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)

Somatostatin analogues are used clinically in a variety of pituitary and gastroenteropancreatic tumours. In addition, they may influence breast and prostate growth either directly through somatostatin receptors or indirectly through inhibition of growth hormone and prolactin release. Somatostatin analogues may interfere with EGF/TGF alpha-stimulated growth of these tumours and can suppress circulating levels of IGF-I in addition.
 ...
PMID:Somatostatin and growth hormone regulation in cancer. 134 53

Specific receptors for bombesin/gastrin-releasing peptide, somatostatin, and EGF were investigated in 15 human colon cancer specimens. Eight of 15 clinical specimens (15%) of colon cancer showed the presence of somatostatin receptors. Octapeptide somatostatin analogs, RC-160 and RC-121, showed 10 times higher binding affinity for somatostatin receptors on colon cancer membranes than somatostatin. Analysis of 125I-Tyr4-bombesin binding data revealed the presence of specific binding sites in six (40%) specimens of human colon cancer. Scatchard analysis of 125I-labeled bombesin indicated a single class of receptors in three specimens with an apparent Kd value of 2.5 nM and two classes of receptors with high (Kd = 0.4 +/- 0.2 nM) and low affinity (Kd = 1.6 +/- 0.4 microM) in three other specimens. The 125I-Tyr4-bombesin binding capacities in the colon cancers for high affinity binding sites were from 6 to 228 fmol/mg protein and for low affinity binding sites 76 +/- 15 pmol/mg protein. None of the membrane preparations made from normal colonic mucosa specimens showed specific binding for 125I-Tyr4-bombesin. Five pseudononapeptide (psi 13-14) bombesin (6-14) antagonists, with different modifications at Positions 6 and 14, synthesized in our laboratory, inhibited the binding of 125I-Tyr4-bombesin in nanomolar concentrations. No correlation was found between the degree of differentiation and the presence of binding sites for somatostatin or bombesin. Specific binding of EGF was detected in 80% of colon cancer specimens. EGF binding capacity in colon cancer membranes was on average twice as high as in normal colon mucosa (50 +/- 21 vs 28 +/- 14 fmol/mg protein, respectively). Specific binding sites for somatostatin and EGF, but not bombesin, were also demonstrated in human colon cancer cell line HT-29. In HCT-116 colon cancer line only EGF receptors were found. These receptor findings and our in vivo studies on inhibition of colon cancer growth support the merit of continued evaluation of somatostatin analogs and bombesin/gastrin-releasing peptide antagonists in the management of colonic carcinoma.
 ...
PMID:The binding of bombesin and somatostatin and their analogs to human colon cancers. 135 46

Female BDF1 mice inoculated with MXT (3.2) estrogen independent mouse mammary carcinoma were treated for three weeks with microcapsules of the luteinizing hormone-releasing hormone (LH-RH) agonist [D-Trp6]LH-RH, the antagonist SB-75, the somatostatin analog RC-160, or combinations. The lack of estrogen dependence of the tumor was proved by bilateral surgical ovariectomy, which had no effect. In two experiments, treatment with 25 micrograms/day doses of each analog alone resulted in a significant inhibition of tumor growth as shown by a 40-53% inhibition of tumor volumes, 38-43% decrease in tumor weights, and histological signs of tumor regression. However, the combination of SB-75 or [D-Trp6]LH-RH with somatostatin analog RC-160 caused greater reduction of tumor volume (68 and 61%) or tumor weights (59 and 56%), than single analogs, and histologically the occurrence of apoptosis and decrease in AgNOR numbers was more pronounced in the groups receiving combination therapy. Specific binding sites for [D-Trp6]LH-RH, EGF, and IGF-I were demonstrated in the tumor membranes. The binding capacity of LH-RH receptors was decreased by treatment with the analogs, the greatest down-regulation being caused by combination therapy. A significant decrease in EGF binding capacity was observed after treatment with the LH-RH analogs, alone or especially in combination with somatostatin analog RC-160. The combination of these analogs also caused a reduction in IGF-I receptors. The finding that LH-RH agonists and antagonists and somatostatin analogs inhibit the growth of estrogen independent mammary tumors, and that combinations are more effective than single analogs, might be of practical importance in human breast cancer therapy.
 ...
PMID:Growth inhibition of estrogen independent MXT mouse mammary carcinomas in mice treated with an agonist or antagonist of LH-RH, an analog of somatostatin, or a combination. 135 75

Previous studies showed that EGF is produced by salivary and duodenal glands and released in saliva and duodenal secretion. Using specific radioimmunoassay of EGF, this study showed that the salivary glands and duodenal mucosa contain high levels of EGF, reaching, respectively, about 38 and 4 micrograms/g of tissue weight. EGF immunoreactivity was also found in high amounts in the pancreatic tissue (20 micrograms/g) and the pancreatic juice (32 ng/mL), where the content of EGF was found to increase in response to feeding, cholecystokinin, or bombesin and to decrease after the administration of atropine and somatostatin. Studies on the binding of EGF revealed that pancreatic acinar membranes possess the specific and saturable EGF receptors with a high affinity sites with Kd of about 4.3 nM and binding capacity of about 62 fmol/mg of protein, and with low affinity sites with Kd of 21 nM and binding capacity of about 180 fmol/mg of protein. The observed high content of immunoreactive EGF in the pancreatic tissue and the presence of high and low affinity binding sites for EGF in the pancreatic acinar membranes, as well as the high EGF output in the pancreatic juice and its alterations in response to hormonal and postprandial stimulation, suggest an important role of EGF in pancreatic physiology.
 ...
PMID:Release and binding of epidermal growth factor in the pancreas of rats. 158 56

