Cancer Research and Treatment

Original Articles

Fibroblast Growth Factor Receptor 1 (FGFR1) Amplification Detected by Droplet Digital Polymerase Chain Reaction (ddPCR) Is a Prognostic Factor in Colorectal Cancers: Jeong Mo Bae, Xianyu Wen, Tae-Shin Kim, Yoonjin Kwak, Nam-Yun Cho, Hye Seung Lee, Gyeong Hoon Kang; Cancer Res Treat. 2020;52(1):74-84. Published online May 8, 2019; DOI: https://doi.org/10.4143/crt.2019.062

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to reveal the clinicopathological characteristics and prognostic implications associated with fibroblast growth factor receptor 1 (FGFR1) amplification in colorectal cancers (CRCs).
Materials and Methods
We measured the copy number of FGFR1 by droplet digital polymerase chain reaction (ddPCR), and analyzed the FGFR1 expression by immunohistochemistry, in 764 surgically resected CRCs (SNUH2007 dataset, 384 CRCs; SNUH Folfox dataset, 380 CRCs).
Results
CRCs with ≥ 3.3 copies of the FGFR1 gene were classified as FGFR1 amplified. FGFR1 amplification was found in 10 of the 384 CRCs (2.6%) in the SNUH2007 dataset, and in 28 of the 380 CRCs (7.4%) in the SNUH Folfox dataset. In the SNUH2007 dataset, there was no association between the FGFR1 copy number status and sex, gross appearance, stage, or differentiation. High FGFR1 expression was associated with female sex and KRAS mutation. At the molecular level, FGFR1 amplification was mutually exclusive with BRAF mutation, microsatellite instability, and MLH1 methylation, in both SNUH2007 and SNUH Folfox datasets. Survival analysis revealed that FGFR1 amplification was associated with significantly worse clinical outcome compared with no FGFR1 amplification, in both SNUH2007 and SNUH Folfox datasets. Within the SNUH2007 dataset, CRC patients with high FGFR1 expression had an inferior progression-free survival compared with those with low FGFR1 expression. The FGFR inhibitor, PD173074, repressed the proliferation of a CRC cell line overexpressing FGFR1, but not of cells with FGFR1 amplification.
Conclusion
FGFR1 amplification measured by ddPCR can be a prognostic indicator of poor clinical outcome in patients with CRCs.

