Publications by authors named "Moo Jun Baek"

56 Publications

Intracellular delivery of oxaliplatin conjugate via cell penetrating peptide for the treatment of colorectal carcinoma in vitro and in vivo.

Int J Pharm 2021 Sep 19;606:120904. Epub 2021 Jul 19.

Department of Electronic Materials and Devices Engineering, Soonchunhyang University, Asan 31538, Republic of Korea; Department of Chemical Engineering, Soonchunhyang University, Asan 31538, Republic of Korea. Electronic address:

Pt-based drugs are one of the main active agents in colorectal cancer treatment. However, drug resistance and dose-dependent side effects are the main barriers that restrict their clinical applications. As an alternative approach to these issues, we designed and synthesized a cell penetrating peptide (CPP) octaarginine-oxaliplatin conjugate that quickly and successfully delivered oxaliplatin into colon cancer cells. The CPP octaarginine is a well-studied cationic peptide that can play a role as a drug delivery vector. In this work, an octaarginine CPP (RRRRRRRR) was conjugated with oxaliplatin via a specific heterobifunctional linker. The in vitro studies showed the conjugate had affinity toward mitochondria inside cells and the MTT assay confirmed that conjugate is active in low micromolar range against colon cancer cells, requiring much lower concentrations than the oxaliplatin alone to reach IC. More importantly, in the in vivo mouse study, the conjugate effectively inhibited tumor growth and showed considerably high antitumor activity, demonstrating the conjugate can perform well in vivo. This strategy may offer a new approach for designing oxaliplatin derivatives or prodrugs with remarkable therapeutic capabilities.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120904DOI Listing
September 2021

Prognostic impact of GPR56 in patients with colorectal cancer.

Neoplasma 2021 May 24;68(3):580-589. Epub 2021 Feb 24.

Division of Colon and Rectal Surgery, Department of Surgery, Yonsei University College of Medicine, Yonsei University Severance Hospital, Seoul, South Korea.

G protein-coupled receptor 56 (GPR56) belongs to the adhesion G protein-coupled receptor subfamily, which plays a role in cell progression and survival. The aim of this study was to investigate the role of the GPR56 gene in a cell line study and the impact of its protein expression on the prognosis of colorectal cancer (CRC) patients. The effect of GPR56 on tumor cell proliferation (WST-1 assay), invasion (Transwell assay), migration (Transwell assay, wound healing assay), and colony-forming ability (semisolid agar colony-forming assay) was explored. The expression levels of GPR56 in tissue samples of 109 CRC patients were evaluated by immunohistochemistry. The prognostic value of GRP56 was analyzed using univariate and multivariate analyses. The downregulation of GPR56 in the CRC cell line reduced cell proliferation as compared with that in a control sample (48 h; p=0.042, 72 h; p=0.001). Downregulation of the GPR56 expression reduced cell invasion and migration abilities and inhibited colony-forming abilities (p<0.005). The 5-year overall survival rate was worse in the high-expression group as compared with that in the low-expression group (51.6% vs. 74.4%, p=0.008). High GPR56 expression was a significant prognostic factor for overall survival of CRC patients in the univariate (p=0.001) and multivariate (p<0.001) analyses. The expression level of GPR56 plays an important role in tumor progression in CRC, and it may serve as a prognostic indicator in CRC patients.
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http://dx.doi.org/10.4149/neo_2021_201209N1333DOI Listing
May 2021

Expression of AMP-activated protein kinase/ten-eleven translocation 2 and their clinical relevance in colorectal cancer.

Oncol Lett 2021 Feb 4;21(2):164. Epub 2021 Jan 4.

Division of Colon and Rectal Surgery, Department of Surgery, College of Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Chungcheongnam-do 31151, Republic of Korea.

Inactivation of the ten-eleven translocation (TET) family members and catalyzation of 5-methylcytosine (5-mC) into 5-hydroxymethylcytosine (5-hmC) is associated with cancer initiation and progression. AMP-activated protein kinase (AMPK) is an enzyme that stabilizes TET2; however, the clinical relevance of AMPK and TET2 expression levels is currently unclear. Therefore, the present study aimed to investigate the clinical implications of AMPK/TET2 expression levels in colorectal cancer (CRC). Immunohistochemistry was used to retrospectively examine the expression levels of AMPK and TET2 in paraffin-embedded specimens obtained from 343 patients with CRC. The results demonstrated that AMPK and TET2 were highly expressed in CRC samples. No significant association was observed between the expression levels of TET2 and patient clinicopathological characteristics (age, tumor location, lymphatic, vascular and perineural invasion, Tumor-Node-Metastasis stages and differentiation); however, patients with low expression levels of TET2 more frequently presented with distant metastasis. By contrast, the expression levels of AMPK were significantly associated with lymph node and distant metastases. The survival analysis results revealed that high expression levels of TET2 were an independent predictor of favorable prognosis compared with low TET2 levels. However, no significant differences in overall survival were observed between patients with high and low expression levels of AMPK. These results described the clinical significance of AMPK/TET2 in CRC. The results of the multivariate analysis demonstrated that high expression levels of TET2 were a predictor of a favorable prognosis, whereas AMPK was not a significant factor for determining patient prognosis; therefore, further functional analysis of AMPK/TET2 expression in CRC is needed.
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http://dx.doi.org/10.3892/ol.2021.12425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798087PMC
February 2021

Prognostic Relevance of HJURP Expression in Patients with Surgically Resected Colorectal Cancer.

