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In external radiotherapy of head and neck (HN) cancers, the reduction of irradiation accuracy due to HN volume reduction often causes a problem. Adaptive radiotherapy (ART) can effectively solve this problem; however, its application to all cases is impractical because of cost and time. Therefore, finding priority cases is essential. This study aimed to predict patients with HN cancers are more likely to need ART based on a quantitative measure of large HN volume reduction and evaluate model accuracy. The study included 172 cases of patients with HN cancer who received external irradiation. The HN volume was calculated using cone-beam computed tomography (CT) for irradiation-guided radiotherapy for all treatment fractions and classified into two groups: cases with a large reduction in the HN volume and cases without a large reduction. Radiomic features were extracted from the primary gross tumor volume (GTV) and nodal GTV of the planning CT. To develop the prediction model, four feature selection methods and two machine-learning algorithms were tested. Predictive performance was evaluated by the area under the curve (AUC), accuracy, sensitivity and specificity. Predictive performance was the highest for the random forest, with an AUC of 0.662. Furthermore, its accuracy, sensitivity and specificity were 0.692, 0.700 and 0.813, respectively. Selected features included radiomic features of the primary GTV, human papillomavirus in oropharyngeal cancer and the implementation of chemotherapy; thus, these features might be related to HN volume change. Our model suggested the potential to predict ART requirements based on HN volume reduction .

We assessed the accuracy of deformable image registration (DIR) accuracy between CT and MR images using an open-source software (Elastix, from Utrecht Medical Center) and a commercial software (Velocity AI Ver. 3.2.0 from Varian Medical Systems, Palo Alto, CA, USA) software. Five male patients’ pelvic regions were studied using publicly available CT, T1-weighted (T1w) MR, and T2-weighted (T2w) MR images. In the cost function of the Elastix, we used six DIR parameter settings with different regularization weights (Elastix0, Elastix0.01, Elastix0.1, Elastix1, Elastix10, and Elastix100). We used MR Corrected Deformable algorithm for Velocity AI. The Dice similarity coefficient (DSC) and mean distance to agreement (MDA) for the prostate, bladder, rectum and left and right femoral heads were used to evaluate DIR accuracy. Except for the bladder, most algorithms produced good DSC and MDA results for all organs. In our study, the mean DSCs for the bladder ranged from 0.75 to 0.88 (CT-T1w) and from 0.72 to 0.76 (CT-T2w). Similarly, the mean MDA ranges were 2.4 to 4.9 mm (CT-T1w), 4.6 to 5.3 mm (CT-T2w). For the Elastix, CT-T1w was outperformed CT-T2w for both DSCs and MDAs at Elastix0, Elastix0.01, and Elastix0.1. In the case of Velocity AI, no significant differences in DSC and MDA of all organs were observed. This implied that the DIR accuracy of CT and MR images might differ depending on the sequence used.

Intractable late urinary toxicity is a serious complication after radiotherapy for patients with localized prostate cancer (LPC). We assessed clinical factors correlated with severe late urinary toxicity in LPC treated with curative image-guided intensity-modulated radiation therapy (IMRT). A total of 452 patients with LPC treated with IMRT between 2002 and 2016 were retrospectively analyzed. Among them, 432 patients received androgen deprivation therapy (ADT). The median total irradiated doses were 80 (range, 76–80) Gy. Each daily dose was 2 Gy per fraction. The median follow-up was 83 (range, 4–210) months. Late urinary toxicity was scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.03. Grade 3 late urinary toxicity was observed in 27 patients. No cases with grade ≥ 4 late urinary toxicity were observed. The 5-, 10-, and 12.5-year grade 3 late urinary toxicity-free survival rates were 97%, 91.8% and 88.1%, respectively. Age, risk classification, total irradiated dose, ADT duration, antithrombotic therapy (AT), cardiovascular disease, hypertension (HT), diabetes mellitus (DM), dyslipidemia (DL), prior transurethral resection of the prostate (TURP) and prior high-intensity focused ultrasound (HIFU) were investigated for correlations with grade 3 late urinary toxicity. In univariate analysis, AT and prior HIFU and no other studied factors, were correlated with grade 3 late urinary toxicity. AT and prior HIFU appear to be predictive of grade 3 late urinary toxicity. Patients with LPC with these relevant clinical factors should be carefully followed up by sharing detailed information with the urology department.