Citations

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A panorama of colon cancer in the era of liquid biopsy
Sylvie Devalle, Veronica Aran, Cesar de Souza Bastos Júnior, Vera Lucia Pannain, Paulo Brackmann, Marcelo Leal Gregório, José Eduardo Ferreira Manso, Vivaldo Moura Neto
The Journal of Liquid Biopsy.2024; 4: 100148. CrossRef
Targeting FGFR1 by β,β-dimethylacrylalkannin suppresses the proliferation of colorectal cancer in cellular and xenograft models
Ran Zhao, Fanxiang Yin, Mangaladoss Fredimoses, Jianhua Zhao, Xiaorong Fu, Beibei Xu, Mengrui Liang, Hanyong Chen, Kangdong Liu, Mingjuan Lei, Kyle Vaughn Laster, Zhi Li, Joydeb Kumar Kundu, Zigang Dong, Mee-Hyun Lee
Phytomedicine.2024; 129: 155612. CrossRef
Single-center analysis of a real-world cohort of patients with metastatic urothelial carcinoma evaluated by NGS: molecular landscape and efficacy of targeted therapies
César Gutiérrez Pérez, Enrique Lastra Aras, Patricia Saiz López, Enrique García Toro, Carmen Blanco Abad, Inmaculada Rodríguez Ledesma, María Pumares González, Miriam Vela Domínguez, Noelia Espinosa Cabria, Guillermo Crespo Herrero
Clinical and Translational Oncology.2024;[Epub] CrossRef
Diphenyl urea‐benzylidene acetohydrazide hybrids as fibroblast growth factor receptor 1 inhibitors and anticancer agents
Heba T. Abdel‐Mohsen, Amira M. Nageeb, Iman A. Y. Ghannam
Drug Development Research.2024;[Epub] CrossRef
Clinical evaluation of a droplet digital PCR assay for detecting POLE mutations and molecular classification of endometrial cancer
Gilhyang Kim, Song Kook Lee, Dong Hoon Suh, Kidong Kim, Jae Hong No, Yong Beom Kim, Hyojin Kim
Journal of Gynecologic Oncology.2022;[Epub] CrossRef
Detection and Quantification of Stagonosporopsis cucurbitacearum in Seeds of Cucurbita maxima Using Droplet Digital Polymerase Chain Reaction
Sergio Murolo, Marwa Moumni, Valeria Mancini, Mohamed Bechir Allagui, Lucia Landi, Gianfranco Romanazzi
Frontiers in Microbiology.2022;[Epub] CrossRef
Fibroblast growth factor 2: Role in prenatal alcohol-induced stimulation of hypothalamic peptide neurons
Guo-Qing Chang, Nushrat Yasmin, Adam D. Collier, Olga Karatayev, Nailya Khalizova, Amanda Onoichenco, Milisia Fam, Avi S. Albeg, Samantha Campbell, Sarah F. Leibowitz
Progress in Neuro-Psychopharmacology and Biological Psychiatry.2022; 116: 110536. CrossRef
Copy Number Alterations as Novel Biomarkers and Therapeutic Targets in Colorectal Cancer
Elaine S. Tan, Todd C. Knepper, Xuefeng Wang, Jennifer B. Permuth, Liang Wang, Jason B. Fleming, Hao Xie
Cancers.2022; 14(9): 2223. CrossRef
Tumor-induced Osteomalacia: A Systematic Review and Individual Patient’s Data Analysis
Domenico Rendina, Veronica Abate, Giuseppe Cacace, Lanfranco D’Elia, Gianpaolo De Filippo, Silvana Del Vecchio, Ferruccio Galletti, Alberto Cuocolo, Pasquale Strazzullo
The Journal of Clinical Endocrinology & Metabolism.2022; 107(8): e3428. CrossRef
Indications of Genomic Abnormalities for Molecular Targeted Therapy in Colorectal Cancer
Koshi Mimori
Nippon Daicho Komonbyo Gakkai Zasshi.2022; 75(10): 449. CrossRef
Onco-ontogeny recapitulates phylogeny – a consideration
P. N. Plowman, C. E. Plowman
Oncogene.2021; 40(8): 1542. CrossRef
Integrating Multi–Omics Data for Gene-Environment Interactions
Yinhao Du, Kun Fan, Xi Lu, Cen Wu
BioTech.2021; 10(1): 3. 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
Fibroblast Growth Factor Receptors (FGFRs) and Noncanonical Partners in Cancer Signaling
Harriet R. Ferguson, Michael P. Smith, Chiara Francavilla
Cells.2021; 10(5): 1201. CrossRef
Identification of Prognostic Dosage-Sensitive Genes in Colorectal Cancer Based on Multi-Omics
Zhiqiang Chang, Xiuxiu Miao, Wenyuan Zhao
Frontiers in Genetics.2020;[Epub] CrossRef
Gene Expression Signature to Predict Prognosis and Adjuvant Chemosensitivity of Colorectal Cancer Patients

Jianxia Li, Jianwei Zhang, Huabin Hu, Yue Cai, Jiayu Ling, Zehua Wu, Yanhong Deng
Cancer Management and Research.2020; Volume 12: 3301. CrossRef
Identification of Genomic Alterations of Perineural Invasion in Patients with Stage II Colorectal Cancer

Hao Su, Chen Chang, Jiajie Hao, Xin Xu, Mandula Bao, Shou Luo, Chuanduo Zhao, Qian Liu, Xishan Wang, Zhixiang Zhou, Haitao Zhou
OncoTargets and Therapy.2020; Volume 13: 11571. CrossRef
Design, Synthesis and Biological Evaluation: 5-amino-1H-pyrazole-1- carbonyl derivatives as FGFR Inhibitors
Yan Zhang, Niefang Yu
Letters in Drug Design & Discovery.2020; 17(11): 1330. CrossRef

