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)

By immunocytochemistry and immunoblotting, we examined normal and neoplastic human tissues with polyclonal antibodies raised against selected peptide regions of proprotein convertase-2 and -3 (PC2 and PC3), two proteases that have been shown to selectively cleave neuroendocrine precursor molecules at pairs of basic residues. Immunoreactivity for both enzymes was detected in neuroendocrine cells of pituitary, gut, pancreas, thyroid, and adrenals and in tumors thereof, but was absent in thyroid follicular cells, parathyroids, adrenal cortex, testes, and a number of nonneuroendocrine tissues, both normal and tumorous. Although both PCs were virtually universal concomitants of the neuroendocrine system, cells with a neural phenotype (e.g. pheochromocytes and Merkel cells) predominantly contained PC2, whereas classic endocrine cells contained mostly PC3. PC3 immunoreactive cells were abundant all along the gastrointestinal tract, whereas PC2 was highly expressed only in the pyloric antrum and proximal third of duodenum. Double immunostaining experiments revealed colocalization of PC3 with virtually all gastrointestinal peptides, whereas PC2 immunoreactivity was mostly expressed in gastrin, cholecystokinin, and somatostatin cells. Noticeably, the proportion of glucagon-producing cells immunoreactive for PC3 was high in the gut and low in pancreatic islets and glucagonomas, whereas the reverse occurred for PC2. At the ultrastructural level, immunostaining was confined to the mature dense core granules, the site of storage of granins and peptide hormones. With the exception of parathyroid cells, PC2 and/or PC3 expression correlated with the occurrence of granins, canonical markers of the secretory granules. Immunoblotting experiments confirmed the identity of the immunocytochemical reactivities. It is concluded that PC2 and PC3 are highly sensitive markers of neuroendocrine differentiation and have distinct distribution patterns, and that antibodies to these enzymes may play an important role in the analysis of tumors.
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PMID:Proprotein convertases (PC1/PC3 and PC2) in normal and neoplastic human tissues: their use as markers of neuroendocrine differentiation. 782 29

Changes in transcription factor and neuropeptide gene expression are likely to be involved in the cascade of genetic and molecular events leading to permanent changes in neuronal activity associated with kindling and epilepsy. Both acute-transient and delayed-sustained changes in transcription factor or immediate early gene (IEG) activity have previously been reported in response to different stimuli. In the present study in situ hybridization was used to investigate the possible time course (30 min-8 week) of IEG and neuropeptide mRNA induction in forebrain in a kindling model of epilepsy. Kindling was produced by daily unilateral stimulation of the amygdala. IEG mRNAs were detected using [35S]-labelled oligonucleotide probes specific for c-fos, c-jun, NGFI-A (PC1) and PC3 transcripts. Possible changes in the level of mRNAs encoding the neuropeptides somatostatin (SOM) and neuropeptide Y (NPY) were also studied. Stimulation-induced seizures produced dramatic bilateral increases in all IEG mRNAs in the dentate gyrus after 30 min to 1 h. Ipsilateral or bilateral increases in c-fos and PC3 mRNA were observed in the piriform cortex of individual animals at 30 min post-stimulation. While the distribution and apparent basal expression of the different IEGs varied (NGFI-A and c-jun > c-fos and PC3), the degree of induction in the dentate gyrus was similar for all IEGs studied (i.e. 200-300%). No long-term changes in IEG mRNA expression were detected beyond 2 h and up to 8 week after the last seizure. Increased levels of preproSOM and preproNPY mRNAs were consistently observed in hilar interneurons, but not in pyramidal or granule cells of the hippocampus, after 1-2 h. These increases were not maintained at later times. The short-term effects on IEG and neuropeptide mRNAs observed suggest that these changes are consequence of seizure activity with the development of kindling. In contrast, no evidence was found of any substantial, long-lasting effects on these parameters associated with the established kindled state.
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PMID:Rapid and transient increases in cellular immediate early gene and neuropeptide mRNAs in cortical and limbic areas after amygdaloid kindling seizures in the rat. 898 7

