Synergistic Tumoricidal Effects of Alpha-Lipoic Acid and Radiotherapy on Human Breast Cancer Cells via HMGB1 / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Radiotherapy (RT) is one of main strategies of cancer treatment. However, some cancer cells are resistant to radiation-induced cell death, including apoptosis. Therefore, alternative approaches targeting different anti-tumor mechanisms such as cell senescence are required. This study aimed to investigate the synergistic effect of alpha-lipoic acid (ALA) on radiation-induced cell death and senescence in MDA-MB-231 human breast cancer cells. @*Materials and Methods@#The cells were divided into four groups depending on the cell treatment (control, ALA, RT, and ALA+RT). Cells were analyzed for morphology, apoptotic cell death, mitochondrial reactive oxygen species, membrane potential, cellular senescence, and cell cycle. @*Results@#Our data showed that ALA significantly promoted apoptotic cell death when combined with RT, as reflected by Annexin V staining, expression of apoptosis-related factors, mitochondrial damages as well as cell morphological changes and reduction of cell numbers. In addition, ALA significantly enhanced radiation-induced cellular senescence, which was shown by increased HMGB1 expression in the cytosol fraction compared to the control, increased p53 expression compared to the control, activation of p38 as well as nuclear factor кB, and G2/M cell cycle arrest. @*Conclusion@#The current study is the first report showing a new mode of action (senescence induction) of ALA beyond apoptotic cell death in MDA-MB-231 cancer cells known to be resistant to RT.

Synergistic Tumoricidal Effects of Alpha-Lipoic Acid and Radiotherapy on Human Breast Cancer Cells via HMGB1 / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Radiotherapy (RT) is one of main strategies of cancer treatment. However, some cancer cells are resistant to radiation-induced cell death, including apoptosis. Therefore, alternative approaches targeting different anti-tumor mechanisms such as cell senescence are required. This study aimed to investigate the synergistic effect of alpha-lipoic acid (ALA) on radiation-induced cell death and senescence in MDA-MB-231 human breast cancer cells. @*Materials and Methods@#The cells were divided into four groups depending on the cell treatment (control, ALA, RT, and ALA+RT). Cells were analyzed for morphology, apoptotic cell death, mitochondrial reactive oxygen species, membrane potential, cellular senescence, and cell cycle. @*Results@#Our data showed that ALA significantly promoted apoptotic cell death when combined with RT, as reflected by Annexin V staining, expression of apoptosis-related factors, mitochondrial damages as well as cell morphological changes and reduction of cell numbers. In addition, ALA significantly enhanced radiation-induced cellular senescence, which was shown by increased HMGB1 expression in the cytosol fraction compared to the control, increased p53 expression compared to the control, activation of p38 as well as nuclear factor кB, and G2/M cell cycle arrest. @*Conclusion@#The current study is the first report showing a new mode of action (senescence induction) of ALA beyond apoptotic cell death in MDA-MB-231 cancer cells known to be resistant to RT.

Effects of the new diagnosis-related group-based payment system and the increased incentive policy rates on the utilization rate of diagnostic laboratory test in Korea

A new diagnosis-related group (DRG) based payment system has been implemented in most public hospitals in Korea. We investigated the effects of the new DRG system and its incentive policy on the utilization rate of diagnostic laboratory tests. Three groups were categorized; 36 hospitals under the new DRG system (participant group), 72 hospitals (control-1) matching with 36 participants according to the number of beds, and 42 tertiary hospitals (control-2). The patients of acute myocardial infarction, cerebral infarction, type 2 diabetes mellitus, and gonarthrosis receiving total arthroplasty were included. We analyzed the mean length of stay and the number of diagnostic laboratory tests conducted during hospitalization of the three groups according to the new DRG system and the incentive policy rates under the new DRG system. Before participating in the new DRG system, the number of diagnostic laboratory tests in the participant group was less than that in the two control groups for all four diseases. However, although the participant group’s length of stay decreased under the new DRG system, the number of diagnostic laboratory tests increased as the maximum incentive policy rate increased. The increment of the number of diagnostic laboratory tests was prominent in the period of a maximum of 35% incentive policy rates. Finally, the number of diagnostic laboratory tests of the participant group was similar to or exceeded that of the control-2 group. The new DRG system’s incentive policy rates played a driving force on the increased utilization rate of the diagnostic laboratory test. For preparing in advance for the change in incentive policy rates, monitoring and guidelines for the utilization of diagnostic laboratory tests are necessary.

