Disease relevance of Sanvar IR

• Early administration of vapreotide for variceal bleeding in patients with cirrhosis [1].
• These data reinforce the view that somatostatin analogue RC-160 and related compounds could be used for treatment of pancreatic cancer [2].
• Histopathological analysis revealed normal tissue and/or mild-moderate dysplasia in hamster buccal mucosa treated with the RC-160 (an improvement compared to pretreatment), whereas 40% of the animals receiving no treatment after DMBA initiation developed invasive squamous cell carcinomas after 20 weeks [3].
• Our results demonstrate that somatostatin analogue RC-160 and bombesin/GRP antagonist RC-3095 can inhibit the growth of the androgen-independent Dunning R-3327-AT-1 prostatic cancer in rats, although the remission produced by RC-3095 may be of short duration due to a down-regulation of bombesin receptors [4].
• These data suggest that administration of RC-160 could inhibit the growth of colon cancer and their hepatic metastases in rats [5].

High impact information on Sanvar IR

• METHODS: We studied the effects of treatment with vapreotide, a somatostatin analogue, begun before endoscopic treatment in 227 patients with cirrhosis who were hospitalized for acute upper gastrointestinal bleeding [1].
• The ability of the carriers and the hybrids to inhibit the binding of 125I-labeled RC-160 to receptors for SST on rat pituitary membrane preparation was also determined [6].
• In H-345 human small cell lung carcinoma cell line, conjugates of RC-121 preserved the cytotoxic activity of their radicals, but the hybrids with RC-160 showed approximately 10 times lower activity [6].
• RC-160 inhibited both CCK-induced intracellular cGMP formation as well as activation of p42-MAP kinase phosphorylation and activity [7].
• These effects are positively regulated by CCK and negatively influenced by RC-160, interacting through CCKA and sst5 receptors, respectively [7].

Chemical compound and disease context of Sanvar IR

• Six different human melanoma cell lines were incubated with octreotide and vapreotide, and a proliferation assay was performed by determining [(3)H]-TdR uptake [8].
• The latter data suggest that octreotide, RC-160, and BIM-23014 act mainly via a pertussis toxin-sensitive G-protein and an adenylyl cyclase-dependent mechanism [9].
• Our findings demonstrate that RC-160 can significantly inhibit the growth of SK-ES-1 and MNNG/HOS osteosarcomas in mice [10].
• Histopathologic changes produced during the treatment of Dunning R3327 prostate cancer with new superactive somatostatin analogs (RC-121 and RC-160) and D-Trp-6 analog of luteinizing hormone-releasing hormone agonist (D-Trp-6-LH-RH) were studied [11].
• Effect of microcapsules of luteinizing hormone-releasing hormone antagonist SB-75 and somatostatin analog RC-160 on endocrine status and tumor growth in the Dunning R-3327H rat prostate cancer model [12].

Biological context of Sanvar IR

• A good correlation between the affinities of RC-160 and SMS-201-995 for each receptor subtype and their potencies to inhibit cell proliferation suggests the involvement of these receptors in cell growth regulation [13].
• Examinations of HT-29, A-549, and R3230AC cancer cell lines revealed no phosphorylation by EGF or dephosphorylation by RC-160 and [D-Trp6]LH-RH [14].
• This shows that phosphorylation regulates binding of LH-RH and may explain the up-regulation by EGF and down-regulation by RC-160 and by LH-RH of the LH-RH response [15].
• Binding experiments were performed on crude membranes by using [125I-labeled Tyr11] somatostatin-14; RC-160 exhibited moderate-to-high affinities for SSTR2, -3, and -5 (IC50, 0.17, 0.1 and 21 nM, respectively) and low affinity for SSTR1 and -4 (IC50, 200 and 620 nM, respectively) [16].
• In studies in vitro, RC-3095, added to the culture medium, significantly inhibited the proliferation of U-87MG and U-373MG cells in the presence of GRP(14-27), as measured by cell number, but only a moderate suppression of growth of both cell lines was observed with somatostatin analogue RC-160 [17].

