• Journal of Digestive Cancer Research
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• 제1권2호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제15권6호
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• pp.2647-2650
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• 2014

Background: Colorectal cancers(CRC) are the third most common cancer in the western world, with surgery preferred for management of non-metastatic disease and post surgical treatment usually arranged according to the TNM staging system. However, there is still prognostic variation between patients who have the same stage. It is increasingly recognized that variations within disease course and clinical outcome in colorectal cancer patients are influenced by not only oncological characteristics of the tumor itself but also host response factors. Recent studies have shown correlation between the inflammatory response and clinical outcomes in various cancers. The neutrophil/lymphocyte ratio (NLR) has been described as a marker for immune response to various stimuli including cancer. Material-Methods: Two hundred eighty-one CRC patients were included in our retrospective analysis, separated into two groups according to a cut-off value for the NLR. Patient data including age, gender, vertical penetration, anatomic location, and differentiation of the tumor, TNM stage, survival rate, and disease-free survival were analyzed for correlations with the NLR. Results: Using ROC curve analysis, we determined a cut-off value of 2.2 for NLR to be best to discriminate between patient survival in the whole group. In univariate analysis, high pretreatment NLR (p=0.001, 95%CI 1.483-4.846), pathologic nodal stage (p<0.001, 95%CI 1.082-3.289) and advanced pathologic TNM stage (p<0.001, 95%CI 1.462-4.213) were predictive of shorter survival. In multivariate analysis, advanced pathologic TNM stage (p=0.001, 95%CI 1.303-26.542) and high pretreatment NLR (p=0.005, 95%CI 1.713-6.378) remained independently associated with poor survival. Conclusions: High pre-treatment NLR is a significant independent predictor of shorter survival in patients with colorectal cancer. This parameter is a simple, easily accessible laboratory value for identifying patients with poorer prognosis.

• Asian Pacific Journal of Cancer Prevention
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• 제16권11호
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• pp.4647-4652
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• 2015

Background: Colorectal cancer (CRC) is becoming one of the most complicated challenges of human health, particularly in developing countries like Iran. In this paper, we try to characterize CRC cases diagnosed < age 50 at-risk for Lynch syndrome within central Iran. Materials and Methods: We designed a descriptive retrospective study to screen all registered CRC patients within 2000-2013 in Poursina Hakim Research Center (PHRC), a referral gastroenterology clinic in central Iran, based on being early-onset (age at diagnosis ${\leq}50years$) and Amsterdam II criteria. We calculated frequencies and percentages by SPSS 19 software to describe clinical and family history characteristics of patients with early-onset CRC. Results: Overall 1,659 CRC patients were included in our study of which 413 (24.9%) were ${\leq}50years$ at diagnosis. Of 219/413 successful calls 67 persons (30.6%) were reported deceased. Family history was positive for 72/219 probands (32.9%) and 53 families (24.2%) were identified as familial colorectal cancer (FCC), with a history of at-least three affected members with any type of cancer in the family, of which 85% fulfilled the Amsterdam II Criteria as hereditary non-polyposis colorectal cancer (HNPCC) families (45/219 or 20.5%). Finally, 14 families were excluded due to proband tumor tissues being unavailable or unwillingness for incorporation. The most common HNPCC-associated extracolonic-cancer among both males and females of the families was stomach, at respectively 31.8 and 32.7 percent. The most common tumor locations among the 31 probands were rectum (32.3%), sigmoid (29.0%), and ascending colon (12.9%). Conclusions: Given the high prevalence of FCC (~1/4 of early-onset Iranian CRC patients), it is necessary to establish a comprehensive cancer genetic counseling and systematic screening program for early detection and to improve cancer prognosis among high risk families.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.3151-3154
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• 2013

Introduction: Colorectal cancers are in the top of the cancer-related causes of death in the world and lymph node metastasis is accepted as the primary prognostic factor. In this study, correlations of FGF19 staining pattern with local invasion and lymph node metastasis in a series of colorectal cancers were investigated. Methods: This studyincluded 81 colorectal cancer patients who underwent surgery in our hospital with no evidence of preoperative radiological distant metastasis. Routine pathological examination of the resection material was performed in order to identify vascular, perineural and serosal infiltration, regional lymph node metastasis and the degree of differentiation. Tumor tissue samples were stained with an immunohistochemistry method for FGF 19 evaluation and the staining pattern was statistically compared with the above mentioned characteristics of the tumors. Results: The patient population consisted of 47 females and 34 males with a median age of 70 years. In 40 patients regional lymph nodes were positive and 51%, 32% and 38% had serosal, perineural and vascular invasion. While 64 cases were moderately-differentiated, 11 cases were well-differentiated and 6 poorlydifferentiated, there was no association with FGF 19 staining, including intensity. Conclusion: No evidence of significant statistically correlation was found between FGF 19 staining pattern and serosal, perineural, vascular invasion, lymph node involvement and degree of differentiation.

