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Combined Transarterial Chemoembolization and External Beam Radiotherapy for Identifying Surgical Candidates for Hepatocellular Carcinoma with Macroscopic Vascular Invasion: A Propensity Score-Weighted Analysis
Sumin Lee, Jinhong Jung, Jonggi Choi, So Yeon Kim, Jin Hyoung Kim, Danbi Lee, Ju Hyun Shim, Kang Mo Kim, Young-Suk Lim, Han Chu Lee, Gi-Won Song, Jin-hong Park, Sang Min Yoon
Received January 18, 2025  Accepted May 20, 2025  Published online May 22, 2025  
DOI: https://doi.org/10.4143/crt.2025.076    [Accepted]
AbstractAbstract PDF
Purpose
To evaluate the role of hepatic resection in patients with objective responses after combined transarterial chemoembolization (TACE) and radiotherapy (RT) for hepatocellular carcinoma (HCC) with macroscopic vascular invasion (MVI).
Materials and Methods
We retrospectively reviewed the patients treated with combined TACE and RT for HCC with MVI between 2010 and 2015. Some of the patients with objective responses underwent hepatic resection or liver transplantation; to investigate the impact of surgery, patients with objective responses who did not undergo surgery were selected as the control group. Survival outcomes were compared using a propensity score-based stabilized inverse probability of treatment weighting method.
Results
Out of the 170 patients with objective responses after combined TACE and RT, 41 patients underwent surgery, including 8 liver transplantations. The unweighted surgery group was younger and had a higher proportion of solitary tumors and unilateral vascular involvement. After adjustment, the 3-year overall survival (OS) rates were 61.0% and 28.6% in the surgery and non-surgery groups, respectively. The most important prognostic factor for OS was surgery (adjusted Cox hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.17–0.46; p<0.001). Complete response after TACE and RT (vs. partial response) was also a significant prognostic factor for OS (adjusted HR, 0.41; 95% CI, 0.27–0.61; p<0.001). There was no surgical mortality. Four patients (9.8%) required additional surgery due to bleeding or graft failure.
Conclusion
Hepatic resection was significantly associated with improved OS in patients who showed objective responses after receiving combined TACE and RT for HCC with MVI.
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Genitourinary cancer
Bilateral Seminal Vesicle Invasion as a Strong Prognostic Indicator in T3b Prostate Cancer Patients Following Radical Prostatectomy: A Comprehensive, Multicenter, Long-term Follow-up Study
Jungyo Suh, In Gab Jeong, Hwang Gyun Jeon, Chang Wook Jeong, Sangchul Lee, Seong Soo Jeon, Seok-Soo Byun, Cheol Kwak, Hanjong Ahn
Cancer Res Treat. 2024;56(3):885-892.   Published online January 5, 2024
DOI: https://doi.org/10.4143/crt.2023.1264
AbstractAbstract PDFPubReaderePub
Purpose
Pathologic T3b (pT3b) prostate cancer, characterized by seminal vesicle invasion (SVI), exhibits variable oncological outcomes post–radical prostatectomy (RP). Identifying prognostic factors is crucial for patient-specific management. This study investigates the impact of bilateral SVI on prognosis in pT3b prostate cancer.
Materials and Methods
We evaluated the medical records of a multi-institutional cohort of men who underwent RP for prostate cancer with SVI between 2000 and 2012. Univariate and multivariable analyses were performed using Kaplan-Meier analysis and covariate-adjusted Cox proportional hazard regression for biochemical recurrence (BCR), clinical progression (CP), and cancer-specific survival (CSS).
Results
Among 770 men who underwent RP without neo-adjuvant treatment, median follow-up was 85.7 months. Patients with bilateral SVI had higher preoperative prostate-specific antigen levels and clinical T category (all p < 0.001). Extracapsular extension, tumor volume, lymph node metastasis (p < 0.001), pathologic Gleason grade group (p < 0.001), and resection margin positivity (p < 0.001) were also higher in patients with bilateral SVI. The 5-, 10-, and 15-year BCR-free survival rates were 23.9%, 11.7%, and 8.5%; CP-free survival rates were 82.8%, 62.5%, and 33.4%; and CSS rates were 96.4%, 88.1%, and 69.5%, respectively. The bilateral SVI group demonstrated significantly lower BCR-free survival rates, CP-free survival rates, and CSS rates (all p < 0.001). Bilateral SVI was independently associated with BCR (hazard ratio, 1.197; 95% confidence interval, p=0.049), CP (p=0.022), and CSS (p=0.038) in covariate-adjusted Cox regression.
Conclusion
Bilateral SVI is a robust, independent prognostic factor for poor oncological outcomes in pT3b prostate cancer.

Citations

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  • Prognostic Impact of Seminal Vesicle Mucosal Invasion in pT3b Prostate Cancer Following Radical Prostatectomy
    Hyun Jung Lee, Won Hoon Song, Seung Soo Lee, Jong Kil Nam, Sung-Woo Park
    Journal of Urologic Oncology.2025; 23(1): 30.     CrossRef
  • Defining the Role of Postoperative Radio-Hormone Therapy in Prostate Cancer
    Harshitha Dudipala, Mai Dabbas, Kshitij Pandit, Sarika D. Gurnani, Rana R. McKay
    Current Oncology Reports.2025;[Epub]     CrossRef
  • Clinical implication of peri-seminal vesicle soft tissue invasion in patients with pT3b prostate cancer
    Sungun Bang, Su-Jin Shin, Do Kyung Kim, Jong Kyou Kwon, Jinhyung Jeon, Kang Su Cho
    Prostate International.2025;[Epub]     CrossRef
  • Role of [18F]-PSMA-1007 PET radiomics for seminal vesicle invasion prediction in primary prostate cancer
    Liang Luo, Xinyi Wang, Hongjun Xie, Hua Liang, Jungang Gao, Yang Li, Yuwei Xia, Mengmeng Zhao, Feng Shi, Cong Shen, Xiaoyi Duan
    Computers in Biology and Medicine.2024; 183: 109249.     CrossRef
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  • 4 Crossref
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Gastrointestinal cancer
Vps34 Inhibits Hepatocellular Carcinoma Invasion by Regulating Endosome-Lysosome Trafficking via Rab7-RILP and Rab11
Chenyang Qi, Liping Zou, Suxia Wang, Xing Mao, Yuan Hu, Jiaoyu Shi, Zhigang Zhang, Huijuan Wu
Cancer Res Treat. 2022;54(1):182-198.   Published online March 26, 2021
DOI: https://doi.org/10.4143/crt.2020.578
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The role of vacuolar protein sorting 34 (Vps34), an indispensable protein required for cell vesicular trafficking, in the biological behavior of hepatocellular carcinoma (HCC) has yet to be studied.
Materials and Methods
In the present study, the expression of Vps34 in HCC and the effect of Vps34 on HCC cell invasion was detected both in vivo and in vitro. Furthermore, by modulating the RILP and Rab11, which regulate juxtanuclear lysosome aggregation and recycling endosome respectively, the underlying mechanism was investigated.
Results
Vps34 was significantly decreased in HCC and negatively correlated with the HCC invasiveness both in vivo and in vitro. Moreover, Vps34 could promote lysosomal juxtanuclear accumulation, reduce the invasive ability of HCC cells via the Rab7-RILP pathway. In addition, the deficiency of Vps34 in HCC cells affected the endosome-lysosome system, resulting in enhanced Rab11 mediated endocytic recycling of cell surface receptor and increased invasion of HCC cells.
Conclusion
Our study reveals that Vps34 acts as an invasion suppressor in HCC cells, and more importantly, the endosome-lysosome trafficking regulated by Vps34 has the potential to become a target pathway in HCC treatment.

