• 한국발생생물학회지:발생과생식
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• 제21권2호
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• pp.139-150
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• 2017

Metformin is the most commonly prescribed anti-diabetic drug with relatively minor side effect. Substantial evidence has suggested that metformin is associated with decreased cancer risk and anticancer activity against diverse cancer cells. The tyrosine kinase inhibitor imatinib has shown powerful activity for treatment of chronic myeloid leukemia and also induces growth arrest and apoptosis in colorectal cancer cells. In this study, we tested the combination of imatinib and metformin against HCT15 colorectal cancer cells for effects on cell viability, cell cycle and autophagy. Our data show that metformin synergistically enhances the imatinib cytotoxicity in HCT15 cells as indicated by combination and drug reduction indices. We also demonstrate that the combination causes synergistic down-regulation of pERK, cell cycle arrest in S and $G_2/M$ phases via reduction of cyclin B1 level. Moreover, the combination resulted in autophagy induction as revealed by increased acidic vesicular organelles and cleaved form of LC3-II. Inhibition of autophagic process by chloroquine led to decreased cell viability, suggesting that induction of autophagy seems to play a cell protective role that may act against anticancer effects. In conclusion, our present data suggest that metformin in combination with imatinib might be a promising therapeutic option in colorectal cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5441-5447
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• 2013

Purpose: To demonstrate the value of sequential determinations of pelvic drainage in the identification of increased risk of anastomotic leakage (AL) after anterior resection for rectal cancer with a double stapling technique. Patients and Methods: Between January 2004 and December 2011, data for the daily postoperative pH of pelvic drainage fluid in 753 consecutive patients with rectal cancer who initially underwent anterior resection with a double stapling technique were reviewed. All patients experienced a total mesorectal excision. Patients with anastomotic leakage (Group AL, n=57) were compared to patients without leakage (Group nAL, n=696). Patients with perioperatively abdominopelvic implants that were likely to affect pH value (determined at $25^{\circ}C$) other than leakage were excluded. Mean postoperative values were compared. Results: Anastomotic leakage was noted in 57 (7.6%) of 753 patients with rectal cancer. The diagnosis of AL was made between the $6^{th}$ and $12^{th}$ postoperative day (POD; mean $8^{th}$ POD). There was no significance of the daily average values of pH on POD1 & 2 in group AL while a significantly sharp declining mean pH value reached its diagnostic point of AL (p<0.001) on POD3. A cut-off value of 6.978 on the $3^{rd}$ POD maximized the sensitivity (98.7.0%) and specificity (94.7%) in assessing the risk of leakage. Conclusion: According to these results, an early and persistent declining of pH value of pelvic drainage fluid after rectal surgery with anastomosis, is a marker of AL. A cut-off value of 6.798 determined at $25^{\circ}C$ on POD3 maximizes sensitivity and specificity.

• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1521-1525
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• 2014

Background: Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide and the association between HPV infection and genital cancers has been well established. This study concerned the possible role of HPV infection in colorectal carcinoma (CRC) in the Iranian population. Materials and Methods: We examined 80 tissues obtained from patients with colorectal cancer consisting of 58 colon cancer samples and 22 rectal cancer samples and 80 tissues from patients with unremarkable pathologic changes as matched controls by sex, study center and anatomical sites. HPV infection and genotypes were detected using nested PCR and sequencing methods, respectively. Results: HPV DNA was detected in 5/80 (6.25%) cases including 1 of 22 (4.54%) patients with rectum cancer and 4 of 58 (6.9%) patients with colon cancer and 1/80 (1.25%) of controls. Furthermore, HPV-18 was detected as the most frequent type and we found no significant correlation between prevalence of HPV infection and anatomical sub- sites. Conclusions: Although a causal relation between human papillomavirus and colorectal cancer was not found through this study, analysis of medical records pointed to a possible role for high- risk types of HPV in increasing the potential of aggressiveness in colorectal cancer. This study shows a particular frequency of HPV genotypes in patients with colorectal cancer in Iran. Since HPV vaccines are limited to a few types of virus, using cohort studies in different geographical zones to screen for patterns of HPV infection in different organs might increase the efficacy and optimization of the current vaccines.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2031-2037
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• 2012

