Publications by authors named "Dongjun Jeong"

48 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpharm.2021.120904DOI Listing
September 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prp.2020.153044DOI Listing
August 2020

Capicua suppresses colorectal cancer progression via repression of ETV4 expression.

Cancer Cell Int 2020 5;20:42. Epub 2020 Feb 5.

1Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk Republic of Korea.

Background: Although major driver gene mutations have been identified, the complex molecular heterogeneity of colorectal cancer (CRC) remains unclear. Capicua (CIC) functions as a tumor suppressor in various types of cancers; however, its role in CRC progression has not been examined.

Methods: Databases for gene expression profile in CRC patient samples were used to evaluate the association of the levels of and () group genes ( (), , and ), the best-characterized CIC targets in terms of CIC functions, with clinicopathological features of CRC. CIC and ETV4 protein levels were also examined in CRC patient tissue samples. Gain- and loss-of function experiments in cell lines and mouse xenograft models were performed to investigate regulatory functions of CIC and ETV4 in CRC cell growth and invasion. qRT-PCR and western blot analyses were performed to verify the CIC regulation of ETV4 expression in CRC cells. Rescue experiments were conducted using siRNA against and CIC-deficient CRC cell lines.

Results: CIC expression was decreased in the tissue samples of CRC patients. Cell invasion, migration, and proliferation were enhanced in CIC-deficient CRC cells and suppressed in CIC-overexpressing cells. Among group genes, levels were most dramatically upregulated and inversely correlated with the CIC levels in CRC patient samples. Furthermore, derepression of was more prominent in CIC-deficient CRC cells, when compared with that observed for and . The enhanced cell proliferative and invasive capabilities in CIC-deficient CRC cells were completely recovered by knockdown of .

Conclusion: Collectively, the CIC-ETV4 axis is not only a key module that controls CRC progression but also a novel therapeutic and/or diagnostic target for CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12935-020-1111-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003492PMC
February 2020

miR551b Regulates Colorectal Cancer Progression by Targeting the ZEB1 Signaling Axis.

Cancers (Basel) 2019 May 27;11(5). Epub 2019 May 27.

Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Cheonan-si 31151, Korea.

Our current understanding of the role of microRNA 551b (miR551b) in the progression of colorectal cancer (CRC) remains limited. Here, studies using both ectopic expression of miR551b and miR551b mimics revealed that miR551b exerts a tumor suppressive effect in CRC cells. Specifically, miR551b was significantly downregulated in both patient-derived CRC tissues and CRC cell lines compared to normal tissues and non-cancer cell lines. Also, miR551b significantly inhibited the motility of CRC cells in vitro, including migration, invasion, and wound healing rates, but did not affect cell proliferation. Mechanistically, miR551b targets and inhibits the expression of ZEB1 (Zinc finger E-box-binding homeobox 1), resulting in the dysregulation of EMT (epithelial-mesenchymal transition) signatures. More importantly, miR551b overexpression was found to reduce the tumor size in a xenograft model of CRC cells in vivo. Furthermore, bioinformatic analyses showed that miR551b expression levels were markedly downregulated in the advanced-stage CRC tissues compared to normal tissues, and ZEB1 was associated with the disease progression in CRC patients. Our findings indicated that miR551b could serve as a potential diagnostic biomarker and could be utilized to improve the therapeutic outcomes of CRC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers11050735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563032PMC
May 2019

Prognostic significance of IFITM1 expression and correlation with microvessel density and epithelial-mesenchymal transition signature in lung adenocarcinoma.

Pathol Res Pract 2019 Jul 6;215(7):152444. Epub 2019 May 6.

Department of Pathology, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea.

We evaluated the relationship between interferon-induced transmembrane protein 1 (IFITM1) expression, epithelial-mesenchymal transition (EMT) signature and angiogenesis in lung adenocarcinoma. Additionally, we examined prognostic significance of IFITM1 according to pTNM stage to confirm that IFITM1 can serve as a complement to the pTNM stage. A total of 141 lung adenocarcinoma specimens were evaluated retrospectively by immunohistochemical staining for IFITM1, EMT markers (e-cadherin, β-catenin, and vimentin), and CD31 to measure microvessel density. IFITM1was expressed in 46.8% of the specimens. IFITM1 expression was significantly correlated with increased microvessel density (P = 0.048). However, IFITM1 expression was not associated with three EMT markers. In a multivariate analysis, IFITM1 was an independent prognostic factor for overall survival in a multivariate analysis (hazard ratio: 2.59, P = 0.01). Online database with data from 720 lung adenocarcinoma patients also revealed a negative prognostic significance of IFITM1 (P < 0.001). Furthermore, high IFITM1 expression was significantly correlated with decreased OS rates in each pTNM stage. IFITM1 is significantly correlated with angiogenesis and it may be used as a useful additional prognostic marker to aid pTNM classification.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prp.2019.152444DOI Listing
July 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/CBM-182221DOI Listing
August 2019

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3393/ac.2017.10.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5951094PMC
April 2018

Loss of RUNX3 is significantly associated with advanced tumor grade and stage in endometrial cancers.

