Molecular and Cellular Characteristics of the Colonic Pseudo-obstruction in Patients With Intractable Constipation

BACKGROUND/AIMS: Chronic intestinal pseudo-obstruction (CIPO) is a disorder characterized by recurrent symptoms suggestive of obstruction such as abdominal pain, proximal distension with extremely suppressed motility in the absence of lumen-occluding lesion, whose etiology/pathophysiology is poorly understood. In this study we investigated a functionally obstructive lesion that could underlie symptoms of CIPO. METHODS: We studied colons surgically removed from 13 patients exhibiting clinical/pathological features of pseudo-obstruction but were unresponsive to standard medical treatments. The colons were characterized morphologically, functionally and molecularly, which were compared between regions and to 28 region-matched controls obtained from colon cancer patients. RESULTS: The colons with pseudo-obstruction exhibited persistent luminal distension proximally, where the smooth muscle was hypertrophied with changes in the cell phenotypes. Distinct luminal narrowing was observed near the distal end of the dilated region, close to the splenic flexure, previously referred to as the "transition zone (TZ)" between the dilated and non-dilated loops. Circular muscles from the TZ responded less to depolarization and cholinergic stimulation, which was associated with down-regulation of L-type calcium channel expression. Smooth muscle contractile protein was also downregulated. Myenteric ganglia and neuronal nitric oxide synthase (nNOS) positive cells were deficient, more severely in the TZ region. Interstitial cells of Cajal was relatively less affected. CONCLUSIONS: The TZ may be the principal site of functional obstruction, leading to proximal distension and smooth muscle hypertrophy, in which partial nNOS depletion could play a key role. The neuromuscular abnormalities probably synergistically contributed to the extremely suppressed motility observed in the colonic pseudo-obstruction.

Validation of the Korean Version of Liver Disease Quality of Life (LDQOL 1.0) Instrument / 대한간학회지

BACKGROUND/AIMS: Assessment of Health-related quality of life (HRQOL) outcomes in treatment of chronic disease is increasingly important. The objective of this study was to validate a Korean translation of the Liver Disease Quality of Life instrument (LDQOL version 1.0) for use in patients with chronic liver disease. METHODS: Two native Korean speakers with fluent English translated LDQOL including instructions, items, and response choices. This Korean translation of the LDQOL was administered to 121 patients with chronic liver disease. Cronbach's alpha coefficients were applied to test an internal consistency reliability of disease-specific scales of the LDQOL. MELD and modified CTP scores were calculated for all patients. Associations of MELD and modified CTP scores with severity of liver disease were analyzed with LDQOL. RESULTS: Internal consistency reliability was good (Cronbach's Alpha=0.69-0.94) in liver disease specific scales, except for the quality of social interaction scale (Cronbach's Alpha= 0.56). Mean modified CTP score and MELD score were 6.2+/-1.9 and 9.3+/-5.3, respectively. Both MELD score and modified CTP score showed correlations with most of the scores of liver disease specific scales of LDQOL 1.0, except for the quality of social interaction and sleep scale. CONCLUSIONS: The Korean version of the liver disease specific scales of the LDQOL 1.0 is validated and useful for measuring HRQOL in Korean patients with chronic liver disease.

Retraction: Tetraarsenic Oxide-mediated Apoptosis in a Cervical Cancer Cell Line, SiHa / Journal of the Korean Cancer Association, 대한암학회지

No abstract available.

