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

Somatostatin octapeptide analogues have a longer half-life and are more potent than natural somatostatin (SS-14). Somatostatin analogues are presently approved for the treatment of gastrointestinal (GI) endocrine cancers such as carcinoids, vipomas and glucagonomas. They are also effective in the treatment of inoperable or relapsing acromegaly. Although symptomatic relief is marked and rapidly induced, the inhibitory effect on tumor growth is modest. However, prolonged stabilizations are frequent. Somatostatin analogues may have wider therapeutic indications. Somatostatin octapeptide analogues are also known to interact with growth factors such as epidermal growth factor and insulin-like growth factor, and have shown cytostatic activity in vitro and in vivo in various experimental models of breast, prostate, lung and GI cancers. Neuroendocrine tumors often express somatostatin receptors. Labelled analogues may be useful for tumor assessment and for the prediction of tumor response to therapy. The role of somatostatin analogues in the treatment of the most frequent cancers is currently under investigation.
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PMID:[Somatostatin analogs in oncology]. 168 67

Nude mice bearing xenografts of HT-29 human colon cancer cell line were treated for 4 weeks with a [D-Trp6] agonist of luteinizing hormone releasing hormone (LH-RH), somatostatin analogue (RC-160), and bombesin/gastrin releasing peptide antagonist (RC-3095). Some inhibitory effect of [D-Trp6] LH-RH microcapsules releasing 25 micrograms/day on tumor growth was observed that could be due to sex steroid deprivation, but the inhibition was not statistically significant. Microcapsules of RC-160, releasing 50 micrograms/day, significantly reduced tumor volume after 21 and 24 days of treatment, but at the end of the experiment the inhibition in tumor volume and weight was not significant. Bombesin/gastrin releasing peptide antagonist RC-3095, at a dose of 20 micrograms/day administered by daily s.c. injections or by continuous infusion using Alzet osmotic minipumps, had the greatest inhibitory effect on tumor growth. Tumor volume, percentage change in tumor volume, and tumor weights were significantly decreased in both groups treated with RC-3095. This is the first report on inhibition of human colon cancer growth in vivo by bombesin antagonists.
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PMID:Inhibition of growth of HT-29 human colon cancer xenografts in nude mice by treatment with bombesin/gastrin releasing peptide antagonist (RC-3095). 168 40

The mechanism responsible for alterations in tumor growth following administration of somatostatin analogues is unknown. Somatostatin analogues, SMS 201-995 and RC-160, have demonstrated the potential to inhibit both tumor growth and vascularity, in vivo and in vitro. We hypothesized that SMS and RC-160 inhibit angiogenesis and this inhibition may alter tumor growth. To test this hypothesis, 2 mm methylcellulose disks containing concentrations of SMS 201-995 and RC-160 at 0, 0.5, 2.5, or 50 micrograms per disk, were implanted on the chorioallantoic membrane (CAM) of 6- to 7-day-old shell-less chick embryos. Inhibition of blood vessel growth in the region of the disk was visually assessed 24-36 hr following disk implantation and graded (0-4) based on the radius of the zone of inhibition from the center of the disk. The overall incidence of inhibition for the somatostatin analogues at concentrations of 0.5, 2.5, and 50 micrograms per disk was 13, 56, and 61% for SMS and 27, 49, and 68% for RC-160, respectively. Overall incidence of inhibition for the positive (inhibitory) control was 70.5% and those for buffer (negative) controls were 3-14%. Somatostatin analogues were associated in a dose-related fashion with both a greater percentage of inhibition of blood vessel growth and an increased grade of inhibition. Inhibition of angiogenesis may be a mechanism responsible for the tumor regression observed in vivo following SMS or RC-160 therapy.
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PMID:Somatostatin analogues inhibit angiogenesis in the chick chorioallantoic membrane. 170 18

Development of effective treatment for patients with carcinoid tumors has been hampered by lack of an experimental model. The authors have established the only long-term cell line of a functioning human pancreatic carcinoid tumor (BON) that produces tumors in nude mice. In this study the authors examined the effect of three agents, alpha-interferon (IFN), a somatostatin analog, SMS 201-995 (SMS), and an inhibitor of polyamine biosynthesis, alpha-difluoromethylornithine (DFMO), on the growth of BON tumors. BON was implanted bilaterally as 3-mm2 pieces (subcutaneously [sc]) into male BALB/c nude mice. In the first study, 23 mice were randomized to four groups: control, IFN (1 x 10(6) units, sc, four times a day), IFN + SMS (300 micrograms/kg, intraperitoneally, three times a day), and IFN + 3% DFMO in drinking water. Treatments were initiated on day of tumor implantation. In the second study, mice were randomized to six groups: control, IFN, SMS, DFMO, IFN + SMS, IFN + DFMO, and IFN + SMS + DFMO. Treatments were started on day 15 after tumor implantation. Tumor area and body weights were measured weekly. In both studies mice were killed on day 28 after BON implantation and tumors removed, weighed, and analyzed for DNA and RNA content. In the first study, IFN either alone or in combination with SMS or DFMO suppressed BON tumor growth. When treatment was initiated after established tumor growth (study 2), however, the only effective treatments for suppression of growth of BON were IFN + DFMO and IFN + DFMO + SMS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Novel therapy for the treatment of human carcinoid. 170 83