Anatomical context of Sanvar IR

• In the second experiment, 3-mm3 fragments of Dunning R-3327-AT-1 tumor were implanted orthotopically into the prostates of Copenhagen rats in order to evaluate the survival time of animals bearing this cancer during treatment with RC-160 released from Alzet osmotic minipumps at a dose of 100 micrograms/day/rat [4].
• RC-160 and somatuline displaced radiolabel from binding sites in gastric and colonic cancer and mucosa with 10-fold lower affinity than the native peptide [18].
• We also investigated the effect of RC-160 microcapsules on hyperprolactinemic female rats implanted with pituitary glands under the kidney capsules [19].
• Both LH-RH antagonist SB-75 and somatostatin analog RC-160 caused a significant inhibition of tumors, and their combination had the strongest tumor inhibitory effect, with the best survival of animals, the lowest tumorous pancreas weight and the highest apoptosis index among groups [20].
• In the present study we investigated the effects of the somatostatin (SS) analogs octreotide, RC-160, and BIM-23014 on GH release by cultured cells of human GH-secreting pituitary tumors, in normal rat anterior pituitary cells, and on gastrin release by cultured cells from a human gastrinoma [9].

Associations of Sanvar IR with other chemical compounds

• In SSTR1-expressing cells, only RC-160 induced stimulation of a tyrosine phosphatase activity [13].
• In SSTR2-expressing cells, orthovanadate suppressed the growth inhibitory effect of RC-160 [16].
• In SSTR5-expressing cells, the phosphatase pathway was not involved in the inhibitory effect of RC-160 on cell growth, since this action was not influenced by tyrosine and serine/threonine phosphatase inhibitors [16].
• Rhenium-labeled somatostatin analog RC-160. 1H NMR and computer modeling conformational analysis [21].
• In cell cultures, the proliferation rate of MNNG/HOS cells, but not of SK-ES-1, was significantly suppressed by RC-160 [10].

Gene context of Sanvar IR

• In addition, in SSTR5-expressing cells, RC-160 inhibited CCK-stimulated intracellular calcium mobilization at doses (EC50, 0.35 nM) similar to those necessary to inhibit somatostatin-14 binding (IC50, 21 nM) and CCK-induced cell proliferation (EC50, 1.1 nM) [16].
• RC-160-induced p27Kip1 up-regulation and inhibition of insulin-dependent cell proliferation are both prevented by pretreatment of CHO/sst2 cells with the MEK1/2 inhibitor PD98059 [22].
• The affinity and density of binding sites for SST analog RC-160 on 80 surgical specimens of prostate cancers were determined by ligand competition assays [23].
• Preclinical studies have focussed on the anticancer effects of octreotide and the related SRIF analogs BIM 23014 and RC-160 [24].
• The levels of GH in serum were decreased in all of the treated groups, but only RC-160 significantly reduced serum insulin-like growth factor I (IGF-I) [25].

Analytical, diagnostic and therapeutic context of Sanvar IR

• The patients in the vapreotide group received significantly fewer blood transfusions (2.0+/-2.2 vs. 2.8+/-2.8 units, P=0.04) [1].
• RESULTS: At the time of endoscopy, active bleeding was evident in 28 of 91 patients in the vapreotide group (31 percent), as compared with 43 of 93 patients in the placebo group (46 percent) (P=0.03) [1].
• The most striking decrease in tumor weight and volume was obtained in animals treated with microcapsules of [D-Trp6]LH-RH combined with the delayed delivery system for RC-160 [26].
• Twelve weeks after treatment, fluorescence had decreased significantly among animals treated for 2 weeks with RC-3095 (control, 0.53 +/- 0.03 V vs. RC-3095, 0.28 +/- 0.03 V; P < 0.0005) or with RC-160 (control, 0.85 +/- 0.03 V vs. RC-160, 0.24 +/- 0.03 V; P < 0.0001) [3].
• A sensitive and specific radioimmunoassay (RIA) for RC-160 was developed and used for following the rate of liberation of this peptide from microcapsules of poly(DL-lactide-coglycolide) [27].

References