OBJECTIVE: The incidence of colorectal carcinomas continues to rise in Korea due to the westernized life style. However, the precise colorectal carcinogenic mechanisms remain to be elucidated. The protein products of oncogenes and cancer suppressor genes play important roles in the carcinogenesis. The effects of the proteins are influenced by post-translational modifications as phosphorylation, acetylation, methylation, and ubiquitination. The aberrant sumoylation plays some roles in carcinogenesis. However, the expression pattern of small ubiquitin-related modifier (SUMO)-2/3 in the colorectal cancer has not been reported. We assessed the expression of SUMO-2/3 and evaluated the expression pattern in colorectal cancer. METHODS: The SUMO-2/3 expression was tested in one normal colon mucosal cell line and 5 colorectal cancer cell lines by Western blot. We collected 322 cases of colorectal cancer operated from January 2000 to December 2010 at Soonchunhyang University Cheonan Hospital. We fabricated the tissue microarray and the expression of SUMO-2/3 was evaluated by immunohistochemistry. The results were analyzed with clinicopathologic parameters. RESULTS: The SUMO-2/3 was not expressed in the normal colon mucosal cell line. However, it was expressed highly in all the 5 colorectal cancer cell lines as the beta-actin. The SUMO-2/3 was expressed in 68.3% of the colorectal cancers and its expression was correlated with the pathological tumor stage stage (odds ratio, 2.89; 95% confidence interval, 1.10 to 7.55; P=0.031). CONCLUSION: The SUMO-2/3 plays some roles in carcinogenesis and progression of the colorectal cancer.
Acetylation ; Actins ; Blotting, Western ; Cell Line ; Colon ; Colorectal Neoplasms ; Genes, Tumor Suppressor ; Immunohistochemistry ; Incidence ; Korea ; Life Style ; Methylation ; Oncogenes ; Phosphorylation ; Protein Processing, Post-Translational ; Proteins ; Sumoylation ; Tissue Array Analysis ; Ubiquitin ; Ubiquitination

BACKGROUND: The exercise stress testing(Treadmill Test) is one of the preferred noninvasive methods of identifying patients with coronary artery disease. ST-segment elevation during or immediately after exercise is uncommon and in most patients, it was associated with prior infarction, left ventricular hypertrophy or left bundle branch block, Exercise-induced ST-segment elevation has been attributed to ventricular wall motion abnormalities, and ischemia due to either coronary vasospasm or ervere proximal coronary stenosis. We examined the clinical, angiographic, and prognostic significance of 16 patients with exercise induced ST-segment elevation. METHODS: 16 patients with exercise-induced ST-segment elevation were retrospectively reviewed. The symptom-limited exercis testing was performedn using a modified Bruce protocol and in patients with acute myocardial infarction(AMI), low level exercise testing(Myocardial infarction protocol) was used. The significant ST-segment elecation was defined as a > or =1mm change present in >1 lead measured at 0.08 sec after J point and in > or =3 consecutive beats. Coronary arteriogram and percutaneous transluminal coronary angioplasty(PTCA) was performed using standard techniques within 7 days of initial exercise testing and a luminal diameter stenosis of >50% was considered significant. RESULTS: 1) We have studied 2076 exercise tests and 16 patients(M/F:15/1, Mean age : 58 years) developed exercise-induced ST-segment elevation. The initial diagnosis were acute myoca rdial infarction(AMI) in 12, variant angina in 2, effort angina in 1 and unstable angina in 1 patient. 9 of 12 patients with AMI were treated with thrombolytic agent(Urokinase 2.5 to 3 million unit) within 6 hours from the onset of chest pain. 2) Mean maximal ST-segment elevation was 2.6mm(range 1-5mm). The leads which showed exercise-induced ST-segment elevation were corresponded to the location of severe coronary stenosis in typical effort angina, to spasm site in variant angina, and to infarction site in AMI. 11 Patients had follow-up exercise testing and showed abolition of exercise-induced ST-segment elevation in 4 of 5 patients with AMI and 1 patient with effort angina after PTCA, and 1 patient with variant angina and 3 of 4 patient with AMI after medication. 