• Biomolecules & Therapeutics
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• v.29 no.3
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• pp.342-351
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• 2021

Liver colonization is initiated through the interplay between tumor cells and adhesion molecules present in liver sinusoidal endothelial cells (LSECs). This crosstalk stimulates tumor COX-2 upregulation and PGE2 secretion. To elucidate the role of the LSEC intercellular adhesion molecule-1 (ICAM-1) in the prometastatic response exerted by tumor and stromal COX-2, we utilized celecoxib (CLX) as a COX-2 inhibitory agent. We analyzed the in vitro proliferative and secretory responses of murine C26 colorectal cancer (CRC) cells to soluble ICAM-1 (sICAM-1), cultured alone or with LSECs, and their effect on LSEC and hepatic stellate cell (HSC) migration and in vivo liver metastasis. CLX reduced sICAM-1-stimulated COX-2 activation and PGE2 secretion in C26 cells cultured alone or cocultured with LSECs. Moreover, CLX abrogated sICAM-1-induced C26 cell proliferation and C26 secretion of promigratory factors for LSECs and HSCs. Interestingly, CLX reduced the protumoral response of HSC, reducing their migratory potential when stimulated with C26 secretomes and impairing their secretion of chemotactic factors for LSECs and C26 cells and proliferative factors for C26 cells. In vivo, CLX abrogated the prometastatic ability of sICAM-1-activated C26 cells while reducing liver metastasis. COX-2 inhibition blocked the creation of a favorable tumor microenvironment (TME) by hindering the intratumoral recruitment of activated HSCs and macrophages in addition to the accumulation of fibrillar collagen. These results point to COX-2 being a key modulator of processes initiated by host ICAM-1 during tumor cell/LSEC/HSC crosstalk, leading to the creation of a prometastatic TME in the liver.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.2
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• pp.120-128
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• 2009

Purpose: Early detection of recurrence is an important factor for long term survival of patients with colorectal cancer. Measurement of serum levels of CEA, CA 19-9, CT and PET/CT has been commonly used in the postoperative surveillance of colorectal cancer. The purpose of this study was to compare the diagnostic ability of PET/CT, tumor marker and CT for recurrence in colorectal cancer patients after treatment. Materials and Methods: F-18 FDG PET/CT imaging was performed in 189 colorectal cancer patients who underwent curative surgical resection and/or chemotherapy. Measurement of serum levels of CEA, CA 19-9 and CT imaging were performed within 2 months of PET/CT examination. Final diagnosis of recurrence was made by biopsy, radiologic studies or clinical follow-up for 6 months after each study. Results: Overall sensitivity, specificity of PET/CT was 94.7%, 91.1%, while those of serum CEA were 44.7% and 97.3%, respectively. Sensitivity and specificity were 94.2%, 90.4% for PET/CT and better than those of combined CEA and CA 19-9 measurement(52.1%, 88.5%) in 174 patients measured available both CEA and CA 19-9 data. In 115 patients with both tumor markers and CT images available, PET/CT showed similar sensitivity but higher specificity(92.9%, 91.3%) compared to combination of tumor markers and CT images(92.9%, 74.1%). Conclusion: PET/CT was superior for detection of recurred colorectal cancer patients compared with both CEA, CA 19-9, and even with combination of both tumor markers and CT. Therefore PET/CT could be used as a routine surveillance examination to detect recurrence or metastasis of colorectal cancer.

• BMB Reports
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• v.48 no.4
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• pp.217-222
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• 2015

Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death worldwide. Distant metastasis is a major cause of mortality in CRC. MicroRNAs (miRNAs) are small non-coding RNA molecules involved in the post-transcriptional and translational regulation of gene expression. Many miRNAs are aberrantly expressed in cancer and influence tumor progression. Accumulating studies suggest that multiple miRNAs are actively involved in the CRC metastasis process. Thus, we aim to introduce the role of miRNAs in multi-steps of CRC metastasis, including cancer cell invasion, intravasation, circulation, extravasation, colonization, angiogenesis, and epithelial-mesenchymal transition (EMT). Moreover, we suggest the potential application of miRNAs as biomarkers for CRC patients with metastasis. [BMB Reports 2015; 48(4): 217-222]

• Journal of Yeungnam Medical Science
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• v.23 no.2
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• pp.143-151
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• 2006

In the past decade, the median duration of survival among patients with advanced colorectal cancer has increased from 12 months to about 18 months, primarily as a results of the introduction of irinotecan and oxaliplatin. Advances in the understanding of the molecular mechanisms underlying the development and progression of cancer have resulted in the discovery of new therapeutic interventions that target specific molecular abnormalities. Their specificity, and therefore their potential to bind preferentially and modify tumor-specific targets, sparing normal tissues and causing fewer side-effects compared to conventional cytotoxic agents, makes them an attractive therapeutic option. The future of this approach for the treatment of solid tumors is promising.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4583-4587
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• 2014