Citations

Citations to this article as recorded by  
  • Mechanism of mTOR/RILP-regulated autophagic flux in increased susceptibility to myocardial ischemia-reperfusion in diabetic mice
    Jiyao Zhao, Wei Shi, Yan Zheng, Junjie Wang, Muzhao Yuan, Yultuz Anwar, Yuxuan He, Haiping Ma, Jianjiang Wu
    Frontiers in Pharmacology.2025;[Epub]     CrossRef
  • GLDC interacts with VPS34 to inhibit tumorigenesis and epithelial-mesenchymal transition in hepatocellular carcinoma
    Zan Song, Hao Dong, Kailing Zhang, Bingke Qiao, Leilei Li, Zhicheng Zhang, Zhili Fan, Jing Li, Yu Li, Mengfei Liu, Ying Liu, Xinyu Gu, Tao Zhang
    Pharmaceutical Science Advances.2025; 3: 100072.     CrossRef
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    Mona Tahoun, Ahmed S. Sadaka
    Human Immunology.2024; 85(3): 110801.     CrossRef
  • Prognostic Lysosome-Related Biomarkers for Predicting Drug Candidates in Hepatocellular Carcinoma: An Insilco Analysis
    Junxiu Xu, Kai Zhang, Genhao Zhang
    Journal of Hepatocellular Carcinoma.2023; Volume 10: 459.     CrossRef
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    Yuan Liu, Qilin Yang, Siwei Chen, Zixiang Li, Leilei Fu
    European Journal of Medicinal Chemistry.2023; 256: 115467.     CrossRef
  • RILP inhibits tumor progression in osteosarcoma via Grb10-mediated inhibition of the PI3K/AKT/mTOR pathway
    Zhun Wei, Kezhou Xia, Di Zheng, Changtian Gong, Weichun Guo
    Molecular Medicine.2023;[Epub]     CrossRef
  • The Role of Phosphatidylinositol 3-Kinase Catalytic Subunit Type 3 in the Pathogenesis of Human Cancer
    Chien-An Chu, Yi-Wen Wang, Yi-Lin Chen, Hui-Wen Chen, Jing-Jing Chuang, Hong-Yi Chang, Chung-Liang Ho, Chen Chang, Nan-Haw Chow, Chung-Ta Lee
    International Journal of Molecular Sciences.2021; 22(20): 10964.     CrossRef
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Evaluation of the American Joint Committee on Cancer (AJCC) 8th Edition Staging System for Hepatocellular Carcinoma in 1,008 Patients with Curative Resection
Sujin Park, Sangjoon Choi, Yoon Ah Cho, Dong Hyun Sinn, Jong Man Kim, Cheol-Keun Park, Sang Yun Ha
Cancer Res Treat. 2020;52(4):1145-1152.   Published online April 28, 2020
DOI: https://doi.org/10.4143/crt.2020.208
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Recently, the 8th edition staging system of the American Joint Committee on Cancer (AJCC) for hepatocellular carcinoma (HCC) was released, including a change in T category. We aimed to validate the new AJCC system.
Materials and Methods
The predictive value of the new AJCC was validated in comparison to the previous edition, in a total 1,008 patients who underwent curative resection for HCC as initial treatment.
Results
The 2-year area under the curve values for recurrence-free survival (RFS) and overall survival (OS) were comparable in the 7th and 8th editions. Stage migration was observed in 63 patients (6.3%); from T2 to T1a for 44 patients and from T3 to T4 for 19 patients. The RFS and OS were not different between T1a and T1b in the 8th edition. For solitary tumors ≤ 2 cm, those with microvascular invasion had lower RFS and OS values than those without although they were all classified as T1a in the 8th edition. Tumors involving a major branch of the portal or hepatic vein (T4 by the 8th edition and T3b by the 7th edition) had shorter RFS and OS than multifocal tumors, at least one of which was > 5 cm (T3 by the 8th edition and T3a by the 7th edition).
Conclusion
The AJCC 8th edition staging system for HCC showed comparable predictive performance to the 7th edition. It is desirable in a future revision to consider sub-stratification of solitary tumors ≤ 2 cm (T1a) depending on the presence of vascular invasion, which is not included in the 8th edition.

Citations

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    Journal of Liver Cancer.2023; 23(1): 1.     CrossRef
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    Yueh-Wei Liu, Wei-Feng Li, Fang-Ying Kuo, Hock-Liew Eng, Chih-Chi Wang, Chih-Che Lin, Chee-Chien Yong, Yi-Hao Yen
    Langenbeck's Archives of Surgery.2023;[Epub]     CrossRef
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    Li Zhang, Guodong Pang, Jing Zhang, Zhenguo Yuan
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    Diwakar Suresh, Akshatha N. Srinivas, Akila Prashant, Suchitha Satish, Prashant Vishwanath, Suma M. Nataraj, Srinivas V. Koduru, Prasanna K. Santhekadur, Divya P. Kumar
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    Yiyin Zhang, Jiaxi Cheng, Cheng Zhong, Qiming Xia, Yirun Li, Peng Chen, Xiaoxiao Fan, Qijiang Mao, Hui Lin, Defei Hong
    Frontiers in Oncology.2022;[Epub]     CrossRef
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    Wang Zhang, Yipeng Wan, Yue Zhang, Qi Liu, Xuan Zhu
    Cancer Management and Research.2022; Volume 14: 2691.     CrossRef
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    Clinical and Molecular Hepatology.2022; 28(4): 583.     CrossRef
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    Er-lei Zhang, Qi Cheng, Zhi-yong Huang, Wei Dong
    Frontiers in Oncology.2021;[Epub]     CrossRef
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    Frontiers in Genetics.2021;[Epub]     CrossRef
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    Ji Hae Nahm, Young Nyun Park
    The Korean Journal of Gastroenterology.2021; 78(5): 268.     CrossRef
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  • 30 Web of Science
  • 17 Crossref
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ZNF488 Enhances the Invasion and Tumorigenesis in Nasopharyngeal Carcinoma Via the Wnt Signaling Pathway Involving Epithelial Mesenchymal Transition
Dan Zong, Li Yin, Qian Zhong, Wen-jie Guo, Jian-hua Xu, Ning Jiang, Zhi-rui Lin, Man-zhi Li, Ping Han, Lin Xu, Xia He, Mu-sheng Zeng
Cancer Res Treat. 2016;48(1):334-344.   Published online March 12, 2015
DOI: https://doi.org/10.4143/crt.2014.311
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to investigate the function of Zinc finger protein 488 (ZNF488) in nasopharyngeal carcinoma (NPC). Materials and Methods The endogenous expression of ZNF488 in NPC tissues, normal nasopharyngeal epithelium tissues and NPC cell lines were detected by quantitative reverse transcription polymerase chain reaction. ZNF488 over-expressing and knock-down NPC cell line models were established through retroviral vector pMSCV mediated over-expression and small interfering RNA (siRNA) mediated knock-down. The invasion and migration capacities were evaluated by wound healing and transwell invasion assays in ZNF488 over-expressing and control cell lines. Soft-agar colony formation and a xenograft experiment were performed to study tumorigenic ability in vitro and in vivo. Immunofluorescence and western blotting analysis were used to examine protein changes followed by ZNF488 over-expression. Microarray analysis was performed to explore gene expression profilings, while luciferase reporter assay to evaluate the transcriptive activity of Tcf/Lef.
Results
ZNF488 was over-expressed in NPC tissues compared with normal tissues, especially higher in 5-8F and S18, which are well-established high metastatic NPC clones. Functional studies indicate that over-expression of ZNF488 provokes invasion, whereas knock-down of ZNF488 alleviates invasive capability. Moreover, over-expression of ZNF488 promotes NPC tumor growth both in vitro and in vivo. Our data further show that over-expression of ZNF488 induces epithelial mesenchymal transition (EMT) by activating the WNT/β-catenin signaling pathway. Conclusion Our data strongly suggest that ZNF488 acts as an oncogene, promoting invasion and tumorigenesis by activating the Wnt/β-catenin pathway to induce EMT in NPC.

