Alpha v beta 3 integrin antagonists enhance chemotherapy response in an orthotopic pancreatic cancer model

dc.contributor.authorSudha, Thangirala
dc.contributor.authorBharali, Dhruba J.
dc.contributor.authorDavis, Paul J.
dc.contributor.authorMousa, Shaker A.
dc.contributor.buuauthorCoşkun, Melis Debreli
dc.contributor.buuauthorÇelikler, Serap
dc.contributor.departmentBursa Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.tr_TR
dc.contributor.orcid0000-0002-4177-3478tr_TR
dc.contributor.researcheridCML-2517-2022tr_TR
dc.contributor.scopusid57194630463tr_TR
dc.contributor.scopusid8234554800tr_TR
dc.date.accessioned2023-01-02T08:21:36Z
dc.date.available2023-01-02T08:21:36Z
dc.date.issued2020-01-27
dc.description.abstractPancreatic cancer decreases survival time and quality of life because of drug resistance and peripheral neuropathy during conventional treatment. This study was undertaken to investigate whether alpha v beta 3 integrin receptor antagonist compounds NDAT and XT199 can suppress the development of cisplatin resistance and cisplatin-induced peripheral neuropathy in an orthotopic pancreatic SUIT2-luc cancer cell mouse model. Anticancer effects of these compounds and their combination with cisplatin were assessed in this tumor mouse model with bioluminescent signaling and histopathology, and a cytokine assay was used to examine expression of inflammatory cytokines IL-1 beta, IL-6, IL-10, and TNF-alpha from plasma samples. To determine the neuroprotective effects of the compounds on cisplatin-induced peripheral neuropathy, behavioral hind-limb posture of the mice was evaluated. The combination therapy of NDAT or XT199 with cisplatin elicited greater inhibition of tumor growth and increased tumor necrosis compared to cisplatin alone. NDAT and XT199 in combination with cisplatin significantly decreased expression of pro-inflammatory cytokines IL-1 beta, IL-6, and TNF-alpha and significantly increased expression of anti-inflammatory cytokine IL-10 in comparison to cisplatin alone. Cisplatin-treated groups showed stocking-glove hind-limb posture, whereas NDAT and XT199 with cisplatin-treated groups displayed normal hind-limb posture. Results clearly suggest that NDAT and XT199 treatment with cisplatin that inactivates NF-kappa B may contribute to increased antitumor and anti-inflammatory efficacy as well as alleviate cisplatin-mediated loss of motor function in this pancreatic tumor mouse model.en_US
dc.description.sponsorshipPharmaceutical Research Institute at Albany College of Pharmacy Health and Sciencesen_US
dc.identifier.citationCoşkun, M. D. vd. (2020). "Alpha v beta 3 integrin antagonists enhance chemotherapy response in an orthotopic pancreatic cancer model". Frontiers in Pharmacology, 11.en_US
dc.identifier.issn1663-9812
dc.identifier.pubmed32174830tr_TR
dc.identifier.scopus2-s2.0-85082498621tr_TR
dc.identifier.urihttps://doi.org/10.3389/fphar.2020.00095
dc.identifier.urihttps://www.frontiersin.org/articles/10.3389/fphar.2020.00095/full
dc.identifier.urihttp://hdl.handle.net/11452/30215
dc.identifier.volume11tr_TR
dc.identifier.wos000525314000001tr_TR
dc.indexed.pubmedPubMeden_US
dc.indexed.scopusScopusen_US
dc.indexed.wosSCIEen_US
dc.language.isoenen_US
dc.publisherFrontiers Mediaen_US
dc.relation.collaborationYurt dışıtr_TR
dc.relation.journalFrontiers in Pharmacologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergitr_TR
