UNIPROT:P61278 - FACTA Search

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Query: UNIPROT:P61278 (somatostatin)
22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of somatostatin analogue RC-160 on the growth of hepatic metastases of colon cancer was investigated in rats using magnetic resonance imaging. Experimental liver metastatic tumors were established in syngeneic BDIX rats after intrasplenic injection of DHD/K12 colon adenocarcinoma cells. Each rat with implanted liver tumors received s.c. injections of somatostatin analogue RC-160 (50 micrograms/kg) or the vehicle (control) twice a day for 4 weeks, starting 3 weeks after tumor inoculation. During the treatment with RC-160, the growth of liver tumors was studied quantitatively by measuring liver tumor volumes in vivo with magnetic resonance imaging at intervals of 7 days. Chronic administration of RC-160 inhibited the growth of hepatic metastases of colon cancer in rats. Significant inhibition of liver tumor growth in RC-160-treated rats was observed throughout the treatment. The final liver tumor volume in the treated rats was decreased by 56.1% as compared to the controls. The treatment with RC-160 reduced the percentage increase in liver tumor volume from 1575 +/- 674% (mean +/- SEM) for the control to 1034 +/- 727% in the treated group. The tumor volume doubling time in treated rats was 3.7 days longer than the controls. The liver tumor growth delay time was 15.1 days. At the end of the treatment, the incidence of ascites and the weights of tumorous livers were also decreased by RC-160 treatment. Administration of RC-160 prolonged the median survival time by 13 days in treated rats. In cell cultures, significant inhibitory effects of somatostatin-14 and RC-160 on the growth of DHD/K12 colon cancer cells were determined by MTT assay and [3H]-thymidine incorporation assay, indicating direct effects of these peptides on the growth of colon cancer cells in vitro. These data suggest that administration of RC-160 could inhibit the growth of colon cancer and their hepatic metastases in rats. Somatostatin analogue RC-160 might be considered as a potential new agent for the treatment of patients with hepatic metastases of colorectal cancers.
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PMID:Inhibitory effect of somatostatin analogue RC-160 on the growth of hepatic metastases of colon cancer in rats: a study with magnetic resonance imaging. 135 23

5-fluorouracil (5-FU) is still the most effective cytotoxic agent for the treatment of human colorectal cancer. Response rates, however, vary between 5-20%. One attempt to improve the effect of 5-FU is through biomodulation. We have previously found the somatostatin analogue, SMS 201.995 (Sandostatin, Sandoz), to inhibit both the in-vitro and in-vivo growth of some human colon cancer cell lines. It may act specifically by means of receptors on the surface of tumour cells, or by reducing the concentration of some growth factors. We report that, when 5-FU at 0.125 and 0.25 micrograms/ml was combined with SMS 201.995 at 10(-12) x 2 to 10(-8) x 2M, an enhanced inhibition of in-vitro growth of two human colorectal cancer cell lines (C170 and LIM 1215) was achieved. Effects were measured using [3H]-thymidine uptake and by a colorimetric assay of cellular respiration (MTT, Promega, Sydney). SMS 201.995 alone has minimal inhibitory effects, whilst 5-FU alone shows inhibition as low as 39.6% of control. When 5-FU was then combined with SMS 201.995, a 10-30% inhibition occurred compared to the 5-FU control. The combination of 5-FU and SMS 201.995 may be a useful method of improving response to human colorectal cancer therapy.
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PMID:SMS 201.995 (Sandostatin) enhances in-vitro effects of 5-fluorouracil in colorectal cancer. 785 48