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    Jae-Ghi Lee, Ilkyu Park, Hannah Lee, Seungyoon Nam, Jisup Kim, Won-Suk Lee, Myunghee Kang, Jung Ho Kim
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    Nathaniel B. Goldstein, Andrea Steel, Landon Tomb, Zachary Berk, Junxiao Hu, Velmurugan Balaya, Laura Hoaglin, Kavya Ganuthula, Meet Patel, Erica Mbika, William A. Robinson, Dennis R. Roop, David A. Norris, Stanca A. Birlea
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    Cell Division.2024;[Epub]     CrossRef
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    Caiyan Yin, Jianwei Yu, Gaohua Liu, Jun He, Peng Wu
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The Bone Morphogenesis Protein-2 (BMP-2) is Associated with Progression to Metastatic Disease in Gastric Cancer
Yong Park, Jee Won Kim, Dae Sik Kim, Eui Bae Kim, Se Jong Park, Jin Yong Park, Woo Suk Choi, Jong Gyu Song, Hee Yun Seo, Sang Cheul Oh, Byung Soo Kim, Jong Jae Park, Yeul Hong Kim, Jun Suk Kim
Cancer Res Treat. 2008;40(3):127-132.   Published online September 30, 2008
DOI: https://doi.org/10.4143/crt.2008.40.3.127
AbstractAbstract PDFPubReaderePub
Purpose

Bone Morphogenetic Proteins (BMPs) are members of the TGF-β superfamily and it has been demonstrated that BMPs enhance migration, invasion and metastasis. The purpose of this study was to identify the association between the serum BMP-2 level and the progression status of gastric cancer.

Materials and Methods

Fifty-five patients with metastatic gastric cancer (metastatic disease group), six patients with early gastric cancer without lymph node metastasis (the EGC group), and ten healthy control subjects were enrolled in this study. The serum BMP-2 level was quantified by use of a commercially available ELISA kit. In EGC group patients and patients with metastatic disease, whole blood was obtained before endoscopic mucosal resection and before the commencement of a scheduled cycle of systemic chemotherapy, respectively.

Results

No significant difference in the mean serum BMP-2 levels was observed between the control subjects and the EGC group patients (87.95 pg/ml for the control subjects and 84.50 pg/ml for the EGC group, p=1.0). However, the metastatic disease group patients had a significantly higher level of serum BMP (179.61 pg/ml) than the control subjects and EGC group patients (87.95 pg/ml for the control subjects and 84.50 pg/ml for the EGC group, p<0.0001). Moreover, the mean serum BMP-2 level from patients with a bone metastasis was significantly higher than the mean serum BMP-2 level from patients without a bone metastasis (204.73 pg/ml versus 173.33 pg/ml, p=0.021).

Conclusions

BMP-2 seems to have a role in progression to metastatic disease in gastric cancer, especially in the late stage of tumorigenesis, including invasion and metastasis. BMP-2 may facilitate bone metastasis in gastric cancer. To confirm these findings, further studies are required with tissue specimens and the use of a cancer cell line.

Citations

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  • Novel Biomarkers in Evaluating Cardiac Function in Patients on Hemodialysis—A Pilot Prospective Observational Cohort Study
    Lazar Chisavu, Viviana Mihaela Ivan, Adelina Mihaescu, Flavia Chisavu, Oana Schiller, Luciana Marc, Flaviu Bob, Adalbert Schiller
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    Tanu Sharma, Anmol Kapoor, Chandi C. Mandal
    Journal of Cellular Physiology.2022; 237(8): 3127.     CrossRef
  • BMP2 inhibits cell proliferation by downregulating EZH2 in gastric cancer
    Zilu Chen, Liyue Yuan, Xiaopeng Li, Junhui Yu, Zhengshui Xu
    Cell Cycle.2022; 21(21): 2298.     CrossRef
  • Emerging Roles for Browning of White Adipose Tissue in Prostate Cancer Malignant Behaviour
    Alejandro Álvarez-Artime, Belén García-Soler, Rosa María Sainz, Juan Carlos Mayo
    International Journal of Molecular Sciences.2021; 22(11): 5560.     CrossRef
  • Magnesium ions regulate mesenchymal stem cells population and osteogenic differentiation: A fuzzy agent-based modeling approach
    Jalil Nourisa, Berit Zeller-Plumhoff, Heike Helmholz, Bérengère Luthringer-Feyerabend, Vladimir Ivannikov, Regine Willumeit-Römer
    Computational and Structural Biotechnology Journal.2021; 19: 4110.     CrossRef
  • BMP Signaling in Development, Stem Cells, and Diseases of the Gastrointestinal Tract
    Yongchun Zhang, Jianwen Que
    Annual Review of Physiology.2020; 82(1): 251.     CrossRef
  • Relaxin enhances bone regeneration with BMP‐2‐loaded hydroxyapatite microspheres
    Sahitya Injamuri, Mohamed N. Rahaman, Youqu Shen, Yue‐Wern Huang
    Journal of Biomedical Materials Research Part A.2020; 108(5): 1231.     CrossRef
  • Annatto-Derived Tocotrienol Promotes Mineralization of MC3T3-E1 Cells by Enhancing BMP-2 Protein Expression via Inhibiting RhoA Activation and HMG-CoA Reductase Gene Expression


