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  • Open Access

    ARTICLE

    Genomic profiling of colorectal cancer in large-scale Chinese patients: amplification and somatic mutations in ERBB2

    YUZHI LIU1,#, EVELYNE BISCHOF2,#, ZHIQIN CHEN1, JIAHUAN ZHOU3, BEI ZHANG4, DING ZHANG4, YONG GAO1,*, MING QUAN1,*

    Oncology Research, Vol.32, No.9, pp. 1429-1438, 2024, DOI:10.32604/or.2024.047309 - 23 August 2024

    Abstract Objectives: Human epidermal growth factor receptor 2 (HER2)-targeted therapies have demonstrated potential benefits for metastatic colorectal cancer (mCRC) patients with HER2 amplification, but are not satisfactory in cases of HER2 mutant CRCs. Methods: Consequently, further elucidation of amplifications and somatic mutations in erythroblastic oncogene B-2 (ERBB2) is imperative. Comprehensive genomic profiling was conducted on 2454 Chinese CRC cases to evaluate genomic alterations in 733 cancer-related genes, tumor mutational burden, microsatellite instability, and programmed death ligand 1 (PD-L1) expression. Results: Among 2454 CRC patients, 85 cases (3.46%) exhibited ERBB2 amplification, and 55 cases (2.24%) carried ERBB2 mutation.… More > Graphic Abstract

    Genomic profiling of colorectal cancer in large-scale Chinese patients: amplification and somatic mutations in ERBB2

  • Open Access

    ARTICLE

    High-throughput computational screening and in vitro evaluation identifies 5-(4-oxo-4H-3,1-benzoxazin-2-yl)-2-[3-(4-oxo-4H-3,1-benzoxazin-2-yl) phenyl]-1H-isoindole-1,3(2H)-dione (C3), as a novel EGFR—HER2 dual inhibitor in gastric tumors

    MESFER AL SHAHRANI, REEM GAHTANI, MOHAMMAD ABOHASSAN, MOHAMMAD ALSHAHRANI, YASSER ALRAEY, AYED DERA, MOHAMMAD RAJEH ASIRI, PRASANNA RAJAGOPALAN*

    Oncology Research, Vol.32, No.2, pp. 251-259, 2024, DOI:10.32604/or.2023.043139 - 28 December 2023

    Abstract Gastric cancers are caused primarily due to the activation and amplification of the EGFR or HER2 kinases resulting in cell proliferation, adhesion, angiogenesis, and metastasis. Conventional therapies are ineffective due to the intra-tumoral heterogeneity and concomitant genetic mutations. Hence, dual inhibition strategies are recommended to increase potency and reduce cytotoxicity. In this study, we have conducted computational high-throughput screening of the ChemBridge library followed by in vitro assays and identified novel selective inhibitors that have a dual impediment of EGFR/HER2 kinase activities. Diversity-based High-throughput Virtual Screening (D-HTVS) was used to screen the whole ChemBridge small molecular… More > Graphic Abstract

    High-throughput computational screening and <i>in vitro</i> evaluation identifies 5-(4-oxo-4H-3,1-benzoxazin-2-yl)-2-[3-(4-oxo-4H-3,1-benzoxazin-2-yl) phenyl]-1H-isoindole-1,3(2H)-dione (C3), as a novel EGFR—HER2 dual inhibitor in gastric tumors

  • Open Access

    ARTICLE

    Prolonged Survival in Patients with Human Epidermal Growth Factor Receptor-2-Overexpressed Metastatic Breast Cancer after Targeted Therapy is Dominantly Contributed by Luminal-Human Epidermal Growth Factor Receptor-2 Population

    Keiichi Kontani1,*, Kana Kuraishi1, Shin-ichiro Hashimoto1, Shoko Norimura2, Nozomi Hashimoto1, Masahiro Ohtani3, Naomi Fujiwara-Honjo4, Manabu Date5, Koji Teramoto6, Hiroyasu Yokomise1

    Oncologie, Vol.23, No.2, pp. 229-239, 2021, DOI:10.32604/Oncologie.2021.016277 - 22 June 2021

