BACKGROUND: There has been a growing realization that a variety of anticancer drugs can induce apoptotic cell death. In the present study, an attempt was made to investigate the responsiveness of gastric cancer cells to various anticancer drugs and to identify which apoptosis-related proteins could be correlated to chemosensitivity. METHODS: Nine human Korean gastric cancer cell lines (SNU-1, -5, -16, -484, -601, -620, -638, -668, and -719) were analyzed. The cytotoxicity of each cell line to camptothecin, cisplatin, mitomycin C, vincristine, 5-FU, epirubicin, and doxorubicin was determined by using a MTT (dimethylthiazole- diphenyltetrazolium-bromide) assay. Apoptosis-related proteins (p53, p21, Bcl-2, Bcl-x, and Bax) were detected using a Western blot assay. RESULTS: Of the nine gastric cancer cell lines, SNU-1 was resistant while SNU-5 was sensitive to anticancer drugs. Mutated p53 was detected in all the cell lines. The highest expression of Bcl-2 was observed in SNU-1 while less or no expression of Bcl-2 was observed in SNU-5, -484, and -601. Bcl-xL was less expressed in SNU-5 than in the other cell lines. CONCLUSIONS: Chemosensitivity in gastric cancer cell lines was correlated mainly with the level of Bcl-2 and partly with that of Bcl-xL. There was no correlation between the chemosensitivity and other apoptosis-related proteins, such as p21, p53, Bax, and Bcl-xS in the studied gastric cancer cell lines.
Blotting, Western ; Camptothecin ; Cell Death ; Cell Line* ; Cisplatin ; Doxorubicin ; Epirubicin ; Fluorouracil ; Humans ; Mitomycin ; Stomach Neoplasms* ; Vincristine

BACKGROUND: A number of theories have been proposed to explain the nature of aging process. Unfortunately, there is so far no theory that can completely explain all aging processes. In the present study, to investigate roles of inducibility of defense mechanisms by oxidative stress, cellular mRNA level of superoxide dismutases (SODs) and metallothionein (MT) as well as their inducibility by paraquat, an intracellular superoxide generator, was examined in the liver and kidney of the mice of aging process. METHODS: The steady-state levels of SODs and MT mRNA and their induction by paraquat were determined by the RT-PCR assay in male mice of 4 ages, 1, 4, 8, and 12 months. RESULTS: In the liver, the steady-state levels of Mn-SOD, Cu/Zn-SOD and MT mRNA increased until 8 months with age and decreased significantly at 12 months. Cu/Zn-SOD and MT mRNA were induced well by paraquat at all ages but Mn-SOD mRNA not at 12 months. In the kidney, their mRNA levels of Mn-SOD, Cu/Zn-SOD and MT increased with age. Mn-SOD mRNA was induced by paraquat only at 1 month but Cu/Zn-SOD mRNA not at all ages. On the other hand, MT mRNA was significantly induced by paraquat at all ages. CONCLUSION: These results suggest that SODs and MT are differentially expressed and induced according to the age and organs. In addition, it is thought that the lack of induction of Mn-SOD by oxidative stress in both the liver and kidney may be one of causative factors in the aging process while Cu/Zn-SOD and MT in the liver and MT in the kidney may play protective roles in the aging process. It is therefore implicated that the tissue antioxidant/prooxidant balance could be one of determinants of mean life span.
Aging ; Animals ; Defense Mechanisms ; Hand ; Humans ; Kidney* ; Liver* ; Male ; Metallothionein* ; Mice* ; Oxidative Stress ; Paraquat* ; RNA, Messenger ; Superoxide Dismutase ; Superoxides*