3) In 12 patients, coronary angiography was performed, and showed 95% and 90% stenosis at proximal LAD in 2 patients with effort angina and >80% stenosis at proximal or mid lesion of infarct-related artery in 7 patients with AMI. In variant angina, one patient showed normal coronary artery and another patient showed 60% stenosis at mid LAD. On LV angiogram, there were moderate to severe hypokinesia instead of akinesia or dyskinesia at infarction site in all patients with AMI and showed normal LV contractility in patients with effort or variant angina. PTCA were successfully performed in 7 patients(effort angina 2, AMI 5). 4) The clinical follow up for 16 patients were obtained for mean follow-up duration of 17 months and during the clinical follow-up, 1 variant angina patient with mild stenosis at proximal LAD was died with ventricular fibrillation after discontinution of medication. There were CABG due to restenosis in 1 patient and cerebrovascular accident in 1 patient. CONCLUSION: 1) The exercise-induced ST-segment elevation signifies severe ischemia due to either severe proximal coronary stenosis or coronary arterial spasm. In AMI, this findings suggests the residual ischemia(or residual viable myocardium) in addition to left ventricular dyssynergy or aneurysm. 2) Adverse cardiac events can be provented by revascularization in patients who had critical coronary stenosis and by medical therapy in those with coronary vasospasm or mild coronary stenosis.
Aneurysm ; Angina, Unstable ; Arteries ; Bundle-Branch Block ; Chest Pain ; Constriction, Pathologic ; Coronary Angiography ; Coronary Artery Disease ; Coronary Stenosis ; Coronary Vasospasm ; Coronary Vessels ; Diagnosis ; Dyskinesias ; Exercise Test ; Follow-Up Studies ; Humans ; Hypertrophy, Left Ventricular ; Hypokinesia ; Infarction ; Ischemia ; Phenobarbital ; Retrospective Studies ; Spasm ; Stroke ; Ventricular Fibrillation

BACKGROUND: Uncomplicated myocardial infarction is often the harbinger of future cardiac events such as unstable angina pectoris,recurrent myocardial infarction or death. The feasibility and safety of exercise testing performed soon after myocardial infarction have been established but the prognostic value of exercise test after myocardial infarction remain inconclusive. The object of this study is to determine whether exercise test results can be utilized to predict of future cardiac events after uncomplicated myocardial infarction. METHODS: The study group comprised 149 patients with an uncomplicated myocradial infarction. A low level exercise test was performed before discharge from the hospital 8 to 10 days after myocardial infarction. The exercise thst results was considered positive if there was new > or =1mm horizontal or downsloping ST segment depression at 0.08 sec after the J point compared with baseline. The patients were followed for the development of new cardiac events. RESULTS: 1) The exercise test after acute myocardial infarction was performed in 149 patients without complication. The mean duration of exercise test was 14 min(range 1-20 min) and the mean work-load(Metabolic equivalents) was 3.7+/-1.1 METs. 2) 37 patients had ST-segment depression, 13 had ST-segment elevation and 27 had an inadequate blood pressure response to exercise. During the exercise, there were angina in 5 patients, dyspnea in 17 and no symptom in 127 patients. 3) During the follow-up period(1 to 75 month, mean 27.4 month), 29 patients experienced post-myocardial infarction angina, 1 had recurrent myocardial infarction, 4 had revascularization therapy(PTCA 2, CABG 2),5 had ischemic cardiomyopathy and 5 died a cardiac death. 4) The patients with cardiac events such as cardiac death, myocardial infarction and post MI angina had a significantly shorter exercise duration(13.1+/-4.0 and 14.6+/-2.7min, p<0.05), lower exercise tolerance(3.5+/-1.0 and 3.9+/-1.0 METs, p<0.05) and lower peak heart rate(117 +/- and 126+/-5, p<0.05). 5) The ST-segment depression, lower exercise tolerance(<3.0 METs) and history of hypertension were associated significantly with cardiac events(p<0.05) but ST-segment elevation, inadequate blood pressure response to exercise, the use of thrombolytic agents and non-Q wave infarction did not predict future cardiac events. Conclusions: The exercise test after acute myocardial infarction is safe and of limited value for predicting patients at risk of cardiac events in the follow-up period. The ST-segment depression and lower exercise tolerance(<3.0 METs) can predict cardiac events and the prognosis of the patients of this group can be improved with aggressive management and careful follow-up.