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Anti-cancer Effects of a Novel Quinoline Derivative 83b1 on Human Esophageal Squamous Cell Carcinoma through Down-Regulation of COX-2 mRNA and PGE₂: Ivan Ho Yuen Pun, Dessy Chan, Sau Hing Chan, Po Yee Chung, Yuan Yuan Zhou, Simon Law, Alfred King Yin Lam, Chung Hin Chui, Albert Sun Chi Chan, Kim Hung Lam, Johnny Cheuk On Tang; Cancer Res Treat. 2017;49(1):219-229. Published online July 18, 2016; DOI: https://doi.org/10.4143/crt.2016.190

Abstract PDF Supplementary Material PubReader ePub

Purpose
83b1 is a novel quinoline derivative that has been shown to inhibit cancer growth in human esophageal squamous cell carcinoma (ESCC). This study was conducted to comprehensively evaluate the cytotoxic effects of 83b1 on a series of ESCC cell lines and investigate the mechanisms by which 83b1 suppresses cancer growth based on molecular docking analysis.
Materials and Methods
A series of ESCC and nontumor immortalized cell lines were exposed to 83b1 and cisplatin (CDDP) in a dose-dependent manner, and the cytotoxicity was examined by a MTS assay kit. Prediction of the molecular targets of 83b1 was conducted by molecular docking analysis. Expression of cyclooxygenase 2 (COX-2) mRNA and COX-2–derived prostaglandin E2 (PGE2) were measured by quantitative real-time polymerase chain reaction and enzymelinked immuno-sorbent assay, respectively. In vivo anti-tumor effect was determined using a nude mice xenografted model transplanted with an ESCC cell line, KYSE-450.
Results
83b1 showed the significant anti-cancer effects on all ESCC cell lines compared to CDDP; however, 83b1 revealed much lower toxic effects on non-tumor cell lines than CDDP. The predicted molecular target of 83b1 is peroxisome proliferator-activated receptor delta (PPARδ), which is a widely known oncoprotein. Additionally the expression of COX-2 mRNA and COX-2–derived PGE2 were down-regulated by 83b1 in a dose-dependent manner in ESCC cell lines. Furthermore, 83b1 was shown to significantly reduce the tumor size in nude mice xenograft.
Conclusion
The results of this study suggest that the potential anti-cancer effects of 83b1 on human esophageal cancers occur through the possible oncotarget, PPARδ, and down-regulation of the cancer related genes and molecules.

