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Supplementary Table 1 from Erythropoietin Induces Lymph Node Lymphangiogenesis and Lymph Node Tumor Metastasis

During radiotherapy, some patients owing to the variability in skin sensitivities, may experience adverse skin reactions for doses at which other patients are asymptomatic. Hence, when abnormal symptoms appear on a patient’s skin, the etiology should be verified. Accordingly, a surface dosimeter on the skin can help ascertain whether accurate doses are irradiated. Furthermore, surface doses are measured in the field junction gaps during craniospinal irradiation or during large-area radiotherapy to avoid adverse reactions due to cumulative skin doses from multiple beams. However, the point dose measurement errors of surface dosimeters exceed approximately 10% and have low-positional accuracies because the attachment sites are approximated with the help of the naked eye. Moreover, accurate information on field junction gaps cannot be obtained. Therefore, in clinical practice, a flexible array dosimeter is required as it can measure the dose distribution on the body surface by adapting its shape to the body curvatures. In this study, we implemented a flexible array dosimeter and, based on its constituent materials, evaluated the attenuation rate associated with its use. A polyester (PET) film was used as the underlying substrate. HgI2 and PbI2 photoconductors were used for their good performances in films. Furthermore, the measurement accuracy was verified through comparisons with Monte Carlo simulation outcomes. The resulting PET film had an attenuation rate of 2.22% at a 50-µm thickness. At the minimum material thickness of 25 µm, the attenuation rates for HgI2 and PbI2 were 4.69% and 5.72%, respectively. Further research is needed to fabricate HgI2-based digital skin dosimeters with a thickness under 25 µm. Radiation detection and pixel resolution should be evaluated to accurately confirm the field junction gap.

Tacrolimus is a key drug in kidney transplantation (KT) with a narrow therapeutic index. The association between the tacrolimus metabolism rate and KT outcomes have not been investigated in large-scale multi-center studies. The Korean Organ Transplantation Registry (KOTRY) datasets were used. A total of 3456 KT recipients were analyzed. The tacrolimus metabolism rate was defined as blood trough concentration of tacrolimus (C0 ) divided by the daily dose (D). The patients were grouped into fast, intermediate, or slow metabolizers by the C0 /D measured 6 months after transplantation. The slow metabolism group was associated with a 2.7 ml/min/1.73 m2 higher adjusted estimated glomerular filtration rate (eGFR) at 6 months [95% confidence interval (C.I.) 1.2-4.3, P = 0.001], less acute rejection (AR) within 6 months [Odds ratio (OR) 0.744, 95% C.I. 0.585-0.947, P = 0.016], and less interstitial fibrosis and tubular atrophy [OR 0.606, 95% C.I. 0.390-0.940, P = 0.025]. Fast tacrolimus metabolism affected the 6-month post-KT eGFR through mediation of AR [natural indirect effect (NIE) -0.434, 95% C.I. -0.856 to -0.012, P = 0.044) and delayed graft function (DGF; NIE -0.119, 95% C.I. -0.231 to -0.007, P = 0.038). Slow tacrolimus metabolism was associated with better post-KT eGFR. AR and DGF were found to be significant mediators.

The postoperative hypofractionated intensity-modulated radiation therapy (POHIM-RT) trial is a phase II study to evaluate toxicity following hypofractionated intensity modulated radiation therapy (IMRT) for cervical cancer. This study describes the results of a benchmark procedure for RT quality assurance of the POHIM-RT trial. Six participating institutions were provided computed tomography for RT planning and an IMRT plan for a sample and were instructed to delineate volumes, create a treatment plan and quality assurance (QA) plan, and submit the results of all procedures. The inter-institutional agreements on RT volume and plan results were evaluated using the kappa value and dice similarity coefficients. The simultaneous truth and performance level estimation (STAPLE) method was employed to generate a consensus target volume. The treatment volumes, organs-at-risk volumes, and results of the RT plan and QA reported by the institutions were acceptable and adhered well to the protocol. In terms of clinical target volume (CTV) delineation, there were differences between the institutions, particularly in vaginal cuff and paracolpium subsites. Consensus CTV was generated from the collected CTVs with the STAPLE method. The participating institutions showed considerable agreement regarding volume, dose and QA results. To improve CTV agreement in CTV, we provided feedback with images of the consensus target volume and detailed written guidelines for specific subsites that were the most heterogeneous.

In patients with early-stage breast cancer, the treatment results of hypofractionated radiation therapy (RT) and conventional RT are evaluated in efficacy and cost.We retrospectively evaluated 280 patients with early-stage (Tis-2N0M0) breast cancer (including 100 hypofractionated RT patients) with regards to treatment outcomes according to the RT schedule. The median whole-breast RT dose was 42.56 Gy/16 fractions for hypofractionated RT and 50.4 Gy/28 fractions for conventional RT. Most patients (n = 260, 92.9%) additionally received a tumor bed boost RT. We used propensity score matching (PSM) analysis to balance the baseline risk factors for recurrence. The co-primary endpoints of this study were disease-free survival (DFS) and ipsilateral breast tumor recurrence (IBTR). DFS or IBTR was analyzed using the Kaplan-Meier survival curve and log-rank test.Total 89 pairs of matched patients (1:1 matching, n = 178) were finally evaluated. The median follow-up was 23.6 months. After matching, the 3-year DFS was 100% in the hypofractionated RT group and 98.4% in the conventional RT group; there was no significant difference in DFS between the groups (Hypofractionated RT showed good IBTR and DFS, which were compatible to those in conventional RT in breast cancer. Hypofractionated RT is expected to be used more widely because of its low cost and convenience.

