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)

We recently reported that human pancreatic cancers differentially respond to the growth inhibitory effects of an estradiol (E2) receptor antagonist, tamoxifen, and a long-acting analogue of somatostatin, Sandostatin. In the present study two human pancreatic cancers, established as xenografts in nude mice, were examined as representative of cancers that respond to either tamoxifen (PGER) or Sandostatin (SKI), for the presence of binding sites for various hormones. Male nude mice were inoculated with either SKI or PGER, by passage of tumor chunks (3 mm2) to the interscapular region. Tumors, obtained from mice after approximately 30 days of in vivo growth, were analyzed for binding to cholecystokinin-octapeptide (CCK), somatostatin and E2, by published procedures, using either crude tumor membranes (CCK), cytosol and nuclear fractions (E2), or cryostat sections of whole tumors (somatostatin). SKI was highly positive for high-affinity (Kd = approximately 1 nM) CCK binding sites at the time of resection with a binding capacity of approximately 1000 fmol/mg protein. With increasing passages, the total number of high-affinity binding sites for CCK, were reduced to non-detectable levels in SKI tumors, while non-saturable binding (Kd = greater than 10 nM) became increasingly evident. Early passages of PGER tumors were similarly positive for high-affinity binding sites for CCK, that steeply declined with increasing passages. Specific binding sites for E2, were observed only in the cytosolic fractions of PGER, with a high binding affinity (Kd = approximately 0.05 nM) and a low binding capacity (15 +/- 3 fmol/mg cytosolic proteins), at all passages examined; E2 binding sites were not detected in cytosolic and nuclear fractions of SKI and in the nuclei of PGER, at all passages. SKI and PGER at different passages were examined for somatostatin binding, and both the early and late passages of PGER were devoid of somatostatin binding sites, while SKI tumors were positive for them. Based on the above results, it appears likely that Sandostatin directly inhibited the growth of SKI tumors, since SKI was positive for somatostatin binding sites; it appears less likely that Sandostatin indirectly mediated its inhibition by attenuating possible stimulatory effects of CCK. Growth inhibitory effects of tamoxifen on PGER were apparently via E2 binding sites, since only the tumors positive for E2 binding sites (PGER) responded to tamoxifen; it remains to be determined if tamoxifen can exert additional effects independent of E2 binding sites on pancreatic cancers.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Specific binding of cholecystokinin, estradiol and somatostatin to human pancreatic cancer xenografts. 168 61

We studied the effects of SMS 201-995 (SMS), a somatostatin analog, and tamoxifen, an antagonist of estrogenic actions, on the growth of human pancreatic cancers (SKI and PGER) in vivo. Male nude mice were inoculated with either SKI or PGER by passage of tumor chunks (3 mm2) to the scapular region. Mice from each tumor group were randomly allocated to one of four treatment groups: group 1, control group; group 2, SMS (100 micrograms/kg t.i.d.); group 3, tamoxifen (10 mg/kg three times a week); and group 4, SMS (100 micrograms/kg t.i.d.) + tamoxifen (10 mg/kg three times a week). The somatostatin analog, SMS, given alone or as a combined regimen with tamoxifen, significantly reduced (a) the rate of growth of SKI, and (b) DNA, RNA, and protein content of the tumors. On the other hand, in the case of PGER tumors, none of the treatment regimens significantly influenced the growth of PGER in vivo. Despite showing no significant effects during the study, PGER tumors in mice receiving tamoxifen alone had significantly lower total DNA, RNA, and protein contents compared to control tumors; this was reversed on combined treatment with SMS. None of the growth parameters of PGER was effected by SMS alone. We conclude that, in the case of SKI, SMS with or without tamoxifen was effective as a growth inhibitory agent, whereas in the case of PGER, tamoxifen alone was effective. This finding suggests that independent pathways mediate the growth-inhibitory effects of tamoxifen and SMS, and that different pancreatic cancers may respond to the two agents differently, some with inhibition, some not.
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PMID:Effect of somatostatin and tamoxifen on the growth of human pancreatic cancers in nude mice. 215 57

Somatostatin inhibits hormone secretion from gastrointestinal endocrine tumors. The purpose of this study was to determine whether SMS 201-995, a long-acting analog, would inhibit the growth of pancreatic adenocarcinomas. Two human pancreatic cancers grown in nude mice were studied: SKI, which has cholecystokinin receptors, and CAV, which does not. Tumors were implanted in groups of six mice each. Treatment groups received SMS 201-995 (100 micrograms/kg three times daily) by intraperitoneal injections and control animals received saline solution. Tumor area was measured twice weekly. After 7 weeks, the tumors and mouse pancreases were excised, weighed, and analyzed for protein and RNA and DNA content. In a second set of experiments, treatment was begun 21 days after transplantation. Mean body weights between groups were not different in any experiment. With treatment beginning on the day of transplantation, the tumor areas of SKI and CAV cancers were reduced by the third and fifth weeks of treatment, respectively. Tumor doubling times were prolonged with treatment in both SKI tumors (5 days) and CAV tumors (6 days). In the SKI treatment groups, tumor weight (52 percent), RNA content (72 percent), and DNA content (60 percent) were decreased at sacrifice compared with those of the control groups. In the CAV treatment group, the mean tumor weight (55 percent) and protein (48 percent), RNA (67 percent) and DNA contents (60 percent) were decreased compared with the CAV control group. Tumor growth of SKI and CAV cancers was also inhibited when treatment was delayed 21 days after transplantation. We conclude that these effects are not mediated by inhibition of cholecystokinin, as seen by similar inhibitory effects on both tumors. Treatment with SMS 201-995 may be an effective hormonal therapy in patients with pancreatic cancers.
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PMID:Inhibition of growth of two human pancreatic adenocarcinomas in vivo by somatostatin analog SMS 201-995. 289 55