Home / Journals / OR / Vol.33, No.2, 2025
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  • Open AccessOpen Access

    REVIEW

    Melanoma-derived extracellular vesicles transfer proangiogenic factors

    MAGDALENA WILCZAK1,2,#, MAGDALENA SURMAN1,#,*, MAłGORZATA PRZYBYłO1,*
    Oncology Research, Vol.33, No.2, pp. 245-262, 2025, DOI:10.32604/or.2024.055449 - 16 January 2025
    Abstract Angiogenesis, the expansion of pre-existing vascular networks, is crucial for normal organ growth and tissue repair, but is also involved in various pathologies, including inflammation, ischemia, diabetes, and cancer. In solid tumors, angiogenesis supports growth, nutrient delivery, waste removal, and metastasis. Tumors can induce angiogenesis through proangiogenic factors including VEGF, FGF-2, PDGF, angiopoietins, HGF, TNF, IL-6, SCF, tryptase, and chymase. This balance is disrupted in tumors, and extracellular vesicles (EVs) contribute to this by transferring proangiogenic factors and increasing their expression in endothelial cells (ECs). Malignant melanoma, a particular type of skin cancer, accounts for More >

  • Open AccessOpen Access

    REVIEW

    Immunotherapy in gastric cancer—A systematic review

    MARTA SANTOS1, DIANA MARTINS1,2,3,4, FERNANDO MENDES1,2,3,4,5,*
    Oncology Research, Vol.33, No.2, pp. 263-281, 2025, DOI:10.32604/or.2024.052207 - 16 January 2025
    Abstract Background: Gastric Cancer (GC) is the 5th most prevalent and 4th most deadly neoplasm globally. Immunotherapy has emerged as a promising treatment approach in GC, potentially improving positive clinical outcomes while addressing the limitations of conventional therapies. GC immunotherapy modalities consist of adoptive cell therapy (ACT), cancer vaccines, and immune checkpoint inhibitors (ICI). Objectives: This systematic review aims to provide an overview of the advances in immune-based therapeutic approaches in GC, highlighting the potential of this therapy as a strategy for GC treatment. Methods: Key studies investigating several immunotherapeutic agents and combination therapies were searched in… More >

    Graphic Abstract

    Immunotherapy in gastric cancer—A systematic review

  • Open AccessOpen Access

    REVIEW

    FOXR2 in cancer development: emerging player and therapeutic opportunities

    PIAO YANG1, MOHSEN SHEYKHHASAN2,*, REZA HEIDARI3, MOHSEN CHAMANARA4,5, PAOLA DAMA6, AMIRHOSSEIN AHMADIEH-YAZDI7, HAMED MANOOCHEHRI8, HAMID TANZADEHPANAH9, HANIE MAHAKI10, NASER KALHOR11, ASHKAN DIRBAZIYAN12, SHARAFALDIN AL-MUSAWI13
    Oncology Research, Vol.33, No.2, pp. 283-300, 2025, DOI:10.32604/or.2024.052939 - 16 January 2025
    Abstract Cancer, a leading cause of global mortality, remains a significant challenge to increasing life expectancy worldwide. Forkhead Box R2 (FOXR2), identified as an oncogene within the FOX gene family, plays a crucial role in developing various endoderm-derived organs. Recent studies have elucidated FOXR2-related pathways and their involvement in both tumor and non-tumor diseases. Dysregulation of FOXR2 has been linked to numerous malignant tumors, spanning the brain, nervous system, thyroid, osteosarcoma, Hodgkin lymphoma, colorectal, liver, pancreatic, lung, breast, ovarian, prostate, female genital tract, endometrial, and uterine cancers. Despite extensive research on FOXR2 dysregulation, its practical applications More >

  • Open AccessOpen Access

    REVIEW

    Insights on Bmi-1 therapeutic targeting in head and neck cancers

    JESSIE REYES-CARMONA*
    Oncology Research, Vol.33, No.2, pp. 301-307, 2025, DOI:10.32604/or.2024.053764 - 16 January 2025
    Abstract The B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) protein of the polycomb complex is an essential mediator of the epigenetic transcriptional silencing by the chromatin structure. It has been reported to be crucial for homeostasis of the stem cells and tumorigenesis. Though years of investigation have clarified Bmi-1’s transcriptional regulation, post-translational modifications, and functions in controlling cellular bioenergetics, pathologies, and DNA damage response, the full potential of this protein with so many diverse roles are still unfulfilled. Bmi-1 is overexpressed in many human malignancies. Unraveling the Bmi-1’s precise functional role in head and neck… More >