Objective: Beclin-1 has recently been observed as an essential marker of autophagy in several cancers. However, the prognostic role of Beclin-1 in colorectal neoplasia remains controversial. Our study aimed to evaluate the potential association between Beclin-1 expression and the outcome of colorectal cancer patients. Materials and Methods: All related studies were systematically searched in Pubmed, Embase, Springer and Chinese National Knowledge Infrastructure databases (CNKI), and then a meta-analysis was performed to determine the association of Beclin-1 expression with clinical outcomes. Finally, a total of 6 articles were included in our analysis. Results: Our data showed that high Beclin-1 expression in patients with CRC was associated with poor prognosis in terms of tumor distant metastasis (OR=2.090, 95%CI=1.061-4.119, p=0.033) and overall survival (RR=1.422, 95%CI=1.032-1.959, p=0.031). However, we did not found any correlation between Beclin-1 over-expression and tumor differentiation (OR=1.711, 95%CI=0.920-3.183, p=0.090). In addition, there was no evidence of publication bias as suggested by Egger's tests for tumor distant metastasis (p=1.000), differentiation (p=1.000) and OS (p=0.308). Conclusions: Our present meta-analysis indicated that elevated Beclin-1 expression iss associated with tumor metastasis and a poor prognosis in patients with CRC. Beclin-1 might serve as an efficient prognostic indicator in CRC, and could be a new molecular target in CRC therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.4037-4043
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• 2012

Despite progress in elucidating mechanisms associated with colorectal cancer and improvement of treatment methods, it remains a frequent cause of death worldwide. New and more effective therapies are therefore urgently needed. Recent studies have shown that immunogenicity of whole ovarian tumor cells and subsequent T cell response were potentiated by oxidation modification with hypochlorous acid (HOCl) in vitro and ex vivo. These results prompted us to investigate the protective antitumor response with an HOCl treated CT26 colorectal cancer cell vaccine in an in vivo mouse model. Administration of HOCl modified vaccine triggered robust antitumor immunity to autologous tumor cells in mice and prolonged survival period significantly. In addition, increased necrosis and apoptosis were found in tumor tissue from the oxidation group. Interestingly, ELISPOT assays showed that specific T cell responses were not elicited in response to the immunizing cellular antigen, in contrast to raising sera antibody titer and antibody binding activity shown by ELISA assay and flow cytometry. Further evaluation of the mechanisms underlying HOCl modified vaccine mediated humoral immunity highlighted the role of antibody-dependent cell-mediated cytotoxicity. These results combined with previous studies suggest that HOCl oxidation modified whole cell vaccine has wide applicability as a cancer vaccine because it can target both T cell- and B cell-specific responses. It may thus represent a promising approach for the immunotherapy of colorectal cancer.

• The Korean Journal of Nuclear Medicine
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• v.17 no.1
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• pp.1-10
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• 1983

Carcinoembryonic antigen (CEA) levels were measured in the serum of 35 normal control subjects and 179 cases of various benign and malignant gastrointestinal diseases. Malignant gastrointestinal tumors include 69 cases of stomach cancer, 24 cases of hepatoma and 33 cases of colorectal cancer. Benign gastrointestinal diseases include 29 cases of peptic ulcer and 24 cases of liver cirrhosis. The results were as followings: 1) Mean serum CEA level in normal control subjects was $6.9{\pm}3.3ng/ml$ and there was; no difference in mean serum CEA level between age and sex difference. 2) In malignant gastrointestinal tumors, mean serum CEA level in colorectal cancer, hepatoma and stomach cancer, were $54.3{\pm}88.9ng/ml,\;62.1{\pm}99.7ng/ml$ respectively. Serum CEA level showed positive rate of 67% in colorectal cancer, 63% in hepatoma and 62% in stomach cancer. There was no difference in mean levels and positivity of serum CEA between these 3 malignant tumor groups. 3) Positivity of serum CEA was 61% in malignant gastrointestinal tumor group in spite of 37% in benign gastrointestinal disease group. In both mean level and positivity of serum CEA, stomach cancer was much higher than peptic ulcer. But there was no difference in mean level and positivity of serum CEA level between hepatoma and liver cirrhosis. 4) In hepatoma serum CEA level showed positive rate of 62.5% and alpha-feto protein showed a rate of 58.3%. 5) Mean serum CEA levels in patients with cancer in rectal, cecal, sigmoid colon, ascending: colon and descending colon were $73.7{\pm}106.7ng/ml,\;69{\pm}84.8ng/ml$, $15.7{\pm}9.1ng/ml,\;7.5{\pm}10.6ng/ml$ and 4.0ng/ml respectively. Positive rate of serum CEA showed 86% in sigmoid. colon cancer, 68% in rectal cancer and 66% in cecal cancer. 6) In considering of histological background, there was no correlation between the degree of differentiation of tumor cell and the serum CEA level in colorectal cancer. According to Duke's classification, the mean serum levels of CEA were $8.8{\pm}11.4ng/ml$ in group A, $15.3{\pm}16.0ng/ml$ in group B and $68.5{\pm}101.5ng/ml$ in group C respectively. Positivity-of serum CEA in group A, Band C were 40%, 50% & 69% respectively. So there was significant correlation between the degree of elevation of serum CEA and tumor extension.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1851-1855
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• 2015