The effects of treatment with the somatostatin analogue Sandostatin, separately and in combination with surgical castration, on the development of azaserine-induced lesions in rat pancreas and N-nitrosobis(2-oxopropyl)amine (BOP)-induced lesions in hamster pancreas were investigated. The animals were divided in 4 groups and treated as follows: (a) controls, injected s.c. with saline solution (0.9% NaCl); (b) orchiectomy directly after the last treatment with carcinogen; (c) Sandostatin (SMS 201-995) subcutaneously; (d) orchiectomy followed by treatment with Sandostatin. No significant suppressive effects on plasma EGF or IGF-I concentrations were noted after Sandostatin treatment, but plasma gastrin levels decreased slightly in the rats, not in the hamsters. In rats, Sandostatin treatment enhanced rather than inhibited growth of acidophilic atypical acinar cell nodules. In hamster pancreas, by contrast, Sandostatin inhibited the development of putative pre-neoplastic ductular lesions. There was no interaction between treatment with Sandostatin and surgical castration. It was concluded that Sandostatin, when administered prophylactically, has an inhibitory effect on the growth of putative pre-neoplastic ductular, but not acinar, lesions.
 ...
PMID:Effects of sandostatin and castration on pancreatic carcinogenesis in rats and hamsters. 173 May 18

Somatostatin is a regulatory hormone or tissue factor which plays an inhibitory role in the normal regulation of several organ systems, including the central nervous system, hypothalamus and pituitary gland, the gastrointestinal tract and the exocrine and endocrine pancreas. Sandostatin is an analogue of somatostatin which has characteristics which makes it a better compound for clinical use than native somatostatin: it inhibits GH preferentially over insulin. It has a long half-life in the circulation, causing a prolonged inhibitory effect in somatostatin-responsive target organs. It is active after subcutaneous administration and rebound hypersecretion does not occur. Sandostatin is very well tolerated by most patients. Somatostatin receptors remain present on a variety of tumours which arise in tissues that contain these receptors normally. High numbers of somatostatin receptors have been found on GH-secreting pituitary tumours and on most metastatic endocrine pancreatic tumours and carcinoids. Sandostatin treatment ameliorates clinical symptoms in most acromegalic patients while GH hypersecretion and elevated concentrations of circulating IGF-I are well controlled. In most patients hormonal hypersecretion from endocrine pancreatic tumours and carcinoids is also suppressed during Sandostatin therapy. This results in an instant improvement in the quality of life. There is preliminary evidence of control of tumour growth. The presence of high numbers of somatostatin receptors on tumours enables in vivo receptor-imaging, with 123iodine coupled to a somatostatin analogue. This newly developed technique provides for the first time the possibility of localization of the primary tumours and their metastases and a prediction of which patients may respond to treatment with Sandostatin. Theoretically this somatostatin-receptor imaging technique represents a new approach which may be extended to other receptor-containing tumours. Therefore it may provide a new, powerful alternative to tumour localization performed with monoclonal antibody technology. Another potential development is the use of beta-emitting isotopes coupled to somatostatin analogues for therapeutic irradiation. Somatostatin analogues exert potent inhibitory effects on the growth of a variety of experimental tumour models in animals. Several mechanisms of action have been proposed including the direct antiproliferative effects of somatostatin and its analogues in a variety of tumour cell cultures. Most well-differentiated human brain tumours like meningiomas and low-grade astrocytomas contain somatostatin receptors, while undifferentiated brain tumours mainly contain EGF receptors. Fifteen percent of human breast carcinomas contain somatostatin receptors; those which do have a better prognosis. It can be concluded that somatostatin is an endogenous, naturally occurring inhibitory growth factor.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:The clinical use of somatostatin analogues in the treatment of cancer. 197 66

Somatostatin analogues can suppress the secretion of some gastrointestinal hormones and growth factors involved in the growth regulation of gastrointestinal cancers and can inhibit the growth of experimental pancreatic tumours. Therefore, in a phase II study 34 patients with metastatic pancreatic (n = 14), colorectal (n = 16) and gastric cancer (n = 4) were treated with three daily subcutaneous injections of 100-200 micrograms of the somatostatin analogue Sandostatin (SMS 201-995). All patients had an extensive tumour load and 13 were pretreated with chemotherapy. Before Sandostatin treatment the patients with pancreatic cancer showed a higher mean plasma concentration of GH (P less than 0.05) and a lower concentration of 'total' somatomedin-C (P less than 0.005) compared with patients with colorectal cancer; there was no significant difference between these two groups in plasma levels of directly assayable somatomedin-C, EGF/TGF-alpha, insulin and prolactin. Within 3 days after start of treatment, somatomedin-C levels initially decreased (without a change in basal plasma GH levels), but returned to pretreatment levels within 4-13 weeks. Plasma insulin levels also were suppressed but only during the first 3-5 days of treatment. Plasma EGF-TGF-alpha levels increased significantly at day 5 of treatment only in the pancreatic cancer patients. Twenty-seven per cent of the patients showed stable disease for 3-9 months, but most patients experienced subjective improvement in the absence of serious side-effects. However, the overall survival remained disappointing, emphasising the need for better treatment regimens.
 ...
PMID:Treatment of patients with metastatic pancreatic and gastrointestinal tumours with the somatostatin analogue Sandostatin: a phase II study including endocrine effects. 197 68

