ArticleOncotarget2015
TCGA data and patient-derived orthotopic xenografts highlight pancreatic cancer-associated angiogenesis.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 47 citations in OpenAlex.
- Ruxolitinib + capecitabine in advanced/metastatic pancreatic cancer after disease progression/intolerance to first-line therapy: JANUS 1 and 2 randomized phase III studies.Investigational new drugs · 2018Trial
- Integrated single cell and bulk RNA sequencing analyses reveal the impact of tryptophan metabolism on prognosis and immunotherapy in colon cancer.Scientific reports · 2025Article
- Clinical Evaluation of the Pancreatic Cancer Microenvironment: Opportunities and Challenges.Cancers · 2024Review
- The role of TGF-β in the tumor microenvironment of pancreatic cancer.Genes & diseases · 2023Review
- TGFβ-derived immune modulatory vaccine: targeting the immunosuppressive and fibrotic tumor microenvironment in a murine model of pancreatic cancer.Journal for immunotherapy of cancer · 2022Article
- A network pharmacology approach to reveal the pharmacological targets and biological mechanism of compound kushen injection for treating pancreatic cancer based on WGCNA and in vitro experiment validation.Chinese medicine · 2021Article
- TGF-β Signaling in Liver, Pancreas, and Gastrointestinal Diseases and Cancer.Gastroenterology · 2021Review
- Role of TGF-β in pancreatic ductal adenocarcinoma progression and PD-L1 expression.Cellular oncology (Dordrecht, Netherlands) · 2021Article
- Quis Custodiet Ipsos Custodes (Who Controls the Controllers)? Two Decades of Studies on HDAC9.Life (Basel, Switzerland) · 2021Review
- Combined inhibition of Ref-1 and STAT3 leads to synergistic tumour inhibition in multiple cancers using 3D and in vivo tumour co-culture models.Journal of cellular and molecular medicine · 2021Article
- The Binary Classification of Protein Kinases.Journal of inflammation research · 2021Article
- Article
- High HDAC9 is associated with poor prognosis and promotes malignant progression in pancreatic ductal adenocarcinoma.Molecular medicine reports · 2020Article
- Gene signature for prognosis in comparison of pancreatic cancer patients with diabetes and non-diabetes.PeerJ · 2020Article
- Targeting the JAK/STAT pathway in solid tumors.Journal of cancer metastasis and treatment · 2020Article
- A Panel of 12-lncRNA Signature Predicts Survival of Pancreatic Adenocarcinoma.Journal of Cancer · 2019Article
- Designer hydrogels: Shedding light on the physical chemistry of the pancreatic cancer microenvironment.Cancer letters · 2018Review
- Cyclooxygenase-2 induces angiogenesis in pancreatic cancer mediated by prostaglandin EOncology letters · 2018Article
- Pancreatic cancer ascites xenograft-an expeditious model mirroring advanced therapeutic resistant disease.Oncotarget · 2017Article
- Enhancing identification of cancer types via lowly-expressed microRNAs.Nucleic acids research · 2017Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Pancreatic ductal adenocarcinomas (PDACs) overexpress pro-angiogenic factors but are not viewed as vascular. Using data from The Cancer Genome Atlas we demonstrate that a subset of PDACs exhibits a strong pro-angiogenic signature that includes 37 genes, such as HDAC9, that are overexpressed in PDAC arising in KRC mice, which express mutated Kras and lack RB. Moreover, patient-derived orthotopic xenografts can exhibit tumor angiogenesis, whereas conditioned media (CM) from KRC-derived pancreatic cancer cells (PCCs) enhance endothelial cell (EC) growth and migration, and activate canonical TGF-β signaling and STAT3. Inhibition of the type I TGF-β receptor with SB505124 does not alter endothelial activation in vitro, but decreases pro-angiogenic gene expression and suppresses angiogenesis in vivo. Conversely, STAT3 silencing or JAK1-2 inhibition with ruxolitinib blocks CM-enhanced EC proliferation. STAT3 disruption also suppresses endothelial HDAC9 and blocks CM-induced HDAC9 expression, whereas HDAC9 re-expression restores CM-enhanced endothelial proliferation. Moreover, ruxolitinib blocks mitogenic EC/PCC cross-talk, and suppresses endothelial p-STAT3 and HDAC9, and PDAC progression and angiogenesis in vivo, while markedly prolonging survival of KRC mice. Thus, targeting JAK1-2 with ruxolitinib blocks a final pathway that is common to multiple pro-angiogenic factors, suppresses EC-mediated PCC proliferation, and may be useful in PDACs with a strong pro-angiogenic signature.
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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.