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)

In the concluding section of this review of cancer destruction by disruption of energy metabolism, the cellular mechanism for interfering with energy production is considered in terms of drug resistance arising independently of previous tumor injury. The occurrence of various degrees of damage to cancerous growths as a consequence of secondary shock is interpreted on the basis of elevated levels of stress hormones, including vasopressin, which have earlier been shown to interfere with energy metabolism in a murine sarcoma. Similarly, the indirect action of various antineoplastic procedures can be related to a role for the endocrine system, with particular reference to vasopressin and inappropriate anti-diuretic hormone secretion syndrome. Multiple drug resistance is also discussed, and the mode of action of the topoisomerase inhibitor doxorubicin is critically examined. The basis of selectivity of disruption of energy metabolism by substances such as hydralazine and L-isoproterenol is discussed from the viewpoint of altered activities of antioxidant enzymes in transformed cells, but these considerations alone are not thought to be sufficient to account for the highly specific nature of the antineoplastic action. Conversely, antioxidant enzymes, more especially those concerned with glutathione metabolism, probably play a major role in multiple drug resistance, although in this respect the case of autoxidative cellular injury awaits attention. Theoretical strategies for the intensification of tumor injury include the aim of prolonging the half-lives of lysophosphatides within damaged tissue. Whereas the clinical application of the principle of tumor destruction through selective disruption of energy metabolism is at present compromised for lack of information, the use of phenothiazines as antineoplastic agents is feasible, and awaits serious exploitation. The relative lack of incapacitating side-effects of phenothiazines should provide an attractive change for the clinical oncologist.
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PMID:Cancer destruction in vivo through disrupted energy metabolism. Part III. Spontaneous drug resistance, selectivity of antineoplastic action, and strategies for intensifying tumor injury. 146 33

Vasoactive drugs have a variety of effects upon splanchnic and hepatic haemodynamics which may alter tumour blood flow and potentiate the delivery of a chemotherapeutic drug to hepatic tumour. We have investigated the effects of vasopressin infusion on hepatic tumour blood flow in an experimental model of liver tumour. Hepatic tumour was induced by the intraportal inoculation of HSN sarcoma cells. Hepatic and splanchnic blood flow was determined using a dual reference microsphere technique before and after an intravenous infusion of vasopressin at a dose of 0.1 mU kg-1 min-1 for 10 min. There was a significant increase in systemic arterial blood pressure associated with a rise in portal venous inflow (P less than 0.01, Wilcoxen Signed rank Test) and a significant fall in hepatic arterial flow (P less than 0.05). The tumour: liver blood flow ratio was significantly increased by vasopressin infusion (P less than 0.02). Vasopressin infusion decreases hepatic arterial flow and increases tumour blood flow which may potentiate the delivery of a regionally delivered chemotherapeutic drug to hepatic tumour.
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PMID:The effects of vasopressin infusion on hepatic haemodynamics in an experimental model of liver metastases. 189 47

Calf serum induced the phospholipase C-mediated hydrolysis of phosphoinositides in normal rat kidney (NRK) cells transformed by a temperature-sensitive Kirsten murine sarcoma virus (tsK-NRK cells). Various growth factors known to induce the phospholipase C reactions in other cell types, such as platelet-derived growth factor, fibroblast growth factor, epidermal growth factor, thrombin, vasopressin, bombesin, cholecystokinin, and prostaglandin F2 alpha, did not induce phospholipase C reactions in the transformed NRK cells. Furthermore, noradrenaline, histamine, dopamine, angiotensin II, carbachol, and tumor growth factor-beta did not induce phospholipase C reactions. However, serotonin did induce phospholipase C reactions. The amount of serotonin contained in the calf serum was sufficient to support 50% of the activity promoted by the serum itself, and calf serum-induced phospholipase C reactions were inhibited to 10-20% of the original level by ketanserin and methysergide, known to be antagonists for the serotonin receptors. Dialysis almost completely removed serotonin from calf serum and reduced the serum-induced phospholipase C reactions. Moreover, the phospholipase C reactions induced by calf serum and serotonin were inhibited by pretreatment of the cells with pertussis toxin or 12-O-tetradecanoylphorbol-13-acetate. These results indicate that serotonin is one of the major serum factors inducing phospholipase C-mediated hydrolysis of phosphoinositides in transformed NRK cells. Serotonin induced phospholipase C reactions not only in tsK-NRK cells but also in nontransformed NRK cells. However, serotonin did not induce these reactions in Swiss 3T3 cells or NIH 3T3 cells.
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PMID:Serotonin as a major serum factor inducing the phospholipase C-mediated hydrolysis of phosphoinositides in normal rat kidney cells. 284 56