    Wan Nuraini Wan Hasan, Kok-Yong Chin, Norzana Abd Ghafar, Ima Nirwana Soelaiman
    Drug Design, Development and Therapy.2020; Volume 14: 969.     CrossRef
  • Detection of circulating BMP5 as a risk factor for Barrett’s esophagus
    Ana C. P. Correia, Silvia Calpe, Nahid Mostafavi, Sanne Johanna Maria Hoefnagel, Maria del Carmen Sancho-Serra, Patricia S. de Koning, Kausilia K. Krishnadath
    Scientific Reports.2020;[Epub]     CrossRef
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    Duc-Hiep Bach, Hyen Joo Park, Sang Kook Lee
    Molecular Therapy - Oncolytics.2018; 8: 1.     CrossRef
  • Embryonic bone morphogenetic protein and nodal induce invasion in melanocytes and melanoma cells
    Tobias Sinnberg, Heike Niessner, Mitch P. Levesque, Christoph Dettweiler, Claus Garbe, Christian Busch
    Biology Open.2018;[Epub]     CrossRef
  • Decreased expression of bone morphogenetic protein-2 is correlated with biochemical recurrence in prostate cancer: Immunohistochemical analysis
    Bum Sik Tae, Seok Cho, Hyun Cheol Kim, Cheol Hwan Kim, Seok Ho Kang, Jeong Gu Lee, Je Jong Kim, Hong Seok Park, Jun Cheon, Mi Mi Oh, Sung Gu Kang
    Scientific Reports.2018;[Epub]     CrossRef
  • Computational model of mesenchymal migration in 3D under chemotaxis
    F. O. Ribeiro, M. J. Gómez-Benito, J. Folgado, P. R. Fernandes, J. M. García-Aznar
    Computer Methods in Biomechanics and Biomedical Engineering.2017; 20(1): 59.     CrossRef
  • Bone morphogenetic protein-2 and tumor growth: Diverse effects and possibilities for therapy
    Haijun Tian, Jie Zhao, Elsa J. Brochmann, Jeffrey C. Wang, Samuel S. Murray
    Cytokine & Growth Factor Reviews.2017; 34: 73.     CrossRef
  • BMP signaling pathways affect differently migration and invasion of esophageal squamous cancer cells
    Min Hu, Facai Cui, Fengzhen Liu, Jinlin Wang, Xiaoxia Wei, Yi Li
    International Journal of Oncology.2017; 50(1): 193.     CrossRef
  • Overexpression of colorectal cancer oncogene CHRDL2 predicts a poor prognosis
    Jian Sun, Xuan Liu, Hong Gao, Long Zhang, Qing Ji, Ziyuan Wang, Lihong Zhou, Yan Wang, Hua Sui, Zhongze Fan, Qi Li
    Oncotarget.2017; 8(7): 11489.     CrossRef
  • BMP10 inhibited the growth and migration of gastric cancer cells
    Haiming Lei, Jian Wang, Peihua Lu, Xinghua Si, Koulan Han, Tingyan Ruan, Junjie Lu
    Tumor Biology.2016; 37(3): 3025.     CrossRef
  • How does the pathophysiological context influence delivery of bone growth factors?
    Xiaohua Yu, Darilis Suárez-González, Andrew S. Khalil, William L. Murphy
    Advanced Drug Delivery Reviews.2015; 84: 68.     CrossRef
  • Inactivation of the Phosphatidylinositol 3‐Kinase/Akt Pathway is Involved in BMP9‐mediated Tumor‐suppressive Effects in Gastric Cancer Cells
    Liang Duan, Liwei Ye, Rui Wu, Haiyan Wang, Xueru Li, Huan Li, Shimei Yuan, He Zha, Hui Sun, Yunyuan Zhang, Xian Chen, Yan Zhang, Lan Zhou
    Journal of Cellular Biochemistry.2015; 116(6): 1080.     CrossRef
  • Identifying an ovarian cancer cell hierarchy regulated by bone morphogenetic protein 2
    Yun-Jung Choi, Patrick N. Ingram, Kun Yang, Lan Coffman, Mangala Iyengar, Shoumei Bai, Dafydd G. Thomas, Euisik Yoon, Ronald J. Buckanovich
    Proceedings of the National Academy of Sciences.2015;[Epub]     CrossRef
  • Association Between BMP-2 and Carcinogenicity
    Branko Skovrlj, Steven M. Koehler, Paul A. Anderson, Sheeraz A. Qureshi, Andrew C. Hecht, James C. Iatridis, Samuel K. Cho
    SPINE.2015; 40(23): 1862.     CrossRef
  • In silico Mechano-Chemical Model of Bone Healing for the Regeneration of Critical Defects: The Effect of BMP-2
    Frederico O. Ribeiro, María José Gómez-Benito, João Folgado, Paulo R. Fernandes, José Manuel García-Aznar, Masaya Yamamoto
    PLOS ONE.2015; 10(6): e0127722.     CrossRef
  • Comparative transcriptome analysis between metastatic and non-metastatic gastric cancer reveals potential biomarkers
    DAN FENG, XIAOFEI YE, ZHENXIN ZHU, ZIRAN WEI, QINGPING CAI, YAJIE WANG
    Molecular Medicine Reports.2015; 11(1): 386.     CrossRef
  • Gastric stem cells and gastric cancer stem cells
    Myoung-Eun Han, Sae-Ock Oh
    Anatomy & Cell Biology.2013; 46(1): 8.     CrossRef
  • Cancer stem cells: the ‘heartbeat’ of gastric cancer
    Guihua Xu, Jie Shen, Xiaohui Ou Yang, Masakiyo Sasahara, Xiulan Su
    Journal of Gastroenterology.2013; 48(7): 781.     CrossRef
  • Serum BMP-2 Up-regulation as an Indicator of Poor Survival in Advanced Non-small Cell Lung Cancer Patients
    Zheng-Hua Fei, Cheng-Yun Yao, Xiao-Lei Yang, Xin-En Huang, Sheng-Lin Ma
    Asian Pacific Journal of Cancer Prevention.2013; 14(9): 5293.     CrossRef
  • P‐glycoprotein (ABCB1) inhibited network of mitochondrion transport along microtubule and BMP signal‐induced cell shape in chimpanzee left cerebrum by systems‐theoretical analysis
    Hong Lin, Lin Wang, Minghu Jiang, Juxiang Huang, Lianxiu Qi
    Cell Biochemistry and Function.2012; 30(7): 582.     CrossRef
  • Bone–vasculature interactions in the mandible: Is bone an angiogenic tissue?
    E.M. Dietrich, K. Antoniades
    Medical Hypotheses.2012; 79(5): 582.     CrossRef
  • Major Determinants of BMP-2 Serum Levels in Hemodialysis Patients
    Elísio Costa, Joana Coimbra, Cristina Catarino, Sandra Ribeiro, Flávio Reis, Henrique Nascimento, João Fernandes, Vasco Miranda, Maria do Sameiro Faria, Luís Belo, Alice Santos-Silva
    Renal Failure.2012; 34(10): 1355.     CrossRef
  • Bone Morphogenetic Protein-4-induced Epithelial-Mesenchymal Transition and Invasiveness Through Smad1-mediated Signal Pathway in Squamous Cell Carcinoma of the Head and Neck
    Ting Xu, Chang-yun Yu, Jin-jie Sun, Yong Liu, Xing-wei Wang, Lei-ming Pi, Yong-quan Tian, Xin Zhang
    Archives of Medical Research.2011; 42(2): 128.     CrossRef
  • Bone Morphogenetic Protein-2 and -4 Play Tumor Suppressive Roles in Human Diffuse-Type Gastric Carcinoma
    Yo-taro Shirai, Shogo Ehata, Masakazu Yashiro, Kazuyoshi Yanagihara, Kosei Hirakawa, Kohei Miyazono
    The American Journal of Pathology.2011; 179(6): 2920.     CrossRef
  • Metastatic function of BMP-2 in gastric cancer cells: The role of PI3K/AKT, MAPK, the NF-κB pathway, and MMP-9 expression
    Myoung Hee Kang, Sang Cheul Oh, Hyun Joo Lee, Han Na Kang, Jung Lim Kim, Jun Suk Kim, Young A. Yoo
    Experimental Cell Research.2011; 317(12): 1746.     CrossRef
  • Downregulation of hemojuvelin prevents inhibitory effects of bone morphogenetic proteins on iron metabolism in hepatocellular carcinoma
    Ulrike Maegdefrau, Stephanie Arndt, Georgi Kivorski, Claus Hellerbrand, Anja-Katrin Bosserhoff
    Laboratory Investigation.2011; 91(11): 1615.     CrossRef
  • Coding polymorphisms of bone morphogenetic protein 2 contribute to the development of childhood IgA nephropathy
    JIN-SOON SUH, WON-HO HAHN, JONG SEOK LEE, HAE JEONG PARK, MI-JA KIM, SUNG WOOK KANG, JOO-HO CHUNG, BYOUNG-SOO CHO
    Experimental and Therapeutic Medicine.2011; 2(2): 337.     CrossRef
  • Bone morphogenetic protein-2 levels are elevated in the patients with gastric cancer and correlate with disease progression
    Yong Park, Myoung Hee Kang, Hee Yeon Seo, Joong Min Park, Chul Won Choi, Yeul Hong Kim, In Sun Kim, Jun Suk Kim, Sang Cheul Oh
    Medical Oncology.2010; 27(4): 1192.     CrossRef
  • The Yin and Yang of bone morphogenetic proteins in cancer
    Ashok Singh, Rebecca J. Morris
    Cytokine & Growth Factor Reviews.2010; 21(4): 299.     CrossRef
  • BMP2 accelerates the motility and invasiveness of gastric cancer cells via activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway
    Myoung Hee Kang, Jun Suk Kim, Ji Eun Seo, Sang Cheul Oh, Young A. Yoo
    Experimental Cell Research.2010; 316(1): 24.     CrossRef
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Antisense Deoxyoligonucleotides Inhibit Activities of Matrix Metalloproteinase-2 in Human Fibrosarcoma HT1080 Cells
Jung Sun Park, Dong On Yang, Seon Hee Lim, Hyeon Gyeong Yoo, Heyon Na Cho, Young Do Jung, Sae Jong Kim, Sun Sik Chung, Boo Ahn Shin
Cancer Res Treat. 2002;34(6):444-449.   Published online December 31, 2002
DOI: https://doi.org/10.4143/crt.2002.34.6.444
AbstractAbstract PDF
PURPOSE
MMP-2, 72 kDa-type IV collagenase, plays a major role in the migration and growth of tumor cells, a process that requires the disintegration of basement membrane. Activation of MMP-2 is correlated with the invasiveness of various tumors. The aim of this study was to determine the sequence-specific phosphorothioated oligodeoxynucleotides (ODNs) inhibiting the translation of MMP-2 mRNA and the subsequent invasiveness of tumor cells.
MATERIALS AND METHODS
Eight types of antisense ODNs were designed and each (8micro gram/ml) were transfected into HT1080 cells. The effects of these antisense ODNs on MMP expression were examined by gelatin zymography, Western blot, Northern blot and matrigel assay.
RESULTS
Antisense-5 (+904~923), antisense-6 (+1274~+1293) and antisense-7 (+1646~+1665) reduced the MMP-2 activity of the culture supernatant in HT1080 fibrosarcoma cells. Treatment with antisense-6 showed inhibition of MMP-2 mRNA and protein, and in vitro invasion in a dose-dependent manner.
CONCLUSION
Antisense-6 might be one of the therapeutic candidates for tumor invasion and metastasis.
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SB203580, a P38 MAPK Inhibitor, Blocks in vitro Invasion by Human Gastric SNU-638 Cells
Ju Chae Park, Hyeon Gyeung Yoo, Hong Su Kim, Min A Jung, Mi Ha Kim, Sang Won Han, Kee Oh Chay, Boo Ahn Shin, Bong Whan Ahn, Young Do Jung
Cancer Res Treat. 2002;34(6):426-431.   Published online December 31, 2002
DOI: https://doi.org/10.4143/crt.2002.34.6.426
AbstractAbstract PDF
PURPOSE
The role of P38 mitogen-activated protein kinase (MAPK) in gastric cancer invasion has not yet been determined. In this study, we examined the effects of SB203580, a specific P38 MAPK inhibitor, on the in vitro invasion of gastric cancer and upon the molecules involved in this process.
MATERIALS AND METHODS
Human gastric cancer SNU-638 cells were maintained in RPMI 1640 supplemented with 10% FBS. BIOCOAT matrigel invasion chambers were used to examine in vitro invasiveness, zymography for gelatinase activity, CAT assay for uPA promoter activity and Western and Northern blotting to determine protein and mRNA levels, respectively.
RESULTS
Treatment of SNU-638 cells with SB203580, a specific P38 MAPK inhibitor, reduced in vitro invasiveness, dose-dependently. SB203580 treatment was found to decrease both mRNA expression and uPA promoter activity in gastric SNU-638 cells. In vitro invasion of SNU-638 cells was partially abrogated by uPA-neutralizing antibodies. The activities of MMPs were not significantly altered by SB203580.
CONCLUSION
Our results suggest that P38 MAPK is a potential therapeutic target for inhibiting uPA-dependent gastric tumor invasiveness and metastasis.

