• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.4981-4985
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• 2015

Background: Colorectal cancer (CRC) is a leading cause of morbidity and mortality worldwide. Targeting autophagic cell death is emerging as a novel strategy in cancer chemotherapy. Aldose reductase (AR) catalyzes the rate limiting step of the polyol pathway of glucose metabolism; besides reducing glucose to sorbitol, AR reduces lipid peroxidation-derived aldehydes and their glutathione conjugates. A complex interplay between autophagic cell death and/or survival may in turn govern tumor metastasis. This exploratory study aimed to investigate the potential role of AR inhibition using a novel inhibitor Fidarestat in the regulation of autophagy in CRC cells. Materials and Methods: For glucose depletion (GD), HT-29 and SW480 CRC cells were rinsed with glucose-free RPMI-1640, followed by incubation in GD medium +/- Fidarestat ($10{\mu}M$). Proteins were extracted by a RIPA-method followed by Western blotting ($35-50{\mu}g$ of protein; n=3). Results: Autophagic regulatory markers, primarily, microtubule associated protein light chain (LC) 3, autophagy-related gene (ATG) 5, ATG 7 and Beclin-1 were expressed in CRC cells; glyceraldehyde-3 phosphate dehydrogenase (GAPDH) was used as an internal reference. LC3 II (14 kDa) expression was relatively high compared to LC3A/B I levels in both CRC cell lines, suggesting occurrence of autophagy. Expression of non-autophagic markers, high mobility group box (HMG)-1 and Bcl-2, was comparatively low. Conclusions: GD +/- ARI induced autophagy in HT-29 and SW-480 cells, thereby implicating Fidarestat as a promising therapeutic agent for colorectal cancer; future studies with more potent ARIs are warranted to fully dissect the molecular regulatory networks for autophagy in colorectal carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.159-163
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• 2016

Background: Colorectal cancer (CRC) is the third most common cancer in the world, and the fourth in Iran in both genders. The aim of this study was to find predictive factors for CRC survival. Materials and Methods: Medical records of 570 patients referred to the radiotherapy oncology department of Shiraz Namazi hospital from 2005 to 2010 were retrospectively analysed. Data were collected by reviewing medical records, and by telephone interviews with patients. Survival analysis was performed using the Cox's regression model with survival probability estimated with Kaplan-Meier curve. The log-rank test was used to compare survival between strata. Data was analyzed with Stata 12. Results: The five-year survival rate and the mean survival time after cancer diagnosis were 58.5% and $67{\pm}4months$. On multivariate analysis, age of diagnosis, disease stage and primary tumor site, lymphovascular invasion and type of treatment (in colon cancer) were significant factors for survival. Conclusions: Age of diagnosis and type of treatment (adjuvant therapy in patients with colon cancer) were two modifiable factors related to survival of CRC patients. Therefore earlier diagnosis might help increase survival.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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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.

• Korean Journal of Clinical Oncology
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• v.14 no.2
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• pp.83-88
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• 2018

Purpose: Double primary colorectal cancer (CRC) and gastric cancer (GC) represent the most common multiple primary malignant tumors (MPMT) in Korea. The recognition and screening of hidden malignancies other than the primary cancer are critical. This study aimed to investigate the clinicopathologic characteristics and survival rates in patients with synchronous or metachronous double primary CRC and GC. Methods: Between January 1994 and May 2018, 11,050 patients were diagnosed with CRC (n=5,454) or GC (n=5,596) at Gil Medical Center. MPMT and metastatic malignant tumors were excluded from this study. A total of 103 patients with double primary CRC and GC were divided into two groups: the synchronous group (n=40) and the metachronous group (n=63). The incidence, clinicopathologic characteristics, and survival rate of the two groups were analyzed. Results: The incidence of synchronous and metachronous double primary CRC and GC was 0.93%. Double primary CRC and GC commonly occurred in male patients aged over 60 years with low comorbidities and minimal previous cancer history. There were significant differences between the synchronous and metachronous groups in terms of age, morbidity, and overall survival. Metachronous group patients were 6 years younger on average (P=0.009), had low comorbidities (P=0.008), and showed a higher 5-year overall survival rate (94.8% and 61.3%, P<0.001) in contrast to synchronous group. Conclusion: When primary cancer (CRC or GC) is detected, it is important to be aware of the possibility of the second primary cancer (GC or CRC) development at that time or during follow-up to achieve early detection and better prognosis.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1193-1196
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• 2016

