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The promotion plan for the Platform of Human Resource Development for Cancer (Ganpro) was initiated by the Ministry of Education, Culture, Sports, Science and Technology of Japan in 2007, establishing a curriculum for medical physicists. In this study, we surveyed the educational outcomes of the medical physicist program over the past 10 years since the initiation of Ganpro. The Japan Society of Medical Physics mailing list was used to announce this survey. The questionnaire was created by members of the Japanese Board for Medical Physicist Qualification, and was intended for the collection of information regarding the characteristics and career paths of medical physics students. Students who participated in the medical physics program from 2007 to 2016 were enrolled. Thirty-one universities (17 accredited and 14 non-accredited) were represented in the survey. In total, 491, 105 and 6 students were enrolled in the Master's, Doctorate and Residency programs, respectively. Most students held a Bachelor's degree in radiological technology (Master's program, 87%; Doctorate program, 72%). A large number of students with a Master's degree worked as radiological technologists (67%), whereas only 9% (n = 32) worked as medical physicists. In contrast, 53% (n = 28) of the students with a Doctorate degree worked as medical physicists. In total, 602 students (from 31 universities) completed the survey. Overall, although the number of the graduates who worked as medical physicists was small, this number increased annually. It thus seems that medical institutions in Japan are recognizing the necessity of licensed medical physicists in the radiotherapy community., (© The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

People sometimes perceive a mind in inorganic entities like robots. Psychological research has shown that mind perception correlates with moral judgments and that immoral behaviors (i.e., intentional harm) facilitate mind perception toward otherwise mindless victims. We conducted a vignette experiment (N = 129; Mage = 21.8 ± 6.0 years) concerning human-robot interactions and extended previous research's results in two ways. First, mind perception toward the robot was facilitated when it received a benevolent behavior, although only when participants took the perspective of an actor. Second, imagining a benevolent interaction led to more positive attitudes toward the robot, and this effect was mediated by mind perception. These results help predict what people's reactions in future human-robot interactions would be like, and have implications for how to design future social rules about the treatment of robots.

Automated organ segmentation from medical images is an indispensable component for clinical applications such as computer-aided diagnosis (CAD) and computer-assisted surgery (CAS). We utilize a multi-atlas segmentation scheme, which has recently been used in different approaches in the literature to achieve more accurate and robust segmentation of anatomical structures in computed tomography (CT) volume data. Among abdominal organs, the pancreas has large inter-patient variability in its position, size and shape. Moreover, the CT intensity of the pancreas closely resembles adjacent tissues, rendering its segmentation a challenging task. Due to this, conventional intensity-based atlas selection for pancreas segmentation often fails to select atlases that are similar in pancreas position and shape to those of the unlabeled target volume. In this paper, we propose a new atlas selection strategy based on vessel structure around the pancreatic tissue and demonstrate its application to a multi-atlas pancreas segmentation. Our method utilizes vessel structure around the pancreas to select atlases with high pancreatic resemblance to the unlabeled volume. Also, we investigate two types of applications of the vessel structure information to the atlas selection. Our segmentations were evaluated on 150 abdominal contrast-enhanced CT volumes. The experimental results showed that our approach can segment the pancreas with an average Jaccard index of 66.3% and an average Dice overlap coefficient of 78.5%., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We investigated the delivery of drugs to the posterior segment of the eye by non-invasive topical instillation using submicron-sized poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs). Surface-modified PLGA NPs were developed to improve the drug delivery efficiency to the retina and were administered as topical eye drops to mice. Chitosan (CS) and glycol chitosan (GCS), which are mucoadhesive polymers, and polysorbate 80 (P80) were used as surface modifiers, and have been reported to increase the association of NPs with cells. Coumarin-6 was used as a model drug and fluorescent marker, and after ocular administration of PLGA NP eye drops, the fluorescence intensity of coumarin-6 was observed in the retina. The fluorescence image analysis indicated that there are several possible routes to the retina and fates of PLGA NPs in ocular tissue, and that these pathways involved the corneal, non-corneal, or uveal routes. Delivery to the mouse retina segments after topical administration was increased by surface modification with CS, GCS, or P80. Surface-modified PLGA NPs are a promising method for retinal drug delivery via topical instillation., (© 2017 Shenyang Pharmaceutical University. Production and hosting by Elsevier B.V.)

A dose audit of 16 facilities in 11 countries has been performed within the framework of the Forum for Nuclear Cooperation in Asia (FNCA) quality assurance program. The quality of radiation dosimetry varies because of the large variation in radiation therapy among the participating countries. One of the most important aspects of international multicentre clinical trials is uniformity of absolute dose between centres. The National Institute of Radiological Sciences (NIRS) in Japan has conducted a dose audit of participating countries since 2006 by using radiophotoluminescent glass dosimeters (RGDs). RGDs have been successfully applied to a domestic postal dose audit in Japan. The authors used the same audit system to perform a dose audit of the FNCA countries. The average and standard deviation of the relative deviation between the measured and intended dose among 46 beams was 0.4% and 1.5% (k = 1), respectively. This is an excellent level of uniformity for the multicountry data. However, of the 46 beams measured, a single beam exceeded the permitted tolerance level of ±5%. We investigated the cause for this and solved the problem. This event highlights the importance of external audits in radiation therapy., (© The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Background: Intensity-modulated radiation therapy (IMRT) reduces the dose delivered to organs at risk. However, there have been few direct comparisons of IMRT with conventional three-dimensional conformal radiotherapy (3DCRT). The aim of this study was to evaluate the clinical benefit of IMRT in terms of toxicity and biochemical control., Methods: The medical records of 203 consecutive patients with localized to non-metastatic (stage T1a-T3bN0M0) prostate cancer between 2007 and 2011 were retrospectively reviewed. The prescribed dose was 76 Gy delivered in 38 fractions in both the 3DCRT and IMRT treatment groups. The frequency of grade 2 or greater late gastrointestinal (GI) and genitourinary toxicity and biochemical control were estimated by the log-rank test and Cox proportional hazards model with and without adjustment by the propensity score for treatment choice., Results: A total of 159 patients were included in the study (3DCRT: 70 patients, IMRT: 89 patients). The median follow-up period was 4.7 years. The estimated 5-year cumulative risk of late GI toxicity was significantly lower in the IMRT group than in the 3DCRT group (3.6 vs 13.2%, respectively, p = 0.022). After adjustment by propensity score, IMRT remained associated with a lower risk of late GI toxicity (hazard ratio 0.22; 95% confidence interval 0.058-0.85; p = 0.028). The 5-year biochemical failure-free rate was 93.2% in the 3DCRT group and 95.4% in the IMRT group (non-significant difference)., Conclusions: The incidence of late GI toxicity was significantly lower in the IMRT group than in the 3DCRT group, while the biochemical control rates were no different between the two groups. These clinical data suggest the benefit of IMRT in the reduction of late GI toxicity.