  • Open AccessOpen Access

    ARTICLE

    KHSRP promotes cancer stem cell maintenance, tumorigenesis, and suppresses anti-tumor immunity in gastric cancer

    YARU DU1,2,#, ZHIHUI PEI1,3,#, SHUQIN HU4, CHUANWEN LIAO1, SHUHAO LIU1,*
    Oncology Research, Vol.33, No.2, pp. 309-325, 2025, DOI:10.32604/or.2024.058273 - 16 January 2025
    Abstract Objectives: KH-type splicing regulatory protein (KHSRP) is an RNA-binding protein involved in several cellular processes, including nuclear splicing, mRNA localization, and cytoplasmic degradation. While KHSRP’s role has been studied in other cancers, its specific involvement in gastric cancer remains poorly understood. This study aims to explore KHSRP expression in gastric cancer and its potential effects on tumor progression and immune response. Methods: KHSRP expression in gastric cancer tissues and normal tissues was analyzed using data from The Cancer Genome Atlas (TCGA) database. The correlation between KHSRP expression, patient survival, and immune response was also assessed.… More >

  • Open AccessOpen Access

    ARTICLE

    Exosomal miR-224-3p promotes lymphangiogenesis and lymph node metastasis by targeting GSK3B in gastric cancer

    ZHENGYANG ZHOU1,#, LEI QIAO1,#, TONGTONG WANG1, WEN PAN1, JINGJING DUAN1, HAIYANG ZHANG2, TING DENG1, YI BA1,*, YI HE1,*
    Oncology Research, Vol.33, No.2, pp. 327-345, 2025, DOI:10.32604/or.2024.050431 - 16 January 2025
    Abstract Background: Patients with gastric cancer (GC) are prone to lymph node metastasis (LNM), which is an important factor for recurrence and poor prognosis of GC. Nowadays, more and more studies have confirmed that exosomes can participate in tumor lymphangiogenesis. An in-depth exploration of the pathological mechanism in the process of LNM in GC may provide effective targets and improve the diagnosis and treatment effect. Materials and Methods: We used sequencing analysis of collected serum to screen out exo-miRNA related to LNM in GC. ELISA, qRT-PCR, Western Blot, RNA pull-down assay, Transwell assay, animal experiments, and other… More >

    Graphic Abstract

    Exosomal miR-224-3p promotes lymphangiogenesis and lymph node metastasis by targeting GSK3B in gastric cancer

  • Open AccessOpen Access

    ARTICLE

    EGR1 inhibits clear cell renal cell carcinoma proliferation and metastasis via the MAPK15 pathway

    NAIXIONG PENG, YUEFENG CAI, DONG CHEN, LING DENG, ZEJIAN ZHANG, WEI LI*
    Oncology Research, Vol.33, No.2, pp. 347-356, 2025, DOI:10.32604/or.2024.056039 - 16 January 2025
    Abstract Background: Clear cell renal carcinoma (ccRCC), the leading histological subtype of RCC, lacks any targeted therapy options. Although some studies have shown that early growth response factor 1 (EGR1) has a significant role in cancer development and progression, its role and underlying mechanisms in ccRCC remain poorly understood. Methods: The Cancer Genome Atlas (TCGA) database was utilized to examine the expression of EGR1 in ccRCC. The expression of EGR1 in 55 ccRCC tissues was evaluated using immunohistochemistry. The link between EGR1 expression and clinicopathological variables was examined through an analysis. Gain-of-function assays were employed to… More >

  • Open AccessOpen Access

    ARTICLE

    Melanoma cell line-derived exosomal miR-424-5p: a key promoter of angiogenesis through LATS2 interaction