Genomic gain and loss of cervical cancer using BAC Chip / 대한산부인과학회지

OBJECTIVE: Cervical cancer has long been linked to the sexually transmitted human papillomavirus (HPV), and the oncoproteins E6 and E7 disrupt the functions of tumour suppressor genes, resulting in genetic alteration. It was shown that loss of heterozygosity at 6p is a common genetic alteration in cervical cancer. However, the molecular genetics of cancer have only recently been understood, and for the development of cervical cancer additional genetic alterations in host cell genes are required. The present study has identified the differential changes of the cervical cancer-associated genetic alterations by a genome-wide array based comparative genomic hybridization (array-CGH). METHODS: We analyzed 15 cases of cervical cancer from St. Mary's hospital of The paraffin-fixed tissue samples were microdissected under microscope and DNA was extracted by the procedures of proteinase K digestion and chloroform extraction. Array-based CGH and genomic PCR were carried out with statistical analyses such as hierarchical clustering and Gene Ontology. The BAC array used in this study consisted of 1,440 human BACs, the space among the clones were approximately 2.08 megabase (Macrogen, Seoul, Korea). RESULTS: All of 15 cases of cervical cancer showed specific gains and losses. The analysis limit of average gains and losses was 53%. A significant positive correlation was found between 1p36.32, 3p14.2, 3q27.1, 7p21.1, 8q24.3 and 11q13.1 changes through the cervical carcinogenesis. The high-level of gain regions, BAC clones encoded GSDMDC1, RECQL4, TP73, ABCF3, ALG3, HDAC9, ESRRA and RPS6KA4 genes. Frequently gained BAC clones encoded genes were PRSS8, FUS, COL18A1, PCOLN3, MAFG and ASPSCR1. The genes encoded by frequently lost BAC clones were PTPRG, GRM7, ZDHHC3, EXOSC7, LRP1B and NR3C2. Also, hierarchical clustering of the expression data readily distinguished genomic alterations in cervical cancer. A subset of cellular processes from each gene was clustered by Gene Ontology database. CONCLUSION: Using Array-CGH, genomic alterations related to cervical cancer were identified to determine whether induction of chromosomal imbalances occurs prior to carcinogenesis. The high resolution of array-CGH combined with human genome database would give a chance to find out possible target genes present in the gained or lost clones.

Protein Expression Profile using Two-Dimensional Gel Analysis in Squamous Cervical Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Screening in cervical cancer is now progressing to discover candidate genes and proteins that may serve as biological markers and that play a role in tumor progression. We examined the protein expression patterns of the squamous cell carcinoma (SCC) tissues from Korean women with using two-dimensional polyacrylamide gel electrophoresis (2-DE) and matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometer. MATERIALS AND METHODS: Normal cervix and SCC tissues were solubilized and 2-DE was performed using pH 3~10 linear IPG strips of 17 cm length. The protein expression was evaluated using PDQuest 2-D software(TM). The differentially expressed protein spots were identified with a MALDI-TOF mass spectrometer, and the peptide mass spectra identifications were performed using the Mascot program and by searching the Swiss-prot or NCBInr databases. RESULTS: A total of 35 proteins were detected in SCC. 17 proteins were up-regulated and 18 proteins weredown-regulated. Among the proteins that were identified, 12 proteins (pigment epithelium derived factor, annexin A2 and A5, keratin 19 and 20, heat shock protein 27, smooth muscle protein 22 alpha, alpha-enolase, squamous cell carcinoma antigen 1 and 2, glutathione S-transferase and apolipoprotein a1) were protein previously known to be involved in tumor, and 21 proteins were newly identified in this study. CONCLUSION: 2-DE offers the total protein expression profiles of SCC tissues; further characterization of these differentially expressed proteins will give a chance to identify the badly needed tumor-specific diagnostic markers for SCC.

