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)

The effect of somatostatin analogue RC-160 on the growth of hepatic metastases of colon cancer was investigated in rats using magnetic resonance imaging. Experimental liver metastatic tumors were established in syngeneic BDIX rats after intrasplenic injection of DHD/K12 colon adenocarcinoma cells. Each rat with implanted liver tumors received s.c. injections of somatostatin analogue RC-160 (50 micrograms/kg) or the vehicle (control) twice a day for 4 weeks, starting 3 weeks after tumor inoculation. During the treatment with RC-160, the growth of liver tumors was studied quantitatively by measuring liver tumor volumes in vivo with magnetic resonance imaging at intervals of 7 days. Chronic administration of RC-160 inhibited the growth of hepatic metastases of colon cancer in rats. Significant inhibition of liver tumor growth in RC-160-treated rats was observed throughout the treatment. The final liver tumor volume in the treated rats was decreased by 56.1% as compared to the controls. The treatment with RC-160 reduced the percentage increase in liver tumor volume from 1575 +/- 674% (mean +/- SEM) for the control to 1034 +/- 727% in the treated group. The tumor volume doubling time in treated rats was 3.7 days longer than the controls. The liver tumor growth delay time was 15.1 days. At the end of the treatment, the incidence of ascites and the weights of tumorous livers were also decreased by RC-160 treatment. Administration of RC-160 prolonged the median survival time by 13 days in treated rats. In cell cultures, significant inhibitory effects of somatostatin-14 and RC-160 on the growth of DHD/K12 colon cancer cells were determined by MTT assay and [3H]-thymidine incorporation assay, indicating direct effects of these peptides on the growth of colon cancer cells in vitro. These data suggest that administration of RC-160 could inhibit the growth of colon cancer and their hepatic metastases in rats. Somatostatin analogue RC-160 might be considered as a potential new agent for the treatment of patients with hepatic metastases of colorectal cancers.
Cancer Res 1992 Nov 01
PMID:Inhibitory effect of somatostatin analogue RC-160 on the growth of hepatic metastases of colon cancer in rats: a study with magnetic resonance imaging. 135 23

Hepatic metastases of colon 320 DM and WidR human colon cancers in nude mice were treated by s.c. injections of somatostatin analogue RC-160 for 4 weeks. Chronic administration of RC-160 significantly inhibited the incidence and growth of liver metastases of these 2 colon-cancer cell lines. After RC-160 treatment, the incidence of liver metastases decreased by 25% for colon 320 DM cells and by 37.5% for WidR cells. The mean number of metastatic tumors in each liver decreased by 47.9% for colon 320 DM and 42.6% for WidR. Survival times of mice with liver tumors of colon 320 DM and WidR cells were prolonged by 20 days and 7 days, respectively. The inhibitory effect of RC-160 on the growth of these 2 colon cancers implanted s.c. was also observed. After administration of RC-160 for 4 weeks, the mean tumor volume in the treated groups was only 39.8% of that of controls for the colon 320 DM line and 58% for the WidR line. Tumor-growth rate and final tumor weight were also significantly decreased, while tumor-volume doubling time and tumor-growth delay time were prolonged. The effect of RC-160 on cellular proliferation in the tumors was studied by in vivo labelling with bromodeoxyuridine and immunoperoxidase staining. The mean labelling index in the treatment group was reduced by 14.9% and 19.5%, respectively, for colon 320 DM and WidR tumors. The cytostatic effect of RC-160 was also evident from the apparent reduction in DNA and protein content in the tumor tissues of these cancer lines. Our findings suggest that somatostatin analogue RC-160 may be useful for the treatment of patients with hepatic metastases of colon cancer.
Int J Cancer 1992 Nov 11
PMID:Treatment of liver metastases of human colon cancers in nude mice with somatostatin analogue RC-160. 135 28

