Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Basic fibroblast growth factor (bFGF) has been thought to act as a neurotrophic factor during early developmental stages in various brain regions, including the hypothalamus. In the present paper, we have studied the effect of bFGF on peptide-containing neurons cultured from the postnatal (1-3 days and 14 days after birth) rat hypothalamus. The addition of bFGF, or acid FGF (aFGF), to serum-free culture medium increased both survival and neurite growth of growth hormone-releasing factor (GRF)-containing neurons. The potency of bFGF was more than 10 times as great as that of aFGF. Insulin-like growth factor I (IGF-I) did not have any significant effect on the survival of GRF neurons. Further, neither IGF-I nor aFGF modified the survival-promoting effect of bFGF on GRF neurons. bFGF promoted the survival of somatostatin- and vasoactive intestinal polypeptide-containing neurons, too.
 ...
PMID:Neurotrophic effects of fibroblast growth factors on peptide-containing neurons in culture from postnatal rat hypothalamus. 162 Feb 87

The distribution of basic fibroblast growth factor (bFGF)-immunoreactivity (IR) was studied in rat sensory and autonomic ganglia. In postnatal and adult sympathetic superior cervical ganglia and in adult parasympathetic otic ganglia no bFGF-staining was found. Postnatal and adult neural crest- and placode-derived sensory ganglia displayed intensive bFGF-IR in a neuronal subpopulation. This subpopulation was characterized by use of consecutive sections of adult dorsal root ganglia stained with antibodies against substance P, somatostatin, bombesin, and bFGF. Basic FGF was colocalized with the somatostatin/bombesin subpopulation but not with substance P.
 ...
PMID:Localization of basic fibroblast growth factor in a subpopulation of rat sensory neurons. 173 9

A clonal multipeptide-secreting cell line (44-2C) was used to study the interaction of basic fibroblast growth factor (bFGF) and GRF. The experiments were carried out in cells maintained under serum-free conditions in the absence of growth factors and hormonal supplements. We have shown that in 44-2C cells, rat hypothalamic GRF (rGRF) stimulates neurotensin, calcitonin, and somatostatin secretion. bFGF is not a mitogen in the 44-2C cells, but does regulate differentiated function by a mechanism involving regulation of RNA stabilization. The results presented here show for the first time that FGF acts as a competence factor mediating the cellular action of rGRF. In FGF-pretreated cells, 4-h exposure to rGRF stimulated RNA and protein synthesis. In this cell line rGRF was biologically active at 10(-14) M, and the ED50 for rGRF-mediated RNA and protein synthesis ranged from 10(-11) to 10(-12) M. We conclude that the interaction of FGF, acting as a permissive factor, and rGRF results in a novel mechanism of action for rGRF. These findings suggest that hypophysiotropic factors affect the cellular milieu in concert with growth factors, such as bFGF.
 ...
PMID:Fibroblast growth factor is a permissive factor mediating the cellular action of rat hypothalamic growth hormone-releasing factor. 244 41

A multiple peptide-synthesizing clonal rat cell line was used to study the effect(s) of GRF and basic fibroblast growth factor (bFGF) on the synthesis and secretion of somatostatin (SS). The presence of SS-specific mRNA in 44-2C cells was shown morphologically by in situ hybridization. The release and cellular content of SS increased significantly after treatment with rat hypothalamic GRF (rGRF), the ED50 for rGRF stimulation of intracellular SS was 1.9 X 10(-11) M. GRF stimulated SS production in serum-supplemented and serum-free cultures. Results obtained after incubation of 44-2C cells with 125I-labeled rGRF indicated uptake and nuclear localization of rGRF by 44-2C cells. FGF stimulated the secretion and cellular content of SS. We propose that bFGF regulates the short term secretion and accumulation of SS and mediates rGRF-stimulated SS expression.
 ...
PMID:Growth hormone-releasing factor and fibroblast growth factor regulate somatostatin gene expression. 289 28

