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)

Several analogues of somatostatin were examined in the Mia PaCa-2 human pancreatic cancer cell line for their ability to promote tyrosine phosphatase activity affecting the receptors for the epidermal growth factor. The inhibition of growth of the Mia PaCa-2 cells in culture was also evaluated to determine the mechanism of action of somatostatin analogues and their relative effectiveness in inhibiting cancer growth. Of the analogues tested D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) caused the greatest stimulation of tyrosine phosphatase activity. Analogue D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121) had less effect but was more potent than somatostatin-14. Analogue D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr(ol) (SMS 201-995) produced no significant dephosphorylation. The analogues displayed the same order of activity in assays on growth inhibition of Mia PaCa-2 cells in cultures. Analogue (SMS-201-995) caused virtually no tyrosine phosphatase stimulation or growth inhibition in this cancer cell line, although it possesses a much higher antisecretory activity than somatostatin-14 in normal tissues. These observations indicate that somatostatin and some of its analogues can act as growth inhibitors in cancer cells through the activation of tyrosine phosphatase. These data reinforce the view that somatostatin analogue RC-160 and related compounds could be used for treatment of pancreatic cancer.
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PMID:Somatostatin analogues inhibit growth of pancreatic cancer by stimulating tyrosine phosphatase. 256 78

The effect of treatment with D-Trp-6-LH-RH, an agonist of luteinizing hormone-releasing hormone (LHRH), and somatostatin analog RC-160 was studied in male Syrian hamsters with N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic carcinoma. The peptides were administered periodically in long-acting microcapsule formulations designed to release controlled doses and maintain continuous blood levels of these analogs. The treatment lasted 60 d. Eighteen wk after administration of BOP, 80% of the animals developed ductal pancreatic adenocarcinomas, typically in multinodular form. Treatment with D-Trp-6-LH-RH resulted in a significant decrease in the tumorous pancreatic weight, and, in 35% of the specimens, changes indicative of histological regression were seen. Similarly, regressive alterations in the tumorous epithelium could be observed in 28% of the tumors in the RC-160 treated group. This regression was not accompanied by accumulation of lymphoid cells and only the epithelial components of the tumors were involved. These data indicate that the analogs D-Trp-6-LH-RH and RC-160 exert antitumoral effects on the experimentally-induced pancreatic cancer. It is unlikely that immunological mechanisms are involved in this response. These inhibitory effects on tumor growth could be mediated by creating a state of sex hormone deprivation of D-Trp-6-LH-RH and by inhibition of the release and/or action of gastrointestinal hormones and growth factors by the somatostatin analog RC-160.
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PMID:Responsiveness of the hamster pancreatic cancer to treatment with microcapsules of D-Trp-6-LH-RH and somatostatin analog RC-160. Histological evidence of improvement. 256 38

Characteristics of binding sites (dissociation constant: Kd and maximal binding capacity: Bmax) for [D-Trp6]-luteinizing hormone-releasing hormone [( D-Trp6]-LH-RH]), somatostatin (SS-14) and epidermal growth factor (EGF) were evaluated in membrane fractions of N-Nitrosobis (2-oxopropyl) amine (BOP)-induced pancreatic adenocarcinoma of hamsters. Intact, normal hamster pancreata did not show any binding sites for [D-Trp6]-LH-RH, but specific [D-Trp6]-LH-RH binding sites with low affinity and high capacity were found after pancreatic cancer was induced with BOP. Membrane binding sites for SS-14 and EGF, with high affinity and low capacity were present, both in normal and cancerous pancreata. Normal hamster pancreatic tissue had significantly higher levels of SS-14 binding sites and lower concentration of EGF binding sites as compared to pancreatic carcinoma. In vivo treatment of hamsters bearing pancreatic cancers with microcapsules of agonist [D-Trp6]-LH-RH and the somatostatin analog RC-160 alone, or in combination, caused histopathological regression of tumors and concomitantly decreased the Kd and Bmax of [D-Trp6]-LH-RH, and increased the Bmax of the SS-14 binding sites. These findings represent the first demonstration of binding sites for [D-Trp6]-LH-RH in pancreatic cancers. Our results also suggest that tumor inhibitory effects of [D-Trp6]-LH-RH and RC-160 in pancreatic cancer could be mediated not only indirectly through suppression of sex-steroids, gastrointestinal hormones and growth factors, but also directly by an action on specific binding sites located on the tumor membranes.
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PMID:Presence of membrane binding sites for [D-TRP6]-luteinizing hormone-releasing hormone in experimental pancreatic cancer. 256 4

