. 1474 73

The clinical outcome of microsurgical reconstruction of large peripheral nerve lesions depends on the availability of suitable graft material. Allogenic nerve grafts are rejected by the immune system. Extracellular-matrix proteins, in contrast to the resident cells, are of low immunogenicity in allografts. Here, human tibial nerve segments were extracted with lysophosphatidyl choline. The obtained cell-free and myelin-free scaffold consisted of empty endoneural tubes with maintained extracellular matrix architecture. The nerve scaffold had mechanical properties comparable to intact nerve, making it suitable for microsurgical reconstruction. Sections of the nerve scaffold were tested as a substrate for the adhesion and neuronal differentiation of human neuroblastoma-derived LAN-5 cells. Nerve extraction removed laminin-2, an isoform of laminin important for peripheral nerve regeneration. Laminin-2 reloading of the nerve scaffold did not improve cell adhesion and axon growth. Chemical crosslinking of heparan sulfate, on the other hand, increased the percentage of adherent cells with outgrowing neurites from 48 to 85%. Combined laminin-2 reloading and heparan sulfate crosslinking reduced the percentage of neurite-forming cells to 22% of the number of adherent cells. Implantation of the nerve scaffold into the peritoneal cavity of mice was not cytotoxic, and neovascularization of the graft material was observed within weeks. In conclusion, extraction of human nerve with detergents revealed a biocompatible nerve scaffold supporting neuronal cell adhesion. Heparan sulfate crosslinking to the scaffold surface improved neurite outgrowth, presumably mediated by midkine, a member of the neurokine family of growth factors, which is secreted by neuroblastoma-derived cells and binds to heparan sulfate.
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PMID:Stimulation of neurite outgrowth in a human nerve scaffold designed for peripheral nerve reconstruction. 1566 Apr 44

Midkine is a heparin-binding growth factor that promotes cell attachment and process extension in undifferentiated bipolar CG-4 cells, an oligodendroglial precursor cell line. We found that CG-4 cells expressed a non-proteoglycan form of neuroglycan C, known as a part-time transmembrane proteoglycan. We demonstrated that neuroglycan C before or after chondroitinase ABC treatment bound to a midkine affinity column. Neuroglycan C lacking chondroitin sulfate chains was eluted with 0.5 m NaCl as a major fraction from the column. We confirmed that CG-4 cells expressed two isoforms of neuroglycan C, I, and III, by isolating cDNA. Among three functional domains of the extracellular part of neuroglycan C, the chondroitin sulfate attachment domain and acidic amino acid cluster box domain showed affinity for midkine, but the epidermal growth factor domain did not. Furthermore, cell surface neuroglycan C could be cross-linked with soluble midkine. Process extension on midkine-coated dishes was inhibited by either a monoclonal anti-neuroglycan C antibody C1 or a glutathione S-transferase-neuroglycan C fusion protein. Finally, stable transfectants of B104 neuroblastoma cells overexpressing neuroglycan C-I or neuroglycan C-III attached to the midkine substrate, spread well, and gave rise to cytoskeletal changes. Based on these results, we conclude that neuroglycan C is a novel component of midkine receptors involved in process elongation.
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PMID:Neuroglycan C is a novel midkine receptor involved in process elongation of oligodendroglial precursor-like cells. 1690 7

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase (RTK) involved in the genesis of several human cancers; indeed, ALK was initially identified in constitutively activated and oncogenic fusion forms--the most common being nucleophosmin (NPM)-ALK--in a non-Hodgkin's lymphoma (NHL) known as anaplastic large-cell lymphoma (ALCL) and subsequent studies identified ALK fusions in the human sarcomas called inflammatory myofibroblastic tumors (IMTs). In addition, two recent reports have suggested that the ALK fusion, TPM4-ALK, may be involved in the genesis of a subset of esophageal squamous cell carcinomas. While the cause-effect relationship between ALK fusions and malignancies such as ALCL and IMT is very well established, more circumstantial links implicate the involvement of the full-length, normal ALK receptor in the genesis of additional malignancies including glioblastoma, neuroblastoma, breast cancer, and others; in these instances, ALK is believed to foster tumorigenesis following activation by autocrine and/or paracrine growth loops involving the reported ALK ligands, pleiotrophin (PTN) and midkine (MK). There are no currently available ALK small-molecule inhibitors approved for clinical cancer therapy; however, recognition of the variety of malignancies in which ALK may play a causative role has recently begun to prompt developmental efforts in this area. This review provides a succinct summary of normal ALK biology, the confirmed and putative roles of ALK fusions and the full-length ALK receptor in the development of human cancers, and efforts to target ALK using small-molecule kinase inhibitors.
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PMID:Development of anaplastic lymphoma kinase (ALK) small-molecule inhibitors for cancer therapy. 1769 47

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase essentially and transiently expressed during development in specific regions of the central and peripheral nervous system. ALK expression persists at a lower level in the adult brain. Thus, it might play an important role in both the normal development and function of the nervous system. The nature of the cognate ligand of this receptor in vertebrates is still a matter of debate. Pleiotrophin and midkine have been proposed as ligands of ALK but several independent studies do not confirm this hypothesis. Interestingly, a recent study proposed that a C-terminal truncated form of Pleiotrophin (Pleiotrophin.15) and not the full length form (Pleiotrophin.18) promotes glioblastoma proliferation in an ALK-dependent fashion. These data were obviously a strong basis to conciliate the conflicting results so far reported in the literature. In the present study, we first purified to homogeneity the two forms of Pleiotrophin secreted by HEK 293 cells. In contrast to agonist monoclonal antibodies, both Pleiotrophin.15 and Pleiotrophin.18 failed to activate ALK in neuroblastoma and glioblastoma cells expressing this receptor. Thus, for our point of view, ALK is still an orphan receptor in vertebrates.
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PMID:In contrast to agonist monoclonal antibodies, both C-terminal truncated form and full length form of Pleiotrophin failed to activate vertebrate ALK (anaplastic lymphoma kinase)? 1790 22


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