3 research outputs found
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Drug capture efficacy using polystyrenesulfonate-coated chemofilter device
Endovascular chemotherapy is an effective treatment option for cancer, however, the therapeutic agents used in this procedure often travel to non-target tissues and cause severe toxicity. Side-effects of chemotherapy range from nausea to life-threatening conditions. A strategy to reduce exposure of healthy tissues and organs to the toxicity of chemotherapeutic agents, such as doxorubicin (DOX), is to remove these drugs from systemic circulation after they have passed through the tumor site. With this goal in mind, different types of ChemoFilter devices have shown promise in alleviating these detrimental side effects. When placed downstream from the targeted tumor during intra-arterial chemotherapy, excess therapeutic agents bind to the device, preventing them from entering systemic circulation. In this study, we evaluated the doxorubicin-binding efficacy of a 3D printed porous cylindrical ChemoFilter device coated with sulfonated pentablock copolymers. Closed-circuit flow models experiments integrating 11 devices (uncoated or coated) at two concentrations of DOX (0.01 mg/mL and 0.05 mg/mL) were conducted. Samples collected from these flow models were used to treat H9c2 cell cultures, a rat embryonic cardiac cell line selected due to DOX cardiotoxicity. After a 24-hour treatment period, cell viability was calculated using the Trypan blue exclusion method. At 0.01 mg/mL DOX and 0.05 mg/mL DOX, the 3D printed polystyrenesulfonate-coated absorbers effectively filtered and eliminated DOX toxicity, increasing the H9c2 cell viability by 12.97% and 23.11%, respectively. These results confirm the ChemoFilter’s ability to successfully absorb DOX in vitro, showing promise for its possible future use in clinical trials
Recommended from our members
Drug capture efficacy using polystyrenesulfonate-coated chemofilter device
Endovascular chemotherapy is an effective treatment option for cancer, however, the therapeutic agents used in this procedure often travel to non-target tissues and cause severe toxicity. Side-effects of chemotherapy range from nausea to life-threatening conditions. A strategy to reduce exposure of healthy tissues and organs to the toxicity of chemotherapeutic agents, such as doxorubicin (DOX), is to remove these drugs from systemic circulation after they have passed through the tumor site. With this goal in mind, different types of ChemoFilter devices have shown promise in alleviating these detrimental side effects. When placed downstream from the targeted tumor during intra-arterial chemotherapy, excess therapeutic agents bind to the device, preventing them from entering systemic circulation. In this study, we evaluated the doxorubicin-binding efficacy of a 3D printed porous cylindrical ChemoFilter device coated with sulfonated pentablock copolymers. Closed-circuit flow models experiments integrating 11 devices (uncoated or coated) at two concentrations of DOX (0.01 mg/mL and 0.05 mg/mL) were conducted. Samples collected from these flow models were used to treat H9c2 cell cultures, a rat embryonic cardiac cell line selected due to DOX cardiotoxicity. After a 24-hour treatment period, cell viability was calculated using the Trypan blue exclusion method. At 0.01 mg/mL DOX and 0.05 mg/mL DOX, the 3D printed polystyrenesulfonate-coated absorbers effectively filtered and eliminated DOX toxicity, increasing the H9c2 cell viability by 12.97% and 23.11%, respectively. These results confirm the ChemoFilter’s ability to successfully absorb DOX in vitro, showing promise for its possible future use in clinical trials
Defining the Magnetic Resonance Features of Renal Lesions and Their Response to Everolimus in a Transgenic Mouse Model of Tuberous Sclerosis Complex.
Tuberous sclerosis complex (TSC) is an inherited genetic disorder characterized by mutations in TSC1 or TSC2 class of tumor suppressers which impact several organs including the kidney. The renal manifestations are usually in the form of angiomyolipoma (AML, in 80% of the cases) and cystadenomas. mTOR inhibitors such as rapamycin and everolimus have shown efficacy in reducing the renal tumor burden. Early treatment prevents the progression of AML; however, the tumors regrow upon cessation of therapy implying a lifelong need for monitoring and management of this morbid disease. There is a critical need for development of imaging strategies to monitor response to therapy and progression of disease which will also facilitate development of newer targeted therapy. In this study we evaluated the potential of multiparametric 1H magnetic resonance imaging (mpMRI) to monitor tumor response to therapy in a preclinical model of TSC, the transgenic mouse A/J Tsc2+/- . We found 2-dimensional T2-weighted sequence with 0.5 mm slice thickness to be optimal for detecting renal lesions as small as 0.016 mm3. Baseline characterization of lesions with MRI to assess physiological parameters such as cellularity and perfusion is critical for distinguishing between cystic and solid lesions. Everolimus treatment for three weeks maintained tumor growth at 36% from baseline, while control tumors displayed steady growth and were 70% larger than baseline at the end of therapy. Apparent diffusion coefficient, T1 values and normalized T2 intensity changes were also indictive of response to treatment. Our results indicate that standardization and implementation of improved MR imaging protocols will significantly enhance the utility of mpMRI in determining the severity and composition of renal lesions for better treatment planning