Cancer Research and Treatment

Original Articles

Gastrointestinal cancer

Anti–PD-L1 Antibody and/or 17β-Estradiol Treatment Induces Changes in the Gut Microbiome in MC38 Colon Tumor Model: Chin-Hee Song, Nayoung Kim, Ryoung Hee Nam, Soo In Choi, Jae Young Jang, Jina Choi, Ha-Na Lee; Cancer Res Treat. 2023;55(3):894-909. Published online January 9, 2023; DOI: https://doi.org/10.4143/crt.2022.1427

Purpose
17β-Estradiol (E2) supplementation suppresses MC38 tumor growth by downregulating the expression of programmed death-ligand 1 (PD-L1). This study aims to figure out the gut microbiota that respond to anti–PD-L1 and/or estrogen treatment in MC38 colon cancer model.
Materials and Methods
A syngeneic colon tumor model was developed by injection of MC38 cells into C57BL/6 background male and female mice. Three days before MC38 cells injection, E2 was supplemented to male mice daily for 1 week. Male and female mice with MC38 tumors (50-100 mm3) were injected with anti–PD-L1 antibody. Fresh feces were collected 26 days after injection of MC38 cells and 16S rRNA metagenomics sequencing of DNA extracted from feces was used to assess gut microbial composition.
Results
At the taxonomic family level, Muribaculaceae was enriched only in the MC38 male control group. In male mice, linear discriminant analysis effect size analysis at the species level revealed that the four microorganisms were commonly regulated in single and combination treatment with anti–PD-L1 and/or E2; a decrease in PAC001068_g_uc and PAC001070_s (family Muribaculaceae) and increase in PAC001716_s and PAC001785_s (family Ruminococcaceae). Interestingly, in the anti–PD-L1 plus E2 group, a decrease in opportunistic pathogens (Enterobacteriaceae group) and an increase in commensal bacteria (Lactobacillus murinus group and Parabacteroides goldsteinii) were observed. Furthermore, the abundance of Parabacteroides goldsteinii was increased in both males and females in the anti–PD-L1 group.
Conclusion
Our results suggest that gut microbial changes induced by the pretreatment of estrogen before anti–PD-L1 might contribute to treatment of MC38 colon cancer.

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Distribution and roles of Ligilactobacillus murinus in hosts
Zhou Chuandong, Jicong Hu, Jiawen Li, Yuting Wu, Chan Wu, Guanxi Lai, Han Shen, Fenglin Wu, Changli Tao, Song Liu, Wenfeng Zhang, Hongwei Shao
Microbiological Research.2024; 282: 127648. CrossRef
Sex differences in colorectal cancer: with a focus on sex hormone–gut microbiome axis
Zihong Wu, Yuqing Huang, Renyi Zhang, Chuan Zheng, Fengming You, Min Wang, Chong Xiao, Xueke Li
Cell Communication and Signaling.2024;[Epub] CrossRef
17β-estradiol in colorectal cancer: friend or foe?
Zihong Wu, Chong Xiao, Jiamei Wang, Min Zhou, Fengming You, Xueke Li
Cell Communication and Signaling.2024;[Epub] CrossRef
Sexual dimorphism of gut microbiota in colorectal cancer
Zihong Wu, Ziming Wang, Jiamei Wang, Chong Xiao, Fengming You, Xueke Li
Chinese Science Bulletin.2024;[Epub] CrossRef
Direct and indirect effects of estrogens, androgens and intestinal microbiota on colorectal cancer
Zihong Wu, Yi Sun, Wenbo Huang, Zhenzhen Jin, Fengming You, Xueke Li, Chong Xiao
Frontiers in Cellular and Infection Microbiology.2024;[Epub] CrossRef
Targeting metabolic pathways: a novel therapeutic direction for type 2 diabetes
Zhihui Song, An Yan, Zehui Guo, Yuhang Zhang, Tao Wen, Zhenzhen Li, Zhihua Yang, Rui Chen, Yi Wang
Frontiers in Cellular and Infection Microbiology.2023;[Epub] CrossRef

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Histopathologic and Molecular Biomarkers of PD-1/PD-L1 Inhibitor Treatment Response among Patients with Microsatellite Instability‒High Colon Cancer: Jaewon Hyung, Eun Jeong Cho, Jihun Kim, Jwa Hoon Kim, Jeong Eun Kim, Yong Sang Hong, Tae Won Kim, Chang Ohk Sung, Sun Young Kim; Cancer Res Treat. 2022;54(4):1175-1190. Published online January 12, 2022; DOI: https://doi.org/10.4143/crt.2021.1133

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Purpose
Recent clinical trials have reported response rates < 50% among patients treated with programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors for microsatellite instability‒high (MSI-H) colorectal cancer (CRC), and factors predicting treatment response have not been fully identified. This study aimed to identify potential biomarkers of PD-1/PD-L1 inhibitor treatment response among patients with MSI-H CRC.
Materials and Methods
MSI-H CRC patients enrolled in three clinical trials of PD-1/PD-L1 blockade at Asan Medical Center (Seoul, Republic of Korea) were screened and classified into two groups according to treatment response. Their histopathologic features and expression of 730 immune-related genes from the NanoString platform were evaluated, and a machine learning–based classification model was built to predict treatment response among MSI-H CRCs patients.
Results
A total of 27 patients (15 responders, 12 non-responders) were included. A high degree of lymphocytic/neutrophilic infiltration and an expansile tumor border were associated with treatment response and prolonged progression-free survival (PFS), while mucinous/signet-ring cell carcinoma was associated with a lack of treatment response and short PFS. Gene expression profiles revealed that the interferon-γ response pathway was enriched in the responder group. Of the top eight differentially expressed immune-related genes, PRAME had the highest fold change in the responder group. Higher expression of PRAME was independently associated with better PFS along with histologic subtypes in the multivariate analysis. The classification model using these genes showed good performance for predicting treatment response.
Conclusion
We identified histologic and immune-related gene expression characteristics associated with treatment response in MSI-H CRC, which may contribute to optimal patient stratification.

