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  • Open Access

    ARTICLE

    Efficacy of Wee1 G2 Checkpoint Kinase and Mouse Double Minute 2 Homolog Inhibitors in Gastrointestinal Stromal Tumors Determined by p53 Status

    Chiao-Ping Chen1,2, Yan-Jei Tang1,2, You-Yan Cai1, Yi-Ru Pan3, Chun-Nan Yeh3,4, Wen-Kuan Huang1,2, Chih-Hong Lo1,2, Yu-Tien Hsiao1,2, Hsuan-Jen Shih1,*, Chiao-En Wu1,2,4,5,*

    Oncology Research, Vol.33, No.11, pp. 3429-3446, 2025, DOI:10.32604/or.2025.066672 - 22 October 2025

    Abstract Background: KIT proto-oncogene, receptor tyrosine kinase (KIT, CD117) and platelet-derived growth factor-alpha (PDGFRA) are key drivers of gastrointestinal stromal tumors (GIST), but resistance to targeted therapy often arises from tumor protein p53 (p53) alterations and loss of cell cycle control. However, the role of p53 status in GIST therapeutic potential has rarely been studied, so this study aimed to employ both wild-type and mutant p53 GIST models to investigate how p53 dysfunction influences the efficacy of p53 pathway-targeted therapies. Methods: The efficacy of the mouse double minute 2 homolog (MDM2) inhibitor (HDM201) and the Wee1… More >

  • Open Access

    ARTICLE

    LncRNA CRYBG3 Regulates Adaptive Radioresistance in Non-Small Cell Lung Cancer Cells through the p53/HSF1/TRAP1 Axis

    Xiangyu Yan1,#, Yusheng Jin1,#, Yan Yuan1, Xubaihe Zhang1, Jiayi Li1, Ying Xu1, Yangyang Ge2, Anqing Wu1,*

    BIOCELL, Vol.49, No.10, pp. 1929-1946, 2025, DOI:10.32604/biocell.2025.066935 - 22 October 2025

    Abstract Objectives: Fractionated radiotherapy represents a standardized and widely adopted treatment modality for cancer management, with approximately 40% of non-small cell lung cancer (NSCLC) patients receiving it. However, repeated irradiation may induce radioresistance in cancer cells, reducing treatment effectiveness and raising recurrence risk. The long noncoding RNA CRYBG3 (lncRNA CRYBG3), which is upregulated in lung cancer cells after X-ray irradiation, contributes to the radioresistance of NSCLC cells by promoting wild-type p53 protein degradation. This study aims to elucidate the mechanism of fractionated irradiation-induced radioresistance, in which lncRNA CRYBG3 regulates radiation-induced mitochondrial damage and reactive oxygen species… More >

  • Open Access

    ARTICLE

    Rhein Inhibits Podocyte Ferroptosis and Epithelial-Mesenchymal Transition in Diabetic Nephropathy by Activating the SIRT1/p53/SLC7A11 Pathway

    Wei Hu1, Dan Xiong2,*

    BIOCELL, Vol.49, No.9, pp. 1711-1731, 2025, DOI:10.32604/biocell.2025.067670 - 25 September 2025

    Abstract Objectives: Podocytes undergo epithelial-mesenchymal transition (EMT) and ferroptosis in response to hyperglycemic stimulation. This is considered an important early event in the development and progression of diabetic nephropathy (DN). Rhein is the main active anthraquinone derivative in several common traditional herbal medicines. This study aimed to investigate the protective effects of Rhein on podocyte ferroptosis and EMT. Methods: The mouse glomerular podocyte cell line MPC5 was stimulated with high glucose (HG), Rhein, and the ferroptosis inhibitor ferrostatin-1 (Fer-1). Mechanistic investigations employed plasmids to overexpress and knockdown Sirtuin-1 (SIRT1), solute carrier family 7 member 11 (SLC7A11),… More >

  • Open Access

    ARTICLE

    Single-Cell Transcriptomic Profiling Reveals KRAS/TP53-Driven Neutrophil Reprogramming in Luad: A Multi-Gene Prognostic Model and Therapeutic Targeting of RHOV

