Transcriptome analysis of iBET-151, a BET inhibitor alone and in combination with paclitaxel in gastric cancer cells

BET inhibitor, as an epigenetic regulator inhibitor, reduces the expression of oncogenes such as Myc and Bcl-2, which affects cancer growth and development. However, it has modest activity because of the narrow therapeutic index. Therefore, combination therapy is necessary to increase the anti-tumor effect. Paclitaxel, an anti-mitotic inhibitor, is used as second-line therapy for gastric cancer (GC) as a monotherapy or combination. In this study, we performed RNA sequencing of GC cells treated with iBET-151 and/or paclitaxel to identify the differentially expressed genes associated with possible mechanisms of synergistic effect. We also performed Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses to determine the most enriched terms and pathways of upregulated and downregulated genes. We found 460 genes in which iBET-151 and paclitaxel combination treatment changed more than single-treatment or no-treatment. Thus, additional functional studies are needed, but our results provide the first evidence of the synergistic effect between iBET-151 and paclitaxel in regulating the transcriptome of GC cells.

Transcriptome analysis of iBET-151, a BET inhibitor alone and in combination with paclitaxel in gastric cancer cells

BET inhibitor, as an epigenetic regulator inhibitor, reduces the expression of oncogenes such as Myc and Bcl-2, which affects cancer growth and development. However, it has modest activity because of the narrow therapeutic index. Therefore, combination therapy is necessary to increase the anti-tumor effect. Paclitaxel, an anti-mitotic inhibitor, is used as second-line therapy for gastric cancer (GC) as a monotherapy or combination. In this study, we performed RNA sequencing of GC cells treated with iBET-151 and/or paclitaxel to identify the differentially expressed genes associated with possible mechanisms of synergistic effect. We also performed Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses to determine the most enriched terms and pathways of upregulated and downregulated genes. We found 460 genes in which iBET-151 and paclitaxel combination treatment changed more than single-treatment or no-treatment. Thus, additional functional studies are needed, but our results provide the first evidence of the synergistic effect between iBET-151 and paclitaxel in regulating the transcriptome of GC cells.

Management of Split Thickness Skin Graft Donor Sites: Comparison of Four Different Dressing Materials

PURPOSE: Split thickness skin graft is a frequently used reconstructive technique in burn wound, but the ideal dressing material of the donor site is yet to be developed. The donor sites have been managed with various dressing materials. The aim of this study is to compare four different dressing materials for management of the donor site in a prospective trial. METHODS: This study is based on 85 patients who had undergone split thickness skin graft from September 2011 to February 2012. The grafts harvested with a same manner and the donor sites were managed with one of the four dressing materials: Aquacel Ag(R), Mepitel(R), Bactigra(R), Op-Site(R). We compared post-operative pain scale, the time required epithelialization, ease of application, post-operative infection and number of dressings. RESULTS: Aquacel Ag(R) was the more painless dressing materials in post-operative day 1, 4, 7, 10 than Mepitel(R), Bactigra(R), Op-Site(R). Number of dressings was more lower for Aquacel Ag(R) with Mepitel(R). Ease of application was more higher for Aquacel Ag(R) with Mepitel(R). But Aquacel Ag(R) was not earliest epithelialization. The incidence of infection was not low in Aquacel Ag(R). CONCLUSION: Aquacel Ag(R) dressing is better than other dressing materials for split thickness skin graft donor site in the number of dressings, ease of application, post-operative pain.

Vardenafil Increases Cell Proliferation in the Dentate Gyrus through Enhancement of Serotonin Expression in the Rat Dorsal Raphe

This study was conducted to evaluate the effects of vardenafil (Levitra), a phosphodiesterase-5 (PDE-5) inhibitor, on cell proliferation in the hippocampal dentate gyrus and on 5-hyroxytryptamine (5-HT, serotonin) synthesis and tryptophan hydroxylase (TPH) expression in the rat dorsal raphe nucleus. Male Sprague-Dawley rats were divided into 6 groups (n=5 in each group): a control group, a 0.5 mg/kg-1 day vardenafil-treated group, a 1 mg/kg-1 day vardenafil-treated group, a 2 mg/kg-1 day vardenafil-treated group, a 1 mg/kg-3 day vardenafil-treated group, and a 1 mg/kg-7 day vardenafil-treated group. 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry was then performed to evaluate cell proliferation in the dentate gyrus. In addition, 5-HT and TPH immunohistochemistry was conducted to evaluate serotonin expression in the dorsal raphe. The results revealed that treatment with vardenafil increased cell proliferation in the dentate gyrus and enhanced 5-HT synthesis and TPH expression in the dorsal raphe in a dose- and duration-dependent manner. The findings demonstrate that the increasing effect of vardenafil on cell proliferation is closely associated with the enhancing effect of vardenafil on serotonin expression under normal conditions.

