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 continuous cell culture line was established from a bone marrow metastasis of small cell anaplastic carcinoma of the lung. The cultures were characterized by light and electron microscopy, and an unusual concentric arrangement of cells was observed, both in sectioned material from the patient's tumor and from the cell cultures. The cells had two types of specialized cell junctions and contained secretory-like granules of the type described in neuroendocrine cells. Lactic dehydrogenase isozyme patterns were the same as those observed in normal human serum, and the karyotype revealed the presence of several marker chromosomes. Vasopressin was present in the cells and secreted into the culture medium in the absence of neurophysin, as shown by the immunoperoxidase technique and radioimmunoassay. Oxytocin was also absent from cells.
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PMID:Isolation and characterization of a hormone-producing cell line from human small cell anaplastic carcinoma of the lung. 19 Apr 10

Vasopressin (VP) and oxytocin (OT) were evaluated as tumor markers for small cell carcinoma of the lung by measuring the concentrations of these hormones in plasma samples obtained from patients at the onset of therapy and during treatment. Patient levels of VP before treatment ranged from 0.9-116 pmol/L, and this hormone was elevated (greater than 2.4 times) in 37 of 80 patients (46%) when values were compared to those of 25 healthy volunteers (normal mean, 2.13 +/- 0.15 pmol/L). Seventeen patients with elevated arginine VP displayed symptoms of the syndrome of inappropriate secretion of antidiuretic hormone. Patient levels of OT ranged from 0.3-124 pmol/L, and OT was elevated (greater than 2.4 times) in 14 of 72 patients (19%) compared with values in normal subjects (normal mean, 2.23 +/- 0.34 pmol/L). Both hormones were elevated in 6 patients. A positive response to treatment (partial or complete remission) was associated with reductions of elevated VP to 34.6 +/- 4.0% and of elevated OT to 34.7 +/- 7.5%, of values before treatment. Relapse was associated with an increase to 334 +/- 93% of remission values for VP (6 patients) and to 307% for OT (1 patient). These results indicate that VP and OT may be suitable plasma markers for a majority of small cell tumors. In most cases, an elevated concentration of hormone was associated with an elevation of the biosynthetically related neurophysin and vice versa. However, there were a number of exceptions, so that an elevated plasma concentration of VP, OT, or a neurophysin was found for 88% of patients with extensive disease and 70% of patients with limited disease.
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PMID:Neuropeptide production by small cell carcinoma: vasopressin and oxytocin as plasma markers of disease. 165 83

A monoclonal antibody (mAb L6) to a small-cell lung carcinoma surface antigen recognizes a common epitope of vasopressin-neurophysin and oxytocin-neurophysin in hypothalamic nuclei. We now report on the identification of a neurophysin-like precursor in human lung carcinoma (LX-1) cell membrane. mAb L6 immunoaffinity chromatography of solubilized membranes resulted in a single band of approximately 45 kDa. Western blot analysis demonstrated immunoreactivity of this band with mAb L6, anti-vasopressin, and an antibody to the vasopressin precursor, pro-pressophysin. N-terminal sequencing of this band demonstrated a 21-amino acid homology with the N terminus of human pro-pressophysin, and substitution of a Cys33 residue in the tumor antigen with Arg33. Absence of immunoreactivity with the antibodies described above in cytosolic extracts and culture medium suggests nonsecretion of processed or intact pro-pressophysin-like peptide. Northern analysis of LX-1 mRNA with a 30-mer to the C terminus of rat pro-pressophysin resulted in a band of approximately 1000 base pairs, 250 base pairs larger than hypothalamic message. In situ hybridization of LX-1 tumor-bearing nude rat brain with the same probe demonstrated specific hybridization in rat hypothalamus and xenografted tumor. These findings suggest expression of a pro-pressophysin-like protein in this tumor cell line that is preferentially targeted to the cell membrane.
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PMID:Expression of neurophysin-related precursor in cell membranes of a small-cell lung carcinoma. 170 22

