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)

Chronic renal insufficiency (CRI) is associated with growth failure in children and laboratory rats and is considered to be due, in part, to co-existent malnutrition. Alterations in hypothalamic control of growth hormone (GH) secretion have been suggested in uremic patients. We sought to determine whether factors unique to CRI play a role in this disturbance of GH regulation. Using in situ hybridization histochemistry, we compared messenger RNA (mRNA) levels for the hypothalamic neurohormones GH-releasing hormone (GHRH) and somatostatin (SRIH) in three groups: rats with CRI induced by 5/6 nephrectomy (NPX, N = 4); sham-operated, ad libitum fed rats (SAL, N = 5); and sham-operated, pair-fed rats (SPF, N = 5). We also measured plasma GH at 10 minute intervals for a six hour period via intra-atrial cannulae. The NPX group had significantly lower hypothalamic GHRH mRNA concentrations than both other groups; in addition, these levels were significantly lower in the SPF than in the SAL group. Concentrations of hypothalamic SRIH mRNA did not differ significantly among the three experimental groups. Six-hour mean plasma GH concentrations were significantly lower in the SPF (18.3 +/- 1.8 micrograms/liter) than in either the SAL (27.0 +/- 3.3 micrograms/liter) or the NPX groups (36.8 +/- 7.2 micrograms/liter); the difference in the mean plasma GH levels in the NPX vs. the SAL group did not attain statistical significance. This study provides evidence for an effect of CRI on the neuroendocrine control of GH secretion not related to caloric intake.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alterations in the neuroendocrine control of growth hormone secretion in the uremic rat. 809 33

The somatostatin analog TT-232 containing a 5 residue ring, was previously shown to inhibit the proliferation of a large number of cancer cell lines in vitro and reduce the size of tumors in animal models in vivo. Its action is accompanied by inhibition of tyrosine kinases and is characterized by the induction of programmed cell death. On the other hand, it was proved to be free of the endocrine effects of the natural compound. The aim of this study was to find the optimal dose and administration route for in vivo tumor therapy in an animal model. We have investigated the dose--and administration route-dependent antitumor activity of TT-232 on S-180 sarcoma tumor transplanted to inbred BDF1 mice from SPF breeding. Long-term administration (i.p., s.c. and i.v. injections) was started either on the day subsequent to tumor transplantation or after the development of tumor. The antineoplastic potential of TT-232 was evaluated on the basis of survival and tumor growth inhibition. In long-term administration (injections twice a day for 2 weeks) a significant, but dose- and administration route-dependent therapeutic efficacy of TT-232 was observed. The optimum dose of TT-232 15 micrograms/kg which resulted in a 30-40% cure rate and 50-70% growth inhibition in S-180 sarcoma tumor. A moderate antitumor effect was achieved by TT-232 when it was administered after the evelopment of tumor. Our study suggests that TT-232 can be a promising antitumor agent.
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PMID:In vivo antitumor activity of TT-232 a novel somatostatin analog. 1065 22

TT-232 a novel tumor-selective somatostatin analog with a five residue ring structure (D-Phe-Cys-Tyr-D-Trp-Lys-Cys-Thr-NH2) was developed by us and published in an earlier work. This synthetic heptapeptide had no effect on growth hormone release, but had a remarkable tyrosine-kinase inhibitory effect and inducted apoptosis. The aim of this study was to compare the therapeutic efficacy of TT-232 used in various long-term administration routes and treatment schedules. The effectiveness of TT-232 was studied on different rodent tumors transplanted to inbred mice from SPF breeding. Intermittent treatment by injections and continuous infusion of TT-232 using a s.c., i.p. or i.v. implanted Alzet type osmotic minipump were compared for therapeutic efficacy. The treatments were started either on the day subsequent to tumor transplantation or after the development of a tumor. On the basis of survival and tumor growth inhibition the infusion of TT-232 for 14 days using an implantable osmotic pump proved to be a much more effective route of treatment in both s.c. and i.v. administration than the intermittent injections applied twice a day for 2 weeks. In the case of S-180 sarcoma the continuous administration of TT-232 for 14 days using s.c. implanted osmotic pump resulted in 60% the i.v. infusion produced 40% long-term (over 80 days) and tumor free survivors. By the continuous administration of TT-232, an 80-100% tumor growth inhibitory effect and a considerable retardation of tumor development could be achieved. Continuous infusion from implanted pumps ensured a constant drug level and resulted in a well-defined, consistent pattern of drug exposure over the full duration of drug administration. In our study the route of infusion has been shown to increase drug efficacy relative to conventional delivery methods.
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PMID:Influence of various administration routes on the antitumor efficacy ofTT-232, a novel somatostatin analog. 1081 Mar 91