Tumor Control and Overall Survival after Stereotactic Body Radiotherapy for Pulmonary Oligometastases from Colorectal Cancer: A Meta-Analysis / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#In pulmonary oligometastases from colorectal cancer (POM-CRC), the primarily recommended local therapy is metastasectomy. Stereotactic body radiotherapy (SBRT) is another local therapy modality that is considered as an alternative option in patients who cannot undergo surgery. The purpose of this meta-analysis is to demonstrate the effects of SBRT on POM-CRC by integrating the relevant studies. @*Materials and Methods@#The authors explored MEDLINE, EMBASE, Cochrane Library, Web of Science, and SCOPUS, and selected studies including patients treated with SBRT for POM-CRC and availability of local control (LC) or overall survival (OS) rate. In this meta-analysis, the effect of SBRT was presented in the form of the LC and OS rates for 1, 2, 3, and 5 years after SBRT as pooled estimates, and the frequency of pulmonary toxicity of grade 3 or higher after SBRT (PTG3-SBRT). @*Results@#Fourteen full texts among the searched 4,984 studies were the objects of this meta-analysis. The overall number of POM-CRC patients was 495 as per the integration of 14 studies. The pooled estimate LC rate at 1, 2, 3, and 5 years after SBRT was 81.0%, 71.5%, 56.0%, and 61.8%, and the OS rate was 86.9%, 70.1%, 57.9%, and 43.0%, respectively. The LC and OS rates gradually declined until 3 years after SBRT in a similar pattern. Among the 14 studies, only two studies reported PTG3-SBRT as 2.2% and 10.8%, respectively. @*Conclusion@#For POM-CRC, SBRT is an ablative therapy with a benefit on LC and OS rates and less adverse effects on the lung.

Effect of Visual Feedback Squat Motion on Core Muscles Thickness of Young People with Lower Back Pain

PURPOSE: This study examined the effect of visual feedback squat on the core muscle thickness of young adults experiencing back pain. METHODS: Thirty adult men and women who experienced back pain were assigned randomly to 15 members of the visual feedback squat group (VSG) and 15 of the normal squat group (NSG) to train three times a week for a total of eight weeks. The core muscle thickness was compared prior to the test for four weeks and eight weeks after the test by dividing it into warm-up exercise, main exercise, and 10 minutes finishing exercise. Before, and four weeks and eight weeks later, the thickness of the core muscle was compared using an ultrasonic imaging system. Repeated measured ANOVA was performed to compare the groups, and a Bonferroni test was performed as a post-hoc test to assess the significance of the timing of the measurements in each group according to the periods. An independent t-test was conducted to test the significance between the groups according to the measurement points. RESULTS: A significant change in the main effects of time and interactions of the time difference in muscle thickness of transvers abdominis were observed between the visual feedback squat and control groups according to the measurement point (p0.05). CONCLUSION: These findings suggest that visual feedback squat exercise is expected to have positive effects on the development of transverse abdominis in core muscles.

Increased Ventrolateral Prefrontal Cortex Activation during Accurate Eyewitness Memory Retrieval: An Exploratory Functional Near-Infrared Spectroscopy Study / 대한법의학회지

We investigated the neural correlates of accurate eyewitness memory retrieval using functional near-infrared spectroscopy. We analyzed oxygenated hemoglobin (HbO₂) concentration in the prefrontal cortex during eyewitness memory retrieval task and examined regional HbO₂ differences between observed objects (target) and unobserved objects (lure). We found that target objects elicited increased activation in the bilateral ventrolateral prefrontal cortex, which is known for monitoring retrieval processing via bottom-up attentional processing. Our results suggest bottom-up attentional mechanisms could be different during accurate eyewitness memory retrieval. These findings indicate that investigating retrieval mechanisms using functional nearinfrared spectroscopy might be useful for establishing an accurate eyewitness recognition model.

