• Journal of Life Science
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• v.32 no.2
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• pp.148-154
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• 2022

Focal adhesion kinase (FAK) is known to regulate cell adhesion, migration, and mechanotransduction in focal adhesions (FAs). However, studies on how FAK activity is regulated in the plasma membrane microdomains according to the composition of extracellular matrix (ECM) proteins are still lacking. A genetically encoded fluorescence resonance energy transfer (FRET)-based biosensor can provide useful information on the activity of intracellular signals with high spatiotemporal resolution. In this study, we analyzed the FAK activities in lipid raft (detergent-resistant membrane) and non-lipid raft (non-detergent-resistant membrane) microdomains using FRET-based membrane targeting FAK biosensors (FAK-Lyn and FAK-KRas biosensors) under four different ECM protein compositions: glass, type 1 collagen, fibronectin, and laminin. Interestingly, FAK activity in response to laminin in a lipid raft microdomain was lower than that in other ECM conditions. Cells subjected to fibronectin showed higher FAK activity in a lipid raft microdomain than that in a non-lipid raft microdomain. Therefore, this study demonstrates that the FAK activity can be distinctively regulated according to the ECM type and the environment of the plasma membrane microdomains.

• Journal of Life Science
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• v.33 no.6
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• pp.523-529
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• 2023

Ubiquitination is a post-translational modification that is involved in the quality control of proteins and responsible for modulating a variety of cellular physiological processes. Protein ubiquitination and deubiquitination are reversible processes that regulate the stability of target substrates. The ubiquitin proteasome system (UPS) helps regulate tumor-promoting processes, such as DNA repair, cell cycle, apoptosis, metastasis, and angiogenesis. The UPS comprises a combination of ubiquitin, ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), and ubiquitin-ligase enzymes (E3), which complete the degradation of target proteins. Ubiquitin-conjugating enzymes (UBE2s) play an inter-mediate role in the UPS process by moving activated ubiquitin to target proteins through E3 ligases. UBE2s consist of 40 members and are classified according to conserved catalytic ubiquitin-conjugating (UBC) domain-flanking extensions in humans. Since UBE2s have specificity to substrates like E3 ligase, the significance of UBE2 has been accentuated in tumorigenesis. The dysregulation of multiple E2 enzymes and their critical roles in modulating oncogenic signaling pathways have been reported in several types of cancer. The elevation of UBE2 expression is correlated with a worse prognosis in cancer patients. In this review, we summarize the basic functions and regulatory mechanisms of UBE2s and suggest the possibility of their use as therapeutic targets for cancer.

• Radiation Oncology Journal
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• v.21 no.1
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• pp.1-9
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• 2003

Purpose : The purpose of this study was to analyze the effect of a Linear accelerator based Photon Knife Radiosurgery System developed by the staff of Keimyung University Dongsan Medical Center for the treatment of cerebral arterlovenous malformation Material and Methods : Between December 1993 and October 2000, 30 patients with cerebral arteriovenous malformation (AVM) were treated with the Linac based Photon knife Radlosurgery System In the Department of Therapeutlc Radiology at Keimyung University Dongsan Medical Center. The median age was 34, ranging from 7 to 63 years, with a 2 : 1 male to female ratio. The locations of the AVM nidi were the frontal lobe (motor cortex), parletal lobe, and the thalamus, In that order. The diameters of the AVM nidi ranged 1.2 to 5.5 cm with a mean on 2.9 cm, and target volumes of between 0.5 and 20.5 cc, with a mean of 5.8 cc. The majority of patients received radiation doses of between 1,500 and 2,500 cGy, w14h a mean of 2,000 cGy, at 80% the isodose line. Twenty-five patients were treated with one isocenter, 4 with two, and 1 with four. The follow-up radiological evaluations were peformed with cranial computed tomogram (CT) or MRI between 6 month and one year interval, and if the AVM nidus had completely disappeared in the CT or MRI, we confirmed thls was a complete obliteration, with a cerebral or magnetic resonance angiogram (MRA). The median iollow-up period was 39 months with a range of 10 to 103 months. Results : Twenty patients were radloiogicaiiy followed up ior over 20 months, with complete obliteration observed in 14 (70%). According to the maximal diameter, all four of the small AVM (<2 cm) completely obliterated, 8 of the 10 patients with a medium AVW (2~3 cm) showed a complete obliteration, and two showed partial obliteration. Among the patients with a large AVM (>3 cm), only one showed complete obliteration, and S showed partial obliteration, but 3 oT these underwent further radiosurgery 3 years later. One who followed up for 20 months fellowing further radiosurgery eventually showed complete obliteration. Ten patients with seizure symptoms had no recurrent seizure due to radiosurgery and medication. One of the eleven patients who suffered intracranlal bleeding developed further bleeding at 9 and 51 months fellowing the radiosurgery although complete obliteration was eventually observed and the patient was managed in hospital then recovered. No patient suffered severe complications fellowing the radiosurgery. Conclusion : The radiosurgery with Linac-based Photon knife radiosurgery system, developed by the staff at our hospital, is a safe and effective treatment for AVM patients having diameters or volumes of less than 3 cm or 10 cm$^{3}$, respectively, located In Inoperable areas or who refused neurosurgery. We suggest that staged AVM radiosurgery may initially be considered, if the AVM target volume is above 10 cm$^{3}$

