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  • Open Access

    ARTICLE

    HE4 Might Participate in Extracellular Matrix Remodeling in Ovarian Cancer via Activation of Fibroblasts

    Yimin Liu1,#, Bin Liu2,3,4,#, Huabin Gao1, Jinlong Wang5, Jingya Duan1, Xiaolan Huang1, Yuexi Liu1, Ying Huang1, Wenjing Liao1, Ruonan Li1,*, Hua Linghu1,*

    Oncology Research, Vol.34, No.1, 2026, DOI:10.32604/or.2025.069007 - 30 December 2025

    Abstract Objectives: High-grade serous ovarian cancer (HGSOC), the most common subtype of epithelial ovarian cancer (EOC), exhibits a mesenchymal phenotype characterized by fibrotic stroma and poor prognosis. Human epididymis protein 4 (HE4), a key diagnostic biomarker for ovarian cancer, is involved in fibrotic processes in several non-malignant diseases. Given the clinical significance of stromal fibrosis in HGSOC and the potential link between HE4 and fibrosis, this study aimed to investigate the role of HE4 in the formation of stromal fibrosis in HGSOC. Methods: A total of 126 patients with gynecological conditions were included and divided into… More > Graphic Abstract

    HE4 Might Participate in Extracellular Matrix Remodeling in Ovarian Cancer via Activation of Fibroblasts

  • Open Access

    REVIEW

    Reprogramming the Tumor Microenvironment in Head and Neck Squamous Cell Carcinoma: Therapeutic Targets and Innovations

    Bruno Špiljak1,#, Bojan Poposki2,#, Stjepanka Lešić3,*

    Oncology Research, Vol.33, No.11, pp. 3269-3292, 2025, DOI:10.32604/or.2025.068395 - 22 October 2025

    Abstract Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer with high recurrence rates and prevalent resistance to therapeutic interventions. Tumor behavior is largely dependent on the tumor microenvironment (TME) that includes immune cells, stromal components, cancer-associated fibroblasts (CAFs), the extracellular matrix (ECM), and an associated cytokine network. In this review, we examine principal mechanisms of the tumorigenic transformation, encompassing immune checkpoint disruption, therapy resistance mediated through CAFs, the contribution of hypoxic niches, and several metabolic dependencies that hold potential as future targets. Novel therapeutics developed and/or repurposed, such as immune checkpoint inhibitors (ICIs),… More >

  • Open Access

    ARTICLE

    TRIM32 Promotes Glycolysis in Keloid Fibroblasts and Progression of Keloid Scars via Regulation of the PI3K/AKT Signaling Pathway

    Yi Zhang1, Hua Jin2,*

    BIOCELL, Vol.49, No.8, pp. 1529-1543, 2025, DOI:10.32604/biocell.2025.066479 - 29 August 2025

    Abstract Objectives: The present study investigated whether Tripartite Motif-Containing Protein 32 (TRIM32) contributes to the aberrant activation of keloid fibroblasts (KFs) via glycolysis. Methods: The expression levels of TRIM32, pyruvate dehydrogenase kinase 1 (PDK1), hexokinase 2 (HK2), and glucose transporter 1 (GLUT1) in normal human skin fibroblasts (NFs) and KFs were analyzed using RT-qPCR analyses and western blotting. Cellular proliferation, invasion, and migration were evaluated using Transwell, wound healing, 5-ethynyl-2-deoxyuridine (EdU), and cell counting kit-8 (CCK-8) assays. The extracellular acidification rate (ECAR) was measured using the XF96 Extracellular Flux Analyzer. Glucose uptake and ATP production were measured using… More >

  • Open Access

    REVIEW

    Research progress on cancer-associated fibroblasts in osteosarcoma

    LIWEN FENG1,2,#,*, YUTING CHEN3,#, WENYI JIN4

    Oncology Research, Vol.33, No.5, pp. 1091-1103, 2025, DOI:10.32604/or.2024.054207 - 18 April 2025

    Abstract Osteosarcoma (OS) is a prevalent primary bone malignancy with limited treatment options. Therefore, it is imperative to investigate and understand the mechanisms underlying OS pathogenesis. Cancer-associated fibroblasts (CAFs) are markedly abundant in tumor stromal cells and are essentially involved in the modulation of tumor occurrence and development. In recent years, CAFs have become a hotspot as researchers aim to elucidate CAF mechanisms that regulate tumor progression. However, most studies on CAFs are limited to a few common cancers, and their association with OS remains elusive. This review describes the role and current knowledge of CAFs More >

  • Open Access

    ARTICLE

    «Silver Bullet of Acidification»: Studying Anti-PD Neuroprotective Mechanisms of Transient pH-Decrease

    Kristina A. Kritskaya, Evgeniya I. Fedotova, Alexander D. Nadeev*, Alexey V. Berezhnov*

    BIOCELL, Vol.49, No.3, pp. 451-464, 2025, DOI:10.32604/biocell.2025.061624 - 31 March 2025

    Abstract Objective: Activation of mitophagy is a promising option to overcome the mitochondrial malfunction that accompanies many diseases. Herein, we investigate the mechanisms underlying the ability of sodium lactate and pyruvate to initiate mitophagy, from the perspective of action on mitochondrial network and expression levels. Methods: Fluorescent and confocal microscopy was used to assess key cell parameters characterizing the state of the mitochondrial network and the level of mitophagy in human fibroblasts carrying mutations in genes encoding LRRK2 and PINK1 after the combined application of lactate and pyruvate and after direct acidification. qRT-PCR was used to… More >