Generally, electron therapy is applied to tumors on or close to the skin surface. However, this causes a variety of skin-related side effects. To alleviate the risk of these side effects, clinical treatment uses skin dosimeters to verify the therapeutic dose. However, dosimeters suffer from poor accuracy, because their attachment sites are approximated with the help of naked eyes. Therefore, a dosimeter based on a flexible material that can adjust to the contours of the human body is required. In this study, the reproducibility, linearity, dose-rate dependence, and percentage depth ionization (PDI) of PbO and HgO film-based dosimeters are evaluated to explore their potential as large-scale flexible dosimeters. The results demonstrate that both dosimeters deliver impressive reproducibility (within 1.5%) and linearity (≥ 0.9990). The relative standard deviations of the dose-rate dependence of the PbO and HgO dosimeters were 0.94% and 1.16% at 6 MeV, respectively, and 1.08% and 1.25% at 9 MeV, respectively, with the PbO dosimeter outperforming the 1.1% of existing diodes. The PDI analysis of the PbO and HgO dosimeters returned values of 0.014 cm (–0.074 cm) and 0.051 cm (–0.016 cm), respectively at 6 MeV (9 MeV) compared to the thimble chamber and R50. Therefore, the maximum error of each dosimeter is within the allowable range of 0.1 cm. In short, the analysis reveals that the PbO dosimeter delivers a superior performance relative to its HgO counterpart and has strong potential for use as a surface dosimeter. Thus, flexible monoxide materials have the necessary qualities to be used for dosimeters that meet the requisite quality assurance standards and can satisfy a variety of radiation-related applications as flexible functional materials.

Radiation therapy uses high-energy radiation that can cause various side effects depending on the patient's exposure. In particular, side effects occur in the skin due to its radiation exposure to reach the target volume. Therefore, side effects are reduced by clinical trials using various skin dosimeters such as films and glass detectors to determine the dose exposed to the skin. However, accurately measuring the doses using these dosimeters is challenging due to human curvature. In this study, a flexible skin dosimeter was produced using the photoconductor materials mercury oxide (HgO) and lead oxide (PbO). The performance of the proposed dosimeter was evaluated by measuring reproducibility, linearity, dose rate independency according to dose, and percent depth dose (PDD) at photon energy beam. The results showed that the flexible skin dosimeter using HgO material has high applicability as a skin dosimeter due to its stability compared to PbO. The results provide useful insights for the radiation therapy field, particularly in areas where radiation measurement is difficult, depending on the human curvature. The proposed flexible skin dosimeter could serve in various radiation detection areas as a flexible, functional material

Background and Aims Biomarkers associated with chronic kidney disease (CKD) may play a crucial role in patients with diabetic kidney diseases. Vascular endothelial growth factor (VEGF)-C and VEGF-D are lymphangiogenic growth factors. It has been well demonstrated that there is lympnagiogenesis in fibrotic kidney disease in human. Previously, we showed that renal VEGF-C and VEGF-D are involved in lymphangiogensis in renal fibrosis model. Recent studies have shown a relationship between sodium load and serum VEGF-C levels in hypertensive patients. Lymphatic endothelial proliferation has been detected in diabetic nephropathy. Thus, serum VEGF-C level has been introduced as a candidate marker of chronic kidney disease. However, until now, there have been few report about serum VEGF-D in patients with diabetic CKD. Thus, we evaluated the relationships between serum VEGF-D and renal function and albuminuria of diabetic CKD. Method We divided diabetic CKD patients into four groups: CKD stage 3, CKD stage 4, and CKD stage 5 (without dialysis). Total forty two Asian patients with diabetic CKD (14 patients with CKD stage 3, 14 patients with CKD stage 4 and 14 patients with CKD stage 5) and seven healthy controls without diabetes mellitus have been enrolled in this study. In this cross-sectional study, we performed comparative analysis with serum level of VEGF-D in patients with each group. We measured the levels of VEGF-D through the multiplexing using Luminex® technology. Results The serum levels of VEGF-D were higher in the CKD 3, CKD 4 and CKD 5 group compared with the control group (25.9±5.6 pg/ml in control group, 60.3±9.7in stage 3, 62.9±8.5 in stage 4, and 66.5±8.0 in stage 5). However, there was not a significant difference between CKD stage III or IV and CKD stage V in serum levels of VEGF-D. Serum VEGF-D level were negatively correlated with estimated glomerular filtration rate and positively correlated with serum creatinine. At GFR level ≥60 ml/min per 1.73 m2, serum VEGF-D were biomarkers in ROC analysis. There was a positive correlation between serum VEGF-D level and albuminuria in patient with diabetic CKD. We also found that serum VEGF-D level also correlated with urine protein-to-creatinine ratio in patient with diabetic CKD. Conclusion Serum VEGF-D is correlated with renal function in patients with diabetic CKD. VEGF levels in the serum correlate to the severity of proteinuria and albuminuria in diabetic CKD patients. Further large-scale studies are required to confirm these findings.