Mol Med Rep 2018 Jun 23;17(6):8173-8179. Epub 2018 Apr 23.

Department of Obstetrics and Gynecology, Soonchunhyang University Cheonan Hospital, Cheonan, South Chungcheong 31151, Republic of Korea.

Loss of runt‑related transcription factor 3 (RUNX3) has been reported in various cancers, and one of the mechanisms mediating loss of RUNX3 expression is DNA methylation. However, the role of RUNX3 expression and its DNA methylation status as prognostic factors in endometrial cancer remain unclear. In the present study, the expression and promoter methylation of RUNX3 was examined in endometrial cancer tissues and cell lines, as well as their association with endometrial cancer prognosis. Fifty‑five endometrial cancer tissues and two endometrial cancer cell lines (HEC1‑α and Ishikawa) were studied. RUNX3 expression and promoter methylation were examined using reverse transcription‑polymerase chain reaction (RT‑PCR), methylation specific PCR (MS‑PCR), and immunohistochemical staining. The demethylating agent 5‑aza‑2'‑deoxycytidine (ADC) was used to reverse the methylation of the RUNX3 promoter. Loss of RUNX3 expression was observed in 50.9% (27/53) of endometrial cancer tissues and in the HEC1‑α cell line by immunohistochemistry and RT‑PCR, respectively. Methylation of the RUNX3 promoter was observed in 62.2% (33/53) of endometrial cancer tissues, 12.5% (1/8) of normal endometrial tissues, and the HEC1‑α cell line by MS‑PCR. Tumor grade and stage were significantly correlated with loss of RUNX3 expression. The expression of RUNX3 was restored by treatment with ADC and resulted in growth inhibition in HEC1‑α cells. The present results suggested that methylation may serve a critical role in the silencing of RUNX3 and loss of RUNX3 expression may serve as a prognostic marker in endometrial cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mmr.2018.8915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983989PMC
June 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.].
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4174/astr.2018.94.1.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765274PMC
January 2018

Capicua suppresses hepatocellular carcinoma progression by controlling the ETV4-MMP1 axis.

Hepatology 2018 06 19;67(6):2287-2301. Epub 2018 Apr 19.

Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, Republic of Korea.

Hepatocellular carcinoma (HCC) is developed by multiple steps accompanying progressive alterations of gene expression, which leads to increased cell proliferation and malignancy. Although environmental factors and intracellular signaling pathways that are critical for HCC progression have been identified, gene expression changes and the related genetic factors contributing to HCC pathogenesis are still insufficiently understood. In this study, we identify a transcriptional repressor, Capicua (CIC), as a suppressor of HCC progression and a potential therapeutic target. Expression of CIC is posttranscriptionally reduced in HCC cells. CIC levels are correlated with survival rates in patients with HCC. CIC overexpression suppresses HCC cell proliferation and invasion, whereas loss of CIC exerts opposite effects in vivo as well as in vitro. Levels of polyoma enhancer activator 3 (PEA3) group genes, the best-known CIC target genes, are correlated with lethality in patients with HCC. Among the PEA3 group genes, ETS translocation variant 4 (ETV4) is the most significantly up-regulated in CIC-deficient HCC cells, consequently promoting HCC progression. Furthermore, it induces expression of matrix metalloproteinase 1 (MMP1), the MMP gene highly relevant to HCC progression, in HCC cells; and knockdown of MMP1 completely blocks the CIC deficiency-induced HCC cell proliferation and invasion.

Conclusion: Our study demonstrates that the CIC-ETV4-MMP1 axis is a regulatory module controlling HCC progression. (Hepatology 2018;67:2287-2301).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep.29738DOI Listing
June 2018

Feasibility of quantifying methylation in stool DNA for early detection of colorectal cancer.

Clin Epigenetics 2017 4;9:126. Epub 2017 Dec 4.

Genomictree, Inc, 44-6 Techno 10-ro Yuseong-gu, Daejeon, 34027 South Korea.