In mucosa-bearing organs with inherent lymphoid populations, classical modes for control of the immune response may be augmented by products of extrinsic sensory afferent nerve endings which arborize through the lamina propria compartment containing large numbers of T and B lymphocytes. Therefore, we sought to determine the role of neuropeptides (substance P, vasoactive intestinal peptide, and somatostatin) in immune response regulation by using a homogeneous line of T lymphocytes (AO40.1 hybrid), whose activation is driven by a specific Ag (OVA) and where the end point (IL-2 release) could not be contributed to by accessory or other cells. IL-2 was quantitated by the rate of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) metabolism with the use of a murine CD4+ IL-2-dependent T lymphocyte line, and dose-response effects of each neuropeptide were examined over a broad concentration range (10(-14)-10(-6) M) encompassing that regarded as physiologic. Vasoactive intestinal peptide stimulated IL-2 release at low concentrations with a marked effect at 10(-14) M that gradually returned to control levels by 10(-7) M. Somatostatin was associated with a substantial augmentation of AO40.1 T lymphocyte IL-2 release at 10(-10) to 10(-8) M concentrations, whereas substance P demonstrated a stimulatory effect only at high concentrations (10(-9) to 10(-6) M). Concomitant [3H]thymidine uptake studies suggested that changes in cell proliferation or viability did not account for neuropeptide-induced effects in our system. With several exceptions, similar results were found with mitogen (Con A)-stimulated AO40.1 cells and human colonic lamina propria mononuclear cells. It was concluded that the three study neuropeptides, over a broad range of concentrations, have profound stimulatory (and occasionally inhibitory) effects upon the function of a cloned T lymphocyte hybrid cell responding to specific Ag and that these events may reflect those of Ag-driven mucosal T lymphocytes exposed to neuropeptides in vivo.
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PMID:Modulation of T lymphocyte function by neuropeptides. Evidence for their role as local immunoregulatory elements. 851 59

Somatostatin and its analogs are antiproliferative in a wide range of normal and neoplastic tissues. In this study we investigated the effect of octreotide (SMS 201-995) on the invasion and growth of three follicular thyroid cancer (FTC) cell lines from one patient in vitro and in vivo. FTC133 was established from the primary tumor, FTC236 from a cervical lymph node metastasis, and FTC238 from a lung metastasis. Invasion was the ability of tumor cells to penetrate 8-microns pore polycarbonate membranes coated with Matrigel. Invasion and proliferation were analyzed using the MTT assay. For in vivo experiments, athymic nude mice were sc inoculated with 500,000 calls of FTC133. The animals were treated twice daily with octreotide sc (100-300 micrograms/kg). RIA studies yielded dose-dependent high plasma levels of octreotide (3.43-6.5 ng/mL). Octreotide had a biphasic effect, enhancing growth at low concentrations (1-10 nmol/mL) and inhibiting it at high concentrations (100 nmol to 1 mumol/mL). Octreotide had also a dose-dependent biphasic effect on the invasion of FTC, inhibiting the invasion of all follicular thyroid cancer lines at high concentrations. However, it affected invasion less than growth. Octreotide (10 nmol/mL) stimulated the invasion of FTC133 by 13%, whereas stimulation was lower in both FTC metastases (FTC236, 6%; FTC238, 7%; P < 0.01). At higher concentrations (100 nmol to 1 mumol/mL), octreotide inhibited invasion of FTC133 by 17% (FTC236, 15%; FTC238, 17%; P < 0.01). During a 3-week treatment period, octreotide had no antiproliferative effect on the growth of FTC133 cells in nude mice. In conclusion, octreotide at low concentrations stimulates and at high concentrations inhibits the growth and invasion of follicular thyroid cancer cells in culture. However, it has no effect on the growth of FTC cells in animal experiments. Thus, the value of octreotide as an antitumoral agent in follicular thyroid cancer must be critically questioned.
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PMID:Somatostatin analog octreotide inhibits the growth of differentiated thyroid cancer cells in vitro, but not in vivo. 867 90

We have recently shown that substance P (SP) participates in the stress-induced modulation of elicited, peritoneal macrophage function. This study reports the in vitro effects of SP on macrophage activity. We show by an MTT bioassay that SP significantly increases cellular metabolic activity. We show by ELISA that preincubating (priming) the macrophages with SP, prior to the incubation with lipopolysaccharide (LPS), results in a significant enhancement of proinflammatory cytokine secretion, relative to LPS alone. Finally, we show that somatostatin can antagonize the SP-induced enhancement of cytokine secretion. The above results demonstrate the importance of the temporal sequence in which stimuli are administered, in vitro, and indicate that SP can act as first signal in the cascade of macrophage activation. We postulate that stress, via the secretion of SP and other sensory neuropeptides, may play a role in the pathogenesis of certain inflammatory diseases of unknown etiology.
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PMID:Substance P primes murine peritoneal macrophages for an augmented proinflammatory cytokine response to lipopolysaccharide. 894 30

