ArticleOncotarget2015
Anti-tumor effect of inhibition of IL-6 signaling in mucoepidermoid carcinoma.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
- Safety and preliminary efficacy of adding tocilizumab to cisplatin/docetaxel for the treatment of locally advanced triple-negative breast cancer patients: prospective phase 1/2 clinical trial.Scientific reports · 2026Trial
- Uncovering the Potential of 3D Spheroids for Modeling the Cellular Crosstalk Within the Tumor Microenvironment in HNSCC.Biotechnology journal · 2026Review
- No evidence for paradoxical effects of tocilizumab in rodents.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Cell culture in salivary gland tumor research: molecular insights of pathogenic targets and personalized medicine.Cytotechnology · 2025Review
- Systematic pharmacology-based strategy to explore the mechanism of Semen Strychni for treatment of papillary thyroid carcinoma.Scientific reports · 2023Article
- Macrophage-Specific NLRC5 Protects From Cardiac Remodeling Through Interaction With HSPA8.JACC. Basic to translational science · 2023Article
- The Role of IL-6 in Cancer Cell Invasiveness and Metastasis-Overview and Therapeutic Opportunities.Cells · 2022Review
- IL-6 inhibitors effectively reverse post-infarction cardiac injury and ischemic myocardial remodeling via the TGF-β1/Smad3 signaling pathway.Experimental and therapeutic medicine · 2022Article
- Mitogen signal-associated pathways, energy metabolism regulation, and mediation of tumor immunogenicity play essential roles in the cellular response of malignant pleural mesotheliomas to platinum-based treatment: a retrospective study.Translational lung cancer research · 2021Article
- Survival of salivary gland cancer stem cells requires mTOR signaling.Cell death & disease · 2021Article
- Anti-tumour effect of tocilizumab for osteosarcoma cell lines.Bone & joint research · 2020Article
- Interleukin-6-mediated epigenetic control of the VEGFR2 gene induces disorganized angiogenesis in human breast tumors.The Journal of biological chemistry · 2020Article
- Anti-inflammatory and anti-apoptosis activity of taraxasterol in ulcerative colitisExperimental and therapeutic medicine · 2019Article
- Regulation of radiosensitivity by 4-methylumbelliferone via the suppression of interleukin-1 in fibrosarcoma cells.Oncology letters · 2019Article
- 5-Hydroxymethylcytosine and ten-eleven translocation dioxygenases in head and neck carcinoma.Journal of Cancer · 2019Article
- Aberrant Epigenetic Regulation in Head and Neck Cancer Due to Distinct EZH2 Overexpression and DNA Hypermethylation.International journal of molecular sciences · 2018Article
- Tumor-derived mesenchymal-stem-cell-secreted IL-6 enhances resistance to cisplatin via the STAT3 pathway in breast cancer.Oncology letters · 2018Article
- The role of STAT3 in leading the crosstalk between human cancers and the immune system.Cancer letters · 2018Review
- Current State of Knowledge on Salivary Gland Cancers.Critical reviews in oncogenesis · 2018Review
- A mathematical model for IL-6-mediated, stem cell driven tumor growth and targeted treatment.PLoS computational biology · 2018Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Mucoepidermoid carcinoma (MEC) is the most frequent malignant salivary gland cancer. Response to chemoradiotherapy is modest, and therefore radical surgery remains the standard-of-care. Emerging evidence suggests that Interleukin (IL)-6 signaling correlates with the survival of cancer stem cells and resistance to therapy. Here, we investigated whether inhibition of IL-6 receptor (IL-6R) signaling with tocilizumab (humanized anti-human IL-6R antibody) sensitizes MEC to chemotherapy using human mucoepidermoid carcinoma cell lines (UM-HMC) and correspondent xenograft models. In vitro, we observed that tocilizumab inhibited STAT3 phosphorylation but had no measurable effect in MEC cell viability (UM-HMC-1,-3A,-3B). In contrast, the anti-tumor effect of single agent tocilizumab on MEC xenografts was comparable to paclitaxel or cisplatin. Combination of tocilizumab with cisplatin or paclitaxel enhanced the inhibitory effect of chemotherapy on xenograft growth (P < 0.05), time to failure (P < 0.01), decreased vascular endothelial growth factor (VEGF) expression and tumor microvessel density (P < 0.05) without added systemic toxicities. Notably, tocilizumab decreased the fraction of MEC cancer stem cells (ALDH(high)CD44(high)) in vitro, and prevented paclitaxel-induced increase in the fraction of cancer stem cells in vivo (P < 0.05). Collectively, these findings demonstrate that tocilizumab enhances the anti-tumor effect of conventional chemotherapy in preclinical models of mucoepidermoid carcinoma, and suggest that patients might benefit from combination therapy with an inhibitor of IL-6R signaling and chemotherapeutic agent such as paclitaxel.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.