• 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.

• 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.15 no.15
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• pp.6421-6423
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• 2014

Background: Recent studies have revealed a prognostic impact of the MPV (mean platelet volume)/platelet count ratio in terms of survival in advanced non-small cell lung cancer. However, there has been no direct analysis of the survival impact of MPV in patients with mCRC. The aim of the study is to evaluate the pretreatment MPV of patients with metastatic and non-metastatic colorectal cancer (non-mCRC) and also the prognostic significance of pretreatment MPV to progression in mCRC patients treated with bevacizumab-combined chemotherapy. Materials and Methods: Fifty-three metastatic and ninety-five non-metastatic colorectal cancer patients were included into the study. Data on sex, age, lymph node status, MPV, platelet and platecrit (PCT) levels were obtained retrospectively from the patient medical records. Results: The MPV was significantly higher in the patients with mCRC compared to those with non-mCRC ($7.895{\pm}1.060$ versus $7.322{\pm}1.136$, p=0.013). The benefit of bevacizumab on PFS was significantly greater among the patients with low MPV than those with high MPV. The hazard ratio (HR) of disease progression was 0.41 (95%CI, 0.174-0.986; p=0.04). In conclusion, despite the retrospective design and small sample size, MPV can be considered a prognostic factor for mCRC patients treated with bevacizumab-combined chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.253-256
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• 2014

Background: The standard treatment in the metastatic colorectal cancer consists of 5-FU based infusional regimens. However, with oral fluoropyrimidines, equal tumor responses may be obtained. Capecitabine causes macrocytosis of the cells by inhibition of DNA synthesis. In this context, a relationship was found between mean corpuscular volume (MCV) and response to therapy in breast cancer patients treated with Capecitabine, but whether this relationship also pertains in colorectal cancer has not been established. Materials and Methods: A total of 102 metastatic colorectal cancer patients treated with a oxaliplatin (XELOX)${\pm}$Bevacizumab combination were retrospectively evaluated. Patients were randomized into three groups. Hematological parameters (MCV, MPV, PCT, PLT, NLR) were recorded retrospectively, before treatment and after 3 cycles of chemotherapy. Results: After three cycles of therapy, 20 (19.6%) patients had progressive disease (PD), 41 (40.1%) had stable disease (SD), and 41 (40.1%) demonstrated a partial response (PR). In 62 (60.7%) treatment was with capesitabin plus XELOX therapy, and in 40 (39.2%) it was XELOX-Bevacizumab combination therapy. There was no difference among three groups before the treatment in terms of MCV, MPV, PCT, PLT, and NLR. MCV showed significant increase in chemotherapy response groups (PR and SD). In addition, a significant decrease was observed for platelet count in chemotherapy response groups. While NLR decrease was seen in only a PR group, PCT decrease was observed in all three groups. PCT and PLT values were higher in patients receiving Bevacizumab. Conclusions: PLT, PCT, MPV, and NLR values were decreased due to Capecitabine-based chemotherapy, however MCV was increased. PCT and PLT values were higher in patients who received Bevacizumab than those who did not. MCV, PLT, and NLR can be considered as important factors in predicting response to colorectal carcinoma treatment.

• Korean Journal of Clinical Oncology
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• v.14 no.2
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• pp.128-134
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• 2018

Purpose: Previous studies have addressed the role of the hypercoagulable state in the pathogenesis of cancer progression and metastasis. In this study, we investigated the association between coagulation factors, including tissue factor (TF) expression, platelet count, and fibrinogen level, and disease recurrence in patients with non-metastatic colorectal cancer. Methods: Patients who underwent curative resection for stage II or III colorectal cancer between 2000 and 2007 were included in this study. Data from a prospectively maintained database were retrospectively reviewed. TF expression was determined by immunohistochemistry using an anti-TF monoclonal antibody. The Kaplan-Meier method was used to estimate 5-year disease-free survival. Results: TF was highly expressed in 257 of 297 patients (86.5%). TF expression was not significantly associated with the platelet counts (P=0.180) or fibrinogen level (P=0.281). The 5-year disease-free survival rate was lower in patients with high TF expression than in patients with low TF expression (72.3% vs. 83.9%, P=0.074). In Cox hazard analysis, high TF expression was an independent risk factor for tumor recurrence (hazard ratio [HR] 2.446; 95% confidence interval [CI], 1.054-5.674; P=0.037). Undifferentiated histologic type (HR, 2.911; 95% CI, 1.308-6.481; P=0.009), venous invasion (HR, 2.784; 95% CI, 1.431-5.417; P=0.003), and lymph node metastasis (HR, 2.497; 95% CI, 1.499-4.158; P<0.001), were also significantly associated with disease recurrence. Conclusion: TF expression is associated with a recurrence in patients with non-metastatic colorectal cancer. However, further studies are required to clarify the underlying mechanisms relating TF expression with oncologic outcomes and its potential role as a therapeutic target.