Five components (hydrogen peroxide, methylglyoxal, dihydroxyacetone, fructose and glucose) of New Zealand manuka honey (Leptospermum scoparium) were analyzed using lucigenin chemiluminescence high-performance liquid chromatography (lucigenin-CL-HPLC). We focused on active oxygen species produced from the components in order to easily detect these five components contained in manuka honey. H 2 O 2 and O 2 - generated from these components were identified by lucigenin-CL and electron spin resonance (ESR), and the bactericidal effect of ROS was confirmed using E. coli. The previously reported assays for Manuka honey components have low specificities and require complicated preprocessing methods. As our results, the detection and identification of these components were possible within 30 min in lucigenin-CL-HPLC system, without any special treatment. It is considered that lucigenin-CL-HPLC is useful for the quality control and the analysis of various honey., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Purpose: A dose escalation study to determine the recommended dose (RD) with stereotactic body radiation therapy (SBRT) for peripheral T2N0M0 non-small cell carcinomas (NSCLC) was conducted. The results of the group with PTV⩾100cc are reported in this paper., Materials and Methods: The continual reassessment method (CRM) was used to determine the dose level that patients should be assigned to and to estimate the maximum tolerated dose (MTD). Dose limiting toxicity (DLT) was Grade 3 or higher radiation pneumonitis (RP), and Grade 2 or higher RP was used as a surrogate DLT. The RD was equal to the MTD. The dose was prescribed at D 95 of the PTV., Results: Thirteen patients were accrued. More patients should have been enrolled but we decided not to prolong the study period. No patients experienced Grade 3 RP. Two patients experienced Grade 2 RP at 50Gy in 4 fractions. The predicted MTD was 50.2Gy. The posterior probability of the Grade 2 RP frequency over 40% was 5.3% for the dose level of 50Gy. The RD was determined to be 50Gy., Conclusions: The RD was determined to be 50Gy in 4 fractions in this population., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Purpose: High-mobility group box-1 (HMGB1) is a nonhistone DNA-binding nuclear protein released from necrotic cells, which is also secreted by activated leukocytes and acts as a primary proinflammatory cytokine. In this study, we compared vitreous HMGB1 levels in ocular sarcoidosis with those in noninflammatory vitreoretinal diseases and evaluated its association with Th cell-related and proinflammatory cytokines., Methods: The study group consisted of 24 patients with ocular sarcoidosis. The control group consisted of 27 patients with proliferative diabetic retinopathy (PDR) and 24 with idiopathic epiretinal membrane (ERM). Vitreous fluid samples were obtained at the beginning of vitrectomy. Vitreous levels of HMGB1 and IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-γ, soluble CD40 ligand (sCD40L), and TNFα were measured., Results: High-mobility group box-1 was detected in the vitreous of 23 of 24 patients (95.8%) with ocular sarcoidosis. Mean vitreous level of HMGB1 was the highest in the sarcoidosis group, followed by the PDR and ERM groups, with significant differences between the three groups. In the sarcoidosis group, vitreous levels of IL-6, IL-10, IL-31, IFN-γ, sCD40L, and TNFα were significantly higher than those in the idiopathic ERM group, and IFN-γ and sCD40L were significantly higher than those in the PDR group. Vitreous HMGB-1 level correlated significantly with IL-10, IFN-γ, and sCD40L levels but not with IL-6, IL-17, IL-31, or TNFα levels., Conclusions: The vitreous level of HMGB1 is elevated in ocular sarcoidosis and is associated with vitreous levels of Th1- and regulatory T-related cytokines, but not with proinflammatory or Th17-related cytokines.

Background The peptide hormone oxytocin acts in the central nervous system and plays an important role in various complex social behaviours. We report the production of a high affinity and specificity antibody for oxytocin and its use in a highly sensitive enzyme immunoassay. Biotin that was chemically bound to oxytocin derivative containing zero to six lysines as bridge was the labelled antigen. Seven labelled antigens were used to develop a highly sensitive enzyme immunoassay. Methods Antioxytocin antiserum was obtained by immunization of oxytocin-bovine thyrogloblin conjugate to rabbit. Oxytocin sample was added to the second antibody-coated microtitre plate and allowed to react overnight at 4℃, then biotinylated oxytocin was added 1 h at 4℃, and horseradish peroxidase-labelled avidin was added and incubated for 1 h at room temperature. The plate was then washed. Horseradish peroxidase activity was measured by a colorimetric method using o-phenylenediamine (490 nm). Results The sensitivity of the enzyme immunoassay improved as the number of lysine residues increased; consequently, biotinylated oxytocin bridged with five lysines was used. A standard curve for oxytocin ranged from 1.0 to 1000 pg/assay. The detection limit of the assay was 2.36 pg, and the reproducibility was 3.6% as CV% ( n = 6). Cross-reactivity with vasopressin and vasotocin was less than 0.01%. Conclusion The sensitivity of the enzyme immunoassay could be improved by increasing the number of lysine residues on the biotin-labelled antigen. The proposed method is sensitive and more specific than conventional immunoassays for oxytocin and can be used to determine plasma oxytocin concentrations.

Magnesium ions (Mg 2+ ) are essential for various enzymatic reactions in the body associated with energy production and activation of the muscles and nerves. Mg 2+ is also involved in blood pressure regulation, maintenance of body temperature, and glucose metabolism. Although various factors including foods and physical conditions have been reported to change serum Mg 2+ status in humans, serum Mg 2+ in dogs exposed to external stress has been unclear. In this study, we examined serum levels of Mg 2+ in dogs at different conditions using the guide dog candidates for the blind. Serum Mg 2+ was decreased in winter and increased in summer. Guide dog candidates in an elementary class of the training showed markedly lower levels of serum Mg 2+ , compared with that of dogs in an advanced class. When healthy adult dogs were subjected to forced exercise using a treadmill, a significant reduction in serum Mg 2+ levels was observed, particularly in winter. These findings suggest that serum levels of Mg 2+ may be influenced by weather fluctuation such as air temperature, nervousness in unaccustomed situations, age, and physical stress induced by exercise. The results indicate that Mg 2+ supplementation should be considered for working dogs, dogs moving or traveling to a new environment, and dogs during winter.

Serum nerve growth factor (NGF) levels are increased by the external stress in mice, humans and horses; however, similar variations have been unclear in dogs. Since dogs are usually subjected to conditions of work, exercise and activity as important partners of humans, we measured serum NGF levels post-exercise and compared them with serum cortisol levels, as a biomarker of physical stress. Serum cortisol levels were immediately elevated post-exercise and returned to basal levels within 1 hr. On the other hand, serum NGF levels were significantly increased 1 hr post-exercise and gradually returned to basal levels. Further research is necessary; nevertheless, we have demonstrated for the first time that serum NGF levels respond to exercise stress in dogs.

The purpose of this study was to evaluate the efficacy and toxicities of carbon-ion radiotherapy (C-ion RT) for locally advanced cervical cancer with bladder invasion by a subset analysis of pooled data from eight prospective clinical trials at the National Institute of Radiological Sciences. Between June 1995 and January 2014, 29 patients with locally advanced cervical cancer with bladder invasion were identified. The median age was 56 years old (range 31-79 years old). The median tumor size at diagnosis on magnetic resonance imaging was 6.7 cm (range 3.5-11.0 cm). Histologically, 20 patients had squamous cell carcinoma and 9 had adenocarcinoma. C-ion RT was performed as a dose-escalation study in the initial trials. All patients received prophylactic whole-pelvic or extended-field irradiation and local boost. The total dose to the cervical tumor was 52.8-74.4 Gy (relative biological effectiveness) in 20 or 24 fractions. Weekly cisplatin (40 mg/m 2 /week, five cycles) was concurrently given to four patients. The median follow-up of all patients was 28.6 months (range 8.8-238.6 months). Grade 2 or higher late complications in the bladder were observed in eight patients, with seven developing vesicovaginal fistula. Six patients had Grade 2 or higher complications in the rectosigmoid colon. The 3-year overall survival rate was 47%, the 3-year local control rate was 66%, and the 3-year disease-free survival rate was 28%. In this study, C-ion RT showed favorable local control with reasonable toxicities, but the results were still unsatisfactory. We have the expectation of improvement of therapeutic effects by using C-ion RT with concurrent chemotherapy., (© The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

