scholarly journals Increased Tissue Penetration of Doxorubicin in Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) after High-Intensity Ultrasound (HIUS)

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Veria Khosrawipour ◽  
Sören Reinhard ◽  
Alice Martino ◽  
Tanja Khosrawipour ◽  
Mohamed Arafkas ◽  
...  

Background. High‐intensity ultrasound (HIUS) has been studied for the past two decades as a new therapeutic option for solid tumor direct treatment and a method for better chemotherapy delivery and perfusion. This treatment approach has not been tested to our knowledge in peritoneal metastatic therapy, where limited tissue penetration of intraperitoneal chemotherapy has been a main problem. Both liquid instillations and pressurized aerosols are affected by this limitation. This study was performed to evaluate whether HIUS improves chemotherapy penetration rates. Methods. High-intensity ultrasound (HIUS) was applied for 0, 5, 30, 60, 120, and 300 seconds on the peritoneal tissue samples from fresh postmortem swine. Samples were then treated with doxorubicin via pressurized intraperitoneal aerosol chemotherapy (PIPAC) under 12 mmHg and 37°C temperature. Tissue penetration of doxorubicin was measured using fluorescence microscopy on frozen thin sections. Results. Macroscopic structural changes, identified by swelling of the superficial layer of the peritoneal surface, were observed after 120 seconds of HIUS. Maximum doxorubicin penetration was significantly higher in peritoneum treated with HIUS for 300 seconds, with a depth of 962.88 ± 161.4 μm (p < 0.05). Samples without HIUS had a penetration depth of 252.25 ± 60.41. Tissue penetration was significantly increased with longer HIUS duration, with up to 3.8-fold increased penetration after 300 sec of HIUS treatment. Conclusion. Our data indicate that HIUS may be used as a method to prepare the peritoneal tissue for intraperitoneal chemotherapy. Higher tissue penetration rates can be achieved without increasing chemotherapy concentrations and preventing structural damage to tissue using short time intervals. More studies need to be performed to analyze the effect of HIUS in combination with intraperitoneal chemotherapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16045-e16045
Author(s):  
Veria Khosrawipour ◽  
Piotr Frelkiewicz ◽  
Sören Reinhard ◽  
Jakub Nicpon ◽  
Tanja Khosrawipour ◽  
...  

e16045 Background: The penetration of chemotherapeutic drugs into metastatic peritoneal nodules remains at levels well below 1 mm, thus significantly limiting the antitumor effect of intraperitoneal chemotherapy (IPC). Recently, high-Intensity ultrasound (HIUS) has been discovered as a potential tool to improve peritoneal diffusion rates. Despite promising preliminary data, basic aspects regarding its technical feasibility, safety and possible limitations remain unclear. This study aims to enhance our current understanding of HIUS and test its applicability using an ex-vivo swine model. Methods: Three postmortem swine were subject to laparotomy with consecutive lavage with 0.9%NaCl saline and HIUS application. For this purpose, a large HIUS radiating pen was introduced into the abdominal cavity and HIUS was applied on two of the four abdominal quadrants for 300 seconds each at an output power of 70 W, 50 % amplitude and 20 kHz frequency. Following the procedure, small intestinal tissue samples were removed for further analyses. Results: In all specimen, peritoneal and subperitoneal layers showed structural changes only visible on a microscopic level. The peritoneal layer was transformed into a mash-like structure while the subperitoneal layer (depth of 142 +/- 28 µm) exhibited microcavities and vascular detachment from surrounding tissues. No bowel rupture or vascular perforations were observed. Conclusions: Our data indicate that HIUS is a technically feasible add-on procedure for IPC with measurable microscopic changes on the peritoneal surface and no apparent bowel toxicity. Pretreatment of the abdominal cavity with HIUS could significantly improve IPC efficacy. Further studies are required to optimize and evaluate this novel approach.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Agata Mikolajczyk ◽  
Tanja Khosrawipour ◽  
Alice Martino ◽  
Joanna Kulas ◽  
Marek Pieczka ◽  
...  

Introduction. Micro- and nanoparticles, with their submicron size, the versatility of physical and chemical properties, and easily modifiable surface, are uniquely positioned to bypass the body’s clearing systems. Nonetheless, two main problems with micro- and nanoparticles arise which limit the intraperitoneal application. The study was performed to evaluate whether HIUS enables the imprinting of microparticles and, therefore, enhances penetration and local endurance in the peritoneum. Methods. High-intensity ultrasound (HIUS) at 20 kilohertz with an output power of 70 W was applied on peritoneal tissue samples from fresh postmortem swine for different time intervals. Before the HIUS application, the surface of the samples was covered with strontium aluminate microparticles before analysis via electron microscopy. In-tissue strontium aluminate penetration and particle distribution size were measured using fluorescence microscopy on frozen thin sections. Results. With increasing HIUS durations (1 versus 5 minutes), increasing strontium aluminate particles were detected in the peritoneum. HIUS leads to a particle selection process with enhancing predominantly the penetration of smaller particles whereas larger particles had a harder time penetrating the peritoneum. Smaller particles were detected up to 277 µm ± 86 µm into the peritoneum. Conclusion. Our data indicate that HIUS might be used as a method to prepare the peritoneal tissue for micro- and nanoparticles. Higher tissue penetration rates without the increase and longer local endurance of the applied substance could be reached. More studies need to be performed to analyze the effect of HIUS in enhancing intraperitoneal drug applications.