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The Relationship of PRAME Expression with Clinicopathologic Parameters and Immunologic Markers in Melanomas: In Silico Analysis
Yasemin Cakir, Banu Lebe
Applied Immunohistochemistry & Molecular Morphology.2025;[Epub] CrossRef
Biomarkers to predict efficacy of immune checkpoint inhibitors in colorectal cancer patients: a systematic review and meta-analysis
Hang Yu, Qingquan Liu, Keting Wu, Shuang Tang
Clinical and Experimental Medicine.2024;[Epub] CrossRef
An Insight into the Peculiarities of Signet-Ring Cell Carcinoma of the Colon – a Narrative Review
Loredana Farcaș, Diana Voskuil-Galoș
Journal of Medical and Radiation Oncology.2024; 4(7): 1. CrossRef
High serum IL-6 correlates with reduced clinical benefit of atezolizumab and bevacizumab in unresectable hepatocellular carcinoma
Hannah Yang, Beodeul Kang, Yeonjung Ha, Sung Hwan Lee, Ilhwan Kim, Hyeyeong Kim, Won Suk Lee, Gwangil Kim, Sanghoon Jung, Sun Young Rha, Vincent E. Gaillard, Jaekyung Cheon, Chan Kim, Hong Jae Chon
JHEP Reports.2023; 5(4): 100672. CrossRef
Identification of ZBTB4 as an immunological biomarker that can inhibit the proliferation and invasion of pancreatic cancer
Zhe Yang, Feiran Chen, Feng Wang, Xiubing Chen, Biaolin Zheng, Xiaomin Liao, Zhejun Deng, Xianxian Ruan, Jing Ning, Qing Li, Haixing Jiang, Shanyu Qin
BMC Cancer.2023;[Epub] CrossRef
PD-L1 Expression in Colorectal Carcinoma: A Comparison of 3 Scoring Methods in a Cohort of Jordanian Patients
Heyam A. Awad, Maher A. Sughayer, Jumana M. Obeid, Yaqoot N. Heilat, Ahmad S. Alhesa, Reda M. Yousef, Nabil M. Hasasna, Shafiq A. Masoud, Tareq Saleh
Applied Immunohistochemistry & Molecular Morphology.2023; 31(6): 379. CrossRef
Systemic Delivery of a STING Agonist‐Loaded Positively Charged Liposome Selectively Targets Tumor Immune Microenvironment and Suppresses Tumor Angiogenesis
Eun‐Jin Go, Hannah Yang, Wooram Park, Seung Joon Lee, Jun‐Hyeok Han, So Jung Kong, Won Suk Lee, Dong Keun Han, Hong Jae Chon, Chan Kim
Small.2023;[Epub] CrossRef
Review of the Immune Checkpoint Inhibitors in the Context of Cancer Treatment
Norah A. Alturki
Journal of Clinical Medicine.2023; 12(13): 4301. CrossRef
Enhancing head and neck tumor management with artificial intelligence: Integration and perspectives
Nian-Nian Zhong, Han-Qi Wang, Xin-Yue Huang, Zi-Zhan Li, Lei-Ming Cao, Fang-Yi Huo, Bing Liu, Lin-Lin Bu
Seminars in Cancer Biology.2023; 95: 52. CrossRef
Artificial intelligence for prediction of response to cancer immunotherapy
Yuhan Yang, Yunuo Zhao, Xici Liu, Juan Huang
Seminars in Cancer Biology.2022; 87: 137. CrossRef

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Prognostic Implications of Extranodal Extension in Relation to Colorectal Cancer Location: Chan Wook Kim, Jihun Kim, Yangsoon Park, Dong-Hyung Cho, Jong Lyul Lee, Yong Sik Yoon, In Ja Park, Seok-Byung Lim, Chang Sik Yu, Jin Cheon Kim; Cancer Res Treat. 2019;51(3):1135-1143. Published online November 29, 2018; DOI: https://doi.org/10.4143/crt.2018.392; Correction in: Cancer Res Treat 2021;53(3):893

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Purpose
Extranodal extension (ENE) is closely associated with the aggressiveness of both colon and rectal cancer. This study evaluated the clinicopathologic significance and prognostic impact of ENE in separate populations of patients with colon and rectal cancers.
Materials and Methods
The medical records of 2,346 patients with colorectal cancer (CRC) who underwent curative surgery at our institution between January 2003 and December 2011 were clinically and histologically reviewed.
Results
ENE was associated with younger age, advanced tumor stage, lymphovascular invasion (LVI), and perineural invasion (PNI) in both colon and rectal cancer. ENE rates differed significantly in patients with right colon (36.9%), left colon (42.6%), and rectal (48.7%) cancers (right vs. left, p=0.037; left vs. rectum, p=0.009). The 5-year disease-free survival (DFS) rate according to ENE status and primary tumor site differed significantly in patients with ENE-negative colon cancer (80.5%), ENE-negative rectal cancer (77.4%), ENE-positive colon cancer (68.6%), and ENE-positive rectal cancer (64.2%) (p<0.001). Multivariate analysis showed that advanced tumor stage, ENE, LVI, PNI, and absence of adjuvant chemotherapy were independently prognostic of reduced DFS in colon and rectal cancer patients.
Conclusion
ENE is closely associated with the aggressiveness of colon and rectal cancers, with its frequency increasing from the right colon to the left colon to the rectum. ENE status is a significant independent predictor of DFS in CRC patients irrespective of tumor location. ENE might be more related with distally located CRC.