Cisplatin-based chemotherapy is commonly used in the treatment of solid tumors; however, this agent is limited by its adverse effects on normal tissues, including the kidneys, ears and peripheral nerves. Mechanisms of cisplatin nephrotoxicity are proposed to involve oxidative stress, inflammation, cellular apoptosis and cell cycle regulation. Sirtuin 3 (Sirt3) is a member of the sirtuin family of NAD+-dependent enzymes with homology to Saccharomyces cerevisiae gene silent information regulator 2. Sirt3 is located in mitochondria and is involved in mitochondrial energy metabolism and function; however, the role of Sirt3 in cisplatin nephrotoxicity remains unclear. In the present study, whether Sirt3 has anti-inflammatory and anti-apoptotic effects on cisplatin-induced nephrotoxicity was investigated in mice. Sirt3 knockout mice (Sirt3(−/−)) and corresponding wild type mice were employed in the present study. Cisplatin nephrotoxicity was induced by intraperitoneal injection of cisplatin (20 mg/kg). After 3 days following cisplatin treatment, blood and kidney tissues were harvested. Renal function and histology were evaluated. Tubular apoptosis, cell adhesion molecule expression, and inflammatory cells were evaluated by immunohistochemistry and western blot analysis. Following the induction of cisplatin nephrotoxicity, renal function was significantly aggravated in Sirt3 knockout (KO) mice. Tubular injury and inflammatory cell infiltration were significantly increased in Sirt3KO mice compared with wild type mice. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end label-positive tubular cells and renal monocyte chemoattractant protein-1 expression levels were increased in Sirt3KO mice compared with in wild type mice. In summary, the absence of Sirt3 aggravated in renal injury by increasing renal inflammation and tubular apoptosis. The results of the present study suggested that Sirt3 may have an important role in cisplatin-induced nephrotoxicity.

Currently, in the radiation diagnosis field, mammography is used for the early detection of breast cancer. In addition, studies are being conducted on a grid to produce high-quality images. Although the grid ratio of the grid, which affects the scattering removal rate, must be increased to improve image quality, it increases the total exposure dose. While the use of automatic exposure control is recommended to minimize this problem, existing mammography equipment, unlike general radiography equipment, is mounted on the back of a detector. Therefore, the device is greatly affected by the detector and supporting device, and it is difficult to control the exposure dose. Accordingly, in this research, an integrated AEC-grid device that simultaneously performs AEC and grid functions was used to minimize the unnecessary exposure dose while removing scattering, thereby realizing superior image quality.

Purpose This study aimed to assess the effects of body mass index (BMI) on survival in cervical cancer patients who had undergone surgery and radiotherapy (RT). Materials and methods We retrospectively reviewed the medical records of 70 cervical cancer patients who underwent surgery and RT from 2007 to 2012. Among them, 40 patients (57.1%) had pelvic lymph node metastases at the time of diagnosis. Sixty-seven patients (95.7%) had received chemotherapy. All patients had undergone surgery and postoperative RT. Median BMI of patients was 22.8 kg/m2 (range, 17.7 to 35.9 kg/m2). Results The median duration of follow-up was 52.3 months (range, 16 to 107 months). Twenty-four patients (34.3%) showed recurrence. Local failure, regional lymph nodal failure, and distant failure occurred in 4 (5.7%), 6 (8.6%), and 17 (24.3%) patients, respectively. The 5-year actuarial pelvic control rate was 83.4%. The 5-year cancer-specific survival (CSS) and disease-free survival (DFS) rates were 85.1% and 65.0%, respectively. The presence of pelvic lymph node metastases (n = 30) and being overweight or obese (n = 34, BMI ≥ 23 kg/m2) were poor prognostic factors for CSS (p = 0.003 and p = 0.045, respectively). Of these, pelvic lymph node metastasis was an independent prognostic factor (p = 0.030) for CSS. Conclusion Overweight or obese cervical cancer patients showed poorer survival outcomes than normal weight or underweight patients. Weight control seems to be important in cervical cancer patients to improve clinical outcomes.

Because systems that reduce radiation exposure during diagnostic procedures must be developed, significant time and financial resources have been invested in constructing radiation dose management systems. In the present study, the characteristics of an existing ionization-based system were compared to those of a system based on the kinetic energy released per unit mass (KERMA). Furthermore, the feasibility of using the KERMA-based system for patient radiation dose management was verified. The ionization-based system corrected the effects resulting from radiation parameter perturbations in general radiography whereas the KERMA-based system did not. Because of this difference, the KERMA-based radiation dose management system might overestimate the patient’s radiation dose due to changes in the radiation conditions. Therefore, if a correction factor describing the correlation between the systems is applied to resolve this issue, then a radiation dose management system can be developed that will enable real-time measurement of the patient’s radiation exposure and acquisition of diagnostic images.

