• Journal of Ginseng Research
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• v.43 no.1
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• pp.68-76
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• 2019

Background: In colorectal cancer (CRC), 40-60% of patients develop metastasis. The epithelial-mesenchymal transition (EMT) is a pivotal and intricate process that increases the metastatic potential of CRC. The aim of this study was to investigate the effect of Korean Red Ginseng extract (RGE) on colorectal metastasis through inhibition of EMT and the metastatic abilities of CRC cells. Methods: To investigate the effect of RGE on the metastatic phenotypes of CRC cells, CT26 and HT29 cells were evaluated by using an adhesion assay, a wound-healing assay, an invasion assay, zymography, and real-time reverse transcription-polymerase chain reaction. Western-blot analysis was conducted to elucidate the molecular mechanisms of RGE, which showed an inhibitory effect on the transforming growth factor-${\beta}1$ ($TGF-{\beta}1$)-induced EMT in HT29 cells. Additionally, the antimetastatic effect of RGE was evaluated in a mouse model of lung metastasis injected with CT26 cells. Results: RGE decreased the adhesion and migration ability of the CT26 cells and TGF-${\beta}1$-treated HT29 cells. The invasion ability was also reduced by RGE treatment through the inhibition of matrix metalloproteinase-9 expression and activity. Moreover, RGE suppressed the TGF-${\beta}1$-induced EMT via TGF-${\beta}1$/Smad-signaling-mediated Snail/E-cadherin expression in HT29 cells and lung tissue in CT26 tumor-bearing mice. Conclusion: Our results demonstrated that RGE inhibited colorectal lung metastasis through a reduction in metastatic phenotypes, such as migration, invasion, and the EMT of CRC cells.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3703-3708
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• 2015

Background: The neutrophil-to-lymphocyte ratio (NLR) is a strong predictor of mortality in patients with colorectal, lung, gastric cancer, pancreatic and metastatic renal cell carcinoma. We here evaluated whether preoperative NLR is an independent prognostic factor for non-metastatic renal cell carcinoma (RCC). Materials and Methods: Data from 327 patients who underwent curative or palliative nephrectomy were evaluated retrospectively. In preoperative blood routine examination, neutrophils and lymphocytes were obtained. The predictive value of NLR for non-metastatic RCC was analyzed. Results: The NLR of 327 patients was $2.72{\pm}2.25$. NLR <1.7 and NLR ${\geq}1.7$ were classified as low and high NLR groups, respectively. Chi-square test showed that the preoperative NLR was significantly correlated with the tumor size (P=0.025), but not with the histological subtype (P=0.095)and the pT stage (P=0.283). Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method. Effects of NLR on OS (P=0.007) and DFS (P=0.011) were significant. To evaluate the independent prognostic significance of NLR, multivariate COX regression models were applied and identified increased NLR as an independent prognostic factor for OS (P=0.015), and DFS (P=0.019). Conclusions: Regarding patient survival, an increased NLR represented an independent risk factor, which might reflect a higher risk for severe cardiovascular and other comorbidities. An elevated blood NLR may be a biomarker of poor OS and DFS in patients with non-metastatic RCC.

• Journal of Chest Surgery
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• v.39 no.11 s.268
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• pp.838-843
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• 2006

Background: The lung is the most common site of metastatic colorectal cancer comprising 10% of all curative resection of colorectal cancer. The reported 5 year survival rate varies among institutions. The purpose of the present study was to present the retrospective analysis of colorectal metastatic lung cancer surgery at our institution. Material and Method: A total of 61 patients undergoing surgery for metastatic colorectal lung cancer between July 1996 and December 2003 were included in the present study. The stage of the primary colorectal cancer, site of pulmonary metastasis, method of lung resection, the number and size of the metastatic nodules, the recurrence rate, and survival were assessed. Result: The 3 and 5 year survival rates were 66% and 41%, respectively. No significant risk factors were identified among the studied variables by either univariate or multivariate analysis. The mean disease free survival rate was 17 months. The most common recurrent site was lung, and among these patients, 3 underwent a second operation and two are still alive. Conclusion: The results of the above data suggest that pulmonary resection of metastatic lung cancer in select patients after curative resection of colon cancer may be a good therapeutic option with the potential for excellent results.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.4071-4075
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• 2016