In order to observe the regulative effects of pentagastrin (PG) and somatostatin (SS) on the growth of two human gastric cancer cell lines (HGC803 and HGC823) in vitro, we observed the effects of PG and SS on proliferation of human gastric cancer cells by means of MTT. The contents such as gastrin, insulin, and glucagon were determined by radioimmunoassay (RIA), and the hexosamine content was determined by Neuhaus' method. The results showed that the growth of the two human gastric cancer cell lines were obviously promoted by PG. On the contrary, the growth and secretion of gastrin and glucagon were inhibited by SS. In addition, the hexosamine content of human gastric cancer cells was significantly increased by PG (7.58 +/- 0.66 versus 4.20 +/- 0.39 pg/cell, (P < 0.05). But the hexosamine content was decreased by SS (2.62 +/- 0.29 versus 4.20 +/- 0.39 pg/cell, P < 0.05). These findings indicate that the growth of gastric cancer cells is regulated by PG and SS, nevertheless a host of problems need to be elucidated.
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PMID:[Regulative effects pentagastrin and somatostatin on growth of human gastric cancer cells in vitro]. 1068 96

The antiproliferative effects of somatostatin and its analogs on human pancreatic cancers were studied: (1) by evaluating the gene expression of somatostatin receptor (sstr) subtypes in human pancreatic cancer cell lines and cancer tissue specimens, (2) by evaluating the antiproliferative effects of somatostatin analogs, and (3) by evaluating the effect of sstr-2 cDNA transduction. Using a reverse transcriptase polymerase chain reaction (RT-PCR), the gene expression of five sstr subtypes (sstr-1 to -5) was examined in eight cell lines, and in ten pancreatic cancer tissues and in the normal surrounding pancreatic tissues. The antiproliferative effects of somatostatin (SS) -14 and its two analogs (SMS 201-995, RC-160) were examined by means of an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (thiazolyl blue)) assay on three cell lines and Panc-1 transfectants with human sstr (hsstr)-2A cDNA. Sstr-2 was expressed in all samples tested. All examined cell lines simultaneously expressed sstr-2 and -5, while most of the examined pancreatic cancer tissues did not express both of these subtypes simultaneously. Somatostatin analogs inhibited epidermal growth factor (EGF)-stimulated pancreatic cancer cell proliferation. The cell proliferation was further and significantly inhibited by 14% in stable transfectants of Panc-1 cells with hsstr-2A. Based on these findings, it is concluded that somatostatin analogs with their antiproliferative effects mediated by sstr-2 could be potentially useful in the treatment of pancreatic cancers.
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PMID:Expression of somatostatin receptor subtypes and growth inhibition in human exocrine pancreatic cancers. 1118 Aug 77

AIM:To explore the effect and mechanism of gastrin and its antagonists prog lumide and somatostatin on colorectal carcinoma and their clinical significance.METHODS:A model of transplanted human colonic carcinoma was established from SW480 cell line in gymnomouse body.The volume and weight of transplanted carcinoma was observed under the effect of pentagatrin (PG), proglumide (PGL) and octapeptide somotostatin (SMS201-995, SMS). The cAMP content of carcinoma cell was determined by radioimmunoassay and the DNA, protein content and cell cycle were determined by flow-cytometry. The amount of viable cells was determined by MTT colorimetric analysis,IP(3) content was determined by radioimmunoassay, Ca(2+) concentration in cell by fluorometry and PKC activity by isotopic enzymolysis. The expression of gastrin, c-myc, c-fos and rasP21 in 48 cases of colorectal carcinoma tissue was detected by the immuno-cytochemistry SP method. Argyrophilia nucleolar organizer regions was determined with argyrophilia stain.RESULTS:The volume,weight, cAMP, DNA and protein content in carcinoma cell, cell amount and proliferation index of S and G(2)M phase in PG group were all significantly higher than those of control group. When PG was at the concentration of 25mg/L, the amount of viable cells, IP(3) content and Ca(2+) concentration in cell and membrane PKC activity in PG group were significantly higher than those in control group; when PGL was at a concentration of 32mg/L, they dropped to the lowest level in PG (25mg/L)+PGL group, but without significant difference from the control group. The positive expression rate of gastrin, c-myc, c-fos and rasP21 in carcinoma tissue was 39.6%, 54.2%, 47.9% and 54.2% respectively and significantly higher than that in mucosa 3cm and 6cm adjacent to carcinoma tissue and normal colorectal mucosa. The positive expression rate of gastrin of highly differentiated adenocarcinoma group was significantly higher than that of poorly differentiated and mucinous adenocar-cinoma groups. The AgNORs count of carcinoma tissue was significantly higher than that in mucosa 3cm and 6cm adjacent to carcinoma tissue and normal colorectal mucosa; and the positive expression of c-myc and c-fos and the AgNORs count in gastrin-positive group was significantly higher than those in gastrin negative group.CONCLUSION:Pentagastrin has a promoting effect on the growth of transplanted human colonic carcinoma from SW480 cell line. PGL has no obvious effect on the growth of human colonic carcinoma SW480 cell line, but could inhibit the growth promoting effect of PG on transplanted carcinoma. Somatostatin can not only inhibit the growth of transplanted human colonic carcinoma from SW480 cell line directly but also depress the growth-promoting effect of gastrin on the transplanted carcinoma. Some colorectal carcinoma cells can produce and secrete gastrin through autocrine, highly differentiated adenocarcinoma express the highest level gastrin.Endogenous gastrin can stimulate the cell division and proliferation of carcinoma cell and promote the growth of colorectal carcinoma regulating the expression of oncogene c-myc, c-fos. Our study has provided experimental basis for the adjuvant treatment using gastrin antagonist such as PGL, somatostatin of patients with colorectal carcinoma.
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PMID:Regulatory effect and mechanism of gastrin and its antagonists on colorectal carcinoma. 1181 78

