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A rebrand for proteasome inhibition in solid tumors via continuous hepatic artery infusion
Carolina M. Larrain, Jack H. Victory, Priyanka P. Desai, Lindsay R. Friedman, Hannah Stepp, Rachel Ashe, Kirsten Remmert, Surajit Sinha, Emily C. Smith, Nicole Russell, Tracey Pu, Alyssa V. Eade, Justine F. Burke, Jason Ho, Michael B. Yaffe, David E. Kleiner, Keith Schmidt, William D. Figg, Jonathan M. Hernandez
Carolina M. Larrain, Jack H. Victory, Priyanka P. Desai, Lindsay R. Friedman, Hannah Stepp, Rachel Ashe, Kirsten Remmert, Surajit Sinha, Emily C. Smith, Nicole Russell, Tracey Pu, Alyssa V. Eade, Justine F. Burke, Jason Ho, Michael B. Yaffe, David E. Kleiner, Keith Schmidt, William D. Figg, Jonathan M. Hernandez
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Research Letter Hepatology Oncology

A rebrand for proteasome inhibition in solid tumors via continuous hepatic artery infusion

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Abstract

Authors

Carolina M. Larrain, Jack H. Victory, Priyanka P. Desai, Lindsay R. Friedman, Hannah Stepp, Rachel Ashe, Kirsten Remmert, Surajit Sinha, Emily C. Smith, Nicole Russell, Tracey Pu, Alyssa V. Eade, Justine F. Burke, Jason Ho, Michael B. Yaffe, David E. Kleiner, Keith Schmidt, William D. Figg, Jonathan M. Hernandez

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Figure 1

Carfilzomib via HAI.

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Carfilzomib via HAI.
(A) CFZ concentrations following 30-minute infusion...
(A) CFZ concentrations following 30-minute infusion (n = 45). (B) CFZ effluent from HAI pump. (C) Left: Perfusion schema. Right: Pre- and posthepatic CFZ concentrations. (D) Bright-field images and IC50 curves for PDO-1 (top) and PDO-2 (bottom) at 10 nM CFZ for 1 hour or 96 hours. Note morphology (yellow arrows). Scale bars: 200 μm. (E and F) Proteasome activity and cell viability after 1 hour of 30 nM CFZ in PDO-1 (E) and PDO-2 (F). (G and H) Proteasome activity and cell viability after 48 hours of 30 nM CFZ in PDO-1 (G) and PDO-2 (H). Color indicates replicates. (I) Left: Perfusion schema. Right: Proteasome activity in tumor at 0 hours and 48 hours of perfusion with CFZ. (J) H&E and cleaved caspase-3 (CC3) staining at 0 hours and 48 hours of CFZ treatment. The box-and-whisker plot shows the median (line in box), 25th and 75th percentiles (box bounds), and minimum/maximum (whiskers). n = 4. Right: Average of CC3-positive nuclei (original magnification, ×10). Mean ± SD, n = 3. Scale bars: 200 μm. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001 by 1-way ANOVA followed by Dunnett’s post hoc test (E–H and J) or 2-tailed Student’s t test (I).

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