Purpose The association between metabolism and cancer has been recently emphasized. This study aimed to find the prognostic significance of obesity in advanced stage rectal cancer patients treated with surgery and radiotherapy (RT). Materials and methods We retrospectively reviewed the medical records of 111 patients who were treated with combined surgery and RT for clinical stage 2-3 (T3 or N+) rectal cancer between 2008 and 2014. The prognostic significance of obesity (body mass index [BMI] ≥25 kg/m(2)) in local control was evaluated. Results The median follow-up was 31.2 months (range, 4.1 to 85.7 months). Twenty-five patients (22.5%) were classified as obese. Treatment failure occurred in 33 patients (29.7%), including local failures in 13 patients (11.7%), regional lymph node failures in 5, and distant metastases in 24. The 3-year local control, recurrence-free survival, and overall survival rates were 88.7%, 73.6%, and 87.7%, respectively. Obesity (n = 25) significantly reduced the local control rate (p = 0.045; 3-year local control, 76.2%), especially in women (n = 37, p = 0.021). Segregation of local control was best achieved by BMI of 25.6 kg/m(2) as a cutoff value. Conclusion Obese rectal cancer patients showed poor local control after combined surgery and RT. More effective local treatment strategies for obese patients are warranted.

// Eun-Tae Park 1 , Sung Kwang Park 1 1 Department of Radiation Oncology, Busan Paik Hospital, Inje University School of Medicine, Busan, Korea Correspondence to: Sung Kwang Park, email: physicist@paik.ac.kr Keywords: head and neck cancer, setup error, cervical spine, organ motion Received: March 07, 2016 Accepted: April 27, 2016 Published: May 31, 2016 ABSTRACT Purpose: The aim of this study is to determine the inter-fractional motion of cervical spine in radiotherapy (RT). Materials and Methods: Eleven localized head and neck cancer patients who were treated from April 2014 to September 2015 were evaluated. Every patient underwent 3 times of computed tomography (CT) simulation with equivalent setting. Left-right (LR, x) and antero-posterior (AP, z) directional shift of cervical spine were evaluated using 33 number of CT image. In regard to random error, geometric changes were evaluated by 22 data set (compared the first obtained CT to second or third CT) by one-sample T test. Systemic error was evaluated by each patients’ data set (11 pairs) by paired T test. Results: The mean random error of LR and AP translational shift of cervical spine were −0.39 ± 3.24 mm and −0.57 ± 0.99 mm respectively. The mean random error of translational change of AP direction showed statistical significance ( p = 0.014). The mean random error of x and z rotational shift were −0.07 ± 0.29° and −0.05 ± 0.35°, respectively. The mean systemic error of translational shift of LR and AP direction were −0.64 ± 2.57 mm and −0.33 ± 1.22 mm, respectively. The mean systemic error of rotational shift of x and z were 0.01 ± 0.18° and −0.27 ± 0.33°, respectively. The mean systemic error of rotational changes of z direction showed statistical difference ( p = 0.022). Conclusions: We have to be aware of the inter-fractional motion of cervical spine in head and neck RT and give enough margins in RT planning.

Purpose This study aimed to evaluate the effects of radiotherapy (RT) on progression-free survival (PFS) for patients with recurrent colorectal cancer. Methods We reviewed the records of 22 patients with recurrent colorectal cancer treated with RT between 2008 and 2014. The median radiation dose for recurrent disease was 57.6 Gy (range, 45–75.6 Gy). Patients were divided into 2 groups according to the type of RT: patients underwent RT without previous history of irradiation (n = 14) and those treated with secondary RT (reirradiation: n = 8) at the time of recurrence. Results The median follow-up period was 24.9 months (range, 4.5–66.6 months). Progression was observed in 14 patients (including 8 with loco-regional failure and 9 with distant metastases). Distant metastases were related to the RT dose (

Yes-associated protein (YAP) activation after acute ischemic kidney injury might be related to interstitial fibrosis and impaired renal tubular regeneration. Verteporfin (VP) is a photosensitizer used in photodynamic therapy to treat age-related macular degeneration. In cancer cells, VP inhibits TEA domain family member (TEAD)-YAP interactions without light stimulation. The protective role of VP in unilateral ureteral obstruction (UUO)-induced renal fibrosis and related mechanisms remains unclear. In this study, we investigate the protective effects of VP on UUO-induced renal tubulointerstitial inflammation and fibrosis and its regulation of the transforming growth factor-&beta, 1 (TGF-&beta, 1)/Smad signaling pathway. We find that VP decreased the UUO-induced increase in tubular injury, inflammation, and extracellular matrix deposition in mice. VP also decreased myofibroblast activation and proliferation in UUO kidneys and NRK-49F cells by modulating Smad2 and Smad3 phosphorylation. Therefore, YAP inhibition might have beneficial effects on UUO-induced tubulointerstitial inflammation and fibrosis by regulating the TGF-&beta, 1/Smad signaling pathway.