We evaluated the prognostic roles of local therapy to bone metastasis (BM) in metastatic renal cell carcinoma (mRCC) patients with BM. This retrospective study included 71 mRCC patients with BM. Local therapy to BM included en bloc resection, curettage, and radiotherapy (RT). RT was classified into RT with biological effective dose (BED) ≥85 Gy and <85 Gy by its therapeutic intensity. Local therapy to BM was given for 64 patients (90 %): en bloc resection, curettage, and RT for 16, 10, and 38 patients, respectively. Fifteen patients received RT with BED ≥85 Gy. The median overall survival (OS) was 25 months (median follow-up 16 months). For 46 patients with solitary BM, patients treated with en bloc resection, curettage, and RT with BED ≥85 Gy showed significantly better OS than those treated with RT with BED <85 Gy or no local therapy (P = 0.006). Because OS was comparable among patients treated with en bloc resection, curettage, and RT with BED ≥85 Gy, these three treatment modalities were defined as "intensive local therapy". Intensive local therapy to BM was also associated with favorable OS with marginal significance (P = 0.052) in a cohort of 25 patients with multiple BM. A multivariate analysis in the whole cohort revealed that intensive local therapy to BM was independently associated with favorable OS (hazard ratio 0.23, P < 0.001) along with Memorial-Sloan Kettering Cancer Center risk category (P < 0.001). Thus, intensive local therapy to BM might improve OS in mRCC patients with BM including multiple BM.

Background: To investigate the prognostic value of oligo-recurrence in patients with brain-only oligometastases of non-small cell lung cancer (NSCLC) treated with stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT)., Methods: Patients treated with SRS or SRT for brain-only NSCLC oligometastases in 6 high-volume institutions in Japan between 1996 and 2008 were reviewed. Eligible patients met 1), 2), and 4) or 1), 3), and 4) of the following: 1) NSCLC with 1 to 4 brain metastases on magnetic resonance imaging (MRI) treated with SRS or SRT; 2) control of the primary lesions (thorax) at the time of SRS or SRT for brain metastases (patients meeting this criterion formed the oligo-recurrence group); 3) with SRS or SRT for brain metastases, concomitant treatment for active primary lesions (thorax) with curative surgery or curative stereotactic body radiotherapy (SBRT), or curative chemoradiotherapy (sync-oligometastases group); and 4) Karnofsky performance status (KPS) ≥70., Results: The median overall survival (OS) of all 61 patients was 26 months (95 % CI: 17.5-34.5 months). The 2-year and 5-year overall survival rates were 60.7 and 15.7 %, respectively. Stratified by oligostatus, the sync-oligometastases group achieved a median OS of 18 months (95 % CI: 14.8-21.1 months) and a 5-year OS of 0 %, while the oligo-recurrence group achieved a median OS of 41 months (95 % CI: 27.8-54.2 months) and a 5-year OS of 18.6 %. On multivariate analysis, oligo-recurrence was the only significant independent factor related to a favorable prognosis (hazard ratio: 0.253 (95 % CI: 0.082-0.043) (p = 0.025)., Conclusions: The presence of oligo-recurrence can predict a favorable prognosis of brain-only oligometastases in patients with NSCLC treated with SRS or SRT.

Background: In transplant patients with localized prostate cancer, irradiation is not proposed as often as it is in healthy adults because of the post-radiation risks, such as ureteral stenosis and gastrointestinal toxicity as the result of fragile tissue. The objective of the study was to analyze the efficacy and feasibility of intensity-modulated radiation therapy (IMRT) for prostate cancer in renal transplant recipients (RTRs)., Methods: Between May 2005 and December 2014, all patients who had undergone IMRT for clinically localized prostate cancer at our institution were retrospectively identified (n = 365). Of these patients, 2 had a history of renal transplantation. We reviewed all available clinical data. One patient had a functioning graft and the other had restarted hemodialysis 7 years after the transplantation., Results: The mean time from renal transplantation to prostate cancer diagnosis was 11 years. The mean follow-up after irradiation was 43 months. The 2 patients remain free of prostate-specific antigen progression. There was no severe acute and chronic genitourinary and gastrointestinal toxicity. Renal function of the patient with a functioning graft as measured by serum creatinine was stable during and after the irradiation., Conclusions: IMRT is feasible and acceptable as a minimally invasive treatment in the carefully selected RTRs with localized prostate cancer. This treatment should be considered a good option for RTRs with localized prostate cancer., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: In young patients with localized prostate cancer, radical prostatectomy is the treatment of choice in the general population. Radiotherapy, such as low-dose rate (LDR) brachytherapy or intensity-modulated radiotherapy, is a viable alternative as well. However, in transplant patients, irradiation is not proposed as often as it is in healthy adults because of the risk of post-radiation ureteral stenosis and gastrointestinal toxicity as the result of fragile tissue. The objective of the study was to assess the efficacy and feasibility of LDR brachytherapy for prostate cancer in renal transplant recipients (RTRs)., Methods: Between May 2007 and December 2014, all patients who had undergone LDR brachytherapy for clinically localized prostate cancer at our institution were retrospectively identified (n = 203). Of these patients, 2 had a history of renal transplantation. We reviewed all available clinical data retrospectively. One patient had a functioning graft and the other had re-started hemodialysis 7 years after the transplantation., Results: The mean time from renal transplantation to prostate cancer diagnosis was 16 years. The mean follow-up after seed implantation was 45 months. There were no peri-operative complications after seed implantation. The 2 patients remained free of prostate-specific antigen progression during the follow-up period. The renal function of the patient with a functioning graft, as measured by serum creatinine, was stable during and after the operation., Conclusions: LDR brachytherapy is technically feasible and acceptable as a minimally invasive treatment in carefully selected RTRs with localized prostate cancer. This treatment should be considered a suitable option for RTRs with localized prostate cancer., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The prognostic value of rectal invasion is still unclear in stage IVA cervical cancer. The objective of this study is to evaluate patient outcome and prognostic factors in stage IVA cervical cancer treated with radiation therapy., Methods: A retrospective review of the medical records of patients treated with definitive photon radiation therapy for pathologically proven stage IVA cervical cancer between 1980 and 2010 was performed. Eligible patients for the present study were diagnosed with clinical stage IVA cervical cancer by cystoscopy or/and proctoscopy, and they received definitive radiation therapy consisting of a combination of external beam radiotherapy and high-dose-rate brachytherapy. All patients underwent CT scans of the abdomen and pelvis., Results: Among the 67 stage IVA patients studied, 53 patients were stage IVA on the basis of bladder invasion, 7 according to rectal mucosal invasion, and 7 because of both bladder and rectal mucosal invasion. Median follow-up of all patients and surviving patients was 19 months (range, 2-235 months) and 114 months (range, 14-223 months), respectively. The 5-year local control (LC), disease-free survival (DFS), and overall survival (OS) rate were 55, 17, and 24%, respectively. Rectal invasion had significant impact on DFS, but bladder invasion had the opposite effect (p = 0.00006 and 0.005, respectively). There were significant differences of LC, DFS and OS rates between patients with and without rectal invasion (p = 0.006, 0.00006 and 0.05, respectively)., Conclusions: Patients with stage IVA cervical cancer had poor prognosis, with 5-year survival of only 24%. Furthermore, in stage IVA, rectal invasion might be a worse prognostic factor than bladder invasion.

