FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2560465010> ?p ?o ?g. }

• W2560465010 abstract "Abstract Patulin (4-Hydroxy-4H-furo 3,2-C-pyran-2(6H)-one) is a first-in-class mycotoxin under development as a novel chemotherapeutic agent. The mechanism of action of Patulin has been reported to include activation of mitogen activated protein kinases (MAPKs) and generation of reactive oxygen species (ROS). We have previously shown Patulin to have activity against myeloma, leukemia, and lymphoma cell lines, as well as primary tumor cells in clinical samples from patients with these diagnoses (Wang BLOOD 2007). Moreover, we have shown that Patulin specifically and potently targets tumor cells over normal cells and effectively killed primary tumor cells of patients with refractory illness. The aim of this study was to determine whether Patulin acts synergistically with the topoisomerase inhibitor doxorubicin or the proteasome inhibitor bortezomib. We hypothesize that drugs with non-cross-reactive modes of action could be complementary. Human tumor cell lines from B-cell lymphoma (DAUDI), T-Cell leukemia and lymphoma (Jurkat and H9, respectively), and myeloid leukemia (HL60) malignancies were tested for their sensitivity to single agents Patulin, bortezomib, and doxorubicin as well as Patulin in combination with the latter two agents (Patulin and bortezomib, P + B; Patulin and doxorubicin, P + D). Cells were treated with a range of concentrations of each single agent and the drugs in combination over 24 hours. Following treatment, cell metabolic activity was assessed using a microculture tetrazolium (MTT) assay and cell viability was assessed by flow cytometry using Annexin V and propidium iodide (PI) staining. Dose-effect curves, median effect plots, and combination index (CI) values were generated in the Compusyn software program for each target cell population. Median-effect doses (IC50s) of individual drugs were interpolated using the y-intercept of median-effect plots. Three dose-effect data points were used to create a range of CI values at different fractions of affect (fa). The lower and upper values of the CI range were used to characterize drug combinations as synergistic, antagonistic, or additive based on Chou’s Symbols for Synergism and Antagonism using CI analysis (Table 1). The role for ROS in the mechanism of action of Patulin was confirmed by flow cytometry showing increased levels of ROS in cell lines following Patulin exposure. Preincubation of cell lines with N-acetyl cysteine (NAC) or concurrent exposure to Patulin and NAC abrogated the cytotoxic activity of the mycotoxin. H9 cells were most sensitive to the effects of Patulin, with an IC50 of 1.2 μM. Combinations of P + B acted synergistically against Jurkat, H9, DAUDI, and HL60 tumor cells; however, P + B also demonstrated moderate antagonism against the Jurkat and H9 cell lines (Table 2). Likewise, combinations of P + D interacted synergistically against Jurkat, H9, DAUDI, and HL60 tumor cell lines while simultaneously demonstrating strong antagonism against the H9 cell line. Patulin kills leukemia and lymphoma cells via generation of intracellular ROS. Synergy of Patulin with either bortezomib or doxorubicin in leukemia and lymphoma cell lines indicates a distinct mechanism of action for the mycotoxin and compared to other chemotherapeutics and supports the rationale for continued development of Patulin as a novel chemotherapeutic mycotoxin. TABLE 1. Chou’s Symbols for Synergism and Antagonism using CI Analysis CI Description &lt; 0.1 Very Strong Synergism 0.1–0.3 Strong Synergism 0.3–0.7 Synergism 0.7–0.85 Moderate Synergism 0.85–0.90 Slight Synergism 0.90–1.10 Nearly Additive 1.10–1.20 Slight Antagonism 1.20–1.45 Moderate Antagonism 1.45–3.3 Antagonism 3.3–10 Strong Antagonism &gt; 10 Very Strong Antagonism TABLE 2. IC50 of single agents patulin, bortezomib, and doxorubicin and CI in hematological cancer cell lines Tumor cell line IC50 of patulin (μM) IC50 of bortezomib (nM) IC50 of doxorubicin (μM) CI: P + B CI: P + D T-Cell Jurkat 1.16 5600 5.2 0.6 -- 1.2 0.1 -- 1.2 H9 1.2 14 0.33 0.4 -- &gt; 1 0.3 -- &gt; 1 B-Cell DAUDI 0.98 1.1 0.19 &lt; 0.1 -- 0.1 &lt; 0.1 -- 0.3 Myeloid HL60 1.7 0.42 0.07 &lt; 0.1 -- 0.1 &lt; 0.1" @default.
• W2560465010 created "2016-12-16" @default.
• W2560465010 creator A5006467806 @default.
• W2560465010 creator A5011386306 @default.
• W2560465010 creator A5023276777 @default.
• W2560465010 creator A5046424825 @default.
• W2560465010 creator A5057013064 @default.
• W2560465010 creator A5071389779 @default.
• W2560465010 date "2008-11-16" @default.
• W2560465010 modified "2023-09-28" @default.
• W2560465010 title "Patulin Acts Synergistically with Doxorubicin and Bortezomib in Cytotoxicity against Hematological Malignancies" @default.
