Annals of Coloproctology

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Association Between c-Met and Lymphangiogenic Factors in Patients With Colorectal Cancer: Han Jo Kim, Moo-Jun Baek, Dong Hyun Kang, Sang-Cheol Lee, Sang Byung Bae, Kyu Taek Lee, Namsu Lee, Hyungjoo Kim, Dongjun Jeong, Tae Sung Ahn, Moon Soo Lee, Dae Sik Hong, Jong-Ho Won; Ann Coloproctol. 2018;34(2):88-93. Published online April 30, 2018; DOI: https://doi.org/10.3393/ac.2017.10.10

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Purpose
Animal models show a strong relationship between lymphangiogenesis and lymph node metastasis. However, the clinical significance of lymphangiogenesis in patients with colorectal cancer (CRC) remains uncertain. This study aimed to evaluate the association between c-Met and lymphangiogenic factors and to elucidate the prognostic significance of c-Met in patients with CRC.
Methods
A total of 379 tissue samples were obtained from surgically resected specimens from patients with CRC at Soonchunhyang University Cheonan Hospital between January 2002 and December 2010. The expressions of c-Met, vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGF receptor (VEGFR)-3, and podoplanin were examined using immunohistochemistry. The expression of c-Met and clinical factors were analyzed.
Results
Of the 379 tissues, 301 (79.4%) had c-Met expression. High expression of c-Met in tumor cells was significantly associated with high expression of VEGF-C (P < 0.001) and VEGFR-3 (P = 0.001). However, no statistically significant association with podoplanin (P = 0.587) or VEGF-D (P = 0.096) was found. Of the 103 evaluable patients, expression of c-Met in tumor cells was significantly associated with advanced clinical stage (P = 0.020), positive lymph node status (P = 0.038), and high expression of VEGF-C (P = 0.020). However, no statistically significant association with podoplanin (P = 0.518), VEGFR-3 (P = 0.085), VEGF-D (P = 0.203), or overall survival (P = 0.360) was found.
Conclusion
Our results provide indirect evidence for an association and possible regulatory link of c-Met with the lymphangiogenic markers, but c-Met expression in patients with CRC is not a prognostic indicator for overall survival.

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Expression Profile of Microenvironmental Factors in the Interface Zone of Colorectal Cancer: Histological-Stromal Biomarkers and Cancer Cell-Cancer-Associated Fibroblast-Related Proteins Combined for the Assessment of Tumor Progression
Ricella Souza da Silva, Eduardo M. Queiroga, Cynthia de Toledo Osório, Karin S. Cunha, Fabiana P. Neves, Julieth P. Andrade, Eliane P. Dias
Pathobiology.2024; 91(2): 99. CrossRef
Recent progress in the imaging of c‐Met aberrant cancers with positron emission tomography
Giuseppe Floresta, Vincenzo Abbate
Medicinal Research Reviews.2022; 42(4): 1588. CrossRef
Involvement of Met receptor pathway in aggressive behavior of colorectal cancer cells induced by parathyroid hormone-related peptide
María Belén Novoa Díaz, Pedro Carriere, Graciela Gigola, Ariel Osvaldo Zwenger, Natalia Calvo, Claudia Gentili
World Journal of Gastroenterology.2022; 28(26): 3177. CrossRef
The potential therapeutic and prognostic impacts of the c‐MET/HGF signaling pathway in colorectal cancer
Seyed Mostafa Parizadeh, Reza Jafarzadeh‐Esfehani, Danial Fazilat‐Panah, Seyed Mahdi Hassanian, Soodabeh Shahidsales, Majid Khazaei, Seyed Mohammad Reza Parizadeh, Majid Ghayour‐Mobarhan, Gordon A. Ferns, Amir Avan
IUBMB Life.2019; 71(7): 802. CrossRef

Expressions and Clinical Significances of Angiopoietin-1, Angiopoietin-2, and Tie-2 Receptor in Patients With Colorectal Cancer: Sunghoon Hong, Hae Il Jung, Tae Sung Ahn, Han-Jo Kim, Kyu-Taek Lee, Moo-Jun Baek, Sang-Byung Bae; Ann Coloproctol. 2017;33(1):9-15. Published online February 28, 2017; DOI: https://doi.org/10.3393/ac.2017.33.1.9

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Abstract PDF

Purpose

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

Methods

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

Results

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

Conclusion

A relationship was found to exist between Ang-2 and Tie-2 expressions. The Ang-2 was correlated with lymph-node metastasis, and high expression of Ang-2 was indicative of poor overall survival. These findings suggest that Ang-2 is a useful prognostic marker in the management of patients with colorectal cancer. In addition, we suggest that Ang/Tie-2 signaling plays an important role in the progression of colorectal cancer.

