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)

Nude mice bearing xenografts of the androgen-independent human prostate cancer DU-145 were treated for 4-5 weeks with somatostatin analog RC-160 or the bombesin/gastrin-releasing peptide (GRP) antagonist RC-3095. Tumor growth in animals treated with somatostatin analog RC-160 at a dose of 100 micrograms/day s.c. was significantly inhibited within 14 days of the start of the experiment. At necropsy, in mice given RC-160, tumor weight and volume were significantly decreased compared with control mice. Treatment with RC-3095 at a dose of 20 micrograms/day s.c. also suppressed tumor growth, the inhibition being significant after 2 weeks, but the reduction in tumor volume and weight was smaller than that produced by RC-160. Therapy with RC-160 significantly decreased serum growth hormone and gastrin levels. Specific binding sites for bombesin, somatostatin and epidermal growth factor (EGF) were found in the DU-145 tumor membranes. Receptors for EGF were significantly down-regulated after therapy with RC-3095 and RC-160. The finding that somatostatin analog RC-160 and bombesin/GRP antagonist RC-3095 inhibit the growth of androgen-independent prostate tumors in mice might be of practical importance for human prostate cancer therapy.
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PMID:Somatostatin analog RC-160 and bombesin/gastrin-releasing peptide antagonist RC-3095 inhibit the growth of androgen-independent DU-145 human prostate cancer line in nude mice. 810 19

A 52-year-old female with metastatic glucagonoma secreting glucagon and chromogranin A was treated with the somatostatin analogue octreotide for 2 years without any additional tumor-reducing interventions. Before therapy plasma glucagon was above 8 micrograms/l (normal < 0.2) and within 2 days 3 x 200 micrograms octreotide daily suppressed plasma glucagon to 2.2-2.5 micrograms/l. Concomitantly, chromogranin A dropped from 0.85 mg/l (normal < 0.1) to 0.2. After 3 weeks the preexisting disabling necrolytic migratory erythema had vanished completely, and weight loss was temporarily stopped. During therapy chromogranin A and plasma glucagon rose, exceeding pretreatment levels after 3 and 14 months, respectively. After 1 year the erythema recurred, responding only transiently to increasing doses of octreotide. The patient died after 2 years of therapy of tumor cachexy despite very high doses of octreotide (4 x 600 micrograms/day). Throughout treatment octreotide did not prevent tumor growth, as demonstrated by computed tomography and sonography. Determination of immunoreactive glucagon before and during octreotide therapy in fractions of plasma samples subjected to gel chromatography revealed a reduction in the ratio of glucagon to preproglucagon from 1.83 (before) to 0.56 (during therapy), indicating inhibition of posttranslational processing of preoproglucagon by octreotide, thereby reducing circulating bioactive glucagon. In summary, octreotide induced a remission of clinical symptoms by inhibiting posttranslational conversion of preproglucagon to glucagon but did not prevent tumor growth. Therefore, octreotide is a valuable therapy for rapid relief of clinical symptoms, thereby improving the possibilities for other tumor-reducing therapies.
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PMID:The long-acting somatostatin analogue octreotide alleviates symptoms by reducing posttranslational conversion of prepro-glucagon to glucagon in a patient with malignant glucagonoma, but does not prevent tumor growth. 818 58