Background: Analysis of gene-gene and gene-environment interactions for complex multifactorial human disease faces challenges regarding statistical methodology. One major difficulty is partly due to the limitations of parametric-statistical methods for detection of gene effects that are dependent solely or partially on interactions with other genes or environmental exposures. Based on our previous case-control study in Chongqing of China, we have found increased risk of colorectal cancer exists in individuals carrying a novel homozygous TT at locus rs1329149 and known homozygous AA at locus rs671. Methods: In this study, we proposed statistical method-crossover analysis in combination with logistic regression model, to further analyze our data and focus on assessing gene-environmental interactions for colorectal cancer. Results: The results of the crossover analysis showed that there are possible multiplicative interactions between loci rs671 and rs1329149 with alcohol consumption. Multifactorial logistic regression analysis also validated that loci rs671 and rs1329149 both exhibited a multiplicative interaction with alcohol consumption. Moreover, we also found additive interactions between any pair of two factors (among the four risk factors: gene loci rs671, rs1329149, age and alcohol consumption) through the crossover analysis, which was not evident on logistic regression. Conclusions: In conclusion, the method based on crossover analysis-logistic regression is successful in assessing additive and multiplicative gene-environment interactions, and in revealing synergistic effects of gene loci rs671 and rs1329149 with alcohol consumption in the pathogenesis and development of colorectal cancer.

• Journal of Korean Biological Nursing Science
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• 제13권2호
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• pp.164-173
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• 2011

Purpose: The colorectal polyps has been regarded as a precursor of colon cancer, and the prevalence and mortality of colon cancer in Korea has increased due to westernized lifestyle and environmental factors. The purpose of this study was to investigate the characteristics and the risk factors on colorectal polyps in adults. Methods: The participants were 956 adults enrolled from health screen examinees underwent colonoscopy at the health promotion center in Seoul. Results: 49.5 percent of examinees has colorectal polyps and the most common sites were ascending colon (27.6%) and sigmoid colon (23.2%). The colorectal polyps showed a significant difference according to gender, age, and health behavior related characteristics including alcohol intake, exercise, and BMI. In male, the relative odds of having an colorectal polyps decreased as exercise (OR=1.74; 95% CI=1.01-1.04), and increased as BMI (OR=1.57; 95% CI=1.07-2.50) and age (OR=1.02; 95% CI=1.02-1.04). In female, it decreased as exercise (OR=2.49; 95% CI=1.52-4.10), and increased as age (OR=1.05; 95% CI=1.02-1.08). Conclusion: Based on the findings of this study, age and exercise were the influencing factors of colorectal polyps in health screen examinees. Therefore, effective exercise and appropriate health education program about colorectal polyps need to be developed and applied in nursing interventions to prevent colorectal polyps in the community dwelling adults.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7327-7331
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• 2014

Background: We had previously showed that the neutrophil lymphocyte ratio (NLR), ${\gamma}$-glutamyl transpeptidase (GGT) and carcinoembryonic antigen (CEA) are prognostic factors for metastatic colorectal cancer (mCRC) patients. In this study we developed a prognostic model based on these three indices. Materials and Methods: A total of 243 patients who were initially diagnosed as mCRC between 2005 and 2010 in the Sun Yat-sen University Cancer Center were studied. The endpoint was overall survival (OS). Results: NLR>3, elevated GGT and elevated CEA were confirmed as independent risk factors which could predict poor prognosis. Patients could be divided into three groups according to the number of risk factors they had. Those with two or three were defined as the high risk group, individuals with one risk factor as the modest risk group and patients without risk factor as the low risk group. The OS values for these three groups were 16.2 months (2.80~68.8), 24.2 months (4.07~79.0), and 37.2 months (12.6~87.8), respectively (p<0.001). Conclusions: We developed a simple but useful model based on NLR, GGT and CEA to provide prognostic information to clinical practice in highly selected mCRC patients. Further prospective and multi-center studies are warranted to test our model.

• Asian Pacific Journal of Cancer Prevention
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• 제16권10호
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• pp.4229-4235
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• 2015

Background: Colorectal cancer (CRC is increasingly becoming a major cause of cancer morbidity and mortality in Jordan. However the population's level of awareness about CRC, CRC screening test preferences and willingness to embrace screening are not known. The aim of this study was to assess the level of CRC awareness and screening preferences among Jordanian patients. Materials and Methods: A survey assessing the CRC knowledge levels was distributed among patients attending outpatient gastroenterology clinics in public hospitals throughout Jordan. A total of 800 surveys were distributed and of these 713 (89.1%) were returned. Results: Only 22% of the participants correctly judged CRC among the choices provided as the commonest cause of cancer related deaths. The majority of participants (68.3%) underestimated their risk for CRC. Only 26.8% correctly judged their life time risk while 5% overestimated their risk. Two thirds of participants (66%) were willing to pay 500 Jordanian Dinars (equivalent to 706 US$) in order to get a prompt colonoscopy if recommended by their physician, while 25.5% reported that they would rather wait for 6 months in order to get a free colonoscopy. Conclusions: Although the participants tended to underestimate their risk for CRC, they were mostly aware of CRC as a major cause of mortality and were willing to embrace the concept of CRC screening and bear the related financial costs. These findings about CRC awareness and propensity for screening provide a good foundation as the Jordanian health system moves forward with initiatives to promote CRC screening and prevention.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5207-5212
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• 2013