Cell Cycle Regulatory Protein Expression Profiles by Adenovirus p53 Infection in Human Papilloma Virus-associated Cervical Cancer Cells / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The tumor suppressor gene, p53, has been established as an essential component for the suppression of tumor cell growth. In this study, we investigated the time-course anticancer effects of adenoviral p53 (Adp53) infection on human ovarian cancer cells to provide insight into the molecular-level understanding of the growth suppression mechanisms involved in Adp53-mediated apoptosis and cell cycle arrest. MATERIALS AND METHODS: Three human cervical cancer cell lines (SiHa, CaSki, HeLa and HT3) were used. The effect of Adp53 infection was studied via cell count assay, cell cycle analysis, FACS, Western blot and macroarray assay. RESULTS: Adp53 exerts a significant role in suppressing cervical cancer cell growth. Adp53 also showed growth inhibitory effects in each cell line, and it induced apoptosis and cell cycle arrest. Adp53 differentially regulated the expression of genes and proteins, and the gene expression profiles in the SiHa cells revealed that the p21, p53 and mdm2 expressions were significantly up-regulated at 24 and 48 hr. Western blot shows that the p21 and p53 expressionlevels were significantly increased after Adp53 infection. In addition, in all cell lines, both the CDK4 and PCNA protein expression levels were decreased 48 h after Adp53 infection. Cell cycle arrest at the G1 phase was induced only in the SiHa and HeLa cells, suggesting that exogenous infection of Adp53 in cancer cells was significantly different from the other HPV-associated cervical cancer cells. CONCLUSION: Adp53 can inhibit cervical cancer cell growth through induction of apoptosis and cell cycle arrest, as well as through the regulation of the cell cycle-related proteins. The Adp53-mediated apoptosis can be employed as an advanced strategy for developing preferential tumor cell-specific delivery.

Adenosine 5'-triphosphate induced NF-kappa B and intracellular calcium mobilization in cervical cancer cells / 대한산부인과학회지

OBJECTIVE: To know the effect of adenosine 5'-triphosphate (ATP) on intracellular calcium level and cell proliferation in cervical cancer cells. METHODS: Study design: Four different human cervical cancer cell lines (Caski, C33A, HeLaS3 and SiHa) were used in this study. The change of intracellular calcium level, cell proliferation and the activity of proliferation- and calcium-related transcription factors by extracellular ATP were examined in these cell lines. RESULTS: Extracellular ATP induced calcium mobilization, cell proliferation and the activation of NF-kappa B in all cell lines used. CONCLUSION: These results suggest that calcium mobilization and NF-kappa B dependent signaling pathway play an important role in the cell proliferation by ATP in cervical cancer.

Tetraarsenic Oxide-mediated Apoptosis in a Cervical Cancer Cell Line, SiHa / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Diarsenic oxide, As2O3, has been reported to be effective in treating acute leukemia, and induce apoptosis in many tumor cells. In this study, the ability of a novel arsenical compound, As4O6 (tetraarsenic oxide), along with As2O3, for its ability to induce cell growth inhibition, as well as apoptosis, in human cervical cancer cells, SiHa cells, were evaluated in vitro. MATERIALS AND METHODS: To examine the levels of apoptosis, SiHa cells were given two sensitive doses, 0.5 and 1micrometer, of arsenical compounds, and a DNA fragmentation assay and FACS analysis were then conducted. In addition, a Western blotting assay was performed to identify target molecules for apoptosis. RESULTS: Both As2O3 and As4O6 induced dose-dependent inhibition of SiHa cell proliferation. In particular, As4O6 was more effective at suppressing SiHa cell growth than As2O3. In parallel with the inhibition of cell proliferation, As4O6 caused a significantly greater increase in the sub-G1 cell population than As2O3, as determined by propidium iodide DNA staining. This was confirmed by a DNA fragmentation assay and annexin V staining. The Western blotting analysis also showed that the expression of proliferating cell nuclear antigen (PCNA) was suppressed to a significantly greater extent by As4O6 than As2O3 at a dose of 0.5micrometer. However, the apoptosis-related protein, Bax, was expressed to a significantly greater extent due to As4O6 than As2O3. CONCLUSIONS: Taken together, these findings suggest that a novel arsenic compound, As4O6, possesses more potent anti-proliferative effects on human cervical cancer cells, with the induction of apoptosis also, at least via the activation of Bax protein in vitro.

