• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6249-6256
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• 2013

One-carbon metabolism plays an important role in colorectal carcinogenesis. Meta-analyses have suggested protective associations of folate and vitamin $B_6$ intakes with colorectal cancer primarily based on studies in Caucasians, and genetic polymorphisms pertaining to the folate metabolism have been a matter of interest. Less investigated are the roles of methionine synthase (MTR) and thymidylate synthetase (TS) polymorphisms in colorectal carcinogenesis. In a study of 816 cases and 815 community controls in Japan, we investigated associations of dietary intakes of folate, methionine, vitamin $B_2$, vitamin $B_6$, and vitamin $B_{12}$ with colorectal cancer risk. The associations with MTR 2756A>G, MTRR 66A>G, and TSER repeat polymorphism were examined in 685 cases and 778 controls. Methionine and vitamin $B_{12}$ intakes were inversely associated with colorectal cancer risk, but the associations were totally confounded by dietary calcium and n-3 fatty acids. The other nutrients showed no association with the risk even without adjustment for calcium and n-3 fatty acids. The TSER 2R allele was dose-dependently associated with an increased risk. The MTR and MTRR polymorphisms were unrelated to colorectal cancer risk. There was no measurable gene-gene or gene-nutrient interaction, but increased risk associated with the TSER 2R allele seemed to be confined to individuals with high folate status. This study does not support protective associations for folate and vitamin $B_6$. The TSER 2R allele may confer an increased risk of colorectal cancer. The role of the TSER polymorphism in colorectal carcinogenesis may differ by ethnicity.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.5
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• pp.383-390
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• 2014

Gastrointestinal motility consists of phasic slow-wave contractions and the migrating motor complex (MMC). Eupatilin (Stillen$^{(R)}$) has been widely used to treat gastritis and peptic ulcers, and various cytokines and neuropeptides are thought to be involved, which can affect gastrointestinal motility. We performed a study to identify the effects of eupatilin on lower gastrointestinal motility with electromechanical recordings of smooth muscles in the human ileum and colon. Ileum and colon samples were obtained from patients undergoing bowel resection. The tissues were immediately stored in oxygenated Krebs-Ringer's bicarbonate solution, and conventional microelectrode recordings from muscle cells and tension recordings from muscle strips and ileal or colonic segments were performed. Eupatilin was perfused into the tissue chamber, and changes in membrane potentials and contractions were measured. Hyperpolarization of resting membrane potential (RMP) was observed after administration of eupatilin. The amplitude, AUC, and frequency of tension recordings from circular and longitudinal smooth muscle strips and bowel segments of the ileum and colon were significantly decreased after admission of eupatilin. Eupatilin elicited dose-dependent decreases during segmental tension recordings. In conclusion, eupatilin (Stillen$^{(R)}$) showed inhibitory effects on the human ileum and colon. We propose that this drug may be useful for treating diseases that increase bowel motility, but further studies are necessary.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1663-1666
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• 2012

Background and Objective: Protein expression in colon and rectal cancer (CRC) and paired normal tissues was examined by two-dimensional gel electrophoresis (2-DE) to identify differentially expressed proteins. Materials and Methods: Five fresh colorectal cancer and paired adjacent normal tissues were obtained and differentially expressed protein spots were determined using PDQuest software, with identification on the basis of MALDI-TOF mass spectra. Results: Compared with normal colorectal mucosa, protein abnormal expression of 65 spots varying more than 1.5 times were found in 2-DE gels from colorectal cancer samples (P<0.05); forty-two proteins were up-regulated and 23 were down-regulated; twelve protein spots were identified using mass spectrometry, of which 8 were up-regulated, includimng HSPB1and Annexin A4, while 4 were down-regulated, the results being consistent with Western blot findings. Conclusions: Two-dimensional electrophoresis reference maps for CRC tissues and adjacent normal mucosa (NMC) were established and 12 differentially expressed proteins were identified. Up-regulated HSPB1 and Annexin A4 may play many important roles in the pathogenesis of colorectal cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3111-3116
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• 2016

