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  • Open Access

    ARTICLE

    Targeting HER2-Positive HCC1954 Breast Cancer Cells by Novel Thiazole-Dihydrobenzisoxazoles: In-Depth Design, Synthesis and Initial In Vitro Study

    Yuri A. Piven1, Danila V. Sorokin2, Nastassia A. Varabyeva1, Alexandra L. Mikhaylova2, Fedor B. Bogdanov2, Elena V. Shafranovskaya1, Raman M. Puzanau3, Fedor A. Lakhvich1, Alexander M. Scherbakov2,4,*

    Oncology Research, Vol.33, No.12, pp. 4049-4072, 2025, DOI:10.32604/or.2025.067832 - 27 November 2025

    Abstract Background: The most aggressive forms of breast cancer are characterized by independence from steroid hormones but a strong dependence on growth factors. In such cancer cells, oncogenic receptors, including human epidermal growth factor receptor 2 (HER2), are activated, and their targeted inhibition represents an attractive therapeutic strategy. The study aimed to develop small-molecule potential dual heat shock protein 90 (HSP90)-HER2 inhibitors and evaluate them as anticancer agents in HER2-positive cells. Methods: The research project involved obtaining a series of compounds with potential dual inhibitory activity against HSP90 and HER2 by targeted organic synthesis, which was… More > Graphic Abstract

    Targeting HER2-Positive HCC1954 Breast Cancer Cells by Novel Thiazole-Dihydrobenzisoxazoles: In-Depth Design, Synthesis and Initial <i>In Vitro</i> Study

  • Open Access

    ARTICLE

    PFDN6L Gene Predicts Good Prognosis Associated with Its Inhibition of the Stem-Ness Properties in Hepatocellular Carcinoma

    Fangyuan Li1,2,#, Xiaoyuan Hu1,#, Xiaoge Gao3, Ling Liu3, Tao Li1, Dan He1, Jiaxing Cheng1, Xiaobiao Ma1, Li Li1,*, Chunlei Ge1,*, Hong Yao1,*

    Oncology Research, Vol.33, No.12, pp. 4029-4048, 2025, DOI:10.32604/or.2025.067628 - 27 November 2025

    Abstract Background: Liver cancer stem cells (LCSCs) are recognized as pivotal drivers of hepatocellular carcinoma (HCC) progression; however, the molecular mechanisms maintaining their stem-like phenotype remain largely unresolved. This work investigates the role of prefoldin subunit 6-like protein (PFDN6L) in shaping LCSC traits and promoting or restraining HCC progression. Methods: PFDN6L, a cytoskeleton-associated chaperone, was studied using multiple in vitro assays—cell growth evaluation, cell cycle profiling, and spheroid culture—alongside analyses of stemness-associated markers (SOX2, CD133, CD44). Tumorigenic capacity was assessed in xenograft mouse models, and signaling pathway interrogation was performed to define underlying mechanisms. Results: In patient samples, More >

  • Open Access

    ARTICLE

    TROP-2 Promotes Cell Proliferation via the AKT-Mediated PKCα Pathway and Is a Novel Target for Antibody-Drug Conjugates in Penile Carcinoma

    Yi Tang1,2,3,4,#, Minyi Situ1,2,3,4,#, Zhiming Wu1,2,3,4,#, Yanjun Wang1,2,3,4,#, Xinpei Deng1,2,3,4, Zhicheng Liu1,2,3,4, Shengjie Guo1,2,3,4, Qianghua Zhou1,2,3,4,*, Gangjun Yuan5,*, Xingliang Tan1,2,3,4,*, Kai Yao1,2,3,4,*

    Oncology Research, Vol.33, No.12, pp. 3973-3989, 2025, DOI:10.32604/or.2025.066184 - 27 November 2025