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Assessment of prognostic indicators and KRAS mutations in rectal cancer using a fractional-order calculus MR diffusion model: whole tumor histogram analysis
Mi Zhou, Hongyun Huang, Deying Bao, Meining Chen, Fulin Lu
Abdominal Radiology.2024;[Epub] CrossRef
Tumour deposits are associated with worse survival than extranodal extension; a network meta‐analysis on tumour nodules in colorectal cancer
Nelleke P M Brouwer, Shannon van Vliet, Joanna IntHout, Johannes H W De Wilt, Femke Simmer, Niek Hugen, Iris D Nagtegaal
Histopathology.2024;[Epub] CrossRef
MRI-based multiregional radiomics for predicting lymph nodes status and prognosis in patients with resectable rectal cancer
Hang Li, Xiao-li Chen, Huan Liu, Tao Lu, Zhen-lin Li
Frontiers in Oncology.2023;[Epub] CrossRef
Prognostic significance of extranodal extension of nodal metastasis in adenocarcinoma of the ampulla of Vater
Jihyun Chun, Yeon Wook Kim, Seo-rin Jeong, Hyung Jun Cho, Kyu-Pyo Kim, Dae Wook Hwang, Seung-Mo Hong
Human Pathology.2023; 137: 36. CrossRef
Dissimilar survival and clinicopathological characteristics of mucinous adenocarcinoma located in pancreatic head and body/tail
Zheng Li, Xiao-Jie Zhang, Chong-Yuan Sun, Ze-Feng Li, He Fei, Dong-Bing Zhao
World Journal of Gastrointestinal Surgery.2023; 15(6): 1178. CrossRef
Effect of visceral fat area on the accuracy of preoperative CT-N staging of colorectal cancer
Meizhen Xie, Gangyi Liu, Yan Dong, Lan Yu, Rui Song, Wei Zhang, Ying Zhang, Shafei Huang, Jiaqian He, Yunping Xiao, Liling Long
European Journal of Radiology.2023; 168: 111131. CrossRef
Prognostic Value of the N1c in Stage III and IV Colorectal Cancer: A Propensity Score Matching Study Based on the Surveillance, Epidemiology, and End Results (SEER) Database
Chongshun Liu, Mengxiang Tian, Haiping Pei, Fengbo Tan, Yuqiang Li
Journal of Investigative Surgery.2022; 35(4): 850. CrossRef
Tumor Deposits and Perineural Invasion had Comparable Impacts on the Survival of Patients With Non-metastatic Colorectal Adenocarcinoma: A Population-Based Propensity Score Matching and Competing Risk Analysis
Bin Luo, Xianzhe Chen, Guanfu Cai, Weixian Hu, Yong Li, Junjiang Wang
Cancer Control.2022;[Epub] CrossRef
The application of apparent diffusion coefficients derived from intratumoral and peritumoral zones for assessing pathologic prognostic factors in rectal cancer
Yi Yuan, Xiao-li Chen, Zhen-lin Li, Guang-wen Chen, Hao Liu, Yi-Sha Liu, Ming-hui Pang, Si-yun Liu, Hong Pu, Hang Li
European Radiology.2022; 32(8): 5106. CrossRef
Beyond N staging in colorectal cancer: Current approaches and future perspectives
Gianluca Arrichiello, Mario Pirozzi, Bianca Arianna Facchini, Sergio Facchini, Fernando Paragliola, Valeria Nacca, Antonella Nicastro, Maria Anna Canciello, Adele Orlando, Marianna Caterino, Davide Ciardiello, Carminia Maria Della Corte, Morena Fasano, St
Frontiers in Oncology.2022;[Epub] CrossRef
Clinical Implication of Perineural and Lymphovascular Invasion in Rectal Cancer Patients Who Underwent Surgery After Preoperative Chemoradiotherapy
Young Il Kim, Chan Wook Kim, Jong Hoon Kim, Jihun Kim, Jun-Soo Ro, Jong Lyul Lee, Yong Sik Yoon, In Ja Park, Seok-Byung Lim, Chang Sik Yu, Jin Cheon Kim
Diseases of the Colon & Rectum.2022; 65(11): 1325. CrossRef
Prognostic Impact of Extranodal Extension in Rectal Cancer Patients Undergoing Radical Resection After Preoperative Chemoradiotherapy
Young Il Kim, Haeyon Cho, Chan Wook Kim, Yangsoon Park, Jihun Kim, Jun-Soo Ro, Jong Lyul Lee, Yong Sik Yoon, In Ja Park, Seok-Byung Lim, Chang Sik Yu, Jin Cheon Kim
Clinical Colorectal Cancer.2021; 20(1): e35. CrossRef
Analysis of the Clinicopathological Characteristics of Stage I–III Colorectal Cancer Patients Deficient in Mismatch Repair Proteins
Yichao Liang, Xinling Cai, Xu Zheng, Hongzhuan Yin
OncoTargets and Therapy.2021; Volume 14: 2203. CrossRef
Clinical significance of extranodal extension in sentinel lymph node positive breast cancer
Xia Yang, XiaoXi Ma, Wentao Yang, Ruohong Shui
Scientific Reports.2020;[Epub] CrossRef

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Long-term Survival in Patients Treated with a Robotic Radiosurgical Device for Liver Metastases: Sebastian Stintzing, Jobst von Einem, Christoph Fueweger, Alfred Haidenberger, Michael Fedorov, Alexander Muavcevic; Cancer Res Treat. 2019;51(1):187-193. Published online April 16, 2018; DOI: https://doi.org/10.4143/crt.2017.594

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Purpose
The treatment of liver metastases with local procedures is a fast progressing field. For the most, long-term survival data is missing raising questions with regard to the efficacy of such modalities when compared to surgical resection. Radiosurgery using the CyberKnife device enables the treatment of liver lesions with a single-session approach. Here we present long-term survival data to explore the curative potential of this strategy.
Materials and Methods
Patients with oligo-metastatic disease limited to the liver have been treated with single-session or hypo-fractioned radiosurgery in curative intent and prospectively followed until death. Follow-up (FU) was performed using magnetic resonance imaging (MRI) 2 months after radiation and at 3-month intervals for the first 2 years. After that annual computed tomography or MRI scans were performed until 5 years post-treatment. Local recurrence in the radiated volume and recurrence outside the treated volume were used to define local and distant progression. Survival times were censored at the time of the last FU.
Results
One hundred twenty-six patients treated between 2005 and 2015 with 194 lesions were included into this study. Median FU was 30.0 months. According to Response Evaluation Criteria in Solid Tumors, 55.2% had a complete remission and 11.3% a partial remission. Seventy-two point two percent recurred outside the radiated lesion and median overall survival was 35.2 months with a 3-year survival rate of 47.7%.
Conclusion
This is currently the largest cohort of stereotactic body radiation therapy treated liver lesions with a median long-term follow of 30 months. Robotic radiosurgery using a single session approach has a high efficacy to control the radiated lesion with the potential to cure patients.

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Robotic Stereotactic Body Radiation Therapy for Oligometastatic Liver Metastases: A Systematic Review of the Literature and Evidence Quality Assessment
Ilektra Kyrochristou, Ilias Giannakodimos, Maria Tolia, Ioannis Georgakopoulos, Nikolaos Pararas, Francesk Mulita, Nikolaos Machairas, Dimitrios Schizas
Diagnostics.2024; 14(10): 1055. CrossRef
Stereotactic Body Radiation therapy for Liver Metastases: Systematic Review and Meta-Analysis With International Stereotactic Radiosurgery Society (ISRS) Practice Guidelines
Ciro Franzese, Alexander V. Louie, Rupesh Kotecha, Zhenwei Zhang, Matthias Guckenberger, Mi-Sook Kim, Alison C. Tree, Ben J. Slotman, Arjun Sahgal, Marta Scorsetti
Practical Radiation Oncology.2024;[Epub] CrossRef
Effectiveness of Robotic Stereotactic Radiotherapy in Patients Undergoing Re-irradiation: A Review
Ahamed Badusha Mohamed Yoosuf, Salem Alshehri, Mohd Zahri Abdul Aziz, Syahir Mansor, Gokula Kumar Appalanaido, Mamdouh Alqathami
Cureus.2023;[Epub] CrossRef
Stereotactic body radiation therapy in patients with liver oligometastases from colorectal cancer: a systematic review
A. N. Moskalenko, V. K. Lyadov, I. V. Sagaydak, M. V. Chernykh, N. N. Britskaya
Pelvic Surgery and Oncology.2022; 12(1): 49. CrossRef
Anti-EGFR Therapy Induces EGF Secretion by Cancer-Associated Fibroblasts to Confer Colorectal Cancer Chemoresistance
Colleen M. Garvey, Roy Lau, Alyssa Sanchez, Ren X. Sun, Emma J. Fong, Michael E. Doche, Oscar Chen, Anthony Jusuf, Heinz-Josef Lenz, Brent Larson, Shannon M. Mumenthaler
Cancers.2020; 12(6): 1393. CrossRef

