epidermal-growth-factor and Acromegaly

This article is aimed at reviewing and analyzing studies that are related to the possible therapeutic use of a potent and ubiquitously-distributed hormone--somato-statin (SS-14), and its analogues. Administration of these substances has provided beneficial effects in treating acromegaly, gastro-intestinal hemorrhagic and hypersecretory disorders, acute pancreatitis, diabetes mellitus, and certain types of cancer. Further studies with SS-14-analogues might provide new therapies for treating certain life-threatening disorders of man.

Topics: Acromegaly; Alzheimer Disease; Epidermal Growth Factor; Gastrointestinal Diseases; Humans; Neoplasms; Pancreatic Diseases; Somatostatin

Acromegaly is closely related to increased oxidative stress and endothelial dysfunction (ED). This study aimed to evaluate, for the first time in the literature, signal peptide-CUB-EGF domain-containing protein 1 (SCUBE-1) and endothelial nitric oxide synthase e(NOS) levels in the setting of acromegaly.. A total of 56 acromegaly patients and a control group composed of 30 healthy volunteers were included in this study. In the postoperative follow-up, patients were grouped as active or in-remission according to their GH and IGF-1 levels in oral glucose stimulation test (OGST). After detailed physical examination of acromegaly patients and the control subjects, 8-hour fasting blood samples were collected to evaluate biochemical parameters including lipid profile, anterior pituitary hormones, and SCUBE-1 and e(NOS) levels.. Inactive and active acromegaly was noted in 78.6% and 21.4% of patients, respectively. The median (min-max) SCUBE-1 levels were significantly higher in the inactive acromegaly and active acromegaly groups than in the control group (1.6(0.4-2.4) and 1.8(1.1-2.5) vs. 0.4(0.2-1.0) ng/mL, respectively, p < 0.001 for each). The median (min-max) e(NOS) levels were significantly higher in the inactive acromegaly and active acromegaly groups than in the control group (132.7 (26.8-602.9) and 137.3 (69.7-488.7) vs. 83.9 (16.4-218.7) pg/mL, p = 0.018 and p = 0.048, respectively). We have also detected positive correlations of e(NOS) with leukocyte (r = 0.307, p = 0.021) and neutrophil counts (r = 0.309, p = 0.021).. Our study revealed for the first time in literature that SCUBE-1 levels, being a novel marker for ED, were significantly higher in acromegaly patients than in control subjects. When supported with clinical studies, SCUBE-1can be used as an early indicator of endothelial damage in acromegaly patients.

Topics: Acromegaly; Epidermal Growth Factor; Glucose; Humans; Insulin-Like Growth Factor I

Somatostatin receptors are highly expressed in almost all meningiomas but in this setting their functional role is not clear. A 59-yr-old woman had been treated with octreotide after an unsuccessful operation for a GH-secreting pituitary adenoma. After 8 yr of treatment, a nuclear magnetic resonance (NMR) scan disclosed a 3 cm meningioma of the tentorium. Mean GH was 2.2 ng/ml and IGF-I 325 ng/ml. Meningioma was resected and tissue was digested to obtain tumor cell suspension. Aim of the study was to measure epidermal growth factor (EGF)-induced proliferation of cultured meningioma cells in the presence of either somatostatin or octreotide. Cells were grown to semiconfluency in Dolbecco's modified eagle medium (D-MEM) supplemented with 10% fetal calf serum (FCS). After 48 h in D-MEM without serum, the medium was replaced by fresh medium plus recombinant EGF (10 ng/ml) and somatostatin or octreotide were added in the final concentrations of 1, 10 and 100 nM. 20 h later 1 microcgCi of 3H-thymidine was added to each well. After 4 h, incorporated radioactivity was measured. While octreotide did not influence significantly cell growth at the three dose tested, somatostatin increased thymidine incorporation dose-dependently (peak 100 nM: 150% +/- 27% vs medium plus EGF, p<0.05). Octreotide effectively suppressed GH secretion in our acromegalic patient but is unlikely that its long-term use could have stimulated the growth of meningioma since it did not significantly influence the in vitro proliferation of the meningioma cells. These results suggest that somatostatin-mediated proliferative effect on meningioma cells is not mediated by the subtype 2 of the somatostatin receptor.