Angina, Unstable ; Blood Pressure ; Cardiomyopathies ; Death ; Depression ; Dyspnea ; Exercise Test* ; Fibrinolytic Agents ; Follow-Up Studies ; Heart ; Humans ; Hypertension ; Infarction ; Myocardial Infarction* ; Prognosis

PURPOSE: Secreted protein acidic and rich in cysteine (SPARC), also known as osteonectin or basement-membrane-40 (BM-40), is a member of a family of matricellular proteins, whose functions are to modulate cell-matrix interactions, growth and angiogenesis in colorectal cancer. In this study, the expression of SPARC was evaluated and its correlations with clinicopathological parameters were investigated. METHODS: The researchers analyzed the expression patterns of SPARC by using immunohistochemistry in 332 cases of colorectal cancer of tissue microarray. The clinicopathological characteristics were defined by using the TNM criteria of the Union for International Cancer Control. Clinicopathological factors such as age, sex, histologic type of the tumor, pathologic tumor stage, TNM stage, and lymphovascular invasion were evaluated according to the SPARC expression. RESULTS: The hazard ratios expressing SPARC in tumor cells, in the stroma, and in both tumor cells and the stroma were 2.10 (P = 0.036), 3.27 (P = 0.003) and 2.12 (P = 0.038), respectively. Patient survival was decreased in patient expressing SPARC in the stroma, and this result showed statistical significance (P = 0.016). CONCLUSION: These findings suggest that SPARC expression in a tumor and in the stroma correlates with disease progression and may be used as a prognostic marker for colorectal cancer.
Colorectal Neoplasms ; Cysteine ; Disease Progression ; Humans ; Immunohistochemistry ; Osteonectin ; Prognosis ; Proteins

PURPOSE: Secreted protein acidic and rich in cysteine (SPARC), also known as osteonectin or basement-membrane-40 (BM-40), is a member of a family of matricellular proteins, whose functions are to modulate cell-matrix interactions, growth and angiogenesis in colorectal cancer. In this study, the expression of SPARC was evaluated and its correlations with clinicopathological parameters were investigated. METHODS: The researchers analyzed the expression patterns of SPARC by using immunohistochemistry in 332 cases of colorectal cancer of tissue microarray. The clinicopathological characteristics were defined by using the TNM criteria of the Union for International Cancer Control. Clinicopathological factors such as age, sex, histologic type of the tumor, pathologic tumor stage, TNM stage, and lymphovascular invasion were evaluated according to the SPARC expression. RESULTS: The hazard ratios expressing SPARC in tumor cells, in the stroma, and in both tumor cells and the stroma were 2.10 (P = 0.036), 3.27 (P = 0.003) and 2.12 (P = 0.038), respectively. Patient survival was decreased in patient expressing SPARC in the stroma, and this result showed statistical significance (P = 0.016). CONCLUSION: These findings suggest that SPARC expression in a tumor and in the stroma correlates with disease progression and may be used as a prognostic marker for colorectal cancer.
Colorectal Neoplasms ; Cysteine ; Disease Progression ; Humans ; Immunohistochemistry ; Osteonectin ; Prognosis ; Proteins