• Geophysics and Geophysical Exploration
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• v.7 no.3
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• pp.164-173
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• 2004

To delineate geothermal water movement at the Pohang geothermal development site, Self-Potential (SP) survey and monitoring were carried out during pumping tests. Before drilling, background SP data have been gathered to figure out overall potential distribution of the site. The pumping test was performed in two separate periods: 24 hours in December 2003 and 72 hours in March 2004. SP monitoring started several days before the pumping tests with a 128-channel automatic recording system. The background SP survey showed a clear positive anomaly at the northern part of the boreholes, which may be interpreted as an up-flow Bone of the deep geothermal water due to electrokinetic potential generated by hydrothermal circulation. The first and second SP monitoring during the pumping tests performed to figure out the fluid flow in the geothermal reservoir but it was not easy to see clear variations of SP due to pumping and pumping stop. Since the area is covered by some 360 m-thick tertiary sediments with very low electrical resistivity (less than 10 ohm-m), the electrokinetic potential due to deep groundwater flow resulted in being seriously attenuated on the surface. However, when we compared the variation of SP with that of groundwater level and temperature of pumping water, we could identify some areas responsible to the pumping. Dominant SP changes are observed in the south-west part of the boreholes during both the preliminary and long-term pumping periods, where 3-D magnetotelluric survey showed low-resistivity anomaly at the depth of $600m\~1,000m$. Overall analysis suggests that there exist hydraulic connection through the southwestern part to the pumping well.

• The Korean Journal of Nuclear Medicine Technology
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• v.14 no.1
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• pp.3-7
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• 2010

Purpose: The usefulness of Positron Emission Tomography (PET) images in diagnosis, staging, recurrent and treatment response evaluation has already been known. However, tumors which are small size, located in lower lobe of lung or upper lobe of liver are shown misalignment, distortion and different Standard Uptake Value (SUV) by respiration in PET images. Therefore, if radiotherapy based on normal respiration, it may cause low treatment response or more side effects because targets which had to treat, out of treat range or over dose to normal tissue. The purpose of this study is to evaluate attenuation-correction with Average CT (ACT) for more accuracy SUV measurement and minimize artifact by respiration. Materials and Methods: 13 patients, who had tumors which are around the diaphragm, underwent ACT scan after Helical CT (HCT) scan with PET/CT (Discovery DSTE 8; GE Healthcare). We quantified the differences between attenuation corrected image with HCT and attenuation corrected image with ACT in artifact size and maximum SUV ($SUV_{max}$). Artifacts were evaluated by measurement of the curved photogenic area in the lower thorax of the PET images for all patients. $SUV_{max}$ was measured separately at the primary tumors. Analysis program was Advantage Workstation v4.3 (GE Healthcare). Patients were injected with 7.4 MBq (0.2 $mC_i$) per kg of $^{18}F$-FDG and scanned 1 hour after injection. The PET acquisition was 3 minute per bed. Results: Significantly lower artifact were observed in PET/ACT images than in PET/HCT images (below-thoracic artifacts caused by under corrected $1.5{\pm}3.5$ cm vs. $13.4{\pm}4.2$ cm). Significantly higher $SUV_{max}$ were noted in PET/ACT images than in PET/HCT images in the primary tumor. Compared with PET/HCT images, $SUV_{max}$ in PET/ACT images were higher by $5.3{\pm}3.9%$ (mean value) tumor. The highest difference was observed in Lower lobe of lung (7.7 to 8.7; 13%). Conclusion: Due to its significantly reduced artifacts in lower thoracic, attenuation corrected image with ACT images provided more reliable $SUV_{max}$ and may be helpful in monitoring treatment response. Moreover, ACT can separate upper lobe of liver and lower lobe of lung, it may be helpful in interpretation. ACT will be clinically useful, considering increased dose caused by ACT scan and adapt.