• 대한한방내과학회지
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• 제40권4호
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• pp.723-729
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• 2019

Objective: This study was aimed at reporting on a patient with repeated recurrence of metastatic colorectal cancer treated with traditional Korean medicine (TKM) alone after operation and chemotherapy. Method: The patient with metastatic colorectal cancer received tumor resections four times and perioperative chemotherapy for repeated recurrence from February 2013 until March 2015. TKM, which included Gunchil-dan and Haeam-dan, was administered until June 2019 to prevent additional relapses. Results: After 49 months of TKM treatment, there was no tumor recurrence. A no evidence of disease (NED) state was maintained from March 2015 to June 2019. Recurrence-free survival (RFS) was shown for 49 months and overall survival (OS) for 78 months. Serious adverse events evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 were not identified. This study suggested that TKM with herbal medicine including aRVS might prolong survival and inhibit recurrence of tumors in patients with metastatic colorectal cancer.

• BMB Reports
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• 제47권9호
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• pp.500-505
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• 2014

Colorectal cancer has become the third most common cancer and leads to high mortality worldwide. Although colorectal cancer has been studied widely, the underlying molecular mechanism remains unclear. PER3 is related to tumor differentiation and the progression of colorectal cancer. High expression of miR-103 is associated with poor prognosis in patients with colorectal cancer. However, the relationship between miR-103 and PER3 in CRC cells remains unclear. In this study, we found that PER3 was downregulated in CRC tissues and CRC cell lines, whereas miR-103 was upregulated in CRC cell lines. We also found that PER3 promoted CRC cells apoptosis. These results indicate that PER3 plays a suppressive role in CRC cells. Moreover, we found that PER3 was targeted, at least partially, by miR-103. Taken together, we provide evidence to characterize the role of PER3 in CRC, which may be a new therapeutic target for CRC.

• 대한한의학회지
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• 제40권1호
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• pp.124-152
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• 2019

Objectives: This study aimed to ascertain what should be considered in the "Guideline for Clinical Trials with Herbal Medicinal Products for Colorectal Cancer" by analyzing the existing guidelines and clinical trials. Methods: The development committee searched guidelines for herbal medicinal products for colorectal cancer that have already been developed. Then, clinical trials for colorectal cancer using herbal medicine were searched. The searched trials were analyzed in terms of inclusion and exclusion of participants, intervention, comparator, outcomes and trial design. Then, we compared the results of our analysis with the regulations and guidelines of the Ministry of Food and Drug Safety in order to identify the issues we will have to consider when making the "Guideline for Clinical Trials with Herbal Medicinal Products for Colorectal Cancer". Several guidelines for anti-tumor agents and clinical trials with herbal medicinal products were searched on the national institution homepage. In addition, 12 articles were searched using a combination of the following search terms: 'colorectal neoplasms', 'herbal medicine', 'Medicine, Korean traditional', 'Medicine, Chinese Traditional', 'medicine, East Asian medicine', 'medicine, Kampo', etc. Results: The characteristics of participants were various, such as people with medical histories of surgeries or recurrent cancers or who complained of chemotherapy-induced side effects. The types of interventions were also various and included decoctions, powders, intravenous fluids, intraperitoneal injections and gargles. Comparators used included placebos and conventional treatments. The outcome measurements used in the studies were quality of life, symptom score, tumor response, and survival duration, etc. Safety was evaluated by recording adverse events. Conclusions: Findings were made by reviewing existing guidelines and comparing them with clinical trials for colorectal cancer and herbal medicinal products. These results will be utilized in the development of the "Guideline for Clinical Trials with Herbal Medicinal Products for Colorectal Cancer".