Aims: Skin colonization of Staphylococcus spp. critically affects the severity of dermatitis in humans and animals. We examined different types of fatty acid salts for their antibacterial activity against Staphylococcus spp. when used in ultrapure soft water (UPSW). We also evaluated their therapeutic effect on a spontaneous canine model of dermatitis., Methods and Results: UPSW, in which Ca(++) and Mg(++) were replaced with Na(+) , was generated using a water softener with cation-exchange resin. Staphylococcus aureus (Staph. aureus), Staphylococcus intermedius (Staph. intermedius), and Staphylococcus pseudintermedius (Staph. pseudintermedius) were incubated with various fatty acid salts in distilled water (DW) or UPSW and the number of bacteria was counted. Among the fatty acids, oleic acid salt and linoleic acid (LA) salt reduced the number of these bacteria. Also, UPSW enhanced the antibacterial effect of LA on Staph. spp. In spontaneously developed itchy dermatitis in companion dogs, shampoo treatment with liquid soap containing 10% LA in UPSW improved skin conditions., Conclusions: LA salt showed antibacterial activity against Staph. spp. Treatment with soap containing LA with UPSW reduced clinical conditions in dogs with dermatitis., Significance and Impact of the Study: Because colonization of Staph. spp. on the skin exacerbates dermatitis, the use of LA-containing soap in UPSW may reduce unpleasant clinical symptoms of the skin., (© 2015 The Society for Applied Microbiology.)

Background: This second questionnaire-based survey was performed to determine the clinical results of definitive esophageal cancer treatment with radiotherapy (RT) or chemoradiotherapy (CRT) between 2004 and 2008., Materials/methods: Clinical results of definitive RT for patients were collected from major Japanese institutions. Patients were classified into three groups: (A) stage I, (B) resectable stages II-III, (C) unresectable stages III-IVA. For group A, all patients treated with RT alone or CRT were included. For groups B and C, only those treated with CRT were included., Results: In total, 990 patients (group A 259, group B 333, group C 398 patients) were included from 11 institutions. In group A, 199 patients (78 %) were treated with CRT, and 60 patients (23 %) received RT alone. In groups B and C, 420 patients (57 %) were treated with full-dose cisplatin/5-FU, and 181 patients (25 %) with low-dose protracted-infusion cisplatin/5-FU. The median and range of the 5-year overall survival rate were 73 % (40-94 %) for group A, 40 % (0-57 %) for group B, and 18 % (6-26 %) for group C, respectively. The 5-year overall survival rates were consistently good for five high-volume centers where more than 20 patients/year with esophageal cancer were treated definitively as compared with the remaining six medium-volume centers (5-15 patients/year). The median and range of the incidence of grade ≥3 late toxicities were 10 % and 6-22 %, respectively., Conclusions: A wide disparity in 5-year overall survival rates among the institutions was still apparent in the second survey for groups A and B.

The aim of this study was to evaluate the toxicity and efficacy of radiotherapy concurrent with weekly cisplatin for T3-4 and N0-1 nasopharyngeal cancer. Between 2005 and 2010, 70 patients with nasopharyngeal cancer (T3-4 N0-1 M0, World Health Organization Type 2-3) from Vietnam, Indonesia, Malaysia and Thailand were registered. Patients were treated with 2D radiotherapy concurrent with weekly cisplatin (30 mg/m(2)). Neither adjuvant nor induction chemotherapy was given. Ninety-three percent of the patients completed at least four cycles of weekly cisplatin during radiotherapy. The median total doses for the primary tumor and positive lymph nodes were 70 and 66 Gy, respectively. The median overall treatment time of concurrent chemoradiotherapy was 52 days. No treatment-related deaths occurred. Grade 3-4 acute toxicities of mucositis, nausea/vomiting and leukopenia were observed in 34%, 4% and 4% of patients, respectively. With a median follow-up time of 52 months for the 40 surviving patients, the 3-year local control, locoregional tumor control, distant metastasis-free survival and overall survival rates were 80%, 75%, 74% and 80%, respectively. In conclusion, the current results illustrate that our concurrent chemoradiotherapy regimen was feasible, but disease control remained insufficient. Further research is encouraged in order to improve clinical outcomes., (© The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Elevated skin surface pH has been reported in patients with atopic dermatitis. In this study, we explored the role of skin pH in the pathogenesis of atopic dermatitis using the NC/Tnd murine atopic dermatitis model. Alkalinization of the skin of asymptomatic NC/Tnd mice housed in specific pathogen-free conditions induced kallikrein 5 and activated protease-activated receptor 2, resulting in thymic stromal lymphopoietin secretion and a cutaneous T-helper 2 allergic response. This was associated with increased transepidermal water loss and development of eczematous lesions in these specific pathogen-free NC/Tnd mice, which normally do not suffer from atopic dermatitis. Injection of recombinant thymic stromal lymphopoietin also induced scratching behavior in the specific pathogen-free NC/Tnd mice. Thymic stromal lymphopoietin production and dermatitis induced by alkalinization of the skin could be blocked by the protease-activated receptor 2 antagonist ENMD-1068. In contrast, weak acidification of eczematous skin in conventionally housed NC/Tnd mice reduced kallikrein 5 activity and ameliorated the dermatitis. Onset of the dermatitis was associated with increased epidermal filaggrin expression and impaired activity of the sodium/hydrogen exchanger 1, a known regulator of skin pH. We conclude that alterations in skin pH directly modulate kallikrein 5 activity leading to skin barrier dysfunction, itch, and dermatitis via the protease-activated receptor 2-thymic stromal lymphopoietin pathway., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate, in Japan Clinical Oncology Group study 0403, the safety and efficacy of stereotactic body radiation therapy (SBRT) in patients with T1N0M0 non-small cell lung cancer (NSCLC)., Methods and Materials: Eligibility criteria included histologically or cytologically proven NSCLC, clinical T1N0M0. Prescribed dose was 48 Gy at the isocenter in 4 fractions. The primary endpoint was the percent (%) 3-year overall survival. The threshold % 3-year survival to be rejected was set at 35% for inoperable patients, whereas the expected % 3-year survival was 80% for operable patients., Results: Between July 2004 and November 2008, 169 patients from 15 institutions were registered. One hundred inoperable and 64 operable patients (total 164) were eligible. Patients' characteristics were 122 male, 47 female; median age 78 years (range, 50-91 years); adenocarcinomas, 90; squamous cell carcinomas, 61; others, 18. Of the 100 inoperable patients, the % 3-year OS was 59.9% (95% confidence interval 49.6%-68.8%). Grade 3 and 4 toxicities were observed in 10 and 2 patients, respectively. No grade 5 toxicity was observed. Of the 64 operable patients, the % 3-year OS was 76.5% (95% confidence interval 64.0%-85.1%). Grade 3 toxicities were observed in 5 patients. No grade 4 and 5 toxicities were observed., Conclusions: Stereotactic body radiation therapy for stage I NSCLC is effective, with low incidences of severe toxicity. This treatment can be considered a standard treatment for inoperable stage I NSCLC. This treatment is promising as an alternative to surgery for operable stage I NSCLC., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background/aim: The aim of the present study was to assess clinical outcomes of postoperative radiotherapy for biliary tract cancer patients., Patients and Methods: Clinical results of 187 patients treated with external irradiation in 31 Japanese Institutions between 2000 and 2011 were retrospectively analyzed. The median radiation dose was 50.4 Gy in fractions of 1.8-2 Gy., Results: Two-year actuarial overall survival and locoregional control (LCs) rates were 56% and 68%, respectively. In multivariate analysis, macroscopic residual tumor (R2) and irradiated doses <54 Gy were significant indicators of poor LC prognosis. For patients with complete resection (R0) or microscopic residual tumor (R1), 2-year LCs were 71% for <54 Gy and 83% for ≥54 Gy; doses ≥54 Gy were associated with high long-term LCs. There was no significant difference in acute adverse event rates between <54 Gy and ≥54 Gy., Conclusion: Postoperative irradiation doses of approximately 54 Gy are safe and effective for R0 or R1 resection patients., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Previous studies that used carotid ultrasound have been largely conflicting in regards to whether or not patients after Kawasaki disease (KD) have a greater carotid intima-media thickness (CIMT) than controls. To test the hypothesis that there are significant differences between the values of CIMT expressed as absolute values and standard deviation scores (SDS) in children and adolescents after KD and controls, we reviewed 12 published articles regarding CIMT on KD patients and controls. The mean ± SD of absolute CIMT (mm) in the KD patients and controls obtained from each article was transformed to SDS (CIMT-SDS) using age-specific reference values established by Jourdan et al. (J: n = 247) and our own data (N: n = 175), and the results among these 12 articles were compared between the two groups and the references for comparison of racial disparities. There were no significant differences in mean absolute CIMT and mean CIMT-SDS for J between KD patients and controls (0.46 ± 0.06 mm vs. 0.44 ± 0.04 mm, p = 0.133, and 1.80 ± 0.84 vs. 1.25 ± 0.12, p = 0.159, respectively). However, there were significant differences in mean CIMT-SDS for N between KD patients and controls (0.60 ± 0.71 vs. 0.01 ± 0.65, p = 0.042). When we assessed the nine articles on Asian subjects, the difference of CIMT-SDS between the two groups was invariably significant only for N (p = 0.015). Compared with the reference values, CIMT-SDS of controls was within the normal range at a rate of 41.6 % for J and 91.6 % for N. These results indicate that age- and race-specific reference values for CIMT are mandatory for performing accurate assessment of the vascular status in healthy children and adolescents, particularly in those after KD considered at increased long-term cardiovascular risk.