Background: FDG PET/CT is at an equivocal stage to recommend for staging of colorectal cancer as compared to contrast-enhanced CT (ceCT). This study was intended to evaluate the value of FDG PET/ceCT in colorectal cancer staging as compared to ceCT alone. Materials and Methods: PET/ceCT was performed for 61 colorectal cancer patients who were prospectively enrolled in the study. Three patients were excluded due to loss to follow-up. PET/ceCT findings and ceCT results alone were read separately. The treatment planning was then determined by tumor board consensus. The criteria for T staging were determined by the findings of ceCT. Nodal positive by PET/ceCT imaging was determined by visual analysis of FDG uptake greater than regional background blood pool activity. The diagnostic accuracy of T and N staging was determined only in patients who received surgery without any neoadjuvant treatment. Results: Of 58 patients, there were 40 with colon cancers including sigmoid cancers and 18 with rectal cancers. PET/ceCT in pre-operative staging detected bone metastasis and metastatic inguinal lymph nodes (M1a) that were undepicted on CT in 2 patients (3%), clearly defined 19 equivocal lesions on ceCT in 18 patients (31%) and excluded 6 metastatic lesions diagnosed by ceCT in 6 patients (10%). These resulted in alteration of management plan in 15 out of the 58 cases (26%) i.e. changing from chemotherapy to surgery (4), changing extent of surgery (9) and avoidance of futile surgery (2). Forty four patients underwent surgery within 45 days after PET/CT. The diagnostic accuracy for N staging with PET/ceCT and ceCT alone was 66% and 48% with false positive rates of 24% (6/25) and 76% (19/25) and false negative rates of 47% (9/19) and 21% (4/19), respectively. All of the false negative lymph nodes from PET/ceCT were less than a centimeter in size and located in peri-lesional regions. The diagnostic accuracy for T staging was 82%. The sensitivity of the peri-lesional fat stranding sign in determining T3 stage was 94% and the specificity was 54%. Conclusions: Our study suggested promising roles of PET/ceCT in initial staging of colorectal cancer with better diagnostic accuracy facilitating management planning.

• Journal of Digestive Cancer Research
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• v.1 no.1
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• pp.29-35
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• 2013

Peritoneal carcinomatosis (PC) is defined as the dissemination of cancer cells in the peritoneal cavity resulting in deposition of malignant cells onto parietal or visceral peritoneal surfaces, and is associated with malignant ascites. In general, PC has been treated similarly to metastatic cancers of the primary tumor, but associated with unfavorable outcomes as compared to other sites of metastatic disease from the same primary tumor origin. It has been known to have the median survival of only 3-6 months with supportive care alone. PC is an intractable problem to physicians because of its poor prognosis and limited treatment options. Recent studies have reported that a combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improved survival in PC of colorectal cancer. This paper gives overviews of the characteristics, symptoms, prognosis, and diagnosis of PC and current treatment options on PC of stomach, colorectal, and unknown primary origin.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.603-608
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• 2016

Background: The investigation of mutation patterns in oncogenes potentially can make available a reliable mechanism for management and treatment decisions for patients with colorectal cancer (CRC). This study concerns the rate of KRAS and BRAF genes mutations in Iranian metastatic colorectal cancer (mCRC) patients, as well as associations of genotypes with clinicopathological features. Materials and Methods: A total of 1,000 mCRC specimens collected from 2008 to 2012 that referred to the Mehr Hospital and Partolab center, Tehran, Iran enrolled in this cross sectional study. Using HRM, Dxs Therascreen and Pyrosequencing methods, we analyzed the mutational status of KRAS and BRAF genes in these. Results: KRAS mutations were present in 33.6% cases (n=336). Of KRAS mutation positive cases, 85.1% were in codon 12 and 14.9% were in codon 13. The most frequent mutation at KRAS codon 12 was Gly12Asp; BRAF mutations were not found in any mCRC patients (n=242). In addition, we observed a strong correlation of KRAS mutations with some clinicopathological characteristics. Conclusions: KRAS mutations are frequent in mCRCs while presence of BRAF mutations in these patients is rare. Moreover, associations of KRAS genotypes with non-mucinous adenocarcinoma and depth of invasion (pT3) were remarkable.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9277-9281
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• 2014