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Advances in Clinical Medicine.2025; 15(01): 1396. CrossRef
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Yin-Chou Hsu, Chi-Wen Luo, Shu-Jyuan Chang, Chiao-Ying Lai, Yu-Tzu Yang, Yi-Zi Chen, Mei-Hsiang Hsu, Cheuk-Kwan Sun, Mei-Ren Pan
Experimental Cell Research.2025; 450(1): 114622. CrossRef
Putative Role of Tie2-Expressing Monocytes/Macrophages in Colorectal Cancer Progression Through Enhancement of Angiogenesis and Metastasis
Eman Amin M. Ali, Alaa Muayad Altaie, Iman M. Talaat, Rifat Hamoudi
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Differential expression of angiogenesis-related genes ‘VEGF’ and ‘angiopoietin-1’ in metastatic and EMAST-positive colorectal cancer patients
Amir Torshizi Esfahani, Somayeh Mohammadpour, Pooya Jalali, Alireza Yaghoobi, Raana Karimpour, Soha Torkamani, Ali Pardakhtchi, Zahra Salehi, Ehsan Nazemalhosseini-Mojarad
Scientific Reports.2024;[Epub] CrossRef
Platelet Angiopoietin-1 Protects Against Murine Models of Tumor Metastasis
Harvey G. Roweth, Isabelle C. Becker, Michael W. Malloy, Emily M. Clarke, Sophie A. Munn, Priya L. Kumar, Ivan Aivasovsky, Kobe Tray, Alec A. Schmaier, Elisabeth M. Battinelli
Arteriosclerosis, Thrombosis, and Vascular Biology.2024; 44(9): 2024. CrossRef
KRAS mutation-driven angiopoietin 2 bestows anti-VEGF resistance in epithelial carcinomas
Kayoko Hosaka, Patrik Andersson, Jieyu Wu, Xingkang He, Qiqiao Du, Xu Jing, Takahiro Seki, Juan Gao, Yin Zhang, Xiaoting Sun, Ping Huang, Yunlong Yang, Minghua Ge, Yihai Cao
Proceedings of the National Academy of Sciences.2023;[Epub] CrossRef
Angiopoietin-2 as a Prognostic Factor in Patients with Incurable Stage IV Colorectal Cancer
Shinya Munakata, Takae Ueyama, Haruna Ishihara, Hiromitsu Komiyama, Ryoichi Tsukamoto, Masaya Kawai, Makoto Takahashi, Yutaka Kojima, Yuichi Tomiki, Kazuhiro Sakamoto
Journal of Gastrointestinal Cancer.2021; 52(1): 237. CrossRef
Dual Antiangiogenesis Agents Bevacizumab Plus Trebananib, without Chemotherapy, in First-line Treatment of Metastatic Colorectal Cancer: Results of a Phase II Study
Jennifer Mooi, Fiona Chionh, Peter Savas, Jessica Da Gama Duarte, Geoffrey Chong, Stephen Brown, Rachel Wong, Timothy J. Price, Alysson Wann, Effie Skrinos, John M. Mariadason, Niall C. Tebbutt
Clinical Cancer Research.2021; 27(8): 2159. CrossRef
6-Gingerol delays tumorigenesis in benzo[a]pyrene and dextran sulphate sodium-induced colorectal cancer in mice
Ebenezer O. Farombi, Babajide O. Ajayi, Isaac A. Adedara
Food and Chemical Toxicology.2020; 142: 111483. CrossRef
High expression of Tie-2 predicts poor prognosis in primary high grade serous ovarian cancer
Minna Sopo, Hanna Sallinen, Kirsi Hämäläinen, Annukka Kivelä, Seppo Ylä-Herttuala, Veli-Matti Kosma, Leea Keski-Nisula, Maarit Anttila, Elizabeth Christie
PLOS ONE.2020; 15(11): e0241484. CrossRef
Evaluation of plasma angiopoietin‐2 and vascular endothelial growth factor in healthy dogs and dogs with systemic inflammatory response syndrome or sepsis
Maya König, Alice Nentwig, Eliane Marti, Jelena Mirkovitch, Katja‐Nicole Adamik, Simone Schuller
Journal of Veterinary Internal Medicine.2019; 33(2): 569. CrossRef
Targeting Receptor Kinases in Colorectal Cancer
Marilina García-Aranda, Maximino Redondo
Cancers.2019; 11(4): 433. CrossRef
Gene expression and promoter methylation of angiogenic and lymphangiogenic factors as prognostic markers in melanoma
Ana Carolina Monteiro, Julienne K. Muenzner, Fernando Andrade, Flávia Eichemberger Rius, Christian Ostalecki, Carol I. Geppert, Abbas Agaimy, Arndt Hartmann, André Fujita, Regine Schneider‐Stock, Miriam Galvonas Jasiulionis
Molecular Oncology.2019; 13(6): 1433. CrossRef
“Vessels in the Storm”: Searching for Prognostic and Predictive Angiogenic Factors in Colorectal Cancer
Adriano Angelucci, Simona Delle Monache, Alessio Cortellini, Monica Di Padova, Corrado Ficorella
International Journal of Molecular Sciences.2018; 19(1): 299. CrossRef
Angiopoietin-2 (Ang-2) is a useful serum tumor marker for liver cancer in the Chinese population
Yuxin Chen, Yanping Wu, Xiao Zhang, Hong Zeng, Ya Liu, Qi Wu, Yan Chen, GuoQing Zhu, Qiuhui Pan, Lei Jin, Lin Guo, Fenyong Sun
Clinica Chimica Acta.2018; 478: 18. CrossRef
Efforts to Find Targets Involving Angiogenesis: Step to Improve the Efficacy of Target Therapy in the Era of Colorectal Cancer Treatment
In Ja Park
Annals of Coloproctology.2017; 33(1): 1. CrossRef

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