Aims: Although a relatively small proportion of all breast cancer (BC), triple negative (TN) BC is responsible for a relatively large proportion of BC deaths because of its worse clinical outcome. To investigate whether a carbon ion beam alone or in combination with cisplatin (CDDP) has a beneficial effect compared to X-rays, we target triple negative (TN) breast cancer stem-like cells (CSCs)., Methods: Human breast CSCs sorted from MDA-MB-231 and MDA-MB-453 cells were treated with a carbon ion beam or X-ray irradiation alone or in combination with CDDP, and then colony, spheroid and tumor formation assays, RT-PCR Array analysis, and immunofluorescence γH2AX foci assay were performed., Results: The colony, spheroid formation, and tumorigenicity assays confirmed that CD44+/CD24- and ESA+/CD24- cells have CSC properties in MDA-MB-231 and MDA-MB-453 cells, respectively. The proportion of CSCs was more enriched after CDDP combination with either X-ray or carbon ion beam, however carbon ion beam combined with CDDP significantly suppressed colony and spheroid formation and more significantly inhibited cell cycle progression (sub-G1 arrest) compared to X-ray combined with CDDP or carbon ion beam alone. RT-PCR Array analysis showed that carbon ion beam combined with CDDP significantly induced apoptosis-related Cytochrome c, almost completely eliminated expression of the CSC markers CD44 and ESA, and significantly inhibited angiogenesis, and metastasis-related HIF1α and CD26 compared to carbon ion beam alone, X-ray alone, or X-ray combined with CDDP. The immunofluorescence assay showed that not only the number but also the size of γH2AX foci in CSCs were larger 24 h after carbon ion beam combined with CDDP compared to those of X-ray alone and X-ray combined with CDDP., Conclusions: Carbon ion beam combined with CDDP has superior potential to kill TN breast CSCs with irreparable severe DNA damage and enhanced apoptosis.

The standard treatment for metastatic liver tumor from breast cancer is systemic medical treatment, and there is controversy regarding the value of local treatment. However, there are some exceptional cases that do benefit from local therapy. We describe the case of a 54-year-old woman with systemic therapy-resistant liver metastasis from breast cancer successfully treated with a single shot of 36-GyE carbon-ion radiotherapy and surviving more than 8 years without local recurrence. This case represents a good example of the usefulness and safety of carbon-ion radiotherapy, and who might benefit from local therapy.

Purpose: Skin toxicity caused by radiotherapy has been visually classified into discrete grades. The present study proposes an objective and continuous assessment method of skin erythema in digital images taken under arbitrary lighting conditions, which is the case for most clinical environments. The purpose of this paper is to show the feasibility of the proposed method., Methods: Clinical data were gathered from six patients who received carbon beam therapy for lung cancer. Skin condition was recorded using an ordinary compact digital camera under unfixed lighting conditions; a laser Doppler flowmeter was used to measure blood flow in the skin. The photos and measurements were taken at 3 h, 30, and 90 days after irradiation. Images were decomposed into hemoglobin and melanin colors using independent component analysis. Pixel values in hemoglobin color images were compared with skin dose and skin blood flow. The uncertainty of the practical photographic method was also studied in nonclinical experiments., Results: The clinical data showed good linearity between skin dose, skin blood flow, and pixel value in the hemoglobin color images; their correlation coefficients were larger than 0.7. It was deduced from the nonclinical that the uncertainty due to the proposed method with photography was 15%; such an uncertainty was not critical for assessment of skin erythema in practical use., Conclusions: Feasibility of the proposed method for assessment of skin erythema using digital images was demonstrated. The numerical relationship obtained helped to predict skin erythema by artificial processing of skin images. Although the proposed method using photographs taken under unfixed lighting conditions increased the uncertainty of skin information in the images, it was shown to be powerful for the assessment of skin conditions because of its flexibility and adaptability.

This multicenter prospective study ( Japanese Radiation Oncology Study Group: JROSG 05-5) aimed to evaluate the effectiveness of postoperative radiotherapy (PORT) in patients with ductal carcinoma in situ (DCIS) with an involved surgical margin or close margin widths of ≤1 mm or less. PORT consisted of whole-breast irradiation (50 Gy in 25 fractions) followed by boost irradiation (10 Gy in 5 fractions). Eligibility criteria were as follows: (i) DCIS without an invasive carcinoma component, (ii) age between 20 and 80 years old, (iii) involved margin or close margin widths of ≤1 mm, (iv) refusal of re-resection, (v) performance status of 0-2, and (vi) written informed consent. The primary endpoint was ipsilateral breast tumor recurrence (IBTR), and secondary endpoints were overall survival (OS), relapse-free survival (RFS), recurrence patterns, and adverse events. A total of 37 patients from 12 institutions were enrolled from January 2007 to May 2009. The median follow-up time was 62 months (range, 28-85 months). The median pathological tumor size was 2.5 cm (range, 0.3-8.5 cm). Of the 37 patients, 21 had involved margins, and 16 had close margins. The 5-year IBTR, OS and RFS rates were 6% (95% confidence interval [CI]: 2-21), 97% (95% CI: 83-99) and 91% (95% CI: 77-97), respectively. Two patients developed local recurrence at the original site after 39 and 58 months. No severe adverse events were found. Our study suggests that this PORT regimen could be a treatment option for patients with DCIS with involved margin or close margin who don't desire re-resection., (© The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

To analyze diffuse lung diseases based on chest region computed tomography (CT) imaging by using a computer-aided diagnosis (CAD) system, it is necessary to first determine the lung regions subject to analysis. The lung regions can be selected relatively easily for healthy individuals, by applying a threshold. Selecting an area by using a threshold-based method can be difficult when dealing with lungs with diffuse lung diseases, owing to the abnormal opacities that characterize the diseases. Trials for determining the lung regions were conducted in this study, through texture analysis and machine learning, by narrowing down the lung regions to rough regions, and by referring to ribs and the diaphragm. This method can be used for determining lung regions for analysis of diffuse lung diseases.