Int J Mol Sci 2020 Oct 26;21(21). Epub 2020 Oct 26.

Department of Pathology, College of Medicine, Soonchunhyang University, 31 Soonchunhyang 6 gil, Dongnam-gu, Cheonan, Chungcheongnam-do 31151, Korea.

HJURP is a key factor for CENP-A deposition and maintenance in centromeres. The role of mis-regulation of histone chaperones in cancer initiation and progression has been studied. However, its role in colorectal cancer is still unclear. In this study, we aimed to evaluate the expression of HJURP in 162 colorectal cancer tissue. To investigate the function of HJURP in the colorectal cancer cell, we suppressed HJURP expression by siRNA and confirmed proliferation, migration, invasion, and anchorage independent of colony forming ability. The association between HJURP expression levels and clinicopathological factors was evaluated in 162 CRC tissues using immunohistochemistry. The overall survival rate in patients of HJURP high expression was higher than those in HJURP low expression in CRC. Suppressing HJURP expression decreased cellular proliferation, invasion, and migration in four CRC cell lines: HT29, HCT116, SW480, SW620 in vitro study. Our findings revealed that the knockdown of HJURP suppressed the proliferation, migration, invasion, and tumorigenicity in CRC cells. Due to its strong association with CRC, HJURP could be a potential prognostic biomarker and a novel target for drug discovery.
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http://dx.doi.org/10.3390/ijms21217928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662712PMC
October 2020

Downregulation of miR-9 correlates with poor prognosis in colorectal cancer.

Pathol Res Pract 2020 Aug 2;216(8):153044. Epub 2020 Jun 2.

Soonchunhyang Medical Science Research Institute, College of Medicine, Soonchunhyang University, 31 Soonchunhyang 6 Gil, Dongnam-gu, Cheonan, Chungcheongnam-do, 330-722, Republic of Korea; Department of Pathology, College of Medicine, Soonchunhyang University, 31 Soonchunhyang 6 Gil, Dongnam-gu, Cheonan, Chungcheongnam-do, 330-722, Republic of Korea. Electronic address:

Introduction: microRNAs (miRNAs) are frequently dysregulated in many human cancers including colorectal cancer (CRC) and are useful candidate biomarkers in liquid biopsy of cancer for their stability in the blood.

Methods: We compared the expression of microRNA-9 (miR-9) in tissues (n = 357) and sera (n = 109) of CRC patients to determine whether miR-9 in serum reflects that in the cancer tissue in parallel. Also, we examined the miR-9 role in CRC by in vitro functional studies in four CRC cell lines.

Results: On multivariate analysis of colorectal cancer tissues and sera, miR-9 low expressions were significantly associated pN stage (tissues; p < 0.01, serum; p = 0.013), and clinical stage (tissues; p < 0.01, serum; p = 0.031). Moreover, patients with low miR-9 expression had shorter survival than those with high miR-9 expression (log-rank test, tissue; p = 0.021, serum; p = 0.011). miR-9 level in serum reflects that in the tumor. The CRC cells with low miR-9 expression was significantly increased cell proliferation, migration, invasion and colony formation than cells with high miR-9 expression.

Conclusion: Serum miR-9 is an useful early detection marker in liquid biopsy of CRC and overexpression of miR-9 in CRC may be a novel prognostic marker as well.
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http://dx.doi.org/10.1016/j.prp.2020.153044DOI Listing
August 2020

Dear Authors and Colleagues.

Authors:
Moo-Jun Baek

Ann Coloproctol 2020 Apr 30;36(2):63. Epub 2020 Apr 30.

Editor-in-Chief of Annals of Coloproctology.

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http://dx.doi.org/10.3393/ac.2020.04.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299563PMC
April 2020

Preoperative neutrophil-lymphocyte ratio and CEA is associated with poor prognosis in patients with synchronous colorectal cancer liver metastasis.

Ann Surg Treat Res 2019 Apr 28;96(4):191-200. Epub 2019 Mar 28.

Department of Surgery, Soonchunhyang University Cheonan Hospital, Cheonan, Korea.

Purpose: Recently, the neutrophil-to-lymphocyte ratio (NLR), an inflammatory response marker, has been reported to be associated with the prognosis in patients with various type of cancer. However, there have been no studies until now that have explored the prognostic role of combined detection of NLR and CEA in patients with synchronous liver-limited colorectal metastases (sCRLM).

Methods: Eighty-three patients who histologically diagnosed as sCRLM were selected. Their laboratory and clinical data were collected retrospectively. Using receiver operating characteristic curve analysis, the cutoff value of NLR was calculated based on which patients were assigned to a high NLR (more than 1.94) group and low NLR (less than 1.94) group. A cutoff value of 100 ng/mL for serum CEA level was used in light of the previous literature.

Results: CEA level and Poorly differentiated histology of colon cancer was significantly correlated with high NLR (P = 0.005 and P = 0.048, respectively). The multivariate analysis identified the high NLR as independent prognostic factors for OS and DFS in all patients (P = 0.010 and P = 0.006, respectively). Patients with both low levels of NLR and CEA had a significantly longer OS and DFS (P = 0.026 and P = 0.009, respectively).

Conclusion: In conclusion, elevated preoperative NLR is strongly correlated with both survival and recurrence in patients who have been diagnosed with resectable sCRLM. The combination of NLR and CEA level could be a more powerful prognostic marker than NLR alone.
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http://dx.doi.org/10.4174/astr.2019.96.4.191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6444047PMC
April 2019

Defensin alpha 6 (DEFA6) is a prognostic marker in colorectal cancer.