1964 ◽  
Vol 21 (1) ◽  
pp. 15-26 ◽  
Author(s):  
Janet A. Smith ◽  
Hector F. DeLuca

Liver mitochondria isolated in 0.44 M sucrose from rats deficient in essential fatty acids (EFA) oxidized citrate, succinate, α-ketoglutarate, glutamate, and pyruvate at a faster rate than did mitochondria isolated from normal rats; however, the oxidation of malate, caprylate, and ß-hydroxybutyrate was not significantly increased. The mitochondria from deficient rats exhibited an increased ATPase activity and extensive structural damage as revealed by electron microscope examination of thin sections. An increase in citrate oxidation and ATPase activity, together with some structural damage, could be demonstrated as early as the 4th week in rats on a fat-free diet. Saturated fat in the diet did not prevent the change in mitochondrial structure but accelerated its appearance. Both the biochemical and structural defects could be reversed within three weeks after feeding deficient rats a source of EFA. In the presence of a phosphate acceptor the effect of EFA deficiency on substrate oxidation was largely eliminated. A trend toward a reduced efficiency of oxidative phosphorylation was noted in mitochondria from EFA-deficient rats, but significant uncoupling was found only in the case of citrate, ß-hydroxybutyrate, and glutamate in the presence of malonate. Together with the increased ATPase activity, the uncoupling of phosphorylation could account for the poor respiratory control found with the deficient preparation. However, EFA deficiency was without effect on the respiration of liver slices, which supports the belief that the observed changes in oxidation and phosphorylation are an artifact resulting from damage sustained by the deficient mitochondria during their isolation.


Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3637
Author(s):  
Xinhui Zhou ◽  
Cuina Wang ◽  
Xiaomeng Sun ◽  
Zixuan Zhao ◽  
Mingruo Guo

This study aimed to compare the effects of high intensity ultrasound (HIU) applied at various amplitudes (20~40%) and for different durations (1~10 min) on the physiochemical and structural properties of goat milk β-lactoglobulin. No significant change was observed in the protein electrophoretic patterns by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Deconvolution and second derivative of the Fourier transform infrared spectra (FTIR) showed that the percentage of β-sheet of goat milk β-lactoglobulin was significantly decreased while those of α-helix and random coils increased after HIU treatment The surface hydrophobicity index and intrinsic fluorescence intensity of samples was enhanced and increased with increasing HIU amplitude or time. Differential scanning calorimetry (DSC) results exhibited that HIU treatments improved the thermal stability of goat milk β-lactoglobulin. Transmission electron microscopy (TEM) of samples showed that the goat milk β-lactoglobulin microstructure had changed and it contained larger aggregates when compared with the untreated goat milk β-lactoglobulin sample. Data suggested that HIU treatments resulted in secondary and tertiary structural changes of goat milk β-lactoglobulin and improved its thermal stability.


2012 ◽  
Vol 56 (12) ◽  
pp. 1894-1905 ◽  
Author(s):  
Dragana Stanic-Vucinic ◽  
Marija Stojadinovic ◽  
Marina Atanaskovic-Markovic ◽  
Jana Ognjenovic ◽  
Hans Grönlund ◽  
...  

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Agata Mikolajczyk ◽  
Tanja Khosrawipour ◽  
Joanna Kulas ◽  
Pawel Migdal ◽  
Mohamed Arafkas ◽  
...  

2017 ◽  
Vol 10 (7) ◽  
pp. 1224-1239 ◽  
Author(s):  
Andrea B. Stefanović ◽  
Jelena R. Jovanović ◽  
Marina B. Dojčinović ◽  
Steva M. Lević ◽  
Viktor A. Nedović ◽  
...  

2020 ◽  
Author(s):  
Roberto Fiorelli ◽  
Gurpaul S. Sidhu ◽  
Arantxa Cebrián-Silla ◽  
Ernesto Luna Melendez ◽  
Shwetal Mehta ◽  
...  

ABSTRACTTo address the inefficiency of passive diffusion for antibody penetration in thick tissue samples, which limits clearing-technique applications, we developed a versatile and simple device to perform antibody incubation under increased barometric pressure. Pressurized immunohistochemistry greatly improves the uniformity, intensity, and depth of fluorescent immunostaining in thick human and mouse brain samples. Furthermore, pressurized immunohistochemistry substantially decreases the time required for classic staining of thin sections.SUBMISSION CATEGORYNew Results


2020 ◽  
Vol 11 (24) ◽  
pp. 7209-7215
Author(s):  
Hien Lau ◽  
Tanja Khosrawipour ◽  
Agata Mikolajczyk ◽  
Piotr Frelkiewicz ◽  
Jakub Nicpon ◽  
...  

2018 ◽  
Vol 44 ◽  
pp. 97-105 ◽  
Author(s):  
Alejandro Martínez-Velasco ◽  
Consuelo Lobato-Calleros ◽  
Blanca E. Hernández-Rodríguez ◽  
Angélica Román-Guerrero ◽  
Jose Alvarez-Ramirez ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document