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Original Article
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
AbstractAbstract PDFPubReaderePub
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.

Citations

Citations to this article as recorded by  
  • 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
    Scientific Reports.2018;[Epub]     CrossRef
  • 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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  • 13 Web of Science
  • 12 Crossref
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Case Report
Reversible Proximal Renal Tubular Dysfunction after One-Time Ifosfamide Exposure
Young Il Kim, Ju Young Yoon, Jun Eul Hwang, Hyun Jeong Shim, Woo Kyun Bae, Sang Hee Cho, Ik-Joo Chung
Cancer Res Treat. 2010;42(4):244-246.   Published online December 31, 2010
DOI: https://doi.org/10.4143/crt.2010.42.4.244
AbstractAbstract PDFPubReaderePub

The alkylating agent ifosfamide is an anti-neoplastic used to treat various pediatric and adult malignancies. Its potential urologic toxicities include glomerulopathy, tubulopathy and hemorrhagic cystitis. This report describes a case of proximal renal tubular dysfunction and hemorrhagic cystitis in a 67-year-old male given ifosfamide for epitheloid sarcoma. He was also receiving an oral hypoglycemic agent for type 2 diabetes mellitus and had a baseline glomerular filtration rate of 51.5 mL/min/1.73 m2. Despite mesna prophylaxis, the patient experienced dysuria and gross hematuria after a single course of ifosfamide plus adriamycin. The abrupt renal impairment and serum/urine electrolyte imbalances that ensued were consistent with Fanconi's syndrome. However, normal renal function and electrolyte status were restored within 14 days, simply through supportive measures. A score of 8 by Naranjo adverse drug reaction probability scale indicated these complications were most likely treatment-related, although they developed without known predisposing factors. The currently undefined role of diabetic nephropathy in adult ifosfamide nephrotoxicity merits future investigation.

Citations

Citations to this article as recorded by  
  • Ifosfamide-induced nephrotoxicity in oncological patients
    Juan Eduardo Quiroz-Aldave, María Del Carmen Durand-Vásquez, Freddy Shanner Chávez-Vásquez, Alexandra Noelia Rodríguez-Angulo, Sonia Elizabeth Gonzáles-Saldaña, Carlos César Alcalde-Loyola, Julia Cristina Coronado-Arroyo, Francisca Elena Zavaleta-Gutiérre
    Expert Review of Anticancer Therapy.2024; 24(1-2): 5.     CrossRef
  • Conditioning Regimens for Relapsed/Refractory Lymphoma Patients Undergoing Autologous Stem Cell Transplantation: BEAM Versus High Dose ICE
    Ahmet Kursad Gunes, Simten Dagdas, Funda Ceran, Mehmet Ali Ucar, Mesude Falay, Cenk Sunu, Meltem Ayli, Nurullah Zengin, Gulsum Ozet
    Indian Journal of Hematology and Blood Transfusion.2021; 37(1): 82.     CrossRef
  • Cancer treatment-induced bone loss (CTIBL): Pathogenesis and clinical implications
    S. D’Oronzo, S. Stucci, M. Tucci, F. Silvestris
    Cancer Treatment Reviews.2015; 41(9): 798.     CrossRef
  • Tubulointerstitial nephritis and cancer chemotherapy: update on a neglected clinical entity
    M. Airy, R. Raghavan, L. D. Truong, G. Eknoyan
    Nephrology Dialysis Transplantation.2013; 28(10): 2502.     CrossRef
  • 8,339 View
  • 57 Download
  • 4 Crossref
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Original Article
Coexisting with Clonal Evolution and BCR-ABL Mutant in CML Patients Treated with Second-generation Tyrosine Kinase Inhibitors Predict the Discrepancy of in vitro Drug Sensitivity
Jae-Sook Ahn, Yeo-Kyeoung Kim, Se Ryeon Lee, Li Yu, Deok-Hwan Yang, Sang-Hee Cho, Hyun Jeong Shim, Woo Kyun Bae, Je-Jung Lee, Ik-Joo Chung, Myung Gun Shin, Hyeoung-Joon Kim
Cancer Res Treat. 2010;42(1):37-41.   Published online March 31, 2010
DOI: https://doi.org/10.4143/crt.2010.42.1.37
AbstractAbstract PDFPubReaderePub
Purpose

Second-generation tyrosine kinase inhibitors (second TKIs) such as nilotinib and dasatinib control the activity of most ABL kinase domain mutations observed in patients with imatinib resistance. Although in vitro data show that both agents can inhibit all mutations except T315I, some discrepancies have been observed in a small subset of mutation clones. Cytogenetic clonal evolution is the important resistance mechanism of chronic myeloid leukemia (CML). Accordingly, we observed the clinical significance of coexisting with clonal evolution and BCR-ABL mutant in CML patients treated with second TKIs.

Materials and Methods

We monitored BCR-ABL transcript kinetics, interrelationship of clones expressing non-mutated and mutant transcripts and clonal aberrations within Philadelphia (Ph) positive and negative clones, respectively, in eight patients with CML receiving dasatinib or nilotinib for 3~41 months.

Results

Clinical responses were correlated with in vitro sensitivity of the BCR-ABL mutants to the second TKIs in four patients. Four patients showed resistance to the second TKIs as compared to in vitro observations; three of them developed chromosomal abnormalities in the Ph chromosome positive or negative metaphases. Another patient lost the original mutation but acquired a more resistant new mutation and became resistant to the second TKI.

Conclusion

Cytogenetic clonal evolution is an independent poor prognostic factor in CML, which could explain the onset of mechanisms for second TKIs resistance to ABL kinase domain mutations. The results indicate that an additional evaluation of chromosomal abnormalities is warranted when BCR-ABL mutants are more resistant than indicated by in vitro data.

