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)

We have recently established an in vitro cell line (metastatic mGH3) derived from lymph node metastases of the rat pituitary somatotroph. Here we examined the in vivo effects of octreotide, a somatostatin analog, against malignant pituitary tumors. Wistar-Furth rats (n=8) were inoculated subcutaneously with mGH3 cells while control rats received injections of equal volumes of the vehicle only. Four rats were treated with octreotide three times daily while another group of four rats were treated with saline only. After 6 weeks of treatment, histopathological and immunohistological analyses were performed. The tumor weights of rats treated with octreotide were significantly lighter than those of untreated rats. All rats implanted mGH3, but not administered treatment, developed inguinal lymph node metastases, whereas none of those implanted mGH3 and treated with octreotide developed such metastases. The proportion of PCNA-stained tumor cells was higher in tumors of untreated rats than in those of octreotide-treated rats. However, the proportion of apoptotic cells in the tumor was not different between treated and untreated rats. Our results suggest that octreotide might be potentially effective for invasive and malignant human pituitary tumors by regulating the tumor cell cycle.
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PMID:Octreotide treatment suppresses malignant somatotrophic pituitary tumor cell growth in rats. 1094 23

The somatostatin analog octreotide was recently found to ameliorate radiation-induced tissue injury in rat intestine. The present study addressed whether octreotide reduces chronic intestinal radiation fibrosis, whether enteroprotection is conferred by direct or indirect mechanisms, and whether the effects are dose-dependent. Using a rat model designed for fractionated irradiation, a segment of small intestine was sham-irradiated or exposed to 67.2 Gy X-radiation in 16 daily fractions. Octreotide (0, 2, or 10 microg/kg/h) was administered subcutaneously by osmotic minipumps for 4 weeks, from 2 days before to 10 days after irradiation. Tissue injury was assessed at 2 weeks (early phase) and 26 weeks (chronic phase) by quantitative histopathology and morphometry. Epithelial and smooth muscle cell proliferation was assessed by proliferating cell nuclear antigen staining; connective tissue mast cell hyperplasia by metachromatic staining; and TGF-beta1 and collagen protein and mRNA by quantitative immunohistochemistry, in situ hybridization, and/or real-time fluorogenic probe reverse transcription-polymerase chain reaction. Octreotide conferred dose-dependent protection against early (p = 0.0003) and chronic (p < 0.0001) tissue injury. Octreotide abrogated radiation-induced chronic increases in extracellular matrix-associated TGF-beta (p < 0.0001), collagen I (p = 0.0001), and collagen III (p = 0.0002) immunoreactivity. Octreotide did not affect radiation-induced changes in steady-state TGF-beta1 mRNA levels, mast cell hyperplasia, or smooth muscle cell proliferation. Octreotide reduced crypt epithelial cell proliferation (p = 0.01), but did not otherwise affect unirradiated intestine. Octreotide confers dose-dependent protection against delayed small bowel radiation toxicity and ameliorates radiation fibrosis predominantly by reducing acute mucosal injury. These data strengthen the rationale for using somatostatin analogs as enteroprotective agents in clinical radiation therapy.
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PMID:Influence of Short-Term Octreotide Administration on Chronic Tissue Injury, Transforming Growth Factor beta (TGF-beta) Overexpression, and Collagen Accumulation in Irradiated Rat Intestine. 1125 25

In TT cells, originating from medullary carcinoma of the human thyroid, the presence of receptors for somatostatin was demonstrated at the ultrastructural level. Inhibitory effect of octreotide (a somatostatin analogue) was observed on proliferation of in vitro cultured TT cells and confirmed by evaluating levels of PCNA and Ki-67 proliferation-associated antigens and examining the extent of DNA damage using the comet assay. Our studies indicate a potential for application of somatostatin analogues to diagnosis and adjunct treatment in thyroid medullary carcinomas.
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PMID:Effect of octreotide on proliferation of in vitro cultured thyroid medullary carcinoma cells. 1137 17

We report an autopsy case of pancreatic and ectopic nesidioblastosis. A five-month-old Japanese girl was born at 35 weeks gestation, and showed clinical symptoms of hyper-insulinemic hypoglycemia before death. At autopsy a tumorous nodule was observed at the portion of the jejunum, 90 cm from Treitz's ligament. The nodule measured 30 x 20 x 20 mm. The ectopic pancreas, also revealed nesidioblastosis histologically. Immunohistologically, both nesidioblastoses were stained positive for chromogranin A, insulin, glucagon and somatostatin. The proliferating cell nuclear antigen (PCNA) and Ki-67 indices were less than 4% in the nesidioblastosis. To our knowledge, this is the first reported case of nesidioblastosis demonstrating proliferating activity with PCNA and Ki-67, and is the third reported case of nesidioblastosis arising in the pancreas and ectopic pancreas.
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PMID:An autopsy case of pancreatic and ectopic nesidioblastosis. 1142 96

