• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.1069-1072
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• 2015

Background: Colorectal cancer (CRC) is an important cause of mortality and morbidity in many communities worldwide. This population based study was conducted to assess determinants of colorectal mortality in Iranian patients. Materials and Methods: A cohort of 1,127 cases of confirmed colorectal cancer registered in a population based registry covering 10 referral hospital in Tehran, Iran, were followed for five years. Information about tumor characteristics, smoking status and family history were collected at base line and survival status were followed every six months by contacting patient or next of kin (if patients died during the follow-up). The cause of death for each case was validated by verbal autopsy and referring to patient medical records at the time of death. The data were analyzed by Stata software using univariate and multivariate analysis (Cox regression). In building the model a p value of less than 5% was considered as significant. Results: The age at diagnosis was $53.5{\pm}14$ years. Sixty one percent were male. Colorectal mortality among the patients was 96.9 person-years among men and 83 person-years among women. Seventy five percent of patients lived for 2.72 years, 50% for 5.83, and 25% for 13 years after the diagnosis of colorectal cancer. The age at diagnosis was significantly different between men and women (p<0.03). Higher tumor grade predicted higher death rate; the adjusted hazard ratios were 1.79 (95%CI, 0.88-3.61), 2.16 (95%CI, 1.07-4.37), and 3.1 (95%CI, 1.51-6.34) for grades II, III, and IV respectively when they were compared with grade I as reference. Ethnicity, marital status, family history of cancer, and smoking were related to survival with different degrees of magnitude. Conclusions: Among many factors related to survival among the colorectal patients, tumor grade and smoking showed the highest magnitudes of association.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.443-446
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• 2012

Purpose: Telomeres play a key role in the maintenance of chromosome integrity and stability, and telomere shortening is involved in initiation and progression of malignancies. The aim of this study was to determine whether telomere length is associated with the colorectal carcinoma. Patients and methods: A total of 148 colorectal cancer (CRC) samples and corresponding adjacent non-cancerous tissues were evaluated for telomere length, P53 mutation, and cyclooxygenase-2 (COX-2) mutation detected by fluorescent immunohistochemistry. Telomere length was estimated by real-time PCR. Samples with a T/S>1.0 have an average telomere length greater than that of the standard DNA; samples with a T/S<1.0 have an average telomere length shorter than that of the standard DNA. Results: Telomeres were shorter in CRCs than in adjacent tissues, regardless of tumor stage and grade, site, or genetic alterations (P=0.004). Telomere length in CRCs also had differences with COX-2 status (P=0.004), but did not differ with P53 status (P=0.101), tumor progression (P=0.244), gender (P=0.542), and metastasis (P=0.488). There was no clear trend between T/S optimal cut-off values (<1 or > 1) and colorectal tumor progression, metastasis, gender, P53 and COX-2 status. Conclusion: These findings suggesting that telomere shortening is associated with colorectal carcinogenesis but does not differ with tumor progression, gender, and metastasis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.1003-1007
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• 2013

Objective: This work aimed to investigate the correlations of tumor-associated macrophages (TAMs) and their subtypes M1 and M2 with liver metastasis of colorectal cancer, and provide useful references for seeking predictors of liver metastasis and studying mechanisms. Methods: 120 patients with colorectal cancer from 2000 to 2009 were divided into low, middle and high liver metastasis groups (group A, B and C, respectively). S-P immunohistochemical staining and microscopic observation were conducted to compare expression in CD68-positive cells (TAMs), CD80-positive cells (M1) and CD163-positive cells (M2) in three groups. Correlations of TAMs, M1, M2, and M2/M1 ratio with clinical and pathological parameters were analyzed. Results: With increase of liver metastatic ability, the number of TAMs decreased gradually, with no significant difference between any two of the three groups (P > 0.05), while the numbers of M1 and M2 were significantly decreased and increased, respectively, with significant difference between any two of three groups (P < 0.05 or P < 0.01). In addition, the M2/M1 ratio increased with increase of liver metastatic ability (P < 0.01). There was no statistical significance of correlation of TAMs with each clinical and pathological parameter. M1 was negatively related with lymphatic metastasis and liver metastatic ability. M2 was positively correlated with preoperative CEA level, lymphatic metastasis, tumor differentiation degree and liver metastatic ability. The same was the case for the M2/M1 ratio. Conclusions: Effects of TAMs on liver metastasis of colorectal cancer do not depend on the total number of TAMs, but on the number and proportion of functional subtypes M1 and M2. M2 number and M2/M1 ratio are more accurate predictors for liver metastasis of colorectal cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.4045-4048
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• 2014