Right ventricular endomyocardial biopsies were performed in 15 patients with unexplained cardiac dysfunction, and the expression of intercellular adhesion molecule-1 (ICAM-1) on the myocardium was examined using the streptavidin-biotin complex method. Three of 15 patients (20%) had histologic evidence of myocarditis, and 2 of 15 patients (13%) had borderline myocarditis. The patients with biopsy-proven myocarditis received immunosuppressive therapy (prednisolone 60 mg/day). Two of the 3 patients demonstrated a substantial increase (>10%) in percent fractional shortening and left ventricular ejection fraction during therapy. Subsequent biopsies revealed ongoing myocarditis in 1 patient, and resolved myocarditis in the other. The remaining patient had persistent cardiac dysfunction, but the subsequent biopsy revealed resolving myocarditis. ICAM-1 immunoreactivity was observed on cardiac myocytes, vascular endothelial cells, and interstitial cells of the patients with myocarditis. However, in patients without myocarditis, ICAM-1 immunoreactivity was observed only on vascular endothelial cells and interstitial cells. ICAM-1 immunoreactivity was still observed on cardiac myocytes in the patients with ongoing or resolving myocarditis during immunosuppressive therapy, but was not detected in the patient with resolved myocarditis. This study demonstrates that ICAM-1 is expressed on cardiac myocytes of patients with myocarditis and persistent cardiac dysfunction despite immunosuppressive therapy. The persistent expression of ICAM-1 may cause chronic inflammation of the myocardium. (Am J Cardiol 1993;72:441-444) Myorcarditis is characterized by an inflammatory infiltrate of the myocardium with necrosis and degeneration of adjacent myocytes.[1] Necrosis of the myocytes is an important feature of this lesion, and is caused by [greater than or equal to] 2 mechanisms: virus-mediated destruction of myofibers and cell-mediated destruction of myofibers.[2] In Coxsackie virus-infected mice deprived of T lymphocytes, there was a significant reduction in the incidence of lethal infection and in the extent of both myocardial inflammation and necrosis despite high virus titers.[3] Therefore, it is believed that T lymphocytes play an important role in the development of myocarditis. T cell-target cell interactions are mediated by cell surface adhesion molecules. Intercellular adhesion molecule-1 (ICAM -1) is a ligand for the lymphocyte function-associated antigen-1 (LFA-1)--dependent adhesion system.[4] It is expressed on a wide variety of cells, and its induction is an important means of regulating LFA-1/ICAM-1 interactions in inflammation.[5,6] In this study, we examined the expression of ICAM-1 on cardiac myocytes in patients with biopsy-proven myocarditis both before and during immunosuppressive therapy. METHODS Patient: Fifteen patients with unexplained cardiac dysfunction, clinically diagnosed as idiopathic dilated cardiomyopathy, underwent right ventricular endomyocardial biopsy between January 1991 and May 1992. Symptomatic heart failure was present in 13 patients, and 2 patients presented with recurrent ventricular tachycardia and cardiac enlargement. All patients underwent echocardiographic study before the biopsy, and all had diffuse left ventricular dysfunction without evidence of valvular heart disease. Mean percent fractional shortening was 17 [+ or -] 5%. Mean left ventricular ejection fraction[7] was 30 [+ or -] 9% (Table I). Only 1 patient had coronary disease, but it could not account for the diffuse left ventricular dysfunction. Patients with congenital heart disease, hypertensive heart disease, alcoholic heart disease, or metabolic disorders such as diabetes mellitus were excluded. All data are expressed as mean [+ or -] SD. [TABULAR DATA I OMITTED] Endomyocardial biopsy and tissue preparation: All biopsies were performed after informed consent had been obtained. Three biopsy specimens, ranging from 1 to 3 mm, were obtained from each patient through the right femoral vein using a Konno-Sakakibara bioptome. Each specimen was divided into 2 portions. One portion was fixed in 10% buffered formalin and embedded in paraffin. The second portion was fixed in periodate-lysine-paraformaldehyde fixative (0.01 M sodium metaperiodic acid, 0.075 M lysine monohydrochloride, 2% paraformaldehyde, 0.0375 M phosphate buffer), the quick frozen in O.C.T. compound (Miles Co., Elkhart, Indiana), and cooled in liquid nitrogen. Both the paraffin-embedded sections and frozen sections were examined by light microscopy and immunohistochemistry. Light microscopic examination: Tissue sections, 3 [Mu] m thick, were cut and stained with hematoxylin-eosin, Masson's trichrome, Periodic-acid-Schiff, and elasticavan-Gieson stains. Each biopsy specimen was examined by 2 cardiac pathologists. The diagnosis of myorcarditis was made according to the Dallas criteria.