    Abstract The prognosis of patients with human epidermal growth factor receptor-2 (HER2)-overexpressed metastatic breast cancer (MBC) has improved drastically following the development of anti-HER2 therapies. We question what factors are involved in the improved outcome by the treatment. One hundred and two MBC patients who received chemotherapy were classified into groups according to breast cancer subtype: luminal/HER2-negative (n = 50), HER2 (n = 26), and triple-negative subtypes (n = 26). Clinicopathologic features and clinical outcomes of the groups were compared. Disease-free intervals in the triple-negative group were significantly shorter than those in the other two groups.… More >

  • Open Access

    ARTICLE

    RPA3 is transcriptionally activated by YY1 and its depletion enhances radiosensitivity of triple-negative and HER2-positive breast cancer

    YANFEI LI1, LULU DAI2, KE CAI2, YINGKUI SONG2, XIQING LIU3,*

    BIOCELL, Vol.45, No.3, pp. 685-694, 2021, DOI:10.32604/biocell.2021.013612 - 03 March 2021

    Abstract RPA3 (Replication Protein A3) (14 kD) is a part of the canonical heterotrimeric replication protein A complex (RPA/RP-A). This study aimed to explore the functional role of RPA3 and the mechanisms of its dysregulation in breast cancer. Data from the Cancer Genome Atlas (TCGA)-breast cancer patients and GSE75688 were utilized for gene expression and survival analysis. Breast cancer cell lines MDA-MB-231 and SK-BR-3 were used for in-vitro cell studies. Clonogenic assay and immunofluorescent staining of γ-H2AX were performed to examine radiation-induced cytotoxicity. Systemic correlation analysis was performed to identify potential transcription factors (TFs) regulating RPA3… More >

  • Open Access

    ARTICLE

    Pomalidomide improves the function of CD133- or HER2-specific CAR T cells

    ZHIXIONG WANG1,2, NA RISU2, JIAYU FU2, HUI LIU3, GUOMIN ZHOU3, QIAN LIU3, YAN ZOU4, JIAXING TANG4, LONG LI4, XUEKAI ZHU4,*

    BIOCELL, Vol.45, No.1, pp. 157-165, 2021, DOI:10.32604/biocell.2021.010261 - 26 January 2021

    Abstract Chimeric antigen receptor (CAR) T-cell therapy is mostly limited to hematological malignancies and has a poor effect on solid tumors. CAR T cells as a kind of immune cell may be affected by some immunomodulatory drugs such as pomalidomide, so the use of pomalidomide may improve the effect of CAR T cells on solid tumors. In this study, CD133- or HER2-specific CAR T cells were chosen to investigate whether pomalidomide can regulate the function of CAR T cells in vitro. We found that pomalidomide can significantly enhance the ability of CD133-CAR T cells and HER2-CAR T More >

  • Open Access

    ARTICLE

    Pyrotinib Sensitizes 5-Fluorouracil-Resistant HER2+ Breast Cancer Cells to 5-Fluorouracil

    Jianing Yi*, Shuai Chen*, Pingyong Yi, Jinlin Luo*, Meng Fang*, Yang Du*, Lianhong Zou*, Peizhi Fan*

    Oncology Research, Vol.28, No.5, pp. 519-831, 2020, DOI:10.3727/096504020X15960154585410

    Abstract 5-Fluorouracil (5-FU) is a widely used chemotherapeutic agent for breast cancer. However, acquired chemoresistance leads to a loss of its efficacy; methods to reverse are urgently needed. Some studies have shown that pyrotinib, an ErbB receptor tyrosine kinase inhibitor, is effective against HER2+ breast cancer. However, whether pyrotinib sensitizes 5-FU-resistant breast cancer cells to 5-FU is unknown. We hypothesized that the combination of pyrotinib and 5-FU would show synergistic antitumor activity, and pyrotinib could reverse 5-FU resistance in HER2+ breast cancer cells in vitro and in vivo. Our data showed that pyrotinib inhibited the growth… More >

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