Membrane receptors for [D-Trp6]-luteinizing hormone-releasing hormone [( D-Trp6]-LH-RH), somatostatin (SS-14), and epidermal growth factor (EGF) were investigated in experimental N-nitrosobis-(2-oxopropyl)-amine (BOP)-induced pancreatic cancers of hamsters and in specimens of normal human pancreas and human pancreatic cancer obtained from autopsies. Membrane receptors for [D-Trp6]-LH-RH were absent in the pancreas of normal hamsters, but appeared after the carcinoma was induced with BOP. Binding capacity of SS-14 receptors was lower in membranes of BOP-induced pancreatic cancers than in the normal pancreas. In the BOP-induced pancreatic cancers, the receptors were also characterized following in vivo treatment of hamsters with microcapsules of the agonist [D-Trp6]-LH-RH, somatostatin analog RC-160, and the combination of both peptides, which resulted in significant tumor inhibition. Therapy with [D-Trp6]-LH-RH and RC-160, alone or in combination, decreased the binding capacity of receptors for [D-Trp6]-LH-RH, but increased Bmax for SS-14. There were no significant changes in characteristics of the EGF receptor following these therapies. Membranes from human pancreatic cancers showed binding sites for [D-Trp6]-LH-RH, but no binding was detected in normal human pancreas. The presence of receptors for LH-RH in pancreatic tumors of hamster and humans raises the intriguing possibility that LH-RH could be involved in complex interactions that contribute to the appearance of pancreatic cancer. The binding capacity of receptors for SS-14 in human pancreatic cancer membranes was lower, while Bmax for EGF was higher, as compared to normal pancreas.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Membrane receptors for peptides in experimental and human pancreatic cancers. 257 55

A membrane receptor and a cytosolic receptor for somatostatin were found in a human undifferentiated pancreatic cancer cell line (MIA PaCa-2). Binding of somatostatin to this membrane receptor activates dephosphorylation of a phosphotyrosyl-membrane protein whose phosphorylation was promoted by epidermal growth factor (EGF). Vanadate, a purported inhibitor of dephosphorylation, interferes with the action of somatostatin. These findings suggest a possible biochemical mechanism by which somatostatin may inhibit the growth of human pancreatic cancers.
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PMID:Stimulation by somatostatin of dephosphorylation of membrane proteins in pancreatic cancer MIA PaCa-2 cell line. 285 31

The hypothesis that somatostatin, a compound with antitrophic effects on the gastrointestinal tract, may affect beneficially the progression of advanced intestinal cancer has been tested in a small pilot study. Ten patients, four with advanced pancreatic cancer, four with advanced colorectal cancer and two with gastric cancer, were treated with a long-acting analogue of somatostatin, SMS 201-995, 50, 100 micrograms subcutaneously twice daily. There were no clinical, radiological or biochemical indicators of a response to this treatment. There are no indications from this study that hormonal manipulation alters the rate of growth of advanced gastrointestinal cancer.
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PMID:SMS 201-995 treatment and advanced intestinal cancer: a pilot study. 297 16