BACKGROUND: Apoptosis can be induced by various anticancer agents. Resistance to apoptosis may play an important role in tumors refractory to chemotherapy. The authors investigated both the induction of apoptosis by camptothecin, a topoisomerase I inhibitor, in gastric cancer cell lines and the roles of apoptosis-elated gene products. METHODS: Two gastric cancer cell lines, SNU- and SNU-6, were examined for response to chemotherapeutic agents. Cytotoxicity was determined by a MTT assay. Apoptosis was measured by a DNA fragmentation assay using agarose gel electrophoresis and electron microscopy. Apoptosis-elated gene products were determined by western blot analysis. RESULTS: The two gastric cancer cell lines (SNU- and SNU-6) showed different sensitivities to camptothecin. Apoptosis of SNU-6 was easily induced by camptothecin, while SNU- was refractory to apoptosis, which was confirmed by DNA fragment assays and electron microscopy. Western blot analysis revealed that the amount of Bcl- in SNU- was 2.68-imes more than that in SNU-6. There were no differences in the levels of Bax, Bcl-L, Bcl-s, and p53 between the two cell lines. CONCLUSIONS: It is thought that Bcl- may play an important role in blocking cell death due to anticancer drugs in gastric cancer cell lines. Thus, chemosensitivity might be increased if this cell death-locking status were to be modified by new biologic therapies for gastric cancer.
Antineoplastic Agents ; Apoptosis* ; Biological Therapy ; Blotting, Western ; Camptothecin ; Cell Death ; Cell Line* ; DNA ; DNA Fragmentation ; DNA Topoisomerases, Type I ; Drug Therapy ; Electrophoresis, Agar Gel ; Microscopy, Electron ; Stomach Neoplasms*

In an attempt to define quantitatively the relation between left atrial size and atrial fibrillation, echocardiography was used to study 58 patients with mitral stenosis and sinus rhythm, 22 patients with mitral stenosis and newly appeared atrial fibrillation, 62 patients with mitral stenosis and atrial fibrillation, 14 patients with sinus rhythm who undergone mitral valve replacement, 18 patients with atrial fibrillation who undergone mitral valve replacement,17 patients with idiopathic atrial fibrillation and 22 control persons. In all groups of mitral stenosis, atrial fibrillation was rare when left atrial dimension was below 40mm but common when this dimension exceeded 40 mm. When left atrial dimension exceeded 50 mm, sinus rhythm was rare even in patients who undergone mitral replacement operation. These data suggest that left atrial size is an important factor in the development of atrial fibrillation. To reduce the risk of systemic embolism complicating atrial fibrillation and to reduce the need of long term anticoagulant therapy postoperatively, the left atrial dimension should be followed closely for the patients with mitral stenosis.
Atrial Fibrillation* ; Echocardiography* ; Embolism ; Heart Atria* ; Humans ; Mitral Valve ; Mitral Valve Stenosis

In order to evaluate the effect of cardiac rhythm on hemodynamic changes and pulmonary arterial atrial natriuretic peptide(ANP) levels after percutaneous mitral valvuloplasty(PMV), we measured and analyzed the correlations between hemodynamic parameters and pulmonary arterial ANP levels in 65 patients with mitral stenosis before, 20 minutes, and 24 hours after PMV. The results are as follows: 1) Normal sinus rhythm was present in 49 patients(group1), whereas the other sixteen (group 2) had chronic atrial fibrillation. 2)PMV decreased mean left atrial pressure(LAP) in both groups(p<0.001). Left atrial volume was also reduced after PMV in group 1(p<0.0001), whereas it was not decreased significantly in group 2. 3) Pulmonary arterial ANP levels at 24 hours after PMV decreased significantly in group 1(p<0.001), compared to those prior to PMV. However there was no significantl changes in group 2. 4) In group 1, there was a significant linear relationship between extents of drop in pulmonary arterial ANP levels and LAP, measured 24hours after PMV. These results suggest that ANP secretion might be influenced not only by hemodynamic changes of the left atrium, but also by possible structural changes of left atrial wall induced by chronic atrial fibrillation.
Atrial Fibrillation ; Atrial Natriuretic Factor ; Heart Atria ; Hemodynamics* ; Humans ; Mitral Valve Stenosis