Postoperative Results of Ossiculoplasty over Stapes Head / 대한이비인후과학회지

BACKGROUD AND OBJECTIVES: Incus erosion with intact stapes head was most common ossicular impairment in chronic otitis media. Here, we aimed to investigate hearing and clinical results of the ossiculoplasties when the stapes head was intact. SUBJECTS AND METHOD: We analyzed 281 patients of ossiculoplasties over stapes head performed from 1990 to 2005. Patients were divided into 3 groups: Si group (n=121) included patients with interposition of prosthesis between malleus and stapes; Sc-PORP group (n=99) included patients with columellarization between tympanic membrane and stapes head with PORP; Sc-SC group (n=61) included patients with columellarization with the autologous materials between tympanic membrane and stapes head. Hearing improvement and extrusion rates of three groups were analyzed. RESULTS: At 6 months after the surgery, the postoperative air-bone gap (ABG) level within 20 dB was 45%, 44%, 25% in Si, Sc-PORP, Sc-Sc, respectively. The closure of ABG was statistically better in Si and Sc-PORP compared with Sc-SC. In canal wall-up mastoidectomy, Sc-PORP showed better hearing results than Si, while Si was better than Sc-PORP in canal wall-down mastoidectomy. At 36 months after the surgery, extrusion-free survival according to the type of ossiculoplasty were 100%, 89.6%, 100% in Si, Sc-PORP, Sc-SC, respectively. CONCLUSION: Si and Sc-PORP provide good hearing results. However, Si has lower extrusion rates than Sc-PORP and remains stable over time.

Significant Gene Selection Using Integrated Microarray Data Set with Batch Effect

In microarray technology, many diverse experimental features can cause biases including RNA sources, microarray production or different platforms, diverse sample processing and various experiment protocols. These systematic effects cause a substantial obstacle in the analysis of microarray data. When such data sets derived from different experimental processes were used, the analysis result was almost inconsistent and it is not reliable. Therefore, one of the most pressing challenges in the microarray field is how to combine data that comes from two different groups. As the novel trial to integrate two data sets with batch effect, we simply applied standardization to microarray data before the significant gene selection. In the gene selection step, we used new defined measure that considers the distance between a gene and an ideal gene as well as the between-slide and within-slide variations. Also we discussed the association of biological functions and different expression patterns in selected discriminative gene set. As a result, we could confirm that batch effect was minimized by standardization and the selected genes from the standardized data included various expression pattems and the significant biological functions.

Follow up Study about Health-Related Quality of Life in Injury Patients

PURPOSE: The purpose of this study is to assess healthrelated quality of life (HRQOL), to compare HRQOL of 3 months after injury with 10 days after injury, and to offer the result of this study to basic data of HRQOL in Korean patients with injury. METHODS: Between November 1, 2003, and March 2, 2004, 100 eligible injury patients who had visited emergency center were enrolled in the study. HRQOL was measured by Korean EuroQol 5 dimensions (KEQ-5D), and assessed in 10 days and 3 months after injury. The severity of injury was measured by Injury Severity Score (ISS). RESULTS: Of the 100 subjects, 54 (54%) were men and 46 (46%) were women, with mean (+/-SD) age of 43.7 (+/-15.2) and mean ISS (+/-SD) of 4.45 (+/-4.38). The KEQ-5D utility index and 5 subdimensional scores of 3 months after injury were significantly higher than those of 10 days after injury. The KEQ-5D utility indexes of 3 months after injury of each group by the ISS, age, sex, educational status and marrital status had significant higher than those of 10 days after injury. CONCLUSION: In this study, we observed that HRLOQ in patients with 3 months after injury was higher than those with 10 days after injury. However, to define the more definite feature of HRLOQ in patients with injury, the study with more and large epidemiologic controlled injury group and detailed variable adjustment should be done.