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    Pathogens.2024; 13(12): 1130.     CrossRef
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Expression of Matrix Metalloproteinases and Its Inhibitor in Gastric Adenocarcinoma
Sung Chul Lim
Cancer Res Treat. 2001;33(3):199-206.   Published online June 30, 2001
DOI: https://doi.org/10.4143/crt.2001.33.3.199
AbstractAbstract PDF
PURPOSE
Matrix metalloproteinases (MMPs) have been associated with tumor cell invasion and metastasis by mediating the degradation of extracellular matrix components. A tissue inhibitor of metalloproteinases (TIMPs) has been reported to inhibit tumor invasion by means of an inactivation of matrix metalloproteinases. An imbalance between MMPs and the associated TIMPs may play a significant role in the invasive phenotype of malignant tumors. Therefore, MMPs and their inhibitors constitute promising agents for developing anticancer therapies. In the present study, the authors investigated the correlation between the expressions of TIMP-1 and MMPs, and the clinical outcome.
MATERIALS AND METHODS
Immunohistochemical staining of MMP-2, -3 and -9, and TIMP-1 was performed on paraffin-embedded tissue sections of 38 early gastric carcinomas and 61 advanced gastric carcinomas.
RESULTS
MMP-2 and -9 were found mainly in tumors of the intestinal type and less frequently in those of diffuse type. There were positive correlations between the presence of MMP-2 and -9 and lymph node status. There were inverse correlations between the TIMP-1 expression and tumor invasiveness.
CONCLUSION
These results suggests that clinical outcomes such as the depth of invasion or metastasis are closely related to the expression of TIMP-1, MMP-2 and MMP-9.