The Assessment of Eyewitness Memory Using Electroencephalogram: Application of Machine Learning Algorithm / 대한법의학회지

This study was conducted to investigate whether memory accuracy can be assessed by analyzing electrophysiological responses (i.e., electroencephalography [EEG]) for retrieval cues related to the witnessed scene. Specifically, we examined the different patterns of EEG signals recorded during witnessed (target) and unwitnessed (lure) stimuli using event-related potential (ERP) analysis. Moreover, using multivariate pattern analysis, we also assessed how accurately single-trial EEG signals can classify target and lure stimuli. Participants watched a staged-crime video (theft crime), and the EEG signals evoked by the objects shown in the video were analyzed (n=56). Compared to the target stimulus, the lure stimulus elicited larger negative ERPs in frontal brain regions 300 to 500 milliseconds after the retrieval cue was presented. Furthermore, the EEG signals observed 450 to 500 milliseconds after the retrieval cue was presented showed the best classification performance related to eyewitness memory, with the mean classification accuracy being 56%. These results suggest that the knowledge and techniques of cognitive neuroscience can be used to estimate eyewitness memory accuracy.

Increased Ventrolateral Prefrontal Cortex Activation during Accurate Eyewitness Memory Retrieval: An Exploratory Functional Near-Infrared Spectroscopy Study / 대한법의학회지

We investigated the neural correlates of accurate eyewitness memory retrieval using functional near-infrared spectroscopy. We analyzed oxygenated hemoglobin (HbOâ‚‚) concentration in the prefrontal cortex during eyewitness memory retrieval task and examined regional HbOâ‚‚ differences between observed objects (target) and unobserved objects (lure). We found that target objects elicited increased activation in the bilateral ventrolateral prefrontal cortex, which is known for monitoring retrieval processing via bottom-up attentional processing. Our results suggest bottom-up attentional mechanisms could be different during accurate eyewitness memory retrieval. These findings indicate that investigating retrieval mechanisms using functional nearinfrared spectroscopy might be useful for establishing an accurate eyewitness recognition model.

The Assessment of Eyewitness Memory Using Electroencephalogram: Application of Machine Learning Algorithm / 대한법의학회지

This study was conducted to investigate whether memory accuracy can be assessed by analyzing electrophysiological responses (i.e., electroencephalography [EEG]) for retrieval cues related to the witnessed scene. Specifically, we examined the different patterns of EEG signals recorded during witnessed (target) and unwitnessed (lure) stimuli using event-related potential (ERP) analysis. Moreover, using multivariate pattern analysis, we also assessed how accurately single-trial EEG signals can classify target and lure stimuli. Participants watched a staged-crime video (theft crime), and the EEG signals evoked by the objects shown in the video were analyzed (n=56). Compared to the target stimulus, the lure stimulus elicited larger negative ERPs in frontal brain regions 300 to 500 milliseconds after the retrieval cue was presented. Furthermore, the EEG signals observed 450 to 500 milliseconds after the retrieval cue was presented showed the best classification performance related to eyewitness memory, with the mean classification accuracy being 56%. These results suggest that the knowledge and techniques of cognitive neuroscience can be used to estimate eyewitness memory accuracy.

Analysis of Motion-dependent Clinical Outcome of Tumor Tracking Stereotactic Body Radiotherapy for Prostate Cancer

BACKGROUND: To analyze clinical outcome of CyberKnife (CK) tumor-tracking stereotactic body radiotherapy (SBRT) for prostate cancer (Pca) according to the magnitude of intra-fractional prostate motion. METHODS: Medical records and daily treatment logs for 71 patients who received CK tumor-tracking SBRT were retrospectively analyzed. Statistical relationships between prostate motion and various outcome results, including local recurrence (LR), biochemical failure (BF), and treatment-related toxicity, were investigated in order to evaluate motion-dependent efficacy of tumor-tracking SBRT for Pca. RESULTS: In a total 71 patients, 3 (4.2%) patients with LR, 12 (16.9%) patients with BF, and 22 (31%) patients with grade-II or worse toxicities to rectal or bladder (22 to rectal, 22 to bladder and 8 patients to both) were observed in a median follow-up of 47 months. Magnitudes of intra-fractional tumor motion along superior-inferior, right-left, and anterior-posterior (AP) axes were 0.15 ± 0.31, 0.12 ± 0.19, and 0.73 ± 0.32 mm, respectively. Radial magnitude was estimated to be 1.0 ± 0.35 mm. Intra-fractional movement was not significantly correlated with tumor control. However, it was significant correlated with the incidence of grade-II or worse toxicity to rectum or bladder particularly when tumor motion was in the AP axis. CONCLUSION: Our quantitative results revealed that toxicity related to SBRT treatment was highly sensitive to intra-fractional prostate movements, although local-tumor control was not affected by such movements. Our results demonstrate that precise motion correction is essential in prostate SBRT, even if it seems to be small.

