ArticleOncotarget2018
Leptin-Notch axis impairs 5-fluorouracil effects on pancreatic cancer.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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.
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
33 citing papers in PubMed, 38 citations in OpenAlex.
- Lactic acid metabolism: gynecological cancer's Achilles' heel.Discover oncology · 2025Review
- Unraveling molecular interconnections and identifying potential therapeutic targets of significance in obesity-cancer link.Journal of the National Cancer Center · 2025Review
- Obesity-Associated Colorectal Cancer.International journal of molecular sciences · 2024Review
- Role of Different Variants of Leptin Receptor in Human Adrenal Tumor Types.International journal of molecular sciences · 2024Article
- White adipocyte dysfunction and obesity-associated pathologies in humans.Nature reviews. Molecular cell biology · 2024Review
- Role of ABCC5 in cancer drug resistance and its potential as a therapeutic target.Frontiers in cell and developmental biology · 2024Review
- Adipokines and epithelial-mesenchymal transition (EMT) in cancer.Molecular and cellular biochemistry · 2023Review
- Assessment of the Role of Leptin and Adiponectinas Biomarkers in Pancreatic Neuroendocrine Neoplasms.Cancers · 2023Article
- Obesity and cancer: focus on leptin.Molecular biology reports · 2023Review
- Targeting of Notch, IL-1, and leptin has therapeutic potential in xenograft colorectal cancer.Turkish journal of biology = Turk biyoloji dergisi · 2023Article
- New insights into the role of adipocytes in pancreatic cancer progression: paving the way towards novel therapeutic targets.Theranostics · 2023Review
- A lipid metabolism-related risk signature for patients with gliomas constructed with TCGA and CGGA data.Medicine · 2022Article
- Role of Leptin and Adiponectin in Endometrial Cancer.International journal of molecular sciences · 2022Review
- Targeting lipid metabolism in the treatment of ovarian cancer.Oncotarget · 2022Review
- The Role of Adipokines in Pancreatic Cancer.Frontiers in oncology · 2022Review
- Obesity and Pancreatic Cancer: Insight into Mechanisms.Cancers · 2021Review
- Signaling Role of Adipocyte Leptin in Prostate Cell Proliferation Induced by Trichomonas vaginalis.The Korean journal of parasitology · 2021Article
- Isolation and Characterization of Human Colon Adenocarcinoma Stem-Like Cells Based on the Endogenous Expression of the Stem Markers.International journal of molecular sciences · 2021Article
- Leptin and Cancer: Updated Functional Roles in Carcinogenesis, Therapeutic Niches, and Developments.International journal of molecular sciences · 2021Review
- Pancreatic Tumorigenesis: Oncogenic KRAS and the Vulnerability of the Pancreas to Obesity.Cancers · 2021Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
5-FU chemotherapy is a current strategy to treat pancreatic cancer (PC), but unfortunately chemoresistance is eventually developed in most patients. Obesity is a risk factor for PC that could affect 5-FU effectiveness through the adipokine leptin, which is a known proliferation, survival factor and Notch inducer. We investigated whether leptin signaling affects 5-FU cytotoxicity on PC. To this end, tumorspheres developed from BxPC-3 and MiaPaCa-2 PC cells were treated with 5-FU, leptin, inhibitors for Notch (DAPT) and leptin signaling (IONP-LPrA2) and ATP-binding cassette of proteins (Probenecid). Leptin treatment decreased 5-FU cytotoxicity, and increased cell proliferation, colony forming ability, stem cell, pluripotency, EMT markers, drug efflux proteins (ABCC5, ABCC11) and Notch. In addition, leptin reduced the 5-FU effects on apoptosis by decreasing pro-apoptotic (Bax, Caspase-3 activation and PARP degradation) and increasing anti-apoptotic factors (RIP and Bcl-XL). Leptin's effects on PC tumorspheres treated with 5-FU were reduced by IONP-LPrA2 and were mainly Notch signaling- dependent and more evident in MiaPaCa-2-derived tumorspheres. Present results suggest that leptin could impair 5-FU cytotoxicity and promote chemoresistance. Therefore, targeting the leptin-Notch axis could be a novel way to improve 5-FU therapy for PC patients, especially in obesity context.
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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.