To evaluate the clinical significance of atrioventricular blocks in acute inferior myocardial infarction, we reviewed the clinical recordes of 75 patients who were diagnosed as acute inferior myocardial infarction with or without associated atrioventricular conduction blocks and compared the difference in clinical observation and laboratory data including coronary angiography between these two groups of patients. We also followed the clinical courses of atrioventrticualr block during admission among the patients with blocks. 1) 40% of 75 patients had atrioventricualr block associated with acute inferior myocardial infarction and there were 7 first-degree, 8 second-degree and 15 third-degree atrioventricular blocks. 2) There was no statistically significant differences between two groups in mean age ; Killip classification : incidence of previous prodromal angina ; incidende of associated initial symptoms such as dyspnea, nausea, and syncope ; risk factors such as smoking, hypertension and previous muocardial infarction and incidence of complication such as ventricular arrhythmias and heart faliure. 3) The peak serum CK(1,442.9+/-1,703.6 vs. 1,942.8+/-2,022.9IU/L, P<0.01)and LDH(1,014.7+/-429.7 vs. 1,579.2+/-1,544.9 IU/L, P<0.01) levels were significantly higher in the patients group with atrioventricualr blocks than in the patient grouop without blocks. 4) Left ventricualr resting ejection fraction obtained by radinuclide geted blood pool heart scan was significantly less in the patient group with atrioventricular blocks than in the patient group without blocks. 5) The prevalence of multivessel disease and that of associated left anterior descending artery lesion showe no differences between two patient groups. 6) Hospatal mortality of two patient groups were 9.8% and 16.6% respectively and had no statistical significance. 7) Among the patients who had associated atrioventricualr blocks, 70% of patients showed temporary course of block for mean 4.8days, and 6.7% developed permanent first degree block.
Arrhythmias, Cardiac ; Arteries ; Atrioventricular Block ; Classification ; Coronary Angiography ; Dyspnea ; Heart ; Humans ; Hypertension ; Incidence ; Infarction ; Inferior Wall Myocardial Infarction* ; Mortality ; Nausea ; Prevalence ; Risk Factors ; Smoke ; Smoking ; Syncope

17 cases of acute myocardial infarction with no or insignificant narrowing of major coronary arteries on angiogram and without any-other types of heart disease were found in a series of 133 consecutively studied patients with acute myocardial infarction(12,7%). There were no differences in risk factors between groups. Although the infarction site were similar in both groups, the patients with normal coronary arteries had fewer complications during hospitalization(p<0.05) and lesser ST segment change during the exercise test before discharge(p<0.05). In the hemodynamic fingings, cardiac index, left ventricualr and diastolic pressure and resional wall motion were similar in both groups of the patients, but ejection fraction was higher(p<0.05) in the patients with the normal coronary arteries. In conclusion, it could be predicted that the acute myocardial infarction with the normal coronary arteries would have the better prognosis. And a transient coronary occlusion, as the most likely pathogenic mechanism of the acute mtocardial infarction with normal coronary arteries, might be studied in the aspect of the thrombosis following lysis, the coronary artery spasm and the platelet aggregation.
Angiography* ; Blood Pressure ; Coronary Occlusion ; Coronary Vessels ; Exercise Test ; Heart Diseases ; Hemodynamics ; Humans ; Infarction ; Myocardial Infarction* ; Platelet Aggregation ; Prognosis ; Risk Factors ; Spasm ; Thrombosis