Purpose: To estimate the maximum tolerated dose (MTD) and to determine the recommended dose (RD) of stereotactic body radiation therapy (SBRT) for peripheral T2N0M0 non-small cell carcinoma (NSCLC) with target volume (PTV) < 100 cc., Materials and Methods: The continual reassessment method (CRM) was used to determine the dose level that patients should be assigned to and to estimate the MTD. Dose limiting toxicity (DLT) was grade 3 radiation pneumonitis (RP) within 180 days after the start of SBRT, grade 2 RP was used as a surrogate DLT. The RD was equal to the MTD. The dose was prescribed at D95 of the PTV., Results: Fifteen patients were accrued. Only 1 experienced grade 2 RP at 60 Gy in 4 fractions. It was difficult to fulfill the dose constraints at 60 Gy in 4 fractions, and the maximum dose level assigned by CRM was changed to 55 Gy in 4 fractions. The lower limit of 95% of the credible interval exceeded the adjacent level, and the RD was determined as 55 Gy in 4 fractions., Conclusions: The RD of SBRT for peripheral T2N0M0 NSCLC with PTV<100 cc was determined to be 55 Gy in 4 fractions., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

To standardize educational programs and clinical training for medical physics students, the Japanese Board for Medical Physicist Qualification (JBMP) began to accredit master's, doctorate, and residency programs for medical physicists in 2012. At present, 16 universities accredited by the JBMP offer 22 courses. In this study, we aimed to survey the current status of educational programs and career paths of students after completion of the medical physicist program in Japan. A questionnaire was sent in August 2014 to 32 universities offering medical physicist programs. The questionnaire was created and organized by the educational course certification committee of the JBMP and comprised two sections: the first collected information about the university attended, and the second collected information about characteristics and career paths of students after completion of medical physicist programs from 2008 to 2014. Thirty universities (16 accredited and 14 non-accredited) completed the survey (response rate 94 %). A total of 209, 40, and 3 students graduated from the master's, doctorate, and residency programs, respectively. Undergraduates entered the medical physicist program constantly, indicating an interest in medical physics among undergraduates. A large percentage of the students held a bachelor's degree in radiological technology (master's program 94 %; doctorate program 70 %); graduates obtained a national radiological technologist license. Regarding career paths, although the number of the graduates who work as medical physicist remains low, 7 % with a master's degree and 50 % with a doctorate degree worked as medical physicists. Our results could be helpful for improving the medical physicist program in Japan.

The conditions and outcomes of Japanese patients with prostate cancer who developed PSA failure after radical prostatectomy (RP), and who were treated via salvage radiotherapy (S-RT), were surveyed. Clinical data on S-RT were gathered in questionnaires completed by facilities participating in the Japanese Radiation Oncology Study Group. S-RT was defined as external-beam radiotherapy delivered to the prostate beds of patients with prostate cancer who had eventually developed PSA failure, although their PSA values had at one stage attained levels <0.2 ng/ml following RP. Hormonal therapy was combined with S-RT in ∼40% of cases. Outcomes were evaluated in 186 cases treated via S-RT alone. The nadir PSA level after RP, and the level upon initiation of S-RT, were 0.0135 ng/ml and 0.292 ng/ml, respectively. The median period between RP and S-RT was 18.6 months. The median follow-up period was 58 months. The 5-year PSA recurrence-free survival (PRFS) and clinical failure-free survival (CFFS) rates were 50.1% (95% CI: 42.8-57.9%) and 90.1% (95% CI: 86.4-95.7%), respectively. PRFS was significantly superior in patients with PSA values ≤0.3 ng/ml upon initiation of S-RT than in those with PSA values >0.3 ng/ml (57.5% vs 40.5%, P = 0.027). In Japan, hormonal therapy is combined with S-RT in ∼40% of cases. The 5-year PRFS and CFFS rates of cases treated via S-RT alone were 50.1% and 90.1%, respectively. A PSA value of 0.3 ng/ml served as a significant cut-off for prediction of PRFS., (© The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Telomerase participates in malignant transformation or immortalization of cells and thus has attracted attention as an anticancer drug target and diagnostic tumor marker. The telomeric repeat amplification protocol (TRAP) and improved TRAP methods (TRAP-fluorescence, TRAP-hybridization, etc.) are widely used forms of this telomerase assay. However, these approaches generally employ acrylamide gel electrophoresis after amplification of telomeric repeats by polymerase chain reaction (PCR), making these TRAP methods time consuming and technically demanding. In this study we developed a novel telomerase assay using microchip electrophoresis for rapid and highly sensitive detection of telomerase activity in cancer cells. The mixed gel of 0.8% hydroxypropyl methylcellulose (HPMC) and 0.3% polyethylene oxide (PEO) with SYBR Gold (fluorescent reagent) was used for microchip electrophoresis. As a result, the product amplified by a telomerase-positive cell could be measured in one cell per assay and detected with high reproducibility (CV=0.67%) in the short time of 100s., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background/aims: To determine the recommended dose (RD) for full-dose S-1 and low-dose gemcitabine combined with radiotherapy in patients with non-metastatic advanced pancreatic cancer., Methodology: Adult patients with non-metastatic advanced pancreatic cancer (Union for International Cancer Control T stage 3 or 4) were eligible. The weekly intravenous gemcitabine (level 0-1: 200 mg/ml,level 2: 300 mg/m on Days 1, 8, 15, 22, 29, 36) dose was escalated starting from level 1 in a 3+3 design along with full dose twice-daily oral S-1 (level 0: 60 mg/m2/day, level 1-2: 80 mg/ml/day), and was administered on the same days as radiotherapy (1.8 Gy x 28 days)., Results: Eight patients were included in this study. A dose-limiting toxicity (DLT) (grade 4 neutropenia) was observed in one of the first three patients in level 1, and three additional patients received the level 1 dose without any severe adverse events. DLTs (grade 3/4 neutropenia) were then observed in the first two patients given level 2 dose. Therefore, level 1 was designated as the RD. Common grade 3/4 toxicities included neutropenia (62.5%), anorexia (37.5%), and pneumonitis (12.5%)., Conclusions: The combination of S-1 and gemcitabine with concurrent radiotherapy is a feasible regimen at the level 1 dose.

Unlabelled: To evaluate the efficacy and the toxicity of prophylactic extended-field carbon-ion radiotherapy (C-ion RT, Protocol 0508) for locally advanced squamous cell carcinoma of the uterine cervix in phase I / II clinical trial. Between May 2006 and January 2012, 26 patients of Protocol 0508 were treated with C-ion RT. The numbers of patients with stage IIB, IIIB, and IVA disease were 13, 11, and 2, respectively. Twenty patients had pelvic lymph node metastases. Median tumor size was 6.1 cm (range, 4.0–10.0 cm). The treatment consisted of extended-field irradiation of 39.0 gray equivalents (GyE) in 13 fractions, and additional 15.0 GyE in 5 fractions was given to the gross tumor volume (GTV) and surrounding tissues. With regard to local boost, 18.0 GyE in 2 fractions was given to GTV only. Total dose to the cervical tumor was 72.0 GyE over 20 fractions. The median follow-up period was 37 months. Twenty-one patients had grade 1 or 2 acute gastrointestinal toxicity, but all patients completed the treatment on schedule. There were no grade 3 or higher late complications, with 8 patients having grade 1 or 2 toxicities, 1 had grade 2 gastrointestinal toxicity and 2 had grade 2 genitourinary toxicity. Four patients (15.4%) developed local recurrence, and 8 patients (30.8%) had distant metastases. The 2-year local control rate, progression-free survival rate and overall survival rate were 83.6%, 61.5% and 73.1%, respectively. There were no severe acute or late complications in this trial. Prophylactic extended-field C-ion RT for locally advanced squamous cell carcinoma of the uterine cervix was a safe treatment. Although the number of patients in this study was small, the results support further investigations to confirm the therapeutic efficacy and to avoid or reduce toxicity., Trial Registration: UMIN-CTR UMIN000016169.