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Effect of Adjuvant Chemotherapy on Stage II Colon Cancer: Analysis of Korean National Data: Min Ki Kim, Daeyoun David Won, Sun Min Park, Taejung Kim, Sung Ryong Kim, Seong Taek Oh, Seung Kook Sohn, Mi Yeon Kang, In Kyu Lee; Cancer Res Treat. 2018;50(4):1149-1163. Published online December 7, 2017; DOI: https://doi.org/10.4143/crt.2017.194

Abstract PDF Supplementary Material PubReader ePub

Purpose
Debates exist regarding the effectiveness of adjuvant chemotherapy for stage II colon cancer. This study aimed to investigate the current status of adjuvant chemotherapy and its impact on survival for Korean stage II colon cancer patients by analyzing the National Quality Assessment data.
Materials and Methods
A total of 7,880 patientswho underwent curative resection for stage II colon adenocarcinoma between January 2011 andDecember 2014 in Koreawere selected randomly as evaluation subjects for the quality assessment. The factors that influenced overall survival were identified. The high-risk group was defined as having at least one of the following: perforation/ obstruction, lymph node harvest less than 12, lymphovascular/perineural invasion, positive resection margin, poor differentiation, or pathologic T4 stage.
Results
The median follow-up period was 38 months (range, 1 to 63 months). Chemotherapy was a favorable prognostic factor for either the high- (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.38 to 0.59; p < 0.001) or low-risk group (HR, 0.74; 95% CI, 0.61 to 0.89; p=0.002) in multivariate analysis. This was also the case in patients over 70 years of age. The hazard ratio was significantly increased as the number of involved risk factors was increased in patients who didn’t receive chemotherapy. Adding oxaliplatin showed no difference in survival (HR, 1.36; 95% CI, 0.91 to 2.03; p=0.132).
Conclusion
Adjuvant chemotherapy can be recommended for stage II colon cancer patients, but the addition of oxaliplatin to the regimen must be selective.

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Colon cancer: the 2023 Korean clinical practice guidelines for diagnosis and treatment
Hyo Seon Ryu, Hyun Jung Kim, Woong Bae Ji, Byung Chang Kim, Ji Hun Kim, Sung Kyung Moon, Sung Il Kang, Han Deok Kwak, Eun Sun Kim, Chang Hyun Kim, Tae Hyung Kim, Gyoung Tae Noh, Byung-Soo Park, Hyeung-Min Park, Jeong Mo Bae, Jung Hoon Bae, Ni Eun Seo, Cha
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Factors Affecting Recurrence and Survival in Stage IIA Colon Cancer Patients
Mert Erciyestepe, Oğuzhan Selvi, Gülhan Dinç, Ahmet Emin Öztürk, Okan Aydın, Şermin Dinç Sonuşen, Tuğçe Kübra Güneş, Tugay Avcı, Sezai Vatansever, Emir Çelik, Muhammed Mustafa Atcı
Oncology.2024; 102(12): 1009. CrossRef
Postoperative chemotherapy use and survival in non-high-risk young and high-risk old-aged patients with stage II colon cancer
Tian Jin, Yingshuang Zhu, Wei Lu, Chenqin Le, Lijuan Wang, Qian Xiao, Kefeng Ding
Holistic Integrative Oncology.2023;[Epub] CrossRef
Risk factors for recurrence in elderly patients with stage II colorectal cancer: a multicenter retrospective study
Takuki Yagyu, Manabu Yamamoto, Akimitsu Tanio, Kazushi Hara, Ken Sugezawa, Chihiro Uejima, Kyoichi Kihara, Shigeru Tatebe, Yasuro Kurisu, Shunsuke Shibata, Toshio Yamamoto, Hiroshi Nishie, Setsujo Shiota, Hiroaki Saito, Takuji Naka, Kenji Sugamura, Kuniyu
BMC Cancer.2022;[Epub] CrossRef
The role of high-risk features in stage II colon cancer after surgical treatment
Patricio Bernardo Lynn, Garrett Yoon, Terry Li, Meng Cao, Michael Grieco, H. Leon Pachter, Russell C. Langan, Patrick Hilden, Joanna Sesti, Jason Maggi
Surgery Open Digestive Advance.2022; 7: 100054. CrossRef
Survival impact of adjuvant chemotherapy in patients with stage IIA colon cancer: Analysis of the National Cancer Database
Pietro Achilli, Jacopo Crippa, Fabian Grass, Kellie L. Mathis, Anne‐Lise D. D'Angelo, Mohamed A. Abd El Aziz, Courtney N. Day, William S. Harmsen, David W. Larson
International Journal of Cancer.2021; 148(1): 161. CrossRef
Associations of P Score With Real-World Survival Improvement Offered by Adjuvant Chemotherapy in Stage II Colon Cancer: A Large Population-Based Longitudinal Cohort Study
Qi Liu, Zezhi Shan, Dakui Luo, Sheng Zhang, Qingguo Li, Xinxiang Li
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Qi Wu, Zhiyuan Zhang, Yijiao Chen, Jiang Chang, Yudong Jiang, Dexiang Zhu, Ye Wei
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Yujin Lee, Inseok Park, Hyunjin Cho, Geumhee Gwak, Keunho Yang, Byung-Noe Bae
Annals of Coloproctology.2021; 37(5): 298. CrossRef
Elderly High-Risk Stage II Colorectal Cancer Patients: Candidates for Improving Outcome?
Min Ki Kim
Annals of Coloproctology.2021; 37(5): 267. CrossRef
Efficacy and tolerability of adjuvant therapy in ≥70-year-old patients with T3N0M0 colorectal cancer: An observational study
Abdullah Sakin, Nurgul Yasar, Suleyman Sahin, Serdar Arici, Saban Secmeler, Orcun Can, Caglayan Geredeli, Cumhur Demir, Sener Cihan
Journal of Oncology Pharmacy Practice.2020; 26(3): 619. CrossRef
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C. Simillis, H. K. S. I. Singh, T. Afxentiou, S. Mills, O. J. Warren, J. J. Smith, P. Riddle, M. Adamina, D. Cunningham, P. P. Tekkis
Colorectal Disease.2020; 22(10): 1231. CrossRef
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Chao Zhang, Songcheng Yin, Yuen Tan, Jinyu Huang, Pengliang Wang, Wenbin Hou, Zhe Zhang, Huimian Xu
American Journal of Clinical Oncology.2020; 43(4): 279. CrossRef
Mucinous Histology Might Be an Indicator for Enhanced Survival Benefit of Chemotherapy in Stage II Colon Cancer
Yong Huang, Kuanxue Ge, Guangshun Fu, Junfeng Chu, Wei Wei
Frontiers in Medicine.2020;[Epub] CrossRef
Re-Evaluation of the Survival Paradox Between Stage IIB/IIC and Stage IIIA Colon Cancer
Hongbo Li, Guangshun Fu, Wei Wei, Yong Huang, Zhenguang Wang, Tao Liang, Shuyun Tian, Honggang Chen, Wei Zhang
Frontiers in Oncology.2020;[Epub] CrossRef
Evaluating the Guiding Role of Elevated Pretreatment Serum Carcinoembryonic Antigen Levels for Adjuvant Chemotherapy in Stage IIA Colon Cancer: A Large Population-Based and Propensity Score-Matched Study
Qi Liu, Yongqiang Huang, Dakui Luo, Sheng Zhang, Sanjun Cai, Qingguo Li, Yanlei Ma, Xinxiang Li
Frontiers in Oncology.2019;[Epub] CrossRef
Adjuvant chemotherapy does not provide survival benefits to elderly patients with stage II colon cancer
Kil-yong Lee, Ji Won Park, Ki-young Lee, Sangsik Cho, Yoon-Hye Kwon, Min Jung Kim, Seung-Bum Ryoo, Seung-Yong Jeong, Kyu Joo Park
Scientific Reports.2019;[Epub] CrossRef
The use of chemotherapy in older patients with stage II and III colon cancer: Variation by age and era of diagnosis
Susan L. Green, David E. Dawe, Zoann Nugent, Winson Y. Cheung, Piotr M. Czaykowski
Journal of Geriatric Oncology.2018;[Epub] CrossRef

