Various Three-Dimensional Culture Methods and Cell Types for Exosome Production

Cell-based therapies have been used as promising treatments for several untreatable diseases. However, cellbased therapies have side effects such as tumorigenesis and immune responses. To overcome these side effects, therapeutic effects of exosomes have been researched as replacements for cell-based therapies. In addition, exosomes reduced the risk that can be induced by cell-based therapies. Exosomes contain biomolecules such as proteins, lipids, and nucleic acids that play an essential role in cell–cell and cell–matrix interactions during biological processes. Since the introduction of exosomes, those have been proven perpetually as one of the most effective and therapeutic methods for incurable diseases. Much research has been conducted to enhance the properties of exosomes, including immune regulation, tissue repair, and regeneration. However, yield rate of exosomes is the critical obstacle that should be overcome for practical cell-free therapy. Three-dimensional (3D) culture methods are introduced as a breakthrough to get higher production yields of exosomes. For example, hanging drop and microwell were well known 3D culture methods and easy to use without invasiveness. However, these methods have limitation in mass production of exosomes. Therefore, a scaffold, spinner flask, and fiber bioreactor were introduced for mass production of exosomes isolated from various cell types. Furthermore, exosomes treatments derived from 3D cultured cells showed enhanced cell proliferation, angiogenesis, and immunosuppressive properties. This review provides therapeutic applications of exosomes using 3D culture methods.

Dosimetric comparison of volumetric modulated arc therapy with robotic stereotactic radiation therapy in hepatocellular carcinoma

PURPOSE: To compare volumetric modulated arc therapy of RapidArc with robotic stereotactic body radiation therapy (SBRT) of CyberKnife in the planning and delivery of SBRT for hepatocellular carcinoma (HCC) treatment by analyzing dosimetric parameters. MATERIALS AND METHODS: Two radiation treatment plans were generated for 29 HCC patients, one using Eclipse for the RapidArc plan and the other using Multiplan for the CyberKnife plan. The prescription dose was 60 Gy in 3 fractions. The dosimetric parameters of planning target volume (PTV) coverage and normal tissue sparing in the RapidArc and the CyberKnife plans were analyzed. RESULTS: The conformity index was 1.05 +/- 0.02 for the CyberKnife plan, and 1.13 +/- 0.10 for the RapidArc plan. The homogeneity index was 1.23 +/- 0.01 for the CyberKnife plan, and 1.10 +/- 0.03 for the RapidArc plan. For the normal liver, there were significant differences between the two plans in the low-dose regions of V1 and V3. The normalized volumes of V60 for the normal liver in the RapidArc plan were drastically increased when the mean dose of the PTVs in RapidArc plan is equivalent to the mean dose of the PTVs in the CyberKnife plan. CONCLUSION: CyberKnife plans show greater dose conformity, especially in small-sized tumors, while RapidArc plans show good dosimetric distribution of low dose sparing in the normal liver and body.

A Study of Characteristics of MicroLion Liquid Ionization Chamber for 6 MV Photon Beam / 의학물리

Recently PTW developed a MicroLion liquid ionization chamber which is water_equivalent and has a small sensitive volume of 0.002 cm3. The aim of this work is to investigate such dosimetric characteristics as dose linearity, dose rate dependency, spatial resolution, and output factors of the chamber for the external radiotherapy photon beam. The results were compared to those of Semiflex chamber, Pinpoint chamber and Diode chamber with the sensitive volumes of 0.125 cm3, 0.03 cm3 and 0.0025 cm3, respectively and evaluated to be suitable for small fields. This study was performed in the 6MV photon energy from a Varian 2300 C/D linac accelerator and the MP3 water phantom (PTW, Freiburg) was used. Penumbras in the varios field sizes ranged from 0.5x0.5 cm2 to 10x10 cm2 were used to evaluate the spatial resolution. Output factors were measured in the field sizes of 0.5x0.5 to 40x40 cm2. Readings of the chamber was linearly proportional to dose. Dose rate dependency was measured from 100 MU/min to 600 MU/min, showed a maximum difference of 5.0%, and outputs decreased with dose rates. The spatial resolutions determined with comparing profiles for the field sizes of 0.5x0.5 cm2 to 10x10 cm2 agreed between every detector except the Semiflex chamber to within 2%. Outputs of detectors were compared to that of Semiflex chamber and showed good agreements within 2% for every chamber. This study shows that MicroLion chamber characterized by a high signal-to-noise ratio and water equivalence could be suitable for the small field dosimetry.

A Pilot Research for Real-Time Specific Patient Quality Assurance Using the Hybrid Optimized Vmat Phantom (Hovp) in Volume Modulated Arc Therapy / 의학물리

The purpose of this was to investigate the measurement of fluence dose map for the specific patient quality assurance. The measurement of fluence map was performed using 2D matrixx detector. The absorbed dose was measured by a glass detector, Gafchromic film and ion chamber in Hybrid Optimized VMAT Phantom (HOVP). For 2D Matrixx, the results of comparison were average passing rate 85.22%+/-1.7 (RT_Target), 89.96%+/-2.15 (LT_Target) and 95.14%+/-1.18 (G4). The dose difference was 11.72%+/-0.531, -11.47%+/-0.991, 7.81%+/-0.857, -4.14%+/-0.761 at the G1, G2, G3, G4. In HOVP, the results of comparison for film were average passing rate (3%, 3 mm) 93.64%+/-3.87, 90.82%+/-0.99. We were measured an absolute dose in steep gradient area G1, G2, G3, G4 using the glass detector. The difference between the measurement and calculation are 8.3% (G1), -5.4% (G2), 6.1% (G3), 7.2% (G4). The using an Ion-chamber were an average relative dose error -1.02%+/-0.222 (Rt_target), 0.96%+/-0.294 (Lt_target). Though we need a more study using a transmission detector. However, a measurement of real-time fluence map will be predicting a dose for real-time specific patient quality assurance in volume modulated arc therapy.