We developed a group of synthetic analogs of GnRH and Somatostatin to inhibit the tumor growth of different kind. The GnRH analogs decreasing the gonadotroph and steroid hormone levels act on the hormone dependent tumors and influence their growth. One of the most effective antitumor analog was patented under the name FOLLIGEN which inhibited the breast cancer caused by DMBA in rats without any side-effects. Other inhibitory analogs of GnRH with long-lasting effect were effective in the treatment of breast, ovary and prostate tumors. Another analog [alpha-Asp(DEA)]6,Gln8-hGnRH showed a very low endocrine but high antitumor effect in both in vitro and in vivo experiments. Its tritium labeled derivative exhibited specific binding sites on human tumor cell lines. We synthesized the analogs of GnRH-III with effective selective antitumor activity which does not alter the ovarian cycle of rats but inhibits the colony-formation of human breast cancer cell lines and has a significant antiproliferative effect. We also synthesized conjugates of potent GnRH analogs with a branched chain polylysine backbone which induce a 33-35% decrease of cell numbers of MCF-7 and MDA-MB-231 human breast cancer cell lines and 45-50% inhibition of cell proliferation. Another conjugate decreased the tumor growth of MDA-MB-231 xenografts by 80% in a treatment of 9 weeks and even tumor free animals could be found among the ones treated. Using these radiolabeled peptide hormone analogs we found that human tumor cell lines and xenografts specifically bind the GnRH conjugates. We also synthesized a series of Somatostatin analogs which inhibit tyrosine kinases and the growth of several breast, prostate and colon tumor cell lines. One of our best analogs was a heptapeptide, TT-232, which strongly inhibited the tyrosine kinase activity and the cell-proliferation in different colon tumor cells. However, it did not inhibit the growth hormone release either in vitro or in vivo from rat pituitary cells. The TT-232 was found to be effective on 60 human tumor cell lines, it significantly inhibited the tumor growth on different animal tumor models, and induced apoptosis, as a result of which some animals became tumor free. The TT-232 inhibited the tumor growth of PC3 prostate xenografts with 60% and caused a 100% survival of mice 60 days after the transplantation. It is being preclinically tested at present. We have shown that the new GnRH analogs acting without any hormonal effect and the Somatostatin analogs with strong antitumor and tyrosine kinase inhibitory activity but no hormonal effect may represent a breakthrough in the research of the antitumor peptides, having direct effect on tumor cells.
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PMID:Peptides and antitumor activity. Development and investigation of some peptides with antitumor activity. 1086 57

The somatostatin analogue (SA) Octreotide has been used as a therapeutic reagent for somatostatin receptor type 2a (SSTR2a)-positive cancers. The purpose of this study is to detect SSTR2a in human prostate carcinomas and to elucidate the effects of SA on SSTR2a-positive prostate carcinoma cells to determine the potential of this drug as a new therapeutic method for advanced prostate carcinoma. Immunohistochemical study of SSTR2a was performed on 95 prostate carcinoma cases, and the results showed expression of SSTR2a in 14 of the 95 cases (14.74%); the histological grade (Gleason) and capsular invasion of the prostate carcinoma were directly related to SSTR2a expression. Among the ten cases of lymph node metastasis, SSTR2a expression was markedly higher. In vitro studies were performed using SSTR2a-positive prostate cancer cells, DU145 and PC3. Migration and invasion abilities of DU145 and PC3 cells were inhibited by SA in a dose-dependent manner. This inhibition was reversed by Rho-kinase inhibitor Y-27632. Morphological changes of the prostate cancer cells treated with SA and Y27632 corroborate the migration and invasion assays, although SA had no effect on proliferation of DU145 and PC3 cells. In conclusion, the somatostatin analogue may be beneficial for patients with advanced prostate carcinoma or to protect from distal metastasis if they are positive for SSTR2a.
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PMID:Somatostatin analogue inhibits the mobility of prostate carcinoma cells: a new therapeutic method for advanced prostate carcinoma. 2087 55

To examine the effect and the molecular mechanisms of the combined treatment of the somatostatin (SST) analogue octreotide with docetaxel: analysis of proliferation, apoptosis and migration in the human prostate cancer cell line PC3, either sensitive (PC3wt) or made resistant to docetaxel (PC3R). We examined the effect of the two drugs individually or in combination on cell proliferation and migration by analysis of apoptosis and cell cycle proteins. The role of octreotide in modulating P-glycoprotein function was examined together with the modulation of SST receptors type 2 and 5 (SSTR2 and SSTR5). We observed an enhanced effect of docetaxel and octreotide given in combination or in sequence compared with either agent alone; this result was particularly evident when docetaxel was given before octreotide in PC3wt and when the two drugs were given together in PC3R cells. In contrast to lanreotide, our data indicate that octreotide does not act as a P-glycoprotein inhibitor in PC3R cells. A role of docetaxel and combined treatment in regulating SSTR2, SSTR5, proliferation and apoptosis gene expression is suggested as the possible mechanism for the enhanced effect observed. In addition, an evaluation of the effect of the combined treatment on cellular migration was examined, showing a moderate loss of invasive properties in PC3R cells. The present results confirm that SST analogues may be combined with docetaxel to increase the antitumour effect in patients with advanced prostate carcinoma.
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PMID:Differential molecular mechanism of docetaxel-octreotide combined treatment according to the docetaxel-resistance status in PC3 prostate cancer cells. 2299 Jan 29