Cancer Biomark 2019 ;24(4):485-495

Department of Surgery, College of Medicine, Soonchunhyang University, Chungcheongnam-do, 330-723, Korea.

Defensin alpha 6 (DEFA6) is a member of the alpha defensin family of microbicidal and cytotoxic peptides that defend against bacteria and viruses. Here, we provide a novel function of DEFA6 in tumorigenesis of colorectal cancer (CRC) in vitro and in vivo. Specifically, DEFA6 is highly expressed in both CRC cancer cell lines as well as patient-derived samples at the level of RNA and protein. By shRNA-mediated loss of function of DEFA6, we found that proliferation, migration, invasion, colony forming ability of CRC cell lines were impaired in the absence of DEFA6 in vitro. Furthermore, DEFA6-deficient cancer cells exhibited significantly reduced growth rates compared to control cells in vivo. More importantly, by analyzing 352 patient-derived samples, we revealed that DEFA6 is associated with overall survival rate of CRC patients and thus an independent prognostic marker for CRC. These results suggest that DEFA6 plays an essential oncogenic role in CRC and serves a good therapeutic target for the disease.
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http://dx.doi.org/10.3233/CBM-182221DOI Listing
August 2019

Promotion of tumor progression and cancer stemness by MUC15 in thyroid cancer via the GPCR/ERK and integrin-FAK signaling pathways.

Oncogenesis 2018 Nov 12;7(11):85. Epub 2018 Nov 12.

Department of Surgery, College of Medicine, Yonsei University, Seoul, Korea.

Thyroid cancer is the fifth most common cancer diagnosed in women worldwide. Notwithstanding advancements in the prognosis and treatment of thyroid cancer, 10-20% of thyroid cancer patients develops chemotherapeutic resistance and experience relapse. According to previous reports and TCGA database, MUC15 (MUCIN 15) upregulation is highly correlated with thyroid cancer progression. However, the role of MUC15 in tumor progression and metastasis is unclear. This study aimed to investigate factors mediating cancer stemness in thyroid cancer. MUC15 plays an important role in sphere formation, as an evident from the expression of stemness markers including SOX2, KLF4, ALDH1A3, and IL6. Furthermore, ectopic expression of MUC15 activated extracellular signal-regulated kinase (ERK) signaling via G-protein-coupled receptor (GPCR)/cyclic AMP (cAMP) and integrin/focal adhesion kinase pathways. Interestingly, ectopic expression of MUC15 did not affect RAF/mitogen-activated protein kinase kinase (MEK)-mediated ERK activation. The present findings may provide novel insights into the development of diagnostic, prognostic, and therapeutic applications of MUC15 in thyroid cancer.
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http://dx.doi.org/10.1038/s41389-018-0094-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232104PMC
November 2018

Interferon-induced transmembrane protein 1-mediated EGFR/SOX2 signaling axis is essential for progression of non-small cell lung cancer.

Int J Cancer 2019 04 8;144(8):2020-2032. Epub 2018 Dec 8.

Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Cheonan, Republic of Korea.

Emerging data indicate that interferon-induced transmembrane protein 1 (IFITM1) plays an important role in many cancers. However, it remains unclear whether IFITM1 is functionally indispensable in nonsmall cell lung cancer (NSCLC). Here, using NSCLC cell lines and patient-derived samples, we show that IFITM1 is essentially required for the progression of NSCLC in vitro and in vivo. Specifically, IFITM1 depletion resulted in a significant reduction in sphere formation, migration, and invasion of NSCLC cells in vitro; these events were inversely correlated with the ectopic expression of IFITM1. In addition, tumor development was significantly impaired in the absence of IFITM1 in vivo. Mechanistically, epidermal growth factor receptor/sex-determining region Y-box 2 (EGFR/SOX2) signaling axis was compromised in the absence of IFITM1, and the ectopic expression of SOX2 partially rescued the defects caused by IFITM1 depletion. More importantly, using 226 patient-derived samples, we demonstrate that a high level of IFITM1 expression is associated with a poor overall survival (OS) rate in adenocarcinoma but not in squamous cell carcinoma. Collectively, these data suggest that IFITM1 is a poor prognostic marker of adenocarcinoma and an attractive target to develop novel therapeutics for NSCLC.
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http://dx.doi.org/10.1002/ijc.31926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587945PMC
April 2019

Melatonin and 5-fluorouracil co-suppress colon cancer stem cells by regulating cellular prion protein-Oct4 axis.

J Pineal Res 2018 Nov 24;65(4):e12519. Epub 2018 Aug 24.

Medical Science Research Institute, Soonchunhyang University Seoul Hospital, Seoul, Korea.

Melatonin suppresses tumor development. However, the exact relationship between melatonin and cancer stem cells (CSCs) is poorly understood. This study found that melatonin inhibits colon CSCs by regulating the PrP -Oct4 axis. In specimens from patients with colorectal cancer, the expressions of cellular prion protein (PrP ) and Oct4 were significantly correlated with metastasis and tumor stages. Co-treatment with 5-fluorouracil (5-FU) and melatonin inhibited the stem cell markers Oct4, Nanog, Sox2, and ALDH1A1 by downregulating PrP . In this way, tumor growth, proliferation, and tumor-mediated angiogenesis were suppressed. In colorectal CSCs, PRNP overexpression protects Oct4 against inhibition by 5-FU and melatonin. In contrast, Nanog, Sox2, and ALDH1A1 have no such protection. These results indicate that PrP directly regulates Oct4, whereas it indirectly regulates Nanog, Sox2, and ALDH1A1. Taken together, our findings suggest that co-treatment with anticancer drug and melatonin is a potential therapy for colorectal cancer. Furthermore, PrP maintains cancer stemness during tumor progression. Therefore, targeting the PrP -Oct4 axis may prove instrumental in colorectal cancer therapy.
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http://dx.doi.org/10.1111/jpi.12519DOI Listing
November 2018

Association Between c-Met and Lymphangiogenic Factors in Patients With Colorectal Cancer.

