ArticleCancers2019
CAFs and TGF-β Signaling Activation by Mast Cells Contribute to Resistance to Gemcitabine/Nabpaclitaxel in Pancreatic Cancer.
Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
70 citing papers in PubMed, 85 citations in OpenAlex.
- Conversational Artificial Intelligence-Enabled Precision Oncology Reveals Context-Specific TGFβ and JAK/STAT Alterations in Pancreatic Cancer.medRxiv : the preprint server for health sciences · 2026Article
- Age- and Treatment-Specific TP53 and PI3K Alterations in Pancreatic Ductal Adenocarcinoma (PDAC) Revealed by Conversational Artificial Intelligence.International journal of molecular sciences · 2026Article
- CAF-derived exosomes: orchestrators of dysregulated signaling pathways in breast cancer progression.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- CHMP4C promotes pancreatic cancer progression by inhibiting necroptosis via the RIPK1/RIPK3/MLKL pathway.Journal of advanced research · 2025Article
- Molecular mechanism of pancreatic ductal adenocarcinoma: The heterogeneity of cancer-associated fibroblasts and key signaling pathways.World journal of clinical oncology · 2025Review
- Role of mast cell in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy.BMC cancer · 2025Article
- BAG6 restricts pancreatic cancer progression by suppressing the release of IL33-presenting extracellular vesicles and the activation of mast cells.Cellular & molecular immunology · 2024Article
- Unbiasedly decoding the tumor microenvironment with single-cell multiomics analysis in pancreatic cancer.Molecular cancer · 2024Review
- Review
- Unveiling the immunosuppressive landscape of pancreatic ductal adenocarcinoma: implications for innovative immunotherapy strategies.Frontiers in oncology · 2024Review
- Article
- Gelatin methacryloyl and Laponite bioink for 3D bioprinted organotypic tumor modeling.Biofabrication · 2023Article
- The role of TGF-β in the tumor microenvironment of pancreatic cancer.Genes & diseases · 2023Review
- Review
- Mast Cells and Resistance to Immunotherapy in Cancer.Archivum immunologiae et therapiae experimentalis · 2023Review
- Article
- Targeting tumor immunosuppressive microenvironment for pancreatic cancer immunotherapy: Current research and future perspective.Frontiers in oncology · 2023Review
- Resistance to Gemcitabine in Pancreatic Ductal Adenocarcinoma: A Physiopathologic and Pharmacologic Review.Cancers · 2022Review
- Dual Effect of Immune Cells within Tumour Microenvironment: Pro- and Anti-Tumour Effects and Their Triggers.Cancers · 2022Review
- Prediction of Survival and Tumor Microenvironment Infiltration Based on Pyroptosis-Related lncRNAs in Pancreatic Cancer.Disease markers · 2022Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Tumor⁻stroma interactions are of key importance for pancreatic ductal adenocarcinoma (PDAC) progression. Our aim was to investigate whether cancer associated fibroblasts (CAFs) and mast cells (MC) affected the sensitivity of PDAC cells to gemcitabine/nabpaclitaxel (GEM/NAB). For this purpose, the combination cytotoxicity and the effect on tumor invasion and angiogenesis were evaluated with or without a conditioned medium from the mast cell line HMC-1 (human mast cell line-1 cells) and CAFs. Beside the clinical outcome of a homogenous population of PDAC patients, receiving GEM/NAB, was correlated to the circulating levels of mast cell tryptase and to a panel of inflammatory and immunosuppressive cytokines. CAFs neither affected drugs' cytotoxicity nor the inhibition of angiogenesis, but promoted tumor cell invasion. The MC instead, caused resistance to drugs by reducing apoptosis, by activating the TGF-β signalling and by promoting tumor invasion. Indeed, the inhibition of TβRI serine/threonine kinase activity by galunisertib restored drugs cytotoxicity. Moreover, MC induced the release of TGF-β1, and increased expression of PAR-2, ERK1/2 and Akt activation. Accordingly, TGF-β1, tryptase and other pro-inflammatory and immunosuppressive cytokines increased in the unresponsive patients. In conclusion, MC play a pivotal role in the resistance to GEM/NAB. A correlation between high level of circulating pro-inflammatory/ immunosuppressive cytokines and unresponsiveness was found in PDAC patients.
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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.