Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitoxantrone is an anthracene derivative that acts as a cytostatic in a variety of cancers. A quantitative analytical method has been established for the determination of mitoxantrone in plasma. The method employed C18 reversed-phase ion-pair chromatography with an isocratic mobile phase of 50.0% methanol in 10 mM phosphate buffer (pH 3.0) plus 0.09% 1-pentanesulphonic acid and ultraviolet detection. Sample preparation consisted of two extraction steps using same organic solvent system at different pH to remove plasma impurities efficiently. Potential adsorption of mitoxantrone onto glassware was considered. Silanization of all glassware with 5% dichlorodimethylsilane in chloroform increased the extraction recovery in plasma from 50 to 85% with high reproducibility. Mitoxantrone was unstable in human plasma. To maintain plasma sample integrity, each millilitre of sample should be fortified with 0.1 ml of 5% vitamin C (in citrate buffer) and kept frozen until analysis. Using this new method, the calibration curve of mitoxantrone in plasma in the range of interest (1-500 ng/ml) showed good linearity (r = 0.996) and precision (both between-day and within-day coefficients of variation less than 10%). The lower detection limit of this assay method was 1 ng. The application of this method allowed us to study the stability of mitoxantrone in plasma, and the pharmacokinetics of mitoxantrone in nasopharyngeal carcinoma patients receiving 12 mg/m2. The study revealed a prolonged terminal phase half-life for mitoxantrone.
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PMID:Novel assay method for mitoxantrone in plasma, and its application in cancer patients. 208 30

In vitro and in vivo studies with N,N',N''-triethylene-thiophosphoramide (thiotepa) alone and in combination with cyclophosphamide (CTX) were carried out using the MCF-7 human breast carcinoma cell line and the EMT6 mouse mammary carcinoma cell line. In vitro, survival curves were essentially linear. The cytotoxicity of thiotepa toward MCF-7 cells was markedly dependent on the presence of oxygen during the period of drug exposure, with a 3-log greater cell kill at 500 mumol with cells that were normally oxygenated compared with hypoxic cells. Incubation of thiotepa with an Aroclor 1254-induced rat liver S-9 homogenate in the presence of a reduced nicotinamide adenine dinucleotide phosphate-regenerating system resulted in an eightfold increase in cytotoxicity toward the MCF-7 cells over a wide range of drug concentrations. The thiotepa metabolite N,N',N''-triethylenephosphoramide (TEPA) was significantly less cytotoxic toward the MCF-7 cells than was thiotepa. Simultaneous and immediately sequential treatments with thiotepa and CTX produced supra-additive cell killing of both cell lines, although the magnitude of the supra-additivity was greater in the MCF-7 cell line than in the EMT6 cell line. These drugs Vppeared to be equally effective as thiol-depleting agents. By DNA alkaline elution, there was a pattern of increasing DNA cross-linking similar to the increasing levels of cytotoxicity of this drug combination as the concentrations of thiotepa increased. In the EMT6 tumor in vivo, the maximally tolerated combination therapy (5 mg/kg x 6, thiotepa, and 100 mg/kg x 3, CTX) produced about 25 days of tumor growth delay, which was not significantly different than expected for additivity of the individual drugs. The survival of EMT6 tumor cells after treatment of the animals with the various single doses of thiotepa and CTX was assayed. Tumor cell killing by thiotepa produced a very steep, linear survival curve through 5 logs with increasing dose. The tumor cell survival cure for CTX to 500 mg/kg had linear tumor cell kill through almost 4 logs. In vivo modeling of quasicontinuous exposure (3 intraperitoneal over 9 hours) versus pulse (single-dose) administration of thiotepa and CTX compared EMT6 tumor cell survival with survival of bone marrow as a representative sensitive normal tissue. With CTX, there was a considerable increase in the therapeutic index (killing of tumor cells/killing of colony forming units-granulocyte macrophage) when the same total dose of drug was administered in multiple injections versus a single injection. For thiotepa, smaller increases in therapeutic index were also observed with the multiple-injection schedule.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Preclinical studies relating to the use of thiotepa in the high-dose setting alone and in combination. 210 64