Hepatocyte growth factor (HGF), a potent mitogen for adult rat hepatocytes in primary culture, has previously been shown to be primarily expressed in the nonparenchymal cells of the liver. Using polyclonal antisera against human and rat HGFs we studied the tissue distribution of HGF immunohistochemically and found the most intense staining in the pancreas islet cells in both man (autopsy cases) and the rat. Differential localization of 4 pancreas islet hormones, glucagon, insulin, somatostatin and pancreatic polypeptide, revealed HGF to be preferentially expressed within the glucagon-positive cells. The results indicate that HGF is primarily produced or stored in A-cells and may act as a growth factor in a paracrine and an endocrine fashion, like various other hormones.
Jpn J Cancer Res 1992 Dec
PMID:Immunohistochemical localization of hepatocyte growth factor protein in pancreas islet A-cells of man and rats. 136 29

The metabolism of serotonin was studied in cancer patients of their first day of their first course of chemotherapeutic drugs either with strongly or moderately emetogenic regimens. It was observed that strongly emetogenic treatments induce greater increases in serotonin release than moderately emetogenic regimens. High-dose cisplatinum (75 +/- 5 or 83.8 +/- 5 mg m-2) produced a marked increase in the plasma levels and in the urinary excretion of 5-hydroxyindole acetic acid (5-HIAA). Neither platelet nor plasma (platelet-free plasma) serotonin were significantly modified by high-dose cisplatinum. Dacarbazine (283 +/- 22 mg m-2), another strongly emetogenic agent, induced acute nausea and emesis paralleled by marked increases in the urinary excretion of 5-HIAA. Both for high-dose cisplatinum and dacarbazine, the increases in serotonin metabolism occurred with a similar time-course than those of vomiting, and lasted for a period of 4 to 8 h. Low-dose cisplatinum (30.8 +/- 3 mg m-2) as well as cyclophosphamide-based chemotherapies (520 +/- 30 mg m-2) produced very small increases in the urinary excretion of 5-HIAA. Platelet and plasma serotonin levels failed to increase in cyclophosphamide-treated patients. Octreotide, a long-acting somatostatin analog, did not inhibit the increase in urinary 5-HIAA and the nausea and vomiting produced by high-dose cisplatinum. These results suggest that for treatments that induce marked increases in serotonin release such as high-dose cisplatinum or dacarbazine: (a) the amount and time course of serotonin release induced by chemotherapeutic drugs determines the severity, time of onset and pattern of emesis observed; (b) platelet serotonin play no role in chemotherapy-induced emesis; (c) strongly emetogenic regimens release serotonin from enterochromaffin cells; and (d) intestinal release of serotonin is the consequence of the damage induced by the chemotherapeutic drugs on the gut mucosa.
Br J Cancer 1992 Jul
PMID:Changes in serotonin metabolism in cancer patients: its relationship to nausea and vomiting induced by chemotherapeutic drugs. 137 60

Somatostatin was originally isolated from the hypothalamus, but has subsequently been found throughout the whole gastrointestinal tract. It exerts an inhibitory effect upon numerous functions of the body, and, therefore, increasing attention has been focused on its potential as a therapeutic agent with cytoprotective properties and a potent inhibitory action on a wide variety of functions in endocrine diseases, cancer and gastrointestinal haemorrhage, including bleeding from oesophageal varices. As somatostatin has a very short plasma half-life and requires administration by continuous infusion to maintain therapeutic levels, stable long-acting analogues have been developed. The analogue octreotide has been shown to have a plasma half-life of 113 minutes and to produce a profound selective inhibition of growth hormone. Hepatic excretion of octreotide has been estimated to be between 30 and 40% in healthy volunteers; no data are available in cirrhotic patients. A review of published data assessing systemic and hepatic haemodynamics in animals and humans over varying dosage regimens of somatostatin and octreotide reveals that cardiac output, arterial pressure and peripheral resistance are modified more in animals than in humans. Hepatic haemodynamics are significantly altered in animals as well as in humans in most of the studies. Circumstantial evidence is provided indicating that the mechanisms of action of somatostatin and octreotide in the therapy of bleeding oesophageal varices are mainly mediated by a splanchnic vasoconstrictive effect. Furthermore, gastric acid suppression and potential enhancement of platelet aggregation may contribute to the beneficial outcome after treatment of oesophageal varices with somatostatin.
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PMID:Somatostatin in acute bleeding oesophageal varices. Pharmacology and rationale for use. 138 68