    JUNWEI DU, QIANG ZHANG, JING ZHANG, MAIERDANJIANG MAIHEMUTI, HAIYANG HE, RENBING JIANG*
    Oncology Research, Vol.33, No.2, pp. 357-367, 2025, DOI:10.32604/or.2024.050878 - 16 January 2025
    Abstract Objectives: Melanoma is a highly aggressive and metastatic form of cancer, and the role of exosomal microRNAs (miRNAs) in its progression remains largely unexplored. This study aimed to investigate the effects of melanoma cell-derived exosomal miR-424-5p on angiogenesis and its underlying mechanisms. Methods: Exosomes were isolated from melanoma cell lines A375 and A2058, and their effects on the proliferation, migration, and angiogenesis of human umbilical vein endothelial cells (HUVECs) were examined. The interaction between miR-424-5p and its target gene, large tumor suppressor kinase 2 (LATS2), was analyzed using luciferase reporter assays and functional experiments. In vivo,… More >

  • Open AccessOpen Access

    ARTICLE

    Circ-PAN3 facilitates hepatocellular carcinoma growth via sponging miR-153 and upregulating cyclin D1

    SHUO YU, MIN WANG, XU LI, XINGJUN GUO, RENYI QIN*
    Oncology Research, Vol.33, No.2, pp. 369-380, 2025, DOI:10.32604/or.2024.046774 - 16 January 2025
    (This article belongs to the Special Issue: Advances in Cancer Therapeutics)
    Abstract Background: Circular RNAs (circRNAs) play a pivotal role in the development and advancement of various cancer types. However, the involvement of circ-PAN3 in hepatocellular carcinoma (HCC) is not well understood. To shed light on this, we conducted a comprehensive study through biochemistry, cell biology, molecular biology, and bioinformatics techniques to investigate the role of circ-PAN3 and its associated pathway in the progression of HCC. Methods: Cell Counting Kit-8 (CCK-8) assay and colony formation assay were utilized to evaluate cell proliferation; Quantitative real-time PCR (RT-qPCR) and Western blot were adopted for assessing mRNA and protein expression;… More >

  • Open AccessOpen Access

    ARTICLE

    Ketogenic diet with oxyresveratrol and zinc inhibits glioblastoma and restores memory function and motor coordination

    TANVI VIJAY GUJARAN1,#, VIGNESH BALAJI EASWARAN1,#, RUNALI SANKHE1, PUGAZHANDHI BAKTHAVATCHALAM2,3, HERMAN SUNIL DSOUZA4, K. SREEDHARA RANGANATH PAI1,*
    Oncology Research, Vol.33, No.2, pp. 381-395, 2025, DOI:10.32604/or.2024.049538 - 16 January 2025
    Abstract Background: To date, there is no effective cure for the highly malignant brain tumor glioblastoma (GBM). GBM is the most common, aggressive central nervous system tumor (CNS). It commonly originates in glial cells such as microglia, oligodendroglia, astrocytes, or subpopulations of cancer stem cells (CSCs). Glucose plays an important role in the, which energy metabolism of normal and cancer cells, but cancer cells exhibit an increased demand for glucose is required for their differentiation and proliferation. The main aim of this study is to explore the anti-cancer efficacy of the ketogenic diet against GBM. Also,… More >

  • Open AccessOpen Access

    ARTICLE

    MCU-i4, a mitochondrial Ca2+ uniporter modulator, induces breast cancer BT474 cell death by enhancing glycolysis, ATP production and reactive oxygen species (ROS) burst

    EDMUND CHEUNG SO1,2,#, LOUIS W. C. CHOW3,#, CHIN-MIN CHUANG4, CING YU CHEN5,6, CHENG-HSUN WU7, LIAN-RU SHIAO8, TING-TSZ OU9, KAR-LOK WONG10, YUK-MAN LEUNG8,*, YI-PING HUANG8,*
    Oncology Research, Vol.33, No.2, pp. 397-406, 2025, DOI:10.32604/or.2024.052743 - 16 January 2025
    (This article belongs to the Special Issue: Recent Advances in Cancer Pharmacology)
    Abstract Objectives: Mitochondrial Ca2+ uniporter (MCU) provides a Ca2+ influx pathway from the cytosol into the mitochondrial matrix and a moderate mitochondrial Ca2+ rise stimulates ATP production and cell growth. MCU is highly expressed in various cancer cells including breast cancer cells, thereby increasing the capacity of mitochondrial Ca2+ uptake, ATP production, and cancer cell proliferation. The objective of this study was to examine MCU inhibition as an anti-cancer mechanism. Methods: The effects of MCU-i4, a newly developed MCU inhibitor, on cell viability, apoptosis, cytosolic Ca2+, mitochondrial Ca2+ and potential, glycolytic rate, generation of ATP, and reactive oxygen species,… More >