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Which Patients with Isolated Para-aortic Lymph Node Metastasis Will Truly Benefit from Extended Lymph Node Dissection for Colon Cancer?: Sung Uk Bae, Hyuk Hur, Byung Soh Min, Seung Hyuk Baik, Kang Young Lee, Nam Kyu Kim; Cancer Res Treat. 2018;50(3):712-719. Published online July 14, 2017; DOI: https://doi.org/10.4143/crt.2017.100

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Purpose
The prognosis of patientswith colon cancer and para-aortic lymph node metastasis (PALNM) is poor. We analyzed the prognostic factors of extramesenteric lymphadenectomy for colon cancer patients with isolated PALNM.
Materials and Methods
We retrospectively reviewed 49 patients with PALNM who underwent curative resection between October 1988 and December 2009.
Results
In univariate analyses, the 5-year overall survival (OS) and disease-free survival (DFS) rates were higher in patients with ≤ 7 positive para-aortic lymph node (PALN) (36.5% and 27.5%) than in those with > 7 PALN (14.3% and 14.3%; p=0.010 and p=0.027, respectively), and preoperative carcinoembryonic antigen (CEA) level > 5 was also correlated with a lower 5-year OS and DFS rate of 21.5% and 11.7% compared with those with CEA ≤ 5 (46.3% and 41.4%; p=0.122 and 0.039, respectively). Multivariate analysis found that the number of positive PALN (hazard ratio [HR], 3.291; 95% confidence interval [CI], 1.309 to 8.275; p=0.011) was an independent prognostic factor for OS and the number of positive PALN (HR, 2.484; 95% CI, 0.993 to 6.211; p=0.052) and preoperative CEA level (HR, 1.953; 95% CI, 0.940 to 4.057; p=0.073) were marginally independent prognostic factors for DFS. According to our prognostic model, the 5-year OS and DFS rate increased to 59.3% and 53.3%, respectively, in patients with ≤ 7 positive PALN and CEA level ≤ 5.
Conclusion
PALN dissection might be beneficial in carefully selected patients with a low CEA level and less extensive PALNM.

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Prognostic factors of para-aortic lymph node metastasis from colorectal cancer in highly selected patients undergoing para-aortic lymph node dissection
Shin Emoto, Yosuke Fukunaga, Manabu Takamatsu, Hiroshi Kawachi, Shuhei Sano, Tetsuro Tominaga, Toshiki Mukai, Tomohiro Yamaguchi, Toshiya Nagasaki, Takashi Akiyoshi, Tsuyoshi Konishi, Satoshi Nagayama, Masashi Ueno
Surgery Today.2024; 54(4): 356. CrossRef
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Rémi Grange, Pascal Rousset, Nicolas Williet, Mathias Guesnon, Laurent Milot, Guillaume Passot, Jean-Marc Phelip, Bertrand Le Roy, Olivier Glehen, Vahan Kepenekian
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Conor Aylward, Jawed Noori, Jack Tyrrell, Niall O'sullivan, Dara O. Kavanagh, John O. Larkin, Brian J. Mehigan, Paul H. McCormick, Michael E. Kelly
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Michelle Zhiyun Chen, Yeng Kwang Tay, Swetha Prabhakaran, Joseph C Kong
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Takayuki Okuno, Masaya Hiyoshi, Yuusuke Kyoden, Junji Yamamoto
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Jun Woo Bong, Sanghee Kang, Pyoungjae Park
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Maurizio Zizzo, Maria Pia Federica Dorma, Magda Zanelli, Francesca Sanguedolce, Maria Chiara Bassi, Andrea Palicelli, Stefano Ascani, Alessandro Giunta
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Jaram Lee, Hyeong-min Park, Soo Young Lee, Chang Hyun Kim, Hyeong Rok Kim
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G.N. Piozzi, H. Park, T.H. Lee, J.S. Kim, H.B. Choi, S.J. Baek, J.M. Kwak, J. Kim, S.H. Kim
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Guglielmo Niccolò Piozzi, Seon Hahn Kim
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Junichi Sakamoto, Heita Ozawa, Hiroki Nakanishi, Shin Fujita, Norikatsu Miyoshi
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International Journal of Colorectal Disease.2019; 34(6): 1121. CrossRef

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FGFR4 Arg388 Is Correlated with Poor Survival in Resected Colon Cancer Promoting Epithelial to Mesenchymal Transition: Sang Hee Cho, Chang Soo Hong, Hee Nam Kim, Min Ho Shin, Ka Rham Kim, Hyun Jeong Shim, Jun Eul Hwang, Woo Kyun Bae, Ik Joo Chung; Cancer Res Treat. 2017;49(3):766-777. Published online November 9, 2016; DOI: https://doi.org/10.4143/crt.2016.457