Ann Coloproctol 2018 Apr 30;34(2):88-93. Epub 2018 Apr 30.

Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea.

Purpose: Animal models show a strong relationship between lymphangiogenesis and lymph node metastasis. However, the clinical significance of lymphangiogenesis in patients with colorectal cancer (CRC) remains uncertain. This study aimed to evaluate the association between c-Met and lymphangiogenic factors and to elucidate the prognostic significance of c-Met in patients with CRC.

Methods: A total of 379 tissue samples were obtained from surgically resected specimens from patients with CRC at Soonchunhyang University Cheonan Hospital between January 2002 and December 2010. The expressions of c-Met, vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGF receptor (VEGFR)-3, and podoplanin were examined using immunohistochemistry. The expression of c-Met and clinical factors were analyzed.

Results: Of the 379 tissues, 301 (79.4%) had c-Met expression. High expression of c-Met in tumor cells was significantly associated with high expression of VEGF-C (P < 0.001) and VEGFR-3 (P = 0.001). However, no statistically significant association with podoplanin (P = 0.587) or VEGF-D (P = 0.096) was found. Of the 103 evaluable patients, expression of c-Met in tumor cells was significantly associated with advanced clinical stage (P = 0.020), positive lymph node status (P = 0.038), and high expression of VEGF-C (P = 0.020). However, no statistically significant association with podoplanin (P = 0.518), VEGFR-3 (P = 0.085), VEGF-D (P = 0.203), or overall survival (P = 0.360) was found.

Conclusion: Our results provide indirect evidence for an association and possible regulatory link of c-Met with the lymphangiogenic markers, but c-Met expression in patients with CRC is not a prognostic indicator for overall survival.
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http://dx.doi.org/10.3393/ac.2017.10.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5951094PMC
April 2018

Protein kinase, membrane‑associated tyrosine/threonine 1 is associated with the progression of colorectal cancer.

Oncol Rep 2018 Jun 13;39(6):2829-2836. Epub 2018 Apr 13.

Department of Surgery, College of Medicine, Soonchunhyang University, Cheonan, Chungcheongnam‑do 31151, Republic of Korea.

The protein kinase, membrane‑associated tyrosine/threonine 1 (PKMYT1) is known to inhibit precocious entry into mitosis by phosphorylating CDK1 at Thr14 and Tyr15 residues. However, the functional importance of PKMYT1 in colorectal cancer (CRC) remains unknown. Thus, it is important to elucidate whether PKYMT1 is indispensable in the tumorigenesis of CRC. To investigate the functional importance of PKMYT1 in CRC tumorigenesis, PKMYT1 was knocked down in CRC cell lines such as SW480, SW620, HCT116 and HT29 by siRNA. PKMYT1‑depleted CRC cells were analyzed to determine proliferation, migration, invasion and colony forming ability. In addition, 179 patient‑derived samples were used to find the correlation of the expression of PKMYT1 with the prognosis of CRC patients. By siRNA‑mediated loss of function of PKMYT1, we observed that proliferation, migration, invasion and colony forming ability of CRC cell lines were significantly impaired in the absence of PKMYT1 in vitro. Furthermore, by analyzing patient‑derived samples, we revealed the association of PKMYT1 with the overall survival rate of CRC patients. These results indicated that PKMYT1 plays an essential oncogenic role in CRC and could serve as a good therapeutic target for the treatment of CRC.
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http://dx.doi.org/10.3892/or.2018.6371DOI Listing
June 2018

CORRIGENDUM: Correction of funding statement in ACKNOWLEDGEMENTS section: Epigenetic inactivation of in colorectal cancer.

Ann Surg Treat Res 2018 03 28;94(3):166. Epub 2018 Feb 28.

Department of Surgery, Soonchunhyang University College of Medicine, Cheonan, Korea.

[This corrects the article on p. 19 in vol. 94, PMID: 29333422.].
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http://dx.doi.org/10.4174/astr.2018.94.3.166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842091PMC
March 2018

Epigenetic inactivation of in colorectal cancer.

Ann Surg Treat Res 2018 Jan 28;94(1):19-25. Epub 2017 Dec 28.

Department of Surgery, Soonchunhyang University College of Medicine, Cheonan, Korea.

Purpose: Emerging evidence indicates that runt-related transcription factor 3 () is an important tumor suppressor gene in several cancer types, including colorectal cancer (CRC). However, the clinical significance of RUNX3 inactivation in CRC remains unclear. The aim of this study was to examine the correlation between clinicopathologic factors and RUNX3 hypermethylation/expression in CRC.

Methods: Sixty-two CRC patients who were treated at the Soonchunhyang University College of Medicine were recruited in this study. The hypermethylation of CpG islands in the RUNX3 promoter and the expression of RUNX3 mRNA were identified by methylation-specific polymerase chain reaction (PCR) and reverse transcriptase-PCR, respectively. The expression of RUNX3 was determined by immunohistochemical staining.

