Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007095 (carcinoid)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies of growth-regulation of neuroendocrine cells have been hampered by a lack of suitable in vitro models. We established and have maintained a functioning human pancreatic carcinoid cell (BON) line. BON cells synthesize and secrete several growth factors. Among those, we have found that serotonin stimulates growth of BON cells through specific receptors linked to cyclic AMP pathway. In this study, effects of other growth factors on growth and serotonin release, and the effects of serotonin and TGF-beta 1 on the polyamine biosynthetic pathway, were examined. TGF-beta 1 inhibited both growth and serotonin release in a dose-dependent fashion. Basic FGF stimulated growth, but failed to affect serotonin release. Other peptide growth factors had no effect on either growth or serotonin release. Serotonin stimulated ODC enzyme activity, but TGF-beta 1 failed to affect ODC enzyme activity. These findings suggest that growth of neuroendocrine cells can be delicately regulated by their own products in an autocrine fashion.
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PMID:Studies of growth regulation in a neuroendocrine cell line. 832 53

Carcinoid tumors originate from the neuroendocrine cells throughout the body and are capable of producing various peptides. Their clinical course is often indolent but can also be aggressive and resistant to therapy. We examined all aspects of carcinoid tumors including the molecular biology oncogenesis, role of angiogenesis, recent advances in imaging, and therapy. The Medline and Cancerlit databases were searched using carcinoid as the keyword. English language manuscripts were reviewed and relevant references from a total of 7741 were found. All titles were screened and all the relevant manuscripts were analyzed; we found 307 references pertinent to the history, epidemiology, clinical behavior, pathology, pathophysiology, molecular biology, radiologic imaging, supportive care of carcinoid syndrome, and results of therapeutic clinical trials. Management of patients with carcinoid tumors requires an understanding of the disease process and a multimodality approach. Introduction of long-acting somatostatin analogues has resulted in significant advances in the palliative care of patients with carcinoid syndrome. However, advanced carcinoid tumor remains incurable. Existing therapies for advanced disease have low biologic activity, high toxicity, or both. Clearly, more research is necessary in the areas of molecular biology, targeted therapy, and development of new drugs Future advances in this field need to focus on clinical and biological predictors of outcome. Early works in the area of tumor biology such as the role of p53, bcl-2, bax, MEN1, FGF TGF PDGF and VEGF expression are of interest and need to be explored further.
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PMID:Carcinoid--a comprehensive review. 1469 Jan 53

FGF and WNT signaling pathways network together during embryogenesis and carcinogenesis. Among 22 FGF family members within human and rodents genomes, FGF20 orthologs are evolutionarily conserved targets of the WNT/beta-catenin signaling pathway. FGF8, FGF17, and FGF18 constitute one of FGF subfamilies. Here, comparative proteomics and comparative genomics analyses on FGF8, FGF17, and FGF18 orthologs were performed. Rat Fgf8 and Fgf17 genes, consisting of five exons, were located within AC096326.7 and AC097410.12 genome sequences, respectively. FGF8, FGF17, and FGF18 orthologs were FGF family members with the N-terminal signal peptide. Human FGF8 isoform F showed 90.6% total-amino-acid identity with rat Fgf8 (268 aa). Human FGF17 showed 98.6% total-amino-acid identity with rat Fgf17 (216 aa). Human FGF18 also showed 98.6 total-amino-acid identity with rat Fgf18. FBXW1 (betaTRCP1 or BTRC1)-FGF8-NPM3 locus at human chromosome 10q24.32, FBXW11 (betaTRCP2 or BTRC2)-FGF18-NPM1 locus at human chromosome 5q35.1, and FGF17-NPM2 locus at human chromosome 8p21.3 were paralogous regions within the human genome. FGF8 mRNA was expressed in DMSO-treated embryonic stem (ES) cells. FGF17 mRNA was expressed in ES cells differentiated to an early endodermal phenotype. FGF18 mRNA was expressed in fetal lung, fetal heart, lung carcinoid, colorectal cancer, and ovarian cancer. FGF18 promoter with double TCF/LEF binding sites rather than FGF8 promoter and FGF17 promoter was more conserved between human and rodents. These facts indicate that FGF18 orthologs were evolutionarily conserved targets of the WNT/beta-catenin signaling pathway.
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PMID:Comparative genomics on FGF8, FGF17, and FGF18 orthologs. 1607 60

WNT, Notch, FGF, and Hedgehog signaling pathways network together during embryogenesis, tissue regeneration, and carcinogenesis. Association of Notch ligands with Notch receptors on neighboring cells leads to cleavage of Notch receptors by metalloprotease and gamma-secretase to induce nuclear translocation of Notch intracellular domain (NICD). Nuclear complex, consisting of CSL (RBPSUH), NICD, Mastermind (MAML), p300 and histone acetyltransferase (HAT), then induces transcriptional activation of Notch target genes, such as HES1, HES5, HES7, HEY1, HEY2 and HEYL. Here, we searched for TCF/LEF-binding site within the promoter region of Notch ligand genes, including DLL1, DLL3, DLL4, JAG1 and JAG2. Because TCF/LEF-binding sites were identified within human JAG1 promoter based on bioinformatics and human intelligence, comparative genomics analyses on JAG1 orthologs were further performed. Chimpanzee JAG1 gene, consisting of 26 exons, was identified within NW_120319.1 genome sequence. XM_525264.1 and XM_514517.1 were not the correct coding sequences for chimpanzee JAG1. Chimpanzee JAG1 gene was found to encode a 1218-amino-acid protein showing 99.5% and 96.2% total-amino-acid identity with human JAG1 and mouse Jag1, respectively. Phylogenetic analysis revealed that JAG1 orthologs were more conserved than those of other Notch ligands. JAG1 gene was identified as evolutionarily conserved target of WNT/beta-catenin signaling pathway based on the conservation of double TCF/LEF-binding sites within 5'-promoter region of mammalian JAG1 orthologs. Human JAG1 mRNA was expressed in embryonic stem (ES) cells, neural tissues, lung carcinoid, gastric cancer, pancreatic cancer, colon cancer, and also in squamous cell carcinoma (SCC) of skin, oral cavity, esophagus, head and neck. JAG1 expression on progenitor cells due to canonical WNT signaling activation induces self-renewal of stem cells due to Notch signaling activation. JAG1, functioning as WNT-dependent Notch signaling activator, is the key molecule maintaining the homeostasis of stem and progenitor cells.
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PMID:Notch ligand, JAG1, is evolutionarily conserved target of canonical WNT signaling pathway in progenitor cells. 1652 28