Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 75-year-old female presented with a suprasellar granular cell tumor. Computed tomography (CT) revealed a high dense suprasellar mass with strong postcontrast enhancement. Magnetic resonance imaging showed a round suprasellar mass, which was hyperintense on the T1-weighted images with nonhomogeneous enhancement after the administration of gadolinium-diethylenetriaminepenta- acetic acid, and hypointense on the T2-weighted images. Cerebral angiography demonstrated no abnormal findings. The tumor was partially removed via a right frontotemporal craniotomy. The histological diagnosis was suprasellar granular cell tumor. Her postoperative course was uneventful other than mild and transient diabetes insipidus. She has remained asymptomatic without CT evidence of tumor regrowth for 20 months after the surgery. Immunohistochemical studies showed positive reaction for S-100 protein in the tumor cell nuclei, but no reaction for glial fibrillary acidic protein, neurofilament protein, Leu-7, oxytocin, beta-endorphin, adrenocorticotropic hormone, and vimentin. This case provides additional evidence for the astrocytic origin of suprasellar granular cell tumor.
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PMID:Suprasellar granular cell tumor. 874 Dec 54

Sandostatin, a synthetic octapeptide analog of a native hormone somatostatin, was labeled with a commonly available, inexpensive radionuclide, 99mTc, and evaluated for its suitability for in vivo imaging. Labeling was accomplished by reduction of the cystine bridge, which provided two sulfhydryl groups for chelation with 99mTc. The complex was examined for thermodynamic stability in vitro and in experimental animals. Receptor specificity of the complex was determined using rat brain cortex membrane rich in somatostatin receptors, and its tissue distribution was studied in nude mice bearing human prostate cancer. In these studies, 99mTc-labeled oxytocin, a nonspecific peptide with similar molecular weight, served as a control and 111In-DTPA-octreotide served as a standard. The labeling method was simple, did not require protecting and deprotecting functional groups and yields were high (ca. 70%). The in vitro and in vivo stability was excellent, and Kd values were in the nanomolar range, similar to those of 111In-DTPA-octreotide. At 24 hours post-injection, the tumor uptake for 99mTc-Sandostatin, expressed as percent of injected dose per gram (% ID/g), was higher, but the tumor/blood and tumor/muscle ratios were lower than those for 111In-DTPA-octreotide. This agent, with its improved target-to-nontarget ratios, should prove to be of value for imaging somatostatin receptor-positive tumors.
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PMID:Sandostatin labeled with 99mTc: in vitro stability, in vivo validity and comparison with 111In-DTPA-octreotide. 887 94

The authors report the case of a 40-year-old woman with a 12-year history of irregular menses, amenorrhea, infertility, galactorrhea, a slightly elevated prolactin level, and a slowly growing pituitary adenoma. She developed recent onset of visual symptoms, prompting craniotomy for removal of an intrasellar tumor. Following surgery, her vision and prolactin levels returned to normal. Light microscopic and immunohistochemical examination of the tumor revealed it to be a neuroblastoma, which was immunohistochemically positive for synaptophysin, S-100 protein, and oxytocin. The neoplasm contained prolactin-positive neuroblastic and pituitary epithelial cells. No other pituitary hormones were found. Electron microscopy demonstrated two cell types: one with frequent neuritic processes containing neurosecretory granules and showing synaptic specialization, and another one compatible with epithelial adenohypophyseal cells. A few cells had ultrastructural features that were transitional between neuronal cells and granulated epithelial cells. Agranular folliculostellate cells were also identified. Immunoelectron microscopy demonstrated prolactin granules in the cytoplasm of the epithelial cells, in a few transitional cells, and in scattered neuritic processes. Ultrastructural and immunohistochemical features of the tumor suggested a transformation of pituitary epithelium to neuroblastic cells. Hyperprolactinemia and associated clinical symptoms may in part be attributed to selective prolactin secretion by neoplastic cells that were differentiating into adenomatous pituitary cells and, to a lesser extent, to cells differentiating into a neuroblastic line. Compression of pituitary stalk might also have been a contributory factor to the increased prolactin levels. Moreover, the oxytocin produced by the neuroblastic cells was considered an additional stimulus for prolactin secretion by neoplastic cells or by the normal pituitary.
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PMID:Differentiating neuroblastoma of pituitary gland: neuroblastic transformation of epithelial adenoma cells. Case report. 889 39