A great deal of information has been accumulated on the synthesis and release of AVP, oxytocin, and their associated neurophysins under normal circumstances. In 1957, Schwartz and Bartter first described SIAD in patients with lung cancer and postulated that the clinical findings were the results of excessive vasopressin secretion. Tumors have been known since 1964 to produce vasopressin, and small cell (oat cell) carcinoma of the lung is by far the most frequent malignant cause of SIAD. The biosynthetic pathway for the synthesis of AVP and its associated neurophysin (and to a lesser extent, oxytocin and its neurophysin) is well described and is similar if not identical to the synthesis of these peptides in the hypothalamus. However, there is little reliable information on the control of peptide synthesis and release by these tumors. The clinical picture of SIAD is well described and occurs in 20% to 40% of patients with SCCL, although up to 88% of patients with extensive SCCL have elevated circulating levels of one or more neurohypophyseal peptides. This information has led to considerable interest in the use of these peptides as tumor markers for the diagnosis, evaluation, and assessment of therapy in these patients. With the recognition of the high incidence of secretion of neurohypophyseal peptides by SCCL, studies have been initiated to determine the value of radioactive vasopressin neurophysin antibodies in localizing tumors that synthesize these peptides. The studies provide potentially useful information in diagnosing and following patients with SCCL and also offer some promise that radiolabeled antineurophysins could eventually be used to treat these patients.
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PMID:Ectopic secretion of neurohypophyseal peptides in patients with malignancy. 193 17

Vasopressin-neurophysin (hNpI), oxytocin-neurophysin (hNpII) and blood osmolality were assayed before any treatment in basal conditions in 35 patients suffering from lung carcinoma (20 oat cell, 6 undifferentiated and 9 well-differentiated epidermoid cell carcinomas). Plasma vasopressin (antidiuretic hormone, ADH) was also assayed in 7 of the 20 patients suffering from oat cell carcinoma. We found a close correlation (r = 0.98) between plasma ADH and hNpI levels in the 7 patients. Further, hNpI was elevated in 13 out of the 20 oat cell carcinoma patients and in none of the epidermoid-cell carcinoma group; however, searching for an abnormality of ADH secretion as reflected by a detectable plasma hNpI level together with subnormal plasma osmolality revealed 2 additional positive results in the oat cell carcinoma group, and 2 out of the 6 in the undifferentiated-cell carcinoma group. hNpII was increased together with an increase in hNpI in 6 oat cell carcinoma patients; it was specifically increased without hNpI increment in 2 additional oat cell carcinoma patients and in 2 patients of the undifferentiated-cell carcinoma group (different from the 2 positive for the hNpI-osmolality ratio). hNpI and hNpII were normal in the majority of undifferentiated and all of the differentiated epidermoid-cell carcinoma group. Hence, our results show that simultaneous measurements of hNpI, hNpII, and blood osmolality could detect abnormalities in 17 out of 20 oat cell carcinoma patients, in 4 of the 9 undifferentiated-cell carcinoma patients, but in none of the differentiated epidermoid-cell carcinoma patients, suggesting that the neurophysin assay can be used for the early detection of oat cell- and possibly other neuroendocrine-derived carcinomas.
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PMID:Neurophysins as markers of vasopressin and oxytocin release. A study in carcinoma of the lung. 196 64

Mouse monoclonal antibody (mAb) L6 identifies an antigen expressed on the cell surface of many different human carcinomas. While studying the binding activity of mAb L6 to intracerebral tumor xenografts of human lung carcinoma LX-1 cells in nude rats using immunohistological techniques, we observed that L6 can also bind to a cytoplasmic antigen expressed in the magnocellular component of the hypothalamo-neurohypophysial system. Double-labeling experiments with antisera to vasopressin and oxytocin confirmed the localization of L6 immunoreactivity within both peptide-containing cell groups. L6 immunoreactivity in Brattleboro rats (with genetic deletion in the vasopressin gene) was exclusively localized within oxytocin neurons. Oxytocin and vasopressin failed to block L6 staining which suggested that its target epitope resides within the neurophysin sequence, and this explanation was supported by the finding that adsorption of L6 with porcine neurophysin completely eliminated hypothalamic immunoreactivity. Western blot analysis of bovine neurophysin and human pituitary extracts identified L6-immunoreactive bands which corresponded to the position of neurophysin and pro-pressophysin, confirming that L6 immunoreactivity in hypothalamus is related to neurophysin. Thus, monoclonal antibody L6, which is highly reactive with a membrane antigen of human lung cancer cell line LX-1, recognizes a cytoplasmic epitope in hypothalamic neurons identified as neurophysin by immunohistochemistry and Western analysis.
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PMID:Identification of neurophysin immunoreactivity in hypothalamus by a monoclonal antibody to a carcinoma cell surface antigen. 211 32