• The Journal of Korean Society for Radiation Therapy
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• v.22 no.2
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• pp.113-122
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• 2010

Purpose: To evaluate the accuracy of a target position at static and dynamic state by using Dynamic phantom for the difference between tumor's actual movement during respiratory gated radiation therapy and skin movement measured by RPM (Real-time Position Management). Materials and Methods: It self-produced Dynamic phantom that moves two-dimensionally to measure a tumor moved by breath. After putting marker block on dynamic phantom, it analyzed the amplitude and status change depending on respiratory time setup in advance by using RPM. It places marker block on dynamic phantom based on this result, inserts Gafchromic EBT film into the target, and investigates 5 Gy respectively at static and dynamic state. And it scanned investigated Gafchromic EBT film and analyzed dose distribution by using automatic calculation. Results: As a result of an analysis of Gafchromic EBT film's radiation amount at static and dynamic state, it could be known that dose distribution involving 90% is distributed within margin of error of 3 mm. Conclusion: As a result of an analysis of dose distribution's change depending on patient's respiratory cycle during respiratory gated radiation therapy, it is expected that the treatment would be possible within recommended margin of error at ICRP 60.

• Journal of radiological science and technology
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• v.35 no.4
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• pp.335-343
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• 2012

Intensity-modulated radiotherapy(IMRT) have the ability to provide better dose conformity and sparing of critical normal tissues than three-dimensional radiotherapy(3DCRT). Especially, with the benefit of health insurance in 2011, its use now increasingly in many modern radiotherapy departments. Also the use of linear accelerator with high-energy photon beams over 10 MV is increasing. As is well known, these linacs have the capacity to produce photonueutrons due to photonuclear reactions in materials with a large atomic number such as the target, flattening filters, collimators, and multi-leaf collimators(MLC). MLC-based IMRT treatments increase the monitor units and the probability of production of photoneutrons from photon-induced nuclear reactions. The purpose of this study is to quantitatively evaluate the dose of photoneutrons produced from 3DCRT and IMRT technique for Rando phantom in cervical cancer. We performed the treatment plans with 3DCRT and IMRT technique using Rando phantom for treatment of cervical cancer. An Rando phantom placed on the couch in the supine position was irradiated using 15 MV photon beams. Optically stimulated luminescence dosimeters(OSLD) were attached to 4 different locations (abdomen, chest, head and neck, eyes) and from center of field size and measured 5 times each of locations. Measured neutron dose from IMRT technique increased by 9.0, 8.6, 8.8, and 14 times than 3DCRT technique for abdomen, chest, head and neck, and eyes, respectively. When using IMRT with 15 MV photonbeams, the photoneutrons contributed a significant portion on out-of-field. It is difficult to prevent high energy photon beams to produce the phtoneutrons due to physical properties, if necessary, It is difficult to prevent high energy photon beams to produce the phtoneutrons due to physical properties, if necessary, it is need to provide the additional safe shielding on a linear accelerator and should therefore reduce the out-of-field dose.

• Progress in Medical Physics
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• v.17 no.1
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• pp.24-31
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• 2006

Automated analysis software was developed to measure the magnitude of the intrafractional and interfractional errors during breast radiation treatments. Error analysis results are important for determining suitable planning target volumes (PTV) prior to Implementing breast-conserving 3-D conformal radiation treatment (CRT). The electrical portal imaging device (EPID) used for this study was a Portal Vision LC250 liquid-filled ionization detector (fast frame-averaging mode, 1.4 frames per second, 256X256 pixels). Twelve patients were imaged for a minimum of 7 treatment days. During each treatment day, an average of 8 to 9 images per field were acquired (dose rate of 400 MU/minute). We developed automated image analysis software to quantitatively analyze 2,931 images (encompassing 720 measurements). Standard deviations ($\sigma$) of intrafractional (breathing motion) and intefractional (setup uncertainty) errors were calculated. The PTV margin to include the clinical target volume (CTV) with 95% confidence level was calculated as $2\;(1.96\;{\sigma})$. To compensate for intra-fractional error (mainly due to breathing motion) the required PTV margin ranged from 2 mm to 4 mm. However, PTV margins compensating for intefractional error ranged from 7 mm to 31 mm. The total average error observed for 12 patients was 17 mm. The intefractional setup error ranged from 2 to 15 times larger than intrafractional errors associated with breathing motion. Prior to 3-D conformal radiation treatment or IMRT breast treatment, the magnitude of setup errors must be measured and properly incorporated into the PTV. To reduce large PTVs for breast IMRT or 3-D CRT, an image-guided system would be extremely valuable, if not required. EPID systems should incorporate automated analysis software as described in this report to process and take advantage of the large numbers of EPID images available for error analysis which will help Individual clinics arrive at an appropriate PTV for their practice. Such systems can also provide valuable patient monitoring information with minimal effort.