Four subclones of the originally cloned Harvey murine sarcoma virus-transformed Madin Darby canine kidney (MDCK) cells have been isolated. These subclones fall into two general classes. Two subclones have a fibroblastic morphology, have lost the growth requirement for prostaglandin E1 (PGE1), do not respond to glucagon or vasopressin, and, in general, appear transformed. Two other subclones have epithelioid morphologies, are growth-stimulated by PGE1, respond to vasopressin with an increase in intracellular cAMP. We propose that these cells represent revertants to a more non-transformed phenotype. Unlike normal cells, however, these revertants grow under anchorage-independent conditions, express detectable but reduced amounts of the transforming gene product, p21, and grow in nude mice. The appearance of such revertants may be one cause of the observed heterogeneity of tumor cells.
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PMID:Revertants of Ha-MuSV-transformed MDCK cells express reduced levels of p21 and possess a more normal phenotype. 300 21

A kidney cell line (MDCK) retains an adenylate cyclase system sensitive to glucagon, vasopressin, isoproterenol and prostaglandin E1. The stimulatory effect of glucagon on cAMP production was selectively lost in a cloned line derived from MDCK cells transformed by Harvey murine sarcoma virus. Sensitivity to glucagon was largely restored by treatment of the transformed cells with prostaglandin E1 or butyrate. Loss and reappearance of glucagon receptors seemed to be responsible for the observation. The parental MDCK line produced prostaglandins and in the transformed line, this function was abolished. These observations suggest that synthesis of glucagon receptors is controlled by endogenously produced prostaglandin in MDCK cells and that loss of glucagon receptors and their responsiveness in the transformed cells occurs as a consequence of the inability of these cells to synthesize this prostaglandin.
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PMID:Loss and restoration of glucagon receptors and responsiveness in a transformed kidney cell line. 629 63

Several angiogenic preparations that have been shown to stimulate plasminogen activator (PA) and collagenase production by cultured bovine capillary endothelial (BCE) cells were tested for their ability to stimulate BCE cell motility in the phagokinetic track assay. Bovine retinal extract, medium conditioned by 3T3-F442A differentiated mouse adipocytes, SK HEP-1 human hepatoma cell lysate, mouse sarcoma 180 cell lysate, and medium conditioned by mouse sarcoma 180 cells stimulated motility 68.7%, 48.5%, 140.9%, 56.5%, and 102.1%, respectively, relative to untreated cells. The motility-stimulating activity of these preparations was dose dependent and linear over the 16-h assay period. Several hormones and growth factors were tested for BCE cell motility-stimulating activity, including insulin, vasopressin, fibroblast growth factor, and a partially purified preparation of sarcoma growth factor, and were found to be ineffective. 12-0-tetradecanoyl-phorbol-acetate (TPA), a potent stimulator of both PA and collagenase activities in BCE cells, also did not stimulate motility, indicating that protease production is not sufficient to stimulate BCE cell motility in this assay. Neither SK HEP-1 hepatoma cell lysate nor TPA was effective in stimulating motility in bovine aortic endothelial (BAE) cells. The inability of SK HEP-1 hepatoma cell lysate to stimulate movement in BAE cells is consistent with the observation that angiogenesis occurs by sprouting of capillaries, not large vessels.
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PMID:Stimulation of motility in cultured bovine capillary endothelial cells by angiogenic preparations. 632 76