Results: Of the 62 CRC tissue samples, 20 (32.3%) presented hypermethylated RUNX3 promoters. Aberrant RUNX3 hypermethylation was found to be associated with vascular (P = 0.006) and lymphatic (P = 0.002) invasion. Hypermethylation of RUNX3 was associated with poor survival outcomes (P = 0.038). However, expression of RUNX3 was not a prognostic factor (P = 0.363).

Conclusion: Hypermethylation of RUNX3 may be a predictor of a poor prognosis in CRC.
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http://dx.doi.org/10.4174/astr.2018.94.1.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765274PMC
January 2018

Clinicopathological Significance of Large Tumor Suppressor () Expression in Gastric Cancer.

J Gastric Cancer 2017 Dec 26;17(4):363-373. Epub 2017 Dec 26.

Department of Surgery, Soonchunhyang University Cheonan Hospital, Cheonan, Korea.

Purpose: The aims of this study were to evaluate the expression of the large tumor suppressor () genes and by immunohistochemical staining of gastric cancer, and to evaluate the clinicopathological significance of expression and its correlation with overall survival (OS).

Materials And Methods: and expression in a tissue microarray was detected by immunohistochemistry, using 264 gastric cancer specimens surgically resected between July 2006 and December 2009.

Results: Low expression of was significantly associated with more advanced American Joint Committee on Cancer (AJCC) stage (P=0.001) and T stage (P=0.032), lymph node (LN) metastasis (P=0.040), perineural invasion (P=0.042), poor histologic grade (P=0.007), and diffuse-type histology by the Lauren classification (P=0.033). Low expression of was significantly correlated with older age (≥65, P=0.027), more advanced AJCC stage (P=0.001) and T stage (P=0.001), LN metastasis (P=0.004), perineural invasion (P=0.004), poor histologic grade (P<0.001), and diffuse-type histology by the Lauren classification (P<0.001). Kaplan-Meier survival analysis revealed significantly poor OS rates in the groups with low (P=0.037) and (P=0.037) expression.

Conclusions: Expression of or is a significant marker for a good prognosis in patients with gastric cancer.
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http://dx.doi.org/10.5230/jgc.2017.17.e41DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5746657PMC
December 2017

Usefulness of metabolic activity of adipose tissue in FDG PET/CT of colorectal cancer.

Abdom Radiol (NY) 2018 08;43(8):2052-2059

Department of Surgery, Soonchunhyang University Cheonan Hospital, Cheonan, 31151, Republic of Korea.

Purpose: To determine the relationship between metabolic activity of adipose tissue on FDG PET/CT and prognosis in colorectal cancer.

Methods: A total of 176 colorectal cancer patients with curative surgical resection were retrospectively enrolled. Volume and metabolic activity of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) on FDG PET/CT images were measured. The maximum standardized uptake value (SUV) of primary tumor (SUVtumor) was also obtained. Univariate analysis with log-rank test and multivariate Cox regression analyses were used to evaluate prognostic values of volume and metabolic activity of SAT and VAT as well as SUVtumor and clinicopathologic factors.

Results: Of 176 patients, 26 experienced recurrence during follow-up. SUVtumor showed significant correlation with serum C-reactive protein level (r = 0.242, p = 0.001), SUV of VAT (r = 0.167, p = 0.026), and size of primary tumor (r = 0.341, p < 0.001). In univariate analysis with log-rank test, SUV of VAT (p = 0.009) and SAT (p = 0.006), volume of VAT (p = 0.015), N stage (p < 0.001), M stage (p < 0.001), tumor involvement of resection margin (p = 0.001), and lymphatic invasion (p = 0.024) were significantly associated with recurrence-free survival (RFS). However, SUVtumor showed no significant association with RFS. In multivariate Cox regression analysis, SUV of VAT (p = 0.016), presence of lymph node metastasis (p < 0.001), and tumor involvement of resection margin (p = 0.011) were independent prognostic factors for RFS.

Conclusions: The SUV of VAT in patients with colorectal cancer is significantly associated with FDG uptake of primary tumor. It is an independent predictor for RFS.
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http://dx.doi.org/10.1007/s00261-017-1418-7DOI Listing
August 2018

Fluorine-18-fluorodeoxyglucose uptake of bone marrow on PET/CT can predict prognosis in patients with colorectal cancer after curative surgical resection.

Eur J Gastroenterol Hepatol 2018 Feb;30(2):187-194

Department of Nuclear Medicine, Cheonan Hospital, Soonchunhyang University, Cheonan, Korea.

Objective: This study investigated the relationship of fluorine-18-fluorodeoxyglucose (F-FDG) uptake of bone marrow (BM) on PET/computed tomography (PET/CT) with clinicopathologic factors and survival in patients with colorectal cancer.

Patients And Methods: The study retrospectively included 226 patients with colorectal cancer who underwent F-FDG PET/CT for staging workup and treated with curative surgical resection. The maximum F-FDG uptake of primary cancer (Tmax) and mean F-FDG uptake of BM [BM standardized uptake value (SUV)] were derived from PET/CT images. The relationships between BM SUV and clinicopathologic factors and prognostic value of BM SUV for predicting recurrence-free survival (RFS) were assessed.

Results: Patients with T3-T4 stage and hepatic metastases had significantly higher values of BM SUV than those with T1-T2 stage and no distant metastases (P<0.05). BM SUV showed significant positive correlation with Tmax, tumor size, serum C-reactive protein level, white blood cell count, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (P<0.05). Univariate survival analysis revealed that N stage, M stage, tumor involvement of resection margin, lymphatic invasion, and BM SUV were significant predictors for RFS (P<0.05), whereas Tmax failed to show significance. In multivariate analysis, N stage (P=0.012 for N1 stage and P=0.020 for N2 stage), tumor involvement of resection margin (P=0.009), and BM SUV (P=0.005) were significantly associated with RFS.

