Adjuvant COX inhibition augments STING signaling and cytolytic T cell infiltration in irradiated 4T1 tumors

Immune therapy is the new frontier of cancer treatment. Therapeutic radiation is a known inducer of immune response and can be limited by immunosuppressive mediators including cyclooxygenase-2 (COX2) that is highly expressed in aggressive triple negative breast cancer (TNBC). A clinical cohort of TNBC tumors revealed poor radiation therapeutic efficacy in tumors expressing high COX2. Herein, we show that radiation combined with adjuvant NSAID (indomethacin) treatment provides a powerful combination to reduce both primary tumor growth and lung metastasis in aggressive 4T1 TNBC tumors, which occurs in part through increased antitumor immune response. Spatial immunological changes including augmented lymphoid infiltration into the tumor epithelium and locally increased cGAS/STING1 and type I IFN gene expression were observed in radiation-indomethacin–treated 4T1 tumors. Thus, radiation and adjuvant NSAID treatment shifts “immune desert phenotypes” toward antitumor M1/TH1 immune mediators in these immunologically challenging tumors. Importantly, radiation-indomethacin combination treatment improved local control of the primary lesion, reduced metastatic burden, and increased median survival when compared with radiation treatment alone. These results show that clinically available NSAIDs can improve radiation therapeutic efficacy through increased antitumor immune response and augmented local generation of cGAS/STING1 and type I IFNs

A note on the optimal lower bound pull-out capacity of inclined strip anchors in sand

A generalized procedure based on finite elements and nonlinear programming has been presented in this paper for finding the optimal lower bound pull-out capacity of inclined strip anchors in sands. The results obtained are compared with the values reported in the literature to validate the suggested method of analysis. The predicted values are found to be in excellent agreement with that of Meyerhof. Key words : limit analysis, lower bound, nonlinear programming, inclined anchors, uplift capacity. </jats:p

A generalized procedure for predicting optimal lower bound break-out factors of strip anchors

A generalized procedure based on finite elements and non-linear programming has been developed and is presented to obtain lower-bound solutions for break-out factors for horizontal and vertical strip anchors embedded in sand. The validity of the method is shown by comparison of predicted values with experimental data and theoretical solutions available in the literature. Une procédure généralisée, basée sur une programmation non-linéaire par éléments finis, a été développée afin d'obtenir la solution en limite inférieure des facteurs de rupture pour des ancrages-plaques horizontaux ou verticaux enfoncés dans du sable. La validité de cette méthode est démontrée en comparant les valeurs calculées à partir de données expérimentales aux solutions théoriques disponibles dans la littérature. </jats:p