  • Open Access

    ARTICLE

    The Anti-Senescence Effect and Mechanism of 17β-Estradiol on Pelvic Organ Prolapse Derived Fibroblasts

    Juan Cheng1,#, Zhiwei Zhao2,#, Ling Wang1, Jirui Wen1, Yali Miao3,*, Jiang Wu1,*

    BIOCELL, Vol.49, No.2, pp. 335-348, 2025, DOI:10.32604/biocell.2025.059573 - 28 February 2025

    Abstract Objectives: Recently, pre-/post-operative Local Estrogen Therapy (LET) has shown effectiveness in alleviating Pelvic Organ Prolapse (POP) symptoms in clinical therapy. However, there is a lack of scientific evidence to support these claims. Therefore, we aimed to explore the anti-senescence effects and mechanisms of 17β-estradiol (E2) on POP-derived fibroblasts. Methods: The primary fibroblast cells were isolated and cultured from the surgical samples of postmenopausal women clinically diagnosed with pelvic organ prolapse (POP) at stages III-IV (quantified using the POP-Q system) and without any other treatment within 6 months. (n = 12, age 50–75). Colorimetric Cell Counting… More >

  • Open Access

    ARTICLE

    CAF-derived exosome-miR-3124-5p promotes malignant biological processes in NSCLC via the TOLLIP/TLR4-MyD88-NF-κB pathway

    TAO SUN1,2, QINGHUA SONG3, HUA LIU1,*

    Oncology Research, Vol.33, No.1, pp. 133-148, 2025, DOI:10.32604/or.2024.054141 - 20 December 2024

    Abstract Background: Lung cancer is a life-threatening disease that occurs worldwide, but is especially common in China. The crucial role of the tumour microenvironment (TME) in non-small cell lung cancer (NSCLC) has attracted recent attention. Cancer-associated fibroblasts (CAFs) are the main factors that contribute to the TME function, and CAF exosomes are closely linked to NSCLC. Methods: The expression levels of miR-3124-5p and Toll-interacting protein (TOLLIP) were analysed by bioinformatics prediction combined with RT-qPCR/Western Blot detection. Fibroblasts were isolated and identified from clinical NSCLC tissues. Transmission electron microscopy and Western Blot were used to identify exosomes… More >

  • Open Access

    REVIEW

    The diverse functions and therapeutic implications of cancer-associated fibroblasts in colorectal cancer

    ZEYIN LAI1, HANGYUAN ZHAO1, HONG DENG1,2,*

    BIOCELL, Vol.48, No.11, pp. 1569-1578, 2024, DOI:10.32604/biocell.2024.053983 - 07 November 2024

    Abstract In the development of colorectal cancer (CRC), cancer-associated fibroblasts (CAFs) play a pivotal role in establishing tumor-permissive extracellular matrix structures, angiogenesis, and modulating the immune status of the tumor microenvironment (TME), thereby influencing tumor metastasis and resistance to radiotherapy and chemotherapy. The pleiotropic effects of CAFs in the TME may be attributed to the heterogeneous origin and high plasticity of their population. Given the specificity of CAFs, they provide a variety of potential target molecules for future CRC treatment, which may play an indispensable role in CRC therapeutic strategies. This review summarizes the origin of More >

  • Open Access

    ARTICLE

    Lysine demethylase 5B transcriptionally regulates TREM1 in human cardiac fibroblasts

    CHUNLING LIANG1,#, JING CHEN2,#, XIAOJIE CHEN1, WEI YAN3, JIE YU4,*

    BIOCELL, Vol.48, No.7, pp. 1105-1113, 2024, DOI:10.32604/biocell.2024.050509 - 03 July 2024

    Abstract Background: A differential gene, triggering receptor expressed on myeloid cells 1 (TREM1), was identified in blood sequencing datasets from myocardial infarction patients and healthy controls. Myocardial fibrosis following myocardial infarction significantly contributes to cardiac dysfunction. Objectives: This study aimed to unveil the intrinsic regulatory mechanism of TREM1 in myocardial fibrosis. Methods: Mimicking pathology by angiotensin II (Ang II) treatment of human cardiac fibroblasts (HCFs), the impacts of TREM1 knockdown on its proliferation, migration, and secretion of the pro-fibrotic matrix were identified. Using the Human Transcription Factor Database (HumanTFDB) website, lysine-specific demethylase 5B (KDM5B) was found to… More >

  • Open Access

    ARTICLE

    CRABP2 regulates infiltration of cancer-associated fibroblasts and immune response in melanoma

    SHUANGSHUANG ZENG1,2, XI CHEN1,2, QIAOLI YI1,2, ABHIMANYU THAKUR3, HUI YANG4,*, YUANLIANG YAN1,2, SHAO LIU1,2,*

    Oncology Research, Vol.32, No.2, pp. 261-272, 2024, DOI:10.32604/or.2023.042345 - 28 December 2023

    Abstract Finding biomarkers for immunotherapy is an urgent issue in cancer treatment. Cellular retinoic acid-binding protein 2 (CRABP2) is a controversial factor in the occurrence and development of human tumors. However, there is limited research on the relationship between CRABP2 and immunotherapy response. This study found that negative correlations of CRABP2 and immune checkpoint markers (PD-1, PD-L1, and CTLA-4) were observed in breast invasive carcinoma (BRCA), skin cutaneous melanoma (SKCM), stomach adenocarcinoma (STAD) and testicular germ cell tumors (TGCT). In particular, in SKCM patients who were treated with PD-1 inhibitors, high levels of CRABP2 predicted poor… More >

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