Health-related Quality of Life in Patients with Injury in the Emergency Department

PURPOSE: The purpose of this study is to assess healthrelated quality of life (HRQOL) in patients with injury in the Emergency department, to compare that HRQOLs with normal control group, and to offer the results of this study as basic data on the HRQOL in Korean patients with injury, in the Emergency department. METHODS: Between November 1, 2003, and March 2, 2004, 266 eligible injury patients who had visited our emergency center were enrolled in the study. The HRQOL was measured by using the Korean Short Form Health Survey-36 (KSF-36)and the Korean EuroQol 5 dimensions (KEQ-5D). The HRQOL was assessed at 10 days after injury. The severity of injury was measured by using the Injury Severity Score (ISS). RESULTS: Of the 266 subjects, 164 (61.7%) were men and 102 (38.3%) were women, with a mean (+/-SD) age of 42.8 (+/-15.2) and mean ISS (+/-SD) of 4.54 (+/-3.98). The KSF- 36 and KEQ-5D scores in patients with injury were significantly lower than those in the normal control group. The HRQOL scores of each group by cause of injury had significant differences in the KSF-36 MCS and the KEQ-5D utility index, but they had no significant differences in the KSF-36 PCS. Women were more likely to have poor HRQOLs than men, but no statistical significance was found. Patients with non-intentional injury and hospitalized were more likely to have poor HRQOLs than patients with intentional injury and discharged, but the statistical significance varied with the measurement tool. CONCLUSION: In this study, we observed that the HRLOQs in patients with injury were lower than those in healthy subjects. However, if more definite feature of HRLOQ in patients with injury are to be defined, a study with a large epidemiologic controlled injury group and with detailed adjustments of the variable is needed.

Loperamide or Diazepam Improves Long-lasting Fecal Incontinence after Low Anterior Resection of the Rectum

PURPOSE: Some patients who underwent low anterior resection of the rectum do not show satisfying improvement in their anorectal function despite of long-term conservative management. The aim of this prospective study was to evaluate whether loperamide or diazepam could improve anorectal symptoms. METHODS: Fifty-two patients who continued to complain of problems with their anorectal function at least 6 months (mean: 1 year and 2 months) after the operation were recruited. The patients were randomly divided into two groups, and 2 mg of loperamide (loperamide-group, n=24) or diazepam (diazepam-group, n=28) was given orally three times a day for 4 weeks. Standardized interviews concerning anorectal function and anorectal physiologic studies were performed before medication, at the fourth week of medication, and 4 weeks after withdrawal from the medication. RESULTS: In both groups during the medication, daily stool frequency, the number of patients with urgency to defecate, and incontinence score significantly decreased, and maximal resting pressure and urge sensation volume significantly increased. In the diazepam-group, the decrease in daily stool frequency, the number of patients with urgency to defecate, and the increase in urge sensation volume continued after withdrawal from the medication. CONCLUSION: Loperamide or diazepam could improve the long-lasting fecal incontinence symptoms after low anterior resection in patients with rectal cancer. In the process, the increase in maximal resting pressure and urge sensation volume seemed to contribute to a significant degree.

Correlation between Health-related Quality of Life Score and Injury Severity Score in Patients with Injury in Emergency Department

PURPOSE: The purpose of this study is to show the correlation between Health-related quality of life (HRQOL) score and injury severity score (ISS) in patients with injury in emergency department. METHODS: Between November 1, 2003, and March 2, 2004, 234 eligible injury patients who had visited our emergency center were enrolled in the study. HRQOL was assessed in 10 days after injury by Korean Short Form Health Survey- 36(KSF-36), Korean EuroQol 5 dimensions (KEQ-5D), and Korean Human Utility Index-3(KHUI-3). The severity of injury was measured by using the ISS. RESULTS: Of the 234 subjects, 149(63.7%) were men and 85(36.3%) were women, with mean(+/-SD) age of 46.1(+/-15.3) and mean ISS(+/-SD) of 4.54(+/-3.98). The KEQ-5D and KHUI-3 scores adjusted by ISS in patients with medical operation or hospitalization were significantly lower than those in patients without medical operation or hospitalization. All HRQOL scores except KSF-36 physical component summary (PCS) and general health (GH) score were significantly lower in patients group with high ISS than in patients group with low ISS. KEQ-5D and KHUI-3 had significant negative correlation with ISS (r=-0.58,-0.52). But there were no significant correlation between KSF-36 score and ISS. CONCLUSION: In this study, we observed that KEQ-5D and KHUI-3 scores in patients with injury were significantly correlated with ISS. However, to define the more definite feature of HRQOL in patients with injury, the study with more and large epidemiologic controlled injury group and detailed variable adjustment should be done.

