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  • Open Access

    ARTICLE

    5-Fluorouracil dose escalation generated desensitized colorectal cancer cells with reduced expression of protein methyltransferases and no epithelial-to-mesenchymal transition potential

    KIMBERLY FENECH1, ISAAC MICALLEF1,2, BYRON BARON1,*

    Oncology Research, Vol.32, No.6, pp. 1047-1061, 2024, DOI:10.32604/or.2024.049173 - 23 May 2024

    Abstract Background: Colorectal cancer (CRC) is one of the most frequently diagnosed cancers. In many cases, the poor prognosis of advanced CRC is associated with resistance to treatment with chemotherapeutic drugs such as 5-Fluorouracil (5-FU). The epithelial-to-mesenchymal transition (EMT) and dysregulation in protein methylation are two mechanisms associated with chemoresistance in many cancers. This study looked into the effect of 5-FU dose escalation on EMT and protein methylation in CRC. Materials and Methods: HCT-116, Caco-2, and DLD-1 CRC cell lines were exposed to dose escalation treatment of 5-FU. The motility and invasive potentials of the cells before… More > Graphic Abstract

    5-Fluorouracil dose escalation generated desensitized colorectal cancer cells with reduced expression of protein methyltransferases and no epithelial-to-mesenchymal transition potential

  • Open Access

    ARTICLE

    Comparison of UGT1A1 Polymorphism as Guidance of Irinotecan Dose Escalation in RAS Wild-Type Metastatic Colorectal Cancer Patients Treated With Cetuximab or Bevacizumab Plus FOLFIRI as the First-Line Therapy

    Hsiang-Lin Tsai*†, Yen-Cheng Chen*‡, Tzu-Chieh Yin*§¶, Wei-Chih Su*‡, Po-Jung Chen*,Tsung-Kun Chang*†, Ching-Chun Li*, Ching-Wen Huang*†, Jaw-Yuan Wang*†‡#**††‡‡

    Oncology Research, Vol.29, No.1, pp. 47-61, 2021, DOI:10.3727/096504022X16451187313084

    Abstract Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) polymorphism plays a crucial role in the increased susceptibility and toxicity of patients to irinotecan. This retrospective, observational study compared the clinical outcomes and adverse events (AEs) in RAS wild-type metastatic colorectal cancer (mCRC) patients treated with cetuximab or bevacizumab plus FOLFIRI with UGT1A1 genotyping and irinotecan dose escalation as the first-line therapy. In total, 173 patients with mCRC with RAS wild-type were enrolled. Among them, 98 patients were treated with cetuximab, whereas 75 patients were treated with bevacizumab. All patients received irinotecan dose escalation based on UGT1A1 genotyping. We compared the progression-free… More >

  • Open Access

    ARTICLE

    Regorafenib Plus FOLFIRI With Irinotecan Dose Escalated According to Uridine Diphosphate Glucuronosyltransferase 1A1 Genotyping in Patients With Metastatic Colorectal Cancer

    Cheng-Jen Ma*†‡, Ching-Wen Huang*‡§, Yung-Sung Yeh*†¶, Hsiang-Lin Tsai*§#**, Huang-Ming Hu††‡‡, I-Chen Wu††‡‡, Tian-Lu Cheng§§¶¶, Jaw-Yuan Wang*†‡§**¶¶

    Oncology Research, Vol.25, No.5, pp. 673-679, 2017, DOI:10.3727/97818823455816X14786040691928

    Abstract We analyzed the results of previously treated patients with metastatic colorectal cancer (mCRC) who received regorafenib plus FOLFIRI with the irinotecan dose escalation on the basis of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) genotyping. Thirteen patients with previously treated mCRC were subjected to UGT1A1 genotyping between October 2013 and June 2015 and were administered regorafenib plus FOLFIRI with irinotecan dose escalation. Patients with UGT1A1*1/*1 and *1/*28 genotypes were administered 180 mg/m2 of irinotecan, whereas those with the UGT1A1*28/*28 genotype were administered 120 mg/m2 of irinotecan. For all patients, the irinotecan dose was increased by 30 mg/m2 every… More >

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