    Abstract Background: Current chemotherapy treatments, including the TIP (Taxol, Ifosfamide, Cisplatin) regimen, have shown limited effects but strong side effects in advanced Penile squamous cell carcinoma (PSCC) patients. Trophoblast cell-surface antigen-2 (TROP-2) is a novel target for antibody-drug conjugate (ADC) drugs and has been proven to be effective in several human cancers. This study aimed to explore the biological function and potential of the ADC target in PSCC cells. Methods: A total of 196 PSCC tumor tissue specimens and clinicopathological data were collected. TROP-2 expression was detected by IHC, and the correlation between TROP-2 expression and… More > Graphic Abstract

    TROP-2 Promotes Cell Proliferation via the AKT-Mediated PKC<b>α</b> Pathway and Is a Novel Target for Antibody-Drug Conjugates in Penile Carcinoma

  • Open Access

    ARTICLE

    Endothelin-1 Mediates Oxaliplatin Resistance via Activation of YAP Signaling in Colorectal Cancer

    Ranran Yang1,2,3,#, Dan Yuan2,#, Chaohan Liang4,#, Siying Zhu4, Jie Huang2, Yingqi Zhang4, Weiling He5, Qinghai Li1,*, Hong Zhang2,*

    Oncology Research, Vol.33, No.12, pp. 3945-3971, 2025, DOI:10.32604/or.2025.064463 - 27 November 2025

    Abstract Background: Colorectal cancer (CRC) is a predominant contributor to global cancer-associated mortality worldwide. Oxaliplatin (OXP), a foundational chemotherapeutic agent for CRC, often exhibits limited efficacy due to the emergence of drug resistance. Although endothelin-1 (EDN1) has been implicated in tumor drug resistance, its role in oxaliplatin resistance in CRC remains poorly defined. This work aimed to define how EDN1 contributes to oxaliplatin resistance and to explore its potential as a therapeutic target. Methods: Public genomic datasets were analyzed to confirm EDN1 upregulation in colorectal cancer (CRC) and its association with poor prognosis. EDN1 expression was… More >

  • Open Access

    ARTICLE

    BMP-2 Inhibits the Inflammatory Response and Promotes Bone Formation in Rats with Femoral Fracture by Activating the AMPK Signaling Pathway

    Yong Huang1, Xiandeng Li1, Qingling Jing1, Qin Zhang1, Chungui Huang2,*

    BIOCELL, Vol.49, No.11, pp. 2195-2216, 2025, DOI:10.32604/biocell.2025.072716 - 24 November 2025

    Abstract Objective: Mesenchymal stem cells (MSCs) are important cells in bone tissue engineering. Bone morphogenetic protein-2 (BMP-2) effectively treats bone defects and nonunion. The purpose of this study is to investigate whether BMP-2 promotes bone formation and femoral fracture healing by inhibiting inflammation and promoting osteogenic differentiation of MSCs, in order to provide an experimental basis for developing more efficient fracture treatment strategies. Methods: Bone marrow-derived MSCs (BMSCs) were isolated from rats and treated with OE-BMP-2, the 5-adenosine monophosphate-activated protein kinase (AMPK) signal agonist 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), and the inhibitor Compound C. Osteogenic differentiation was evaluated through… More >

  • Open Access

    ARTICLE

    ELM-APDPs: An Explainable Ensemble Learning Method for Accurate Prediction of Druggable Proteins

    Mujeebu Rehman1, Qinghua Liu1, Ali Ghulam2, Tariq Ahmad3, Jawad Khan4,*, Dildar Hussain5,*, Yeong Hyeon Gu5

    CMES-Computer Modeling in Engineering & Sciences, Vol.145, No.1, pp. 779-805, 2025, DOI:10.32604/cmes.2025.067412 - 30 October 2025

    Abstract Identifying druggable proteins, which are capable of binding therapeutic compounds, remains a critical and resource-intensive challenge in drug discovery. To address this, we propose CEL-IDP (Comparison of Ensemble Learning Methods for Identification of Druggable Proteins), a computational framework combining three feature extraction methods Dipeptide Deviation from Expected Mean (DDE), Enhanced Amino Acid Composition (EAAC), and Enhanced Grouped Amino Acid Composition (EGAAC) with ensemble learning strategies (Bagging, Boosting, Stacking) to classify druggable proteins from sequence data. DDE captures dipeptide frequency deviations, EAAC encodes positional amino acid information, and EGAAC groups residues by physicochemical properties to generate… More >