Effects of cell growth inhibition on the combination of cisplatin with green tea extracts / 부인종양

OBJECTIVE: The chemotherapeutic agent cisplatin (cis-diamminedichloroplatinum (II)) is particularly effective against cervical cancer. The purpose of this study is to elucidate combination effect of cisplatin and green tea extracts on the growth inhibition of TC-1 cell. METHODS: To observe the anti-proliferative effects, we treated different doses of cisplatin (0.1, 0.5, 2.5 uM), GTP (1, 5, 25 ug/ml) and EGCG (25, 50, 100 uM). to TC-1 cells. Also, we treated 0.5 uM of cisplatin and different doses of GTP (1 and 5 ug/ml) or EGCG (25 and 50 uM). Cell viability was scored by use of MTT assay. In addition, E6 gene expression patterns in TC-1 cell were investigated by using RT-PCR. RESULTS: Cell growth inhibition in a dose dependent was observed at the different concentration of ciaplatin, GTP and EGCG. Also, in the groups treated by 0.5 uM of cisplatin and GTP (1 and 5 ug/ml) or EGCG (25 and 50 uM), the inhibition of cell growth showed with 12.2%, 6.9% and 63.4%, 72.2% as compared to the group treated by cisplatin only. In RT-PCR, down regulation of E6 was shown. CONCLUSION: Additive effect of the combination of cisplatin with GTP or EGCG on the inhibition of cell growth was observed. This effect suggests the possibility lowering the concentration of chemotherapeutic drugs, which alleviate the side effect of drugs.

Correlation of adenoassociated virus type 2 and high-risk human papillomavirus type 16 and 18 infection in the cervix of Korean women / 대한산부인과학회지

OBJECTIVE: Previous studies were showed that adenoassocited virus (AAV) infection was had negative effects on human papillomavirus (HPV) infection and that the cervical cancer cell growth is inhibited by AAV infection. We detected of AAV 2 and high-risk HPV infection and researched correlation with AAV 2 and HPV in cervical cell. METHODS: Cell of normal cervix (49 persons), infected HPV cervix (45 persons), cervical intraepithelial neoplasm (CIN) I (31 persons), II (20 persons), III (35 persons), and invasive cancer (30 persons) were investigated by PCR using AAV-2 and HPV type 16 and 18 specific primers. RESULTS: AAV 2 was detected in 8 out of 49 normal cervix (16.3%), 2 out of 45 infected HPV cervix (4.4%), 3 out of 31 CIN I (9.7%), 4 out of 20 CIN II (20%), 8 out of 35 CIN III (22.8%), and 3 out of 30 invasive cervical cancer cases (30%). However, HPV 16 was detected in 5 out of 49 normal cervix (10.2%), 20 out of 45 infected HPV cervix (44.4%), 13 out of 31 CIN I (42%), 11 out of 20 CIN II (55%), 19 out of 35 CIN III (54.3%), and 21 out of 30 invasive cervical cancer cases (70%). HPV 18 was detected in 6 out of 49 normal cervix (12.2%), 18 out of 45 infected HPV cervix (40%), 16 out of 31 CIN I (51.6%), 10 out of 20 CIN II (50%), 22 out of 35 CIN III (62.8%), and 13 out of 30 invasive cervical cancer cases (43.3%). CONCLUSION: AAV 2 was detected in normal and infected HPV cervix, CIN (I, II, III) and invasive cervical cancer. As compared to normal, CIN I and CIN II, suggesting significant correlation between AAV 2 and HPV type 16. Further, researches continue to be done relationship to AAV 2 and HPV infection in cervix.