Purpose This study aimed to identify the feasibility of the maximum standardized uptake value (SUVmax) on baseline 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) as a predictive factor for prognosis in early stage primary lung cancer treated with stereotactic body radiotherapy (SBRT). Materials and methods Twenty-seven T1-3N0M0 primary lung cancer patients treated with curative SBRT between 2010 and 2018 were retrospectively evaluated. Four patients (14.8%) treated with SBRT to address residual tumor after wedge resection and one patient (3.7%) with local recurrence after resection were included. The SUVmax at baseline PET/CT was assessed to determine its relationship with prognosis after SBRT. Patients were divided into two groups based on maximum SUVmax on pre-treatment FDG PET/CT, estimated by receiver operating characteristic curve. Results The median follow-up period was 17.7 months (range, 2.3 to 60.0 months). The actuarial 2-year local control, progressionfree survival (PFS), and overall survival were 80.4%, 66.0%, and 78.2%, respectively. With regard to failure patterns, 5 patients exhibited local failure (in-field failure, 18.5%), 1 (3.7%) experienced regional nodal relapse, and other 2 (7.4%) developed distant failure. SUVmax was significantly correlated with progression (p = 0.08, optimal cut-off point SUVmax > 5.1). PFS was significantly influenced by pretreatment SUVmax (SUVmax > 5.1 vs. SUVmax ≤ 5.1; p = 0.012) and T stage (T1 vs. T2-3; p = 0.012). Conclusion SUVmax at pre-treatment FDG PET/CT demonstrated a predictive value for PFS after SBRT for lung cancer.

Objective. This study used a continuous glucose monitoring system (CGMS) to investigate the glucose profiles and assess the degree of hyperglycemic excursion after kidney or liver transplantation during the early period after operation. Methods. Patients to whom a CGMS was attached during a postoperative period of approximately one month after transplantation were included. The CGM data of 31 patients including 24 with kidney transplantation (KT) and seven with liver transplantation (LT) were analyzed. Results. Hyperglycemia over 126 mg/dL (fasting) or 200 g/dL (postprandial) occurred in 42.1% (8/19) and 16.7% (1/6) of KT and LT patients, respectively, during this early period after transplantation, except for patients with preexisting diabetes (5 KT, 1 LT). The average mean amplitude of glycemic excursion (MAGE) and mean absolute glucose (MAG) levels were 91.18±26.51 vs. 65.66±22.55 (P<0.05) and 24.62±7.78 vs. 18.18±7.07 (P<0.05) in KT vs. LT patients, respectively, in patients without preexisting DM or PTDM patients who showed normal glucose levels. Average increase from the lowest level to the peak glucose value was higher in KT patients than LT patients (P<0.05). Conclusions. The transplanted organ also needs to be considered as an important factor affecting glucose control and the occurrence of more severe glucose excursions in patients who receive transplantation although immunosuppression agents are well-known important factors; however, our study was limited to the early posttransplantation period. Further studies involving CGM follow-up at regular intervals based on the time since transplantation are needed.

Posttransplant erythrocytosis (PTE) is a common complication of renal transplantation, which can occur in approximately 10% to 15% of renal transplant patients and usually affects males with relatively good renal function. It is also associated with an increased incidence of thromboembolic events. Clinical manifestations of PTE include malaise, headache, plethora, lethargy, and dizziness. It is correlated with use of cyclosporin, gender, posttransplant renal function, and type of antihypertensive medication. The angio- tensin receptor blocker (ARB) or angiotensin-converting enzyme inhibitor is preferred as an initial treatment for PTE because these agents are effective and reasonably safe in the majority of patients with PTE, and can also provide a necessary antihypertensive effect for kidney transplant patients. We report here on a 35-year-old male who had erythrocytosis after renal transplantation. After renal transplantation, his level of hemoglobin was 21 g/dL. We treated this patient with ARB and his symptoms and signs have been completely relieved.

The purpose of this study is to evaluate the clinical usefulness of modulated arc (mARC) treatment techniques. The mARC treatment plans of the non-small cell lung cancer (NSCLC) patients were performed in order to verify the clinical usefulness of mARC. A pre study was conducted to find the most competent plan condition of mARC treatment and the usefulness of mARC treatment plan was evaluated by comparing it with the other Arc treatment plans such as Tomotherapy and RapidArc. In the case of mARC, the optimal condition for the mARC plan was determined by comparing the dosimetric performance of the mARC plans with the use of various parameters. The various parameters includes the photon energies (6 MV, 10 MV), optimization point angle (6{\deg}-10{\deg} intervals), and total segment number (36-59 segment). The best dosimetric performance of mARC was observed at 10 MV photon energy and the point angle 6 degree, and 59 segments. The each treatment plans of three different techniques were compared with the following parameters: conformity index (CI), homogeneity index (HI), target coverage, dose in the OARs, monitor units (MU), beam on time and the normal tissue complication probability (NTCP). As a result, all three different treatment techniques show the similar target coverage. The mARC results the lowest V20 and MU per fraction compared with both RapidArc and Tomotherapy plan. The mARC plan reduces the beam on time as well. Therefore, the results of this study provided a satisfactory result which mARC technique is considered as a useful clinical technique for radiation treatment., Comment: 11 pages, 4 figures

