Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The biochemical, pharmacological and immunological characterization of cells derived from human neuroblastoma tumors recently acquired great interest, since these cells may be a putative donor source for transplantation in animal models of neurological disorders. We measured monoamine levels, tyrosine hydroxylase (TH) immunostaining, and the expression of major histocompatibility cell surface antigens (MHC) in 7 human neuroblastoma cell lines. Three cell lines (LAN5, NB69 and CHP126) had high levels of monoamines. TH immunostaining was strongly positive in CHP126 and LAN5, and NB69. MHC were not detected in any of the cells with high catecholamine levels. Treatment with neuroleptics increased the metabolism of dopamine in LAN5 but not in NB69. The implantation of LAN5 cells in immunocompetent, unilaterally 6-hydroxydopamine-lesioned rats decreased the apomorphine-induced contralateral rotation. The effect of the implant was greatest in animals in which LAN5 neuroblastoma cells, pretreated with dibutyryl cyclic adenosine monophosphate (DBcAMP) and prostaglandin E1 (PGE1, were implanted into the cerebral ventricle ipsilateral to the lesion, and then irrigated with DBcAMP administered through a totally implanted drug delivery system. The effect of the implant decreased after the second week. Neuroblastoma cells were found in approximately 50% of the implanted animals. TH immunostaining was weak or absent in the grafted animals. Inflammatory changes were present in the majority of the brains examined. Extensive tumor growth was present in one animal implanted with untreated cells. Grafting of cells treated with DBcAMP and PGE1 plus with mitomycin C and bromodeoxyuridine in animals immunosuppressed with cyclosporin A reduced the apomorphine-induced rotation to 40-60% of baseline levels and this reduction persisted beyond the period of infusion with DBcAMP. Intraventricular infusion of DBcAMP in animals injected with cell culture medium produced a transient reduction of rotation to 70% of baseline. The amphetamine-induced rotation was not significantly reduced during the 4 weeks follow up. Atypical cells, consistent with surviving neuroblastoma cells, were observed in the brain of all transplanted animals. TH immunostaining was weak or negative in most cases. Human neuroblastoma cells may be an alternative donor tissue for the study of the effects of transplantation in animal models of Parkinson's disease.
 ...
PMID:Biochemical properties of monoamine-rich human neuroblastoma cells. 256 96

Neuroblastoma is the most common extracranial tumor in children, and cytogenetically, chromosome 1p deletions, extrachromosomal double minutes, and homogeneously staining regions (HSRs) are commonly observed in cell lines and in tumors in advanced stages. It is found that an HSR represents genomic amplification of N-myc, which plays a key role in determining the aggressiveness of neuroblastoma. However, stage IV neuroblastomas or cell lines which lack N-myc amplification are also progressive, and some of them show evidence of N-myc expression in terms of mRNA and/or N-Myc oncoprotein. It was recently shown that a small proximal locus mapped between 1p35-36.1 and 1p36.23 may function as a suppressor gene of N-myc amplification. In neuroblastoma, a pattern of diploidy is associated with rapid tumor growth and poor survival. Expression of bcl-2 proto-oncogene is strongly associated with unfavorable histology, while expressions of Ha-ras and trk-A proto-oncogenes indicate a favorable prognosis. trk-A proto-oncogene encodes a receptor for nerve growth factor. Genetic characteristics of neuroblastomas found by urinary catecholamine mass screening are also discussed.
 ...
PMID:Genetic clinical markers of human neuroblastoma with special reference to N-myc oncogene: amplified or not amplified?--An overview. 865 15

Neuroblastoma, a childhood neoplasm arising from neural crest cells, is characterized by a diversity of clinical behavior, ranging from spontaneous remission to rapid tumor progression and death. To some extent, outcome can be predicted by the stage of disease and age at diagnosis. The molecular events responsible for the variability in response to treatment and rate of tumor growth, however, remain largely unknown. Over the past decade, transformation-linked genetic changes have been identified in neuroblastoma tumors that have contributed to our understanding of tumor predisposition, metastasis, treatment responsiveness, and prognosis. This review discusses the recent advances in the understanding of neuroblastoma at the cellular and molecular levels, and the role that tumor biology plays in determining appropriate risk-based treatment for patients with neuroblastoma.
 ...
PMID:Advances in the diagnosis and treatment of neuroblastoma. 946 84