A sensitive radioimmunoassay was developed for human epidermal growth factor (hEGF) in saliva and gastric juice. This method was sufficiently sensitive for an accurate measurement of hEGF in these biological fluids. The minimal detectable concentration of EGF was 30 ng/L. The imprecision profile of EGF standard curve had a CV less than 10% in the range of 0.1-3.0 micrograms/L. Serial dilution curves of saliva and gastric juice paralleled that of standard EGF. The antibody to hEGF showed no cross-reactivity with a large excess of growth factors, such as human transforming growth factor alpha, human insulin-like growth factor I, and platelet-derived growth factor (c-sis). No detectable cross-reactivity was observed with some biological gut peptides: somatostatin, gastrin, secretin or pancreatic polypeptide. The intra-assay CV for saliva and gastric juice was less than 10%, and the recoveries were 93.9 +/- 8.7% and 93.7 +/- 11.3%, respectively for saliva and gastric juice. Gel exclusion chromatography revealed hEGF-like substances, heterogeneous in size in saliva and gastric juice, the origins and physiological functions of which are unknown.
 ...
PMID:Radioimmunoassay of epidermal growth factor in human saliva and gastric juice. 204 84

Somatostatin receptors (SS-R) were measured with in vitro receptor autoradiography using the SS analog 125I-[Tyr3]-SMS 201-995 as radioligand in 342 breast-tumor samples. In a group of 158 "small" tumor samples (mean section surface: 14 mm2 +/- 0.4; mean +/- SEM), 34 tumors (21%) were SS-R positive. In a group of 72 "large" tumor samples (mean size: 180 mm2 +/- 8; mean +/- SEM), 33 tumors (46%) were SS-R positive. In this second group, more than half of the tumors had a non-homogeneous distribution of SS-R, i.e., tumor regions within SS-R positive tumors were SS-R negative. In a group of 48 additional patients, we could show that primaries and their metastases, or double primaries from right and left breasts, or 2 primaries resected consecutively, could both occasionally be SS-R positive. Finally, in 71 SS-R-positive primary tumors, 18 tumor samples were found to have simultaneously Epidermal Growth Factor receptors (EGF-R); in 12 of these 18 cases, the 2 receptor types were not topographically overlapping. Whereas SS-R were located on tumor tissue, EGF-R were often seen on adjacent normal lobules and ducts. These results show that a subgroup of breast tumors contain SS-R, in several cases non-homogeneously distributed. Their location does not coincide with that of EGF-R. Metastasis of SS-R-positive primaries may be SS-R-positive, as are sometimes second primaries. For evaluation of SS-R incidence and distribution, autoradiography is of advantage, specially if it is performed on large tumor samples, since it allows precise identification of the tissue elements containing these receptors.
 ...
PMID:Somatostatin receptor incidence and distribution in breast cancer using receptor autoradiography: relationship to EGF receptors. 216 44

Somatostatin (SS) receptors as well as EGF receptors have been shown to be present in various brain tumors such as meningiomas or glia-derived tumors. Using receptor autoradiography for both receptors, their localization on adjacent tumor sections was investigated and a correlation was attempted. In glia-derived tumors, there was an inverse relationship for the incidence of the two receptors in individual tumors: in a majority of cases (five of eight) of well-differentiated astrocytomas (I-II), SS receptors were present, but in none of the cases (zero of eight) EGF receptors were detected. In undifferentiated glioblastomas, the reverse situation was observed, no SS receptors were found (0 of 14) but EGF receptors were present in a majority of tumors (8 of 14). In astrocytomas III both types of receptors were normally seen. These data suggest that in glia-derived tumors, SS receptors are markers for the well-differentiated cases as opposed to EGF receptors. In meningiomas, SS receptors are found in all (27 of 27) tumors and EGF receptors in a large percentage (23 of 27) of the same tumors. However, in some cases a coincidence of both receptors on the same cell can be excluded. Furthermore, no effect of the SS analog SMS 201-995 on basal or EGF-stimulated growth of meningiomas in culture could be detected. Nevertheless, the coexistence of the two receptor types in meningiomas may be suggestive for a potential functional interaction between EGF and SS.
 ...
PMID:Coincidence of EGF receptors and somatostatin receptors in meningiomas but inverse, differentiation-dependent relationship in glial tumors. 253 15


1 2 3 4 5 Next >>