Sirtuin 2 (SIRT2), a NAD(+)-dependent histone deacetylase, is involved in carcinogenesis and genomic instability and modulates proinflammatory immune responses. However, its role in renal inflammatory injury has not been demonstrated. In this study, we explored the expression patterns of CXCL2 and CCL2 in kidney tissue from Sirt2(-/-) and Sirt2(+/+) mice and in mouse proximal tubular epithelial (MPT) cells. CXCL2 and CCL2 were significantly downregulated at both the mRNA and the protein levels in kidneys of LPS-treated Sirt2(-/-) mice compared with those of LPS-treated Sirt2(+/+) mice. Furthermore, SIRT2 deficiency ameliorated LPS-induced infiltration of neutrophils and macrophages, acute tubular injury, and decrease of renal function. Supporting these observations, CXCL2 and CCL2 expression levels were lower in MPT cells treated with SIRT2-siRNA than in cells treated with control-siRNA, and adenovirus-mediated overexpression of SIRT2 in MPT cells significantly increased the LPS-induced expression of CXCL2 and CCL2 at the mRNA and protein levels. In addition, SIRT2 interacted with mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1), and SIRT2-knockdown increased the acetylation of MKP-1 and suppressed the phosphorylation of p38 MAPK and c-Jun N-terminal kinase in LPS-treated MPT cells. SIRT2 also regulated p65 binding to the promoters of CXCL2 and CCL2. Taken together, these findings indicate that SIRT2 is associated with expression of renal CXCL2 and CCL2 and that regulation of SIRT2 might be an important therapeutic target for renal inflammatory injury.

Currently, the American Association of Physicists in Medicine (AAPM) recommends measuring the surface field size once a week by using an analog film in order to verify light and radiation field coincidence in the Quality Assurance (QA) of radiotherapy. However, the use of the film does not allow for a quantitative method of evaluation, and measuring the light field with radiation field detectors in a 2D array is difficult. Therefore, we used an amorphous-Se (a-Se) digital radiation detection system to measure the light and radiation fields simultaneously for a quantitative QA system, and the feasibility of using such a system was confirmed by ensuring the coincidence of the light and the radiation field measurements. The characteristics of the analog film and the a-Se digital radiation detection system were compared by delivering to each doses of 100, 10 monitor units(MU) of radiation at a rate of 400 MU/min to a radiation field 100 × 100 mm2 in size from a 100 cm source-surface distance (SSD). A 0.5 mm to 0.6 mm difference was measured in the X-axis, and a 0.3 mm difference was measured in the Y-axis. The difference in the measurements of the coincidence of light and the radiation field was less than 0.3 mm, which is relatively insignificant. These results indicate that the use of an a-Se digital radiation detection system is adequate for quality assurance of radiotherapy using light and radiation field coincidence. In addition, the experiment is considered to have provided valuable results in that the a-Se based digital radiation detection system enables simple and accurate QA for clinical radiation therapy by assessing the coincidence in the alignment of the light and the radiation fields.

Intensity-modulated radiotherapy (IMRT) improves dose conformity and saves critical organs. IMRT is widely used in cases of head and neck, prostate, and brain cancer due to the close location of the targets to critical structures. However, because IMRT has a larger amount of radiation exposure than 3 dimensional-conformal radiation therapy (3D-CRT), it has disadvantages such as increases in the low dose irradiation to normal tissues and in the accumulated dose for the whole volume due to leakage and transmission of the multi-leaf collimator (MLC). The increased accumulated dose and the larger low dose may increase the occurrence of secondary malignant neoplasms. For these reasons, the jaw-tracking function of the TrueBeam (Varian Medical Systems, Palo Alto, CA) was developed to reduce the leakage and the transmission dose of the MLC with linear accelerators. However, the change in the superficial dose has not been verified with a quantitative analysis of the dose reduction in a brain tumor. Therefore, in the present study, we intended to verify the clinical possibility of utilizing the jaw-tracking function for a brain tumor by comparing treatment plans and superficial doses. To accomplish this, we made three types of original treatment plans using Eclipse11 (Varian Medical Systems, Palo Alto, CA): 1) farther than 2 cm from the organs at risk (OAR); 2) within 2 cm of the OAR; and 3) intersecting with the OAR. Jaw-tracking treatment plans were also made with copies of the original treatment plan using Smart LMC Version 11.0.31 (Varian Medical Systems, Palo Alto, CA). A comparison between the original treatment plans and jaw-tracking treatment plans was performed using the difference of the mean dose and maximum dose to the OARs in cumulative Dose Volume Histogram (DVH). In addition, the dependencies of the effects of transmission and the scattering doses according to jaw motion were assessed through the difference in the surface doses. In the DVH comparison, a maximum dose difference of 0.4% was observed between the planning methods in the case of over 2 cm distance, and the maximum dose of 0.6% was obtained for within the 2 cm distance. For the case intersecting with the OAR, the maximum dose difference of 2.3% was achieved. According to these results, the differences in the mean doses and the maximum doses to the OARs ware larger when the OARs and the planning target volume (PTV) were closer. In addition, small differences in the surface dose measurements were observed. In the case of the inside field, the differences were under 2% of the prescription dose while the difference was under 0.1% in the case of the outside field. Therefore, treatment plans with the jaw-tracking function consistently affected the dose reduction for a brain tumor, and the clinical possibility could be verified as the surface dose was not increased.