Background: Colorectal cancer (CRC) screening is the most efficient strategy to reduce disease-related mortality. Frequent aberrant DNA methylation is known to occur in selected genes and early during CRC development, which has emerged as a new epigenetic biomarker for early detection of CRC. Previously, we reported that we identified that CpG sites of were aberrantly methylated in tumor tissues of most CRC patients through comprehensive methylation analysis and demonstrated a high potential of quantification of methylation in blood for early detection of colorectal cancer. In this study, we aim to investigate the feasibility of quantifying methylation in stool DNA for the early detection of CRC. The objective of this study was to confirm a high frequency of methylation in tumor tissues at various stages of CRC and investigate the feasibility of a quantitative test for methylation in fecal DNA by highly sensitive and accurate real-time PCR for early detection of CRC.

Methods: Bisulfite-pyrosequencing assay was performed to measure the methylation status in tissue samples. For methylation analysis in stool DNA, a highly sensitive and accurate method was applied which implements consecutive two rounds of PCR consisting of unidirectional linear target enrichment (LTE) of and quantitative methylation-specific real time PCR (qMSP) for , named as me LTE-qMSP assay. Its limit of detection was 0.1% methylation (corresponding to ~ 6 copies in total ~ 6200 genome copies).

Results: Positive methylation was observed in 100% of primary tumors, 90.6% of adenomatous polyps, 94.1% of hyperplastic polyps, and 0% of normal tissues. methylation level also significantly ( < 0.01) increased according to the severity of lesions. In stool DNA test for methylation by LTE-qMSP comparing CRC patients with various stages (I to IV) ( = 50) and precancerous lesions ( = 21) with healthy subjects ( = 22), the overall sensitivity was 90.0% for detecting CRC and 33.3% for detecting small polyps, with a specificity of 90.9%.

Conclusions: Taken together, our result indicates that stool DNA-based methylation test by LTE-qMSP is a potential noninvasive diagnostic tool for early detection of CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13148-017-0426-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5715626PMC
September 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmech.2017.08.063DOI Listing
December 2017

Prognostic Significance of EDIL3 Expression and Correlation with Mesenchymal Phenotype and Microvessel Density in Lung Adenocarcinoma.

Sci Rep 2017 08 17;7(1):8649. Epub 2017 Aug 17.

Department of Pathology, Ajou University School of Medicine, Suwon, Republic of Korea.

We examined the prognostic significance of Epidermal Growth Factor-like repeats and Discoidin I-Like Domains 3 (EDIL3) expression and its correlations with mesenchymal phenotype and microvessel density in non-small cell lung carcinoma (NSCLC). A total of 268 NSCLC specimens were evaluated retrospectively by immunohistochemical staining for EDIL3, EMT markers (e-cadherin, β-catenin, and vimentin), and CD31 to measure microvessel density. EDIL3, e-cadherin, β-catenin, and vimentin were expressed in 16%, 22.8%, 3.7%, and 10.1% of the specimens, respectively. The mRNA level of EDIL3 in tumor was correlated with the level of EDIL3 protein expression using immunohistochemistry. In lung adenocarcinoma patients, EDIL3 expression was significantly correlated with low e-cadherin expression, high vimentin expression, and increased microvessel density (P < 0.001, P = 0.001, and P = 0.023, respectively). In lung squamous cell carcinoma patients, EDIL3 expression was significantly correlated with low e-cadherin expression and high vimentin expression (P = 0.021 and P = 0.002, respectively). In lung adenocarcinoma patients, EDIL3 was an independent prognostic factor for overall survival in a multivariate analysis (hazard ratio: 2.552, P = 0.004). EDIL3 is significantly correlated with mesenchymal phenotype, angiogenesis, and tumor progression in lung adenocarcinoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-017-08851-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5561239PMC
August 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ol.2017.6203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5494651PMC
July 2017

Intracellular and transdermal protein delivery mediated by non-covalent interactions with a synthetic guanidine-rich molecular carrier.

Int J Pharm 2017 Aug 17;528(1-2):646-654. Epub 2017 Jun 17.