  • Open AccessOpen Access

    ARTICLE

    Circular RNA circAGAP1 promotes sunitinib sensitivity in renal cell carcinoma via sponging multiple PDGFR-targeted miRNAs

    QI LV1,#, GANGMIN WANG2,#, YI HONG1, TIANYI ZHU1, SHUANG QIN1, SAIFEI SUN1, YUTING WANG1, YAOHUA LIU1, QING ZHANG1, CHUNHUI MA3,*, PEIJUN WANG1,*
    Oncology Research, Vol.33, No.2, pp. 407-420, 2025, DOI:10.32604/or.2024.047698 - 16 January 2025
    Abstract Background: Sunitinib resistance is a major challenge in advanced renal cell carcinoma (RCC). Clinically, elucidating the underlying mechanisms and developing practical countermeasures for sunitinib resistance in RCC is desirable. In previous studies, we found that circAGAP1 expression was significantly upregulated in clear cell RCC (ccRCC) and was strongly associated with poor prognosis. However, the role of circAGAP1 in sunitinib resistance in ccRCC remains unclear. Methods: We used public databases for bioinformatics analysis to identify the binding targets of circAGAP1. Additionally, the effects of circAGAP1 on the proliferation, clonogenesis, apoptosis, and migration of ccRCC cells were… More >

    Graphic Abstract

    Circular RNA circAGAP1 promotes sunitinib sensitivity in renal cell carcinoma via sponging multiple PDGFR-targeted miRNAs

  • Open AccessOpen Access

    ARTICLE

    Apigenin facilitates apoptosis of acute lymphoblastic leukemia cells via AMP-activated protein kinase-mediated ferroptosis

    CANCAN HE1,2,*, TINGTING ZHANG3, WEI XIONG4, SHENGYU WANG5, XIN SUN6
    Oncology Research, Vol.33, No.2, pp. 421-429, 2025, DOI:10.32604/or.2024.049757 - 16 January 2025
    Abstract Background: The outcomes of pediatric patients with acute lymphoblastic leukemia (ALL) remain far less than favorable. While apigenin is an anti-cancer agent, studies on the mechanism by which it regulates ALL cell cycle progression are inadequate. Ferroptosis and AMP-activated protein kinase (AMPK) signaling are important processes for ALL patients. However, it remains unclear whether apigenin works by affecting AMPK and apoptosis. Materials and Methods: SUP-B15 and T-cell Jurkat ALL cells were treated with apigenin, and cell viability and apoptosis were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays, respectively.… More >

  • Open AccessOpen Access

    ARTICLE

    Comprehensive analysis reveals PLK3 as a promising immune target and prognostic indicator in glioma

    TIANYUN ZHU1,2,#, CUNYAN ZHAO1,2,#, RUI GONG1,2, AO QIAN1, XIAOSHU WANG1, FANGHUI LU2, GANG HUO1, LIANGJUN QIAO3, SONG CHEN1,*
    Oncology Research, Vol.33, No.2, pp. 431-442, 2025, DOI:10.32604/or.2024.050794 - 16 January 2025
    Abstract Background: PLK3, which played an important role in cell cycle progression and stress response, was identified as highly expressed in various carcinomas. However, the functions, molecular characteristics, and prognostic value of PLK3 in glioma remained unexplored. Methods: We analyzed PLK3 expression in glioma samples from multiple databases. Both overexpression and knockdown of Plk3 were performed to investigate tumor cell growth in glioma, and the transplanted glioma mouse model demonstrated the role of Plk3 on tumor progression. Immunohistochemistry was conducted to detect PLK3 expression and immune cell infiltration. The trans-well assay for PLK3 on the immune… More >

