Rationale and Objectives
The aim of this study was to explore the antitumor effects on mice xenografted ovarian carcinoma using the technique of ultrasound-mediated drug release from paclitaxel-loaded lipid microbubbles (PLMs).
Materials and Methods
Twenty-five ovarian cancer–bearing nude mice were randomly divided into five groups of five mice each. Each group received a unique kind of treatment once a day. These treatments were PLMs combined with ultrasound, intravenous paclitaxel administration, non–drug-loaded microbubbles combined with ultrasound, intravenous PLM administration, and normal saline administration (the control group). After 7 days of consecutive treatment, all mice were sacrificed, and their tumors were harvested to measure volumes and weights. The tumor inhibition rate was calculated by weight. Expressions of vascular endothelial growth factor (VEGF) and p53 in tumor tissues were detected by immunohistochemical staining.
Results
Mean tumor volume and weight were the lowest in the first group (PLMs combined with ultrasound), so this group’s tumor inhibition rate was the highest ( P < .05). On immunohistology, VEGF and p53 expression levels were lowest ( P < .05) in the first group.
Conclusion
Ultrasound irradiation mediates PLM destruction so that the drug is released from the vehicles at the same time. It helps achieve targeted chemotherapy in tumor tissues. This technique has potential to be adopted as a novel tool for ovarian cancer chemotherapy.
Ovarian carcinoma is the leading cause of death in patients with gynecologic malignancies ( ). Because of the insidious onset of the disease and the lack of reliable screening tests, the majority of patients already have advanced disease when diagnosed. Although most patients respond initially to the standard treatment of modern surgical intervention and platinum or paclitaxel chemotherapy, because intravenous (IV) chemotherapy intensity is limited by myelotoxicity and other serious side effects, the majority of patients will eventually relapse and die of the disease ( ).
Another approach to the treatment of women with advanced ovarian cancer is the direct instillation of chemotherapy into the peritoneal cavity. First proposed by Dedrick et al ( ), intraperitoneal (IP) therapy is designed to maximize drug delivery to the tumor while avoiding much of the systemic toxicity associated with the IV administration of the drug. In particular, the combined application of IV and IP chemotherapy can greatly improve the median progression-free survival time ( ). However, the toxicity resulting from this method of therapy is not trivial. Apart from the most common toxicities, such as neutropenia, nausea, vomiting, and fatigue, researchers have also observed abdominal pain, catheter-related infections, and so on ( ). Also, IP therapy calls for such high familiarity with peritoneal administration and catheter-placement techniques that many clinicians are reluctant to embrace it. Therefore, a novel form of chemotherapy with improved outcomes is needed for the treatment of ovarian cancer.
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Materials and methods
Preparation of Paclitaxel-loaded Microbubbles
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Animal Preparation
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Treatment
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Tumor Growth Measurement
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Immunohistochemical Staining of VEGF and p53
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Image Analysis
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Statistical Analysis
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Results
Animal Models
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Effects of Treatments on Tumor Growth
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Table 1
Tumor Growth Suppression in Each Group
Group_n_ Tumor Volume (mm 3 ) Tumor Weight (mg) Tumor Inhibition Rate (%) 1 5 918.1 ± 249.2 ⁎ , † 825.6 ± 214.6 ⁎ , † 45.2 2 5 1,128.1 ± 178.4 ⁎ 956.1 ± 138.6 ⁎ 36.5 3 5 1,435.4 ± 249.7 ⁎ 1,234.9 ± 139.0 ⁎ 18.0 4 5 1,724.9 ± 278.2 ⁎ 1,478.7 ± 242.4 ⁎ 5.9 5 5 1,752.9 ± 332.2 1,506.7 ± 304.4 0
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Expression of VEGF and p53 in Tumor Tissues
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Table 2
Vascular Endothelial Growth Factor (VEGF) and p53 Expression in Each Group
Group_n_ VEGF Slide Density p53 Slide Density 1 5 0.13524 ± 0.00162 ⁎ , † 0.12228 ± 0.00193 ⁎ , † 2 5 0.17455 ± 0.00231 ⁎ 0.18333 ± 0.00480 ⁎ 3 5 0.19246 ± 0.00583 ⁎ 0.20653 ± 0.00329 ⁎ 4 5 0.22470 ± 0.00751 ⁎ 0.23587 ± 0.001469 ⁎ 5 5 0.26938 ± 0.00672 0.33093 ± 0.00550
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Discussion
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