Department of Chemistry, Pohang University of Science and Technology, 77 Cheongamro, Pohang, 37673, Republic of Korea. Electronic address:

The impermeability of the cell plasma membrane is one of the major barriers for protein transduction into mammalian cells, and it also limits the use of proteins as therapeutic agents. Protein transduction has usually been achieved based on certain invasive processes or cell penetrating peptides (CPP). Herein we report our study in which a synthetic guanidine-rich molecular carrier is used as a delivery vector for intracellular and transdermal delivery of proteins. First a sorbitol-based molecular carrier having 8 guanidine units (Sor-G8) was synthesized, and then was simply mixed with a cargo protein of varying sizes to form the non-covalent complex of carrier-cargo proteins. These ionic complexes were shown to have efficient cellular uptake properties. The optimum conditions including the molar ratio between cargo protein and carrier, and the treatment time have been defined. Several protein cargoes were successfully examined with differing sizes and molecular weights: green fluorescent protein (MW 27kDa), albumin (66kDa), concanavalin A (102kDa), and immunoglobulin G (150kDa). These non-covalent complexes were also found to have excellent transdermal penetration ability into the mouse skin. The skin penetration depth was studied histologically by light microscopy as well as two-photon microscopy thus generating a depth profile. These complexes were largely found in the epidermis and dermis layers, i.e. down to ca. 100μm depth of the mouse skin. Our synthetic Sor-G8 carrier was found to be substantially more efficient that Arg8 in both the intracellular transduction and the transdermal delivery of proteins. The mechanism of the cellular uptake of the complex was briefly studied, and the results suggested macropinocytosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpharm.2017.06.030DOI Listing
August 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00432-017-2393-7DOI Listing
August 2017

STAT5A-mediated NOX5-L expression promotes the proliferation and metastasis of breast cancer cells.

Exp Cell Res 2017 02 26;351(1):51-58. Epub 2016 Dec 26.

Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea; Department of Functional Genomics, Korea University of Science and Technology (UST), Daejeon 305-333, Republic of Korea. Electronic address:

NADPH oxidase (NOX) generates reactive oxygen species (ROS) and has been suggested to mediate cell proliferation in some cancers. Here, we show that an increase in the expression of NOX5 long form (NOX5-L) is critical for tumor progression in breast tumor tissues. Immunostaining of clinical samples indicated that NOX5 was overexpressed in 41.1% of breast ductal carcinoma samples. NOX5-L depletion consistently suppressed cell proliferation, invasion, and migration in vitro. Antibody-mediated neutralization of NOX5-L attenuated tumor progression in a mouse xenograft model. Promoter analysis revealed that NOX5-L expression is regulated by STAT5A in breast cancer cells. Based on our novel findings, we suggest that inhibition of NOX5-L may be a promising therapeutic strategy that exerts anti-cancer effects via the modulation of ROS-mediated cell signaling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yexcr.2016.12.020DOI Listing
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.13325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349895PMC
December 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4143/crt.2016.066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266389PMC
January 2017

Q787Q EGFR Polymorphism as a Prognostic Factor for Lung Squamous Cell Carcinoma.

Oncology 2016 22;90(5):289-98. Epub 2016 Mar 22.

Department of Pathology, Ajou University School of Medicine, Suwon, Korea.

Objective: EGFR genetic polymorphisms have been investigated for carcinogenesis in various tumors including lung cancer. We evaluated EGFR mutations in four exons, with an emphasis on the Q787Q EGFR polymorphism in non-small-cell lung cancer.

Methods: To determine the presence of the Q787Q polymorphism in patients with lung cancer, we performed direct sequencing analyses of four exons for 83 squamous cell carcinomas and 80 adenocarcinomas untreated with EGFR tyrosine kinase inhibitors.

Results: The Q787Q EGFR polymorphism was more frequently detected in squamous cell carcinoma patients than in adenocarcinoma patients (24 vs. 15.9%). The group of patients with the Q787Q EGFR polymorphism included more males and heavy smokers compared with other patient groups. The presence of the Q787Q EGFR polymorphism significantly and negatively affected the overall survival rate among patients with non-small-cell carcinoma (p = 0.011), particularly those with squamous cell carcinoma (p = 0.037). Among stage I and II squamous cell carcinoma patients, those with the Q787Q EGFR polymorphism had a poor prognosis (p = 0.032).

Conclusions: The Q787Q EGFR polymorphism allows stratifying lung squamous cell carcinoma patients and could be an independent prognostic marker, particularly among those in stages I and II.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000444495DOI Listing
December 2016

GPR171 expression enhances proliferation and metastasis of lung cancer cells.

Oncotarget 2016 Feb;7(7):7856-65

Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.

G protein-coupled receptors (GPCRs) are among the most significant therapeutic targets and some of them promote the growth and metastasis of cancer. Here, we show that an increase in the levels of GPR171 is crucial for lung cancer tumor progression in vitro and in vivo. Immunostaining of clinical samples indicated that GPR171 was overexpressed in 46.8% of lung carcinoma tissues. Depletion of GPR171 with an anti-GPR171 antibody decreased proliferation of lung carcinoma cells and attenuated tumor progression in a mouse xenograft model. Knockdown of GPR171 also inhibited migration and invasion of the lung cancer cell lines. Notably, inhibition of GPR171 synergistically enhanced the tumoricidal activity of an epidermal growth factor receptor (EGFR) inhibitor in lung cancer cells. These results indicate that GPR171 blockade is a promising antineoplastic strategy and provide a preclinical rationale for combined inhibition of GPR171 and EGFR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.6856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4884959PMC
February 2016

RhoA is associated with invasion and poor prognosis in colorectal cancer.