  • Open Access

    ARTICLE

    Diverse PD-1, CD163, and FOXP3 Profiles in Primary and Metastatic Microenvironments of Prostate Cancer

    Ana Clara Ciglioni Salustiano1,2, Gabriela Barbosa1,3,4, Rodolfo Borges dos Reis2,4, Amílcar Castro de Mattos5,6, Athanase Billis6, Leonardo O. Reis1,3,4,*

    Oncology Research, Vol.33, No.11, pp. 3417-3428, 2025, DOI:10.32604/or.2025.068023 - 22 October 2025

    Abstract Objective: The tumor microenvironment plays a pivotal role in prostate cancer progression and may differ across metastatic sites. This study aimed to evaluate and compare the primary and metastatic prostate adenocarcinoma tumor microenvironment. Methods: A total of 27 formalin-fixed paraffin-embedded tissue samples derived from 17 patients diagnosed with prostate adenocarcinoma, including the primary tumors, and the corresponding metastatic lymphatic and hematogenous lesions from various anatomical sites. Immunohistochemical labeling was performed using antibodies against Cluster of Differentiation 3 epsilon chain (CD3e), CD8 alpha chain (CD8a), Cluster of Differentiation 68 (CD68), Cluster of Differentiation 163 (CD163), Forkhead… More > Graphic Abstract

    Diverse PD-1, CD163, and FOXP3 Profiles in Primary and Metastatic Microenvironments of Prostate Cancer

  • 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

    Strain-Specific Trajectories of Behavioural, Neuroinflammatory, and Microbiota Changes under Chronic Stress in Rats with Contrast Levels of Nervous System Excitability

    Anastasia Vylegzhanina1,2, Irina Shalaginova2,*, Dana Korolevich1, Dmitry Katserov1, Alexandra Semenova1, Maria Sidorova1, Sergey Eresko3, Marat Airapetov3, Marina Pavlova2, Anna Levina2, Natalia Dyuzhikova2

    BIOCELL, Vol.49, No.10, pp. 2007-2031, 2025, DOI:10.32604/biocell.2025.071198 - 22 October 2025

    Abstract Objectives: Chronic stress can trigger neuroinflammation and gut microbiota alterations, contributing to post-stress disorders. Individual differences in stress responses, shaped by genetic and physiological factors, require better characterization. We aimed to investigate the long-term effects of chronic stress in rats selectively bred for high and low nervous system excitability. Methods: Adult male rats from two strains selectively bred for high (HT) and low (LT) excitability thresholds of the nervous system underwent a 15-day chronic emotional-pain stress protocol. Behavioral assessments (elevated plus maze), cytokine levels (TNF, IL-1β, IL-6, IL-10) in the hippocampus and amygdala measured by… More >

  • Open Access

    REVIEW

    Targeting AMPK for Cancer Therapy: Metabolic Reprogramming as a Therapeutic Strategy

    Minseo Hong, Jea-Hyun Baek*

    Oncology Research, Vol.33, No.10, pp. 2699-2724, 2025, DOI:10.32604/or.2025.067487 - 26 September 2025

    Abstract AMP-activated protein kinase (AMPK) is a highly conserved serine/threonine kinase that functions as a central regulator of cellular energy status. In cancer, where metabolic reprogramming enables rapid proliferation and survival under stress, AMPK functions as a metabolic checkpoint that restrains tumor growth by inhibiting biosynthetic pathways and promoting catabolic processes, such as autophagy and fatty acid oxidation. Given its role in opposing many hallmarks of cancer metabolism, AMPK has attracted significant interest as a therapeutic target. This review examines the molecular mechanisms by which AMPK influences tumor progression and evaluates the preclinical and clinical evidence… More >

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