Who Really Benefits from 3D-Based Planning of Brachytherapy for Cervical Cancer?

BACKGROUND: Although intracavitary radiotherapy (ICR) is essential for the radiation therapy of cervical cancer, few institutions in Korea perform 3-dimensional (3D)-based ICR. To identify patients who would benefit from 3D-based ICR, dosimetric parameters for tumor targets and organs at risk (OARs) were compared between 2-dimensional (2D)- and 3D-based ICR. METHODS: Twenty patients with locally advanced cervical cancer who underwent external beam radiation therapy (EBRT) following 3D-based ICR were retrospectively evaluated. New 2D-based plans based on the Manchester system were developed. Tumor size was measured by magnetic resonance imaging. RESULTS: The mean high risk clinical target volume (HR-CTV) D90 value was about 10% lower for 2D- than for 3D-based plans (88.4% vs. 97.7%; P = 0.068). Tumor coverage did not differ between 2D- and 3D-based plans in patients with tumors ≤ 4 cm at the time of brachytherapy, but the mean HR-CTV D90 values in patients with tumors > 4 cm were significantly higher for 3D-based plans than for 2D-based plans (96.0% vs. 78.1%; P = 0.017). Similar results were found for patients with tumors > 5 cm initially. Other dosimetric parameters for OARs were similar between 2D- and 3D-based plans, except that mean sigmoid D2cc was higher for 2D- than for 3D-based plans (67.5% vs. 58.8%; P = 0.043). CONCLUSION: These findings indicate that 3D-based ICR plans improve tumor coverage while satisfying the dose constraints for OARs. 3D-based ICR should be considered in patients with tumors > 4 cm size at the time of brachytherapy or > 5 cm initially.

Carotid sparing intensity modulated radiotherapy on early glottic cancer: preliminary study

PURPOSE: To compare the dose distribution between carotid sparing intensity modulated radiotherapy (IMRT) and opposed lateral field technique (LAFT), and to determine the effects of carotid sparing IMRT in early glottic cancer patients who have risk factors for atherosclerosis. MATERIALS AND METHODS: Ten early glottic cancer patients were treated with carotid sparing IMRT. For each patient, the conventional LAFT plan was developed for comparison. IMRT and LAFT plans were compared in terms of planning target volume (PTV) coverage, conformity index, homogeneity index, and the doses to planning organ at risk volume (PRV) for carotid arteries, spinal cord and pharyngeal constrictor muscle. RESULTS: Recurrence was not observed in any patients during the follow-up period. V95% for PTV showed no significant difference between IMRT and LAFT plans, while V100% was significantly higher in the IMRT plan (95.5% vs. 94.6%, p = 0.005). The homogeneity index (11.6%) and conformity index (1.4) in the IMRT plan were significantly better than those in the LAFT plans (8.5% and 5.1, respectively) (p = 0.005). The median V5Gy (90.0%), V25Gy (13.5%), and V50Gy (0%) for carotid artery PRV in the IMRT plan were significantly lower than those in the LAFT plan (99.1%, 89.0%, and 77.3%, respectively) (p = 0.005). CONCLUSION: Our study suggests that carotid sparing IMRT can significantly decrease the dose to carotid arteries compared to LAFT, and it would be considered for early glottic cancer patient with high risk of atherosclerosis.

Stereotactic Body Radiation Therapy for Low- to Intermediate-risk Prostate Adenocarcinoma

The aim of the present study was to evaluate the efficacy and toxicity of stereotactic body radiation therapy (SBRT) for low- to intermediate-risk prostate adenocarcinoma. Thirty-nine patients were retrospectively reviewed. The SBRT was delivered using the CyberKnife with the fiducial tracking method combined with In-tempo imaging. The gross target volume, which included the prostate only, was delineated on the fused CT/MRI scans. The prescription dose was delivered every other day as 5 fractions of 7.5 Gy. Venous blood was obtained before and after SBRT to assess the prostate-specific antigen (PSA) level. Toxicity was evaluated using the CTCAE, v4.03. The median follow-up time was 30.0 months. The median initial PSA level was 7.7 ng/mL. PSA levels decreased in all patients treated with SBRT, and after 5 months, the median PSA was less than 2 ng/mL. The rate of overall 3-yr actuarial biochemical failure free survival was 93.9%. Acute side effects were generally comparable with those of previous studies. The PSA change and toxicity after SBRT for low- to intermediate-risk prostate adenocarcinoma indicates favorable biochemical responses and tolerable levels of toxicity. Additionally short course treatment may produce cost benefit and convenience to patients.