dc.relation.tubitak2214-A (1059B141401097)tr_TR
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectPancreatic canceren_US
dc.subjectNF-kappa Ben_US
dc.subjectCisplatinen_US
dc.subjectAlpha v beta 3 integrin receptor antagonisten_US
dc.subjectPeripheral neuropathyen_US
dc.subjectMotor dysfunctionen_US
dc.subjectInduced peripheral neurotoxicityen_US
dc.subjectTetraiodothyroacetic aicden_US
dc.subjectMultidrag-resistanceen_US
dc.subjectThyroid-hormoneen_US
dc.subjectAlpha(v)beta(3) antagonistsen_US
dc.subjectInflammatory cytokinesen_US
dc.subjectTargeted deliveryen_US
dc.subjectOxidative stressen_US
dc.subjectDrug-resistanceen_US
dc.subjectPharmacology & pharmacyen_US
dc.subject.emtree3 [3 [3 (4, 5 dihydroimidazol 2 ylamino)propyloxylisoxazol 5 yl]carbonylamino] 2 (phenylsulfonylamino)propionic aciden_US
dc.subject.emtreeAntineoplastic agenten_US
dc.subject.emtreeCisplatinen_US
dc.subject.emtreeInterleukin 10en_US
dc.subject.emtreeImmunoglobulin enhancer binding proteinen_US
dc.subject.emtreeInterleukin 1betaen_US
dc.subject.emtreeInterleukin 6en_US
dc.subject.emtreeReceptor blocking agenten_US
dc.subject.emtreeTumor necrosis factoren_US
dc.subject.emtreeUnclassified drugen_US
dc.subject.emtreeVitronectin receptoren_US
dc.subject.emtreeVitronectin receptor antagonisten_US
dc.subject.emtreeXt 199en_US
dc.subject.emtree[[4 [4 [3 [3 [poly 2 (2 hydroxyacetotoxy)]propanamido]aminopropoxy] 3,5 diiodophenoxy] 3,5 diiodophenyl] acetic acid]en_US
dc.subject.emtreeAnimal cellen_US
dc.subject.emtreeAnimal experimenten_US
dc.subject.emtreeAnimal modelen_US
dc.subject.emtreeAnimal tissueen_US
dc.subject.emtreeAntineoplastic activityen_US
dc.subject.emtreeArticleen_US
dc.subject.emtreeBioluminescenceen_US
dc.subject.emtreeBody positionen_US
dc.subject.emtreeCancer combination chemotherapyen_US
dc.subject.emtreeCancer inhibitionen_US
dc.subject.emtreeCancer modelen_US
dc.subject.emtreeCancer resistanceen_US
dc.subject.emtreeControlled studyen_US
dc.subject.emtreeDrug efficacyen_US
dc.subject.emtreeDrug potentiationen_US
dc.subject.emtreeFemaleen_US
dc.subject.emtreeHindlimben_US
dc.subject.emtreeHistopathologyen_US
dc.subject.emtreeInterleukin 10 blood levelen_US
dc.subject.emtreeInterleukin 1beta blood levelen_US
dc.subject.emtreeInterleukin 6 blood levelen_US
dc.subject.emtreeMonotherapyen_US
dc.subject.emtreeMotor dysfunctionen_US
dc.subject.emtreeMouseen_US
dc.subject.emtreeNeuroprotectionen_US
dc.subject.emtreeNonhumanen_US
dc.subject.emtreePancreas canceren_US
dc.subject.emtreePancreatic cancer cell lineen_US
dc.subject.emtreePeripheral neuropathyen_US
dc.subject.emtreeProtein blood levelen_US
dc.subject.emtreeProtein determinationen_US
dc.subject.emtreeProtein expressionen_US
dc.subject.emtreeSignal transductionen_US
dc.subject.emtreeSUIT2-luc cancer cell lineen_US
dc.subject.emtreeTranscription initiationen_US
dc.subject.emtreeTreatment responseen_US
dc.subject.emtreeTumor necrosisen_US
dc.subject.emtreeTumor necrosis factor blood levelen_US
dc.subject.scopusIntegrin; Thyroid Hormones; Nano-Diamino-Tetracen_US
dc.subject.wosPharmacology & pharmacyen_US
dc.titleAlpha v beta 3 integrin antagonists enhance chemotherapy response in an orthotopic pancreatic cancer modelen_US
dc.typeArticle
dc.wos.quartileQ1en_US

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