Purpose: To investigate clinicopathological features in patients with recurrent colorectal cancer within 1 year and more than 1 year after curative resection. Materials and Methods: We retrospectively evaluated 103 patients with disease recurrence before versus after 1 year of resection. Thirty-two patients (31%) were diagnosed with recurrence less than 1 year after curative resection for colorectal cancer (early recurrence) and 71 (69%) after more than 1 year (non-early recurrence). Results: The early recurrence group displayed a significantly lower overall survival rate for both colon cancer (p=0, 01) and rectal cancer (p<0.001). Inadequate lymph node dissection was a significant predictor for early relapse. There were no statistically significant differences in clinicopathological variables such as age, sex, primary tumor localization, stage, depth of invasion, lymphovascular invasion and perineural invasion between the early and non-early recurrence groups. However, a K-ras mutation subgroup was significantly associated with early recurrence (p<0.001). Conclusions: Poor survival is associated with early recurrence for patients undergoing resection for non-metastatic colorectal cancer, as well as K-ras mutation.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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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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• v.15 no.13
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• pp.5365-5369
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• 2014

Background: The lymph node ratio (LNR) has been shown to be an important prognostic factor for colorectal cancer. However, studies focusing on the prognostic impact of LNR in rectal cancer patients who received neoadjuvant chemoradiotherapy (CRT) followed by curative resection have been limited. The aim of this study was to investigate LNR in rectal cancer patients who received neoadjuvant chemoradiotherapy (CRT) followed by curative resection. Materials and Methods: A total of 131 consecutive rectal cancer patients who underwent neoadjuvant CRT and total mesorectal excision were included in this study. Patients were divided into two groups according to the LNR (${\leq}0.2$ [n=86], >0.2 [n=45]) to evaluate the prognostic effect on overall survival (OS) and disease-free survival (DFS). Results: The median number of retrieved and metastatic lymph node (LN) was 14 (range 1-48) and 2 (range 1-10), respectively. The median LNR was 0.154 (range 0.04-1.0). In multivariate analysis, LNR was shown to be an independent prognostic factor for both overall survival (hazard ratio[HR]=3.778; 95% confidence interval [CI] 1.741-8.198; p=0.001) and disease-free survival (HR=3.637; 95%CI 1.838-7.195; p<0.001). Increased LNR was significantly associated with worse OS and DFS in patients with <12 harvested LNs, and as well as in those ${\geq}12$ harvested LNs (p<0.05). In addition, LNR had a prognostic impact on both OS and DFS in patients with N1 staging (p<0.001). Conclusions: LNR is an independent prognostic factor in ypN-positive rectal cancer patients, both in patients with <12 harvested LNs, and as well as in those ${\geq}12$ harvested LNs. LNR provides better prognostic value than pN staging. Therefore, it should be used as an additional prognostic indicator in ypN-positive rectal cancer patients.

• Journal of Chest Surgery
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• v.48 no.6
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• pp.447-451
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• 2015

This report describes the case of a 57-year-old man with an anterior mediastinal tumor. Four years previously, he underwent laparoscopic anterior resection for sigmoid colon cancer. Thirty months after that procedure, bilateral pulmonary metastasectomy was performed. Twelve months later, follow-up computed tomography revealed a 1-cm pulmonary nodule on the upper lobe of the right lung and a solid mass on the anterior mediastinum, and the patient was also observed to have an elevated serum carcinoembryonic antigen (CEA) level. Repeated pulmonary nodule resection and total thymectomy were performed. Immunohistochemical staining of the anterior mediastinal tumor revealed adenocarcinoma, and his serum CEA level returned to normal after the operation. These findings strongly suggested metastatic thymic adenocarcinoma from a colorectal cancer.