Citations

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Synthesis and biological evaluation of novel 2-morpholino-4-anilinoquinoline derivatives as antitumor agents against HepG2 cell line
Ahmed Al-Sheikh, Malak A. Jaber, Hana'a Khalaf, Nour AlKhawaja, Duaa Abuarqoub
RSC Advances.2024; 14(5): 3304. CrossRef
Natural alkaloids as potential treatments for esophageal squamous-cell carcinoma: A comprehensive review
Eugene Jamot Ndebia, Gabriel Tchuente Kamsu
Gastroenterology & Endoscopy.2024; 2(3): 131. CrossRef
Arachidonic acid metabolism as a novel pathogenic factor in gastrointestinal cancers
Weiqin Lu, Aihemaitijiang Aihaiti, Paziliya Abudukeranmu, Yajun Liu, Huihui Gao
Molecular and Cellular Biochemistry.2024;[Epub] CrossRef
Downregulation of chemokine (C‑C motif) ligand 5 induced by a novel 8‑hydroxyquinoline derivative (91b1) suppresses tumor invasiveness in esophageal carcinoma
Johnny Tang, Dessy Chan, Po-Yee Chung, Yijiang Liu, Alfred Lam, Simon Law, Wolin Huang, Albert Chan, Kim-Hung Lam, Yuanyuan Zhou
International Journal of Molecular Medicine.2024;[Epub] CrossRef
Peroxisome proliferator-activated receptors regulate the progression and treatment of gastrointestinal cancers
Min Zhang, Shujie He
Frontiers in Pharmacology.2023;[Epub] CrossRef
Roles of Nuclear Receptors in Esophageal Cancer
Lihao Deng, Jiaxuan Liu, Wei-Dong Chen, Yan-Dong Wang
Current Pharmaceutical Biotechnology.2023; 24(12): 1489. CrossRef
Synthesis and biological activities of new phthalimide and thiazolidine derivatives
Flaviana A. Santos, Marcel L. Almeida, Vitor A. S. Silva, Douglas C. F. Viana, Michelly C. Pereira, André S. L. Lucena, Maira G. R. Pitta, Marina R. Galdino-Pitta, Moacyr J. B. de Melo Rêgo, Ivan da Rocha Pitta
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Role of Prostaglandin E2 in the Progression of Gastrointestinal Cancer
David Jay Wilson, Raymond N. DuBois
Cancer Prevention Research.2022; 15(6): 355. CrossRef
The Anticancer Effect of a Novel Quinoline Derivative 91b1 through Downregulation of Lumican
Yuanyuan Zhou, Zhongguo Zhou, Dessy Chan, Po yee Chung, Yongqi Wang, Albert Sun chi Chan, Simon Law, Kim hung Lam, Johnny Cheuk On Tang
International Journal of Molecular Sciences.2022; 23(21): 13181. CrossRef
Synthesis and biological evaluations of N′-substituted methylene-4-(quinoline-4-amino) benzoylhydrazides as potential anti-hepatoma agents
Baicun Li, Feifeng Zhu, Fengming He, Qingqing Huang, Xiaoguang Liu, Tong Wu, Taige Zhao, Yingkun Qiu, Zhen Wu, Yuhua Xue, Meijuan Fang
Bioorganic Chemistry.2020; 96: 103592. CrossRef
Feasibility of Repurposing Clioquinol for Cancer Therapy
Raheel Khan, Harras Khan, Yassen Abdullah, Q. Ping Dou
Recent Patents on Anti-Cancer Drug Discovery.2020; 15(1): 14. CrossRef
DFIQ, a Novel Quinoline Derivative, Shows Anticancer Potential by Inducing Apoptosis and Autophagy in NSCLC Cell and In Vivo Zebrafish Xenograft Models
Hurng-Wern Huang, Yung-Ding Bow, Chia-Yih Wang, Yen-Chun Chen, Pei-Rong Fu, Kuo-Feng Chang, Tso-Wen Wang, Chih-Hua Tseng, Yeh-Long Chen, Chien-Chih Chiu
Cancers.2020; 12(5): 1348. CrossRef
Reverse Screening Methods to Search for the Protein Targets of Chemopreventive Compounds
Hongbin Huang, Guigui Zhang, Yuquan Zhou, Chenru Lin, Suling Chen, Yutong Lin, Shangkang Mai, Zunnan Huang
Frontiers in Chemistry.2018;[Epub] CrossRef
The roles of the COX2/PGE2/EP axis in therapeutic resistance
Dali Tong, Qiuli Liu, Lin-ang Wang, Qiubo Xie, Jian Pang, Yiqiang Huang, Luofu Wang, Gaolei Liu, Dianzheng Zhang, Weihua Lan, Jun Jiang
Cancer and Metastasis Reviews.2018; 37(2-3): 355. CrossRef
Expression of Insulin-Like Growth Factor Binding Protein-5 (IGFBP5) Reverses Cisplatin-Resistance in Esophageal Carcinoma
Dessy Chan, Yuanyuan Zhou, Chung Hin Chui, Kim Hung Lam, Simon Law, Albert Sun-chi Chan, Xingshu Li, Alfred King-yin Lam, Johnny Cheuk On Tang
Cells.2018; 7(10): 143. CrossRef
Targeting DNA Binding for NF-κB as an Anticancer Approach in Hepatocellular Carcinoma
Po Chung, Pik Lam, Yuanyuan Zhou, Jessica Gasparello, Alessia Finotti, Adriana Chilin, Giovanni Marzaro, Roberto Gambari, Zhaoxiang Bian, Wai Kwok, Wai Wong, Xi Wang, Alfred Lam, Albert Chan, Xingshu Li, Jessica Ma, Chung Chui, Kim Lam, Johnny Tang
Cells.2018; 7(10): 177. CrossRef