We evaluated the effect of seven classes of neuropeptides [bradykinin, cholecystokinin 26-33 (CCK), neurotensin, arginine-8 vasopressin (AVP), tyr-4 bombesin (BN), somatostatin, and motilin] on 18 human lung cancer and four human breast cancer cell lines to determine the pattern of responses. Flow cytometric analysis of Indo-1 AM-loaded cells was used to quantitate the intracellular calcium response of individual cells produced by these peptides alone or in simultaneous or sequential combinations. All 18 lung cancer cell lines responded to one or more peptide classes with classic small cell lines displaying the greatest responsiveness, followed by variant small-cell lines and non-small-cell lung cancer cell lines. Breast cancer cell lines demonstrated little or no response to any peptide. There was great variability in the magnitude of response and pattern of response in individual cell lines and between cell lines. Bradykinin was the most potent peptide and produced responses in the largest number of lung cancer cell lines. Simultaneous administration of active peptides produced greater intracellular calcium release than single peptides, though in a less than additive manner. Response to each peptide was followed by a refractory period lasting several hours or more. The refractoriness was peptide-specific, implying that each peptide has a distinct pathway, at least at the receptor level. Bradykinin antagonists could abrogate the calcium response to bradykinin but not to other peptides. Similarly, specific peptide antagonists for CCK, BN, and AVP blocked the response for only their specific agonist.(ABSTRACT TRUNCATED AT 250 WORDS)
J Natl Cancer Inst Monogr 1992
PMID:Effects of neuropeptides on human lung and breast cancer cells. 138 87

The presence of somatostatin receptors was evaluated in samples of 39 surgically removed human renal cell carcinomas with receptor autoradiography on tumor sections by using iodinated [Tyr3]octreotide as the radioligand. All types, grades and stages of tumors were represented. Twenty-eight of 39 renal cell carcinomas (72%) were shown to be somatostatin receptor positive. The receptors were saturable, of high affinity (KD = 0.8 nM), and were specific for somatostatin and bioactive somatostatin analogues. No evident correlations were found between the status of somatostatin receptors in the tumor and the age or sex of the patients, the histopathological type or grade of the tumor, or the tumor-node-metastasis stage of the disease. However, numerous cases considered to be of poor prognosis were somatostatin receptor positive. No functional correlates for these receptors have been established, although the presence of somatostatin receptors in human kidneys and somatostatin effects on renal tubular functions in normal human volunteers have been reported. In a patient scanned in vivo for islet cell carcinoma with an 123I-labeled somatostatin analogue, bilateral renal cell carcinomas were also visualized; multiple bilateral renal cell carcinomas were identified on the 1- and 4-h images taken after injection of 123I-labeled somatostatin analogue. In conclusion, the high incidence of somatostatin receptors in renal cell carcinomas may have diagnostic value when performing in vivo imaging of somatostatin receptors and it may have potential therapeutic implications.
Cancer Res 1992 Nov 01
PMID:Somatostatin receptors in human renal cell carcinomas. 139 33

The purpose of this study was to assess the effects of a somatostatin analog (SMS 201-995), in vitro and in vivo on mice colonic adenocarcinoma cells CT 26. To perform the in vitro study 50,000 neoplasic cells were grown in RPMI 1640 culture medium with different concentrations of SMS and DNA synthesis determination was made. For the in vivo study, 100,000 cells in balb C mice were implanted. Several doses of SMS (200 micrograms/kg/12 h and 100 micrograms/kg/12 h) were given. The weight, size and DNA content of the tumors was determined. No in vitro effect of SMS was demonstrated. Nevertheless, an in vivo inhibition was found for all the parameters studied. A confirmation of these results in other cell lines could point towards possible hormonal manipulation in the treatment of colonic cancer.
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PMID:[Effect of somatostatin analog SMS 201-995 on the growth in vitro and in vivo of colonic adenocarcinoma CT 26 in mice]. 153 76