Patients with prostatic carcinoma on oral oestrogen therapy have an altered coagulation system and suffer cardiovascular side effects. Oestrogens--especially oral oestrogens--are potent inducers of liver synthesised proteins, including coagulation factors. We have assessed the effect of non-oral oestrogen on the coagulation system in patients with prostatic carcinoma. Twelve patients were given monthly intramuscular injections of 320 mg polyoestradiol phosphate (PEP). No additional oestrogens were given. No change was found in any of the coagulation factors, including factor VII, with the exception of a significant decrease in antithrombin III. No patient, including 38 patients treated with PEP, had any cardiovascular complications after a mean follow-up period of 12.9 +/- 0.7 months; 76% of the patients responded to treatment. Parenteral administration of oestrogen caused a less marked change in the coagulation system than oral administration and should be the treatment of choice for prostatic carcinoma.
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PMID:Effect of parenteral oestrogen on the coagulation system in patients with prostatic carcinoma. 211 Aug 42

A new hepatobiliary contrast agent (Mn-DPDP) was used in the detection of liver metastases in six rabbits with seven hepatic V2 carcinomas. This contrast agent is derived from pyridoxyl-5-phosphate which is biomimetically designed to be secreted by the hepatocyte. After Mn-DPDP administration, a 105% increase in liver signal to noise was obtained using a 200/20 (TR/TE) pulsing sequence, and a 62% decrease in intensity was observed using a 1200/60 pulsing sequence. Liver V2 carcinoma contrast enhancement increased 427% using the 200/20 pulsing sequence and 176% using the 1200/60 pulsing sequence. Four of seven V2 carcinomas were not detectable prior to the administration of Mn-DPDP (50 mumol/kg). Two neoplasms were only detectable in retrospect (after Mn-DPDP) on the 1200/60 sequence. The smallest neoplasms detected in this study were 1-4 mm. Mn-DPDP appears to be a promising MRI contrast agent.
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PMID:Detection of hepatic malignancies using Mn-DPDP (manganese dipyridoxal diphosphate) hepatobiliary MRI contrast agent. 211 11

Thyrotoxicosis may be held responsible for osteoporosis. The question is whether a very slight subclinical hyperthyroidism, as is desirable in the post-operative treatment of differentiated thyroid carcinoma, can in the long run be detrimental to bone tissue. In a series of 37 patients, aged 50.9 +/- 11.1 years, presenting with the features of subclinical hyperthyroidism of 8.0 +/- 4.8 years duration, the authors have been unable to find any change in paraclinical parameters of bone and calcium-phosphate metabolism. Thirty-six of these 37 patients showed no abnormal decrease of vertebral bone density measured by dual photon absorptiometry.
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PMID:[Bone density after iatrogenic subclinical long-term thyrotoxicosis. Measurement by dual photon absorptiometry]. 214 86

Receptor-mediated regulation of the sodium-phosphate symporter, and hence sodium-dependent phosphate uptake, typically relates to epithelial cells of renal origin. In this study we have characterized sodium-dependent phosphate uptake and aspects of its receptor-mediated regulation in the HeLa cell line, a cell line derived from a human epithelioid carcinoma. Phosphate uptake (greater than 90% sodium dependent; Vmax = 4.02 +/- 0.24 nmol.mg and Km = 0.11 +/- 0.02 mM phosphate at 140 mM sodium) was kinetically similar to that observed in opossum kidney cells. Incubation with vasoactive intestinal peptide (VIP) resulted in a dose-dependent (50% maximal dose of 8.8 +/- 3.6 nM) approximately fivefold increase in basal adenosine 3',5'-cyclic monophosphate (cAMP) levels (basal = 14.6 +/- 1.7 pmol.mg protein-1.15 min-1; VIP stimulated = 72.7 +/- 13.2 pmol.mg protein-1.15 min-1), as well as a dose-dependent maximal 32.6 +/- 5.5% decrease in sodium-dependent phosphate uptake (50% maximal decrease of 46.2 +/- 21.2 nM). The VIP-induced decrease in phosphate uptake was due to decrease in maximal transport (VmaxVIP = 2.78 +/- 0.16 nmol.mg protein-1.3 min-1) and not to a change in the affinity of the transporter for phosphate (KmVIP = 0.11 +/- 0.01 mM phosphate). Preincubation of HeLa cells with forskolin and cholera toxin, which stimulate adenylate cyclase, resulted in dose-dependent decreases in sodium-dependent phosphate uptake. Incubation with 8-bromo-cAMP and dibutyryl cAMP, permeant analogues of cAMP, similarly resulted in a dose-dependent decrease in sodium-dependent phosphate uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HeLa cells express cAMP-inhibitable sodium-dependent phosphate uptake. 215 43