Background: Colorectal cancer (CRC) is the commonest malignancy in the lower gastrointestinal tract in both men and women. It is the third leading cause of cancer-dependent death in the world. In Iran the incidence of colorectal cancer has increased during the last 25 years. Materials and Methods: In this article we analyzed the survival of 447 colorectal patients of Taleghani hospital in Tehran using parametric competing-risks models. The cancers of these patients were diagnosed during 1985 - 2012 and followed up to 2013. The purpose was to assess the association between survival of patients with colorectal cancer in the presence of competing-risks and prognostic factors using parametric models. The analysis was carried out using R software version 3.0.2. Results: The prognostic variables included in the model were age at diagnosis, tumour site, body mass index and sex. The effect of age at diagnosis and body mass index on survival time was statistically significant. The median survival for Iranian patients with colorectal cancer is about 20 years. Conclusions: Survival function based on Weibull model compared with Kaplan-Meier survival function is smooth. Iranian data suggest a younger age distribution compared to Western reports for CRC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2459-2463
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• 2015

Background: To investigate the expression and clinical significance of zinc finger protein 217 (ZNF217) in human colorectal carcinoma (CRC). Materials and Methods: The expression of ZNF217 in 60 CRC tissues and matched tumor adjacent tissues, collected between January 2013 and June 2014, was assessed immunohistochemically. The relationship between the expression of ZNF217 and clinicopathlogical features was analyzed by Pearson chi-square test. In addition, siRNA was used to down-regulate the expression of ZNF217 in CRC cells. The effects of ZNF217 for cell migration and invasion were measured by wound healing assay and transwell assay, respectively. Results: The expression level of ZNF217 was significantly higher in CRC tissues than in tumor adjacent tissues (p<0.05), positively correlating with tumor size, lymphatic metastasis and advanced TNM stage (p<0.05). Down-regulation of ZNF217 in CRC cells could significantly suppress cell migration and invasion. Conclusions: ZNF217 is overexpressed in colorectal carcinoma tissues and is associated with tumor malignant clinicopathological features. ZNF217 may promote CRC progression by inducing cell migration and invasion.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4595-4599
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• 2014

Background: Colorectal cancer is a serious health problem. Early detection of colorectal cancer is crucial for treatment and reducing mortality. Beliefs related to colorectal cancer have been found to be a factor in a person's decision about colorectal cancer screening programs. To determine such beliefs, a valid and reliable instrument is necessary. Objective:The aim of this study was to adapt and determine the psychometric properties of the Persian version of Champion's Health Belief Model Scale of breast cancer screening in the measurement of beliefs toward colorectal cancer (CRC) screening. Materials and Methods: The 'forward-backward' procedure was applied to translate the instrument from English into Persian. This study was conducted in Iran from June 2012 to May 2013. A convenience sample of 200 individuals aged 50 years and older was recruited from the population at the outpatient clinics in the three teaching hospitals. Validity was assessed using content, face and construct validity. To test reliability, the internal consistency was assessed by using Cronbach's alpha coefficient and test-retest (intraclass correlation coefficient) analyses. Exploratory factor analysis was used to assess the construct validity and determine the factors of adapted Champion's Health Belief Model Scale. Results: The mean age of the participants were 62.5 years (SD=10.8 years) and the majority of them (75.5 percent) were female. The results of exploratory factor analysis indicated a six-factor solution for the questionnaire (benefits, motivation and confidence, seriousness, susceptibility, emotional barriers and background barriers) that jointly accounted for 55.52% of variance observed. Cronbach's alpha of the subscales ranged from 0.57 to 0.89 and test-retest reliability ranged from 0.81 to 0.93 indicating a good range of reliability. Conclusions: The findings of this study suggest that the Persian version of Champion's Health Belief Model Scale of CRC screening has good psychometric properties and could be an appropriate measure for health beliefs related to CRC screening in national and international studies.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9185-9190
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• 2014