The Accuracy of Noncontrast Helical Computerized Tomography Versus Intravenous Pyelography in Patients with Suspected Acute Urolithiasis in the Emergency Department

PURPOSE: This study was performed to compare the accuracy of noncontrast helical computerized tomography (NHCT) with that of intravenous pyelography (IVP) in the evaluation of urolithiasis in the emergency room (ER). METHODS: Between November 2003 and February 2004, a total of 47 consecutive patients presenting to the emergency department with acute flank pain were evaluated with NHCT followed by IVP. The mean of the time interval between NHCT and IVP was less than 5 minutes. All 47 sets of evaluations were later assessed randomly by an independent consulting radiologist for the presence, size, and location of a stone, ureteral dilatation, and secondary signs of ureteral obstruction. RESULTS: Forty-three of the 47 patients were diagnosed with urolithiasis. In 39 of the 43 patients diagnosed with ureteral calculi, the NHCT made the diagnosis. IVP made the diagnosis in 26 of the 43 patients. NHCT had a 90.7% sensitivity, 100% specificity, and 68% accuracy. Compared with IVP, using the McNemar test, NHCT was significantly better able to predict the presence of urolithiasis (p<0.001). CONCLUSIONS: Unnenhanced helical CT is superior to IVP in the demonstration of ureteral calculi in patients with suspected acute urolithiasis in the ER.

Changes of Telomerase Activity and Proliferation by Inhibition of Reverse Transcriptase Activity in Human Cancer Cell / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Activation of telomerase is proposed to be an essential step in cancer cell immortalization and cancer progression. 3'-azido-2',3'-dideoxythymidine (AZT), a reverse transcriptase inhibitor, was reported to be incorporated in telomeric sequences of immortalized cells in culture and to suppress the activity of telomerase and the cell proliferation. In this study, after induction of cancer cell senescence with long-term treatment of AZT, we investigated the dynamics of telomerase subunits (hTERT, hTR, TEP), transcription factors (c-Myc, Mad1), telomerase activity, and finally, telomere length in a human breast cancer cell line. MATERIALS AND METGODS: Human breast cancer cell (MDA-MB-231) was treated with AZT. Senescence was measured by senescence-associated beta-gal staining and apoptosis was counted by dTd enzyme assay. Telomerase activity (by TRAP assay), expression of telomerase subunit genes (by RT-PCR and real-time PCR) and telomere length (by Southern blot analysis) were measured after the AZT treatment. RESULTS: We found evidences of senescence, apoptosis and growth delay after AZT treatment. In addition, AZT- treated cancer cells showed inhibition of telomerase activity and shortening of telomere length in a dose- and duration-dependent way. Among the telomerase subunits, hTERT and c-Myc were the first factors to change after AZT treatment, subsequently, followed by the changes of hTR, Mad1 and TEP. CONCLUSION: The suppression of hTERT and c-Myc by AZT treatment was the initial genetic phenomenon, subsequently followed by the changes of hTR, Mad1 and TEP.

The life of Dr. John William Heron, the second superintendent of Chejungwon / 의사학

The purpose of this paper is to overview the life of John W. Heron, M. D. who was the first appointed medical missionary to Korea by the Presbyterian Church USA. Although he was a competent doctor as well as a devoted missionary, he is not well-known yet, because he died early after 5 years' service in Korea. Dr. Heron was born in Derbyshire, England on June 15, 1856. His father, Rev. E. S. Heron, was a Scotch Minister of Congregational Church. His family emigrated to America in 1870 when he was fourteen years old and settled in Knoxville, Tennessee. In 1881, he was admitted to the University of Tennessee Medical School and graduated with highest honors in 1883. After training in New York University Hospital, he refused the offer of professorship from the University of Tennessee to become a medical missionary to Korea. He arrived in Seoul on June 21, 1885 and began to work in Royal Government Hospital, Chejungwon, the predecessor of Severance Hospital. In 1887, he became the superintendent of the Hospital following Dr. Horace N. Allen. He also worked for the Royal family and sometimes traveled to the rural areas to care for the patients. He started Chejungwon Church which later became Namdaemoon Presbyterian Church. In 1887, Dr. Heron worked as a member of the Bible translation committee and in 1889, he was elected as the chairman of the Public Committee of the Presbyterian Churches. In 1890, he established 'The Korean Religious Tract Society (Chosunsyungkyoseohoi) with Underwood and Ohlinger. The society published and replenished Christian books, periodical magazines and booklets. In the Summer of 1890, Dr. Heron did his best to take care of the sick suffering from an epidemic dysentery and himself got infected because of the terrible overwork. He passed away on July 26th, 1890. On his deathbed, he told his soldier and native friends around him as follow: "Jesus loves you. He gave His life for you. Stand by Him!" The martyrdom of Dr. Heron should be remembered in the Korean history of mission, because he was the first victim among the foreign missionaries who had lived and worked in Seoul for Korean mission. Dr. Heron's mind of love, service and devotion should be remembered by the medical doctors working today in caring for the patients suffering from physical and spiritual illnesses.