Citations

Citations to this article as recorded by  
  • T315I – a gatekeeper point mutation and its impact on the prognosis of chronic myeloid leukemia
    Bushra Kaleem, Sadaf Shahab, Tahir Sultan Shamsi
    Advances in Laboratory Medicine / Avances en Medicina de Laboratorio.2024; 5(4): 412.     CrossRef
  • Impacto de la mutación T315I en el pronóstico de la leucemia mieloide crónica
    Bushra Kaleem, Sadaf Shahab, Tahir Sultan Shamsi
    Advances in Laboratory Medicine / Avances en Medicina de Laboratorio.2024; 5(4): 418.     CrossRef
  • BCR-ABL1 mutation development during first-line treatment with dasatinib or imatinib for chronic myeloid leukemia in chronic phase
    T P Hughes, G Saglio, A Quintás-Cardama, M J Mauro, D-W Kim, J H Lipton, M B Bradley-Garelik, J Ukropec, A Hochhaus
    Leukemia.2015; 29(9): 1832.     CrossRef
  • 10,708 View
  • 53 Download
  • 3 Crossref
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Case Report
Severe Hypothyroidism Induced by Thyroid Metastasis of Cholangiocarcinoma
Woo Kyun Bae, Hyun Jeong Shim, Yoo Duk Choi, Jin Woong Kim, Sang Hee Cho, Ho Cheol Kang, Ik Joo Chung
Cancer Res Treat. 2009;41(1):56-58.   Published online March 31, 2009
DOI: https://doi.org/10.4143/crt.2009.41.1.56
AbstractAbstract PDFPubReaderePub

We report a case of severe hypothyroidism in a cholangiocarcinoma patient with metastasis to the thyroid gland. A 58-year-old man was admitted for upper abdominal discomfort and multiple palpable neck nodules. Abdominal computed tomography (CT) demonstrated the presence of a 4.7-cm tumor in the right hepatic lobe, and core needle biopsy revealed it to be cholangiocarcinoma. Neck CT showed a diffuse, low attenuation thyroid gland, and fine-needle aspiration (FNA) demonstrated metastatic adenocarcinoma. Thyroid function tests were initially normal, but the size of the thyroid gland decreased and severe hypothyroidism developed after chemotherapy was implemented for cholangiocarcinoma. In a patient with malignant disease and a goiter, the possibility of a metastatic tumor involving the thyroid should be seriously considered. Metastatic thyroid cancer and thyroid dysfunction are probably infrequent, but diagnosis is important in the institution of appropriate therapy.

Citations

Citations to this article as recorded by  
  • The interplay between thyroid and liver: implications for clinical practice
    E. Piantanida, S. Ippolito, D. Gallo, E. Masiello, P. Premoli, C. Cusini, S. Rosetti, J. Sabatino, S. Segato, F. Trimarchi, L. Bartalena, M. L. Tanda
    Journal of Endocrinological Investigation.2020; 43(7): 885.     CrossRef
  • Metastasis to the Thyroid Gland: A Critical Review
    Iain J. Nixon, Andrés Coca-Pelaz, Anna I. Kaleva, Asterios Triantafyllou, Peter Angelos, Randall P. Owen, Alessandra Rinaldo, Ashok R. Shaha, Carl E. Silver, Alfio Ferlito
    Annals of Surgical Oncology.2017; 24(6): 1533.     CrossRef
  • Thyroid metastasectomy
    Pablo H. Montero, Tihana Ibrahimpasic, Iain J. Nixon, Ashok R. Shaha
    Journal of Surgical Oncology.2014; 109(1): 36.     CrossRef
  • Metastatic Carcinoma to the Thyroid Gland: A Single Institution 20-Year Experience and Review of the Literature
    Parnian Ahmadi Moghaddam, Kristine M. Cornejo, Ashraf Khan
    Endocrine Pathology.2013; 24(3): 116.     CrossRef
  • Thyroid gland metastasis arising from primary liver cholangiocarcinoma: The first case report involving surgical operation
    Min Ho Park, Jin Seong Cho, Ji Shin Lee, Hee Kyung Kim, Jung Han Yoon
    International Journal of Surgery Case Reports.2012; 3(2): 78.     CrossRef
  • Metastases to the Thyroid: A Review of the Literature from the Last Decade
    Alice Y. Chung, Thuy B. Tran, Kevin T. Brumund, Robert A. Weisman, Michael Bouvet
    Thyroid.2012; 22(3): 258.     CrossRef
  • Metastasis of Dermatofibrosarcoma from the Abdominal Wall to the Thyroid Gland: Case Report
    Alexander Kreze, Andrea Zápotocká, Tomáš Urbanec, Jiří Koskuba, Mikuláš Pura, Pavel Vítek, Pavol Praženica, Eva Traboulsi
    Case Reports in Medicine.2012; 2012: 1.     CrossRef
  • Solitary Extramedullary Plasmacytoma of the Thyroid Involved by Papillary Carcinoma: A Case Report and Review of the Literature
    Darren K. Patten, Maisam Fazel, Roberto Dina, Neil Tolley
    Endocrine Pathology.2011; 22(3): 155.     CrossRef
  • Thyroid Dysfunction Induced by Metastatic Thyroid Cancer: Report of Two Cases
    Kang Hee Ahn, Bo Kyung Choi, Won Jin Kim, Bo Gwang Choi, Yun Kyung Jeon, Sang Soo Kim, Soo Hyung Lee, Bo Hyun Kim, Yong Ki Kim, In Ju Kim
    Endocrinology and Metabolism.2010; 25(4): 370.     CrossRef
  • 9,405 View
  • 45 Download
  • 9 Crossref
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