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Clinical Significance of Tyrosine Hydroxylase mRNA Transcripts in Peripheral Blood at Diagnosis in Patients with Neuroblastoma: Na Hee Lee, Meong Hi Son, Young Bae Choi, Eunsang Yi, Ji Won Lee, Keon Hee Yoo, Ki Woong Sung, Hong Hoe Koo; Cancer Res Treat. 2016;48(4):1399-1407. Published online March 24, 2016; DOI: https://doi.org/10.4143/crt.2015.481

Abstract PDF PubReader ePub

Purpose
The purpose of this study is to investigate the clinical significance of tyrosine hydroxylase (TH) expression in peripheral blood (PB) at diagnosis in patients with neuroblastoma.
Materials and Methods
TH mRNA expression in PB was measured by reverse transcription quantitative real-time polymerase chain reaction in 210 patients who were newly diagnosed with neuroblastoma from July 2005 to June 2015 and the clinical significance of TH expression in PB at diagnosis was evaluated.
Results
TH expression was positive in 60 patients (28.6%). Fifty of 60 TH-positive patients had metastatic tumors and the remaining 10 had localized tumors. TH expression was associated with high-risk features (i.e., advanced stage, older age, unfavorable pathology, and MYCN amplification) at diagnosis. Among TH-positive patients, higher TH expression level was observed in high-risk patients than in low- or intermediate-risk patients (p=0.035). The probability of 5-year progression-free survival (PFS) was lower in TH-positive patients than in TH-negative patients (63.8±6.9% vs. 94.7±2.1%, p < 0.001). In analysis confined to high-risk patients, the 5-year probability of PFS remained lower in TH-positive patients (55.7±8.2% vs. 89.6±5.8%, p < 0.001). Among TH-positive patients, a higher expression level of TH was associated with a worse outcome. In multivariate analyses, positive TH expression in PB at diagnosis was an independent poor prognostic factor for PFS.
Conclusion
The treatment intensity should be tailored according to TH expression in PB at diagnosis.

Citations

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A comprehensive overview of liquid biopsy applications in pediatric solid tumors
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Ernest Osei, Nidaa Al-Ani, Aladdin Al-Asady, Susan Dang
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Case Report

A Case of Desmoplastic Small Round Cell Tumor Diagnosed in a Young Female Patient: Ji-Won Kim, Jin Hyun Park, Hyeon Jin Cho, Ji-Hyun Kwon, Youngil Koh, Su-Jung Kim, Se Hyung Kim, Se-Hoon Lee, Seock-Ah Im, Yong-Tae Kim, Woo Ho Kim; Cancer Res Treat. 2009;41(4):233-236. Published online December 31, 2009; DOI: https://doi.org/10.4143/crt.2009.41.4.233

Abstract PDF PubReader ePub

Desmoplastic small round cell tumor is a very rare malignancy. We report the case of a 26-year-old woman who suffered from dyspepsia and abdominal pain for 2 months. We performed an endoscopic biopsy of the duodenal mass and diagnosed her disease as desmoplastic small round cell tumor using immunohistochemical staining, fluorescence in situ hybridization, and reverse transcriptase polymerase chain reaction. Because the mass invaded the pancreas and superior mesenteric vein as well as duodenum and the disease was disseminated to liver and peritoneum, she received palliative chemotherapy using vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide. The maximal response to chemotherapy was stable disease. The patient expired 9 months after diagnosis.