Effect of early chemoradiotherapy in patients with limited stage small cell lung cancer

PURPOSE: We evaluated the effect of early chemoradiotherapy on the treatment of patients with limited stage small cell lung cancer (LS-SCLC). MATERIALS AND METHODS: Between January 2006 and December 2011, thirty-one patients with histologically proven LS-SCLC who were treated with two cycles of chemotherapy followed by concurrent chemoradiotherapy and consolidation chemotherapy were retrospectively analyzed. The chemotherapy regimen was composed of etoposide and cisplatin. Thoracic radiotherapy consisted of 50 to 60 Gy (median, 54 Gy) given in 5 to 6.5 weeks. RESULTS: The follow-up period ranged from 5 to 53 months (median, 22 months). After chemoradiotherapy, 35.5% of the patients (11 patients) showed complete response, 61.3% (19 patients) showed partial response, 3.2% (one patient) showed progressive disease, resulting in an overall response rate of 96.8% (30 patients). The 1-, 2-, and 3-year overall survival (OS) rates were 66.5%, 41.0%, and 28.1%, respectively, with a median OS of 21.3 months. The 1-, 2-, and 3-year progression free survival (PFS) rates were 49.8%, 22.8%, and 13.7%, respectively, with median PFS of 12 months. The patterns of failure were: locoregional recurrences in 29.0% (nine patients), distant metastasis in 9.7% (three patients), and both locoregional and distant metastasis in 9.7% (three patients). Grade 3 or 4 toxicities of leukopenia, anemia, and thrombocytopenia were observed in 32.2%, 29.0%, and 25.8%, respectively. Grade 3 radiation esophagitis and radiation pneumonitis were shown in 12.9% and 6.4%, respectively. CONCLUSION: We conclude that early chemoradiotherapy for LS-SCLC provides feasible and acceptable local control and safety.

Dosimetry by Using EBT2 Film for Total Skin Electron Beam Therapy (TSET) / 의학물리

For treatment of Total Skin Electron beam Therapy (TSET), measurement of dose at various conditions is need on the contrary to usual radiotherapy. When treating TSET with modified Stanford technique based on linear accelerator, the energy of treatment electron beam, the spatial dose distribution and the actual doses deposited on the surface of the patient were measured by using EBT2. The measured energy of the electron beam was agreed with the value that measured by ionization chamber, and the spatial dose distribution at the patient position and the doses at several point on the patient's skin could be easily measured by EBT2 film. The dose on the patient that was measured by EBT2 film showed good agreement with the data measured simultaneously by TLD. With the results of this study, it was proven that the EBT2 film can be one of the useful dosimeter for TSET.

Study on Absorbed Dose Determination of Electron Beam Quality for Cross-calibration with Plane-parallel Ionization Chamber / 의학물리

Absorbed dose to water based protocols recommended that plane-parallel chambers be calibrated against calibrated cylindrical chambers in a high energy electron beam with R50>7 g/cm2 (E> or =16 MeV). However, such high-energy electron beams are not available at all radiotherapy centers. In this study, we are compared the absorbed dose to water determined according to cross-calibration method in a high energy electron beam of 16 MeV and in electron beam energies of 12 MeV below the cross-calibration quality remark. Absorbed dose were performed for PTW 30013, Wellhofer FC65G Farmer type cylindrical chamber and for PTW 34001, Wellhofer PPC40 Roos type plane-parallel chamber. The cylindrical and the plane-parallel chamber to be calibrated are compared by alternately positioning each at reference depth, zref=0.6R50-0.1 in water phantom. The DW of plane-parallel chamber are derived using across-calibration method at high-energy electron beams of 16, 20 MeV. Then a good agreement is obtained the DW of plane-parallel chamber in 12 MeV. The agreement between 20 MeV and 12 MeV are within 0.2% for IAEA TRS-398.