• Radiation Oncology Journal
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• v.32 no.4
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• pp.221-230
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• 2014

Purpose: To evaluate the risk of vertebral compression fracture (VCF) after conventional radiotherapy (RT) for colorectal cancer (CRC) with spine metastasis and to identify risk factors for VCF in metastatic and non-metastatic irradiated spines. Materials and Methods: We retrospectively reviewed 68 spinal segments in 16 patients who received conventional RT between 2009 and 2012. Fracture was defined as a newly developed VCF or progression of an existing fracture. The target volume included all metastatic spinal segments and one additional non-metastatic vertebra adjacent to the tumor-involved spines. Results: The median follow-up was 7.8 months. Among all 68 spinal segments, there were six fracture events (8.8%) including three new VCFs and three fracture progressions. Observed VCF rates in vertebral segments with prior irradiation or pre-existing compression fracture were 30.0% and 75.0% respectively, compared with 5.2% and 4.7% for segments without prior irradiation or pre-existing compression fracture, respectively (both p < 0.05). The 1-year fracture-free probability was 87.8% (95% CI, 78.2-97.4). On multivariate analysis, prior irradiation (HR, 7.30; 95% CI, 1.31-40.86) and pre-existing compression fracture (HR, 18.45; 95% CI, 3.42-99.52) were independent risk factors for VCF. Conclusion: The incidence of VCF following conventional RT to the spine is not particularly high, regardless of metastatic tumor involvement. Spines that received irradiation and/or have pre-existing compression fracture before RT have an increased risk of VCF and require close observation.

• 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.16 no.14
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• pp.6149-6154
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• 2015

Background: There is no suggested molecular indicator for the determination of which patients will benefit from anti-angiogenetic treatment in metastatic colorectal cancers. Materials and Methods: In this study, VEGF and $HIF-1{\alpha}$ expression and their clinical significance were studied in tumor tissues of patients with colorectal cancer receiving bevacizumab-based treatment. VEGF and $HIF-1{\alpha}$ were assessed by immunohistochemistry in the primary tumors of 53 metastatic colorectal cancer patients receiving chemotherapy in combination with first line bevacizumab. Results: The clinical benefit rate in the low-VEGF expression group was 38%, while it was 62% in the high expression group. While the median progression-free survival (PFS) was 10 months in the high-VEGF expression group, it was 8 months in the low-VEGF expression group (p = 0.009). The median overall survival (OS) was found to be 26 months vs 15 months. Thus, when VEGF was strongly expressed it was in favor of that group and the difference was statistically significant (p = 0.03). High VEGF expression rate was an independent factor that correlated with OS or PFS (p=0.016 and 0.009, respectively). Conclusions: The data showed that VEGF may have predictive value for determining the treatment of CRC.

• The Journal of Internal Korean Medicine
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• v.40 no.4
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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.

• The Journal of Internal Korean Medicine
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• v.41 no.6
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• pp.1274-1281
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• 2020

Objective: This case report shows symptom improvements in stage IV metastatic colorectal cancer treated with a Korean medicine-based integrative cancer treatment (ICT). Methods: A 61-year-old male patient diagnosed with colorectal cancer in November 2017 and metastasis to the lung, peritoneum, and liver in September 2020 was treated with Integrative Cancer Treatment (ICT) for abdominal pain, abdominal discomfort, and anorexia for 1 month. Clinical outcomes were measured with the National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE), a numeral rating (NRS), the Eastern Cooperative Oncology Group (ECOG), and the Functional Assessment of Cancer Therapy-General (FACT-G) scales. Results: After treatment, the patient's abdominal pain was improved from NRS 8 to 1, and the ECOG score of the patient was improved from grade 3 to 2. Integrative Cancer Treatment. Also the score improved on the FACT-G test, and there were no serious side effects of grade 3 or higher according to the NCI-CTCAE. Conclusion: This case study suggests that Korean medicine-based ICT may help to improve abdominal pain and quality of life in patients with metastatic colorectal cancer.