• Development and Reproduction
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• v.21 no.2
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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.

• Natural Product Sciences
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• v.28 no.2
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• pp.80-88
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• 2022

Colorectal cancer is one of the most common cancers globally, ranking second for the number of cancer-related deaths. Metastasis has been reported as the main cause of death in patients with colorectal cancer. Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a transcription factor that functions as a tumor suppressor by inhibiting cellular proliferation, migration, and invasion. In our previous efforts to generate natural product-motivated PPAR-γ ligands, the compounds 1 and 2 were obtained. These compounds activated PPAR-γ and inhibited the migration and invasion of HCT116 colorectal cancer cells, and they were also found to inhibit the epithelial-to-mesenchymal transition, which is a key process in cancer metastasis. Compounds 1 and 2 upregulated expression of the epithelial marker (E-cadherin), and downregulated expression of the mesenchymal marker (N-cadherin) and transcriptional factor (Snail). Therefore, the PPAR-γ agonists 1 and 2 could serve as a valuable model for the study on anti-metastatic leads for the treatment of colorectal cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8469-8474
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• 2014

Introduction: Recent studies have indicated that down-regulation of the suppressor of cytokine signaling-1 (SOCS-1) gene results in tumor formation and that SOCS-1 acts as a tumor suppressor gene. SOCS-1 has been also suggested to function as a tumor suppressor with colorectal cancer. Objectives: In the present study, we aimed to determine the association of SOCS-1 expression in colorectal cancer tissues with clinicopathologic characteristics immunohistochemically and also to identify its prognostic significance. Materials and Methods: SOCS-1 expression was studied immunohistochemically in 67 patients diagnosed with resected colorectal carcinomas and 30 control subjects. Results: SOCS-1 expression was found in 46.3% of tumor tissues and 46.7% of the control group. Statistical analyses did not establish any significant association between SOCS-1 expression and clinicopathologic characteristics. Also, no significant association with SOCS-1 expression was found using progression-free survival and overall survival analyses (p=0.326 and p=0.360, respectively). Conclusions: Our results show that SOCS-1 has no prognostic significance in colorectal cancer.

• Journal of Korean Biological Nursing Science
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• v.17 no.4
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• pp.306-314
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• 2015

Purpose: The purpose of this study was to evaluate symptoms, depression and quality of life in colorectal cancer patients who underwent stoma reversal, and to assess the factors related to their quality of life. Methods: A descriptive study was conducted on 125 colorectal cancer patients who underwent stoma reversal in a tertiary hospital in Korea. Data were collected using the Korean versions of the European Organization for Research and Treatment of Cancer-Quality of Life Core 30 and Colorectal Cancer Specific Questionnaire 38 (EORTC QLQ-C30 and CR38), and the Hospital Anxiety-Depression Scale. Data were analyzed using descriptive statistics, t-test, one-way ANOVA, Pearson's correlation, and multiple regression analyses. Results: Participants experienced sexual problems, difficulties in defecation, and nausea/vomiting. About twenty-two percent of the patients were depressed and the mean score for global quality of life was $64.40{\pm}19.43$. The multiple regression showed that social and cognitive functioning, depression, and the location of the anastomosis were the important factors that made contributions to the quality of life in colorectal patients with stoma reversal. Conclusion: Our results suggest that symptom management and emotional support should be incorporated into nursing interventions to improve the quality of life in colorectal patients with stoma reversal.

• Journal of Korean Academy of Nursing
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• v.49 no.3
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• pp.274-285
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• 2019

Purpose: This study aimed to examine the effects of a mobile navigation program on uncertainty, resilience, and growth through uncertainty in colorectal cancer patients. Methods: To verify the effectiveness of the mobile navigation program, 61 participants diagnosed with colorectal cancer undergoing surgery were selected. A nonequivalent control group nonsynchronized design was used to evaluate the program. Uncertainty was measured using the Korean version of the Uncertainty in Illness Scale, resilience was measured using the Korean version of the Connor-Davidson Resilience Scale, and growth through uncertainty was measured using the Growth through Uncertainty Scale. Results: Compared with the control group, patients in the mobile navigation program group showed significant differences in scores for uncertainty (F=7.22, p=.009) and resilience (F=4.31, p=.042), but not for growth through uncertainty (F=2.76, p=.102). Conclusion: These results suggest that the mobile navigation program has positive effects on decreasing uncertainty and increasing resilience among colorectal cancer patients. The mobile navigation program could play a significant role in assisting colorectal cancer patients in regard to the continuity and usability of the program.