Vapreotide (RC-160), a somatostatin analog, was labeled with 99mTC by a direct method and also by using CPTA [1,4,8,11-tetraazacyclotetradecane] as a bifunctional chelating agent. The labeled compounds were evaluated in nude mice bearing experimental human prostate cancers. In these studies, 111In-DTPA-D-Phe-Octreotide (111In-DTPA-octreotide) served as a standard and 99mTc-oxytocin as a receptor-non-specific control. 99mTc-octreotide was also used. The 24 htumor uptake of 99mTc-RC-160 was nearly 400% higher, (p < 0.05), than that of 111In-DTPA-octreotide and diminished upon receptor blocking. In all tissues except the kidneys, the uptake of 99mTc-RC-160 was also higher than that of 111In-DTPA-octreotide. The uptake of 99mTc-RC-160 was influenced by the amount of peptide injected and the best tumor/muscle and tumor/blood ratios were obtained when only one micrograms of the peptide (200 Ci/mmol) was administered.
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PMID:Radiolabeled somatostatin analogs in prostate cancer. 908 Apr 82

An alternatively spliced mRNA coding for a variant estrogen receptor (ER) missing exon 4 (ERdelta4) was detected in the breast tumor cell line MCF7 and meningioma tissue by using the reversed transcriptase PCR technique. The trans-activational properties of this mutant ER were assessed in embryo carcinoma P19EC and human choriocarcinoma JEG3 cells by co-transfection of the ERdelta4 expression vector with an oxytocin promoter construct containing an estrogen-responsive element. ERdelta4 did not trans-activate the oxytocin promoter in either a hormone-dependent or -independent manner. Co-transfection of ERdelta4 together with the wtER did not show any interference of ERdelta4 on the stimulation of the oxytocin promoter by the wtER. ERdelta4 was translated in vitro. Its capacity to bind estradiol, and the binding of the variant to a synthetic estrogen-responsive element were compared to those of the wild-type receptor. ERdelta4 did not bind to a synthetic estrogen-responsive element, nor did it bind estradiol. Hence, ERdelta4 appears to be a silent variant and we speculate that it is without any role in tumor progression.
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PMID:Functional analysis of an alternatively spliced estrogen receptor lacking exon 4 isolated from MCF-7 breast cancer cells and meningioma tissue. 939 58

Developmental aspects of oxytocin (OT) receptors (OTR) in uterine tissues before puberty are not known. Bovine ovaries secrete some estradiol, but no progesterone, before puberty; the circulating levels of estradiol are between 1 and 3 pg/ml until puberty. Cross-bred Angus-Brahman heifers, in which puberty occurs around 12 months of age, were used to determine the concentrations of OTR from the late fetal stage to adulthood. PGF2alpha release in response to OT was determined in 3-, 6-, and 9-month-old heifers (n = 4 each). Myometrium, endometrium, and cervical mucosa were obtained from 3-week-old, 3-month-old, 6-month-old, and 9-month-old heifers and from adult cows at estrus. Whole uterus and cervix were taken from third trimester fetuses and at birth. [3H]OT binding and specificity, localization of immunoreactive (ir) OTR, OTR messenger RNA, and OT-induced release of PGF2alpha were determined. The uterus from fetuses and the neonate expressed OTR messenger RNA and bound [3H]OT. At 3 weeks of age, OTR concentrations per mg protein were very low, but at 3 months of age they had increased markedly in all three tissues. At 6 and 9 months of age, levels of OTR had risen further and were similar to those in adult cows at estrus. Prepubertal uterus also possessed separate vasopressin VP1 subtype receptors. The ir-OTR was localized in luminal epithelial cells of endometrium and cervical mucosa, most of which were ir positive, whereas in myometrium, clusters of ir-OTR-positive cells were found among large numbers of ir-OTR-negative cells. The PGF2alpha response to OT was insignificant in heifers of all age groups, in contrast to that in cows at estrus. Endometrial cells from 4- to 5-month-old heifers did not respond to OT with PG release in the absence or presence of added arachidonic acid. Tumor promoters, lipopolysaccharide, and interleukin-2 also failed to elicit PG release in vitro, although they induced PG release in similar cell cultures from cyclic cows. In summary, uterine tissues of prepubertal heifers have high levels of OTR, which appear to be developmentally regulated. These receptors are not coupled to PG synthase, or alternatively, the PG synthase gene is not expressed before puberty, possibly because the tissues have had no previous exposure to progesterone.
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PMID:Ontogeny of oxytocin receptors and oxytocin-induced stimulation of prostaglandin synthesis in prepubertal heifers. 960 82

