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)

We have investigated the effects of desmopressin (DDAVP), a synthetic analog of the natural hormone vasopressin, on experimental lung colonization of mammary tumor cells using a syngeneic BALB/c mouse model. Coinjection of DDAVP (1-2 microg/kg body weight) at the time of i.v. inoculation of F3II carcinoma cells or LM3 adenocarcinoma cells significantly inhibited the formation of experimental lung metastases. In both cases, the number of pulmonary nodules was reduced about 70%. Inhibition of metastasis was also obtained with i.v. administration of DDAVP 24 h after tumor cell inoculation. Interestingly, the inhibition of lung metastasis was not due to direct cytotoxic effects of DDAVP on mammary tumor cells. The in vitro formation of multicellular aggregates in the presence of citrated plasma from control and DDAVP-treated mice was also examined. Control plasma rapidly induced a significant tumor cell aggregation. In contrast, in the presence of plasma from DDAVP-treated mice, tumor cells remained as a single cell suspension. DDAVP may help to dissolve the protective fibrin shield of circulating tumor cells. Our data suggest, for the first time, that adjuvant DDAVP therapy may impair successful implantation of circulating mammary tumor cells.
Breast Cancer Res Treat 1999 Oct
PMID:Antimetastatic effect of desmopressin in a mouse mammary tumor model. 1061 3

It is proposed that neuropeptide production by tumours is an important part of a special process of oncogenic transformation rather than a pre-existing condition of progenitor cells; this concept is called Selective Tumour gene Expression of Peptides essential for Survival (STEPS). All small-cell lung cancers and breast cancers evidently express the vasopressin gene, and this gene seems to be structurally normal in all but exceptional cases. Vasopressin gene expression in cancer cells leads to the production of both normal and abnormal forms of tumour vasopressin mRNA and proteins. Although the necessary post-translational processing enzymes are expressed in these cells, most processing seems to be extragranular, and most of the protein products become components of the plasma membrane. Small-cell lung cancer and breast cancer cells also express normal genes for all vasopressin receptors and produce normal vasopressin receptor mRNAs and V1a and V1b receptor proteins, and the vasopressin-activated calcium mobilising (VACM) protein; plus both normal and abnormal forms of the V2 receptor. Through these receptors, vasopressin exercises multifaceted effects on tumour growth and metabolism. A normal protein vasopressin gene promoter seems to be present in small-cell lung cancer cells, and this promoter contains all of the transcriptional elements known to be involved in gene regulation within hypothalamic neurones. Since these elements largely account for regulation of tumour gene expression observed in vitro, it is likely that as yet unknown factors are selectively produced by tumours in vivo to account for the observed seemingly autonomous or unregulated production of hormone in tumour patients. Promoter elements thought to be responsible for selective vasopressin gene expression in small-cell lung cancer probably include an E-box and a neurone restrictive silencer element close to the transcription start site. It is possible that transcription factors acting at these same elements can explain selective vasopressin expression, not only in small-cell tumours, but also in all other tumours such as breast cancer. By extrapolation, similar mechanisms might also be responsible for the expression of additional features that characterize the 'neuroendocrine' profile of these cancers.
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PMID:Gene regulation of vasopressin and vasopressin receptors in cancer. 1079 4

The expression of the three key peptide processing enzyme families, represented by CPE, PAM, and PC1/3 plus PC2, were examined in MCF-7 and ZR-75-1 breast cancer cell lines. Both of these cell lines express vasopressin receptors as well as the vasopressin gene, but the processing of vasopressin gene-related proteins appears to be limited. Products of the expected size for, CPE, PAM and PC1/PC3 could be amplified by reverse transcription-polymerase chain reaction (RT-PCR) from both cell lines. Cloning and sequencing of these RT-PCR products revealed that each enzyme mRNA had a structure identical to that published for the human form of the respective enzyme. Western analysis provided evidence that mRNAs for these enzymes are translated into proteins. Alternatively, PC2 mRNA was identified to be present in MCF-7 cells both by RT-PCR and Western blot analysis, but could not be demonstrated for ZR-75-1 cells. Our findings suggest that the key processing enzymes needed to generate active vasopressin and other neuropeptide growth factors are present in breast cancer cells.
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PMID:Key peptide processing enzymes are expressed by breast cancer cells. 1127 71

A 71-year-old woman showed disorientation 7 days after simple mastectomy for right breast cancer. Computed tomography of the brain was normal. The level of serum sodium was very low (110 mEq/l), while the urine sodium level was normal. The osmolality of urine was higher (342 mosmol/kg) than that of serum (220 mosmol/kg). These data suggested a syndrome of inappropriate secretion of antidiuretic hormone. A fluid restriction, infusion of hypertonic saline and administration of diuretics gradually increased the level of serum sodium. Subsequently, disorientation disappeared. This is a rare case of the syndrome of inappropriate secretion of antidiuretic hormone caused by simple mastectomy, a relatively minor surgical procedure.
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PMID:Breast cancer presenting with the syndrome of inappropriate secretion of antidiuretic hormone after simple mastectomy. 1157 42

