Cancer Research and Treatment

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

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

12,829 View
250 Download
13 Web of Science
12 Crossref

Case Reports

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

Abstract PDF PubReader ePub

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

A Case of Synchronous Gastric Non - Hodgkin's Lymphoma and Renal Cell Carcinoma: Je Jung Lee, Moo Rim Park, Young Eun Joo, Young Jin Kim, Hyeoung Joon Kim, Chan Choi, Ik Joo Chung; J Korean Cancer Assoc. 1999;31(3):635-640.

Abstract PDF: We report a 58-year-old man who developed synchronous gastric non-Hodgkin`s lymphoma (NHL) and renal cell carcinoma. He presented with epigastric discomfort for 2 months. Endoscopic finding of the stomach disclosed a large inegular ulceration with nodular margin on the upper body. Constrast enhanced CT scan of the abdomen showed an ulceration and focal wall thickening in the greater curvature side of stomach, and an enhanced bulging mass in the left kidney incidentally. The tissue obtained by radical proximal gastrectomy and nephrectomy showed diffuse large B-cell lymphoma on stomach and chromophobic type of renal cell carcinoma on kidney. To our knowledge, this is the first report of synchronous gastric NHL and renal cell carcinoma in Korea.

2,703 View
13 Download

Original Articles

Multidrug Resistance ( MDR 1 ) Gene Expression in Adult Acute Leukemia : Espression of P-glycoprotein and MDR 1 mRNA and its implication on clinical outcome in adult: Hyeoung Joon Kim, Ik Joo Chung, Jae Sung Seo, Keyong Sang Choi, Moo Rim Park, Kang Woo Baek, Youl Bae; J Korean Cancer Assoc. 1995;27(6):1017-1030.

Abstract PDF: Resistance to multiple chemotherapeutic agents is mainly related to the production of P- glycoproteins, a transmembrane drug efflux pump that is encoded by the multidrug resistance(MDR) gene, MDR I. To investigate whether MDR 1 could be involved in clinical resistance to chemotherapy in adult acute leukemias, We have analyzed prospectively 39 samples from 32 patients(27 at presentation, 5 after relapse) with acute leukemia for the evaluation of overexpression of MDR 1 mRNA and P-glycoprotein by using polymerase chain reactions(PCR) and flow cytometric assay, respectively. The induction rate of first complete remission differed between MDR 1 mRNA-positive and negative groups(37% v 84%, respectively; p=0.02). The survival rate(Kaplan-Meier method) in MDR 1 mRNA negative group was significantly higher than that in MDR 1 mRNA positive group(p=0.02). These results suggest that PCR assay of MDR 1 mRNA is a convenient method to detect expression of MDR 1 gene, and it may be a prognostic factor in the treatment of acute leukemia.

2,268 View
12 Download

Clinical Results of Allogeneic Bone Marrow Transplantation in Adults ( 2 ) : 1992 ~ 1995: Seok Goo Cho, Ik Joo Chung, Jung Hyun Choi, jing Hong You, Dogn Wook Kim, Chi Hwa Han, Woo Sung Min, Whan Sik Sin, Chong Won Park, Cjun Choo Kim, Dong Jip Kim, In Ah Kim, Su Mi Chung, Ihl Bhong Choi; J Korean Cancer Assoc. 1996;28(2):308-316.

Abstract PDF: Allogeneic bone marrow transplantation has been accepted as a powerful therapeutic modality to overcome for successfull clinical reuslts in malignant hematologic disease and severe aplastic anemia in spite of various barriers. We analysed 62 patients who had been admitted to Catholic BMT Center and have performed since malignant hematologic disesaes and severe aplastic anemia were determined to be the subject of National Public Health Care Program(between Oct. l992 and Mar. 1995). Number of patients with acute myelogenous leukemia(AML), acute lymphoblastic leukemia(ALL), chronic myelogenous leukemia(CML) and severe aplastic anemia(SAA) were 17, 4, 21, 20 respectively. We have used pretransplant conditionig regimens which were consisted of total body irradiation(TBI, fractionated 1320 cGy) and cyclophosphamide(CY, 120mg/kg) in leukemic disease(39/42) and anti-thymocyte globulin(ATG, 1.5 vial/10kg, Pasteur Merieux), CY(200mg/kg) and procar- baziine(6.25 mg/kg for 6 days, rutulard, Roche) in SAA(17/20). Cyclosporin A and short course methotrexate were used to prevent graft-versus-host disease(GVHD). Disease-free overall survival rate was 71% in aute leukemia, 67% in CML and 85% in SAA respectively. Maior complications were acute GVHD<35% grade I-IV among them, grade III-IV 14.5%),CMV antigenemia(l1.2%), herpes zoster(9.6%), veno-occlussive disease(8%), TTP-like syndrome(4.8%), chronic GVHD(3%) and interstitial pneumonia(1.6%). Major causes of death were leukemic relapse(9.7%), primary engraftment failure/rejection(6.5%), acute GVHD(3%) and TTP-like syndrome(3%). We suggest again that allogeneic BMT should be considered as the effective therapeutic modality to cure malignant hematologic diseases and aplastic anemia. For the purpose of obtaining better clinical outcome of allogeneic BMT, it should be early performed as soon as possible in clinial course.