A Case of Cytomegalovirus Gastric Ulcer Mimicking Gastric Cancer in an Immunocompetent Host / 대한소화기내시경학회지

A 27-year-old woman presented with epigastric pain. Abdominal computed tomography revealed an irregular ulcer with circumferential thickening of the gastric antral wall. An endoscopy suggested advanced gastric cancer or gastric lymphoma. Biopsy of the lesion showed an inclusion body of the cytomegalovirus and positive immunohistochemical staining of the infected cell for cytomegalovirus. A thorough evaluation of her immune system revealed no abnormality. General supportive treatment for gastric ulcer did not relieve her symptoms. Intravenous infusion of ganciclovir improved her symptoms and healed the ulcer. We report a case of cytomegalovirus-associated gastric ulcer mimicking malignancy in an immunocompetent woman.

Significance of Non-erosive Minimal Esophageal Lesions in Gastro-esophageal Reflux Disorder

BACKGROUND: Non-erosive reflux disorder, which represents more than 60% of gastro-esophageal reflux disorders, lacks objective parameters for diagnosis. The purpose of this study was to evaluate the correlation between non-erosive minimal lesions at the lower esophagus and gastro-esophageal reflux disorder. METHODS: Patients were asked to answer a symptom questionnaire. The endoscopic findings were either graded by LA classification or recorded as non-erosive minimal lesions. Patients with minimal lesions were treated with rabeprazole or a placebo and responses were evaluated at weeks 1 and 4. RESULTS: In 8 centers, 3454 patients were screened. In patients with heartburn or acid regurgitation as the most bothersome symptom, 23.7% had endoscopy negative reflux disorder, 40.1% showed minimal lesions, and 36.2% had mucosal break esophagitis. Thirty-four percent of patients with minimal lesions and 39.1% of patients with LA 'grade A' mild esophagitis reported typical reflux symptoms as their main symptom. In patients with minimal lesions, medication with rabeprazole reduced symptoms significantly at weeks 1 and 4, but not with the placebo. CONCLUSION: Patients with non-erosive minimal esophageal lesions had similar reflux symptoms comparable to those with mild erosive reflux esophagitis, and reflux symptoms were improved with a short-term proton pump inhibitor. Thus, non-erosive minimal esophageal lesion constitutes a great part of gastro-esophageal reflux disorder.

A Case of Early Developed Left Ventricular Free Wall Rupture Followed by Acute Inferior Myocardial Infarction

Myocardial free wall rupture is the most serious complication of acute myocardial infarction. Although it is not uncommon, it is difficult to treat successfully. We report a case of acute inferior myocardial infarction complicated with left ventricular free wall rupture that occurred 8 hours after onset of chest pain. In this case, progression of mild pericardial effusion to cardiac tamponade was monitored by transhtoracic echocardiography. Pericardiocentesis and draninage failed to treat cardiac tamponade, and surgical repair was performed successfully. The patient discharged uneventfully on 28th day and followed regularly at the outpatient department.

A Case of Multiple Systemic Embolism Associatied with Left Atrial Free-Floating Ball Thrombus

Left atrial thrombus is frequently associated with rheumatic mitral valvular heart disease. Left atrial thrombus is usually attached to the atrial wall, but rarely it is freely floating in the cavity. In that case the patient may present with the symptoms of acute hemodynamic decompensation due to the so-called "hole-in-one" effect or multiple systemic embolism. We report a case of multiple systemic embolism associated with left atrial free-floating ball thrombus in mitral valvular heart disease.

A Case of Q Wave Acute Myocardial Infarction in Patients with Myocardial Bridging Caused by Fibrous Band

Myocardial bridging is defined that short segments of coronary artery descend into the myocardium for a variable distance and each systolic contraction of these fibers can cause narrowing of the artery. Systolic narrow-ing may rarely be caused by connective tissue such as fibrous band. Myocardial ischemia, infarction and sudden death may be seen in some patients with myocardial bridging. Myocardial infarction in association with isolated myocardial bridges with systolic narrowing is uncommon. We report a case of Q wave myocardial infarction in a patient with angiographic systolic narrowing at the middle segment left anterior descending coronary artery which was caused by fibrous band.