We previously found that expression of the vasopressin gene is a common feature of human breast cancer. In the present study we first examined 21 different cases of benign fibrocystic breast disease for vasopressin expression using immunohistochemistry and antibodies directed against vasopressin (anti-VP) and against vasopressin-associated glycopeptide (anti-VAG). All cases examined were negative for vasopressin gene expression using these antibodies. Alternatively, we examined 16 cases of breast ductal carcinoma in situ (DCIS) using the second of these antibodies (anti-VAG), and all of these cases were positive for vasopressin gene expression. Our results suggest that products of vasopressin gene expression are not markers of cellular proliferation in the breast, and might rather represent an early part of the carcinogenic process in this tissue.
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PMID:Immunohistochemical evaluation of vasopressin expression in breast fibrocystic disease and ductal carcinoma in situ (DCIS). 1458 71

The purpose of this study was to define the maximal tolerated dose (MTD), extramedullary toxicities, and pharmacokinetics of docetaxel combined with high-dose melphalan and carboplatin with autologous hematopoietic progenitor cell support. Fifty-nine patients with advanced refractory malignancy (32 breast cancer, 10 non-Hodgkin lymphoma, 6 germ cell tumors, 4 Hodgkin disease, 4 ovarian cancer, 2 sarcoma, and 1 unknown primary adenocarcinoma) with a median of 3 prior chemotherapy regimens and a median of 3 organs involved were enrolled. Treatment included docetaxel (150-550 mg/m2 infused over 2 hours on day -6), melphalan (150-165 mg/m2 infused over 15 minutes from day -5 to -3), and carboplatin (1000-1300 mg/m2 as a 72-hour continuous infusion from day -5). Five patients died from direct regimen-related organ toxicity (2 capillary leak syndrome, 2 enterocolitis, and 1 hepatic toxicity), and 1 additional patient died from pulmonary aspergillosis. The docetaxel MTD was defined as 400 mg/m 2 , combined with melphalan (150 mg/m2 ) and carboplatin (1000 mg/m2 ). The MTD cohort was expanded to enroll a total of 26 patients, 1 of whom died from toxic enterocolitis. The remaining 25 patients presented the following extramedullary toxicity profile, which was manageable and largely reversible: stomatitis, myoarthralgias, peripheral neuropathy, gastrointestinal and cutaneous toxicities, and syndrome of inappropriate antidiuretic hormone secretion. Docetaxel exhibited linear pharmacokinetics in the dose range tested (150-550 mg/m2 ). Pharmacodynamic correlations were noted between the docetaxel area under the curve and peripheral neuropathy or stomatitis. The response rate among 38 patients with measurable disease was 95%, with 47% complete responses. At a median follow-up of 26 months (range, 7-72 months), the 3-year event-free survival and overall survival were 26% and 36%, respectively. In conclusion, a 4-fold dose escalation of docetaxel, combined with melphalan and carboplatin, is feasible with autologous hematopoietic progenitor cell support. The notable activity of this regimen in treatment-refractory patients warrants its further evaluation.
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PMID:Phase I and pharmacokinetic study of docetaxel combined with melphalan and carboplatin, with autologous hematopoietic progenitor cell support, in patients with advanced refractory malignancies. 1581 95

Desmopressin (DDAVP) is a synthetic vasopressin analog capable of inducing an increase in the plasma levels of von Willebrand factor and coagulation factor VIII. DDAVP has been used during surgery to prevent bleeding in patients with coagulation defects. We have previously demonstrated that adjuvant perioperative DDAVP therapy inhibits lung and lymph node metastasis in a breast cancer model. Here the effect of DDAVP on experimental lung colonization of B16 melanoma cells was investigated in a transgenic mice model with high levels of tissue inhibitor of metalloproteinases-1 (TIMP-1) in the systemic circulation. Transgenic C57BL/6j-CBA mice overexpressing human TIMP-1 in the liver under the control of the mouse albumin promoter/enhancer were employed. Treatment with DDAVP (2 microg/kg/dose) at the time of intravenous injection of B16 cells significantly inhibited the formation of lung metastases in TIMP-1 transgenic animals (p = 0.021), while no significant effect was obtained in control hybrid mice. The inhibition was not due to direct cytotoxic effects of DDAVP on tumor cells and no expression of vasopressin receptors was detected in B16 cells. Our data indicate that DDAVP therapy may impair successful implantation of circulating melanoma cells and suggest that high levels of circulating TIMP-1 display a cooperative role in the antitumor activity of the compound.
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PMID:Desmopressin reduces melanoma lung metastasis in transgenic mice overexpressing tissue inhibitor of metalloproteinases-1. 1720 83