    Yinghui Ye1,#, Yulou Luo2,#, Yutian Sun3, Yujie Zhang1, Jiaxin Lin4, Ziling Yang5, Anping Xu6,*, Bei Xue1,*

    Oncology Research, Vol.33, No.6, pp. 1383-1404, 2025, DOI:10.32604/or.2025.062584 - 29 May 2025

    Abstract Objectives: The tumorigenic progression of Lung adenocarcinoma (LUAD), the predominant NSCLC subtype, is predominantly driven by co-occurring mutations in KRAS proto-oncogene (KRAS)/Tumor protein p53 (TP53). However, their impact on tumor microenvironment (TME) heterogeneity, particularly neutrophil dynamics, remains poorly understood. This present study aims to elucidate how KRAS/TP53 mutations reprogram the TME and develop a neutrophil-centric prognostic signature for LUAD. Methods: Leveraging single-cell RNA sequencing data and transcriptome data, neutrophil subpopulations were identified using Seurat and CellChat R packages, with trajectory analysis via Monocle2 R package. High-dimensional weighted gene co-expression network analysis (hdWGCNA), univariate Cox regression,… More >

  • Open Access

    REVIEW

    Cell Death of Tumor Melanocytes and Treatment Options

    Olga Koval1,2,*, Maria Zhilnikova1, Maria Balantaeva1,2, Mikhail Biryukov1,2, Vasiliy Atamanov1,3

    BIOCELL, Vol.49, No.3, pp. 355-379, 2025, DOI:10.32604/biocell.2025.059987 - 31 March 2025

    Abstract Melanomas are aggressive cancers, with a high rate of metastatic disease. Cutaneous (CM) and uveal (UM) melanomas are intrinsically different diseases, and most cell death inducers effective for CM do not function for UM. This is primarily due to the fact the eye is an immunologically privileged organ, and it fails to achieve the efficacy of immune checkpoint inhibitors (ICIs) comparable to that for CM. However, approaches utilizing specific melanoma-associated antigens are being developed for metastatic forms of CM and UM. The most promising to date are gp100 and tyrosinase related protein 1 (TYRP1), primarily… More >

  • Open Access

    REVIEW

    Targeting MDM2-p53 interaction for breast cancer therapy

    AMJAD YOUSUF1, NAJEEB ULLAH KHAN2,*

    Oncology Research, Vol.33, No.4, pp. 851-861, 2025, DOI:10.32604/or.2025.058956 - 19 March 2025

    Abstract Breast cancer is a significant global concern, with limited effective treatment options. Therefore, therapies with high efficacy and low complications, unlike the existing chemotherapies, are urgently required. To address this issue, advances have been made in therapies targeting molecular pathways related to the murine double minute 2 proto-oncogene (MDM2)-tumor proteinp53 (TP53) interaction. This review aims to investigate the efficacy of MDM2 inhibition in restoring TP53 activity in breast cancer cells, as evidenced by clinical studies, reviews, and trials. TP53 is a tumor suppressor and MDM2 facilitates proteasomal degradation of TP53. MDM2 and TP53 activity More > Graphic Abstract

    Targeting MDM2-p53 interaction for breast cancer therapy

  • Open Access

    REVIEW

    p53: A player in the tumor microenvironment

    SHUANG ZHAO1,#, HONGYONG WEN2,#, BAIQI WANG2, QINGLIN XIONG1, LANXIN LI1, AILAN CHENG1,*

    Oncology Research, Vol.33, No.4, pp. 795-810, 2025, DOI:10.32604/or.2025.057317 - 19 March 2025

    Abstract Approximately half of all cancers have p53 inactivating mutations, in addition to which most malignancies inactivate the p53 pathway by increasing p53 inhibitors, decreasing p53 activators, or inactivating p53 downstream targets. A growing number of researches have demonstrated that p53 can influence tumor progression through the tumor microenvironment (TME). TME is involved in the process of tumor development and metastasis and affects the clinical prognosis of patients. p53 participates in host immunity and engages in the immune landscape of the TME, but the specific mechanisms remain to be investigated. This review briefly explores the More >

