Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biochemical evidence suggests that ectopic hormone production is much more common than suspected clinically. The majority of lung carcinomas of oat cell or carcinoid type appear to synthesise ACTH and related peptides, calcitonin and less frequently, chorionic gonadotrophin and vasopressin. The primary amino acid sequences of ectopic hormones closely resemble their normal counterparts but ectopic hormone producing tumours contain greater proportions of high molecular weight, subunit and fragment forms than the normal gland of origin. Assays for ectopic hormones are clinically useful in diagnosis, tumour localisation, and monitoring patients with ectopic hormonal syndromes. Currently the clinical value of hormone assays in the routine management of common forms of malignancy in the absence of overt ectopic hormonal syndromes is unproven. However, better characterisation of hormonal forms relatively specific for neoplasia together with improved assay specificity and sensitivity may enhance the clinical value of ectopic hormones as tumour markers, particularly in malignancies which are commonly associated with ectopic hormone production (e.g. lung cancer).
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PMID:Ectopic hormones--biochemical aspects. 625 53

A 58-year-old man with bronchogenic oat cell carcinoma developed a typical syndrome of inappropriate secretion of antidiuretic hormone. The tumor tissue obtained at autopsy had been serially transplanted in nude mice for more than four years with 20 passages. The levels of vasopressin were remarkably increased in the plasma of nude mice bearing this tumor [24.4 +/- 18.3 (S.D.) pg/ml, n = 3] as well as in the tumor tissues ]134.3 +/- 72.2 ng/g, n = 3]. Furthermore, human nicotine-stimulated neurophysin was detected in both plasma and tumor tissues (7.4 +/- 3.7 ng/ml, n = 3, and 2.28 +/- 0.90 micrograms/g, n = 3, respectively). On ad libitum intake of water, nude mice bearing this tumor excreted significantly less urine with higher sodium concentration than did controls, but serum sodium concentrations did not differ from those of controls. When tumor-bearing mice were hydrated with 2 ml of water twice a day i.p., their diuretic response was found to be suppressed in parallel with the tumor size. However, these mice did not become hyponatremic because they drank less water. When a larger amount of water was loaded which could not be compensated by restriction of water drinking, serum sodium concentrations were markedly decreased. On the basis of these results, the lung cancer, when transplanted into nude mice, produced and secreted its own antidiuretic hormone, which induced inappropriate secretion of antidiuretic hormone in the mice. These mice may provide a useful experimental model for the study of excessive secretion of antidiuretic hormone and associated pathophysiological disorders.
Cancer Res 1981 Apr
PMID:Inappropriate secretion of antidiuretic hormone in nude mice bearing a human bronchogenic oat cell carcinoma. 626 Mar 43

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.
Cancer 1981 Mar 15
PMID:Hormone production by cultures of small-cell carcinoma of the lung. 626 22

Ninety-eight patients with small cell carcinoma of the bronchus (SCCB) were treated with a combination of cyclophosphamide, methotrexate with calcium leucovorin rescue, and lomustine (CCNU). VP-16-213 was given on relapse. Response rate and survival were analyzed according to extent of tumor, presence of the syndrome of inappropriate antidiuretic hormone production (SIADH), and, in 38 patients, size of intrathoracic tumor as measured by computerized tomographic (CT) scanning. The median survival of the entire group was 34.6 weeks. In patients with limited disease the median survival was 46 weeks compared to 29 weeks for those with extensive disease. This difference in survival between patients with limited and extensive disease was most marked in those showing a partial response (median survival, 45.9 and 28 weeks, respectively). Patients with ectopic antidiuretic hormone production had a poor prognosis even if they had achieved a complete response. Only one partial response to VP-16-213 occurred. There was a strong correlation between initial intrathoracic tumor size as assessed by total cross-sectional area on CT scan and response and survival. When the total area exceeded 30 cm2 there were no complete responders, but there were complete responses in eight of 21 patients when the area was less than 30 cm2. The relationship between intrathoracic tumor size and response rate was present when analyzed according to disease extent, age, sex, and performance status. A clear relationship between total tumor area and survival was also found. When SCCB is treated with chemotherapy alone, the prognosis is better for those patients who present with limited disease, without SIADH, and with small intrathoracic tumor. In this group it is possible that further intensification of therapy may result in prolonged survival.
Cancer Treat Rep 1982 Mar
PMID:Tumor size, response rate, and prognosis in small cell carcinoma of the bronchus treated by combination chemotherapy. 627 86

Previous studies have suggested that ectopic production of adrenocorticotropic hormone (ACTH) or antidiuretic hormone (ADH) may occur commonly in patients with small cell carcinoma of the lung (SCCL) and that evidence of such production may be elicited only by provocative tests of water excretion and adrenal function. We studied 28 patients with SCCL and 29 patients with other cancers. Adrenal function, assessed by measuring the 8 am plasma cortisol, the 8 am to 4 pm diurnal variation in plasma cortisol, and the suppressibility of the 8 am plasma cortisol following administration of 1 mg of dexamethasone, was found to be abnormal in 28.5, 71, and 25 percent, respectively, of the patients with SCCL, compared with 18, 65, and 29.5 percent in patients with other types of cancer (P greater than 0.3). The possibility of ectopic ADH secretion was assessed by a standard water loading test, which showed excretion impairment in 60 percent of patients with SCCL and 68 percent of patients with other cancers (P greater than 0.9). Neither the stage of neoplastic disease, sites of metastatic deposits, nor performance status of the patients correlated with abnormalities of water and cortisol metabolism, indicating that such abnormalities are common in patients with all types of cancer. These data do not suggest that subclinical disturbances of adrenal function or water excretion are characteristic of any histologic type of cancer. The precise mechanism(s) underlying these abnormalities are unknown.
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PMID:Frequency of abnormalities of cortisol secretion and water metabolism in patients with small cell carcinoma of the lung and other malignancies. 628 Sep 29