Application of Gabexate Mesylate IC against MMP - 9 Using ex vivo Model in Gastric Cancer: Prognostic Factor and Selection Criteria for Anti - MMP Treatment / 대한암학회지

PURPOSE: Among the many biological characteristics of cancer, matrix metalloproteinases(MMPs) are essential for tumor invasion and metastasis. The correction of the imbalance between MMPs and tissue inhibitors of matrix metalloproteinase (TIMP) has been suggested as a possible goal for the control of invasive phenotype of the cancer. To test the possible inhibition of MMP-9 in ex vivo model and the selection of the patients who are sensitive to MMP inhibitory (MMPI) treatment, we evaluated IC50 of the gabexate mesylate (Foy) against MMP-9 and compared them to the clinical parameters and patients survivals. MATERIALS AND METHODS: Thirty-four paired normal and gastric cancer tissues were tested for the IC50 of the gabexate mesylate. MMP-9 activity was measured by zymography. RESULTS: MMP-9 expression (percent of sample band density to control band) (p=0.04) and IC50 (p=0.02) of cancer tissues were significantly higher than those of normal tissues. Cancer tissue IC50 was higher than that of normal tissues in cases when the tumor mass diameter was longer than 5 cm (p=0.03) as well as in higher T-stage (p=0.04), lymph node metastasis (p=0.04) and in advanced stages (p=0.04). There was a tendency of increased IC50 of diffuse and mixed type than that of intestinal type (diffuse & mixed: 11.0+-20.8 mg/ml, intestinal: 2.7+-3.9 mg/ml; p 0.07), in spite of no difference in MMP-9 expression (diffuse & mixed: 40.3+49.2%, intestinal: 51.0+-58.0%). In early gastric cancer (EGC), there was no difference in IC50 between normal and cancer tissues whereas cancer tissue IC50 was higher than that of normal tissue in advanced gastric cancer (p 0.02). There was a tendency of increment of ICo in cancer tissues of advanced gastric cancer than that of EGC whereas no difference was found in MMP-9 expression between these types of cancers. Poor prognosis was found in high IC50 patients in curatively resected patients (p=0.04). In multivariate analysis, high IC50 was suggested as a possible independent prognostic factor. CONCLUSION: We could differentiate the high risk patients using IC50 of gabexate mesylate in ex vivo model. This model can be applied in detecting patients with poor prognosis and patients who can have a possible benefit with MMPI treatment.