The influence of a somatostatin analogue, SMS 201-995 (SMS), on the growth of an androgen-dependent mouse mammary tumor, Shionogi carcinoma 115 (SC115), was studied. Treatment of SC115 tumor-transplanted male mice with s.c. injections of SMS (0.04, 0.2, 1, and 5 micrograms twice a day) resulted in a dose-dependent inhibition of tumor growth. The growth-inhibitory effect of SMS reached its peak at a dose of 1 microgram twice a day. SMS was found not to elicit its growth-inhibitory effect through lowering plasma testosterone levels or down-regulating androgen receptor of SC115 tumors. Since specific binding sites for somatostatin were not observed in the membrane fractions of SC115 tumors and SMS did not inhibit the proliferation of primarily cultured SC115 tumor cells, a direct inhibitory mechanism of SMS on SC115 tumors was unlikely to be operative. Since SMS is a very potent inhibitor of growth hormone (GH) secretion, it was speculated that SMS might inhibit the growth of SC115 tumors indirectly through down-regulation of plasma GH levels. This possibility was evaluated by studying the influence of GH replacement on the growth of SC115 tumors grown in SMS-treated mice. GH replacement was done both in a male secretory pattern (intermittent injection, human GH 500 micrograms/kg twice a day) and in a female secretory pattern (continuous infusion, 1000 micrograms/kg/day). Intermittent injections of GH fully restored the growth of SC115 tumors in the SMS-treated mice to that in the normal controls but continuous infusion of GH was without effect. These results suggest that SMS inhibits the growth of SC115 tumors through suppression of GH secretion, and that the mode of GH administration is an important determinant of its action on SC115 tumor growth.
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PMID:Inhibitory effect of a somatostatin analogue (SMS 201-995) on the growth of androgen-dependent mouse mammary tumor (Shionogi carcinoma 115). 834 Feb 54

Somatostatin analogs are used in the control of hormonal hypersecretion and tumor growth of patients with acromegaly, islet cell carcinomas and carcinoids. Recently we showed that somatostatin receptor positive tumors can be visualized in vivo after the administration of radionuclide-labeled somatostatin analogs. Receptor imaging was positive in 18/21 islet cell tumors, 32/37 carcinoids, 26/28 paragangliomas, 9/14 medullary thyroid carcinomas, and 5/7 small cell lung cancers. Somatostatin receptor imaging is an easy, harmless and painless diagnostic method. It localizes multiple and/or metastatic tumors, predicts the successful control of hormonal hypersecretion by octreotide and seems to be of prognostic value in certain types of cancer. This scintigraphic method might help in patient selection for clinical trials with somatostatin analogs in the treatment of neuroendocrine cancers.
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PMID:Validation of somatostatin receptor scintigraphy in the localization of neuroendocrine tumors. 839 30

A prospective study was performed to determine the efficacy of octreotide (Sandostatin; SMS 201-995) 200 micrograms tid in controlling tumor growth. The study included 21 patients with metastasized endocrine GEP tumors: 6 gastrinomas, 8 carcinoid syndromes, 7 nonfunctioning tumors. Treatment was performed for 3 to 59 months (median 15 months). Evaluation of the response to octreotide was facilitated in 12 patients by a pretreatment observation period of 3 to 47 months (median 17 months) during which the natural growth behavior was determined. Based on the presence or absence of a control period prior to treatment, 5 patients were considered to be responders, 7 as questionable responders (no pretreatment phase available), and 9 as nonresponders. None of the 21 patients had documented shrinkage of the tumor mass. The most favorable response was tumor standstill. In all but one responder an escape to an initially favorable response occurred after 6 to 28 months (median 14 months). Proved inhibition of growth was paralleled by a reduction of serum and urine hormone parameters, whereas unaltered progression of tumor growth was observed also in the presence of hormone suppression. Tumor growth and hormone release was inhibited in the absence and presence of somatostatin receptors on the tumor. It is concluded that octreotide exerts a limited effect on metastatic GEP tumor growth. The evaluation of a response to octreotide is facilitated by an observation period prior to the drug that provides information on growth characteristics of the tumor. The presence of octreotide receptors does not predict the success of therapy.
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PMID:Somatostatin analog sandostatin and inhibition of tumor growth in patients with metastatic endocrine gastroenteropancreatic tumors. 839 52