Verification of X-sight Lung Tracking System in the CyberKnife / 의학물리

To track moving tumor in real time, CyberKnife system imports a technique of the synchrony respiratory tracking system. The fiducial marker which are detectable in X-ray images were demand in CyberKnife Robotic radiosurgery system. It issued as reference markers to locate and track tumor location during patient alignment and treatment delivery. Fiducial marker implantation is an invasive surgical operation that carries a relatively high risk of pneumothorax. Most recently, it was developed a direct lung tumor registration method that does not require the use of fiducials. The purpose of this study is to measure the accuracy of target applying X-sight lung tracking using the Gafchromic film in dynamic moving thorax phantom. The X-sight Lung Tracking quality assurance motion phantom simulates simple respiratory motion of a lung tumor and provides Gafchromic dosimetry film-based test capability at locations inside the phantom corresponding to a typical lung tumor. The total average error for the X-sight Lung Tracking System with a moving target was 0.85+/-0.22 mm. The results were considered reliable and applicable for lung tumor treatment in CyberKnife radiosurgery system. Clinically, breathing patterns of patients may vary during radiation therapy. Therefore, additional studies with a set real patient data are necessary to evaluate the target accuracy for the X-sight Lung Tracking system.

Verification of X-sight Lung Tracking System in the CyberKnife / 의학물리

To track moving tumor in real time, CyberKnife system imports a technique of the synchrony respiratory tracking system. The fiducial marker which are detectable in X-ray images were demand in CyberKnife Robotic radiosurgery system. It issued as reference markers to locate and track tumor location during patient alignment and treatment delivery. Fiducial marker implantation is an invasive surgical operation that carries a relatively high risk of pneumothorax. Most recently, it was developed a direct lung tumor registration method that does not require the use of fiducials. The purpose of this study is to measure the accuracy of target applying X-sight lung tracking using the Gafchromic film in dynamic moving thorax phantom. The X-sight Lung Tracking quality assurance motion phantom simulates simple respiratory motion of a lung tumor and provides Gafchromic dosimetry film-based test capability at locations inside the phantom corresponding to a typical lung tumor. The total average error for the X-sight Lung Tracking System with a moving target was 0.85+/-0.22 mm. The results were considered reliable and applicable for lung tumor treatment in CyberKnife radiosurgery system. Clinically, breathing patterns of patients may vary during radiation therapy. Therefore, additional studies with a set real patient data are necessary to evaluate the target accuracy for the X-sight Lung Tracking system.

Analysis of Dose Distribution on Critical Organs for Radiosurgery with CyberKnife Real-Time Tumor Tracking System / 의학물리

We measured the dose distribution for spinal cord and tumor using Gafchromic film, applying 3D and 4D-Treatment Planning for lung tumor within the phantom. A measured dose distribution was compared with a calculated dose distribution generated from 3D radiation treatment planning and 4D radiation treatment planning system. The agreement of the dose distribution in tumor for 3D and 4D treatment planning was 90.6%, 97.64% using gamma index computed for a distance to agreement of 1 mm and a dose difference of 3%. However, a gamma agreement index of 3% dose difference tolerence of and 2 mm distance to agreement, the accordance of the dose distribution around cord for 3D and 4D radiation treatment planning was 57.13%, 90.4%. There are significant differences between a calculated dose and a measured dose for 3D radiation treatment planning, no significant differences for 4D treatment planning. The results provide the effectiveness of the 4D treatment planning as compared to 3D. We suggest that the 4-dimensional treatment planning should be considered in the case where such equipments as Cyberknife with the real time tracking system are used to treat the tumors in the moving organ.

Analysis of Accuracy of Apparent Activity According to Calibration Method for High Dose Rate Brachytherapy Source / 의학물리

The aim of this study is to introduce the accuracy of Ir-192 source's apparent activity using the well-type chamber and the Farmer-type ionization chamber in the high dose rate brachytherapy. We measured the apparent activity of Ir-192 that each medical center in the country has and the apparent activity of calibration certificate provided by manufacturer is compared with that by our experimental measurement. The number of sources used for the activity comparison was 5. The accuracy of the measured activity was in the range of -2.8% to -1.0% and -2.1% to 0.2% for the Farmer-type chamber system (Jig) and for the well-type, respectively. The maximum difference was within 1.0% for comparison with two calibration's tool. Our results demonstrate that well-type chamber as wall as Farmer-type chamber is a appropriate system as the routine source calibration procedures in HDR brachytherapy. Whenever a new source is installed to use in clinics, by periods, a source calibration should be carried out.