The anti-estrogenic drug tamoxifen, which is used therapeutically for treatment and prevention of breast cancer, can lead to the development of thrombosis. We found that tamoxifen rapidly increased intracellular free calcium [Ca2+]i in human platelets from both male and female donors. Thus 10 microM tamoxifen increased [Ca2+]i above the resting level by 197 +/- 19%. Tamoxifen acted synergistically with thrombin, ADP, and vasopressin to increase [Ca2+]i. The anti-estrogen ICI 182780 did not attenuate the effects of tamoxifen to increase [Ca2+]i; however, phospholipase C inhibitor U-73122 blocked this effect. 4-hydroxytamoxifen, a major metabolite of tamoxifen, also increased [Ca2+]i, but other tamoxifen metabolites and synthetic derivatives did not. Three hydroxylated derivatives of triphenylethylene (corresponding to the hydrophobic core of tamoxifen) which are transitional structures between tamoxifen (Ca agonist) and diethylstilbestrol (Ca antagonist) increased [Ca2+]i slightly (6% to 24%) and partially inhibited thrombin-induced [Ca2+]i elevation (68% to 79%). Therefore the dimethylaminoethyl moiety is responsible for tamoxifen being a Ca agonist rather than antagonist. 4-Hydroxytamoxifen and polymer-conjugated derivatives of 4-hydroxytamoxifen increased [Ca2+]i, with similar efficacy. The ability of tamoxifen to increase [Ca2+]i in platelets, leading to platelet activation, and its ability to act synergistically with other platelet agonists may contribute to development of tamoxifen-induced thrombosis.
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PMID:Tamoxifen stimulates calcium entry into human platelets. 1804 5

The electrolyte imbalance in advanced cancer patients, including hyperkalemia, hypercalcemia and hyponatremia, can be induced by various factors. Hyperkalemia is occasionally induced by chemotherapy for very large malignant tumors, due to tumor lysis syndrome. Hypercalcemia and hyponatremia are often observed in patients with breast cancer, renal cancer, prostate cancer, and the like, as a paraneoplastic syndrome. Some part of hypercalcemia results from osteolysis, but the majority is induced by hormonal factors, such as parathyroid hormone-related protein. One of the paraneoplastic causes of hyponatremia is antidiuretic hormone-producing tumor. These disorders could be morbid or even motile, resulting from encephalopathy or arrhythmia in some cases. However, it should be kept in mind that they could be improved or cured by prompt treatment. Recently, after approval of the molecular targeted drugs for epidermal growth factor receptors, such as cetuximab and panitumumab, the incidence of hypomagnesia with use of these monoclonal antibodies, is relatively frequent. In addition, small molecular targeted drugs, such as m-TORinhibitors and ABL kinase inhibitors, also exert adverse reactions including hypomagnesia and hypophosphatemia. Careful monitoring of the serum concentration of magnesium and phosphate ions, to which little attention was paid previously, is a key issue in these cases.
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PMID:[Cancer and electrolytes imbalance]. 2056 1

A case of brain metastasis from peritoneal serous surface papillary carcinoma (SSPC) was reported. This 68-year-old woman was admitted to our department because of decreased consciousness level for the last few days. Her medical past history revealed breast cancer and SSPC of the peritoneum at the age of 64. On admission she was comatose and irritable. Serum and urine examination revealed the syndrome of inappropriate secretion of antidiuretic hormone that was treated with strict restriction of water intake. MRI of the brain demonstrated a nonspecific mass in the subcortical area of the right superior parietal lobule. The mass was successfully removed in en bloc fashion. Pathological diagnosis was SSPC that was compatible with the previous diagnosis obtained from the peritoneum four years previously. Although the patient received whole brain radiation therapy postoperatively, her condition deteriorated rapidly. She died four months after brain surgery. SSPC of the peritoneum is a rare malignant tumor that is defined as a primary tumor histologically indistinguishable from serous carcinoma of the ovary, diffusely involving the peritoneal surface but sparing or only superficially invading the ovaries. Because of the prolongation of survival resulting from advanced chemotherapy for SSPC of the peritoneum, more patients live long enough to develop brain metastasis. Therefore, SSPC of the peritoneum should be kept in mind in the differential diagnosis of a primary site for brain metastasis.
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PMID:[A case of serous surface papillary carcinoma of the peritoneum metastatic to the brain]. 2162 41


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