Background: There are increasing data about microRNAs (miRNA) in the literature, providing abundant evidence that they play important roles in pathogenesis and development of colorectal cancer. In this study, we aimed to investigate the miRNA expression profiles in surgically resected specimens of patients with recurrent and non-recurrent colorectal cancer. Materials and Methods: The study population included 40 patients with stage II colorectal cancer (20 patients with recurrent tumors, and 20 sex and age matched patients without recurrence), who underwent curative colectomy between 2004 and 2011 without adjuvant therapy. Expression of 16 miRNAs (miRNA-9, 21, 30d, 31, 106a, 127, 133a, 133b, 135b, 143, 145, 155, 182, 200a, 200c, 362) was verified by quantitative real-time polymerase chain reaction (qRT-PCR) in all resected colon cancer tissue samples and in corresponding normal colonic tissues. Data analyses were carried out using SPSS 15 software. Values were statistically significantly changed in 40 cancer tissues when compared to the corresponding 40 normal colonic tissues (p<0.001). MiR-30d, miR-133a, miR-143, miR-145 and miR-362 expression was statistically significantly downregulated in 40 resected colorectal cancer tissue samples (p<0.001). When we compared subgroups, miRNA expression profiles of 20 recurrent cancer tissues were similar to all 40 cancer tissues. However in 20 non-recurrent cancer tissues, miR-133a expression was not significantly downregulated, moreover miR-133b expression was significantly upregulated (p<0.05). Conclusions: Our study revealed dysregulation of expression of ten miRNAs in Turkish colon cancer patients. These miRNAs may be used as potential biomarkers for early detection, screening and surveillance of colorectal cancer, with functional effects on tumor cell behavior.

• Biomedical Science Letters
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• v.11 no.4
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• pp.481-486
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• 2005

This study was performed to define roles of telomerase and apoptosis and their relationships with clinicopathologic characteristics in colorectal cancers. We performed TRAP (Telomeric Repeat Amplification Protoco1)-ELISA assay for telomerase activity and immunohistochemistry of active caspase-3 expression for apoptosis in 35 colorectal cancers. Increased telomerase activity was detected in $71.4\%$ (25/35) and average apoptotic index was 14.6 per 1000 tumor cells. Telomerase activity and caspase 3 expression had no significant association with clinicopathological characteristics, however, increased telomerase activity was more frequently found in progressed colorectal cancers. Although there is no definitive relation, low apoptotic index group was more frequent in cases with increased telomerase activity. These date indicate that telomerase might be involved in progression of colorectal cancers. We suggest that there is a need for further study to define the relationship between telomerase and apoptosis in colorectal cancers.

• Biomedical Science Letters
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• v.27 no.4
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• pp.329-333
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• 2021

We previously identified that tumor cells genetically modified with a 4-1BBL co-stimulatory molecule had anticancer effects in a CT26 mouse colorectal tumor model. To identify the distinction between immune cells in a mouse tumor model treated with tumor cells genetically modified with 4-1BBL or β-gal, we examined the immune cells in CT26-WT, CT26-βgal, and CT26-4-1BBL tumor bearing mice 21 days after tumor cell administration. The CD8+ T cells population in mice treated with tumor cells genetically modified with 4-1BBL was significantly increased on day 21 compared to that of tumor cells genetically modified with β-gal in the spleen and tumor tissue. The CD4+ T cell population was not different between the two mice groups. The Foxp3+CD25^high CD4 T cell population decreased on day 21 in tumor tissues, but the decrease was not significant. We also found that CD8 T cells had pivotal roles in inhibiting tumor growth by treating mice with ant-CD4 and CD8 antibodies. These results suggest that tumor cells genetically modified with 4-1BBL could inhibit tumor growth by affecting on CD8 T lymphocytes.