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  • Research on the mechanisms of taraxerol for the treatment of gastric cancer effect based on network pharmacology
    Bingjie Huo, Yanru Song, Bibo Tan, Jianbo Li, Jie Zhang, Fengbin Zhang, Liang Chang
    International Journal of Immunopathology and Pharmacology.2022;[Epub]     CrossRef
  • Potential Antioxidant and Antiphotoaging Effects of Fagopyrum esculentum Honey on Human Dermal Fibroblasts
    Hye-Bin Kim, Sungkwan An, Seunghee Bae
    Asian Journal of Beauty and Cosmetology.2022; 20(1): 43.     CrossRef
  • Regulatory Mechanism and Experimental Verification of Patchouli Alcohol on Gastric Cancer Cell Based on Network Pharmacology
    Yanru Song, Liang Chang, Xiaoyuan Wang, Bibo Tan, Jianbo Li, Jie Zhang, Fengbin Zhang, Lianmei Zhao, Guangjie Liu, Bingjie Huo
    Frontiers in Oncology.2021;[Epub]     CrossRef
  • Germacrone exerts anti-cancer effects on gastric cancer through induction of cell cycle arrest and promotion of apoptosis
    Lei Wu, Lifen Wang, Xiangguo Tian, Junyong Zhang, Hua Feng
    BMC Complementary Medicine and Therapies.2020;[Epub]     CrossRef
  • Paeonol exerts potential activities to inhibit the growth, migration and invasion of human gastric cancer BGC823 cells via downregulating MMP-2 and MMP-9
    Zhong-Kuan Lyu, Chang-Ling Li, Yan Jin, Yu-Zhao Liu, Xi Zhang, Fang Zhang, Lu-Ning Ning, Er-Shun Liang, Min Ma, Wei Gao, Ming-Xiang Zhang, De-Shan Liu
    Molecular Medicine Reports.2017; 16(5): 7513.     CrossRef
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Membrane-type Matrix Metalloproteinase-1 Induced Invasive and Angiogenic Activities in Chick Chorioallantoic Membrane (CAM) Model
Joo Won Jeong, Tae Kwon Sohn, Dae Yeul Yu, Kyu Won Kim
J Korean Cancer Assoc. 2001;33(1):49-55.
AbstractAbstract PDF
PURPOSE
Matrix metalloproteinases (MMPs) have been reported to play critical roles in the endothelial cell migration and matrix remodeling during angiogenic process. To investigate the roles of the membrane type MMP (MT1-MMP) by the matrix remodeling of endothelial cells, MT1-MMP expression vector was transfected into bovine aortic endothelial cells (BAECs). Increased ex+pression of MT1-MMP in BAECs enhanced the activation of MMP-2, invasion and migration of BAECs. Moreover, the capacity of tube formation was increased by MT1-MMP transfectants. These observations indicate that MT1-MMP is involved in the angiogenic process of endothelial cells in vitro. In this study, we attempted these effects were confirmed in vivo system.
MATERIALS AND METHODS
In this study, we used MT1- MMP or Antisense MT1-MMP stable transfectants in HT1080 human fibrosarcoma cells. Chorioallantoic membrane (CAM) assay was used for the detection of angiogenesis in vivo and modified CAM assay for quantification of invasion of MT1-MMP transfected cells.
RESULTS
In CAM assay, the formation of microvessels was stimulated by MT1-MMP transfectants. Invasive capacity of HT1080 cells was also increased in a novel in vivo metastasis model, PCR based CAM assay.
CONCLUSION
These results identify the function of MT1- MMP during the neovascularization process.
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Effect of Hepatocyte Growth Factor on the Expression of E-cadherin in Gastric Carcinoma Cell Lines
Sang Uk Han, Won Hung Lee, Wook Hwan Kim, Myung Wook Kim, Jae Ho Lee, Sang Yong Song, Kuhn Uk Lee
J Korean Cancer Assoc. 2000;32(5):852-862.
AbstractAbstract PDF
PURPOSE
Previously, we reported that the expression of E-cadherin was significantly decreased according to the increase of the level of hepatocyte growth factor (HGF) in gastric cancer tissue. In this work, the effect of HGF on the cell-cell adhesion and intracellular distribution of E-cadherin in the gastric carcinoma cell lines were studied. MATERIALS AND METHODS: Western blot analysis was performed to confirm the presence or abscence of c-Met and E-cadherin in SNU-1, 5, and 16 cells. Tyrosine phosphorylation of c-Met, E-cadherin, alpha-, beta-, gamma-catenins was checked by immunoprecipitation. The morphologic changes induced by HGF were studied with immunocytochemical staining. Functional proportion of E-cadherin was estimated by cell fractionation. The effect of HGF on cell proliferation and invasion was also assessed.
RESULTS
Among SNU-1, 5, and 16 cell lines, only SNU-16 cells expressed both E-cadherin and c-Met. A morphological change from epithelial shape to fibroblastic one was observed in the SNU-16 cells after treatment with HGF. In addition, E-cadherin expression of the SNU-16 cells was shifted from the membrane and to the cytoplasm, and the functional fraction of E-cadherin was decreased in the SNU-16 cells treated with HGF. On the other hand, HGF increased the proliferation and invasion of the SNU-16 cells.
CONCLUSION
These results suggest that HGF may regulate cell adhesion in gastric carcinomas via the cellular redistribution and functional change of E-cadherin.
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Combined Resection in Advanced Gastric Cancer
Dong Woo Shin, Chang Hak Yoo, Sung Hoon Noh, Jin Sik Min
J Korean Cancer Assoc. 1999;31(3):448-457.
AbstractAbstract PDF
PURPOSE
Prognosis of primary gastric cancer invading neighboring organs is very poor. However, with en bloc resection, a relatively favorable prognosis can be expected even in patients with such advanced cancer. But there has been controversy on the effectiveness of gastrectomy combined with en bloc resection of the invaded organs, and we conducted this study to evaluate the prognostic effects as well as the outcome of the combined resection.
MATERIALS AND METHODS
Among 2,603 who underwent gastrectomy due to gastric carcinoma from January 1987 to December 1994 at the Department of Surgery, Yonsei University College of Medicine, 157 patients (6.0%) in whom curative combined resections of grossly invaded adjacent organs (cT4) were perfonned entered this study. Any case with distant metastasis was excluded. Comparisons and multivariate analysis between the invasion (pT3) group and the non-invasion (pT4) group were made for age, sex, tumor size, location, Borrmann type, depth of invasion, lymph node metastasis, histologic type and 5-year survival rate.
RESULTS
One-organ combined resection was done in 60 (38.2%) patients; Two-organ, in 80 (51.0%) patients; and three-organ, in 17 (10.8%) patients. Most commonly combined organ was distal pancreas and transverse colon was the next. Histologic confirmation of invasion was made in 40.9%. 157 patients with T4 were divided into pT3 or pT4. Significant differences were found in type of operation, location of tumor, and TNM staging. Postoperative complications of combined resection were observed in 48 cases (30.6%) and the wound infection was the most frequent one. There were only 2 cases (1.3%) of immediate postoperative mortality in the combined group, and the causes of death were pulmonary complication and acute renal failure. Five-year survival rate (5-YSR) of pT3 group was 43.0% and that of pT4 was 26.2%. In comparison of 5-YSR according to TNM stages, no significant difference was found between pT3 and pT4 (45.0% vs. 66.7% in IIIa; 25.4% vs. 18.4% in IV). No difference of 5-YSR was observed in the groups categorized according to the number of resected organs. The comparison of 5-YSR between the 157 curatively-combined cases and the 63 palliatively-combined cases showed a significant difference (35.6% vs. 4.2%, p=0.000). Multivariate analysis showed that lymph node metastasis and microscopic tumor invasion served as significant parametets.