Topics: Acromegaly; Cell Division; Epidermal Growth Factor; Female; Humans; Magnetic Resonance Imaging; Meningeal Neoplasms; Meningioma; Middle Aged; Octreotide; Receptors, Somatostatin; Somatostatin; Tumor Cells, Cultured

Twenty-seven plurihormonal and 21 growth hormone- prolactin- (GH- PRL-) mixed cell adenomas obtained from patients with acromegaly undergoing transnasal-transsphenoidal surgery were investigated immunohistochemically for expression of Epidermal Growth Factor (EGF), Transforming Growth Factor alpha (TGF alpha), Insulin-like Growth Factor-1 (IGF-1), Estrogen Receptor-Related Protein (ERRP), Multidrug Resistance Marker (MDRM), Protein Kinase C (PKC), Gs alpha,. Cathepsin D and p53. Five plurihormonal adenomas grew invasively. The panel of markers used in this study represents a selection of functional and proliferative markers thought to be associated with the function and development of pituitary adenomas. Our results imply that the growth factors (EGF, TGF alpha, IGF-1), the cell signalling protein Gs alpha and the MDRM are expressed by both types of pituitary adenomas in a similar pattern. Non-invasive GH-PRL-mixed cell adenomas showed an increased expression of IGF-1, TGF alpha and MDRM compared to non-invasive plurihormonal adenomas. No factor was found which would reliably distinguish between invasive and non-invasive adenomas. We failed to confirm the findings of others that p53 and cathepsin D might be indicators of tumor aggressiveness. A participation of ERRP and PKC in the development of bi- and plurihormonal adenomas with acromegaly appears unlikely, as the immunostains were all negative.

Topics: Acromegaly; Adenoma; Adult; Aged; ATP Binding Cassette Transporter, Subfamily B, Member 1; Biomarkers, Tumor; Cathepsins; Cell Count; Epidermal Growth Factor; Female; Growth Hormone; GTP-Binding Protein alpha Subunits, Gs; Humans; Immunoenzyme Techniques; Insulin-Like Growth Factor I; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Transforming Growth Factor alpha

The human septal cartilage is of ectodermal origin and contributes to midfacial growth and development. Acromegaly is an endocrine disease due to growth hormone (Gh) excess originating from a somatotrophic adenoma of the pituitary gland. Excessive Gh levels lead to high insulin-like growth factor I (IGF I) concentrations, which are known to stimulate cartilage growth in vivo and in vitro. One of the salient clinical pictures is coarsening of the midface and enlargement of the septal cartilage. Septal cartilage was obtained from 8 acromegalic patients during transnasal hypophysectomy and from 10 healthy adults during septoplasty to analyse the following aspects of cartilage biochemistry, metabolism and growth. 1. Intracellular glycogen, the major source of energy of chondrocytes, was determined enzymatically and found to be drastically reduced in acromegaly. 2. Several intracellular enzymes, related to biomatrix degradation, showed a strict local pattern of distribution. Cathepsin B activity, a neutral proteinase degrading both the helical and nonhelical region of the collagen molecule was significantly increased in acromegaly, whereas alkaline phosphatase activity, an enzyme related to mineralization of the cartilage at the chondroosseous junction was depressed in acromegaly. 3. The cell density in some areas of the septal cartilage was increased in acromegaly, whereas the clonal proliferation rate of its chondrocytes in response to serum and growth factors was decreased. Chondrocytes both of healthy adults and acromegalic patients could be effectively stimulated by insulin-like growth factor I and II and to a lesser extent by epidermal growth factor.

Topics: Acromegaly; Adult; Alkaline Phosphatase; beta-N-Acetylhexosaminidases; Cathepsin B; Cathepsin D; Cell Count; Cell Division; Cells, Cultured; Clone Cells; Epidermal Growth Factor; Female; Glycogen; Humans; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Male; Nasal Septum

Topics: Acromegaly; Adenoma; Colonic Neoplasms; Epidermal Growth Factor; ErbB Receptors; Female; Growth Substances; Humans; Middle Aged; Receptors, Cell Surface