ArticlePloS one2012
Pan-Bcl-2 inhibitor AT-101 enhances tumor cell killing by EGFR targeted T cells.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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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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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
10 citing papers in PubMed, 14 citations in OpenAlex.
- Gossypol Acetic Acid Alleviates the Ferroptosis of Chondrocytes in Osteoarthritis by Inhibiting GPX4 Methylation.Current medicinal chemistry · 2025Article
- Bioenergetic alteration in gastrointestinal cancers: The good, the bad and the ugly.World journal of gastroenterology · 2023Review
- Plant Polyphenol Gossypol Induced Cell Death and Its Association with Gene Expression in Mouse Macrophages.Biomolecules · 2023Article
- Identification ofMolecules (Basel, Switzerland) · 2022Article
- Preclinical Efficacy and Toxicity Analysis of the Pan-Histone Deacetylase Inhibitor Gossypol for the Therapy of Colorectal Cancer or Hepatocellular Carcinoma.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Gossypol decreased cell viability and down-regulated the expression of a number of genes in human colon cancer cells.Scientific reports · 2021Article
- Isolation of Cottonseed Extracts That Affect Human Cancer Cell Growth.Scientific reports · 2018Article
- Sequential treatment with AT-101 enhances cisplatin chemosensitivity in human non-small cell lung cancer cells through inhibition of apurinic/apyrimidinic endonuclease 1-activated IL-6/STAT3 signaling pathway.Drug design, development and therapy · 2014Article
- Adoptive T-cell transfer therapy and oncogene-targeted therapy for melanoma: the search for synergy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Review
- Targeting and killing of glioblastoma with activated T cells armed with bispecific antibodies.BMC cancer · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Pancreatic cancer is a deadly disease and has the worst prognosis among almost all cancers and is in dire need of new and improved therapeutic strategies. Conditioning of tumor cells with chemotherapeutic drug has been shown to enhance the anti-tumor effects of cancer vaccines and adoptive cell therapy. In this study, we investigated the immunomodulatory effects of pan-Bcl-2 inhibitor AT-101 on pancreatic cancer (PC) cell cytotoxicity by activated T cells (ATC). The effects of AT-101 on cytotoxicity, early apoptosis, and Granzyme B (GrzB) and IFN-γ signaling pathways were evaluated during EGFR bispecific antibody armed ATC (aATC)-mediated killing of L3.6pl and MiaPaCa-2 PC cells pre-sensitized with AT-101. We found that pretreatment of tumor cells with AT-101 enhanced susceptibility of L3.6pl and MiaPaCa-2 tumor cells to ATC and aATC-mediated cytotoxicity, which was in part mediated via enhanced release of cytolytic granule GrzB from ATC and aATC. AT-101-sensitized L3.6pl cells showed up-regulation of IFN-γ-mediated induction in the phosphorylation of Ser(727)-Stat1 (pS(727)-Stat1), and IFN-γ induced dephosphorylation of phospho-Tyr(705)-Stat3 (pY(705)-Stat3). Priming (conditioning) of PC cells with AT-101 can significantly enhance the anti-tumor activity of EGFRBi armed ATC through increased IFN-γ induced activation of pS(727)-Stat1 and inhibition of pY(705)-Stat3 phosphorylation, and resulting in increased ratio of pro-apoptotic to anti-apoptotic proteins. Our results verify enhanced cytotoxicity after a novel chemotherapy conditioning strategy against PC that warrants further in vivo and clinical investigations.
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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.