We investigated the first site of distant failure after carbon ion radiotherapy (C-ion RT) for locally advanced cervical cancer in three clinical trials. A total of 91 cases were enrolled in the three trials (Protocol 9702, 9704 and 9902). Histologically, 36 cases had squamous cell carcinoma (SqCC) and 55 cases had adenocarcinoma (AC), including 13 with adenosquamous cell carcinoma. The number of cases with Stage IIB, IIIB and IVA disease was 21, 59 and 11, respectively. Of the 91 cases, 42 had positive pelvic lymph nodes (PLNs). The median tumor size was 6.0 cm (range, 3.0–12.0 cm). The median follow-up duration for all cases was 40 months (range, 7–181 months). A total of 40 cases developed distant failure as the first site of failure: 13 of 36 (36.1%) SqCC cases had distant failure, with 9 of them with para-aortic lymph node (PALN) failure; 27 of 55 (44.0%) AC cases had distant failure, and 23 of them had distant failure excluding PALN metastasis. Distant failure rates of SqCC cases who had positive and negative PLNs before C-ion RT were 61.1% and 11.1%, respectively (P = 0.0045). Those of AC cases were 54.2% and 45.2%, respectively (P = 0.507). In conclusion, there were high rates of distant failure after C-ion RT in AC cases regardless of PLN status, and there were high rates of distant failure after C-ion RT, especially PALN failure, in SqCC cases with positive PLNs.

Monocytes and kidney-resident macrophages are considered to be involved in the pathogenesis of renal ischemia-reperfusion injury (IRI). Several subsets of monocytes and macrophages are localized in the injured tissue, but the pathologic roles of these cells are not fully understood. Here, we show that CD169(+) monocytes and macrophages have a critical role in preventing excessive inflammation in IRI by downregulating intercellular adhesion molecule-1 (ICAM-1) expression on vascular endothelial cells. Mice depleted of CD169(+) cells showed enhanced endothelial ICAM-1 expression and developed irreversible renal damage associated with infiltration of a large number of neutrophils. The perivascular localization of CD169(+) monocytes and macrophages indicated direct interaction with blood vessels, and coculture experiments showed that the direct interaction of CD169(+) cell-depleted peripheral blood leukocytes augments the expression levels of ICAM-1 on endothelial cells. Notably, the transfer of Ly6C(lo) monocytes into CD169(+) cell-depleted mice rescued the mice from lethal renal injury and normalized renal ICAM-1 expression levels, indicating that the Ly6C(lo) subset of CD169(+) monocytes has a major role in the regulation of inflammation. Our findings highlight the previously unknown role of CD169(+) monocytes and macrophages in the maintenance of vascular homeostasis and provide new approaches to the treatment of renal IRI., (Copyright © 2015 by the American Society of Nephrology.)

Tissue engineering is a rapidly advancing technology in the field of regenerative medicine. For the transplantation of cell sheets, a carrier must maintain the shape of a cell sheet from a culture dish to affected sites as well as release the sheet easily onto the lesion. In this study, we examined the utility of a novel, poly(lactic acid)-based carrier for cell sheets transplantation to the cornea of dogs and the skin of rats. The poly(lactic acid)-based carrier easily picked a cell sheet up from the dish, fit to the shape of the transplantation sites, and saved time for cell sheets detachment comparing to a conventional carrier. Thus, the poly(lactic acid)-based carrier would be useful for easy cell sheet transplantations.

Introduction: Stereotactic body radiotherapy (SBRT) planning for spinal metastases is a challenging task that involves complex target shapes and steep dose gradients proximal to the spinal cord. The aim of the present study is to investigate dosimetric variability among delivery systems and institutions doing spine SBRT.Materials and Methods: Three institutions (in Japan, Canada, and the USA) participated in this retrospective treatment planning study. Computed tomography (CT) datasets for three patients including fully delineated targets and organs-at-risk (OAR) were distributed to all three institutions for planning. Delivery systems included the Clinac 21EX, Vero4DRT, Synergy S, and CyberKnife. All treatment plans were generated using a prescribed dose of 24 Gy in 2 fractions and met the following objectives: the evaluated planning target volume (PTV evl , defined as the PTV minus spinal cord) should receive greater than 16.8 Gy in at least 95% of the volume (D 95 > 16.8 Gy) and a maximum dose to the less than 140% of the prescribed dose (D max < 33.6 Gy). The maximum dose of planning risk volume (PRV) cord or thecal sac was limited to 0.035 cm 3 receiving less than 17 Gy. Aside from minimum and maximum dose objectives for the PTV evl , there were no criteria regarding the shape of the PTV evl dose-volume histogram (DVH). For each completed treatment plan, the following DVH parameters were evaluated for the PTV evl : D 95 , D 80 , D 50 , D 2 and sigma-index (S-index, standard deviation of the differential DVH)., Results: The PTV evl and OAR dose volume constraints were satisfied in all treatment plans. For Case 1, the mean PTV evl D 50 was 25.4 ± 1.5 Gy (range: 23.7 - 27.8 Gy), for Case 2 it was 26.7 ± 2.0 Gy (23.6 - 28.6 Gy), and for Case 3 it was 26.0 ± 1.3 Gy (24.1 - 27.3 Gy). The mean PTV evl D 2 was 27.3 ± 2.2 Gy (24.4 - 30.2 Gy), 28.9 ± 3.0 Gy (24.5 - 31.4 Gy) and 28.7 ± 2.7 Gy (25.2 - 31.6 Gy) for Cases 1, 2, and 3, respectively. However, there were statistically significant variations in the DVH parameters of PTV evl between apparatuses (CyberKnife versus non-CyberKnife) and among institutions (between 2 CyberKnife sites or between 2 conventional accelerator sites)., Conclusions: Although all institutions met the minimum prescribed objectives, inter-institutional and inter-apparatus target dose variations were observed. Further study is necessary to determine target dose constraints that may minimize inter-institutional variations and lead to plan standardization.

A single nucleotide polymorphism in the plasma PAF-AH enzyme, i.e., G994T, which causes the substitution of Val at amino acid 279 with Phe (V279F), has been found in the Japanese population. This enzyme preferentially degrades oxidatively modulated or truncated phospholipids; therefore, it has been suggested that this enzyme may prevent the accumulation of proinflammatory and proatherogenic oxidized phospholipids. This hypothesis is supported by the higher prevalence of the V279F mutation in patients with asthmatic and atherosclerotic diseases, as compared with healthy controls. This mutation is rare in the Caucasian population. The plasma PAF-AH mass and enzyme activity are distributed over a wide range in the plasma and they are positively correlated with low-density lipoprotein (LDL) cholesterol. However, several clinical studies in the Caucasian population have suggested that this enzyme has the opposite role. This enzyme plays an active role in the development and progression of atherosclerosis via proinflammatory and proatherogenic lysophosphatidylcholine and oxidized fatty acids produced through the oxidation of LDL by this enzyme. Thus, plasma PAF-AH is a unique enzyme with dual roles in human inflammatory diseases. In this chapter, on the basis of recent findings we describe the association between a naturally occurring missense mutation in plasma PAF-AH and human diseases especially including atherosclerosis and asthma., (© 2015 Elsevier Inc. All rights reserved.)