CONCLUSION
En bloc combined resection of adjacent invaded organs along with systematic lymph node dissection would be beneficial to gastric cancer patients with neighboring organ invasion.
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Clinicopathologic Significance of Lymphatic Vessel Invasion and Blood Vessel Invasion in Gastric Cancer
Sang Wook Kim, Ki Hyeok Lah, Chang Hak Yoo, Yong Il Kim, Sung Hoon Noh, Jin Sik Min
J Korean Cancer Assoc. 1999;31(1):16-23.
AbstractAbstract PDF
PURPOSE
The vessel invasion by cancer cells can be easily detected with the photomicroscope, but still there is an arguement on the value as a prognostic factor. The following study was conducted to evaluate the clinicopathologic significance of blood vessel invasion (BVI) and lymphatic vessel invasion (LVI) as a potential prognostic factor in gastric cancer treatment.
MATERIALS AND METHODS
618 patients who had undergone gastrectomies for gastric cancer at the Department of Surgery, Yonsei University College of Medicine, from August, 1993 to December, 1994, were retrospectively reviewed. Patients, based on the presence of BVI and/or LVI by HE stain, were arranged into three groups: Group 1 (n=338) consisted of patients with no evidence of BVI and LVI; group 2 (n=224), with evidence of either BVI or LVI; group 3 (n=56), with evidence of both BVI and LVI. The clinicopathologic features were analyzed and the survival rates of BVI, LVI and the three groups were studied.
RESULTS
BVI-positive patients were seen in 10.5% of all patients, and LVI-positive, in 43.9%. Certain factors such as tumor size, gross type, depth of invasion, lymph node metastasis, distant metastasis, and TNM staging showed significant differences among the three groups by univariate analyses. Survival rates between the BVI-positive (48.1%) and the BVI-negative (73.9%) and between the LVI-positive (55.4%) and the LVI-negative (82.6%) showed significant differences. 3-year survival rates of group 1, 2, and 3 were 82.5%, 59.7%, and 42.0%, respectively, with significant differences. But multivariate analysis demonstrated that distant metastasis, lymph node metastasis, depth of invasion, age, and gross type served as significant prognostic parameters while BVI and LVI did not.
CONCLUSION
Patients with BVI and/or LVI were associated with larger tumor size, infiltrative type tumor, deeper gastric wall invasion, more lymph node metastases, and advanced stages of tumor. BVI and LVI also played significantly adverse influence in the survival time in univariate analysis. With further studies on their roles in clinicopathologic features, lymphovascular invasion would be a useful prognostic factor in gastric cancer.
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Role of Cell Surface Mucin on Invasion and Metastasis of HM7 Colon Cancer Cells
Wan Hee Yoon, Hae Duck Park, Kyu Lim, Byung Doo Hwang
J Korean Cancer Assoc. 1997;29(2):309-320.
AbstractAbstract PDF
PURPOSE
Mucinous colorectal cancers have a poorer prognosis than which colorectal cancer produce low amount of mucin, but the exact mechanism is not well understood. The present study was undertaken to elucidate the exact mechanism of invasion and metastasis of high mucin producing colon cancer cells using mucin glycosylation inhibitor, benzyl-alpha-N-acetylgalactosamine.
MATERIALS AND METHODS
To evaluate the effect of glycosylated mucin on invasion and metastasis, in vitro invasion, metalloproteinases (MMPs) activity, cell-matrix protein binding, cell-cell aggregation, as well as endothelial leukocyte adhesion molecule (ELAM-1) binding and cell surface expression of various mucin related antigens were analyzed.
RESULTS
MMPs activity in conditioned medium and invasion of ECM-coated porous filters by benzyl-alpha-GalNAc treated HM7 cells were decreased. There was no difference between control and treated HM7 cells in terms of matrix protein binding assay, but treated HM7 cells showed higher homotypic cell adhesion. The binding activity of treated HM7 cells to ELAM-1 was significantly decreased and fixed cell binding of MoAb SNH-3, 19-9 (specific for sialyl-Lewis X and sialyl-Lewis A) were also significantly decreased.
CONCLUSION
These results suggest that glycosylated mucin modulates ELAM-1 binding, MMPs activity and homotypic cell adhesion, therefore enhance invasive and metastatic properties of human colon cancer cells.
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Determination of Lymphadenectomy in Primary Penile Carcinoma According to the Corpus Cavernosum Invasion
Tack Lee, Sung Joon Hong
J Korean Cancer Assoc. 1994;26(5):801-806.
AbstractAbstract PDF
A total of 31 patients with penile carcinoma were retrosrectively analysed. Patients were treated either by partial or total penectomy. Twenty one patients had corpus cavernosum inva- sion and other 7 patients exhibited no such invasion. Tumor grades were well differentiated (GI) in 7, moderately differentiated(GII) in 12 and poorly differentiated(GIII) in 10 respectively. Twenty patients underwent inguinal node dissectian. Metastatic nodes could be correlated with cavernosal invasion but not with tumor grade. When tumor grade and stage were analyzed simultaneously, none of Tl GI-III patients(0/4) developed nodal metastasis, but 75% of patients(12/16) with T., GI-III develaped metastasis. Thereby justifying 'wait and see' approach in patients without cavernosal invasion, but early or praphylactic lymphadenectomy should be performed in patients with cavernosal invaaion.
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The Effect of laminin and Type 4 Collagen on the Adhesion and Invasion of Human Gastrocytes and Gastric Cancer Cells In Vitro
Byung Sik Kim, Jin Cheon Kim, Seon Ae Roh, Kun Choon Park, Kuk Jin Choe
J Korean Cancer Assoc. 1995;27(3):360-374.
AbstractAbstract PDF
Extracellular matrix is important in the metastasis of tumor, and basement membrane acts not only as tissue barrier but also as adhesive substrate for tumor cell invasion. Laminin and type IV collagen are major components of basement membrane and important in tumor invasion. Adhesion and invasion studies about metastasis of the tumor have been performed mainly in colon cancer or breast cancer but rare in gastric cancer. The purpose of this study was to investigate the difference in the ability of adhesion to the basement membrane and their biological activity between the normal gastrocyte and gastric cancer cells. Then, The role of basement membrane in tumor invasion was assessed by the evaluation of the invasion of gastric cancer cells of different histological differentiation. Gastrocytes;, ere isolated from the surgically resected specimen by treating with collagenase and deoxyribonuclease. Normal gastrocytes were maintained viable up to 24 hours after isolation. The isolated cells were confirmed as gastric epithelial cells by indirect immuno- fluorescence staining for cytokeratin. Although the adhesion of normal gastrocyte was lower than that of gastric cancer cells, gastrocyte was bound to laminin and type IV collagen. The substrates were shown to play an important role for the differentiation and regeneration of gastrocytes also. In the invasion assay using transwell cell culture chamber coated with matrigel, laminin and type IV collagen enhanced tumor cell invasion (p<0.05). However, there was no difference according to histological differentiation. In conclusion, it can be suggested that laminin and type IV collagen must be important for the biologicaf activity of normal gastrocyte and metastasis of gastric cancer celL Type IV collagen enhances the invasion of gastric cancer cell more than laminin does.