Conclusion: Increased BM SUV was observed in patients with advanced stage and increased serum inflammatory markers. BM SUV was an independent predictor for RFS in colorectal cancer.
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http://dx.doi.org/10.1097/MEG.0000000000001018DOI Listing
February 2018

Karyopherin α-2 is a reliable marker for identification of patients with high-risk stage II colorectal cancer.

J Cancer Res Clin Oncol 2017 Dec 5;143(12):2493-2503. Epub 2017 Sep 5.

Department of Surgery, College of Medicine, Soonchunhyang University, 31 Soonchunhyang 6 gil, Dongnam-gu, Cheonan, Chungcheongnam-do, 330-723, Republic of Korea.

Purpose: Adjuvant chemotherapy (AC) is frequently considered in patients with high-risk stage II colorectal cancer (CRC). Among patients with stage II CRC who do not receive AC because they are not considered to be at high risk, 20-25% will develop recurrence and die from the disease. Elevated levels of KPNA2 have been observed in various cancers, and overexpression of KPNA2 is related to CRC progression.

Methods: We examined the expression of KPNA2 using 293 CRC tissues, including 118 with stage II CRC, and investigated the applicability of KPNA2 as a biomarker to predict high-risk stage II CRC. Moreover, we further investigated the role of KPNA2 as an oncogene in CRC carcinogenesis using in vitro functional studies.

Results: High KPNA2 expression was associated with vascular (p = 0.027) and lymphatic invasion (p = 0.009) in patients with stage II CRC. On multivariate analysis, high KPNA2 expression (HR 3.174, 95% CI 2.060-4.889; p < 0.001) was independently associated with survival in patients with CRC. The overall survival rate in patients with high KPNA2 expression was higher than that in patients with low KPNA2 expression in CRC (p < 0.001), even in patients with stage II CRC (p = 0.001). Additionally, KPNA2 was associated with tumorigenesis and cancer progression in CRC cells; high KPNA2 expression was associated with increased cell proliferation (p < 0.05), migration (p = 0.03), invasion (p = 0.001), and semisolid agar colony formation (p < 0.001).

Conclusion: KPNA2 expression is useful for identification of patients with high-risk stage II CRC who could benefit from AC and that KPNA2 may also be a promising therapeutic target.
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http://dx.doi.org/10.1007/s00432-017-2512-5DOI Listing
December 2017

Doxorubicin-loaded oligonucleotide conjugated gold nanoparticles: A promising in vivo drug delivery system for colorectal cancer therapy.

Eur J Med Chem 2017 Dec 31;142:416-423. Epub 2017 Aug 31.

Department of Chemistry, Soonchunhyang University, Asan 31538, Republic of Korea. Electronic address:

In this study, we propose doxorubicin (DOX) loaded oligonucleotides (ONTs) attached to gold nanoparticles (AuNPs) as a drug delivery system for cancer chemotherapy. DOX is one of the representative cancer chemotherapy agents and is widely used by many researchers as a chemotherapy agent in the drug delivery system. Due to the advantages of AuNPs such as simple steps in synthesis, high surface-area-to-volume ratio, and biocompatibility, we utilized AuNPs as drug delivery vehicle. AuNPs were synthesized by chemical reduction to be 13 nm diameter. The G-C rich oligonucleotides were used both for drug loading sites and AuNPs capping agents. 80% of DOX in solution could be bound to ONTs on AuNPs to became DOX-loaded AuNPs coated with ONTs (Doxorubicin-Oligomer-AuNP, DOA), and about 28% of loaded DOX was released from the as-prepared DOA. Confocal microscopy observation showed that DOA was well transported into cells, and finally the DOX was released into the cell nucleus. The drug's efficacies such as in vitro cytotoxicity and in vivo tumor growth inhibition were demonstrated with SW480 colon cancer cell line and a xenograft mouse model. MTT assay was performed to see the cytotoxicity effect on SW480 cells treated with DOA for 24 h, and the cell viability was determined to be 41.77% (p < 0.001). When DOA was administered regularly to a tumor bearing mouse, the tumor growth inhibition degree was examined by measuring the tumor size. The treatment-control (T/C) ratio was found to be 0.69. Thus, our results suggest the use of DOAs as promising drug delivery systems for colorectal cancer therapy.
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http://dx.doi.org/10.1016/j.ejmech.2017.08.063DOI Listing
December 2017

Limitation and Value of Using the Adenoma Detection Rate for Colonoscopy Quality Assurance.

Ann Coloproctol 2017 Jun 30;33(3):81. Epub 2017 Jun 30.

Department of Surgery, Soonchunhyang University Cheonan Hospital, Cheonan, Korea.

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http://dx.doi.org/10.3393/ac.2017.33.3.81DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5534497PMC
June 2017

Oncogenic function of angiopoietin-2 and its modulation of tumor progression in colorectal carcinoma.

Oncol Lett 2017 Jul 18;14(1):553-560. Epub 2017 May 18.

Department of Pathology, College of Medicine, Soonchunhyang University, Dongnam-gu, Cheonan, Chungcheongnam-do 330-721, Republic of Korea.

