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  • Open Access

    ARTICLE

    Plexin A2 Knockdown Enhances Apoptosis in Chemotherapy Treated Melanoma Cells

    Nadezhda Palkina1, Aleksandra Esimbekova1, Ekaterina Lapkina1, Victoriia Kutsenko1, Ivan Zinchenko1, Egor Dereviankin1, Elena Anisimova2, Andrei Savchenko2, Tatiana Ruksha1,*

    Oncology Research, Vol.34, No.5, 2026, DOI:10.32604/or.2026.069234 - 22 April 2026

    Abstract Background: Cancer cells are characterized by the ability to exit reversibly from the cell cycle to resist an unfavorable environment. This study elucidates alterations in adhesion molecule expression in melanoma cells acquiring resistance to dacarbazine (DTIC) and entering the G0 state. Plexin A2 (PLXNA2) was identified as a focal adhesion-related molecule implicated in carcinogenesis. Methods: Applying siRNA-mediated knockdown, the effects of altered PLXNA2 expression in melanoma cells were evaluated. PLXNA2 expression was determined by real-time quantitative reverse transcription PCR, immunoblotting, and immunocytochemistry. Cell cycle phase distribution among dacarbazine-treated cells and their apoptosis levels were quantified by… More >

  • Open Access

    REVIEW

    Understanding the Tumor Microenvironmental Mechanisms Driving Immunotherapy Resistance in Colorectal Cancer Liver Metastases

    Candela Cives-Losada1,2, Cristiana Soldani2, Michela Anna Polidoro2, Barbara Franceschini2, Ana Lleo3,4, Marcello Di Martino1,5, Matteo Donadon1,5,*

    Oncology Research, Vol.34, No.4, 2026, DOI:10.32604/or.2025.074093 - 23 March 2026

    Abstract Colorectal cancer (CRC) is the second deadliest cancer worldwide, being the presence of metastasis, mainly in the liver, a major contributor to high mortality rates in affected patients. The tumor microenvironment (TME)—comprised of interacting endothelial, stromal, and immune cells—plays a critical role in creating a supportive niche for tumor cell colonization and immune evasion and, thus, the establishment of metastases. The liver’s intrinsic nature further facilitates the development of immune tolerance, mediated by regulatory T cells, myeloid-derived suppressor cells, and soluble factors such as anti-inflammatory cytokines, which together dampen antitumor immune responses. This immunosuppressive milieu More > Graphic Abstract

    Understanding the Tumor Microenvironmental Mechanisms Driving Immunotherapy Resistance in Colorectal Cancer Liver Metastases

  • Open Access

    ARTICLE

    miR-100-5p Enhances Cell Cycle-Mediated Chemoresistance by Modulating the CTDSPL/pRB/E2F1 Signaling Pathway in Oxaliplatin-Resistant Colorectal Cancer Cells

    Yen-Pin Chen1,2,3, Rathinasamy Baskaran4, Hema Sri Devi4, Chaouhan Hitesh Singh4, Yu-Jung Lin4,5, Marthandam Asokan Shibu6, Wei-Wen Kuo7, Shih-Chieh Liao8, Ming-Cheng Chen9, Tso-Fu Wang10, Chi-Cheng Li11, Tsung-Jung Ho12, Tzu-Ching Shih13, Shinn-Zong Lin14,15,16,*, Chih-Yang Huang4,17,18,19,*

    Oncology Research, Vol.34, No.4, 2026, DOI:10.32604/or.2026.073080 - 23 March 2026

    Abstract Objective: MicroRNAs (miRNAs) are small, non-coding RNAs that play a key role in the development of chemoresistance in various cancer types, including colorectal cancer (CRC). In this study, we aimed to study the underlying mechanisms of miRNA in chemotherapy-resistant CRC. Methods: LoVo CRC cell line was exposed to oxaliplatin at an increased dose, and cells were cultured in the presence of oxaliplatin to develop LoVoOXR cells. Microarray and Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR), western blot, and transwell assay were used to evaluate the chemoresistance in LoVoOXR CRC cells. Results: Microarray and qRT-PCR analysis showed… More >

  • Open Access

    ARTICLE

    The FN1-ITGB4 Axis Drives Acquired Chemoresistance in Bladder Cancer by Activating FAK Signaling

    Xiaoyu Zhang1,#, RenFei Zong1,#, Yan Sun1, Nan Chen2, Kunyao Zhu1, Hang Tong1, Tinghao Li1, Junlong Zhu1, Zijia Qin1, Linfeng Wu1, Aimin Wang1, Weiyang He1,*

    Oncology Research, Vol.34, No.2, 2026, DOI:10.32604/or.2025.072084 - 19 January 2026

    Abstract Objective: While cisplatin-based chemotherapy is pivotal for advanced bladder cancer, acquired resistance remains a major obstacle. This study investigates key molecular drivers of this resistance and potential reversal strategies. Methods: We established GC (Gemcitabine and Cisplatin)-resistant T24-R and UC3-R cell lines from T24 and UM-UC-3 (UC3) cells. Transcriptomic and proteomic analyses identified differentially expressed molecules. Apoptosis and cell viability were assessed by flow cytometry and CCK-8 (Cell Counting Kit-8) assays, while RT-qPCR (Reverse Transcription Quantitative Polymerase Chain Reaction) and Western blot analyzed gene and protein expression. Immunofluorescence evaluated FAK (Focal Adhesion Kinase) phosphorylation, and a… More >

  • Open Access

    ARTICLE

    Utilization of a UPLC-MS/MS Approach to Elucidate the Role of ABCB1-Mediated Paclitaxel Resistance in Non-Small Cell Lung Cancer Cells