Direct experimental evidence shows that tumor growth and metastases are angiogenesis-dependent. Neuroblastoma (NB) is the most common extracranial malignant solid tumor of childhood. In this study, we investigated 2 human NB cell lines, LAN-5 and GI-LI-N, for their capacity to secrete 2 extracellular matrix-degrading enzymes, MMP-2 and MMP-9, and to induce in vitro human microvascular endothelial cells (EC) to proliferate and in vivo angiogenesis in the chick embryo chorio-allantoic membrane (CAM) assay. Conditioned medium (CM) from both cell lines stimulated in vitro EC proliferation and the effect of LAN-5 CM was higher than that of GI-LI-N cells. Moreover, anti-VEGF, but not anti-FGF2 antibodies, prevented growth increment of EC. NB cell lines secreted the active form of MMP-2 almost exclusively, LAN-5 cells more than GI-LI-N cells. Both cell lines, LAN-5 cells more than GI-LI-N ones, induced angiogenesis in the CAM assay. Our data suggest that the 2 NB cell lines are angiogenic, to LAN-5 cells more than GI-LI-N ones. LAN-5 cells are indeed endowed with a more aggressive and invasive phenotype.
 ...
PMID:Human neuroblastoma cells produce extracellular matrix-degrading enzymes, induce endothelial cell proliferation and are angiogenic in vivo. 966 9

Neuroblastoma is a malignant solid tumor of childhood with a poor prognosis. The growth of solid tumors has been shown to be dependent on new blood vessel formation, i.e. angiogenesis. Several steps in the metastatic process have also been found to be angiogenesis-dependent. Neuroblastomas grow quickly, are highly vascularized, and metastasize early, and hence inhibition of angiogenesis--angiostatic therapy--may be indicated in this disease. In order to investigate the effects of angiostatic agents in this disease, a new animal experimental model for human neuroblastoma was developed. Three angiostatic agents were tested in the model: TNP-470, the synthetic analogue of fumagillin, given subcutaneously, and the endogenous steroid 2-methoxyestradiol and its derivative 2-propynylestradiol, given orally. TNP-470 administration resulted in a significant reduction of the tumor growth rate and microvascular counts, and of the fraction of viable tumor cells, compared to controls. The fraction of apoptotic tumor cells increased threefold, while that of proliferative cells remained unaltered. This can explain the reduced net growth. Treatment with the angiostatic and chemotherapeutic steroids 2-methoxyestradiol and 2-propynylestradiol yielded similar results. However, the mechanism of action of these steroids was bimodal; the effect occurring both through inhibition of tumor angiogenesis and through induction of tumor cell apoptosis. It was shown for the first time that inhibition of angiogenesis regardless of agent induces striking chromaffin differentiation, observed as increased expression of insulin-like growth factor II gene, tyrosine hydroxylase, and chromogranin A, and increased formation of cellular processes. It is suggested that inhibition of angiogenesis induces metabolic stress, resulting in chromaffin differentiation and apoptosis. Such agonal differentiation may be the link between angiostatic therapy and tumor cell apoptosis. Angiostatic agents administered as single therapy have an objective tumoristatic effect in our neuroblastoma model. Angiostatic treatment of neuroblastoma is a new and promising treatment modality that merits clinical investigation.
 ...
PMID:Angiostatic treatment of neuroblastoma. 1037 67