Angiopoietin-2 (Ang-2) has been investigated in cancer primarily in terms of its angiogenic function, and its role as an oncogene has yet to be elucidated. The current study hypothesized that Ang-2 may be an oncogene and have a function in tumor progression. An investigation of the function of Ang-2 in the LoVo colorectal cancer (CRC) cell line , which expresses a high level of Ang-2, was performed by knocking down endogenous expression with a targeted short hairpin RNA. The aggressive phenotypic effects of Ang-2 on experimental and control group cells were assessed using cell proliferation, migration and invasion assays. The association between Ang-2 expression levels and clinicopathological factors was evaluated in 415 CRC tissues using immunohistochemistry. Suppressing Ang-2 expression decreased cellular proliferation, invasion and migration in an study. Ang-2 overexpression was observed in 46% of patients with CRC and was significantly associated with pT (P=0.048), pN (P<0.001), venous invasion (P=0.023), lymphatic invasion (P<0.001) and tumor-node-metastasis stage (P=0.022). Furthermore, Ang-2 overexpression was an independent prognostic factor in pN stages 1 and 2. These results reveal that Ang-2 may be an oncogene in colorectal carcinogenesis and its expression may exert aggressive phenotypic effects during tumor progression. In addition, Ang-2 expression may serve as a prognostic marker and a potential drug target.
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http://dx.doi.org/10.3892/ol.2017.6203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5494651PMC
July 2017

Solute carrier organic anion transporter family member 4A1 (SLCO4A1) as a prognosis marker of colorectal cancer.

J Cancer Res Clin Oncol 2017 Aug 4;143(8):1437-1447. Epub 2017 Apr 4.

Soonchunhyang Medical Science Research Institute, Soonchunhyang University, Cheonan, Chungcheongnam-do, Republic of Korea.

Purpose: Solute carrier organic anion transporter family member 4A1 (SLCO4A1) is involved in the transport of various compounds, including sugars, bile salts, organic acids, metal ions, amine compounds, and estrogen. SLCO4A1 is highly expressed in several cancers and a gender bias has been observed in colorectal cancer (CRC). We investigated SLCO4A1 expression, its prognostic value in patients with CRC, and its role in CRC cell proliferation and metastasis.

Methods: SLCO4A1 expression was assessed by immunohistochemistry (IHC) on specimens from 84 patients with CRC. The association of SLCO4A1 expression with clinicopathological features was examined. To confirm the biological role of SLCO4A1 in CRC, four CRC cell lines expressing SLCO4A1 were used and SLCO4A1 expression was knocked down by siRNA. Cell proliferation, MTT, migration, invasion, and semisolid agar colony formation assays were performed.

Results: SLCO4A1 was overexpressed in 32% of the CRC samples. SLCO4A1 overexpression and pathologic T stage were independent prognostic factors of decreased survival (P = 0.021). Kaplan-Meier analysis indicated a decreased cumulative survival for patients highly expressing SLCO4A1 compared to patients showing low SLCO4A1 expression (Log-rank test, P = 0.025). In cell lines, SLCO4A1 knockdown resulted in a significant decrease of viability, invasion, and migration when compared to control cells. Semisolid colony formation assay indicated that SLCO4A1-knocked down cells presented poor carcinogenic abilities compared to control cells.

Conclusions: SLCO4A1 may be a valuable marker of poor prognostic for CRC. Furthermore, SLCO4A1 plays an important role in CRC cell proliferation, migration, invasion, and carcinogenesis.
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http://dx.doi.org/10.1007/s00432-017-2393-7DOI Listing
August 2017

The efficacy of laparoscopic cholecystectomy without discontinuation in patients on antithrombotic therapy.

Ann Surg Treat Res 2017 Mar 24;92(3):143-148. Epub 2017 Feb 24.

Department of Surgery, Soonchunhyang University Cheonan Hospital, Cheonan, Korea.

Purpose: Laparoscopic cholecystectomy (LC) is one of the most commonly performed surgeries in the world today. However, there is no consensus regarding whether LC can be performed in patients with acute cholecystitis while on antithrombotic therapy. The objective of our study was to describe postoperative outcomes of patients who underwent emergent LC without interruption to antithrombotic therapy.

Methods: We performed a retrospective review of patients who underwent LC for acute cholecystitis while on antithrombotic therapy from 2010 to 2015 at Soonchunhyang Universtiy Cheonan Hospital. Patients were divided into 2 groups as underwent emergent LC and elective LC.

Results: A total of 67 patients (emergent group, 22; elective group, 45) were included in the analysis. Elective group had significantly longer duration between the admission and operation (8 [7-10] days . 2 [1-3] days, P < 0.001) and longer duration of antithrombotic drugs discontinuation (7 days . 1 [0-3] days, P < 0.001). Emergent group had significantly more postoperative anemia (6 patients . 0 patient, P = 0.001) and 3 of 6 patients received packed RBC transfusion in postoperative period. However, there was no significant difference in length of postoperative stays, length of intensive care unit stays and mortality rates.

Conclusion: Emergent LC without interruption to antithrombotic therapy was relatively safe and useful. A well-designed multicenter study is needed to confirm the safety and efficacy of LC without suspension of antithrombotic therapy and to provide a simple guideline.
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http://dx.doi.org/10.4174/astr.2017.92.3.143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344804PMC
March 2017

Expressions and Clinical Significances of Angiopoietin-1, Angiopoietin-2, and Tie-2 Receptor in Patients With Colorectal Cancer.

Ann Coloproctol 2017 Feb 28;33(1):9-15. Epub 2017 Feb 28.

Division of Hematology and Oncology, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Korea.

