ABSTRACT
INTRODUCTION: The association between dermatomyositis and cancer is clearly established, but its frequency remains difficult to define. EXEGESIS: We report the case of an association between a dermatomyositis and a cancer of the piriform antrum. Four months after surgical treatment and radiotherapy, the increased macro-CK level gave us reason to suspect a cancer relapse with pulmonary, hepatic, splenic and renal metastases without progressive clinical signs. CONCLUSION: Mitochondrial macro-CK detection must evoke the presence of neoplasia with or without metastasis, which would be a poor prognosis, as has been shown in our patient.
Subject(s)
Carcinoma, Squamous Cell/diagnosis , Creatine Kinase/blood , Dermatomyositis/complications , Pharyngeal Neoplasms/diagnosis , Carcinoma, Squamous Cell/blood , Humans , Macromolecular Substances , Male , Middle Aged , Pharyngeal Neoplasms/bloodABSTRACT
Cultured rat aortic smooth muscle cells (SMC) metabolize 12(S)hydroxyeicosatetraenoic acid (12(S)HETE) by two different pathways; beta-oxidation leading to 16:3(8-OH), and 10-11 reductase activity producing 20:3(12-OH) which is beta-oxidized to 16:2(8-OH). In this work, we demonstrate that 10-11 reductase activity is modulated in cultured rat aortic SMC as a function of cell state (proliferating vs quiescent) and stimulated by serum. Most of the 20:3(12-OH) is recovered in the incubation medium but a significant part is esterified into phospholipids. By comparison with its parent compound, 12(S)HETE, 20:3 (12-OH) is mainly incorporated into phosphatidyl-choline and phosphatidyl-ethanolamine, suggesting that it may affect cellular functions. Taken together, these findings may be relevant to the effects of 12(S)HETE on vascular SMC functions related to atherosclerotic development.
Subject(s)
Hydroxyeicosatetraenoic Acids/metabolism , Muscle Proteins/metabolism , Muscle, Smooth, Vascular/drug effects , Oxidoreductases/metabolism , 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid , Animals , Aorta , Blood Physiological Phenomena , Cattle , Cell Division , Cells, Cultured , Chromatography, High Pressure Liquid , Culture Media/pharmacology , Membrane Lipids/metabolism , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/metabolism , Phospholipids/metabolism , RatsABSTRACT
Fatty acid profiles of various lipid fractions were determined in carefully selected insulin-dependent and non-insulin-dependent diabetics to assess relationships between serum fatty acid composition and type of diabetes. Clear-cut hypertriglyceridemia with slight hypercholesterolemia was found in both diabetic types. The decrease of lignoceric acid in sphingomyelin is the only alteration found in both types of diabetes. In the insulin-dependent diabetics, there were increases in levels of oleic acid and of alpha-linolenic acid in esterified cholesterol, and in levels of alpha-linolenic acid in the triglyceride fraction. In the non-insulin-dependent diabetics, there were increases in levels of oleic acid and total monounsaturated fatty acids in the triglyceride fraction and there was an increase in levels of saturated fatty acids and a decrease in levels of polyunsaturated acids in phosphatidylcholine; in sphingomyelin, dihomogamma-linoleic acid levels were enhanced. Arachidonic acid levels were normal in our patient population.
Subject(s)
Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 2/blood , Fatty Acids/blood , Adult , Aged , Cholesterol/blood , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 2/metabolism , Fatty Acids/metabolism , Female , Humans , Male , Middle Aged , Phosphatidylcholines/blood , Sphingomyelins/blood , Triglycerides/bloodABSTRACT
12(S)-HETE, a major lipoxygenase-derived compound from arachidonic acid is incorporated and metabolized by vascular smooth muscle cells via beta-oxidation. We have now identified for the first time in this cell type 12(S)-HETE metabolites formed by a combination of reductase and oxidation pathways. HPLC and GC-MS analysis of time-course experiments allow us to characterize two different metabolic pathways: a direct peroxisomal beta-oxidation of 12(S)-HETE leading to the formation of 16:3 (8-OH) which accumulates first and a reduction of one of the conjugated double bonds of 12(S)-HETE giving the dihydro-intermediate 20:3(12-OH) that transiently accumulates before being converted itself by peroxisomal beta-oxidation to 16:2(8-OH). Taken together these results may suggest that the transient accumulation of 20:3(12-OH) through transcellular metabolism of 12(S)-HETE may represent a part of the modulatory effect of 12(S)-HETE on vascular function.
Subject(s)
Hydroxyeicosatetraenoic Acids/metabolism , Muscle, Smooth, Vascular/metabolism , 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid , Animals , Aorta, Thoracic/cytology , Aorta, Thoracic/metabolism , Cells, Cultured , Gas Chromatography-Mass Spectrometry , Lipids/isolation & purification , Male , Muscle, Smooth, Vascular/cytology , Phospholipids/biosynthesis , Rats , Rats, WistarABSTRACT
The hydroxylated derivatives of polyunsaturated fatty acids may be potent modulators of basic biological responses involved in pathological processes, including atherosclerosis. The object of the present investigation was to study the effects of monohydroxylated fatty acids (namely 12-HETE) on the properties of aortic smooth muscle cells (SMC) in culture. The changes in cell expression of differentiation antigen alpha-SM actin and 2P1A2 was followed by computerized morphometry, using specific monoclonal antibodies and the activation of cells by measuring cell motility. In addition, intracellular [Ca2+]i mobilization and IP3 formation were studied. Finally, the metabolic routes of monohydroxylated compounds and their effects on PGI2 secretion were reported. The results demonstrate that 12-HETE is able to stimulate the phenotypic modulation. PGI2 production and motility of arterial SMCs, despite any detectable activity in increasing [Ca2+]i or IP3 formation. By contrast with parent compounds 15-HETE and 13-HODE, which appear as potent prodifferentiating molecules, 12-HETE is specifically metabolized via a 10-11 reductase pathway in addition to the classical beta-oxidation pathway. Taken together, our results suggest that cellular metabolism of 12-HETE, produced by platelets in the vicinity of the arterial intima, and also by cells present inside the atherosclerotic intima, or associated with modified LDL may play a key role in the atherosclerotic process.