Preliminary studies are reported on the use of 131I-labelled antibodies against vasopressin associated human neurophysin to image tumors in patients with small cell carcinoma of the lung (SCCL). The rabbit polyclonal antibodies used in these studies were affinity purified on columns of neurophysin-Sepharose. Patients were pre-screened for the presence of neurophysin producing tumors by plasma RIA. Six patients who screened positive received approximately 1 mCi/70 kg body weight of radioiodinated antibody preparation, and scintigraphy was subsequently performed at 24 h, 48 h, and 72 h using a subtraction technique based on simultaneous imaging with radiopharmaceutical agents labelled with technetium-99m. Tumor was clearly demonstrated at 72 h in all five patients who had measurable lesions at the time of study, while no positive image was noted for one patient in complete clinical remission. Since approximately 70% of all SCCL patients have neurophysin-producing tumors, our findings suggest that neurophysin antibodies may be effectively used to scan tumors in a majority of patients with SCCL.
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PMID:Imaging of small cell carcinoma using 131I-labelled antibodies to vasopressin associated human neurophysin (VP-HNP) 255 81

Plasma human neurophysins (HNPs) were evaluated as tumor markers for patients with small cell carcinoma of the lung (SCCL) who were entered on limited disease and extensive disease treatment trials conducted by Cancer and Acute Leukemia Group B (CALGB). HNP values obtained before treatment showed 44% of tumors secreting vasopressin-associated HNP (VP-HNP), 14% secreting oxytocin-associated HNP (OT-HNP), and 11% producing both HNPs. There was a significantly higher incidence of HNP-secreting tumors for patients with extensive disease and two or more metastatic lesions than for patients with limited disease. There were no clear differences in response to treatment or in survival between patients with HNP-secreting tumors and those with nonsecreting tumors. Response to treatment evaluated by the change in plasma HNP, gave a 91% agreement with independently derived clinical impressions. Our data indicates that HNP evaluations provide sufficient sensitivity to forecast clinical response when it cannot be clearly assessed by conventional methods.
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PMID:Neurophysins as tumor markers for small cell carcinoma of the lung. A cancer and Leukemia Group B evaluation. 284 78

Continuous cell lines have been established from a variety of biopsy and postmortem species of tumor from patients with small-cell carcinoma of the lung (SCCL) and have been maintained over several years. The medium from the cultures has been assayed for peptide, glycoprotein, and steroid hormones. Significant amounts of 14 hormones including calcitonin, adrenocorticotropin (ACTH), parathormone, luteinizing hormone, chorionic gonadotropin, glucagon, growth hormone, somatostatin, prolactin, beta-endorpin, lipotropin, oxytocin-neurophysin, vasopressin-neurophysin, and estradiol have been demonstrated. Up to ten different hormones have been produced by a single cell line. Most produce ACTH and all evaluated so far produce estradiol. These studies indicate that cells from SCCL have a potential for producing a wide variety of hormones and that this characteristic can be maintained for prolonged periods of culture in vitro.
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PMID:Hormone production by cultures of small-cell carcinoma of the lung. 626 22

At diagnosis, 65% of 103 patients with small cell carcinoma of the lung were found to have elevated plasma concentrations of vasopressin-associated human neurophysin (VP-HNP), oxytocin-associated human neurophysin (OT-HNP), or both, which were thought to be related to tumor secretion of these proteins. The remainder of patients were designated as nonsecretors (24%) or possible secretors (11%), depending upon plasma concentration of the neurophysins prior to therapy. There was a significantly higher percentage of secretors among patients with extensive disease (82%) than among those with limited disease (40%) (P = 0.001). However, within each stage group, there was no correlation between secretory status and response to therapy, survival, or histologic subtype. In addition, patients who initially were nonsecretors or possible secretors maintained this status throughout the course of disease remission and subsequent relapse. These findings suggest the possibility of biochemical differences between tumors which present as limited disease and those which present as extensive disease. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) was infrequent in limited disease but was present in 33% of patients with extensive disease. SIADH was not seen without VP-HNP elevation; however, with extensive disease, 49% of patients with elevated VP-HNP had SIADH. In contrast, elevated plasma concentrations of the neurophysins were seen in only 19.6% of 56 patients with non-small cell carcinoma of the lung. The levels were in general lower than those in patients with small cell carcinoma and were seen at approximately equal frequencies in each major cellular subtype.
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PMID:Human neurophysins in carcinoma of the lung: relation to histology, disease stage, response rate, survival, and syndrome of inappropriate antidiuretic hormone secretion. 631 32


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