Cyclo-oxygenase-2(Cox-2), a key regulator of inflammation-producing prostaglandins, promotes cell proliferation and growth. Therefore, a better understanding of the regulatory mechanisms of Cox-2 could lead to novel targeted cancer therapies. MicroRNAs are strongly implicated in colorectal cancer but their specific roles and functions have yet to be fully elucidated. MiR-1297 plays an important role in lung adenocarcinoma and laryngeal squamous cell carcinoma, but its significance in colorectal cancer (CRC) has yet to be reported. In our present study, we found miR-1297 to be down regulated in both CRC-derived cell lines and clinical CRC samples, when compared with normal tissues. Furthermore, miR-1297 could inhibit human colorectal cancer LOVO and HCT116 cell proliferation, migration, and invasion in vitro and tumorigenesis in vivo by targeting Cox-2. Moreover, miR-1297 directly binds to the 3'-UTR of Cox-2, and the expression level was drastically decreased in LOVO and HCT116 cells following overexpression of miR-1297. Additionally, Cox-2 expression levels are inversely correlated with miR-1297 expression in human colorectal cancer xenograft tissues. These results imply that miR-1297 has the potential to provide a new approach to colorectal cancer therapy by directly inhibiting Cox-2 expression.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6385-6390
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• 2015

Background: Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with risk of developing cancer. For colorectal cancer the importance of mutations in mismatch repair genes has been extensively documented. Materials and Methods: In this study we focused on the Arg194Trp polymorphism of the DNA repair gene XRCC1, involved in base excision repair (BER) and its role in colorectal cancer in Kashmiri population. A case-control study was conducted including 100 cases of colorectal cancer, and 100 hospital-based age- and sex-matched healthy controls to examine the role of XRCC1 genetic polymorphisms in the context of colorectal cancer risk for the Kashmiri population. Results: Genotype analysis of XRCC1 Arg194Trp was conducted with a restriction fragment length polymorphism (RFLP) method. The overall association between the XRCC1 polymorphism and the CRC cases was found to be significant (p < 0.05) with both the heterozygous genotype (Arg/Trp) as well as homozygous variant genotype (Trp/Trp) being moderately associated with the elevated risk for CRC [OR=2.01 (95% CI=1.03-3.94) and OR=5.2(95% CI=1.42-19.5)] respectively. Conclusions: Our results suggest an increased risk for CRC in individuals with XRCC1 Arg194Trp polymorphism suggesting BER repair pathway modulates the risk of developing colorectal cancer in the Kashmiri population.

• Journal of Digestive Cancer Research
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• v.1 no.2
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• pp.95-99
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• 2013

MicroRNA (miRNA) dysregulations are associated with various types of human cancers, and miRNAs can function as tumor suppressors and oncogenes. Emerging evidence has shown that miRNA pathway is also altered during colorectal tumorigenesis. The detection of cancer-related miRNAs in stool samples may become useful diagnostic marker for colorectal cancer, because miRNAs in stool samples has high stability, and maintains a high portion of its original level. Recent studies reported that stool-based miRNAs can offer more sensitivity and specificity than currently used stool-based screening methods for CRC. In addition, unlike fecal occult blood test, sampling on consecutive dates and special dietary restrictions are not required. In this review, the authors discuss stool-based miRNA for the early diagnosis of CRC and perspectives on future application.