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4263-4266
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• 2012

Colorectal cancer has become a major disease threatening human health. To establish animal models that exhibit the characteristics of human colorectal cancer will not only help to study the mechanisms underlying the genesis and development effectively, but also provide ideal carriers for the screening of medicines and examining their therapeutic effects. In this study, we established a stable, colon cancer nude mouse model highly expressing green fluorescent protein (GFP) for spontaneous metastasis after surgical orthotopic implantation (SOI). GFP-labeled colon cancer models for metastasis after SOI were successfully established in all of 15 nude mice and there were no surgery-related complications or deaths. In week 3, primary tumors expressing GFP were observed in all model animals under fluoroscopy and two metastatic tumors were monitored by fluorescent imaging at the same time. The tumor volumes progressively increased with time. Seven out of 15 tumor transplanted mice died and the major causes of death were intestinal obstruction and cachexia resulting from malignant tumor growth. Eight model animals survived at the end of the experiment, 6 of which had metastases (6 cases to mesenteric lymph nodes, 4 hepatic, 2 pancreatic and 1 mediastinal lymph node). Our results indicate that our GFP-labeled colon cancer orthotopic transplantation model is useful with a high success rate; the transplanted tumors exhibit similar biological properties to human colorectal cancer, and can be used for real-time, in vivo, non-invasive and dynamic observation and analysis of the growth and metastasis of tumor cells.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7091-7095
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• 2014

Background: The study aimed to evaluate the incidence of CpG island promoter methylation of BMP6, a member of the transforming growth factor beta family, in tissue samples from colorectal cancers (CRC) and look for its association with BMP6 expression and clinicopathological correlation. Materials and Methods: Methylation specific PCR for the BMP6 promoter region was performed with 85 frozen tissue samples of CRC and 45 of normal colon. Methylation status of MLH1 was also determined by the same method. Expression of BMP6 was evaluated by immunohistochemistry (IHC), using Allred's scoring system. The methylation status was analyzed against clinical and pathological parameters in CRC. Results: The study revealed BMP6 hypermethylation in 34 of 85 tumor specimens (40%), and 15 out of 45 normal tissue samples from CRC (33%). The incidence of hypermethylation was inversely correlated with IHC score. Allred's scores of 7 or more were correlated with lower frequency of BMP6 hypermethylation (29% compared to 50% in the remaining, p-value 0.049). However, there was no association between hypermethylation status and any clinicopathological parameters. The methylation status of BMP6 was not correlated with that of MLH1, a key methylation determinant in CRC. On survival analysis, there was no significant difference in progress-free survival (PFS) between the cases with and without hypermethylation (2-year PFS 74% and 76%, respectively). Conclusions: CpG island methylation of BMP6 is found in high frequency in CRC and this epigenetic event is associated with suppressed protein expression in the tumor tissue. However, the marker is not associated with tumor progression of the disease.

• Journal of Genetic Medicine
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• 제20권2호
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• pp.52-59
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• 2023

Purpose: Colorectal cancer (CRC) is a common malignancy worldwide and the second leading cause of cancer-related deaths. In addition, lymph node metastasis in CRC is considered an important prognostic factor for predicting disease recurrence and patient survival. Recent studies demonstrated that the microbiome makes substantial contributions to tumor progression, however, there is still unknown about the microbiome associated with lymph node metastasis of CRC. Here, we first reported the microbial and tumor-infiltrating immune cell differences in CRC according to the lymph node metastasis status. Materials and Methods: Using Next Generation Sequencing data acquired from 368 individuals diagnosed with CRC (N0, 266; N1, 102), we applied the LEfSe to elucidate microbial differences. Subsequent utilization of the Kaplan-Meier survival analysis enabled the identification of particular genera exerting significant influence on patient survival outcomes. Results: We found 18 genera in the N1 group and 3 genera in the N0 group according to CRC lymph node metastasis stages. In addition, we found that the genera Crenobacter (P=0.046), Maricaulis (P=0.093), and Arsenicicoccus (P=0.035) in the N0 group and Cecembia (P=0.08) and Asanoa (P=0.088) in the N1 group were significantly associated with patient survival according to CRC lymph node metastasis stages. Further, Cecembia is highly correlated to tumor-infiltrating immune cells in lymph node metastasized CRC. Concolusion: Our study highlights that tumor-infiltrating immune cells and intratumoral microbe diversity are associated with CRC. Also, this potential microbiome-based oncology diagnostic tool warrants further exploration.