We treated a patient in whom a hepatocellular carcinoma and a hyperplastic nodule of the liver concomitantly grew in association with long term phosphate diethylstilbestrol therapy for a carcinoma of the prostate. A 72-year-old Japanese man was admitted for investigation of hepatic masses. A diagnosis of prostate carcinoma had been made seven years ago and phosphate diethylstilbestrol 200 mg daily had been prescribed. A small mass was first detected in the liver four years later and another mass appeared three years after the appearance of the first mass. Histology of the excised tissue showed the former mass to be a hyperplastic nodule and the latter one hepatocellular carcinoma. Findings of cirrhosis, hepatitis or fibrosis were nil but fatty metamorphosis of the hepatocytes was apparent. These histological changes were considered to be associated with long-term phosphate diethylstilbestrol therapy therefore careful follow-up using amazing diagnosis is recommended for patients on phosphate diethylstilbestrol therapy.
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PMID:Association of hepatocellular carcinoma and a hyperplastic nodule after phosphate diethylstilbestrol therapy. 216 76

The regulation of phospholipase C has been investigated in both intact and streptolysin-O permeabilized human HeLa carcinoma cells. Stimulation of phospholipase C by histamine and guanosine-5'-O-thiotriphosphate (GTP[S]) requires the presence of at least 10 nM free Ca2+, but is not significantly further increased by raising [Ca2+]i to greater than 10(-6) M. The pH optimum of the inositol phosphate response is at pH 6.8, while small changes in intracellular pH, as occur during hormonal stimulation (0.2-0.4 unit) attenuate the histamine/GTP[S]-induced stimulation of phospholipase C. Increasing cellular cAMP levels, either through addition of cell permeable cAMP analogues to intact cells or by stimulation with isoproterenol, does not affect histamine responsiveness, arguing against cross-talk between both signalling pathways. In contrast, we found that the response to histamine and/or GTP[S] is largely inhibited after brief pretreatment of the cells with phorbol esters or synthetic diacylglycerol prior to permeabilization, suggesting that protein kinase C exerts feedback inhibition at the level of, or downstream from, the putative GTP-binding protein.
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PMID:Regulation of phosphoinositide hydrolysis induced by histamine and guanine nucleotides in human HeLa carcinoma cells. Calcium and pH dependence and inhibitory role of protein kinase C. 216 83

Eighty six consecutive thallium-technetium subtraction parathyroid scans performed over a three year period for hypercalcaemia have been evaluated. Twelve had chronic renal failure, 11 had hypercalcaemia due to non-hyperparathyroid causes and in 10 the imaging study was technically inadequate. The remaining 53 technically adequate studies performed for hypercalcaemia clinically thought to be possibly due to hyperparathyroidism have been analysed. Of 20 (38%) positive scans, 13 came to surgery (10 correctly localized parathyroid adenomas, 2 with multiple gland hyperplasia, and 1 papillary carcinoma of the thyroid). Of 33 (62%) negative scans, 9 had surgical exploration on the basis of strong clinical grounds and all had parathyroid adenomas. Multiple biochemical parameters have been assessed in relation to a positive outcome on scan. The adjusted calcium-phosphate product and the ratio of the adjusted calcium-phosphate product to creatinine (Ca x P/Cr) were both significantly lower in the scan positive group (P less than 0.01). The scan positive group had a significantly higher mean level of PTH (P less than 0.001) and lower mean level of phosphate (P less than 0.001). The present experience shows that parathyroid imaging is useful in localizing parathyroid adenomas in 50% of cases (10 out of 19). This figure is at the lower end of the range of previously published results. It is less effective in demonstrating multiple gland hyperplasia. The decision as to whether to undertake surgical exploration when the scan is negative has been based successfully on clinical judgement. We feel that an analysis of this nature is important, as it gives insights into the practical relevance of parathyroid imaging in the context of routine clinical work.
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PMID:A clinical audit of thallium-technetium subtraction parathyroid scans. 217 Sep 59

The effects of parenterally given polyestradiol phosphate (80 or 160 mg i.m. monthly) and bilateral subcapsular orchiectomy on blood coagulation and fibrinolytic parameters were compared in 11 patients with prostatic carcinoma. Estrogen therapy lowered antithrombin III, plasminogen and plasminogen activator inhibitor activities, whereas these parameters remained unchanged in orchiectomized patients. There were no significant changes in platelet count, fibrinogen, factor VII, protein C and alpha 2-antiplasmin in either group. Estrogen had unfavorable effects on hemostatic laboratory parameters in the direction of a hypercoagulable state. However, no thromboembolic complications were encountered.
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PMID:The effect of parenteral estrogen versus orchiectomy on blood coagulation and fibrinolysis in prostatic cancer patients. 217 41


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