Manipulation of hepatic blood flow may improve drug delivery to hepatic tumour. Somatostatin and its long acting analogues are known to elicit effects upon hepatic and splanchnic blood flow in experimental animals and patients with portal hypertension. This study investigates the effects of SMS 201-995 (sandostatin) infusion on hepatic, splanchnic and tumour blood flow in an experimental model of liver metastases. Hepatic tumour was induced by the intraportal inoculation of 10(6) HSN sarcoma cells and blood flow measured using the dual reference microsphere method before and after infusion of SMS 201-995. There was a significant decrease in hepatic arterial flow and a significant increase in the tumour:liver blood flow ratio associated with a marked reduction in blood flow to normal hepatic parenchyma. Portal venous inflow and tumour blood flow were not significantly affected. SMS 201-995 infusion may lead to preferential delivery of concomitantly injected cytotoxic drugs to hepatic tumour. In addition, the reduction in growth of hepatic tumour may be due to a reduction in nutritive, arterial blood flow to hepatic tumour.
Br J Cancer 1992 Mar
PMID:The effects of sandostatin (Octreotide, SMS 201-995) infusion on splanchnic and hepatic blood flow in an experimental model of hepatic metastases. 155 93

The function of the pituitary-gonadal axis in normal (immunocompetent) and nude (immunocompromised) mice, like that of other species, can be suppressed by luteinizing hormone-releasing hormone (LH-RH) agonists and antagonists administered by continuous release systems and, therefore, nude mice provide a valuable model for investigation of the effects of LH-RH analogues on growth of xenografts of human cancers. To extend our findings further, we treated male nude mice bearing xenografts of human prostate adenocarcinoma PC-82, for 42 days, with sustained release formulations (microcapsules or microgranules) of the agonist [D-Trp6]LH-RH, the antagonist [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Pal(3)3,D-Cit6,D-Ala10]LH- RH (SB-75), or the somatostatin analogue D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160). At necropsy, in mice given microcapsules releasing 25 micrograms/day of [D-Trp6]-LH-RH, tumor weight and volume were significantly decreased, compared with control mice, and weights of testes, ventral prostate, and seminal vesicles were also reduced in this group. In mice which received microgranules liberating 50 micrograms/day of antagonist SB-75, there was a greater decrease in tumor weight and volume than that produced by the agonist and a significant reduction in the weight of the testes and accessory sex organs. Histological parameters also demonstrated significant tumor inhibition, with the best results being obtained by treatment with the antagonist SB-75. The tumor inhibition induced by SB-75 was demonstrated to be due to decreased cellular proliferation, with enhanced cellular death (i.e., apoptosis) of the PC-82 cells. Microcapsules releasing 50 micrograms/day of RC-160 decreased tumor weight and volume by 23% and 28%, respectively, but this reduction was not significant. Serum levels of testosterone were decreased by 90% in mice given the LH-RH agonist and by 94% in response to the antagonist SB-75. Serum levels of prostate-specific antigen were significantly lower in mice treated with LH-RH analogues, with the antagonist SB-75 causing a greater reduction. A ratio of prostate-specific antigen to tumor weight suggests that levels of serum prostate-specific antigen may be correlated with tumor mass. Using sensitive multipoint micromethods, one class of binding sites for LH-RH, with a dissociation constant of 7.8 +/- 1.2 nM and a maximal binding capacity of 126.4 +/- 23.1 fmol/mg protein, was found in the control tumors. Tumors from mice treated with either LH-RH agonist or antagonist, but not somatostatin analogue RC-160, showed a significant reduction in maximal binding capacity for LH-RH, compared to control tumors.(ABSTRACT TRUNCATED AT 400 WORDS)
Cancer Res 1992 May 01
PMID:Sustained release formulations of luteinizing hormone-releasing hormone antagonist SB-75 inhibit proliferation and enhance apoptotic cell death of human prostate carcinoma (PC-82) in male nude mice. 156 23


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