Purpose: Angiopoietin-1 (Ang-1) plays a crucial role in vascular and hematopoietic development, mainly through its cognate receptor, Tie-2. Increased levels of Ang-2 have been shown to be correlated with abnormal tumor angiogenesis in several malignancies. Hence, we estimated the increased expression of Ang-2 relative to Ang-1 in patients with colorectal cancer and correlated our finding with prognosis in order to investigate the relationships between the expressions of Ang-1/Ang-2/Tie-2 receptor and the clinical parameters or overall survival of such patients.

Methods: We retrospectively analyzed 114 tissue samples from patients with colorectal cancer by using immunohistochemistry (IHC) to examine Ang-1, Ang-2, and Tie-2 expressions and to investigate the relationship between those expressions and clinical parameters or overall survival of such patients. A Western blot analysis was used for Ang-2 expression.

Results: IHC staining showed a link between Ang-1 and Tie-2 (P = 0.018), as well as meaningful correlations between Ang-2 and Tie-2 receptor (P = 0.022) and between lymph-node metastasis and Ang-2 (P = 0.025). The stronger the IHC staining for Ang-2 expression was, the shorter the cumulative survival was (P = 0.016).

Conclusion: A relationship was found to exist between Ang-2 and Tie-2 expressions. The Ang-2 was correlated with lymph-node metastasis, and high expression of Ang-2 was indicative of poor overall survival. These findings suggest that Ang-2 is a useful prognostic marker in the management of patients with colorectal cancer. In addition, we suggest that Ang/Tie-2 signaling plays an important role in the progression of colorectal cancer.
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http://dx.doi.org/10.3393/ac.2017.33.1.9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346784PMC
February 2017

Interferon-induced transmembrane protein 1 (IFITM1) is required for the progression of colorectal cancer.

Oncotarget 2016 Dec;7(52):86039-86050

Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Republic of Korea.

Interferon-induced transmembrane protein 1 (IFITM1) has been shown to be implicated in multiple cancers, yet little is known about biological significance of IFITM1 in colorectal cancer. Here, we show that IFITM1 is highly expressed in metastatic colorectal cancer cell lines as well as colorectal patient-derived tumor samples, and its expression is associated with a poor prognosis of the disease. Also, IFITM1 depletion resulted in a significant reduction in the mobility of cancer cell lines, whereas ectopic expression of IFITM1 promoted the migration of cancer cells. Epithelial-mesenchymal transition (EMT) signature was dysregulated by both loss and gain of function of IFITM1, which was partially reverted by Caveolin-1 (CAV1). Therefore, these results suggest that IFITM1 may be a prognostic marker and an attractive target to achieve better therapeutic outcomes in colorectal cancer.
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http://dx.doi.org/10.18632/oncotarget.13325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349895PMC
December 2016

Complete tubular duplication of colon in an adult: a rare cause of colovaginal fistula.

Ann Surg Treat Res 2016 Oct 30;91(4):207-211. Epub 2016 Sep 30.

Department of Surgery, Soonchunhyang University Cheonan Hospital, Cheonan, Korea.

Alimentary tract duplications are uncommon congenital anomalies that usually present during the first decade of life. Complete duplication of the colon in adults is very rare and difficult to diagnose preoperatively. We report a case of a 40-year-old female with complete tubular duplication which was initially misdiagnosed as a salpingeal abscess due to colovaginal fistula.
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http://dx.doi.org/10.4174/astr.2016.91.4.207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5064232PMC
October 2016

Overexpression of PD-L1 and PD-L2 Is Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma.

Cancer Res Treat 2017 Jan 7;49(1):246-254. Epub 2016 Jul 7.

Department of Surgery, Soonchunhyang University Cheonan Hospital, Cheonan, Korea.

Purpose: Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies. Recently, the overexpression of programmed cell death 1 (PD-1) and PD-1 ligand 1 (PD-L1) has been shown to correlate with poor prognosis in many cancers. However, the expression of PD-L1 or PD-1 ligand 2 (PD-L2) and clinical outcomes have not been fully investigated in HCC.

Materials And Methods: Formalin-fixed paraffin-embedded samples were obtained from 85 patients with HCC who underwent surgery. The expression of PD-Ls (PD-L1, PD-L2) was evaluated by immunohistochemical analysis.

Results: The proportion of high expression groups of PD-L1 and PD-L2 was 27.1% and 23.5%, respectively. Univariate analysis revealed that tumor size (p < 0.001), histological differentiation (p=0.010), PD-L1 expression (p < 0.001), and PD-L2 expression (p=0.039) were significant prognostic factors of overall survival in patients with HCC. Multivariate analysis revealed that overall tumor size (hazard ratio [HR], 4.131; 95% confidence interval [CI], 2.233 to 7.643; p < 0.001 and HR, 3.455; 95% CI, 1.967 to 6.067; p < 0.001) and PD-L1 expression (HR, 5.172; 95% CI, 2.661 to 10.054; p < 0.001 and HR, 3.730; 95% CI, 1.453 to 9.574; p=0.006) were independent prognostic values for overall and disease-free survival. Patients with high expression of PD-Ls had a significantly poorer survival than those with low expression (p < 0.001, p=0.034).

Conclusion: The overexpression of PD-Ls in HCC patients is correlated with survival and tumor recurrence. Further evaluation of PD-1 and PD-Ls as therapeutic targets and predictive biomarkers for HCC is warranted.
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http://dx.doi.org/10.4143/crt.2016.066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266389PMC
January 2017
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