The authors have established a long-term tissue culture cell line (BON) derived from a metastatic human carcinoid tumor of the pancreas. The cells have been in continuous passage for 46 months. Tissue culture cells produce tumors in a dose-dependent fashion after SC inoculation of cell suspensions in athymic nude mice. BON tumors, grown in nude mice, are histologically identical to the original tumor; they possess gastrin and somatostatin receptors, synthesize serotonin and chromogranin A, and have a doubling time of approximately 13 days. The antiproliferative effects of the long-acting somatostatin analogue, SMS 201-995 (300 micrograms/kg, t.i.d.), and 2% alpha-difluoromethylornithine on BON xenografts in nude mice were examined. Tumor size was significantly decreased by day 14 of treatment with either agent and at all points of analysis thereafter until the animals were killed (day 33). In addition, tumor weight, DNA, RNA, and protein contents were significantly decreased in treated mice compared with controls. Establishment of this human carcinoid xenograft line, BON, provides an excellent model to study further the biological behavior of carcinoid tumors and the in vivo effect of chemotherapeutic agents on tumor growth.
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PMID:Establishment and characterization of a human carcinoid in nude mice and effect of various agents on tumor growth. 171 29

The effects of treatment with a somatostatin analog (Sandostatin, SMS201-995) were investigated in female rats with dimethylbenzanthracene (DMBA)-induced rat mammary tumors. A 3-week treatment was performed using sandostatin, the LHRH-agonist buserelin alone, or buserelin in combination with sandostatin. Twice daily sandostatin treatment was performed with dosages of 0.05 microgram, 0.2 microgram, 1 microgram, 5 micrograms, and 20 micrograms. Buserelin was used in a 2 x 5 micrograms/day dosage. The combined results from six different experiments show that the various dosages of sandostatin caused no tumor growth inhibition. Somatostatin receptors could not be demonstrated in these mammary tumors. Sandostatin treatment by daily injections did not suppress levels of growth hormone, prolactin, or epidermal growth factor-like activities. Estrogen (ER) and progesterone (PgR) receptor contents of the mammary tumors were not changed. In contrast, buserelin treatment caused highly significant tumor remission. The combined treatment with sandostatin and buserelin did not alter the treatment results obtained after treatment with buserelin alone. In conclusion, sandostatin treatment in this tumor model had no direct growth inhibitory effect and did not cause an endocrine inhibition of mammary tumor growth. However, these results do not exclude antitumor effects in human breast cancer in view of the presence of somatostatin receptors in approximately 20-45% of human tumors, besides possible different endocrine effects.
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PMID:The somatostatin analog Sandostatin (SMS201-995) in treatment of DMBA-induced rat mammary tumors. 196 5

This study addresses, in an animal tumor model, the clinical problem of "escape from castration inhibition." Somatuline (BIM-23014C), an octapeptide analogue of somatostatin with enhanced potency and longer duration of biological activity was administered as a therapeutic agent, over a period of 90 and 197 days, to male Copenhagen rats bearing syngeneic Dunning R-3327-H prostate tumors. Androgen sensitivity was confirmed by the response of tumors to castration and by the significant inhibition of tumor growth in intact animals by treatment with a luteinizing hormone-releasing hormone antagonist (BIM-21009). Inhibition of tumor growth resulting from castration persisted for 102 days, after which progressive regrowth occurred, indicating an escape from castration inhibition. When Somatuline treatment was initiated as an adjuvant therapy 5 days after castration, the rate of tumor regrowth during escape was significantly retarded. During the period of 197 days postcastration, tumors in the vehicle-treated, intact controls grew to an average diameter of 38.6 +/- 7.6 mm and tumors in vehicle-treated castrate controls grew to an average diameter of 23.3 +/- 4.1 mm (60% test/control). Treatment with the luteinizing hormone-releasing hormone antagonist induced no significant additional tumor inhibitory effects in castrated animals which developed tumors having an average diameter of 30.2 +/- 8.2 mm (78% test/control). Treatment of tumors in castrate animals with Somatuline, on the other hand, induced a significant (P less than 0.01) tumor-inhibitory effect that was greater than that produced by castration alone, developing an average tumor diameter of only 14.3 +/- 2.6 mm, (37% test/control). A growth inhibitory effect was also inducible in animals having tumors that had already escaped castration inhibition. The relative nontoxicity of a somatostatin analogue such as Somatuline suggests that chronic or maintenance therapy of slow-growing prostate cancers may be both feasible and acceptable in a clinical setting.
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PMID:Treatment of R-3327 prostate tumors with a somatostatin analogue (somatuline) as adjuvant therapy following surgical castration. 197 Feb 75

