Sudha, ThangiralaBharali, Dhruba J.Davis, Paul J.Mousa, Shaker A.2023-01-022023-01-022020-01-27Coşkun, M. D. vd. (2020). "Alpha v beta 3 integrin antagonists enhance chemotherapy response in an orthotopic pancreatic cancer model". Frontiers in Pharmacology, 11.1663-9812https://doi.org/10.3389/fphar.2020.00095https://www.frontiersin.org/articles/10.3389/fphar.2020.00095/fullhttp://hdl.handle.net/11452/30215Pancreatic 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.eninfo:eu-repo/semantics/openAccessPancreatic cancerNF-kappa BCisplatinAlpha v beta 3 integrin receptor antagonistPeripheral neuropathyMotor dysfunctionInduced peripheral neurotoxicityTetraiodothyroacetic aicdMultidrag-resistanceThyroid-hormoneAlpha(v)beta(3) antagonistsInflammatory cytokinesTargeted deliveryOxidative stressDrug-resistancePharmacology & pharmacyArticle0005253140000012-s2.0-850824986211132174830Pharmacology & pharmacyIntegrin; Thyroid Hormones; Nano-Diamino-Tetrac3 [3 [3 (4, 5 dihydroimidazol 2 ylamino)propyloxylisoxazol 5 yl]carbonylamino] 2 (phenylsulfonylamino)propionic acidAntineoplastic agentCisplatinInterleukin 10Immunoglobulin enhancer binding proteinInterleukin 1betaInterleukin 6Receptor blocking agentTumor necrosis factorUnclassified drugVitronectin receptorVitronectin receptor antagonistXt 199[[4 [4 [3 [3 [poly 2 (2 hydroxyacetotoxy)]propanamido]aminopropoxy] 3,5 diiodophenoxy] 3,5 diiodophenyl] acetic acid]Animal cellAnimal experimentAnimal modelAnimal tissueAntineoplastic activityArticleBioluminescenceBody positionCancer combination chemotherapyCancer inhibitionCancer modelCancer resistanceControlled studyDrug efficacyDrug potentiationFemaleHindlimbHistopathologyInterleukin 10 blood levelInterleukin 1beta blood levelInterleukin 6 blood levelMonotherapyMotor dysfunctionMouseNeuroprotectionNonhumanPancreas cancerPancreatic cancer cell linePeripheral neuropathyProtein blood levelProtein determinationProtein expressionSignal transductionSUIT2-luc cancer cell lineTranscription initiationTreatment responseTumor necrosisTumor necrosis factor blood level