Abstract PDF PubReader ePub

Purpose
Fibroblast growth factor receptor 4 (FGFR4) plays an important role in cancer progression during tumor proliferation, invasion, and metastasis. This study evaluated the prognostic role of FGFR4 polymorphism in patientswith resected colon cancer, including the underlying mechanism.
Materials and Methods
FGFR4 polymorphism was characterized in patientswho received curative resection for stage III colon cancer. FGFR4-dependent signal pathways involving cell proliferation, invasion, and migration according to genotypes were also evaluated in transfected colon cancer cell lines.
Results
Among a total of 273 patients, the GG of FGFR4 showed significantly better overall survival than the AG or AA, regardless of adjuvant treatment. In the group of AG or AA, combination of folinic acid, fluorouracil, and oxaliplatin (FOLFOX) resulted in better survival than fluorouracil/leucovorin or no adjuvant chemotherapy. However, in GG, there was no difference among treatment regimens. Using multivariate analyses, the Arg388 carriers, together with age, N stage, poor differentiation, absence of a lymphocyte response, and no adjuvant chemotherapy, had a significantly worse OS than patients with the Gly388 allele. In transfected colon cancer cells, overexpression of Arg388 significantly increased cell proliferation and changes in epithelial to mesenchymal transition markers compared with cells overexpressing the Gly388 allele.
Conclusion
The Arg388 allele of FGFR4 may be a biomarker and a candidate target for adjuvant treatment of patients with resected colon cancer.

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Predictive significance of FGFR4 p.G388R polymorphism in metastatic colorectal cancer patients receiving trifluridine/tipiracil (TAS-102) treatment
Alessandro Ottaiano, Mariachiara Santorsola, Monica Ianniello, Anna Ceccarelli, Marika Casillo, Francesco Sabbatino, Nadia Petrillo, Marco Cascella, Francesco Caraglia, Carmine Picone, Francesco Perri, Roberto Sirica, Silvia Zappavigna, Guglielmo Nasti, G
Journal of Translational Medicine.2024;[Epub] CrossRef
Comprehensive analysis of the prognostic value and immune infiltration of FGFR family members in gastric cancer
Chengcheng Yang, Dingli Song, Fengyu Zhao, Jie Wu, Boxiang Zhang, Hong Ren, Qi Sun, Sida Qin
Frontiers in Oncology.2022;[Epub] CrossRef
Inhibition of FGF‐FGFR and VEGF‐VEGFR signalling in cancer treatment
Guihong Liu, Tao Chen, Zhenyu Ding, Yang Wang, Yuquan Wei, Xiawei Wei
Cell Proliferation.2021;[Epub] CrossRef
Every breath you take: Impacts of environmental dust exposure on intestinal barrier function–from the gut-lung axis to COVID-19
Meli’sa S. Crawford, Tara M. Nordgren, Declan F. McCole
American Journal of Physiology-Gastrointestinal and Liver Physiology.2021; 320(4): G586. CrossRef
FGFR4 Gly388Arg Polymorphism Reveals a Poor Prognosis, Especially in Asian Cancer Patients: A Meta-Analysis
Jung Han Kim, Soo Young Jeong, Hyun Joo Jang, Sung Taek Park, Hyeong Su Kim
Frontiers in Oncology.2021;[Epub] CrossRef
FGF/FGFR-Dependent Molecular Mechanisms Underlying Anti-Cancer Drug Resistance
Jakub Szymczyk, Katarzyna Sluzalska, Izabela Materla, Lukasz Opalinski, Jacek Otlewski, Malgorzata Zakrzewska
Cancers.2021; 13(22): 5796. CrossRef
Fibroblast growth factor receptor 4 increases epidermal growth factor receptor (EGFR) signaling by inducing amphiregulin expression and attenuates response to EGFR inhibitors in colon cancer
Chang‐Soo Hong, Eun‐Gene Sun, Ji‐Na Choi, Dae‐Hwan Kim, Jo‐Heon Kim, Kyung‐Hyun Ryu, Hyun‐Jeong Shim, Jun‐Eul Hwang, Woo‐Kyun Bae, Hyeong‐Rok Kim, Kyung Keun Kim, Chaeyong Jung, Ik‐Joo Chung, Sang‐Hee Cho
Cancer Science.2020; 111(9): 3268. CrossRef
Mahanine induces apoptosis, cell cycle arrest, inhibition of cell migration, invasion and PI3K/AKT/mTOR signalling pathway in glioma cells and inhibits tumor growth in vivo
Maohua Chen, Xiangqian Yin, Chuan Lu, Xiandong Chen, Huajun Ba, Jianyong Cai, Jun Sun
Chemico-Biological Interactions.2019; 299: 1. CrossRef
Fibroblast growth factor receptor 4 (FGFR4) as detected by immunohistochemistry is associated with postoperative residual disease in ovarian cancer
Sabine Heublein, Michael S. Anglesio, Frederik Marmé, Stefan Kommoss
Journal of Cancer Research and Clinical Oncology.2019; 145(9): 2251. CrossRef
TAp73 inhibits cell invasion and migration by directly activating KAI1 expression in colorectal carcinoma
Woo-Kyun Bae, Chang-Soo Hong, Mi-Ra Park, Eun-Gene Sun, Ji-Hee Lee, Keunsoo Kang, Kyung-Hyun Ryu, Hyun-Jeong Shim, Jun-Eul Hwang, Sang-Hee Cho, Ik-Joo Chung
Cancer Letters.2018; 415: 106. CrossRef
The FGFR4-388arg Variant Promotes Lung Cancer Progression by N-Cadherin Induction
Álvaro Quintanal-Villalonga, Laura Ojeda-Márquez, Ángela Marrugal, Patricia Yagüe, Santiago Ponce-Aix, Ana Salinas, Amancio Carnero, Irene Ferrer, Sonia Molina-Pinelo, Luis Paz-Ares
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Effects of FGFR gene polymorphisms on response and toxicity of cyclophosphamide-epirubicin-docetaxel-based chemotherapy in breast cancer patients
Lu Chen, Huijie Qi, Liudi Zhang, Haixia Li, Jie Shao, Haifei Chen, Mingkang Zhong, Xiaojin Shi, Ting Ye, Qunyi Li
BMC Cancer.2018;[Epub] CrossRef

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Dose KRAS Mutation Status Affect on the Effect of VEGF Therapy in Metastatic Colon Cancer Patients?: Seung Tae Kim, Kyong Hwa Park, Sang Won Shin, Yeul Hong Kim; Cancer Res Treat. 2014;46(1):48-54. Published online January 15, 2014; DOI: https://doi.org/10.4143/crt.2014.46.1.48