Int J Oncol 2016 Feb 8;48(2):714-22. Epub 2015 Dec 8.

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

Colorectal cancer is one of the most common cancers and is the fourth leading cause of cancer death in Korea. Mortality of colorectal cancer is strongly associated with the metastatic spread of the disease. As such, it is important to find and characterize signaling pathways involved in colon cancer metastasis. We investigated the functional importance of RhoA using human cell lines as well as 150 colorectal cancer patient-derived samples as it remains unclear whether RhoA functions as either an oncogene or a tumor suppressor in colon cancer. RhoA was highly expressed in metastatic cancer cell lines. Although cancer cell proliferation was only moderately impaired after depletion of RhoA, RhoA-depleted cancer cells exhibited markedly reduced migration and invasion ability in vitro. Furthermore, we found that RhoA is associated with the invasion of lymph nodes and blood vessels in the patient colorectal cancer samples. Most notably, patients with higher RhoA expression had a significantly poorer 5-year survival rate after surgery. These results suggest that RhoA is a marker of poor prognosis in colorectal cancer and may be a promising target for cancer treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ijo.2015.3281DOI Listing
February 2016

Pivotal role of vascular endothelial growth factor pathway in tumor angiogenesis.

Ann Surg Treat Res 2015 Jul 11;89(1):1-8. Epub 2015 Jun 11.

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

The shaping of new blood vessels is a significant event in cancer growth and metastasis. Therefore, the molecular system of cancer angiogenesis has garnered considerable interest in cancer research. The vascular endothelial growth factor (VEGF) and VEGF receptor pathway are recognized as the key regulators of the angiogenic process. Activation of the VEGF/VEGF-receptor pathway initiates signaling cascades that promote endothelial cell growth, migration, and differentiation. Recently, VEGF was shown to play a role in the recruitment of bone marrow-derived endothelial progenitor cells to neovascularization sites. The role of VEGF in promoting tumor angiogenesis and the occurrence of human cancers has led to the rational design and development of agents that selectively target this pathway. Moreover, these anti-VEGF/VEGF receptor agents show therapeutic potential by inhibition of angiogenesis and tumor growth in preclinical models. In this review, we summarize the role of the VEGF pathway during tumor angiogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4174/astr.2015.89.1.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481026PMC
July 2015

Astrocyte elevated gene-1 overexpression in hepatocellular carcinoma: an independent prognostic factor.

Ann Surg Treat Res 2015 Feb 27;88(2):77-85. Epub 2015 Jan 27.

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

Purpose: Astrocyte elevated gene-1 (AEG-1) plays important roles in tumorigenesis such as proliferation, invasion, metastasis, angiogenesis, and chemoresistance. We examined the expression of AEG-1 in patients with hepatocellular carcinoma (HCC).

Methods: Eighty-five samples were collected from patients with HCC who underwent surgery and were histopathologically confirmed to have HCC. Two independent pathologists, experienced in evaluating immunohistochemistry and blinded to the clinical outcomes of the patients, reviewed all samples. They determined AEG-1 expression semiquantitatively by assessing the percentage of positively stained immunoreactive cells and staining intensity. Clinicopathological data were analyzed in association with prognosis.

Results: The association was estimated by univariate and multivariate analyses with Cox regression. Tumor size (hazard ratio [HR], 2.285; 95% confidence interval [CI], 1.175-4.447; P = 0.015), microvascular invasion (HR, 6.754; 95% CI, 1.631-27.965; P = 0.008), and AEG-1 expression (HR, 4.756; 95% CI, 1.697-13.329; P = 0.003) were independent prognostic factors for overall survival. Those for disease-free survival rate were tumor size (HR, 2.245; 95% CI, 1.282-3.933; P = 0.005) and AEG-1 expression (HR, 1.916; 95% CI, 1.035-3.545; P = 0.038). The cumulative 5-year survival and recurrence rates were 89.2% and 50.0% in the low-expressing group and 24.5% and 82.4% in the high-expressing group, respectively.

Conclusion: The results suggest that AEG-1 overexpression could serve as a valuable prognostic marker in patients with HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4174/astr.2015.88.2.77DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4325651PMC
February 2015
-->