Effects of transforming growth factor-beta (TGF-${\beta}$) were investigated in human colorectal cancer, and the influence of cantharidinate in inhibiting TGF-${\beta}1$ expression was explored. Relationships among TGF-${\beta}1$ and sex, age, tumor size, tumor location, tumor stage were also analyzed. H&E and immunohistochemistry staining were employed to assess colorectal cancer and TGF-${\beta}1$ expression, respectively. Then, HCT-116 CRC cells were randomly divided into four groups, controls, no serum-treated, chemotherapy and cantharidinate-treated. Immunohistochemistry and real-time PCR were employed to assess the expression of TGF-${\beta}1$ in CRC cells. Our data showed that the expression of TGF-${\beta}1$ might be associated with tumor size and tumor location (P<0.05). The expression of TGF-${\beta}1$ in CRC groups was higher than in adjacent groups (P<0.05). In addition, the expression of TGF-${\beta}1$ in cantharidinate-treated group was much lower than in CRC group (P<0.05). Taken together, these results suggest that TGF-${\beta}1$ plays an important role in CRC development. Cantharidinate might inhibit the expression of TGF-${\beta}1$ and control the development of colorectal cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7241-7244
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• 2014

Background: To determine the accuracy of preoperative urinary symptoms, urinalysis, computed tomography (CT) and cystoscopic findings for the diagnosis of urinary bladder invasion in patients with colorectal cancer. Materials and Methods: Records of patients with colorectal cancer and a suspicion of bladder invasion, who underwent tumor resection with partial or total cystectomy between 2002 and 2013 at the Faculty of Medicine Siriraj Hospital, were reviewed. Correlations between preoperative urinary symptoms, urinalysis, cystoscopic finding, CT imaging and final pathological reports were analyzed. Results: This study included 90 eligible cases (71% male). The most common site of primary colorectal cancer was the sigmoid colon (44%), followed by the rectum (33%). Final pathological reports showed definite bladder invasion in 53 cases (59%). Significant features for predicting definite tumor invasion were gross hematuria (OR 13.6, sensitivity 39%, specificity 73%), and visible tumor during cystoscopy (OR 5.33, sensitivity 50%, specificity 84%). Predictive signs in CT imaging were gross tumor invasion (OR 7.07, sensitivity 89%, specificity 46%), abnormal enhancing mass at bladder wall (OR 4.09, sensitivity 68%, specificity 66%), irregular bladder mucosa (OR 3.53, sensitivity 70%, specificity 60% ), and loss of perivesical fat plane (OR 3.17, sensitivity 81%, specificity 43%). However, urinary analysis and other urinary tract symptoms were poor predictors of bladder involvement. Conclusions: The present study demonstrated that the most relevant preoperative predictors of definite bladder invasion in patients with colorectal cancer are gross hematuria, a visible tumor during cystoscopy, and abnormal CT findings.

• Biomedical Science Letters
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• v.18 no.4
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• pp.413-419
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• 2012

The melanoma differentiation-associated gene-7 (MDA-7) protein, also known as interleukin-24 (IL-24), is a novel candidate of tumor suppressor that can induce apoptosis experimentally in a variety of human malignant cells. However, there have been few studies about its role in colorectal cancer. We performed immunohistochemical detection of MDA-7/IL-24 in 399 tissue samples from primary colorectal adenocarcinoma patients using a tissue microarray. Western blotting was then done to confirm the immunohistochemical observations. MDA-7/IL-24 immunoreactivity was observed in 116 (29.1%) of the 399 colorectal adenocarcinoma cases. Analysis of the MDA-7/IL-24 expression by Western blotting confirmed the immunohistochemical results. The tumors with a negative MDA-7/IL-24 expression more frequently showed poor differentiation (P=0004), lymph node metastasis (P=0.001), deep invasion (P=0.008) and high stage (P=0.001). A subset of colorectal adenocarcinoma revealed a decreased expression of MDA-7/IL-24, and this was associated with progressive pathologic features. These findings suggest that loss of MDA-7/IL-24 expression may play a role in tumor growth and progression of colorectal adenocarcinomas.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3963-3969
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• 2016

Purpose:To assess IGFBP-6 expression in relation with the presence of the metabolic syndrome, adiponectin receptors (AdipoR1 and AdipoR2) and IGF-IR levels in colorectal adenocarcinoma cases. Materials and Methods: IGFBP-6 mRNA and protein levels were analyzed using real-time quantitative PCR and Western blotting in 46 patients. ELISA and flow cytometry were used for evaluation of AdipoR1, AdipoR2 and IGF-IR. Results: The results showed that IGFBP-6 mRNA expression and the IGFBP-6 content were higher in tumor tissue samples of colorectal cancer patients with tahtn without metabolic syndrome. In addition, the IGFBP-6 mRNA expression was associated with tumor invasion (tumor size) and the IGFBP-6 protein level was associated with nodal status. Positive correlations and positive nonlinear relations were found between the IGFBP-6 level and the AdipoR1 and AdipoR2 contents in colorectal cancer patients. Conclusions: The IGFBP-6 mRNA level and protein level were found to be associated with presence of metabolic syndrome. Positive correlations indicated probable cross-talk between the IGF-IR-mediated and adiponectin-mediated signaling pathways in colorectal carcinomas. IGFBP-6 may be considered as a potential biomarker associated with lymphogenous metastasis and the metabolic syndrome in colorectal cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2119-2123
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• 2016