The aim of this study was to investigate early histological and stereological changes in enterocytes, lymphocytes, mast cells, serotonin- and somatostatin-secreting cells in colon mucosa the first day after the end of combined radiotherapy and chemotherapy. For experimental model 20 Beagle dogs were used. Ten dogs were given platinol every 5 days over 20 days and they were irradiated 20 days with 32 Gy (every second day with a fractional dose of 3.2 Gy) onto the whole pelvis and tail. Another 10 dogs represented a control group. For detection of apoptosis the TUNEL technique was used, whereas immunohistochemical methods were performed for detection of somatostatin- and serotonin-secreting cells, and for proliferating cell nuclear antigen in epithelial cells. The volume density of enterocytes in apoptosis was increased, and Vv of paracrine cells (mast cells, somatostatin and serotonin positive cells) was significantly increased in the treated group compared to the control group. In the treated group a significantly lower Vv of lymphocytes and PCNA-positive enterocytes was shown compared to the control group. The results of our experiments showed that combined radiotherapy and chemotherapy caused loss of enterocytes and lymphocytes early after the therapy. It was associated with an increased volume density of paracrine cells. These morphological changes in the colon mucosa might be the earliest changes leading to disruption of the mucosal barrier, malabsoption syndrome, stenosis, inflammation and other complications resulting from the radiotherapy and chemotherapy.
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PMID:Colon mucosal cells after combined radiotherapy and chemotherapy. 1168 31

The resistance of advanced colorectal cancers to therapy is often related to mutations in the p53 tumor suppressor gene. Because somatostatin (SRIF) receptors (ssts) are present in colorectal carcinomas, the treatment with targeted cytotoxic SRIF analogue AN-238, consisting of 2-pyrrolinodoxorubicin (AN-201) linked to octapeptide SRIF carrier RC-121, may overcome this resistance by producing a higher concentration of the cytotoxic agent in the tumors. Four colon cancer cell lines, HCT-116 and LoVo expressing wild-type p53, and HCT-15 and HT-29 with mutated p53, were investigated. HCT-116, HCT-15, and HT-29, but not LoVo possess functional ssts. We analyzed changes in p53, p21, and proliferating cell nuclear antigen (PCNA) concentrations in these cells in vitro by immunoblotting after exposure to AN-238, its radical AN-201, or doxorubicin (DOX). Equitoxic doses of AN-238, AN-201, or DOX affected p53, p21, and PCNA differently. Analysis of the p21:p53 ratios revealed that DOX increased p53 levels, but most of p53 was mutated and inactive, whereas AN-238 produced smaller changes in p53 concentrations but enhanced its activity. In HCT-15 cells, PCNA:p21 ratios, which are indicators of proliferation and repair processes, remained unchanged after exposure to AN-238 but were increased by DOX. In vivo studies in nude mice demonstrated that AN-238, AN-201, and DOX were equally effective on HCT-116 tumors that express wild-type p53. However, AN-238 also inhibited the growth of HCT-15 and HT-29 cancers that express mutant p53, whereas AN-201 and DOX showed no effect. None of the compounds could suppress the proliferation of LoVo tumors that lack functional ssts. In conclusion, cytotoxic SRIF analogue AN-238 inhibits the growth of experimental colon cancers that express ssts, regardless of their p53 status.
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PMID:Targeted cytotoxic somatostatin analogue AN-238 inhibits somatostatin receptor-positive experimental colon cancers independently of their p53 status. 1183 May 33

To clarify how Syrian hamsters of the APA strain (APA hamsters) keep a diabetic condition for a long period, the functional and histochemical changes in the pancreatic islets of diabetic APA hamsters were examined. By glucose tolerance test, no glucose-induced insulin secretion was seen in the diabetic APA hamsters. By immunohistochemistry, it was revealed that at 24 hr after SZ-injection, the number of islets had decreased and that remnant islets had become markedly smaller. The islets had hardly any insulin-immunoreactive cells and consisted of cells stained by anti-glucagon and somatostatin antibodies. One, three and six months after SZ-injection, a small number of cells with vacuolative changes, which were positive for PAS staining, were observed in most islets and the vacuolated cells were stained mainly by anti-insulin antibody. In addition, a number of PCNA-positive cells were observed, especially in the periphery of the vacuolated cells, while TUNEL-positive cells were not detected. This data suggests that beta-cells proliferating as a result of the replication of the resident beta-cells in islets had fallen into degeneration and necrosis by a stress, such as the glycogen deposition in hyperglycemia and hyperlipidemia. Consequently, secretion of insulin was maintained at low levels, which allowed the hamsters to live without insulin therapy in the diabetic condition for over 6 months.
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PMID:Functional and histochemical analysis on pancreatic islets of APA hamsters with SZ-induced hyperglycemia and hyperlipidemia. 1187 Nov 58

