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  • 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 survival (PFS),… More >

  • Open Access

    ARTICLE

    Lactate Maintains BCR/Abl Expression and Signaling in Chronic Myeloid Leukemia Cells Under Nutrient Restriction

    Angela Silvano*†1, Giulio Menegazzi*1, Silvia Peppicelli*1, Caterina Mancini*, Alessio Biagioni*, Alessandro Tubita*, Ignazia Tusa*, Jessica Ruzzolini*, Matteo Lulli*, Elisabetta Rovida*, Persio Dello Sbarba*

    Oncology Research, Vol.29, No.1, pp. 33-46, 2021, DOI:10.3727/096504022X16442289212164

    Abstract This study was directed to deepen the effects of nutrient shortage on BCR/Ablprotein expression and signaling in chronic myeloid leukemia (CML) cells. The backbone of the study was cell culture in medium lacking glucose, the consumption of which we had previously shown to drive BCR/Ablprotein suppression, and glutamine, the other main nutrient besides glucose. In this context, we focused on the role of lactate, the main by-product of glucose metabolism under conditions of rapid cell growth, in particular as a modulator of the maintenance of CML stem/progenitor cell potential, a crucial determinant of disease course and relapse of disease. The… More >

  • Open Access

    ARTICLE

    Real-World Data: Fruquintinib in Treating Metastatic Colorectal Cancer

    Shuai Liu*†1, Lu Lu*†1, Feng Pan, Chunsheng Yang*†, Jing Liang§, Jinfeng Liu, Jian Wang#, Rong Shen**, Fu-Ze Xin††, Nan Zhang*†

    Oncology Research, Vol.29, No.1, pp. 25-31, 2021, DOI:10.3727/096504022X16427607626672

    Abstract Fruquintinib, also called HMPL-013, was first discovered by Hutchison Whampoa Pharmaceuticals Co. Ltd., Shanghai, China, and it is an oral vascular endothelial growth factor receptor (VEGFR) inhibitor. In clinical trials, fruquintinib has demonstrated a survival benefit in metastatic colorectal cancer (mCRC) patients. The purpose of this study was to retrospectively evaluate the efficacy and toxicity of fruquintinib in real-world patients. We collected data from patients with mCRC treated with oral fruquintinib from 2018 to 2020 in six different institutions. Patients with mCRC initially received 5 mg of oral fruquintinib daily for 3 weeks. Progression-free survival (PFS) was evaluated using the… More >

  • Open Access

    ARTICLE

    STAT3 Polymorphism Associates With mTOR Inhibitor-Induced Interstitial Lung Disease in Patients With Renal Cell Carcinoma

    Kazuhiro Yamamoto*, Takeshi Ioroi*, Kazuaki Shinomiya, Ayaka Yoshida*, Kenichi Harada, Masato Fujisawa, Tomohiro Omura*, Yasuaki Ikemi§, Shunsaku Nakagawa§, Atsushi Yonezawa§, Osamu Ogawa, Kazuo Matsubara§, Takuya Iwamoto#, Kohei Nishikawa**, Sayaka Hayashi††, Daichi Tohara††, Yoji Murakami‡‡, Takanobu Motoshima‡‡, Hirofumi Jono††, Ikuko Yano

    Oncology Research, Vol.29, No.1, pp. 11-23, 2021, DOI:10.3727/096504022X16418911579334

    Abstract We evaluated the association of signal transducer and activator of transcription 3 (STAT3) polymorphisms with the incidence of mammalian target of rapamycin (mTOR) inhibitor-induced interstitial lung disease (ILD) in patients with renal cell carcinoma (RCC). We also used lung-derived cell lines to investigate the mechanisms of this association. Japanese patients with metastatic RCC who were treated with mTOR inhibitors were genotyped for the STAT3 polymorphism, rs4796793 (−1697C/G). We evaluated the association of the STAT3 genotype with the incidence of ILD and therapeutic outcome. In the 57 patients included in the primary analysis, the ILD rate within 140 days was significantly… More >

  • Open Access

    ARTICLE

    MYCN Directly Targets NeuroD1 to Promote Cellular Proliferation in Neuroblastoma

    Fangjin Lu*, Bin Mu, Ge Jin*, Lin Zhu, Ping Mu§

    Oncology Research, Vol.29, No.1, pp. 1-10, 2021, DOI:10.3727/096504021X16401852341873

    Abstract NeuroD1 is a neuronal differentiation factor that contains a basic helix–loop–helix (bHLH) motif. Recently, NeuroD1 was found to be associated with tumorigenesis in neuroblastoma (NB) and is known to promote cell proliferation and migration in these cells. Here we found that MYCN regulates the expression of NeuroD1 in NB cells and that the downregulation of MYCN using short hairpin RNAs (shRNA) results in the inhibition of cellular proliferation in NB cells. Moreover, the phenotype induced by MYCN shRNA was rescued by the exogenous expression of NeuroD1. Chromatin immunoprecipitation (ChIP) assay showed that MYCN directly binds to the E-box element in… More >

  • Open Access

    ARTICLE

    DPY19L3 promotes vasculogenic mimicry by its C-mannosyltransferase activity

    HASSAN BAYDOUN1, YUJI KATO1, HIROKI KAMO1, ANNA HÜSCH1,2, HAYATO MIZUTA1, RYOTA KAWAHARA1, SIRO SIMIZU1,*

    Oncology Research, Vol.32, No.4, pp. 607-614, 2024, DOI:10.32604/or.2023.030304

    Abstract

    C-mannosylation is a post-translational modification that occurs intracellularly in the endoplasmic reticulum. In humans, biosynthesis of C-mannosylation in proteins containing thrombospondin type 1 repeat is catalyzed by the DPY19 family; nonetheless, biological functions of protein C-mannosylation are not yet fully understood, especially in tumor progression. Vasculogenic mimicry (VM) is the formation of fluid-conducting channels by highly invasive and genetically deregulated tumor cells, enabling the tumors to form matrix-embedded vasculogenic structures, containing plasma and blood cells to meet the metabolic demands of rapidly growing tumors. In this study, we focused on DPY19L3, a C-mannosyltransferase, and aimed to unravel its role in… More >

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