Abstract

Interstitial fluid pressure (IFP) in tumor tissue is significantly higher than that in normal tissue, which reduces the effectiveness of therapeutic drugs. There are several methods to decrease the IFP, such as normalizing blood vessel, decreasing hyaluronic acid and collagen fiber content in the extracellular matrix (ECM), and recovering lymphatic function. Reducing tumor IFP might be developed as a novel approach in cancer therapy. In this study, we aimed to elucidate the relationship between ultrasound combined with microbubble therapy and IFP, and the associated mechanism. VX2 tumor in rabbit was treated with ultrasound combined with microbubbles at different intensities. The IFP was measured using the wick-in-needle (WIN) method. The collagen and reticular fibers were stained by Masson and Gordon–Sweets, respectively. The results showed that low-frequency non-focus ultrasound combined with microbubbles therapy influences the IFP in tumor tissues; low-frequency non-focus ultrasound with low pressure increased the IFP, whereas middle–high pressure decreased the IFP. The results showed that the structure and content of collagen and reticular fibers in tumor tissue were rarely influenced by the treatment. Our study provides a novel approach of reduced IFP antitumor therapy.

Highlights

  • Increasing incidence of cancer and associated mortality have forced innovations in tumor therapy

  • Microbubbles filled into the tumor rapidly and evenly, and no filling defect was observed in all the groups before treatment

  • The peak intensity (PI) in the 3MPa-ultrasound combined with microbubble (USMB) and 5MPa-USMB groups decreased by 66.3% and 86.7% (p < 0.05), respectively, after treatment compared with that before treatment

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Summary

Introduction

Increasing incidence of cancer and associated mortality have forced innovations in tumor therapy. It has been reported that higher interstitial fluid pressure (IFP) in solid tumors leads to lower penetration efficiency of chemotherapy drugs from the capillary to tumor tissues, limiting their antitumor effect (Heldin et al, 2004). IFP is determined by hydrostatic pressure and oncotic pressure in the capillary and interstitial space, and it is influenced by hydraulic conductivity and plasma protein reflectance. The pressure in normal tissues is slightly negative, ensuring easy material penetration from the blood vessels to the interstitial space. The pressure in many solid tumors is positive

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