Impaired Synthesis of Stromal Components in Response to @entity68586 Improves Vascular Function, Drug Delivery, and Survival in XXXX .

@entity1 @entity788 @entity5 @entity73 @entity19 @entity2269 @entity9367 @entity68586 @entity2483
PURPOSE: @entity788 stromal microenvironment is considered to be the major reason for failure of conventional and targeted therapy for this disease. The @entity2269 , comprising mainly collagen and glycosaminoglycans like hyaluronan (HA), is responsible for compression of vasculature in the @entity5 resulting in @entity73 and poor prognosis. @entity68586 , a water-soluble prodrug of @entity9367 currently in phase I clinical trial, has been very effective in multiple animal models of @entity788 . However, whether @entity68586 will have efficacious delivery into the @entity5 despite the @entity2269 has not been evaluated before. EXPERIMENT DESIGN: @entity1 @entity5 -derived xenografts (PDX) and spontaneous @entity788 @entity19 were treated with 0.42 and 0.21 mg/kg body weight for 30 days. Stromal components were determined by IHC and ELISA-based assays. Vascular functionality and drug delivery to the @entity5 were assessed following treatment with @entity68586 . RESULT: Our current study shows that treatment with @entity68586 resulted in @entity2483 and collagen in the @entity788 stroma of both the spontaneous KPC @entity19 as well as in @entity1 @entity5 xenografts. Furthermore, treatment with @entity68586 improved functional vasculature in the @entity5 resulting in four times more functional vessels in the treated animals compared with untreated animals. Consistent with this observation, @entity68586 also resulted in increased drug delivery into the @entity5 compared with untreated animals. Along with this, @entity68586 also decreased viability of the stromal cells along with the @entity5 cells in @entity788 . CONCLUSIONS: In conclusion, these results are extremely promising as they indicate that @entity68586 , along with having anticancer effects is also able to deplete stroma in @entity788 , which makes it an effective therapy for @entity788 . Clin Cancer Res; 22(2); 415-25.   2015 AACR.