Abstract PDF PubReader ePub

PURPOSE
Mutations affecting the KRAS gene are an established negative predictor for anti-epidermal growth factor receptor (anti-EGFR) therapies in metastatic colorectal cancer (CRC). However, the role of KRAS mutation as a biomarker for anti-vascular endothelial growth factor (VEGF) remains controversial.
MATERIALS AND METHODS
We analyzed retrospective data from 32 CRC patients who were available for KRAS mutation status and received cytotoxic chemotherapy plus bevacizumab as a first-line therapy. Six of 32 patients received anti-EGFR therapies. We used KRAS mutation status as a predictive or prognostic factor in CRC patients receiving bevacizumab.
RESULTS
We observed mutations in KRAS in 59.4% of patients. Bevacizumab was used in combination with oxaliplatin based regimens. There was no significant difference for progression free survival (PFS) and overall survival (OS) in patients with oxaliplatin based cytotoxic chemotherapy plus bevacizumab according to the status of KRAS mutation. After first-line therapy, 28 patients (87.5%) received second-line therapy. In univariate analysis, KRAS mutations did not have a major prognostic value for PFS (hazard ratio, 1.007; 95% confidence interval [CI], 0.469 to 2.162; p>0.05) or OS (hazard ratio, 0.548; 95% CI, 0.226 to 1.328; p>0.05). In addition, anti-EGFR therapies did not affect the impact on OS.
CONCLUSION
KRAS mutation is neither a predictive for bevacizumab nor a prognostic for OS in CRC patients receiving anti-VEGF therapy.

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The KRAS-Mutant Consensus Molecular Subtype 3 Reveals an Immunosuppressive Tumor Microenvironment in Colorectal Cancer
Pariyada Tanjak, Amphun Chaiboonchoe, Tharathorn Suwatthanarak, Onchira Acharayothin, Kullanist Thanormjit, Jantappapa Chanthercrob, Thanawat Suwatthanarak, Bundit Wannasuphaphol, Kemmapon Chumchuen, Bhoom Suktitipat, Somponnat Sampattavanich, Krittiya Ko
Cancers.2023; 15(4): 1098. CrossRef
Evaluation of the Prognostic Value of Low-Frequency KRAS Mutation Detection in Circulating Tumor DNA of Patients with Metastatic Colorectal Cancer
Chien-Yu Lin, Ming-Yin Shen, William Tzu-Liang Chen, Chin-An Yang
Journal of Personalized Medicine.2023; 13(7): 1051. CrossRef
Advances in Tumor-Stroma Interactions: Emerging Role of Cytokine Network in Colorectal and Pancreatic Cancer
Chiara Bazzichetto, Fabiana Conciatori, Italia Falcone, Francesco Cognetti, Michele Milella, Ludovica Ciuffreda
Journal of Oncology.2019; 2019: 1. CrossRef
Role of RAS mutation status as a prognostic factor for patients with advanced colorectal cancer treated with first-line chemotherapy based on fluoropyrimidines and oxaliplatin, with or without bevavizumab: A retrospective analysis
Javier Garde Noguera, Eloisa Jantus-Lewintre, Mireia Gil-Raga, Elena Evgenyeva, Sonia Maciá Escalante, Antonio Llombart-Cussac, Carlos Camps Herrero
Molecular and Clinical Oncology.2017; 6(3): 403. CrossRef
MEK inhibitor can reverse the resistance to bevacizumab in A549 cells harboring Kirsten rat sarcoma oncogene homolog mutation
Yuan Wang, Ping Yan, Zhentao Liu, Xiaodan Yang, Yaping Wang, Zhirong Shen, Hua Bai, Jie Wang, Zhijie Wang
Thoracic Cancer.2016; 7(3): 279. CrossRef
Medullary carcinoma of the colon: can the undifferentiated be differentiated?
Anne-Marie Kanstrup Fiehn, Morten Grauslund, Anders Glenthøj, Linea Cecilie Melchior, Ben Vainer, Gro Linno Willemoe
Virchows Archiv.2015; 466(1): 13. CrossRef
Efficacy of combination chemotherapy using a novel oral chemotherapeutic agent, TAS-102, together with bevacizumab, cetuximab, or panitumumab on human colorectal cancer xenografts
Hiroshi Tsukihara, Fumio Nakagawa, Kazuki Sakamoto, Keiji Ishida, Nozomu Tanaka, Hiroyuki Okabe, Junji Uchida, Kenichi Matsuo, Teiji Takechi
Oncology Reports.2015;[Epub] CrossRef
CSBF/C10orf99, a novel potential cytokine, inhibits colon cancer cell growth through inducing G1 arrest
Wen Pan, Yingying Cheng, Heyu Zhang, Baocai Liu, Xiaoning Mo, Ting Li, Lin Li, Xiaojing Cheng, Lianhai Zhang, Jiafu Ji, Pingzhang Wang, Wenling Han
Scientific Reports.2014;[Epub] CrossRef

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A Retrospective Study of First-Line Combination Chemotherapy in Advanced Colorectal Cancer: A Korean Single-Center Experience: Soon Il Lee, Se Hoon Park, Do Hyoung Lim, Keon Woo Park, Jeeyun Lee, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Won Ki Kang; Cancer Res Treat. 2011;43(2):96-101. Published online June 30, 2011; DOI: https://doi.org/10.4143/crt.2011.43.2.96

Abstract PDF PubReader ePub

PURPOSE
Fluoropyrimidine-based combination chemotherapy, in combination with either oxaliplatin or irinotecan, has demonstrated efficacy and tolerability in treatment of advanced colorectal cancer (ACC).
MATERIALS AND METHODS
Between January 2006 and December 2007, a total of 478 ACC patients were treated with combination chemotherapy in first-line settings. Combination therapies included: 5-fluorouracil, folinic acid plus oxaliplatin (FOLFOX, n=172), 5-fluorouracil, folinic acid plus irinotecan (FOLFIRI, n=95), capecitabine plus oxaliplatin (XELOX, n=155), and capecitabine plus irinotecan (XELIRI, n=56). FOLFOX and FOLFIRI were repeated every 2 weeks, whereas XELOX and XELIRI were repeated every 3 weeks until occurrence of disease progression or unacceptable toxicity, or until a patient chose to discontinue treatment.
RESULTS
The median age was 58 years (range, 19 to 84 years) and the median chemotherapy durations for FOLFOX, FOLFIRI, XELOX, and XELIRI were 4.9, 4.5, 5.7, and 5.4 months, respectively. Combination chemotherapy regimens were generally well tolerated. The estimated median progression-free-survival (PFS) for all patients was 6.8 months (95% confidence interval, 6.3 to 7.3 months). No statistically significant difference in PFS was found among regimens used as first-line chemotherapy. Sixty percent (n=290) of patients received second or further lines of therapy after failure.
CONCLUSION
Fluoropyrimidine-based combination chemotherapy regimens appear to be equally active and tolerable as first-line therapy for ACC.