Somatostatin receptors (SSTRs) have been detected in many normal and malignant tissues. This wide expression has been used for diagnostic, prognostic and therapeutic purposes. Five SSTR subtypes (SSTR 1-5) have been identified whose activation is responsible for the signal transduction through many different intracellular pathways. In the present study the expression of SSTR mRNA was determined by reverse-transcriptase (RT)-PCR in 42 meningiomas. About 88% of the tumors analyzed (37/42) were positive for at least one of the five SSTR subtypes displaying a variable pattern of expression of the different SSTR subtypes. SSTRI and SSTR2 were the most frequently mRNA detected (69% and 79% of the sample analyzed, respectively). The other subtypes were found in the 43%, 33% and 33% of cases for SSTR3, SSTR4 and SSTR5, respectively. In 22, out of 42 patients (52%) three or more SSTRs were detected. The expression of the different SSTR subtypes did not correlate with the expression of bcl-2 (apoptosis-associated protein) and MIB-1 (a proliferation marker), assessed by immunohistochemistry in a series of 34 tumor samples, while a correlation between the expression of SSTR3 and p53 was observed (p = 0.08). To evaluate a possible role of SSTR in the control of human meningioma cell proliferation, seven primary cell cultures obtained from fresh meningioma surgical tissues, were analyzed for their proliferative behavior by MTT assay and for their response to SST by [3H]-thymidine incorporation. In four out of six tumors (in one case no SSTR were detected) the treatment with SST caused a significant inhibition of DNA synthesis induced by the tumor-promoter phorbol myristate acetate. The evidence of the expression of SSTRs, mainly of SSTR2, in this series of specimens we analyzed altogether with in vitro antiproliferative effects of SST may open interesting perspectives for the diagnosis and the therapy of meningiomas.
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PMID:Expression of somatostatin receptor mRNA in human meningiomas and their implication in in vitro antiproliferative activity. 1501 81

Somatostatin can suppress the growth of various tumor cells including colonic cancer. Activated Wnt/ beta-catenin signaling pathway plays a critical role in tumorgenesis and development of colorectal cancer. However, the effect of somatostatin on Wnt/beta-catenin signaling pathway remains unknown. Thus, we investigated the effect of octreotide on Wnt/beta-catenin signaling pathway in human colonic cancer cell SW480. The results of 3-(4,5-imethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) and flow cytometric assays showed that octreotide inhibited growth, induced apoptosis and arrested the G1 cell cycle of SW480 cells in a dose-dependent manner. We demonstrated that octreotide significally up-regulated and down-regulated 13 genes and 17 genes in Wnt/beta-catenin signaling using microarray, respectively. Furthermore, as evidenced by western blot, beta-catenin protein level decreased, whereas phosphorylated beta-catenin protein level increased under octreotide. The present study reveals that octreotide can inhibit human colonic cancer cell growth through inhibition of Wnt/beta-catenin signaling pathway.
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PMID:Octreotide inhibits growth of colonic cancer SW480 cells by modulating the Wnt/P-catenin pathway. 1932 Feb 86

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