Background: The goal of this study was to compare the rate of recurrence and occurrence of complications in colorectal cancer patients after two kinds of laparoscopy and laparotomy. Materials and Methods: A follow-up study was carried out among 358 patients who suffered from colorectal cancer from 2012-2014. The data were gathered from colorectal research center in Shiraz, Shahid Faghihi hospital, and analyzed using the chi-square test, logistic regression, and multinomial regression. Results: The average age of these patients was $56.3{\pm}14.6$, 55.0% being men. Moreover, 57.8% of them underwent laparoscopy surgery and 42.2% of the patients underwent laparotomysurgery and the conversion rate was 58.0% which ultimately was put under the category of laparotomy surgery. After biennial median follow-up, differences in the occurrence of complications such as bleeding (hemorrhage), fever, intestine blockage and wound infection in these two kinds of surgery werestatistically significant (P<0.05). However, the rate of recurrence and the patients' ultimate status (alive without disease, alive with disease, and death) did not significantly differ between these two surgery groups. Conclusions: Post-operation complications were laparoscopy surgery were less than those in laparotomy. However, the outcomes such as patients' ultimate status and recurrence were similar between the two groups.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1975-1979
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• 2013

Aim: To investigate the level of expression of proto-oncogene Wip1 and its physiological significance in colorectal cancer. Methods: Immunohistochemistry, semi-quantitative RT-PCR, and Western blotting were used to analyze Wip1 mRNA and protein expression in 120 cases of colorectal cancer and normal tissues to study relationships with clinical symptoms and disease prognosis. Results: The level of Wip1 protein expression was found to be significantly higher in colorectal cancer tissues (85% (102/120)) than in normal tissues (30% (36/120)) (P<0.05). The relative amount of Wip1 protein in colorectal cancer tissue was also found to be significantly higher (P<0.05) than in normal tissues ($1.060{\pm}0.02$ and $0.640{\pm}0.023$, respectively). Semi-quantitative RT-PCR showed average Wip1 mRNA expression levels to be $1.113{\pm}0.018$ and $0.658{\pm}0.036$ for colorectal cancer tissue and adjacent normal tissue (P<0.05). The level of Wip1 protein expression was not correlated with age, gender, or tumor site, but appeared linked with lymph node metastasis, Dukes stage, histological grade, and liver metastasis. Individuals with high and low levels of Wip1 expression showed statistically significant differences in the five-year overall survival and recurrence-free survival rates (P<0.05). Conclusion: Wip1 mRNA and protein are highly expressed in colorectal cancers and may be associated with colorectal cancer development and progression.

• BMB Reports
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• v.44 no.5
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• pp.317-322
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• 2011

Hereditary non-polyposis Colorectal Cancer (HNPCC) is an autosomal dominant inheritance syndrome. HNPCC is the most common hereditary variant of colorectal cancer (CRC), which accounts for 2-5% CRCs, mainly due to hMLH1 and hMSH2 mutations that impair DNA repair functions. Our study aimed to identify the patterns of hMSH2 and hMLH1 mutations in Chinese HNPCC patients. Ninety-eight unrelated families from China meeting Amsterdam or Bethesda criteria were included in our study. Germline mutations in MLH1 and MSH2 genes, located in the exons and the splice-site junctions, were screened in the 98 probands by direct sequencing. Eleven mutations were found in ten patients (11%), with six in MLH1 (54.5%) and five in MSH2 (45.5%) genes. One patient had mutations in both MLH1 and MSH2 genes. Three novel mutations in MLH1 gene (c.157_160delGAGG, c.2157dupT and c.-64G>T) were found for the first time, and one suspected hotspot in MSH2 (c.1168C>T) was revealed.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.631-638
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• 2016

Radiation proctitis is a common complication after radiotherapy for pelvic malignant tumors. This study was conducted to assess the efficacy of novel almagate enemas in hemorrhagic chronic radiation proctitis (CRP) and evaluate risk factors related to rectal deep ulcer or fistula secondary to CRP. All patients underwent a colonoscopy to confirm the diagnosis of CRP and symptoms were graded. Typical endoscopic and pathological images, risk factors, and quality of life were also recorded. A total of 59 patients were enrolled. Gynecological cancers composed 93.1% of the primary malignancies. Complete or obvious reduction of bleeding was observed in 90% (53/59) patients after almagate enema. The mean score of bleeding improved from 2.17 to 0.83 (P<0.001) after the enemas. The mean response time was 12 days. No adverse effects were found. Moreover, long-term successful rate in controlling bleeding was 69% and the quality of life was dramatically improved (P=0.001). The efficacy was equivalent to rectal sucralfate, but the almagate with its antacid properties acted more rapidly than sucralfate. Furthermore, we firstly found that moderate to severe anemia was the risk factor of CRP patients who developed rectal deep ulcer or fistulas (P= 0.015). We also found abnormal hyaline-like thick wall vessels, which revealed endarteritis obliterans and the fibrosis underlying this disease. These findings indicate that almagate enema is a novel effective, rapid and well-tolerated method for hemorrhagic CRP. Moderate to severe anemia is a risk factor for deep ulceration or fistula.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.665-669
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• 2012