The results of octreotide scintigraphy, performed in two patients with malignant endocrine pancreatic tumors, were compared with the effect of somatostatin-14 and its analogue octreotide on hormonal levels and clinical outcome. Radiolabeled octreotide failed to demonstrate any tumor localisation in a patient with a malignant insulinoma. Nevertheless, IV injection of somatostatin and octreotide resulted in a significant decrease in peripheral insulin levels. Moreover in this patient, chronic treatment with a high dose of octreotide subcutaneously was able to transiently lower the incidence of hypoglycemic events. In a second patient with metastatic PP-oma, 111In-octreotide disclosed a pancreatic tumor in the tail of the pancreas and metastatic supraclavicular lymph nodes. In this patient IV administration of somatostatin and octreotide inhibited the hormonal secretion of the tumor but subcutaneous injection of octreotide induced hardly any decrease in plasma PP levels and failed to affect tumor growth. These observations find a possible reason for this in the heterogeneous affinity of the somatostatin receptors in endocrine pancreatic tumors. They indicate that octreotide scintigraphy alone should not be used to select patients with neuroendocrine tumors who can benefit from chronic treatment with the somatostatin analogue.
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PMID:111In-octreotide scintigraphy: a tool to select patients with endocrine pancreatic tumors for octreotide treatment? 853 89

The effects of octreotide, a long-acting somatostatin agonist selective of the sstr2/sstr3/sstr5 receptor subtypes, on ectopic GH secretion and tumor growth were investigated in Wistar-Furth female rats implanted with GH secreting (GC) cells which express mostly somatostatin receptors of the sstr1 and sstr2 subtypes. Octreotide dose dependently inhibited thymidine incorporation (-57%) and GH secretion (-41%) from GC cells in culture. In vivo, 6 weeks after GC cell implantation, plasma GH, IGF-1 and insulin levels were highly elevated. Cluster analysis of GH secretory dynamics revealed that GH secretion was less pulsatile in GC-implanted than in control animals. Furthermore, in GC-implanted animals, passive immunization either with SRIH or GHRH antisera, did not affect GH plasma levels. Three weeks after GC cell implantation, when tumors became palpable, octreotide (1 micrograms/h/kg BW) or saline was infused constantly for three weeks by osmotic minipumps. In octreotide treated rats, GH, IGF-1 and insulin levels were not different from sham-implanted animals and tumors weight were reduced by 80%. High affinity somatostatin binding sites were found in equivalent amounts on tumors from octreotide-treated or saline-treated animals. These findings indicate that GH secretion in GC-rats is mainly derived from the tumors and independent of hypothalamic control and that octreotide reduces both GH secretion and tumor growth. We conclude that the GC-implanted rat represents a good animal model to test the antisecretory and antitrophic properties of somatostatin analogs in vivo.
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PMID:Effects of chronic octreotide treatment on GH secretory dynamics and tumor growth in rats bearing an ectopic somatotroph (GC) tumor. 870 39

Somatostatin receptors are expressed by a large variety of human tumors. In vitro receptor autoradiographic studies have shown that these tumors can express more than one somatostatin receptor subtype. Whereas the majority of tumors bind octreotide with high affinity, some, i.e., prostate tumors, bind octreotide with low affinity only. The discovery of five somatostatin receptor subtypes, sst1-5, by gene cloning has increased our understanding of somatostatin receptor structure and function. Using in situ hybridization techniques, we found that various human tumors, identified as somatostatin receptor-positive in binding studies, expressed sst2 mRNA in the majority of cases, whereas sst1 and sst3 were less frequent. Often, all three sst were expressed simultaneously. In another recent in situ hybridization study, primary prostate cancers were shown to preferentially express sst1, rather than sst2 or sst3. Moreover, a high incidence of sst5 was found in growth hormone (GH)-producing pituitary adenomas and, to a lesser extent, in active pituitary adenomas; gastroenteropancreatic (GEP) tumors showed all possible combinations, but with a predominance of sst2. Overall, the presence of sst2 mRNA and/or sst5 generally correlated with the presence of octreotide-binding sites, but with exceptions. These results indicate the highly variable abundance of sst mRNAs in individual somatostatin receptor-containing tumors. Somatostatin receptors were not only found in tumoural tissue, but also in the peritumoral vascular system. This was particularly well studied in colorectal carcinomas, where the peritumoral veins were shown to express in all cases a high density of somatostatin receptors, probably of the sst2 type, binding octreotide with high affinity. Therefore, the host peritumoral vascular system may be a possible target of somatostatin action in tumor development. Somatostatin may act locally on tumor growth through two different mechanisms dependent on local somatostatin receptor expression: through direct action on tumor cells or through action on peritumoral vessels, which may alter the hemodynamics of the tumoral blood circulation.
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PMID:Somatostatin receptors and their subtypes in human tumors and in peritumoral vessels. 876 77