    Sha Hu1,2,#, Wenjing Wang1,#, Qianfang Hu3,#, Rujuan Zheng1,2, Qinghe Huang1,2, Hui Shi1,2, Xinyuan Ding3,*, Wenjuan Wang1,2,*, Zengyan Zhu1,2,*

    Oncology Research, Vol.34, No.2, 2026, DOI:10.32604/or.2025.068967 - 19 January 2026

    Abstract Objectives: Acquired resistance to paclitaxel represents a critical barrier to the effective chemotherapy of non-small cell lung cancer (NSCLC). The present study aimed to elucidate the molecular and pharmacological mechanisms promoting paclitaxel resistance in NSCLC and to explore potential strategies for overcoming this resistance. Methods: Here, we report an integrated pharmacological and analytical approach to quantify paclitaxel disposition and overcome resistance in a A549/TAX cell model (paclitaxel-resistant A549 cells). Results: Cell counting kit-8 (CCK-8) assay, colony formation, and apoptosis assays confirmed that A549/TAX cells exhibited marked resistance to paclitaxel relative to parental A549 cells. Based on… More >

  • Open Access

    ARTICLE

    miR-512-3p/RPS6KA2 Axis Regulates Cisplatin Resistance in Ovarian Cancer via Autophagy and Ferroptosis

    Jianfa Wu1,2,3, Huang Chen3, Sihong Wang1,2, Lei Peng1,2, Xiaoying Hu1,2, Zhou Liu1,2,*

    Oncology Research, Vol.34, No.1, 2026, DOI:10.32604/or.2025.070542 - 30 December 2025

    Abstract Objectives: Ribosomal protein S6 kinase A2 (RPS6KA2) has been identified as a potential prognostic biomarker in several cancers, including breast cancer, glioblastoma, and prostate cancer. However, its functional significance in ovarian cancer is not well characterized. This study was designed to explore the therapeutic relevance of modulating RPS6KA2 in the context of ovarian cancer, particularly in relation to cisplatin resistance. Methods: The expression levels of RPS6KA2 and key regulators involved in autophagy and ferroptosis were assessed using quantitative reverse transcription-PCR, immunofluorescence staining, immunohistochemistry, and western blotting. Prognostic associations were conducted using the Kaplan-Meier Plotter database.… More >

  • 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

    REVIEW

    Mechanistic Insights into the Role of Melatonin in Cancer Cell Chemoresistance

    Russel J. Reiter1,*, Ramaswamy Sharma2,*, Walter Manucha3, Walter Balduini4, Doris Loh5, Demetrios A. Spandidos6, Alejandro Romero7, Vasiliki E. Georgakopoulou8, Wei Zhu9

    BIOCELL, Vol.49, No.11, pp. 2033-2067, 2025, DOI:10.32604/biocell.2025.067661 - 24 November 2025

    Abstract The development of cancer cell resistance to conventional treatments continues to be a major obstacle in the successful treatment of tumors of many types. The discovery of a highly efficient direct and indirect free radical scavenger, melatonin, in the mitochondrial matrix may be a factor in determining both the occurrence of cancer cell drug insensitivity as well as radioresistance. This relates to two of the known hallmarks of cancer, i.e., exaggerated free radical generation in the mitochondria and the development of Warburg type metabolism (glycolysis). The hypothesis elaborated in this report assumes that the high… More >

  • Open Access

    ARTICLE

    Association of urinary tract infection and low albumin/globulin ratio with chemoresistance to gemcitabine-cisplatin in advanced urothelial carcinoma

    Jingcheng Lyu1,2,#, Ruiyu Yue1,2,#, Yichen Zhu1,2, Ye Tian1,2,*, Xinyi Hu1,2,*

    Canadian Journal of Urology, Vol.32, No.5, pp. 411-422, 2025, DOI:10.32604/cju.2025.066758 - 30 October 2025

    Abstract Objective: Urothelial carcinoma (UC) remains a prevalent malignancy with high recurrence and chemoresistance rates despite gemcitabine-cisplatin (GC) chemotherapy. The study aimed to identify clinical risk factors for chemoresistance in advanced UC patients and develop a predictive model. Method: A retrospective analysis was conducted on 375 UC patients who received postoperative GC chemotherapy between 2013 and 2024. Patients were categorized into chemotherapy-resistant (CR, n = 91) and non-chemotherapy resistant (NCR, n = 284) groups based on tumor progression. Clinical, pathological, and laboratory variables were compared using t-tests and chi-square tests. Kaplan-Meier assessed overall survival (OS), and binary More >

  • Open Access

    REVIEW

    Promising roles of vitamin D receptor and APRO family proteins for the development of cancer stem cells targeted malignant tumor therapy

    MOEKA NAKASHIMA, NAOKO SUGA, AKARI FUKUMOTO, SAYURI YOSHIKAWA, SATORU MATSUDA*

    Oncology Research, Vol.33, No.5, pp. 1007-1017, 2025, DOI:10.32604/or.2025.059657 - 18 April 2025

    Abstract Malignant tumors are heterogeneous diseases characterized by uncontrolled cell proliferation, invasion, metastasis, and/or recurrence of their malignancies. In particular, cancer stem cells (CSCs) within these tumors might be responsible for the property of invasiveness and/or therapies-resistance. CSCs are a self-renewing, awfully tumorigenic subpopulation of cancer cells, which are notorious for strong chemoresistance and are frequently responsible the aggravated invasion, metastasis, and/or recurrence. Developing targeting therapies against CSCs, therefore, may be deliberated a more encouraging mission for the greater cancer therapy. Innovation for a more potent anti-CSC treatment has been required as soon as possible.… More > Graphic Abstract

    Promising roles of vitamin D receptor and APRO family proteins for the development of cancer stem cells targeted malignant tumor therapy

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