In the present work, first we reviewed and completed our previous experiments on the antiproliferative effect of oxytocin (OT) in breast cancer cell lines. In vitro, OT 10 nM and 100 nM inhibited cell proliferation of MDA-MB231 (human breast carcinoma) and TS/A (mouse mammary carcinoma) cell lines. In vivo, OT significantly reduced the growth of TS/A mammary tumors. Both effects are mediated by specific receptors (OTR) distributed on cell surface. Second, using immunohistochemistry and RT-PCR we detected OTR and OTR mRNA in normal and pathological breast tissue. There is no correlation among OTR presence in breast carcinomas and the age of patients, tumor stage, estrogen receptor positivity, oncogene expression and proliferation rate of the same tumor. On the contrary, progesterone and OTR expression are correlated. These data confirm our previous evidence of a role of OT and OTR in normal and neoplastic breast cells.
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PMID:Oxytocin receptor within the breast: biological function and distribution. 970 81

A method for labeling proteins and peptides with (methoxycarbonyl cyclopentadienyl)tricarbonyl rhenium and technetium is described. The precursors used for this labeling are conveniently produced from perrhenate and pertechnetate, respectively, using a double ligand transfer reaction. For labeling the lysine residues of the model protein bovine serum albumin, the technetium methyl ester was saponified and then transformed into its N-hydroxysuccinimidyl ester. For the labeling of the model peptides leucine enkephalin, substance P, oxytocin, and the tumor imaging/therapy candidate octreotide, the rhenium methyl ester was saponified and activated using either 1-hydoxybenzotriazole or 1-hydroxy-7-azabenzotriazole. The activation and peptide-coupling reactions were followed using reversed-phase (C18) HPLC and yields averaged approximately 70%.
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PMID:Protein and peptide labeling with (cyclopentadienyl)tricarbonyl rhenium and technetium. 981 71

The effects of Ehrlich Ascites Carcinoma (EAC) cells on the responses of isolated uterine smooth muscles obtained from normal non-pregnant and pregnant mice to oxytocin and acetylcholine (ACh) were investigated. The contractions of normal uterine smooth muscles to oxytocin "0.1, 1 and 10 mU" and to ACh "0.1, 1 and 10 uM" were significantly reduced in the presence of EAC cells. On the other hand, induction of pregnancy in control non-tumor bearing mice significantly increases the sensitivity of the uterine smooth muscles to oxytocin as well as to ACh. In tumor bearing mice, the induction of pregnancy significantly reduced the sensitivity of the uterine smooth muscles to oxytocin and ACh when compared with the uterine muscles obtained from pregnant non-tumor bearing mice. The results of the present study indicate that the presence of tumor cells decreases the responses of the uterine smooth muscles to oxytocin and ACh, while pregnancy increases the uterine contractions induced by oxytocin and ACh. Furthermore, induction of pregnancy in tumor bearing animals reduces the responsiveness of uterine smooth muscles to oxytocin and ACh.
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PMID:Effects of Ehrlich ascites carcinoma cells on the responses of non-pregnant and pregnant uterine smooth muscles of mice to oxytocin and acetylcholine. 989 59

Oxytocin (OT) receptors (OTRs) have been demonstrated in a number of human breast tumors and tumor cells, but it was not clear whether the receptors were functional. We examined the regulation and function of OTR in a tumor cell line, Hs578T, derived from human breast. These cells expressed moderate levels of OTR when cultured in 10% FBS, as demonstrated by RT-PCR and binding analyses. Serum deprivation resulted in the loss of OTRs, with no effect on cell viability. Restoration of serum and addition of 1 microM dexamethasone (DEX) increased OTR levels by about 9-fold. Up-regulation was blocked by the addition of phospholipase C and PKC inhibitors. Serum/DEX treatment also increased steady state OTR messenger RNA levels. OT increased intracellular Ca2+ in a time- and dose-responsive manner, and the effects of OT were lost when OTRs were down-regulated by serum starvation. Serum/DEX up-regulation of OTR restored the responsiveness to OT. OT also stimulated ERK-2 (extracellular signal-regulated protein kinase) phosphorylation and PGE2 synthesis in Hs578T cells. In addition to showing that OTRs in the breast tumor cells are functional, these studies show that Hs578T cells can be used to study molecular regulation of OTR gene expression and intracellular signaling pathways stimulated by OT.
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PMID:Demonstration of functional oxytocin receptors in human breast Hs578T cells and their up-regulation through a protein kinase C-dependent pathway. 1021 79


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