Renal tubulointerstitial fibrosis is characterized by sustained inflammation and excessive extracellular matrix (ECM) accumulation, leading to chronic kidney disease. Valproic acid (VPA) has anticancer activity through regulation of cell differentiation and apoptosis via inhibition of histone deacetylase (HDAC) activity and is considered a class I HDAC inhibitor. In this study, the effect of VPA on unilateral ureteral obstruction (UUO)-induced renal fibrosis by modulation of renal inflammation and ECM gene transcription was investigated. VPA treatment increased histone H3 acetylation in both sham- and UUO-operated kidneys and decreased the UUO-induced increase in tubular injury and ECM deposition in mice. VPA also decreased myofibroblast activation and proliferation in UUO kidneys and NRK-49F cells. Finally, it was demonstrated that the anti-fibrotic effect of VPA was associated with regulation of ECM protein promoter enrichment at an acetylated histone H3 site. In conclusion, the findings indicate that VPA may have a beneficial effect on UUO-induced renal fibrosis via regulation of myofibroblast activation, proliferation, and ECM protein production by chromatin remodeling and ECM protein promoter transcription.

Renal fibrosis is a common feature of all progressive chronic kidney diseases. Sirtuin 3(SIRT3) is one of the mitochondrial sirtuins, and plays a role in the regulation of mitochondrialbiogenesis, oxidative stress, fatty acid metabolism, and aging. Recently, honokiol (HKL), as apharmaceutical SIRT3 activator, has been observed to have a protective effect against pressureoverload‐induced cardiac hypertrophy by increasing SIRT3 activity. In this study, we investigatedwhether HKL, as a SIRT3 activator, also has protective effects against unilateral ureteral obstruction(UUO)‐induced renal tubulointerstitial fibrosis through SIRT3‐dependent regulation ofmitochondrial dynamics and the nuclear factor‐&kappa, B (NF‐&kappa, B)/transforming growth factor‐&beta, 1 (TGF‐&beta, 1)/Smad signaling pathway. We found that HKL decreased the UUO‐induced increase in tubularinjury and extracellular matrix (ECM) deposition in mice. HKL also decreased myofibroblastactivation and proliferation in UUO kidneys and NRK‐49F cells. Finally, we showed that HKLtreatment decreased UUO‐induced mitochondrial fission and promoted mitochondrial fusionthrough SIRT3‐dependent effects. In conclusion, activation of SIRT3 via HKL treatment might havebeneficial effects on UUO‐induced renal fibrosis through SIRT3‐dependent regulation ofmitochondrial dynamics and the NF‐&kappa, B/TGF‐&beta, 1/Smad signaling pathway.

In-vivo dosimetry is essential to verify the position and the intensity of the radiation therapy, such as cranio-spinal irradiation (CSI) and total body irradiation (TBI). Various kinds of devices, such as a thermo-luminesence dosimeters (TLDs), metal-oxide semiconductor field effect transistors (MOSFETs), semiconductor diodes, and gafchromic films, are used in in-vivo dosimetry, and these have their respective pros and cons. An optically-stimulated luminescent nanodot dosimeter (OSLnD) made of Al2O3: C was developed to measure the radiation dose during diagnostics, but it is now used for clinical purposes. In this study, the characteristics of the OSLnD, such as its dose rate dependency, dose linearity, angular dependency, and field junction, were investigated under a 6 MV X-ray beam. The OSLnD showed a linear response at doses from 20 to 300 cGy in the dose linearity test. Also, the dose rate dependency was shown to be less than 3%, angular dependency to be less than 2%. The experimental results proved the OSLnD to be useful for measurements of the external dose and for intensity modulated radiotherapy (IMRT) in clinical radiotherapy.

Purpose The purpose of this study was to determine the optimal biologically equivalent dose (BED) for stereotactic body radiotherapy (SBRT) by comparing local control rates in proportion to various total doses and fractionation schedules. Materials and Methods Thirty-four patients with early non-small-cell lung cancer and a single metastatic lung tumor were included in this study. Differences in local control rates were evaluated according to gender, primary tumor site, response, tumor size, and BED. For comparison of BEDs, the prescribed dose for SBRT was stratified according to three groups: high (BED > 146 Gy), medium to high (BED, 106 to 146 Gy), and low to medium (BED < 106 Gy). Results For all patients, the overall local control rate was 85.3% at two years after treatment. Five local recurrences were observed, and, notably, all of them were observed in the low to medium BED group. Significantly higher local control rates were observed for patients with a complete response than for those with a partial response or stable disease (p < 0.001). Twenty-six patients with a tumor size of < 3 cm showed no dose-response relationship in the low to medium, medium to high, and high BED groups, whereas eight patients with a tumor size of ≥ 3 cm showed a significant dose-response relationship. The observed 2-year local recurrence-free survival rates in patients with a tumor size of < 3 cm and in those with a tumor size of ≥ 3 cm were 96.2% and 50.0%, respectively, which were significantly different (p=0.007). Conclusion BED > 100 Gy is required in order to achieve a > 85% local control rate regardless of tumor size. The optimal dose for small tumors of < 3 cm appears to be within a range below 150 Gy BED. Escalation of BED to high levels (> 150 Gy) may be required for patients with a tumor size larger than 3 cm.

