Figure 6.
Targeted depletion of HA releases water from the gel-fluid phase and lowers fluid pressures. (A) Real-time, intravital IFP in BxPC3/HAS3 xenografts measured by PC (blue line) and WN (red line) before and during systemic treatment with PEGPH20 (arrow). The significantly higher baseline IFP values measured by the PC converge with those measured by the WN after targeted depletion of HA and mobilization of complexed fluid. (B) HA content in BxPC3/HAS3 tumors 2 h posttreatment with vehicle (V) or PEGPH20 (P), demonstrating significant depletion in enzyme-treated tumors. ∗∗∗∗p < 0.0001. (C) Water content of BxPC3/HAS3 tumors 2 h after vehicle or PEGPH20 treatment, showing significant reduction in tumors from enzyme-treated animals. ∗∗∗∗p < 0.0001. (D) Real-time, intravital IFP in autochthonous PDA measured by PC (blue line) and WN (red line) during intravenous treatment with PEGPH20 (arrow). (E) Real-time, intravital IFP in autochthonous PDA measured by PC (blue line) and WN (red line) after intratumoral injection of PEGPH20 (arrow). (F) Cardiac cessation had modest effects on interstitial fluid pressures measured with either the PC (blue symbols) or WN (red symbols). Each line connecting a pair of points represents an independent animal. ∗p < 0.05. (G) The mean change in IFP after cardiac cessation recorded by the PC (blue symbols) in autochthonous KPC PDA and xenografts was −3.5 ± 1.1 mmHg and −2.1 ± 0.5 mmHg, respectively. The WN-recorded pressures (red symbols) changed by an average of −1.3 ± 0.9 mmHg in autochthonous PDA and −1.7 ± 0.9 mmHg in xenografts.