• W2560465010 doi "https://doi.org/10.1182/blood.v112.11.2664.2664" @default.
• W2560465010 hasPublicationYear "2008" @default.
• W2560465010 type Work @default.
• W2560465010 sameAs 2560465010 @default.
• W2560465010 citedByCount "0" @default.
• W2560465010 crossrefType "journal-article" @default.
• W2560465010 hasAuthorship W2560465010A5006467806 @default.
• W2560465010 hasAuthorship W2560465010A5011386306 @default.
• W2560465010 hasAuthorship W2560465010A5023276777 @default.
• W2560465010 hasAuthorship W2560465010A5046424825 @default.
• W2560465010 hasAuthorship W2560465010A5057013064 @default.
• W2560465010 hasAuthorship W2560465010A5071389779 @default.
• W2560465010 hasConcept C126322002 @default.
• W2560465010 hasConcept C185592680 @default.
• W2560465010 hasConcept C190283241 @default.
• W2560465010 hasConcept C203014093 @default.
• W2560465010 hasConcept C2775934118 @default.
• W2560465010 hasConcept C2776364478 @default.
• W2560465010 hasConcept C2776694085 @default.
• W2560465010 hasConcept C2777478702 @default.
• W2560465010 hasConcept C2778367456 @default.
• W2560465010 hasConcept C2778729363 @default.
• W2560465010 hasConcept C2779550045 @default.
• W2560465010 hasConcept C2780783641 @default.
• W2560465010 hasConcept C2781303535 @default.
• W2560465010 hasConcept C31573885 @default.
• W2560465010 hasConcept C31903555 @default.
• W2560465010 hasConcept C502942594 @default.
• W2560465010 hasConcept C53227056 @default.
• W2560465010 hasConcept C55493867 @default.
• W2560465010 hasConcept C71924100 @default.
• W2560465010 hasConcept C84699730 @default.
• W2560465010 hasConcept C98274493 @default.
• W2560465010 hasConceptScore W2560465010C126322002 @default.
• W2560465010 hasConceptScore W2560465010C185592680 @default.
• W2560465010 hasConceptScore W2560465010C190283241 @default.
• W2560465010 hasConceptScore W2560465010C203014093 @default.
• W2560465010 hasConceptScore W2560465010C2775934118 @default.
• W2560465010 hasConceptScore W2560465010C2776364478 @default.
• W2560465010 hasConceptScore W2560465010C2776694085 @default.
• W2560465010 hasConceptScore W2560465010C2777478702 @default.
• W2560465010 hasConceptScore W2560465010C2778367456 @default.
• W2560465010 hasConceptScore W2560465010C2778729363 @default.
• W2560465010 hasConceptScore W2560465010C2779550045 @default.
• W2560465010 hasConceptScore W2560465010C2780783641 @default.
• W2560465010 hasConceptScore W2560465010C2781303535 @default.
• W2560465010 hasConceptScore W2560465010C31573885 @default.
• W2560465010 hasConceptScore W2560465010C31903555 @default.
• W2560465010 hasConceptScore W2560465010C502942594 @default.
• W2560465010 hasConceptScore W2560465010C53227056 @default.
• W2560465010 hasConceptScore W2560465010C55493867 @default.
• W2560465010 hasConceptScore W2560465010C71924100 @default.
• W2560465010 hasConceptScore W2560465010C84699730 @default.
• W2560465010 hasConceptScore W2560465010C98274493 @default.
• W2560465010 hasLocation W25604650101 @default.
• W2560465010 hasOpenAccess W2560465010 @default.
• W2560465010 hasPrimaryLocation W25604650101 @default.
• W2560465010 hasRelatedWork W1973074169 @default.
• W2560465010 hasRelatedWork W1987378323 @default.
• W2560465010 hasRelatedWork W2006269123 @default.
• W2560465010 hasRelatedWork W2053393533 @default.
• W2560465010 hasRelatedWork W2355269513 @default.
• W2560465010 hasRelatedWork W2395292353 @default.
• W2560465010 hasRelatedWork W2412955604 @default.
• W2560465010 hasRelatedWork W2556085825 @default.
• W2560465010 hasRelatedWork W2559180163 @default.
• W2560465010 hasRelatedWork W2578830389 @default.
• W2560465010 hasRelatedWork W2583616640 @default.
• W2560465010 hasRelatedWork W2589605497 @default.
• W2560465010 hasRelatedWork W2589826466 @default.
• W2560465010 hasRelatedWork W2594181272 @default.
• W2560465010 hasRelatedWork W2979635961 @default.
• W2560465010 hasRelatedWork W2979735353 @default.
• W2560465010 hasRelatedWork W2989206149 @default.
• W2560465010 hasRelatedWork W2992223253 @default.
• W2560465010 hasRelatedWork W3032661471 @default.
• W2560465010 hasRelatedWork W3045015177 @default.
• W2560465010 isParatext "false" @default.
• W2560465010 isRetracted "false" @default.
• W2560465010 magId "2560465010" @default.
• W2560465010 workType "article" @default.