We examined the effects of thyroid-stimulating hormone (TSH) on basic fibroblast growth factor (basic FGF) expression in isolated ovine thyroid follicles in vitro, and the effects of exogenous basic FGF on thyroid growth and function, to elucidate the significance of increased basic FGF expression during TSH-induced rat thyroid hyperplasia in vivo. Primary cultures of ovine thyroid follicles were maintained in serum-free Ham's modified F-12M medium containing transferrin, somatostatin, and glycyl-histidyl-lysine (designated 3H) with or without basic FGF alone, or in combination with TSH (100 microU/mL) and cortisol (10 nM). Following 48 h incubation, cells were harvested and total RNA prepared for the detection of basic FGF mRNA using Northern blot analysis and ribonuclease protection assay. Basic FGF in the cytoplasm and extracellular matrix fractions was quantified by radioimmunoassay. Basic FGF mRNA transcripts of 3.7, 3.0, and 2.2 kb, respectively, were found in thyroid follicles cultured in 3H medium, and the abundance of each increased between 2- and 3-fold following incubation with 10-50 microU/mL TSH, although higher concentrations of TSH were less effective. Similar results were seen using a more sensitive ribonuclease protection assay. Cells cultured in control, 3H medium contained 2.4 +/- 0.5 fmol immunoreactive basic FGF/micrograms cell DNA within the cytoplasm and 21.1 +/- 1.5 fmol/micrograms DNA within the extracellular matrix (mean +/- SD, n = 6). A significant increase (p < 0.05) in basic FGF content was seen in both cell compartments following incubation with 50 or 100 microU/mL TSH, while 250 microU/mL was less effective.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Basic fibroblast growth factor (basic FGF) in isolated ovine thyroid follicles: thyrotropin stimulation and effects of basic FGF on DNA synthesis, iodine uptake and organification, and the release of insulin-like growth factors (IGFs) and IGF-binding proteins. 751 16

With regard to diabetic retinopathy, in addition to the demonstration by the DCCT study that prevention is achieved by good metabolic control, our present knowledge on physiopathology leads us to imagine three types of possible therapeutic approach; inhibition of glucotoxicity, improvement of capillary flow, blockade of angiogenesis. 1) Inhibition of glucotoxicity Aldose reductase inhibitors can prevent cataract in diabetic or galactosemic rats. The effect of these drugs on retinopathy, evaluated in some clinical trials, remains controversial, suggesting a minor role. Aminoguanidine is an inhibitor of formation of advanced glycosylation end-products (AGE). This compound has been tested on a model of experimental retinopathy in rats. Parallel to the AGE decrease in retina, formation of microaneurysms and loss of endothelial cells in capillaries were delayed. Clinical tolerance allows human application and randomised trials will give further information on this potentially efficient drug. 2) Improvement of capillary flow This objective can be obtained by drugs inhibiting platelet aggregation or improving erythrocyte or leucocyte deformability. Clinical trials using such compounds were not very conclusive. 3) Blockade of angiogenesis Proliferation of new vessels is a rather severe stage of diabetic retinopathy. Angiogenesis is due to factors locally produced (as FGF, TGF and u-PA produced by anoxic tissues), systemic (IGF-1) or released by inflammatory reaction (IL1, TNF alpha and beta). One imagines usage of drugs which inhibit these factors and prevent angiogenesis. At the present time, two approaches have been used in proliferative retinopathy worsening despite panphotocoagulation; analogues of somatostatin and interferon alpha. The promissing results of these pilot studies have to be confirmed.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Outlook for the future in the treatment of diabetic retinopathy]. 752 51

Acidic fibroblast growth factor (aFGF) is a member of the structurally related heparin-binding growth factor family. The best studied members of this family are aFGF and basic FGF (bFGF), which are potent mitogens and differentiation factors for mesoderm-derived cells, including fibroblasts. This study was designed to verify the immunohistochemical expression of aFGF in normal human endocrine cells of the gut and in related endocrine tumours. We examined normal gastrointestinal mucosa from seven different subjects and 41 gut endocrine tumours from different sites, including stomach, duodenum, and small and large intestine, using an aFGF polyclonal antibody with no cross-reactivity for bFGF. We localized aFGF in a fraction of serotonin-producing enterochromaffin (EC) cells of the normal gut, while it was absent in gastrin (G), CCK, secretion (S), somatostatin (D) and glicentin (L) cells. aFGF immunoreactivity was also expressed in serotonin producing EC cell tumours, but not in other functional types of gut endocrine neoplasms investigated, including gastric ECL cell, duodenal somatostatin and gastrin cell, and rectal L cell tumours. A positive correlation was found between expression of aFGF and the amount of tumour fibrous stroma, suggesting that aFGF may be involved in proliferation and activity of stromal fibroblasts.
 ...
PMID:Immunohistochemical localization of acidic fibroblast growth factor in normal human enterochromaffin cells and related gastrointestinal tumours. 908 14