Neuroblastoma, a neural crest-derived childhood tumor of the sympathetic nervous system, may in some cases differentiate to a benign ganglioneuroma or regress due to apoptosis. However, the majority of neuroblastomas are diagnosed as metastatic tumors with a poor prognosis despite intensive multimodal therapy. The neuropeptide somatostatin (SOM) has been shown to inhibit neuroblastoma growth and induce apoptosis in vitro. Therapeutic effects of SOM analogues are dependent on tumor expression of high-affinity receptors. In the present study, human neuroblastoma SH-SY5Y cells were grown as xenografts in nude rats. In vivo SOM receptor expression in the xenografts was identified using scintigraphy with 111In-pentetreotide. Rats were randomized to treatment with the long-acting SOM analogue octreotide (10 microg s.c. every 12 h), 13-cis-retinoic acid (4 mg orally every 24 h), or vasoactive intestinal peptide (40 microg s.c. every 24 h) and compared with controls. Tumor volume was assessed every second day and tumor weight after 10-12 d. Octreotide treatment inhibited neuroblastoma growth significantly with reduced tumor volumes at 10 and 12 d compared with untreated controls (mean 3.56 and 4.24 versus 6.48 and 8.01 mL, respectively; p < 0.01). Also, tumor weights after 10-12 d were reduced in octreotide-treated animals (n = 8, median weight 2.90 g, range 1.67-5.57 g) compared with untreated rats (n = 14, 7.54 g, 1.65-10.82 g, p = 0.005). Serum IGF-I decreased significantly over time both in rats treated with octreotide and in untreated controls. It is concluded that treatment with the SOM analogue octreotide may significantly decrease neuroblastoma tumor growth in vivo. Further studies are warranted to establish the role of SOM analogues in the treatment of children with unfavorable neuroblastoma.
 ...
PMID:The somatostatin analogue octreotide inhibits neuroblastoma growth in vivo. 1047 50

Neuroblastoma (NBL) and medulloblastoma (MBL) are tumors of the neuroectoderm that occur in children. NBL and MBL express Trk family tyrosine kinase receptors, which regulate growth, differentiation, and cell death. CEP-751 (KT-6587), an indolocarbazole derivative, is an inhibitor of Trk family tyrosine kinases at nanomolar concentrations. This study was designed to determine the effect of CEP-751 on the growth of NBL and MBL cell lines as xenografts. In vivo studies were conducted on four NBL cell lines (IMR-5, CHP-134, NBL-S, and SY5Y) and three MBL cell lines (D283, D341, and DAOY) using two treatment schedules: (a) treatment was started after the tumors were measurable (therapeutic study); or (b) 4-6 days after inoculation, before tumors were palpable (prevention study). CEP-751 was given at 21 mg/kg/dose administered twice a day, 7 days a week; the carrier vehicle was used as a control. In therapeutic studies, a significant difference in tumor size was seen between treated and control animals with IMR-5 on day 8 (P = 0.01), NBL-S on day 17 (P = 0.016), and CHP-134 on day 15 (P = 0.034). CEP-751 also had a significant growth-inhibitory effect on the MBL line D283 (on day 39, P = 0.031). Inhibition of tumor growth of D341 did not reach statistical significance, and no inhibition was apparent with DAOY. In prevention studies, CEP-751 showed a modest growth-inhibitory effect on IMR5 (P = 0.062) and CHP-134 (P = 0.049). Furthermore, inhibition of growth was greater in the SY5Y cell line transfected with TrkB compared with the untransfected parent cell line expressing no detectable TrkB. Terminal deoxynucleotidyl transferase-mediated nick end labeling studies showed CEP-751 induced apoptosis in the treated CHP-134 tumors, whereas no evidence of apoptosis was seen in the control tumors. Finally, there was no apparent toxicity identified in any of the treated mice. These results suggest that CEP-751 may be a useful therapeutic agent for NBL or MBL.
 ...
PMID:Antitumor activity of CEP-751 (KT-6587) on human neuroblastoma and medulloblastoma xenografts. 1058 76