Using animal models of acinar and ductal pancreatic cancer, we investigated the effect of analogs of hypothalamic hormones on tumor growth. In Wistar/Lewis rats bearing the acinar pancreatic tumor DNCP-322, chronic administration of [L-5-Br-Trp8]somatostatin-14 significantly decreased tumor weights and volume. Somatostatin-28 and the cyclic hexapeptide analog of somatostatin cyclo(Pro-Phe-D-Trp-Lys-Thr-Phe) failed to influence the growth of this tumor. The agonistic analog of luteinizing hormone-releasing hormone [D-Trp6]LH-RH also significantly decreased tumor weight and volume in this model and reduced testosterone levels and the weights of the ventral prostate and tests. In Syrian hamsters bearing ductal type of pancreatic carcinoma, chronic administration of [L-5-Br-Trp8]somatostatin diminished tumor weights and volume. The percentage change in tumor volume was significantly decreased when compared to control animals. In one experiment, cyclic hexapeptide of somatostatin also inhibited growth of this tumor. [D-Trp6]LH-RH, given twice daily or injected in the form of microcapsules for constant controlled release, significantly decreased tumor weight and volume and suppressed serum testosterone levels. Hamsters castrated 4 days after transplantation of the pancreatic tumors showed a significant decrease in weight and volume of these tumors. This suggests that pancreatic cancers may, at least in part, be sex hormone sensitive. [D-Trp6]LH-RH may decrease the growth of pancreatic carcinomas by suppressing androgens. Somatostatin analogs reduce the growth of pancreatic ductal and acinar cancers, probably by inhibiting the release or stimulatory action of gastrointestinal hormones on tumor cells (or both). Inhibition of animal models of pancreatic tumors by chronic administration of somatostatin analogs and [D-Trp6]LH-RH suggests that these compounds should be considered for the development of a new hormonal therapy for cancer of the pancreas.
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PMID:Inhibition of growth of pancreatic carcinomas in animal models by analogs of hypothalamic hormones. 614 60

A new approach to the treatment of endocrine-dependent tumors based on analogs of hypothalamic hormones is in the early stages of development, but appears promising and significant. Administration of hypothalamic hormones can mimic hypophysectomy and gonadectomy, and is essentially devoid of side effects. A successful use of agonistic analogs of LH-RH for treatment of endocrine-dependent prostate cancer has been documented in several hundred patients. Experimental studies suggest that agonists and/or antagonists of LH-RH might be useful for treatment of breast cancer and pituitary tumors. Our work in animal models also indicates that analogs of somatostatin, alone or combined with LH-RH agonists, could be considered for therapy of chondrosarcomas, osteosarcomas, and pancreatic cancer. Experiments are in progress on the use of LH-RH analogs for treatment of ovarian cancer, neoplasms of the female genital tract, and for protection against gonadal damage during chemotherapy. These investigations should extend the concepts of endocrine treatment of cancers.
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PMID:Antitumor effects of analogs of hypothalamic hormones in endocrine-dependent cancers. 614 69

Obstructive ileus is not common, but is a very distressing syndrome in a palliative care unit. The case of a 86-year-old woman with obstructive ileus due to advanced pancreatic cancer is presented. Successful management was made possible by a new somatostatin analogue (Vapreotide), administered i.m. at weekly intervals. Vapreotide was found to reduce nausea and vomiting considerably, by inhibiting the release and action of gastrointestinal hormones and the secretory and motor functions of stomach and intestines. The role of somatostatin analogues in the management of obstructive ileus in advanced cancer is discussed.
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PMID:Vapreotide, a new somatostatin analogue in the palliative management of obstructive ileus in advanced cancer. 791 84

The effects of hormones and synthetic analogues have been examined on the growth of 2 human pancreatic cancer cell lines, MiaPaCa2 a well-established cell line and PANI which was derived in our own laboratories from a tumour specimen. The hormones/growth factors included gastrin (G-17), epidermal growth factor (EGF) and bombesin, while the synthetic analogues used were a gastrin receptor antagonist (CR 1718), a somatostatin analogue (RC-160) and a bombesin receptor antagonist (ICI 216,140). Cell proliferation was assessed by the [75Se]selenomethionine uptake method which has been shown to correlate with cell counts. The effect of each hormone or growth factor on growth was expressed as a percentage of the untreated control. There were 5 replicates in each experiment, and each one was repeated at least 3 times. In vitro growth of both cell lines was unaffected by gastrin, bombesin or the respective antagonists (CR1718 and ICI 216140). The somatostatin analogue RC-160 also had no effect on basal growth. Significant growth stimulation of both MiaPaCa2 and PANI was seen with epidermal growth factor. We tested the hypothesis that somatostatin analogues may inhibit EGF-stimulated growth on both MiaPaCa2, a somatostatin receptor positive cell line, and on PANI which is negative for somatostatin receptors. RC-160 did not inhibit EGF-stimulated growth of either MiaPaCA2 or PANI. Both cell lines were established in vivo as xenografts in nude mice. The effect of RC-160 on tumour growth was measured. RC-160 inhibited the growth of MiaPaCa2, the somatostatin receptor-positive cell line, but not of PANI.
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PMID:Effect of gastrointestinal hormones and synthetic analogues on the growth of pancreatic cancer. 755 55


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