Background: Physical activity has been found to play a role in cancer prevention. The purpose of this matched case-control study was to investigate the association between physical activity levels, water intake, constipation and colorectal cancer (CRC). Materials and Methods: Two hundred and thirty-two patients diagnosed with CRC (125 male, 107 female) were enrolled in this case-control study. Cases were matched to 271 population controls (137 male, 134 female). Results: Drinking more than 4 cups of water daily decreased the risk of CRC by 33-42%; however, this effect was non-significant. Having constipation was found to be a significant risk factor for developing CRC with an OR=6.284 (95%CI=2.741-14.40). With reference to sedentary behavior, minimum activity (600-3000 Metabolic Equivalents Task (MET)) had 43% protection against CRC and the level of Health Enhancing Physical Activity OR was 0.58 (at 95%CI; 0.37-0.92). A significant negative association was found between CRC and physical activity levels expressed as both METs and MET-hours/week (p for trend=0.017 and 0.03, respectively). Among females, a significant trend of reduction in CRC by 62% was observed with increasing the level of physical activity expressed in MET (p for trend=0.04). Conclusions: The risk of CRC may be reduced by adopting a healthy lifestyle and practicing physically activity regularly, especially among females. Consuming adequate amounts of water and healthy bowel motility could also reduce the risk of CRC.

• Journal of Preventive Medicine and Public Health
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• 제45권4호
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• pp.251-258
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• 2012

Objectives: The purpose of this paper was to elucidate the potential methylation levels of adjacent normal and cancer tissues by comparing them with normal colorectal tissues, and to describe the correlations between the methylation and clinical parameters in Korean colorectal cancer (CRC) patients. Methods: Hypermethylation profiles of nine genes (RASSF1, APC, $p16^{INK4a}$, Twist1, E-cadherin, TIMP3, Smad4, COX2, and ABCB1) were examined with 100 sets of cancer tissues and 14 normal colorectal tissues. We determined the hypermethylation at a given level by a percent of methylation ratio value of 10 using quantitative methylation real-time polymerase chain reaction. Results: Nine genes' hypermethylation levels in Korean CRC patient tissues were increased more higher than normal colorectal tissues. However, the amounts of $p16^{INK4a}$ and E-cadherin gene hypermethylation in normal and CRC tissues were not significantly different nor did TIMP3 gene hypermethylation in adjacent normal and cancer tissues differ significantly. The hypermethylation of TIMP3, Ecadherin, ABCB1, and COX2 genes among other genes were abundantly found in normal colorectal tissues. The hypermethylation of nine genes' methylation in cancer tissues was not significantly associated with any clinical parameters. In Cohen's kappa test, it was moderately observed that RASSF1 was related with E-cadherin, and Smad4 with ABCB1 and COX2. Conclusions: This study provides evidence for different hypermethylation patterns of cancer-associated genes in normal and CRC tissues, which may serve as useful information on CRC cancer progression.

• Journal of Preventive Medicine and Public Health
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• 제41권1호
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• pp.23-29
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• 2008

Objectives : We examined the association between alcohol consumption and incidence of colorectal cancer in elderly Koreans. Methods : The cohort members (n=14,304) consisted of 4,834 males and 9,470 females derived from the Korea Elderly Pharmacoepidemiologic Cohort (KEPEC), a population-based dynamic cohort. They were aged 65 years old or older and lived in Busan between 1993-1998; they were beneficiaries of the Korean Medical Insurance Corporation (KMIC). Baseline information was surveyed by a self-administered, mailed questionnaire. This study population was restricted to 14,304 participants who reported alcohol drinking habits on the questionnaire and had not been diagnosed with colorectal cancer at baseline. The adjusted hazard ratios (aHR) of status, type, frequency and daily average amount of alcohol consumption were computed with Cox's proportional hazard model, with the never-drinkers as a reference group and controlling for age and gender. Results : After 4.82 person-years of mean follow-up 112 cases of colorectal cancer occurred. The incidence densities of colorectal cancer were 161 (95% CI=123-200) for never-drinkers, 219 (95% CI=125-339) for ex-drinkers, and 137 (95% CI=84-189) for current-drinkers per 100,000 person-year. The status, type, frequency, and daily average amount of alcohol consumption were not significantly related to the incidence of colorectal cancer after controlling for age and gender. Conclusions : There was no significant association between alcohol consumption and colorectal cancer among elderly people after controlling for age and gender.