The present study was performed to investigate the possible synthesis of a common precursor molecule for calcitonin (CT), adrenocporticotropin (ACTH) and beta-lipotropin (beta-LPH)/ beta-endorphin (beta-EP) by the human medullary thyroid carcinoma (MTC). In a patient with MTC but without Cushing's syndrome, the response of plasma CT, ACTH and cortisol levels to a calcium infusion, lysine vasopressin (LVP) and dexamethasone were measured. A parallel increase of these hormones in response to calcium and LVP was seen, while there was a paradoxical increase of CT during dexamethasone infusion. Incubation of MTC fragments obtained at surgery showed a significant correlation of the secretion of CT, ACTH and beta-LPH/ beta-EP in response to calcium, LVP and dexamethasone. The concomitant release of these hormones in vivo and in vitro could be compatible with the synthesis of a common precursor molecule for CT, ACTH and beta-LPH/ beta-EP in MTC, although this was not substantiated by gel-chromatography of the tumor extract. Corticotropin releasing factor, a regulator of the normal processing of pro-opiococorticoid precursor molecule in the anterior pituitary gland, is also able to activate ACTH, beta-LPH/ beta-EP and calcitonin secretion from the malignant C-cell of the thyroid.
Eur J Cancer Clin Oncol 1982 Mar
PMID:Concomitant secretion of calcitonin, beta-endorphin and ACTH from medullary thyroid carcinoma in vivo and in vitro. 628 16

The biological activity of parathyroid hormone (PTH) has been investigated by measuring intracellular accumulation of cyclic AMP (cAMP) in human kidney cortical cultures. Enzyme dispersed cortical cells from non-invaded kidney poles of patients undergoing nephrectomy for cancer were used after 5 days of primary culture. Bovine PTH (1-84) produced a significant increase of cAMP accumulation in cultured cells at a dose (53.7 ng/ml) 10-fold lower than that found for the minimal stimulatory effect when using preparations of human purified plasma membranes. The action of bovine PTH (1-84) was very rapid, a response was detected after 5 min and a ceiling effect after 30 min. Cortical cells showed a slightly lower sensitivity to synthetic bovine PTH (1-34) (half maximal increase dose: 0.66 microgram/ml), compared to bovine PTH (1-84) (half maximal increase dose: 0.32 microgram/ml), but revealed a higher sensitivity to human PTH purified from the medium of parathyroid cell cultures (half maximal increase dose: 11.2 ng/ml). Arginine-vasopressin (AVP) also increased the cAMP accumulation of kidney cortical cultured cells, with a potency and efficacy lower than that of human 'culture' PTH, while in kidney medullary cells in primary culture AVP exerted a strong response and the effect of PTH was poor or absent. Calcitonin and glucagon were weak stimulators of kidney cortical cell cAMP accumulation.
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PMID:Parathyroid hormone bioassay using human kidney cortical cells in primary culture. 628 83

The endocrine status of 106 patients with undifferentiated small cell carcinoma of the lung was evaluated before treatment was begun. Almost one half of the patients had evidence of abnormal control of the secretion of adrenal cortical steroids, manifested by loss of diurnal rhythmicity or dexamethasone suppressibility. Only two had the clinical syndrome of ectopic ACTH secretion. Evidence of inappropriate secretion of vasopressin was found in 38% of the patients, most of whom also had abnormalities of corticosteroid secretory pattern. About one half of the patients had evidence of abnormal glucose tolerance, and many also had a paradoxical rise of plasma growth hormone concentration after glucose administration. The levels of the other hormones studies were normal. The pattern of hormone abnormality observed in these patients appears to be relatively specific for small cell undifferentiated carcinoma, and is different from that observed in other pulmonary tumors. Patients with abnormal control of plasma cortisol had a worse prognosis than those with normal adrenal function, largely because of decreased response rates to chemotherapy. Other endocrine abnormalities were of no prognostic significance.
Cancer 1982 Nov 15
PMID:Endocrine function in small cell undifferentiated carcinoma of the lung. 629 25

From 1976 to 1980, 18 of the 250 patients (7%) seen with small cell carcinoma of the lung had clinically evident inappropriate secretion of antidiuretic hormone (ADH). Hyponatremia was usually severe (116 +/- 7 meq/l), and eight patients showed symptoms of water intoxication at the time of diagnosis. Of the eight patients who had plasma ADH measured at diagnosis, seven had elevated values (mean 52.0, range 16.1 - greater than 250 pg/ml). Intensive combination chemotherapy produced objective tumor responses in all patients, and syndrome of inappropriate ADH secretion (SIADH) resolved in 16 of 17 evaluable patients within three weeks of initiation of treatment. ADH values after therapy were normal, and all patients maintained a normal serum sodium during the period of tumor remission in spite of unrestricted fluid intake. All 17 evaluable patients have developed progressive cancer, but only 10 have manifested recurrent SIADH. Patient survival was similar to the overall population of small cell carcinoma patients without SIADH. The indirect methods of treatment for SIADH (fluid restriction, demeclocycline, lithium, urea) are frequently of transient value while awaiting a response to chemotherapy or in patients with resistant tumors. However, the initial treatment of choice for SIADH associated with small cell carcinoma of the lung is combination chemotherapy.
Cancer 1983 Jan 01
PMID:Management of the syndrome of inappropriate antidiuretic hormone secretion in small cell lung cancer. 629 92

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.
Cancer Treat Rep 1983 Nov
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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