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Expression in Matrix - Metalloproteinases ( MMP-2 , MMP-9 ) in Gastric Cancer as new Targets for Biotherapy
Hyun Cheol Chung, Jae Yong cho, Sun Young Rha, Joon Oh Park, Joong Bae Ahn, Choong In Lee, Nae Choon Yoo, Joo Hang Kim, Jae Kyung Roh, Sung Hoon Noh, Jin Sik Min, Byung Soo Kim, Ho Yeong Lim, Jin Hyu Choi
J Korean Cancer Assoc. 1995;27(6):897-907.
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The proteolytic processes are thought to be the critical point in tumor invasion and metastasis, mainly by matrix-metalloproteinases (MMPs) and serine proteases. We measured the activities of MMP-9 and MMP-2 in the 120 normal and cancer tissue samples from the same patients using gelatin zymography. Inactive MMP-9(92 kD) was expressed in 73.3% of the normal and 87.5% of the cancer tissues, respectively (p=0.009), while active MMP-9(82 kD) was expressed in 24.2% and 53.3%, respectively (p=0.0001). Inactive MMP-2 (72kD) was expressed in 33.3% of the normal and 55.0% of the cancer tissues, respectively (p=0.001), while active MMP-2(62kD) was expressed in 4.2% and 31.7%, respectively (p=0.0001). In Tl state, only frequency of expression and enzymatic activity of the active MMP-2(62kD) were increased, while from T2 stage, the expression and the activation of the both MMP-9 and MMP-2 were increased as the cancer progressed. The expression frequency of the MMP-9 was more common than of the MMP-2. The co-expression rate of the active forms (82 kD, 62 kD), activites of 82 kD and 62 kD, and the activation rates of the both MMPs were increased as the cancer invades and metastasizes to distant lymph node areas. In conclusion, MMP-2 activation was the main causes of the increased MMPs activity during the Tl phase of the gastric cancer, while production and activation of the both MMP-9 and MMP-2 were increased as the cancer progressed. Therefore, we suggest that the different expression and activation of the MMPs in the gastric cancer progression can be a potential therapeutic target in gastric cancer biotherapy.
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Localization of Urokinase Type Plaminogen Activator Receptor on Tumor Cells by Tmmunohistochemistry
Hye Won Park, Yoon Hoh Kook, Sung Bae Choi, ng Yong Cha
J Korean Cancer Assoc. 1996;28(1):159-168.
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Urokinase type plasminogen activator(uPA) plays important role in invasion and metastasis of cancer. Its actions are activated and amplified by a specific cell-surface receptor (urokinase type plasminogen activator receptor: uPAR). The present study was undertaken to determine the importance of the uPAR for migration and invasion of cancer cells through immunohistochemical localization of uPAR. HEp3 cells were cultured in monolayer and suspended, then they were stained by immunofluorescence, APAAP(alkaline phosphatase anti-alkaline phosphatase) and immunoperoxidase method. The receptor(uPAR) was found to be located at cellular contact sites. In suspension uPAR staining of HEp3 cells showed focal distribution. In vivo model of invasion, the uPAR was localized on leading edge of tumor of cholioallatoic membrane(CAM) inoculated with HEp3 cells. This suggests that uPAR might play crucial role in migration and invasion of cancer cells through mediating proteolysis at cellular contact sites especially in leading edge of the tumor.
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Expression of Matrix-metalloproteinase- 9 ( MMP- 9 ) in Breast Cancer
Sun Young Rha, Se Joong Kim, Hyun Cheol Chung, Joo Hang Kim, Jae Kyung Roh, Kyung Shik Lee, Byung Soo Kim
J Korean Cancer Assoc. 1996;28(2):247-253.
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The degradation of the basement membrane by matrix-metalloproteinase(MMP) and serine protease is a critical point in tumor invasion and metastasis. We measured the activity of MMP-9 from 28 normal, 12 benign, and 126 breast cancer tissues using gelatin zymography with an image analysis system. Inactive MMP-9 was expressed in 17.5% of the cancer patients compared to 2.5% in 40 non-cancerous tissues(p=0.008). The active form of MMP-9(82kD) was expressed only in T2-T4 stages. During the early phase of breast cancer (DCIS and Tl stage) progression, only the production of inactive MMP-9 was increased. However, as the cancer grew or invaded skin(T2-T4), or with lymphovascular permeation, both production and activation of MMP-9 were increased. In conclusion, MMP-9 productian was the main cause of increased MMP-9 activity during the ear1y phase, while both production and activation were increased in the late phase of breast cancer.
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Cininicopathological Study of Esophageal Invading Carcinoma of the Upper Third Part of the Stomach
Sung Hoon Noh, Chang Hak Yoo, Yong Il Kim, Coong Bai Kim, Jin Sik Min, Kyung Shik Lee
J Korean Cancer Assoc. 1996;28(5):852-860.
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To evaluate clinicopathological characteristics and prognostic factors of esophageal invading cancer of the upper third of the stomach, we analyzed retrospectively 198 patients who underwent total gastrectomy for adenocarcinoma arising from the upper third of the stomach during 1987 to 1993 at Deparment of Surgery, Yonsei University, College of Medicine and divided into two groups as esophageal invading group(n=39) and non-invading group(n=159). Esophageal invading group had larger tumor size and higher rates of serosal invasion, lymph node metastasis, liver and peritoneal metastasis than non-invading group. Therefore more advanced stage and palliative resection were observed in esophageal invading group. The 5-year survival rate of esophageal invading group(37.6%) was significantly lower than that of non-invading group(60.8%). The significant prognostic factors of esophageal invading group using Cox's proportional hazard method were lymph node metastasis and curability of gastric resection. In conclusion, esophageal invading gastric cancer had more aggressive behavior than that of non-invading group and frozen section of proximal resection margin during operation should be performed for curative resection. For some of patients with far advanced upper third gastric cancer, neoadjuvant chemotherapy, early postoperative intraperitoneal chemotherapy(EPIC) or intraperitoneal hyperthermic chemotherapy(IPHC) may provide better qualiity of life and survival benefit.
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Cancer Res Treat : Cancer Research and Treatment
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