FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2313754129> ?p ?o ?g. }

• W2313754129 abstract "Background: Resistance arises in patients with small cell lung cancer (SCLC) following treatment with chemotherapeutic agents. Suicide gene (SG) therapy is a novel treatment strategy for cancer in which the introduced therapeutic gene encodes an enzyme capable of transforming a non-toxic prodrug into a cell poison. By coupling the SCLC specific promoter Insulinoma-associated 1 (INSM1) to the SG, it is possible to target SG expression and resulting cytotoxicity exclusive to SCLC cells. The aim of this project was to investigate the influence of chemo-resistance on transcriptional targeted SG therapy. Results: As an in vitro model of chemo-resistance we used a number of SCLC cell lines resistant to different chemotherapeutic agents used in first-line treatment of SCLC patients. Protein expression analysis showed the cells lines to vary in expression of a several proteins correlated to development of resistance. Despite of this the INSM1 promoter activity was found to be equally or increased in chemo-resistant compared to chemo-sensitive cells as measured by luciferase reporter assays and determination of INSM1 mRNA levels by RT-PCR. Additionally, in tumor xenografts stably expressing EGFP from the INSM1 promoter it was apparent that the INSM1 promoter activity is very strong and stable in vivo. Cytotoxic effects of two different SG systems driven by the INSM1 promoter were tested in the chemo-resistant cell lines by MTT assays. One consisted of the fusion SG of yeast-cytosine-deaminase (YCD) and yeast-uracil-phosphoribosyl-transferase (YUPRT) and the prodrug 5-fluorocytosin (5-FC). The other system consisted of the Nitroreductase (NTR) gene and SN27686 prodrug. While equal sensitivity was found in chemo-sensitive and -resistant cells towards YCD-YUPRT/5-FC therapy, the NTR/SN276868 system showed reduced cytotoxicity in cells resistant to alkylating agents. Importantly, equal cytotoxicity could be obtained in these chemo-resistant cells upon NTR/SN27686 therapy by exposing cells to higher prodrug doses, still not inducing off-target toxicity in NTR-negative cells. Finally, the combination of YCD-YUPRT/5-FC SG therapy with standard chemotherapy and with NTR/SN27686 SG therapy, respectively, were tested and evaluated by MTT assay. In contrast to chemo-sensitive cells, where the combination therapy had no additive effect, significantly additive cytotoxicity was achieved in chemo-resistant SCLC cells exposed to combination therapy compared to single agent therapy. Conclusion: The results demonstrate that targeted SG therapy is equally effective in chemo-resistant and -sensitive SCLC cells and that additional effect can be achieved in chemo-resistant SCLC cells when SG therapy is given in combination with chemotherapy or another SG therapy system. INSM1-driven SG therapy therefore seems potent to be effective in the treatment of SCLC patients with chemo-resistant tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 832. doi:1538-7445.AM2012-832" @default.
• W2313754129 created "2016-06-24" @default.
• W2313754129 creator A5004172331 @default.
• W2313754129 creator A5013721197 @default.
• W2313754129 creator A5014712279 @default.
• W2313754129 creator A5044697465 @default.
• W2313754129 creator A5065012596 @default.
• W2313754129 creator A5078278512 @default.
• W2313754129 date "2012-04-15" @default.
• W2313754129 modified "2023-09-28" @default.
• W2313754129 title "Abstract 832: Suicide gene therapy is effective for treating chemo-resistant small cell lung cancer cells" @default.
• W2313754129 doi "https://doi.org/10.1158/1538-7445.am2012-832" @default.
• W2313754129 hasPublicationYear "2012" @default.
• W2313754129 type Work @default.
• W2313754129 sameAs 2313754129 @default.
• W2313754129 citedByCount "0" @default.
• W2313754129 crossrefType "proceedings-article" @default.
• W2313754129 hasAuthorship W2313754129A5004172331 @default.
• W2313754129 hasAuthorship W2313754129A5013721197 @default.
• W2313754129 hasAuthorship W2313754129A5014712279 @default.