PURPOSE: In addition to cyclooxygenase-2 (COX-2) which is related to prostaglandin E2 synthesis, other enzymes such as cytosolic phospholipase A2 (cPLA2), microsomal prostaglandin E2 synthase-1 (mPGES-1), and 15-prostaglandin dehydrogenase (15-PGDH) have been suggested to be related to carcinogenesis of colorectal cancer (CRC). The aim of this study was to investigate the roles of cPLA2, COX-2, mPGES-1, and 15-PGDH in tumor progression. MATERIALS AND METHODS: cPLA2, COX-2, mPGES-1, 15-PGDH, and vascular endothelial growth factor (VEGF) expressions were immunohistochemically examined in 89 CRC, and their expressions were compared with each other or clinicopathologic parameters as well as VEGF as tumor progression parameters. RESULTS: cPLA2 was expressed in 54.5%, COX-2 in 80.5%, mPGES-1 in 96.4%, 15-PGDH in 46.1%, and VEGF in 65.9%. The expression of cPLA2 correlated with VEGF expression. COX-2 expression was correlated with the depth of invasion, tumor stage, cPLA2, and VEGF expressions. Moreover, VEGF revealed the highest expression in the tissues positive for both cPLA2 and COX-2. Furthermore, 15-PGDH expression was inversely correlated with VEGF expression. CONCLUSION: The present study demonstrates that cPLA2 and mPGES-1, in addition to COX-2, are constitutively overexpressed, and that 15-PGDH might be attenuated in colorectal cancer. Furthermore, cPLA2 and 15-PGDH as well as COX-2 could have an important role in tumor progression.
Aged ; Colorectal Neoplasms/*enzymology ; Cyclooxygenase 2/*metabolism ; Female ; *Gene Expression Regulation, Enzymologic ; Group IV Phospholipases A2/*metabolism ; Humans ; Hydroxyprostaglandin Dehydrogenases/*metabolism ; Immunohistochemistry ; Intramolecular Oxidoreductases/metabolism ; Male ; Middle Aged

We report a case of infective endocarditis after flexible sigmoidoscopy. In addition to persistent bacteremia with methicillin-resistant Staphylococcus aureus (MRSA), we found an oscillating intracardiac mass on the tricuspid valve in this patient. The patient had no underlying heart disease or risk factor for the infection due to MRSA. Vancomycin treatment for 42 days was adequate for this case. The pathogen might colonize the patient's rectum and then invade through intestinal mucosa during the endoscopic procedure.
Bacteremia ; Colon ; Endocarditis* ; Heart Diseases ; Humans ; Intestinal Mucosa ; Methicillin Resistance* ; Methicillin-Resistant Staphylococcus aureus* ; Rectum ; Risk Factors ; Sigmoidoscopy* ; Tricuspid Valve ; Vancomycin

PURPOSE: Cyclooxygenase (COX)-2 is an inducible isoform responsive to cytokines, mitogens, and growth factors, and is believed to be an important enzyme related to colorectal cancer (CRC). Existing evidence suggests that COX-2 expression is normally suppressed by wild-type p53 but not mutant p53, suggesting that loss of p53 function may result in the induction of COX-2 expression. The aim of this study was to determine the relationship between COX-2 expression and p53 levels in CRC. MATERIALS AND METHODS: Patients with sporadic colorectal adenocarcinoma (n=161) who underwent curative surgery in Chosun University Hospital were enrolled in this study. Expression of COX-2 and p53 proteins was examined by immunohistochemistry in paraffin-embedded cancer tissue blocks, and the relationship between COX-2 and/or p53 expression with clinicopathologic parameters was analyzed. RESUTLS: Expression of COX- 2 was positive in 47.8% of colorectal cancers, and significantly associated with the depth of tumor invasion (p= 0.042). In contrast, p53 was positive in 50.3% of the cases, and was associated with both age (p=0.025) and the depth of tumor invasion (p=0.014). There was no correlation between COX-2 expression and p53 expression (p=0.118). CONCLUSION: These results suggest that COX-2 expression might play an important role in the progression of colorectal cancer. However, COX-2 expression was not associated with mutational p53. Further studies are needed to clarify the regulatory mechanisms governing COX-2 overexpression in colorectal cancers.
Adenocarcinoma/*metabolism/pathology/surgery ; Aged ; Colorectal Neoplasms/*metabolism/pathology/surgery ; Cyclooxygenase 2/*metabolism ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Mutation ; Tumor Suppressor Protein p53/genetics/*metabolism