Background: There is an established link between obesity related metabolic derangement and colorectal cancer development. Recently, we developed a metabolic-colorectal cancer risk score. In this follow-up study, we studied its association with colorectal neoplasm by measuring two major metabolic syndrome biomarkers, leptin and adiponectin. Objectives: To evaluate the serum levels of leptin and adiponectin in patients with colorectal polyps and colorectal cancer and to determine any correlation with metabolic risk score. Results: In total, 130 individuals were studied: 30 controls without colonic pathology, 18 with colonic adenoma (CAP), and 82 with colorectal adenocarcinoma (CRC, 17 cases of T1-2 and 65 cases of T3-4). The metabolic risk scores in CAP and T1-2 CRC were higher than those in the controls and T3-4 CRC cases. There were no statistically significant differences in leptin levels among CAPs, CRCs, and controls. Both leptin and adiponectin levels reflected differences in body mass index and metabolic risk scores. Cases in the CAP group and early T-stage CRC groups had lower adiponectin levels (14.03 and 13.01 mg/ml, respectively) than the no polyps group (19.5mg/ml, p = 0.03). The average serum adiponectin level in the invasive cancer group (18.5 ng/ml) was comparable with that of the control group. Conclusions: The level of serum adiponectin was positively correlated with the metabolic risk score. Decreased serum adiponectin was significantly associated with the development of colorectal adenoma and early stage colorectal carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9385-9390
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• 2014

Introduction: Human adiponectin (ApN) is a 30 kDa glycoprotein of 244-amino acids which is extensively produced by adipocytes. ApN acts via two receptors, namely adiponectin receptor-1 (Adipo-R1) and adiponectin receptor-2 (Adipo-R2). Studies have shown the presence of Adipo-R1 and Adipo-R2 expression immunohistochemically in human colorectal cancers (CRCs). However, only a few studies exist which investigated effects of adiponectin receptor expression on CRC characteristics. Objectives: In the present study, we aimed to explore Adipo-R1/-R2 expression in human colorectal cancers and any association with clinicopathological characteristics and survival. Materials and Methods: The study enrolled 58 colorectal cancer patients with tumor resection and a control group of 30 subjects with normal colon mucosa. Results: Positivity for Adipo-R1/-R2 expression was significantly more common in the control group in comparison to the patient group (both p<0.001). There was no significant association between Adipo-R1/-R2 expression and clinicopathological characteristics including age, sex tumor location, pTNM stage, Duke's stage, metastasis, histological differentiation, perineural invasion, venous invasion sex, lymphatic invasion, cancer-related mortality, tumor size and recurrence. Adipo- R1/-R2 positivity was also not significantly linked to progression-free or overall survival [p values (0.871, 0.758) and (0.274, 0.232), respectively]. Conclusions: Although significantly reduced Adipo-R1/-R2 expression was found in colorectal cancer patients, it had no influence on survival.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4289-4294
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• 2013

Background: The purpose of this study was to assess the predictive effect of preoperative CEA and CA 19-9 levels on the prognosis of colorectal and gastric cancer patients. Materials and Methods: CEA and CA 19-9 were evaluated preoperatively in patients undergoing surgery for colorectal cancer (n=116) and gastric cancer (n=49). Patients with CEA levels <5 ng/mL were classified as CEA Group 1, 5-30 ng/mL as CEA Group 2 and >30 ng/mL were classified as CEA Group 3. Similarly the patients with a CA 19-9 level <35 U/mL were classified as CA 19-9 Group 1, with 35-100 U/mL as Group 2 and with >100 U/mL as Group and 3. TNM stages and histologic grades were noted according to histopathological reports. Patients with a TNM grade 0 or 1 were classified as Group A, TNM grade 2 patients constituted Group B and TNM grade 3 and 4 patients constituted Group C. Demographic characteristics, tumor locations and blood types of the patients were all recorded and these data were compared with the preoperative CEA and CA19-9 values. Results: A significant correlation between CA 19-9 levels (>100 U/mL) and TNM stage (in advanced stages) was determined. We also determined a significant correlation between TNM stages and positive vlaues for both CEA and CA 19-9 in colorectal and gastric cancer patients. In comparison between CEA and CA 19-9 levels and age, gender, tumor location, ABO blood group, and tumor histologic grade, no significant correlation was found. Conclusions: Positive levels of both CEA and CA 19-9 can be considered to indicate an advanced stage in colorectal and gastric cancer patients.