Effects of Risperidone on the Schedule-Induced Polydipsia in Rats / 신경정신의학

OBJECTIVES: This study was designed to evaluate the effects of risperidone on the schedule-induced polydipsia (SIP) which is one of animal model of obsessive-compulsive disorder in rats. We administered risperidone as a serotonin and dopamine blocking agent, fluoxetine as a selective serotonin reuptake inhibitor, and haloperidol as a dopamine antagonist to rats which showed schedule-induced polydipsic behaviour. METHODS: Sprage-Dawley rats weighing 200 - 250gm were individually housed and main-tained and allowed free access to water. The rats were placed on a restricted diet. To induce polydipsia, rats were placed in the cage where a pellet dispenser automatically dispensed 90mg pellets on a fixed-time 60 seconds (FT 60s) feeding schedule over 150 minute test session per day. Water was available at all times in the cage. After 4 weeks of daily exposure to the FT 60s feeding schedule, experimental rats met a predetermined criterion for polydipsic behavior (greater than 3 times of water per session on average). 5 groups of rats were administered risperidone (0.1mg/kg, i.p), risperidone (0.5mg/kg, i.p), fluoxetine (5mg/kg, i.p.), haloperidol (0.1mg/kg, i.p.), and vehicle (1cc/kg, i.p. ) for 3 weeks. The rats were tested once a week to access schedule induced polydipsic behavior. Water bottles were weighed before and after the 150-minute test session. The chronic effects of administration of experimental drugs on schedule induced polydipsic behavior were analyzed with ANOVA and Scheffe test as a posthoc comparison. In order to measure water consumption in non-polydipsic food-deprived rats, a separate group of rats (N=8) was individually housed and given a single bolus (14.5gm) of food per day which maintained them at their average body weight. RESULTS: The results were as follows; 1) After 4 weeks of scheduled feeding procedure, the experimental group showed significant differences than the bolus control in the amount of water consumption as compared with their average water intakes for 4 weeks. At the same periods, there were no differences between the experimental group and the bolus control in the body weight. 2) The fluoxetine group showed significant decrease in the amount of water intake at 1st, 2nd, and 3rd weeks of drug treatment as compared with their average amount of polydipsic water intakes. The risperidone 0.1mg group and the risperidone 0.5mg group showed significant decrease in the amount of water intake at the 3rd weeks of drug treatment as compared with their baseline of polydipsic water intakes. However, the haloperidol group and the vehicle control group showed no changes of amounts of water intake for 3 weeks of treatment as compared with their baseline of polydipsic water intakes. 3) The fluoxetine group (22.5+/-10.4ml) showed significantly lower amounts of water intake than haloperidol group (41.3+/-7.1ml) at 2nd weeks of drug treatment. And also the fluoxetine group (18.8+/-3.5ml) showed significantly lower amounts of water intake than the haloperidol group (35.0+/-11.7ml) and the vehicle control (34.4+/-6.8ml) at 3rd weeks of drug treatment. The risperidone 0.1mg group and the risperidone 0.5mg group showed significantly lower amounts of water intake than the haloperidol group (35.0+/-11.7ml) at 2nd weeks and the vehicle control (37.5+/-12.5 , 34.4+/-6.8ml) at 2nd and 3rd weeks of drug treatment. CONCLUSIONS: Above findings suggest that the fixed time feeding procedure for schedule induced polydipsia could be applied as an effective animal model of obsessive compulsive disorder for the evaluation of pharmacological challenge study. We confirmed that chronic treatment with risperidone revealed antipolydipsic effect as effective as fluoxetine on the schedule-induced polydipsic behaviour but the onset of effect was later than fluoxetine.

Prospective Evaluation of Colorectal Polyps in 1,683 Consecutive Colonoscopies / 대한소화기내시경학회지

BACKGROUND AND AIMS: The colorectal polyp, particularly the adenoma, has been regarded as a precursor of cancer. The incidence of colorectal polyps has been reported at various rates according to investigation centers in foreign countries. In Korea, the incidence of colorectal polyps has been reported as very low according to the few reports, which was involved a few cases and were partial. Therefore, the aim of this study is to evaluate prospectively the incidence and the clinicopathologic features of colorectal polyps. METHODS: A colonoscope was inserted up into the cecum in 1,889 patients among 2,001 trials from Oct. 1996 to Aug. 1997 (success rate: 94.4%). Of the 1,889 full colonoscopies, the following were excluded; 1) referred patients with suspicious colorectal cancer or polyps, 2) patients with suspicious rectal cancer determined by rectal examination, 3) patients who had follow-up colonoscopy after a polypectomy or cancer surgery, and 4) patients who had periodic colonoscopy due to FAP or HNPCC. There were a total of 1,683 full colonoscopies in this study. The majority of the total cases involved a colonoscopy due to benign anal disease, irritable bowel syndrome, or routinechecks for health. RESULTS: There were 946 men (56.2%) and 737 women (43.8%). The mean age was 48.2 yrs (13~88 yrs) for men and 48.1 yrs (18~89 yrs) for women. 422 patients were found to have 645 colorectal polyps (1.52 polyps per patient). The incidence of polyps was 25.1% (32.0% for men, 16.1% for women) and increased after the 6th decade in men (44.0%) and in women (23.0%). 281 patients were found to have 426 colorectal adenomas. The incidence of adenomas was 16.6% (21.9% for men, 9.9% for women) and increased after the 6th decade, 32.0% in men, and 15.9% in women. Solitary polyps were present in 277 patients (65.6%) while 94 patients (22.3%) had two polyps and 51 patients (12.1%) had between 3 and 8 polyps. The polyp retrieval rate was 96.9%. There were 426 adenomas (66.0%), 75 hyperplastic (11.7%), 120 inflammatory (18.6%), and 24 miscellaneous (3.7%) polyps. Of the 426 adenoma, there were 397 tubular adenoma (93.2%), 18 tubulovillous adenoma (4.3%), 4 villous adenoma (0.9%), 6 in situ carcinoma (1.4%), and 1 invasive carcinoma (0.2%). 6 in situ carcinoma's were detected in tubular adenoma and 1 invasive carcinoma in tubulovillous adenoma. Of 645 polyps, the sessile type was 87.9%. The polyp size varied from 1 mm to 25 mm and 79.2% were under 5mm. Also, 85.7% of adenomas were sessile and 74.7% were under 5mm. 22.0% of polyps were located in rectum, 35.4% in sigmoid colon, 9.5% in descending colon, 13.3% in transverse colon, 19.8% in ascending colon and cecum. The distribution of adenoma was similar to that of polyp. 40.1% of adenoma showed moderate to severe dysplasia. CONCLUSIONS: This study revealed that the incidence of polyp in Korea was higher than that in previous reports and 42.6% of polyps were proximal to rectosigmoid colon. Therefore, we suggest that we should try to detect and remove colorectal polyps by more active colonoscopy.