Because the acetyl group of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF) is essential for its biological activity, the degradation of PAF is the most important mechanism that regulates the level of PAF. The enzyme that catalyzes the hydrolysis of acetyl group at the sn-2 position of PAF was termed PAF-acetylhydrolase (PAF-AH). Subsequent research revealed that the PAF-AH family includes intracellular forms called PAF-AH I and PAF-AH II as well as an extracellular isoform, plasma PAF-AH. PAF-AH I forms a complex consisting of catalytic subunits α1, α2, and β regulatory subunits. PAF-AH I was identified from the brain, and previous studies focused on the role of PAF-AH I in brain development. However, subsequent studies found that PAF-AH I is involved in diverse functions such as spermatogenesis, amyloid-β generation, cancer pathogenesis, and protein trafficking. Another intracellular enzyme, PAF-AH II, has no homology with PAF-AH I, although this enzyme shares sequence similarity to plasma PAF-AH. Because PAF-AH preferentially hydrolyzes oxidatively modulated or truncated phospholipids, it is considered to play a protective role against oxidative stress. Homologs of this enzyme are widely distributed among evolutionarily diverse organisms. For example, studies of Caenorhabditis elegans PAF-AH II demonstrate its contribution to epidermal morphogenesis. Extracellular plasma PAF-AH associates strongly with plasma lipoproteins. Because PAF-AH is mainly associated with LDL particles, it is considered to play an anti-inflammatory role by removing oxidized phospholipids generated in LDLs exposed to oxidative stress. In this overview, we describe the crucial roles of these three PAF-degrading enzymes in cell function and cell pathology., (© 2015 Elsevier Inc. All rights reserved.)

Iodine-131 (I-131) has been used for the ablation of residual thyroid remnants and cancer cells in well-differentiated thyroid cancers. It has also been used for metastatic well-differentiated thyroid cancers, especially lung and bone metastases. For small lung metastases, I-131 treatment has curative potential, particularly in young patients. Suppression of the thyroid stimulating hormone is also important for prolonging the survival of thyroid cancer patients. Strontium-89 (Sr-89) chloride has a mechanism similar to calcium, and it has been used for the treatment of bone metastases, especially osteoblastic metastases. It has been reported to have analgesic effects in an average of 76% of cases, and it is more effective if used in the early bone metastatic phase. Ibritumomab tiuxetan (Zevalin) is an anti-CD20 mouse monoclonal antibody labeled with Yttrium-90 (Y-90). It is used for treatment-resistant low grade or follicular B-cell non-Hodgkin's lymphomas and mantle lymphomas. Recently, radium-223 (Ra-223) has been used for bone metastases from castration resistant prostate cancers, and in a phase III trial, it has been proven to prolong survival of these patients. Cancer therapy using unsealed radioisotopes has been thought to be promising because it exhibits more targeted therapy than external beam irradiation. Therefore, if many more ideal targeting agents are developed in the future, this treatment might be used more commonly. As many agents such as I-131, Sr-89, and Ra-223 are available for treating bone metastasis, the combined use of other treatments such as high precision radiotherapy, bisphosphonates, hormonal agents, and molecular targeted agents should be investigated.

Brn4, which encodes a POU transcription factor, is the gene responsible for DFN3, an X chromosome-linked, non-syndromic type of hearing loss. Brn4-deficient mice have a low endocochlear potential (EP), hearing loss, and ultrastructural alterations in spiral ligament fibrocytes, however the molecular pathology through which Brn4 deficiency causes low EP is still unclear. Mutations in the Gjb2 and Gjb6 genes encoding the gap junction proteins connexin26 (Cx26) and connexin30 (Cx30) genes, respectively, which encode gap junction proteins and are expressed in cochlear fibrocytes and non-sensory epithelial cells (i.e., cochlear supporting cells) to maintain the proper EP, are responsible for hereditary sensorineural deafness. It has been hypothesized that the gap junction in the cochlea provides an intercellular passage by which K+ is transported to maintain the EP at the high level necessary for sensory hair cell excitation. Here we analyzed the formation of gap junction plaques in cochlear supporting cells of Brn4-deficient mice at different stages by confocal microscopy and three-dimensional graphic reconstructions. Gap junctions from control mice, which are composed mainly of Cx26 and Cx30, formed linear plaques along the cell-cell junction sites with adjacent cells. These plaques formed pentagonal or hexagonal outlines of the normal inner sulcus cells and border cells. Gap junction plaques in Brn4-deficient mice did not, however, show the normal linear structure but instead formed small spots around the cell-cell junction sites. Gap junction lengths were significantly shorter, and the level of Cx26 and Cx30 was significantly reduced in Brn4-deficient mice compared with littermate controls. Thus the Brn4 mutation affected the assembly and localization of gap junction proteins at the cell borders of cochlear supporting cells, suggesting that Brn4 substantially contributes to cochlear gap junction properties to maintain the proper EP in cochleae, similar to connexin-related deafness.

Object: Temozolomide (TMZ) may enhance antitumor immunity in patients with glioblastoma multiforme (GBM). In this paper the authors report on a prospective Phase I/IIa clinical trial of fractionated radiotherapy (FRT) concomitant with TMZ therapy, followed by treatment with autologous formalin-fixed tumor vaccine (AFTV) and TMZ maintenance in patients with newly diagnosed GBM., Methods: Twenty-four patients (age 16-75 years, Karnofsky Performance Scale score ≥ 60% before initiation of FRT) with newly diagnosed GBM received a total dose of 60 Gy of FRT with daily concurrent TMZ. After a 4-week interval, the patients received 3 AFTV injections and the first course of TMZ maintenance chemotherapy for 5 days, followed by multiple courses of TMZ for 5 days in each 28-day cycle., Results: This treatment regimen was well tolerated by all patients. The percentage of patients with progression-free survival (PFS) ≥ 24 months was 33%. The median PFS, median overall survival (OS), and the actuarial 2- and 3-year survival rates of the 24 patients were 8.2 months, 22.2 months, 47%, and 38%, respectively. The median PFS in patients with a delayed-type hypersensitivity (DTH) response after the third AFTV injection (DTH-2) of 10 mm or larger surpassed the median length of follow-up for progression-free patients (29.5 months), which was significantly greater than the median PFS in patients with a smaller DTH-2 response., Conclusions: The treatment regimen was well tolerated and resulted in favorable PFS and OS for newly diagnosed GBM patients. Clinical trial registration no.: UMIN000001426 (UMIN clinical trials registry, Japan).

Cardiac scintigraphy accounted for 2.5 % of all 3,884 patients based on a survey ques- tionnaire of pediatric nuclear medicine examinations performed at 14 Japanese institutes in 2011. Myocardial perfusion imaging, classified as cardiac scintigraphy, is essential to detect myocardial ischemia in patients after Kawasaki disease (KD), although its less frequent performance is reported. Adenosine is widely noticed as a medication for pharma- cological stress testing in coronary arterial lesions after KD. We describe characteristics of adenosine including newly-devised administration protocol and pathway making of intravenous injection for stress testing. We comment on optimal radiopharmaceutical administered doses proposed in Japanese consensus guidelines for pediatric nuclear medi- cine. Their proposal doses approximate that calculated by Pediatric Dosage Card of Euro- pean Association of Nuclear Medicine. We hope myocardial perfusion imaging is performed under appropriate management of pediatric radiopharmaceutical administration.