Citations

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Intra-Abdominal Desmoplastic Small Round Cell Tumor: Current Treatment Options and Perspectives
Guixia Wei, Xinyao Shu, Yuwen Zhou, Xia Liu, Xiaorong Chen, Meng Qiu
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A Case Report of Abdominal Desmoplastic Small Round Cell Tumor in a Young Tunisian Woman
Karim Nacef, Mohamed Ali Chaouch, Rym Bouriga, Mohamed Ben Khalifa, Asma Chaouch, Mossab Ghannouchi, Moez Boudokhane
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Primary desmoplastic small-round-cell tumor of the ovary
Ahmed Atef, Khaled Gaballa, Mohammad Zuhdy, Khalid Atallah, Wagdi Elkashef, Shadi Awny, Basma Gadelhak, Basel Refky
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Tumor intraabdominal desmoplásico de células pequeñas y redondas
Andrés Alejandro Briseño-Hernández, Deissy Roxana Quezada-López, Lilia Edith Corona-Cobián, Agar Castañeda-Chávez, Alfonso Tonatiuh Duarte-Ojeda, Michel Dassaejv Macías-Amezcua
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Intra-abdominal desmoplastic small round cell tumour
Andrés Alejandro Briseño-Hernández, Deissy Roxana Quezada-López, Lilia Edith Corona-Cobián, Agar Castañeda-Chávez, Alfonso Tonatiuh Duarte-Ojeda, Michel Dassaejv Macías-Amezcua
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Qi Liu, Nan Liu, DeXing Chen
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Izaskun Markinez Gordobil, Inmaculada Ruiz, Raúl Jiménez, Eloisa Villarreal, Aintzane Lizarazu, Nerea Borda, Xabier Arteaga, Miguel Ángel Medrano, Esther Guisasola, Adolfo Beguiristain, José María E. Navascués
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Hafida Benhammane, Leila Chbani, Abdelmalek Ousadden, Ouadii Mouquit, Siham Tizniti, Afaf Riffi Amarti, Nouafal Mellas, Omar El Mesbahi
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Analysis of Prognostic Factors of Pediatric-Type Sarcomas in Adult Patients
Hee Kyung Ahn, Ji Eun Uhm, Jeeyun Lee, Do Hoon Lim, Sung Wook Seo, Ki-Sun Sung, Su Jin Lee, Duk Joo Lee, Kyung Kee Baek, Won-Seog Kim, Joon Oh Park
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Original Article

The Association of p53 Mutation with Human Papillomavirus Type 16 , 18 Infection and its Clinical Significance: Chang Soo Park, Yong Sang Song, Chang Won Koh, Hye Won Jeon, Soon Beom Kang, Hyo Pyo Lee; J Korean Cancer Assoc. 1996;28(1):122-138.

Abstract PDF: Recent several studies have suggested that inactivation of p53 gene could occur by two theoretical mechanisms in cervical cancer. The E6 transforming protein of oncogenic human papillomavirus(HPV) binds to and promotes the degradation of p53 protein, or the mutation of the p53 gene could result in its inactivation without HPV infection. The purpose of this study were to investigate HPV infection and p53 mutation according to the status of lymph node metastasis and to analyse the relationship and role of HPV infection and p53 alteration in the advance and metastasis of cervical cancer. Paraffin embedded tissue sections were obtained from 30 patients with cervical cancer, each l5 patients with or without lymph node metastasis. The PCR and Southern blotting were used for the detection of HPV l6/18 DNA. Alteration of p53 activity was evaluated by immunohistochemistry using MAb DO7 and polymerase chain reaction with single stranded conformation polymorphism(PCR-SSCP). There was no significant difference in HPV infection between two groups, 73.3%(l l/15) in negative lymph node group and 80.0%(l2/15) in positive lymph node group. Although by immunohistochemistry p53 alterations were found more frequently in positive lymph node group(46.7%) than in negative lymph node group(20.0%), there was no significant difference between two groups. HPV negative cervical cancers had more p53 alterations(57.l%) than HPV positive cervical cancers(26.1%). However, there was no significant inverse relationship between HPV infection and p53 alteration. In conclusion, these data suggest that HPV infection and p53 alteration may play an important role independantly in the development of cervical cancer and p53 alteration may be associated with the advance and metastasis in some cases.

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