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Nineteen-year, real-world experience of first-line combination chemotherapy in patients with metastatic colorectal cancer: a propensity score analysis from southern Thailand
Jirapat Wonglhow, Chirawadee Sathitruangsak, Arunee Dechaphunkul, Patrapim Sunpaweravong
Journal of International Medical Research.2023;[Epub] CrossRef
Polymorphisms in TYMS for Prediction of Capecitabine-Induced Hand-Foot Syndrome in Chinese Patients with Colorectal Cancer
Si-Qi Dong, Tong-Min Wang, Jiang-Bo Zhang, Yong-Qiao He, Wen-Qiong Xue, Zi-Yi Wu, Da-Wei Yang, Lian-Jing Cao, Jing-Wen Huang, Xi-Zhao Li, Pei-Fen Zhang, Xiao-Hui Zheng, Wei-Hua Jia
Cancer Research and Treatment.2021; 53(3): 724. CrossRef

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Clinicopathologic Characteristics, Surgical Treatment and Outcomes for Splenic Flexure Colon Cancer: Chan Wook Kim, Ui Sup Shin, Chang Sik Yu, Jin Cheon Kim; Cancer Res Treat. 2010;42(2):69-76. Published online June 30, 2010; DOI: https://doi.org/10.4143/crt.2010.42.2.69

Abstract PDF PubReader ePub

Purpose

This current study examined the clinicopathologic characteristics of patients with splenic flexure (SF) colon cancer and the association with the surgical outcomes to find the optimal procedure to treat this malady.

Materials and Methods

A total of 167 operated patients with SF colon cancer were consecutively recruited between 1993 and 2003. The clinicopathological, operative and survival data was reviewed and analyzed.

Results

For the SF colon cancer patients, the proportion of males was higher than that for the right-sided colon patients or the sigmoid-descending junction & sigmoid (SD & S) colon patients (p≤0.05, respectively) and the age at the time of diagnosis was younger (p≤0.05). Obstruction was more frequent in the patients with SF colon cancer than that for the patients with colon cancer at other sites (p≤0.001). The incidence of mucinous adenocarcinoma for the SF patients was similar to that for the patients with right-sided colon cancer, but it was higher than that for the patients with SD & S colon cancer (11.4% vs. 6.5%, p=0.248 or 2.5%, respectively, p=0.001). Disease-free and overall survival did not differ between the patients who underwent a left hemicolectomy and extended surgery such as combined splenectomy or subtotal colectomy. Multivariate analysis showed that old age (≥60 years) and a N1-2 and M1 status were the independent risk factors for overall survival.

Conclusion

The SF colon cancers exhibited exclusively different characteristics as compared to colon cancers at other site colon cancers. It appears that left hemicolectomy was generally sufficient for a satisfactory oncological outcome, obviating concurrent splenectomy.

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Clinical Significance of Lymph Node Micrometastasis in Stage I and II Colon Cancer: Sun Jin Park, Kil Yeon Lee, Si Young Kim; Cancer Res Treat. 2008;40(2):75-80. Published online June 30, 2008; DOI: https://doi.org/10.4143/crt.2008.40.2.75

Abstract PDF PubReader ePub

Purpose

A 25% rate of recurrence after performing complete resection in node-negative colon cancer patients suggests that their nodal staging is frequently suboptimal. Moreover, the value of occult cancer cells in tumor-free lymph nodes still remains uncertain. The authors evaluated the prognostic significance of the pathologic parameters, including the lymph node occult disease (micrometastases) detected by immunohistochemistry, in patients with node-negative colon cancer.

Materials and Methods

The study included 160 patients with curatively resected stage I or II colon cancer and they were without rectal cancer. 2852 lymph nodes were re-examined by re-do hematoxylin and eosin (H-E) staining and immunohistochemical staining. The detection rates were compared with the clinicopathologic characteristics and with the cancer-specific survival.

Results

Occult metastases were detected in 8 patients (5%). However, no clinicopathologic parameter was found to be correlated with the presence of micrometastasis. Twenty patients developed recurrence at a median follow-up of 45.7 months: 14 died of colon cancer and 9 died from noncancer-related causes. Univariate analysis showed that lymphatic invasion and the number of retrieved lymph nodes significantly influenced survival, and multivariate analysis revealed that the stage, the number of retrieved lymph nodes and lymphatic invasion were independently related to the prognosis.

Conclusions

Inadequate lymph node retrieval and lymphatic invasion were found to be associated with a poorer outcome for node-negative colon cancer patients. The presence of immunostained tumors cells in pN0 lymph nodes was found to have no significant effect on survival, but these tumor were identified by re-do H-E staining. Maximal attention should be paid to the total number of lymph nodes that are retrieved during surgery for colon cancer patients.

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Review Article

Tumor Angiogenesis: Initiation and Targeting - Therapeutic Targeting of an FGF-Binding Protein, an Angiogenic Switch Molecule, and Indicator of Early Stages of Gastrointestinal Adenocarcinomas -: Elena Tassi, Anton Wellstein; Cancer Res Treat. 2006;38(4):189-197. Published online December 31, 2006; DOI: https://doi.org/10.4143/crt.2006.38.4.189

Abstract PDF PubReader ePub

Tumor angiogenesis has been related to the initiation as well as progression toward more aggressive behavior of human tumors. In particular, the activity of angiogenic factors is crucial for tumor progression. We previously characterized a secreted fibroblast growth factor-binding protein (FGF-BP) as a chaperone molecule, which binds to various FGFs, enhances FGF-mediated biochemical and biologic events and importantly is a crucial rate-limiting factor for tumor-dependent angiogenesis. We generated monoclonal antibodies that target FGF-BP protein and used them as a tool to evaluate frequency and pattern of FGF-BP expression during the malignant progression of pancreas and colorectal carcinoma in archival tissue samples. We found that FGF-BP is dramatically upregulated during the initiation of colorectal and pancreatic adenocarcinoma. Crucial genetic events underlying the initiation and progression of colorectal and pancreatic adenocarcinoma with a particular focus on the modulation of angiogenesis and antiangiogenic therapies are discussed. We propose that the upregulation of the secreted FGF-BP protein during early phases of pancreas and colon cancer could make this protein a possible serum marker indicating the presence of high-risk premalignant lesions. Furthermore, the biological activity of FGF-BP is neutralized by monoclonal antibodies suggesting the potential for antibody-based therapeutic targeting.

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