The mitogen activated protein (MAP) kinase cascade represents one of the major regulator of cell growth by hormones and growth factors. However, although the activation of this intracellular pathway has been often regarded as mediator of cell proliferation, in many cell types the increase in MAP kinase (also called extra-cellular signal regulated kinase: ERK) activity may result in cell growth arrest, depending on the length or the intensity of the stimulation. In this review we examine recent data concerning the effects of somatostatin on the MAP kinase cascade through one of its major receptor subtype, the somatostatin receptor 1 (SSTR1), stably expressed in CHO-K1 cells. Somatostatin inhibits the proliferative effects of basic FGF (bFGF) in CHO-SSTR1 cell line. However, in these cells, somatostatin robustly activates the MAP kinase and augments bFGF-induced stimulation of ERK. We show that the activation of ERK via SSTR1 is mediated by the betagamma subunit of a pertussis toxin-sensitive G-protein and requires both the small G protein Ras and the serine/threonine kinase Raf-1. Moreover the phosphatidyl inositol-3kinase and the cytosolic tyrosine kinase c-src participate in the signal transduction regulated by SSTRI to activate ERK, as well as it is involved the protein tyrosine phosphatase (PTP) SHP-2. Previous studies have suggested that somatostatin-stimulated PTP activity mediates the growth inhibitory actions of somatostatin, in CHO-SSTR1 cells. Thus, the activation of SHP-2 by SSTR1 may mediate the antiproliferative activity of somatostatin. SHP-2 may. in turn, regulate the activity of kinases upstream of ERK that require tyrosine dephosphorylation to be activated, such as c-src. Finally, the synergism between somatostatin and bFGF in the activation of ERK results in an increased expression of the cyclin-dependent kinase inhibitor p21cip/WAF1 as molecular effector of the antiproliferative activity of somatostatin.
 ...
PMID:Somatostatin receptor 1 (SSTR1)-mediated inhibition of cell proliferation correlates with the activation of the MAP kinase cascade: role of the phosphotyrosine phosphatase SHP-2. 1108 1

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.
 ...
PMID:Carcinoid--a comprehensive review. 1469 Jan 53

The amniote organizer (Hensen's node) can induce a complete nervous system when grafted into a peripheral region of a host embryo. Although BMP inhibition has been implicated in neural induction, non-neural cells cannot respond to BMP antagonists unless previously exposed to a node graft for at least 5 hours before BMP inhibitors. To define signals and responses during the first 5 hours of node signals, a differential screen was conducted. Here we describe three early response genes: two of them, Asterix and Obelix, encode previously undescribed proteins of unknown function but Obelix appears to be a nuclear RNA-binding protein. The third is TrkC, a neurotrophin receptor. All three genes are induced by a node graft within 4-5 hours but they differ in the extent to which they are inducible by FGF: FGF is both necessary and sufficient to induce Asterix, sufficient but not necessary to induce Obelix and neither sufficient nor necessary for induction of TrkC. These genes are also not induced by retinoic acid, Noggin, Chordin, Dkk1, Cerberus, HGF/SF, Somatostatin or ionomycin-mediated Calcium entry. Comparison of the expression and regulation of these genes with other early neural markers reveals three distinct "epochs", or temporal waves, of gene expression accompanying neural induction by a grafted organizer, which are mirrored by specific stages of normal neural plate development. The results are consistent with neural induction being a cascade of responses elicited by different signals, culminating in the formation of a patterned nervous system.
 ...
PMID:Distinct steps of neural induction revealed by Asterix, Obelix and TrkC, genes induced by different signals from the organizer. 2155 72


1 2 Next >>