Pituitary cells appear to be programmed to proliferate in response to cyclic adenosine monophosphate (cAMP), leading to tumorigenesis. Stimulatory neurohormones and inhibitory inputs normally act in opposition to control cAMP levels, but receptor/postreceptor alterations may affect their relative effects. Most growth hormone (GH), corticotropin (ACTH)-, prolactin (PRL)-, and gonadotropin-secreting adenomas and nonfunctioning pituitary adenomas (NFPA) possess specific thyrotropin-releasing hormone (TRH) receptors, normally coupled with cytosolic [Ca2+]i increase and diacyl glycerol production. These cells are also sensitive to other peptides such as vasoactive intestinal peptide (VIP) and pituitary adenylyl cyclase-activating peptide (PACAP), which activate adenylyl cyclase in many hormone-secreting adenomas and in all NFPA. The two main inhibitory agents controlling pituitary function are somatostatin (SS) and dopamine (DA), which have been reported to reduce hormone hypersecretion and tumor growth in a variable percentage of patients. Inhibition of adenylyl cyclase activity and cytosolic [Ca2-]i levels is involved in the transduction of DA signals in normal and tumoral mammotrophs, but in GH-secreting adenomas DA receptors are exclusively and defectively coupled only with [Ca2+]i reduction. The abnormal expression of these receptors can amplify stimulatory signals with both secretory and proliferative potential. The availability of specific G proteins may qualify the cell response to inhibitory agents. For example, in a subset of NFPA, SS alone or DA alone causes an abnormal increase in [Ca2+]i levels due to Ca2+ mobilization from intracellular stores.
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PMID:Cellular abnormalities in pituitary tumors. 876 79

Among the five cloned somatostatin receptor subtypes (sst1 to sst5), sst2 mediates the antiproliferative effect of somatostatin analogues in vitro. Somatostatin analogues have been shown to inhibit cell growth in vitro and in vivo in pancreatic cancer models that expressed sst2. We recently demonstrated the loss of sst2 gene expression in human pancreatic adenocarcinomas and most of the derived pancreatic cancer cell lines. In the present study, we corrected the sst2 defect in human pancreatic cancer BxPC-3 and Capan-1 cells by stable transfection with human sst2 cDNA. In the absence of exogenous ligand, both BxPC-3 and Capan-1 cells expressing sst2 showed a significant reduction in cell growth. This inhibitory effect was blocked by treatment with antiserum to somatostatin. sst2-expressing cells produced somatostatin-like immunoreactivity that mainly corresponded to somatostatin 14, indicating the induction of a negative autocrine loop. In other respects, sst2 expression in Capan-1 cells induced a significant reduction of clonogenicity in soft agar. Moreover, a significantly reduced (Capan-1 cells) or suppressed (BxPC-3 cells) tumor growth in athymic nude mice was observed. The reversal of tumorigenicity induced by the restoration of sst2 expression suggests that the loss of sst2 contributes to the malignancy of human pancreatic cancers.
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PMID:sst2 somatostatin receptor expression reverses tumorigenicity of human pancreatic cancer cells. 904 Dec 1


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