• W2313754129 hasAuthorship W2313754129A5044697465 @default.
• W2313754129 hasAuthorship W2313754129A5065012596 @default.
• W2313754129 hasAuthorship W2313754129A5078278512 @default.
• W2313754129 hasConcept C104317684 @default.
• W2313754129 hasConcept C111599444 @default.
• W2313754129 hasConcept C121608353 @default.
• W2313754129 hasConcept C150194340 @default.
• W2313754129 hasConcept C153911025 @default.
• W2313754129 hasConcept C161733203 @default.
• W2313754129 hasConcept C173396325 @default.
• W2313754129 hasConcept C185592680 @default.
• W2313754129 hasConcept C207001950 @default.
• W2313754129 hasConcept C2777748644 @default.
• W2313754129 hasConcept C34981463 @default.
• W2313754129 hasConcept C502942594 @default.
• W2313754129 hasConcept C54355233 @default.
• W2313754129 hasConcept C55493867 @default.
• W2313754129 hasConcept C81885089 @default.
• W2313754129 hasConcept C86803240 @default.
• W2313754129 hasConcept C96232424 @default.
• W2313754129 hasConceptScore W2313754129C104317684 @default.
• W2313754129 hasConceptScore W2313754129C111599444 @default.
• W2313754129 hasConceptScore W2313754129C121608353 @default.
• W2313754129 hasConceptScore W2313754129C150194340 @default.
• W2313754129 hasConceptScore W2313754129C153911025 @default.
• W2313754129 hasConceptScore W2313754129C161733203 @default.
• W2313754129 hasConceptScore W2313754129C173396325 @default.
• W2313754129 hasConceptScore W2313754129C185592680 @default.
• W2313754129 hasConceptScore W2313754129C207001950 @default.
• W2313754129 hasConceptScore W2313754129C2777748644 @default.
• W2313754129 hasConceptScore W2313754129C34981463 @default.
• W2313754129 hasConceptScore W2313754129C502942594 @default.
• W2313754129 hasConceptScore W2313754129C54355233 @default.
• W2313754129 hasConceptScore W2313754129C55493867 @default.
• W2313754129 hasConceptScore W2313754129C81885089 @default.
• W2313754129 hasConceptScore W2313754129C86803240 @default.
• W2313754129 hasConceptScore W2313754129C96232424 @default.
• W2313754129 hasLocation W23137541291 @default.
• W2313754129 hasOpenAccess W2313754129 @default.
• W2313754129 hasPrimaryLocation W23137541291 @default.
• W2313754129 hasRelatedWork W1976151688 @default.
• W2313754129 hasRelatedWork W2010734065 @default.
• W2313754129 hasRelatedWork W2019522166 @default.
• W2313754129 hasRelatedWork W2037805301 @default.
• W2313754129 hasRelatedWork W2042581702 @default.
• W2313754129 hasRelatedWork W2077594056 @default.
• W2313754129 hasRelatedWork W2081634649 @default.
• W2313754129 hasRelatedWork W2091708359 @default.
• W2313754129 hasRelatedWork W2113923002 @default.
• W2313754129 hasRelatedWork W2162610375 @default.
• W2313754129 hasRelatedWork W2372241904 @default.
• W2313754129 hasRelatedWork W2386476358 @default.
• W2313754129 hasRelatedWork W2571476314 @default.
• W2313754129 hasRelatedWork W2770878806 @default.
• W2313754129 hasRelatedWork W2887954396 @default.
• W2313754129 hasRelatedWork W2919156302 @default.
• W2313754129 hasRelatedWork W2923897117 @default.
• W2313754129 hasRelatedWork W3003911587 @default.
• W2313754129 hasRelatedWork W3040019917 @default.
• W2313754129 hasRelatedWork W3128251948 @default.
• W2313754129 isParatext "false" @default.
• W2313754129 isRetracted "false" @default.
• W2313754129 magId "2313754129" @default.
• W2313754129 workType "article" @default.