  • Open Access

    ARTICLE

    Protective Effects of Probiotics against Methotrexate-Induced Intestinal Toxicity in the Mice Model

    KSENIA S. STAFEEVA1, NATALIA A. SAMOYLOVA1, OLGA A. KARANDEEVA1, VERONIKA V. NESTEROVA1, KIRILL A. STARODUBTSEV1, EVGENY V. MIKHAILOV2, ILYA O. KRUTOV2, EVGENY S. POPOV3, NATALIA S. RODIONOVA4, ANASTASIA V. KOKINA1,5, ARTEM P. GUREEV1,5,*

    BIOCELL, Vol.49, No.1, pp. 7-20, 2025, DOI:10.32604/biocell.2024.058339 - 24 January 2025

    Abstract Objective: The objective of this study was to determine the level of methotrexate (MTX) toxicity in the intestines of mice and to evaluate the protective effect of probiotics composed of Streptococcus, Bifidobacterium, and Lactobacillus species on intestinal cells during MTX treatment. Methods: Mice were divided into three groups: control, MTX group (received MTX injections), and MTX + probiotics group (received MTX injections along with a diet containing probiotics). Morphological and histological changes, the level of mitochondrial DNA (mtDNA) damage, the level of lipid peroxidation products, and gene expression in the mice’s small intestine were assessed. Results: We… More > Graphic Abstract

    Protective Effects of Probiotics against Methotrexate-Induced Intestinal Toxicity in the Mice Model

  • Open Access

    ARTICLE

    CircRNA circ_0015278 induces ferroptosis in lung adenocarcinoma through the miR-1228/P53 axis

    LIANGJIANG XIA1, GUANGBIN LI2, QINGWU ZHOU3, YU FENG2,*, HAITAO MA2,*

    Oncology Research, Vol.33, No.2, pp. 465-475, 2025, DOI:10.32604/or.2024.050835 - 16 January 2025

    Abstract Background: Circular RNAs play an important role in regulating lung adenocarcinoma (LUAD). Bioinformatics analysis identified circ_0015278 as differentially expressed in LUAD. However, the biological mechanism of circ_0015278 in LUAD has not been fully clarified, especially in ferroptosis. Materials and Methods: Bioinformatics analysis was employed to explore the downstream mechanisms of Circ_0015278, subsequently confirmed by luciferase reporter assays. The impact of Circ_0015278 on cell proliferation, migration, invasion, and ferroptosis was investigated through a loss-of-function experiment. A xenotransplantation mouse model elucidated the effect of Circ_0015278 on tumour growth. Results: Circ_0015278 exhibited downregulation in LUAD. It inhibited cell proliferation, More >

  • Open Access

    ARTICLE

    DNAJA4, DNAJB11 and DNAJC10 induce cell transformation by inhibiting p53 and oncogene-induced senescence

    HYEON JU LEE1, CHANG SEOP LEE1, SI HOON KIM1, SOOKYUNG KIM1, JEONG MI KIM1, SUN-WHA IM1, YU-JIN JUNG2, SEUNG-PYO HONG3, HYUNJUNG LEE3, JONG-IL KIM3,4,5, JEONG A. HAN1,*

    BIOCELL, Vol.48, No.10, pp. 1455-1464, 2024, DOI:10.32604/biocell.2024.054538 - 02 October 2024

    Abstract Objective: Transformation from normal cells to malignant cells is the basis for tumorigenesis. While this cell transformation is known to result from aberrant activation or inactivation of associated genes, these genes have not yet been fully identified. In addition, DNAJs, proteins with a J domain, are known to be molecular co-chaperones, but their cellular functions remain largely unexplored. In this context, we here identified DNAJA4, DNAJB11, and DNAJC10 as pro-transforming genes and elucidated their action mechanisms. Methods: Senescence-associated (SA)-β-galactosidase staining and western blotting were used to analyze cellular senescence and protein expression. Soft agar assay was used… More >

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