1,720,995 research outputs found
Pharmaceuticals compositions which inhibit vascular proliferation and method of use thereof
No full textThe present invention relates to a method of treating vascular proliferation in a patient in need thereof. The method includes the step of administering a therapeutically effective amount of a type-1 somatostatin agonist to said patient
Composti farmaceutici che inibiscono la proliferazione di adenomi ipofisari e modi d’uso che ne derivano
No full textSi descrive l'utilizzzo di analoghi della somatostatina com inibitori della vitalità cellulare ipofisaria in vitro
Pharmaceutical compositions which inhibit vascular proliferation and method of use thereof
No full textMetodo per modulare la proliferazione del carcinoma midollare della tiroide (MTC)
No full textSi descrive l'impiego di analoghi della somatostatina per modulare la proliferazione di cellule di carcinoma midollare della tiroide
Characterization of new selective somatostatin receptor subtype-2 (sst2) antagonists, BIM-23627 and BIM-23454. Effects of BIM-23627 on GH release in anesthetized male rats after short-term high-dose dexamethasone treatment.
No full textThe somatostatin subtype-2 receptor antagonist BIM-23627 improves the catabolic effects induced by long-term glucocorticoid treatment in the rat
No full textSomatostatin receptor subtypes 2 and 5 differentially affect proliferation in vitro of the human medullary thyroid carcinoma cell line TT
No full textSomatostatin and its receptors (SSTR1 to SSTR5) are expressed in normal human parafollicular C cells and medullary thyroid carcinoma (MTC), but the role of SSTR subtypes in cell growth regulation is still not clear. The present study demonstrates that the human MTC cell line TT stably expresses all the SSTR subtypes and responds to SSTR2 and SSTR5 activation by subtype-selective agonists with two different patterns in terms of [(3)H]thymidine ([(3)H]thy) incorporation and cell number. The SSTR2 preferential agonists (BIM-23120, BIM-23197, BIM-23190, and BIM-23014; 10(-9)-10(-6) M), significantly suppressed [(3)H]thy incorporation (58-13%) and reduced cell proliferation (50-28%), whereas the SSTR5-selective agonist, BIM-23206 (10(-9)-10(-6) M), significantly increased [(3)H]thy incorporation in TT cells (80-175%), but failed to influence cell proliferation. SSTR2 antagonist (BIM-23627) counteracted the action of SSTR2 preferential agonists on TT cells. Furthermore, increasing concentrations of SSTR5-selective agonists, BIM-23206, dose-dependently prevented the suppression of TT cell [(3)H]thy incorporation and proliferation produced by SSTR2 preferential agonist, BIM-23120, showing an antagonism between these compounds. The following conclusions were reached: 1) the human MTC cell line TT expresses all SSTR subtypes; 2) SSTR2 activation inhibits DNA synthesis and cell proliferation, whereas SSTR5 activation increases DNA synthesis; and 3) SSTR2 preferential agonist (BIM-23120) can antagonise SSTR5-selective agonist (BIM-23206) action and vice versa. These findings suggest a tissue-specific function and a tissue-specific interaction between the two receptors
Somatostatin receptor subtype 1 selective activation reduces cell growth and calcitonin secretion in a human medullary thyroid carcinoma cell line.
No full textMedullary thyroid carcinoma (MTC) is a rare and aggressive tumor and so far medical therapy has provided inconclusive results. In the human MTC cell line TT, expressing all somatostatin (SST) receptor subtypes, cell proliferation decreases with SST and SST receptor subtype 2 (sst(2)), but not sst(5), selective agonist
treatment, whereas calcitonin (CT) expression and secretion are reduced by SST, but not by sst(2) and sst(5) agonists. The effectiveness of two new SST analogs, BIM-23926 and BIM-23745, selectively interacting with sst(1), was investigated in
the TT cell line. DNA synthesis is significantly reduced by BIM-23926 (27-40% at 10(-10)-10(-6)M) and BIM-23745 (32-90% at 10(-8)-10(-6)M). Viable cell number is also significantly reduced by both BIM-23926 (40% at 10(-12)-10(-6)M) and
BIM-23745 ( approximately 40% at 10(-10)-10(-6)M). Treatment with sst(1)-selective agonists significantly reduces CT secretion and gene expression, with a reduction of CREB phosphorylation. These findings suggest that potent sst(1)-selective agonists could have a therapeutic role in MTC
Somatostatin, but not somatostatin receptor subtypes 2 and 5 selective agonists, inhibits calcitonin secretion and gene expression in the human medullary thyroid carcinoma cell line, TT.
No full textSomatostatin (SRIH) analogs are commonly used to treat symptoms in medullary thyroid carcinoma (MTC), that expresses SRIH receptors (SSTR1 to SSTR5), as does the human MTC cell line TT. The aim of this work was to evaluate whether SRIH, SSTR2 and SSTR5-selective agonists influence calcitonin (CT) secretion and gene expression in the TT cell line. CT secretion was evaluated by chemiluminescence, and gene expression was analyzed by Northern blot. TT cell line proliferation was also assessed by [(3)H] thymidine ([(3)H]thy) incorporation and viable cell number count. SRIH significantly (p < 0.05) reduced [(3)H]thy incorporation (approx. 50 %), viable cell number (approx. 20 %), CT secretion (-30 %) and CT gene expression (approx. 2-fold). Exposure to the SSTR2-selective agonist, BIM-23120, and to the SSTR5-selective agonist, BIM-23 206, did not modify CT secretion and mRNA levels in TT cells. Thus, SRIH inhibits DNA synthesis, cell proliferation, CT secretion and CT gene expression in the TT cell line, while SSTR2 and 5 selective agonists, although influencing DNA synthesis and cell proliferation, do not modify CT gene expression, suggesting that SRIH may influence gene expression acting through SSTRs other than subtypes 2 and 5. Furthermore, these findings may explain the erratic response of MTC patients in terms of CT plasma levels to treatment with SRIH analogs, like octreotide and lanreotide, which interact mainly with SSTR2 and 5
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