Aim: The distribution of DNA repair gene XRCC1 and XRCC3 genotypes was used to assess the potential influence of genetic polymorphisms on risk of colorectal cancer, and interactions with other factors. Methods: a 1:2 matched case-control study was conducted with 485 cases and 970 controls. XRCC1 and XRCC2 genotype polymorphisms were based upon duplex polymerase-chain-reaction with the confronting-two-pairprimer (PCR-CTPP) method. Results:The XRCC1 399Cln allele polymorphism was found to be associated with an increased colorectal cancer risk, while an non-significant inversely association was noted for XRCC3 241Thr/Thr genotype. We also found that individuals with the XRCC1 399 Gln and XRCC3 241Met alleles had an elevated risk, while XRCC3241Thr/Thr was proctective. Conclusion: This study is the first to provide evidence of importance of XRCC1 and XRCC3 gene polymorphisms for risk of colorectal cancer in the Chinese population.

• Journal of Preventive Medicine and Public Health
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• v.46 no.2
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• pp.74-81
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• 2013

Objectives: The objective of this study was to evaluate the performance of risk-adjusted mortality models for colorectal cancer surgery. Methods: We investigated patients (n=652) who had undergone colorectal cancer surgery (colectomy, colectomy of the rectum and sigmoid colon, total colectomy, total proctectomy) at five teaching hospitals during 2008. Mortality was defined as 30-day or in-hospital surgical mortality. Risk-adjusted mortality models were constructed using claims data (basic model) with the addition of TNM staging (TNM model), physiological data (physiological model), surgical data (surgical model), or all clinical data (composite model). Multiple logistic regression analysis was performed to develop the risk-adjustment models. To compare the performance of the models, both c-statistics using Hanley-McNeil pair-wise testing and the ratio of the observed to the expected mortality within quartiles of mortality risk were evaluated to assess the abilities of discrimination and calibration. Results: The physiological model (c=0.92), surgical model (c=0.92), and composite model (c=0.93) displayed a similar improvement in discrimination, whereas the TNM model (c=0.87) displayed little improvement over the basic model (c=0.86). The discriminatory power of the models did not differ by the Hanley-McNeil test (p>0.05). Within each quartile of mortality, the composite and surgical models displayed an expected mortality ratio close to 1. Conclusions: The addition of clinical data to claims data efficiently enhances the performance of the risk-adjusted postoperative mortality models in colorectal cancer surgery. We recommended that the performance of models should be evaluated through both discrimination and calibration.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.965-970
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• 2015

Colorectal cancer is one of the most severe subtypes of cancer, and has the highest propensity to manifest as metastatic disease. Because of the lack of knowledge of events that correlate with tumor cell migration and invasion, few therapeutic options are available. The current study aimed to explore the mechanism of colorectal cancer in hope of identifying the ideal target for future treatment. We first discovered the pro-tumor effect of a controversial cell cycle regulator, cylin-dependent kinase inhibitor 3 (CDKN3), which is highly expressed in colorectal cancer, and the possible related signaling pathways, by bioinformatics tools. We found that CDKN3 had remarkable effects in suppressing colorectal cancer cell proliferation and migration, inducing cell cycle arrest and apoptosis in a colorectal cancer cell line, SW480 cells. Our study, for the first time, provided consistent evidence showing overexpression of cell cycle regulator CDKN3, in colorectal cancer. The in vitro studies in SW480 cells revealed a unique role of CDKN3 in regulating cellular behavior of colorectal cancer cells, and implied the possibility of targeting CDKN3 as a novel treatment for colorectal cancer.