Clinical Significance of Lymph Node Micrometastasis in Dukes' Stage A&B Colorectal Cancer: An Immunohistochemical Study

PURPOSE: Lymph node metastasis is the most important prognostic factor in colorectal cancer. However, 20~30% of patients with lymph node negative colorectal cancer die of recurrent disease. We investigated whether the detection of micrometastasis is of any clinical significance in Dukes' stage A & B colorectal cancer. METHODS: Ninety patients who underwent curative resection of colorectal cancer from Aug. of 1996 to Jan. of 1999 were entered the study. For examination, we used paraffin blocks of lymph nodes which were metastasis-free by conventional histopathology. After preparation of tissue blocks using the serial sectioning technique, the specimens were stained with immunohistochemical method using anticytokeratin antibody. And the hematoxylin-eosin staining was repeated. RESULTS: We disclosed micrometastases in 15 of 90 cases, mostly located in subcapsular sinuses. And in 8 of 15 cases, we also found metastases in repeated H&E staining. There were no significant relationship between the detection of micrometastases and the depth of wall invasion, the histological grade and the status of lymphovascular invasion. With median follow-up of 15 months, we found no significant difference in recurrence between the micrometasis positive and negative groups. CONCLUSIONS: The result showed that the micrometastasis of lymph node in colorectal caner might increase the risk for development of tumor recurrence. But because of small numbers of recurrent cases and relatively short follow-up period, there was no statistically significant relationship between micrometastasis negative and positive groups.

Semi - quantitative Comparison of Terminal Restriction Fragment Length and Telomerase in Breast Cancer for Biotherapy / 대한암학회지

PURPOSE: We determined the clinical significance of telomerase activity and telomere length in breast cancer patients and also developed the measuring system of telomerase activity change with RNAse A pre-treatment. MATERIALS AND METHODS: We measured the telomerase activity in 71 breast cancer tissues and paired normal tissues with TRAP (Telomeric Repeat Amplification Protocol) assay. Telomerase activity was calculated by computer-assisted densitometry compared to telomerase activity of the 293 control cell line. To develop the measuring system of telomerase activity modulation, we measured the telomerase activity after the treatment with RNAse A, 150microgram/ml, which inhibited 70% of telomerase activity compared to control in the 293 control cell line. In 59 paired tissues with telomerase activity, terminal restriction fragment (TRFs) length were measured using Southern blotting. RESULTS: Sixty-three out of 71 cancer tissues showed telomerase activity (88.7%), while no telomerase activity was detected in their paired normal tissues. Telomerase activity was correlated to the node metastasis (p=0.02) and stage (p=0.005), but not to the tumor size or the hormonal receptor status. TRFs were neither specific to tumor tissues nor related to any of the clinical parameters. However, changes of TRFs of the tumor tissues from their paired normal tissues were correlated to the telomerase activities. Also the patients with different TRFs between cancer and normal tissues were in more advanced stage. After pre-treatment with the 150microgram/ml of RNAse A, telomerase activity in the tumor tissues showed variable inhibition. Relative inhibition, the ratio of inhibited telomerase activity in each tumor tissue compared to the inhibition of 293 control cell line, was proportional to the telomerase activity. CONCLUSION: In breast cancer, telomerase activity was specific to the tumor tissues and correlated to tumor progression. A combination of telomerase activity and TRFs changes can be used as a guidline in detecting a better candidate for telomerase inhibition. Semi-quantitative assay with RI system can be used in evaluating the changes of telomerase activity after treatment with a new telomerase inhibitor with TRAP assay.