The aims of this study were to investigate in the human cerebellar cortex the structural and biological ontogenetic features, the possible presence of alterations in cases of sudden unexplained fetal and infant death, and the involvement of the maternal cigarette smoking in developmental abnormalities. We analyzed 52 brains of fetal and infant death victims, aged from the second gestational trimester to 12th postnatal month. In the cerebellar cortex we evaluated, besides the morphological aspects, the expression of several biomarkers implicated in proliferative processes (c-fos, proliferating cell nuclear antigen, and apoptosis) as well as the presence of the neurotransmitter somatostatin, which is strongly implicated in central nervous system differentiation, and of EN2 gene. The observed features of the cerebellar cortex, mainly confined to the transient external granular layer, were high proliferative activity and high expression of both somatostatin and EN2 gene in prenatal life and high apoptotic index after birth. In 41% of the sudden unexplained death victims, in the greater part with smoking mothers, we observed different biopathological alterations of the cerebellar cortex. Maternal smoking is increasingly being demonstrated to be one of the main contributors to developmental neurological alterations in the offspring.
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PMID:Ontogenesis of human cerebellar cortex and biopathological characterization in sudden unexplained fetal and infant death. 1733 3

The role of bone marrow (BM)-derived cells in the process of pancreatic islet regeneration remains unclear. The purpose of this study was to determine the role of BM cells in the repair process or regeneration of pancreatic islets in mice using chimeric green fluorescent protein (GFP) expressing BM cells. BM-infused chimeric mice were made diabetic by streptozotocin (STZ) injection or 60% partial pancreatectomy. GFP-positive cells within the islets and pancreas were studied immunohistologically. STZ treatment induced a 10-fold increase in PCNA-positive cells within the islets on day 7 posttreatment. GFP-positive cells increased in number within the islets as well as in the pancreatic parenchyma immediately after STZ injection. The partial pancreatectomy induced 2- to 3-fold increases on day 7 to 28 posttreatment. GFP-positive cells increased in number in pancreatic parenchyma but not within the islets. BM traffic to the pancreas significantly increased in the 2 models inducing islet regeneration. In both models, GFP-positive cells were not positive for antibodies against insulin, glucagon, or somatostatin, but were positive for markers of macrophages or fibroblasts, suggesting their involvement in the initiation of islet regeneration.
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PMID:Bone marrow traffic to regenerating islets induced by streptozotocin injection and partial pancreatectomy in mice. 1837 97

We evaluated the effect of islet neogenesis-associated protein pentadecapeptide (INGAP-PP) upon islet beta- and non-beta cell differentiation from mouse embryonic stem (mES) cells. ES-D3 cell lines were cultured following Lumelsky's protocol with or without INGAP-PP (5 microg/ml) at different stages. Gene expression was quantified using qPCR. mES cells were fixed and immunostained using anti insulin-, somatostatin-, glucagon-, Pdx-1-, Ngn-3-, Nkx-6.1 and PGP9.5 specific antibodies. PCNA was used to measure replication rate. Bcl(2) (immunostaining) and caspase-3 (enzyme activity and gene expression) were determined as apoptosis markers. INGAP-PP increased IAPP, Glut-2, Kir-6.2, SUR-1 and insulin gene expression, and the percentage of insulin-immunostained cells. Conversely, INGAP-PP reduced significantly glucagon and somatostatin gene expression and immunopositivity. While nestin gene expression was not affected, there was a significant reduction in the percentage of PGP9.5-immunostained cells. Pdx-1 gene expression increased by 115% in INGAP-PP treated cells, as well as the percentage of Pdx-1, Ngn-3 and Nkx-6.1 immunopositive cells. Neither caspase-3 (expression and activity) nor Bcl(2) positively immunostained cells were affected by INGAP-PP. Accordingly, INGAP-PP would promote stem cell differentiation into a beta-like cell phenotype, simultaneously decreasing its differentiation toward non-beta-cell precursors. Therefore, INGAP-PP would be potentially useful to obtain beta-cells from stem cells for replacement therapy.
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PMID:Selective effect of INGAP-PP upon mouse embryonic stem cell differentiation toward islet cells. 1915 49


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