  • Open AccessOpen Access

    ARTICLE

    EMP2 promotes hepatocellular carcinoma proliferation and invasion by activating cellular autophagy

    HAIYING PANG1,#, FENGBO WU1,#, YU ZHANG1, NAN ZHANG2, CHUNTING WANG1, QIU LI1, GU HE1,*, PENG ZHANG3,*
    Oncology Research, Vol.33, No.2, pp. 443-464, 2025, DOI:10.32604/or.2024.043948 - 16 January 2025
    (This article belongs to the Special Issue: Signaling Pathway Crosstalk in Malignant Tumors: Molecular Targets and Combinatorial Therapeutics)
    Abstract Background: EMP2 is a tumor-associated membrane protein belonging to the GAS-3/PMP22 gene family. EMP2 expression demonstrates significant tissue specificity and heterogeneity in various human tissues and tumor tissues, where it may play a role in either promoting or inhibiting tumor growth. This study aimed to investigate the expression level, biological functions, and molecular mechanisms of EMP2 in liver cancer. Methods: we analyzed the mRNA expression levels of EMPs family genes in hepatocellular carcinoma (HCC) tissues and normal liver tissues based on the TCGA database and immunohistochemical analysis of tissue microarrays. Subsequently, we constructed HCC cell… More >

    Graphic Abstract

    EMP2 promotes hepatocellular carcinoma proliferation and invasion by activating cellular autophagy

  • Open AccessOpen 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 AccessOpen Access

    ARTICLE

    Chitosan capped-NLCs enhanced codelivery of gefitinib and simvastatin into MDR HCC: impact of compositions on cell death, JNK3, and Telomerase

    GAMALELDIN I. HARISA1,*, RIYAD F. ALZHRANI1, ABDULRAHMAN A. ALLUHAIDAN1, SULTAN M. ALAMRI1, AHMED H. BAKHEIT2, HANADI H. ASIRI2, SABRY M. ATTIA3
    Oncology Research, Vol.33, No.2, pp. 477-492, 2025, DOI:10.32604/or.2024.053337 - 16 January 2025
    Abstract Background: Hepatocellular carcinoma (HCC) is a health problem due to multi-drug resistance (MDR). Codelivery of multiple oncotherapy in one cargo as chimeric cancer therapy (CCT) is suggested as a solution for MDR. This study aims to engineer chitosan-coated nanostructure lipid carriers (NLCs) loaded with gefitinib (GF) and simvastatin (SV) as CCT for HCC. Methods: Both GF and SV-loaded nanostructure lipids carriers (GFSVNLC) and chitosan-capped GF and SV-loaded nanostructure lipids carriers (CGFSVNLC) formulations were assembled by top-down techniques. Moreover, particle size (PS), zeta potential (ZP), and polydispersity index (PDI) were measured by Zetasizer. The biosafety of… More >

    Graphic Abstract

    Chitosan capped-NLCs enhanced codelivery of gefitinib and simvastatin into MDR HCC: impact of compositions on cell death, JNK3, and Telomerase

  • Open AccessOpen Access

    ARTICLE

    Loss of Arhgap39 facilitates cell migration and invasion in murine hepatocellular cancer cells

    HUNG-WEI LIN1, PEI YU LEE1, YU-SHIUAN CHANG1, MAU-SUN CHANG1,2,*
    Oncology Research, Vol.33, No.2, pp. 493-503, 2025, DOI:10.32604/or.2024.053791 - 16 January 2025
    Abstract Background: Rho GTPases are essential regulators for cellular movement and intracellular membrane trafficking. Their enzymatic activities fluctuate between active GTP-bound and inactive GDP-bound states regulated by GTPase activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs). Arhgap39/Vilse/Porf-2 is a newly identified GAP. The role of Arhgap39 in migration and invasion has not been addressed thoroughly. Methods: The Arhgap39 gene was knocked out by Crispr-Cas9 gene editing in mouse Hepa1-6 and Hepa-1c1c7 cells to analyze the impact of Arhgap39 depletion on migration and invasion. Results: Loss of Arhgap39 noticeably increased the migration and invasive potential. Purified Arhgap39… More >

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