ArticleOncotarget2016
Intratumoral heterogeneity of the therapeutical response to gemcitabine and metformin.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed.
- Article
- Metformin Suppresses Stemness of Non-Small-Cell Lung Cancer Induced by Paclitaxel through FOXO3a.International journal of molecular sciences · 2023Article
- The promising therapeutic effects of metformin on metabolic reprogramming of cancer-associated fibroblasts in solid tumors.Cellular & molecular biology letters · 2022Article
- Resistance to Gemcitabine in Pancreatic Ductal Adenocarcinoma: A Physiopathologic and Pharmacologic Review.Cancers · 2022Review
- Lipolysis-Stimulated Lipoprotein Receptor Impairs Hepatocellular Carcinoma and Inhibits the Oncogenic Activity of YAP1Frontiers in oncology · 2022Article
- Targeting pancreatic cancer with combinatorial treatment of CPI-613 and inhibitors of lactate metabolism.PloS one · 2022Article
- Voluntary wheel running behaviour as a tool to assess the severity in a mouse pancreatic cancer model.PloS one · 2021Article
- Cold Atmospheric Plasma Treatment for Pancreatic Cancer-The Importance of Pancreatic Stellate Cells.Cancers · 2020Review
- Selective phytochemicals targeting pancreatic stellate cells as new anti-fibrotic agents for chronic pancreatitis and pancreatic cancer.Acta pharmaceutica Sinica. B · 2020Review
- Benefits of non-invasive methods compared to telemetry for distress analysis in a murine model of pancreatic cancer.Journal of advanced research · 2020Article
- LW6 enhances chemosensitivity to gemcitabine and inhibits autophagic flux in pancreatic cancer.Journal of advanced research · 2019Article
- A novel multi-parametric analysis of non-invasive methods to assess animal distress during chronic pancreatitis.Scientific reports · 2019Article
- Grading Distress of Different Animal Models for Gastrointestinal Diseases Based on Plasma Corticosterone Kinetics.Animals : an open access journal from MDPI · 2019Article
- Article
- The role of stromal cancer-associated fibroblasts in pancreatic cancer.Journal of hematology & oncology · 2017Review
- Metformin Inhibits Gemcitabine Induced Apoptosis in Pancreatic Cancer Cell Lines.Journal of Cancer · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer heterogeneity and microenvironmental aspects within a tumor are considered key factors influencing resistance of carcinoma cells to distinct chemotherapeutical agents. We evaluated a high concentration of metformin in combination with gemcitabine on a syngeneic orthotopic mouse model using 6606PDA cells. We observed reduced tumor size and reduced cancer cell proliferation after three weeks of chemotherapy with either compound and noticed an additive effect between gemcitabine and metformin on tumor weight. Interestingly, distinct areas of the carcinoma responded differently to either compound. Metformin inhibited the proliferation of cancer cells close to the desmoplastic reaction, whereas gemcitabine inhibited the proliferation of cancer cells mainly 360-570 μm distant to the desmoplastic reaction. Indeed, co-culture of pancreatic stellate cells with 6606PDA, 7265PDA or MIA PaCa-2 cells increased gemcitabine resistance. Metformin resistance, however, was increased by high glucose concentration in the medium. Other factors such as hypoxia or the pH of the medium had no influence on gemcitabine or metformin induced inhibition of cancer cell proliferation. These data demonstrate a spatial heterogeneity in drug resistance within pancreatic adenocarcinomas and that microenvironmental aspects such as supply of glucose and the presence of pancreatic stellate cells regulate cancer cell sensitivity towards metformin or gemcitabine.
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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.