• 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.13 no.7
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• pp.3123-3127
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• 2012

Objective: Experimental studies have suggested green tea to be a chemopreventive agent for colorectal cancer, and many studies have examined possible associations. However, the conclusions were inconsistent or even contradictory, so we performed a meta-analysis based on published case-control studies to explore if green tea is indeed a protective factor. Methods: PubMed was searched up to May $10^{th}$, 2012 for relevant studies, and references of included studies were manually searched. Finally 13 eligible studies, involving 12,636 cases and 38,419 controls were identified. After data extraction, a meta-analysis was performed using CMA v2 software. Results: The results indicated there may be a weak but not statistically significant reduced risk of colorectal cancer with high dose of green tea intake (OR=0.95, 95% CI:0.81-1.11, p=0.490.69-0.98). This protective effect was also found in all subgroups, except in American and European populations. Sensitivity analysis indicated the result to be robust. Publication bias was not detected by either funnel plot or Egger tests. Conclusion: The results of this meta-analysis indicate a weak lower tendency for colorectal cancer development with green tea consumption, but available epidemiologic data are insufficient to conclude that green tea may protect against colorectal cancer in humans.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5395-5399
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• 2014

Purpose: This study was designed to evaluate the outcomes of laparoscopic colorectal resection in a period of learning curve completed by surgeons with different experience and aptitudes with a view to making clear whether seniors had a better learning curve compared with juniors. Methods: From May 2010 to August 2012, the first twenty patients underwent laparoscopic colorectal resection completed by each surgeon were selected for analysis retrospectively. A total of 240 patients treated by 5 seniors and 7 juniors were divided into the senior group (n=100) and the junior group (n=140). The short-term outcomes of laparoscopic surgery of the two groups were compared. Results: The mean numbers of lymph nodes harvested were $21.2{\pm}11.0$ in the senior group and $17.3{\pm}11.5$ in the junior group (p=0.010); The mean operative times were $187.9{\pm}60.0min$ as compared to $231.3{\pm}55.7min$ (p=0.006), and blood loss values were $177.0{\pm}100.7ml$ and $234.0{\pm}185ml$, respectively (p=0.001); Conversion rate in the senior group was obviously lower than in the junior group (10.0% vs 20.7%, p=0.027) and the mean time to passing of first flatus were $3.3{\pm}0.9$ and $3.8{\pm}0.9$ days (p=0.001). For low rectal cancer, the sphincter preserving rates were 68.7% and 35.3% (p=0.027). Conclusions: Seniors could perform laparoscopic colorectal resection with relatively better oncological outcomes and quicker recovery, and seniors could master the laparoscopic skill more easily and quickly. Seniors had a better learning curve for laparoscopic colorectal cancer resection compared to juniors.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.791-793
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• 2013

Colorectal cancer is one of the most common cancers. The aim of this study is determination its trends in Kerman province and individual cities separately until year 2016. This analytical and modeling study was based of cancer registry data of Kerman University of Medical Sciences, collected during 2001-2010. Among 20,351 cancer case, 792 were colorectal cancer cases in age group 18-93 years with a mean of 59.4 and standard deviation of 15.1. By applying time series and data trends, incidences were predicted until 2016 for the province and each city, with adjustment for population size. In colorectal cases, 413 (52%) were male, and 379 (48%) were female. The annual increasing rate in Kerman province overall was and can be expected to be 6%, and in the cities of the province Rafsanjan, Bardsir, Bam, Kerman, Baft, Sirjan, Jiroft, Kahnuj and Manujan had an increasing range from 5 to 14% by the year 2016. But in Ravar, Zarand and Shahrbabak reduction in rates of at least 2% could be predicted. The time series showed that the trend of colorectal cancer in female will increase 15% and in male 7% by year 2016. Given the trend of this cancer is increasing so that resources will be consumed in the treatment of the patients, efforts shoudlbe focused on prevention and early diagnosis of the disease. Screening could have an important role leading to improved survival.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8651-8656
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• 2014

Purpose: To study the expression of angiogenin-2 (Ang-2) and its receptor Tie-2 in colorectal cancer and discuss the possible mechanisms behind this process. Materials and Methods: Using the streptavidin-peroxidase (SP) immunohistochemical method, paraffin sections from 100 colorectal cancer samples and 10 samples from tumor-adjacent normal tissue (> 2 cm from the edge of the gross tumor) were tested for protein expression of Ang-2, Tie-2, PI3K, and AKT. Reverse transcription-polymerase chain reaction and Western blots were further used to measure expression of the 4 genes and proteins in 20 freshly-resected colorectal cancer samples and tumor-adjacent normal tissues. Results: In colorectal cancer tissues, the expression of the Ang-2, Tie-2, PI3K, and AKT genes and their proteins was significantly higher than in tumor-adjacent normal tissues. Protein expression in poorly-differentiated adenocarcinoma was higher than that in well and moderately differentiated adenocarcinoma. According to Duke's classification, the protein expression in Stages C and D was significantly higher than that in Stages A and B. In the group with lymphatic metastasis, the protein expression was higher than that without lymphatic metastasis. Conclusions: In colorectal cancer, the expression of the Ang-2, Tie-2, PI3K, and AKT genes and their proteins is markedly higher than those in tumor-adjacent normal tissues. No correlation was observed between protein expression and gender, location, or histologic type. Correlations did exist between protein expression and differentiation level, stage of Duke's classification, and lymphatic metastasis; in colorectal cancer tissues with lower differentiation levels, higher stages of Duke's classification, and lymphatic metastasis, the expression of all 4 proteins was higher. The study of their expression patterns and relationships with aggression and metastasis will provide a valuable experimental foundation for assessing prognosis and targeted therapy of colorectal cancer.