We have observed that the tyrosine kinase inhibitors genistein and tyrphostin can selectively block angiotensin II mediated and vasopressin-mediated contractions in porcine coronary arterial strips, without affecting the action of acetylcholine. Therefore, we assessed the presence of tyrosine kinase activity in the porcine coronary artery tissue, using an assay specific for sarcoma virus (src) related tyrosine kinases. In both membrane and cytosolic fractions of porcine coronary artery, we detected src-related tyrosine kinase activity that could be inhibited by both genistein and tyrphostin. The tyrosine kinase activity in membrane extracts was separated into two peaks by sequential chromatography on hydroxylapatite and Mono-Q columns. Protein in both peaks exhibited Western blot cross-reactivity with anti-src antibodies and contained tyrosine kinase activity that was inhibited by genistein and tyrphostin. We conclude that porcine coronary artery tissue contains src-related tyrosine kinase activity. However, because of the comparatively low sensitivity of the isolated src kinase activity towards genistein and tyrphostin, compared with the much higher sensitivity of the contractile response to these inhibitors, a direct role for c-rsc in the regulation of contractions elicited by agonists such as angiotensin II and arginine vasopressin cannot yet be assigned.
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PMID:Detection of sarcoma virus family tyrosine kinase activity in coronary arterial tissue. 878 7

In a minority of patients with malignant tumors, signs and symptoms develop that cannot be explained on the basis of the mass effect produced by the primary tumor or its metastases, or production of a hormone normally associated with the tissue type that has given rise to the malignant tumor; these peculiar symptom complexes are known as paraneoplastic syndromes, and may be divided into endocrinologic, dermatologic, hematologic, neurologic, and osteoarticular manifestations. In the head and neck region in particular, the syndrome of inappropriate antidiuretic hormone production (SIADH, or Schwartz-Bartter syndrome) is a well-recognized form of paraneoplastic syndrome that may accompany head and neck malignancies. Most of such tumors are squamous carcinomas, with lesser numbers of olfactory neuroblastomas, small cell neuroendocrine carcinomas, adenoid cystic carcinomas, and undifferentiated carcinomas; sarcoma was reported in only a single instance. The lesions associated with the development of SIADH have most often been located in the oral cavity, and less often in the larynx, nasopharynx, hypopharynx, nasal cavity, maxillary sinus, parapharyngeal space, salivary glands, and oropharynx. Key features of SIADH include serum hypo-osmolality; an unexpectedly high urinary specific gravity; an absence of edema or dehydration; normal adrenal, thyroid, and renal function; hyponatremia; and an elevation of plasma vasopressin.
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PMID:Syndrome of inappropriate antidiuretic hormone secretion associated with head neck cancers: review of the literature. 934 88

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

We report a case of intracranial germ cell tumor that showed pathological changes from neurohypophyseal germinoma to mixed germ cell tumors consisting exclusively of undifferentiated sarcomatous component after radiochemotherapy. Three surgical specimens and autopsied brain from the patient were histologically examined. An initial specimen from the neurohypophyseal tumor was diagnosed as germinoma with a two-cell pattern. Five years later, after repeated radiochemotherapy, the second specimen resected from the right temporal lobe showed mixed germ cell tumors consisting of the three components of germinoma, choriocarcinoma, and immature teratoma. Six months later after intensive radiotherapy, the right temporal tumor recurred and was surgically removed. The histological diagnosis was mixed germ cell tumors with abundant immature teratoma component. The patient died of uncontrollable tumor growth with repeated intratumoral hemorrhages. The autopsied brain showed sarcoma with angionecrosis. This pathological alteration indicated an increase in the sarcomatous component after undergoing various treatments. We discuss the histological changes of intracranial germ cell tumor modified by treatment.
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PMID:Mixed germ cell tumors with abundant sarcomatous component in the temporal lobe after radiochemotherapy of neurohypophyseal germinoma: a case report. 1809 24


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