2,257 View
14 Download

Autologous Bone Marrow Transplantation for Acute Myeloid Leukemia in First Remission ; Purging with hyperthermia and ether-lipid in vitro: Woo Sung Min, Seok Goo Cho, Ik Joo Chung, Dong Wook Kim, Chi Wha Han, Choon Choo Kim, Dong Jip Kim; J Korean Cancer Assoc. 1996;28(4):670-678.

Abstract PDF: From January 1992 to March 1995, 11 patients with acute myelagenous leukemia in the first remission in whom successfully hemopoiesis recovered after infusing autologous marrow stem cells purged by hyperthermia and ether-lipid. The median age of them was 29 years(rang l6 to 47). There were 5 males and 6 females. According to FAB classification, M1: 4, M3: 3, M4: 2 and M5: 2. All patients received two or three intensification chemotherapy after the first remission to make minimal residual disease. The median interval between achieving first remission and auto-grafting was 6.7 months (rang 4.5 to 10.5). Of the 11 patients, 7 patients received condition regimens that included total body irradiation and 4 patients received various combination of cytotoxic drugs. The marrow stem cells were harvested and treated with hyperthermia (4l¡ÆC) for one hour with 45 ￥ig/ml of ether-lipid. Median follow up was 24 months (rang 8 to 35), Minimum follow up was 13 months. The procedure related death was one case with Aspergillus pneumonia. The hematopoietic recovery of 10 patients was prompt with normal trilineage regeneration without any life-threatening complication. The median number of days, after the first marrow infusion, to achieve a total neutrophil count > 0.5 x l08/1, was 24 (range 10 to 41) and the median number of days to achieve platelet count of > 50 x 108/1, unsupported by platelet transfusion was 5l (range 12 to 250). The probability of disease-free survival(DFS) is 54% at 3 years. Four patients relapsed at 6.7.11. and 24 month post-ABMT. Eventhough the number of patients and the observation period were short, the autologous marrow transplantation with purged by hyperthermia and ether-lipid seems to be acceptable for the patients with AML as a regimen of the late intensification.

2,439 View
16 Download

CD34+ Selected Peripheral Blood Stem Cell Transplantation: Hoon Kook, Hyeoung Joon Kim, Jin Soo Hwang, Keun Mo Kim, Keun Mo Kim, Ik Joo Chung, Tai Ju Hwang; J Korean Cancer Assoc. 1996;28(5):910-921.

Abstract PDF: The CD34 antigen is a 115 kDa glycoprotein that marks 1%-4% of human bone marrow cells, including virtually all committed progenitor cells and long-term reconstituting stem cells. The selection of CD34+ cells may be useful in several areas of clinical stem cell transplantation, including purging of tumor cells, T cell depletion, stem cell expansion and gene therapy. Using immunomagnetic beads method (Isolex-50TM), we report hereby the first two Korean experiences of CD34+ selected peripheral blood stem cell (PBSC) transplantations. As a mean of tumor cell purging, CD34+ cells were positively selected from mobilized PBPCs and infused to a 5-year-old girl with a relapsed stage IV neuroblastoma with resultant early short-term trilineage hematopoietic recovery. In the second patient with chronic myelogenous leukemia who showed poor graft function after having underwent an initial partially-matched bone marrow transplant, CD34+ selected allogeneic PBSC transplantation was attempted to reduce the likelihood of inducing graft-versus-host disease. Augmentation of marrow function was noted with infused PBSCs which were depleted of T cells to the degree of log3.65. As CD34+ selected PBSCs are capable of restoring hematopoietic recovery after high dose therapy, further development of selection technique to ensure high purging efficiency without significant loss of stem cells and further identification of best mobilizing and conditioning regimens are required in this new field of clinical transplantation.

2,638 View
19 Download

Engraftment Syndrome after Peripheral Blood Stem Cell Auto - transplantation - A report of the case -: Bong Seok Choi, Yeo Hyeon Ahn, You Jeong, Ik Joo Chung, Hyeoung Joon Kim, Hoon Kook, Tai Ju Hwang; J Korean Cancer Assoc. 1996;28(5):921-927.

Abstract PDF: We experienced two cases of engraftment syndrome (ES) in a 17-year-old boy with malignant lymphoma and in a 53-year-old female patient with small cell lung cancer following peripheral blood stem cell auto-transplantation. ES is a reproducible clinical constellation of fever, skin rash, capillary leak and pulmonary infiltrates without infection, characteristically observed during engraftment in patients undergoing autoglogous bone marrow or peripheral stem cell transplantation. The incidence of ES has been reported to be about 60%. The early recognition of ES followed by administration of steroids might obviate the unnecessary use of antibiotics and help improve clinical manifestaions in the critical post-transplant neutropenic period.

2,420 View
16 Download

First
Prev
Page of 1
Next
Last

Search