• The Journal of Korean Society for Radiation Therapy
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• v.32
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• pp.85-92
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• 2020

Purpose: To find out the advantages of thermoplastic bolus compared to conventional bolus, which is mainly used in clinical practice, We evaluated Two cases in terms of dose and location reproducibility to assess Usability of thermoplastic Bolus for skin VMAT radiotherapy. Materials and Methods: Two patient's treated with left breast skin lesion were simulated using thermoplastic Bolus and planned with 2arc VMAT. the prescription dose was irradiated to 95% or more of the target volume. We evaluated The reproducibility of the bolus position by measuring the length of the air gap in the CBCT (Cone Beam CT) image. to evaluate dose reproducibility, we compared The dose distribution in the plan and CBCT and measured in vivo for patient 2. Results: The difference between the air gap in patient 1's simulation CT and the mean air gap (M1) during 10 treatments in the CBCT image was -0.42±1.24mm. In patient 2, the difference between the average air gap between the skin and the bolus (M2) during 14 treatments was -1.08±1.3mm, and the air gap between the bolus (M3) was 0.49±1.16. The difference in the dose distribution between Plan CT and CBCT was -1.38% for PTV1 D95 and 0.39% for SKIN (max) in patient 1. In patient 2, PTV1 D95 showed a difference of 0.63% and SKIN (max) -0.53%. The in vivo measurement showed a difference of -1.47% from the planned dose. Conclusion: thermoplastic Bolus is simpler and takes less time to manufacture compared to those produced by 3D printer. Also compared to conventional bolus, it has high reproducibility in the set-up side and stable results in terms of dose delivery.

• The Journal of Korean Society for Radiation Therapy
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• v.32
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• pp.93-109
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• 2020

Purpose: The radiochromic film (Gafchromic EBT3, Ashland Advanced Materials, USA) and 3-dimensional analysis system dosimetry checkTM (DC, MathResolutions, USA) were evaluated for patient-specific quality assurance (QA) of helical tomotherapy. Materials and Methods: Depending on the tumors' positions, three types of targets, which are the abdominal tumor (130.6㎤), retroperitoneal tumor (849.0㎤), and the whole abdominal metastasis tumor (3131.0㎤) applied to the humanoid phantom (Anderson Rando Phantom, USA). We established a total of 12 comparative treatment plans by the four geometric conditions of the beam irradiation, which are the different field widths (FW) of 2.5-cm, 5.0-cm, and pitches of 0.287, 0.43. Ionization measurements (1D) with EBT3 by inserting the cheese phantom (2D) were compared to DC measurements of the 3D dose reconstruction on CT images from beam fluence log information. For the clinical feasibility evaluation of the DC, dose reconstruction has been performed using the same cheese phantom with the EBT3 method. Recalculated dose distributions revealed the dose error information during the actual irradiation on the same CT images quantitatively compared to the treatment plan. The Thread effect, which might appear in the Helical Tomotherapy, was analyzed by ripple amplitude (%). We also performed gamma index analysis (DD: 3mm/ DTA: 3%, pass threshold limit: 95%) for pattern check of the dose distribution. Results: Ripple amplitude measurement resulted in the highest average of 23.1% in the peritoneum tumor. In the radiochromic film analysis, the absolute dose was on average 0.9±0.4%, and gamma index analysis was on average 96.4±2.2% (Passing rate: >95%), which could be limited to the large target sizes such as the whole abdominal metastasis tumor. In the DC analysis with the humanoid phantom for FW of 5.0-cm, the three regions' average was 91.8±6.4% in the 2D and 3D plan. The three planes (axial, coronal, and sagittal) and dose profile could be analyzed with the entire peritoneum tumor and the whole abdominal metastasis target, with planned dose distributions. The dose errors based on the dose-volume histogram in the DC evaluations increased depending on FW and pitch. Conclusion: The DC method could implement a dose error analysis on the 3D patient image data by the measured beam fluence log information only without any dosimetry tools for patient-specific quality assurance. Also, there may be no limit to apply for the tumor location and size; therefore, the DC could be useful in patient-specific QAl during the treatment of Helical Tomotherapy of large and irregular tumors.