Angiogenesis is essential for tumor growth and metastasis and depends on the production of angiogenic factors by tumor cells. Neuroblastoma (NB) is a common pediatric tumor of neural crest origin, which is biologically and clinically heterogeneous. Increased tumor vascular index correlates with poor outcome of NB. To determine which angiogenic factors contribute to NB angiogenesis and thereby support tumor progression, we examined the expression of eight angiogenic factors [vascular endothelial growth factor (VEGF), VEGF-B, VEGF-C, basic fibroblast growth factor, angiopoietin (Ang)-1, Ang-2, transforming growth factor alpha, and platelet-derived growth factor (PDGF)] by semiquantitative RT-PCR in 37 NB primary tumors and in 22 NB cell lines. We also analyzed the relationship between angiogenic factor expression and clinicopathological factors as well as patient survival. All eight angiogenic factors examined were expressed at various levels in NB cell lines and tumors, suggesting their involvement in NB angiogenesis. The expression levels of most angiogenic factors were correlated with each other, suggesting their synergy in regulating the angiogenic process. Significantly higher expression levels of VEGF, VEGF-B, VEGF-C, basic fibroblast growth factor, Ang-2, transforming growth factor alpha, and PDGF-A (P < 0.0001-0.026) were found in advanced-stage tumors (stages 3 and 4) compared with low-stage tumors (stages 1, 2, and 4S). Expression of PDGF-A was significantly associated with patient survival (P = 0.04). The redundancy in angiogenic factor expression suggests that inhibition of VEGF bioactivity alone might not be a sufficient approach for antiangiogenic therapy of human NB.
 ...
PMID:High-level expression of angiogenic factors is associated with advanced tumor stage in human neuroblastomas. 1081 14

Neuroblastoma (NB), the most common extracranial solid tumor in childhood is associated with poor prognosis in patients with advanced tumor stages. Natural human cytotoxic anti-NB IgM antibodies present in the serum of healthy humans are discussed as a potential novel immunotherapeutic regimen against human NB because these antibodies have been shown to affect growth arrest of solid s.c. xenografts of human NB in nude rats. Subcutaneously induced tumors, however, exhibit a different growth pattern compared with the typical growth pattern of NB tumors in humans. Therefore, we developed in this study a novel metastatic tumor model in nude rats that reflects the clinical appearance of human NB and used this model to study the therapeutic efficacy of human anti-NB IgM. Intra-aortal injection of human NB cells in nude rats resulted in the development of large invasive adrenal gland tumors and micrometastases in the liver and bones. Apparently, adrenal glands provide most favorable growth conditions for human NB cells, as documented by the preferential and rapid growth of NB cells in this location. We studied three different treatment protocols of natural human anti-NB IgM. Anti-NB IgM completely inhibited tumor formation and metastases when injected simultaneously with human LAN-1 NB cells (P < 0.05). When antibody treatment was started 6 days after tumor cell injection (i.e., micrometastatic stage), tumor growth was inhibited by 90% (P < 0.05). An anti-NB IgM therapy directed against established tumors (14 days after tumor cell injection) shrank adrenal gland tumors by 90% (P < 0.05). Analysis of the tumors revealed both complement activation and an induction of apoptosis as two independent mechanisms of antitumor function. This study strongly suggests human anti-NB IgM antibodies as new agents for the therapy of neuroblastoma.
 ...
PMID:A novel metastatic animal model reflecting the clinical appearance of human neuroblastoma: growth arrest of orthotopic tumors by natural, cytotoxic human immunoglobulin M antibodies. 1130 75

Neuroblastoma is notable for its cellular heterogeneity and unpredictable outcome. Tumors are a variable mixture of primitive malignant neuroblasts, more differentiated ganglionic cells, Schwann and endothelial cells. Although often fatal, neuroblastomas can spontaneously regress, possibly due to favorable autocrine and paracrine interactions among these cells. Here, pigment epithelium-derived factor (PEDF), a potent inhibitor of angiogenesis and inducer of neural differentiation, is shown to be produced by ganglionic cells and Schwann cells, but not by more primitive tumor cells. Although undifferentiated neuroblastoma tumor cell secretions were angiogenic primarily due to vascular endothelial growth factor, secretions of Schwann cells were anti-angiogenic due to PEDF. In addition, PEDF was the major factor responsible for Schwann cell's ability to induce tumor cell differentiation in vitro and recombinant PEDF had the same effect in vitro and in vivo. Both the growth and the survival of Schwann cells were enhanced by PEDF. Thus PEDF may serve as a multifunctional antitumor agent in neuroblastomas, inhibiting angiogenesis while promoting the numbers of Schwann cells and differentiated tumor cells that in turn produce PEDF, suggesting that its clinical administration could stimulate a multifaceted antitumor feedback loop with the potential to limit and possibly regress tumor growth.
 ...
PMID:Pigment epithelium-derived factor (PEDF) in neuroblastoma: a multifunctional mediator of Schwann cell antitumor activity. 1179 7


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