Syrian golden hamsters bearing N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic carcinomas were treated for 2 months with the delayed delivery systems of the agonist D-Trp-6-LH-RH (microcapsules releasing 25 micrograms/day for 30 days), the somatostatin analog RC-160 (the microcapsules liberating 48.2 micrograms/day for 30 days), or with the combination of these two analogues. The increase in the dose of RC-160 was possible in view of the lack of toxicity of this analog. This higher dose of RC-160 exerted a greater suppressive effect on pancreatic cancers than the regimens previously used (5-25 micrograms/day). RC-160, D-Trp-6-LH-RH, and their combination reduced the number of pancreatic carcinomas and significantly inhibited tumor growth as compared with the controls. The combination had the strongest tumor-inhibitory effect and reduced tumor weight by 85% as compared with controls. Both the light and electron microscopic analysis of the tumors showed that the inhibitory effect was due to the enhancement of apoptosis (programmed cell death) of tumor cells. Insulin-like growth factor (IGF-I) receptors were detected immunohistochemically in the untreated tumors and their number decreased after the treatment with the analogues. Binding of D-Trp-6-LH-RH and RC-160 to tumor cells was shown immunohistochemically and receptors to these analogues and IGF-I were also determined biochemically by radioligand titration. Treatment with D-Trp-6-LH-RH and RC-160 decreased the binding capacity of receptors for D-Trp-6-LH-RH and IGF-I, producing down-regulation of these receptors. This suggests that pancreatic tumor cells with receptors to these peptides are sensitive to the treatment. This work reinforces the view that the combination of high doses of somatostatin analog RC-160 with LH-RH agonists or antagonists should be considered for the development of a new hormonal therapy for ductal pancreatic cancers.
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PMID:Inhibitory effects of analogs of luteinizing hormone-releasing hormone and somatostatin on pancreatic cancers in hamsters. Events that accompany tumor regression. 197 71

Somatic mutations in the alpha-chain (alpha s) of the stimulatory regulatory protein of adenylyl cyclase (Gs) causing constitutive activation of the enzyme have been identified in a subset of human GH-secreting pituitary adenomas. This study reports on the differences between acromegalic patients bearing tumors without (group 1; n = 51) or with (group 2; n = 29) this alteration. No difference in age, sex, clinical features, duration of the disease, or cure rate was observed between the two groups. By contrast, group 2 patients had higher basal GH levels than group 1. Moreover, a significant difference in sellar morphology was found; group 2 patients more frequently showed sellas of normal size (grade I) than group 1. Hypersecretory activity of group 2 tumors was also apparent at electron microscopy; contrary to those of group 1, cells of group 2 tumors were densely granulated and showed prominent rough endoplasmic reticulum and Golgi complex. With respect to group 1, group 2 patients were less responsive to GH-releasing hormone, while they were more sensitive to somatostatin- and dopamine-induced GH inhibition. These results suggest that patients with constitutively active adenylyl cyclase have hyperactive tumors; the sensitivity of these tumors to inhibitory agents (somatostatin and dopamine), possibly counteracting the expression of activating mutations, might explain the low rate of tumor growth.
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PMID:Clinical, biochemical, and morphological correlates in patients bearing growth hormone-secreting pituitary tumors with or without constitutively active adenylyl cyclase. 197 58

The knowledge that (1) the normal thyroid contains somatostatin, (2) polypeptide growth factors influence thyroid cell function, and (3) thyroid cells contain steroid hormone receptors prompted us to add somatostatin analogue No. 201-995 (SMS) (5 ng/ml) and/or tamoxifen citrate (TAM) (5 mumol/L) to 7-day monolayer cultures (50,000 cells/well) of three separate human thyroid carcinoma cell lines: DR081 (medullary), WR082 (follicular), and NPA'87 (papillary). Results, tabulated as cell numbers/well (X10(5) on day 7, revealed that TAM inhibited growth of medullary and follicular cells and that TAM plus SMS inhibited growth of papillary cells. In vivo studies of subcutaneous tumor cell xenografts in nude mice have documented that TAM (5 mg subcutaneous pellet) significantly inhibits the growth of medullary implants. Flow cytometric DNA studies of medullary cell cultures demonstrated a reduced G2 + M phase with TAM treatment. For papillary cell implants, TAM plus SMS (5 micrograms subcutaneously, twice daily) did not suppress tumor growth. All three cell lines were negative for estrogen receptor; addition of estradiol (5 ng/ml) to medullary cell cultures neither stimulated replication nor reversed the inhibitory effects of TAM in vitro. We conclude that (1) TAM slowed the growth of a cell line of human medullary carcinoma, both in vitro and in vivo; (2) this effect was not reversed by estradiol; (3) TAM plus SMS inhibited replication of a papillary carcinoma cell line in vitro, but not in vivo; and (4) TAM alone and TAM plus SMS inhibited replication of cultures of a human follicular thyroid carcinoma cell line. TAM and SMS may be useful in treatment of some human thyroid carcinomas.
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PMID:Effects of tamoxifen and somatostatin analogue on growth of human medullary, follicular, and papillary thyroid carcinoma cell lines: tissue culture and nude mouse xenograft studies. 197 45


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