The number of people awaiting organ transplantation continues to exceed the number of organs available for transplantation, especially at a time when kidney transplantation is recognized as the best treatment option for end stage renal disease. There may be many reasons for this disparity of organ supply and demand, including the lack of consent, absence of an experienced coordinator team to help in closing the widening gap between organ supply and demand, and an unstandardized critical care management of potential organ donors. According to the report of the Korean Organ Transplant Registry in March 2014, due to a serious organ shortage in Korea, kidneys of deceased donors with low initial estimated glomerular filtration rate of

Ui Jun Park, M.D., Won Hyun Cho, M.D., Hyoung Tae Kim, M.D., Min Young Kim, R.N., Yong-Lim Kim, M.D., Chan-Duck Kim, M.D., Jang-Hee Cho, M.D., Young Hoon Kim, M.D., Suk Joo Park, M.D., Sang Young Chung, M.D., Soo Jin Na Choi, M.D., Ho Kyun Lee, M.D., Sung Kwang Park, M.D., Sik Lee, M.D. and Hee Chul Yu, M.D. Department of Surgery, Keimyung University Dongsan Medical Center, Keimyung University School of Medicine, Department of Internal Medicine, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Department of Internal Medicine, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan, Department of Surgery, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Department of Internal Medicine, Surgery, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea

Metabolic syndrome is characterized by insulin resistance, dyslipidemia and hypertension. These metabolic changes contribute to the development of obesity-induced kidney injury. AMP-activated protein kinase (AMPK) is a ubiquitous enzyme that is involved in the cellular metabolic response to metabolic stress. Metformin, an AMPK activator, has been reported to exert a protective effect against non-alcoholic steatohepatitis. However, little is known about its role in the pathogenesis of obesity-induced renal injury. The aim of this study was to investigate the effects of metformin on high-fat diet (HFD)-induced kidney injury. Obesity was induced by HFD (60% of total calories from fat, 20% protein and 20% carbohydrates) in 6-week-old C57BL/6 mice. Mice were fed HFD plus 0.5% metformin. The effects of metformin on HFD-induced renal injury were evaluated by determining metabolic parameters, serum adipokine levels and renal AMPK/acetyl-CoA carboxylase (ACC) activities, as well as a histological examination. HFD induced metabolic derangement, systemic insulin resistance and glomerular mesangial matrix expansion. The administration of metformin reduced HFD-induced metabolic derangement and renal injury. The administration of metformin reduced the HFD-induced increase in adipokine expression and macrophage infiltration. Moreover, renal AMPK activity, which was decreased by HFD, was recovered following the administration of metformin; in addition, fatty acid oxidation was increased by the inhibition of ACC. These results indicate that metformin exerts beneficial effects on obesity-induced renal injury by regulating systemic inflammation, insulin resistance and the renal AMPK/ACC pathway. The clinical application of metformin to obese or early diabetic patients may be helpful in preventing obesity- or diabetes-related kidney disease.

As the number of cancer patients and its death rate increases, this study is to understand the occurrences in cancer patients in Busan area and to provide active help for treatment, prevention and management of cancer patients. It was investigated and analyzed based on 4462 patients who were diagnosed with cancer and received radiation therapy from Jan. 2011 to Dec. 2012 at tertiary medical institution in Busan area. The seven main cancer types were breast cancer, cervical cancer, lung cancer, colon rectal cancer, brain tumor, laryngopharyngeal cancer and liver cancer. The most common type of cancer was breast cancer which takes up 38.1% of cancer patients stood out from other cancer types. Breast cancer is that shows increasing trend and in need of appropriate countermeasures and managements for decreasing cancer risk. Therefore the causes and prevention of breast cancer analysis, an appropriate management program is required.

The use of the dosimetry have been increasingly recognized as high radiation energy and radiation treatment planning(RTP) have rapidly developed in radiotherapy. There are many types of detectors for the dosimetry such as ionization chamber, film, TLD, diode, and etc. Among such detectors, the diode detector uses a photoconductor materials that generate electrical signals by the incident radiation energy. Though many research groups are recently interested in such materials, there is few experimental results except for silicon in the radiation therapy field. In this study, the feasibility of photoconductor materials was verified as a dosimeter through the evaluation of response properties at a high radiation energy. For the fabricated detectors based on HgI2 and PbI2, reproducibility, linearity, and pulse-rate response were analyzed. Such evaluations are essential factors for the use of dosimeter. From results, linearity and reproducibility of the fabricated HgI2 detector indicated about 7% error. The fabricated PbI2 detector showed 1.7% error in linearity, and 12.2% error in reproducibility.