Restoration of Wild - type p53 Induces Chemo-sensitization in the Gastric Cancer Cell Line with Mutant p53 / 대한암학회지

PURPOSE: It has been theorized that p53 may be involved in the sensitivity to chemotherapeutic agents. We evaluated the chemosensitivity of wild p53 after transduction into gastric cancer cell lines with mutant p53. MATERIALS AND METHODS: YCC-3(parent cell line with mutant p53), YCC-3v(parent cell line transduced with vector alone) and YCC-3C3(clone with wild p53) cell lines were used in this study. p53 protein expression was measured by ELISA assay. Tumorigenicity and drug sensitivity were evaluated by soft agar and proliferation assay, respectively. Cell cycle analysis was performed by flowcytometry. Telomerase activity was measured by TRAP assay and terminal restriction fragment(TRF) length was measured after Southern blot analysis. RESULTS: Even though p53 production from the YCC-3C3 cell line was three times higher than those of YCC-3 and YCC-3v cell lines, the cell cycle was the same in these three cell lines. In the YCC-3C3 cell line, drug sensitivity to etoposide and cisplatin was increased when we compared it to those of the YCC-3v cell line(etoposide, 50% versus 83%; cisplatin, 67% versus 83%). However, there was no chemo-sensitization effect with vincristine, vinblastine and carboplatin. After exposure to cisplatin, a G0/G1 check-point effect was found in the YCC-3C3 cell line, but not in the YCC-3v cell line. No differences were found in telomerase activity, TRFs length or DNA fragmentation between the YCC-3v and YCC-3C3 cell lines after cisplatin treatment. CONCLUSION: Wild-type p53 gene transduction in the gastric cancer cell line induced sensitization to the cytotoxicity of etoposide and cisplatin. This suggests the possible application of combined chemo-gene therapy with an EP regimen and wild-type p53 in gastric cancer patients with p53 mutation.

Effect on Malignant Phenotype of Gastric Cancer Cell Line after p53 Gene Transduction / 대한암학회지

PURPOSE: To evaluate the effect of wild type p53 gene transduction on the malignant phenotypes for metastasis in gastric cancer, we compared the biological phenpotypes of gastric cancer cell lines based on p53 gene status. Then, after retrovirus-mediated wild-type p53 gene transduction, we compared those phenotypes among parent YCC-3 cell line, vector transduced YCC-3v cell line and a clone of YCC-3C3. MATERIAL AND METHODS: Four human gastric cancer celi lines were used; YCC-l(mutant), YCC-2(wild), YCC-3(mutant) and AGS(wild). DNAs of the cell lines were analyzed to evaluate the mobility shift with PCR-SSCP. Tumorigenecity and proliferation were evaluated by soft agar assay and proliferation assay. Migratory capacity was measured by adhesion assay and Boyden chamber assay. p53 protein expression was measured by Western blot analysis and VEGF, WAF-1 were measured by ELISA assay. Angiogenic activity was measured by cross-feeding assay and cell cycle analysis was performed by flowcytometry. In vivo tumorigenicity was measured by xenograft in nude mice. RESULTS: YCC-3 cell line with mutant p53 gene expressed all the phenotypes for the metastasis such as tumorigenicity, migration and angiogenesis. In a stable clone of YCC-3C3, no differences were found in proliferation, cell cycle and WAP-1 expression when compared to those of the control YCC-3v and parent YCC-3 cell line, even if increased p53 protein production was found by Western blot analysis. However, both in vitro and in vivo tumorigenicity were decreased in a stably transduced YCC-3C3 clone. The adhesive capacity was also decreased in YCC-3C3 clone whereas the endothelial cell growth stimulatory effect and VEGF production showed no difference compared to those of the YCC-3v cell line. CONCLUSION: Wild-type p53 gene transduction in gastric cancer cell line decreased tumorigenicity which resulted from decreased colony forming activity and adhesive capacity but not formed changes of angiogenic activity. This suggested the possible application of anti- metastasis strategy with p53 gene therapy in gastric cancer.