[1] Immunohistochemical examination: The sections were incubated with monoclonal mouse antihuman ICAM-1/CD54 (anti-ICAM-1) (Boehringer Mannheim Biochemica, Mannheim, Germany), diluted to 5 to 20 [Mu]/ml, for 24 hours at 4 [degrees] C. After washing 3 times with phospate-buffered saline solution for 10 minutes each, the samples were reacted with biotinylated rabbit antimouse immunoglobin G + immunoglobin A + immunoglobin M (Nichirei Co., Tokyo, Japan) for 10 minutes at room temperature. After three 5-minute washings in phosphate-buffered saline, the samples were incubated with peroxidase-conjugated streptavidin (Nichirei Co., Tokyo, Japan) for 5 minutes at room temperature. The labeling peroxidase was visualized with diaminobenzidine and hydrogen peroxide. The samples were counterstained with hematoxylin for 3 minutes. Control slides omitted the anti-ICAM-1. Specimens with an inflammatory cell infiltrate were incubated with monoclonal mouse antihuman T cell, CD45RO (DAKO-CD45RO, UCHL-1) (DAKO Japan Co., Kyoto, Japan) and monoclonal mouse antihuman B cell, Cd20 (DAKO-CD20, L26) (DAKO Japan Co., Kyoto, Japan) for differentiation of the inflammatory cells, using the streptavidinbiotin complex method. Immunosuppressive therapy: All patients who had histologic evidence of active myocarditis received prednisolone 60 mg/day for 4 weeks, The dosage of prednisolone was then tapered by 10 mg/day every 2 weeks, until patients were receiving 20 mg/day. Echocardiography, cardiac-gated blood pool imaging, and endomyocardial biopsies were then repeated. RESULTS Pathologic findings: Three of the 15 patients (20%, cases 4,8 and 13) had histologic evidence of myocarditis. The myocardium contained lymphocytes, macrophages, and fibroblasts with necrosis of adjacent myofibers. T cells were prominent (Figure 1). Two of the 15 patients (13%, cases 3 and 5) had borderline myocarditis, based on an inflammatory cell infiltrate without myocyte necrosis. The remaining 10 patients (67%) had no myocarditis. Immunohistochemical findings: ICAM-1 immuno-reactivity was seen on cardiac myocytes, vascular endothelial cells, and interstitial cells in the 3 patients with myocarditis. In the remaining patients with borderline myocarditis or no myocarditis, ICAM-1 immunoreactivity was observed only on vascular endothelial cells and interstitial cells, and not on cardiac myocytes (Figure 2). Paraffin-embedded sections incubated with 20 [Mu] g/ml anti-ICAM-1 showed the same immunohistochemical staining as frozen sections incubated with 5 [Mu] g/ml anti-ICAM-1. Control subjects had no ICAM-1 immunoreactivity in the myocardium. Treatment and outcome: All 3 patients with myocarditis received immunosuppressive therapy. Two of the patients had a decrease in the incidence of ventricular tachycardia, and a substantial increase (>10%) in percent fractional shortening and left ventricular ejection fraction (Figure 3). The subsequent biopsies revealed ongoing myocarditis (case 4) and resolved myocarditis (case 8). One patient (case 13) had persistent cardiac dysfunction (Figure 3), but the subsequent biopsy demonstrated resolving myocarditis. ICAM-1 immunoreactivity on the cardiac myocytes was still observed in patients with ongoing myocarditis or resolving myocarditis (Figure 4). However, in the patient with resolved myocarditis, ICAM-1 immunoreactivity disappeared on the cardiac myocytes. DISCUSSION T cell-mediated cytotoxicity is thought to require cell-to-cell interactions mediated by LFA-1/ICAM-1 interactions. This has been demonstrated by blocking T-cell killing with antibody to ICAM-1.[8] ICAM-1 is normally expressed in only a few cell types, but at inflammatory sites, cytokines induce ICAM-1 in a wide variety of cell types.[5,6,9] There have been few reports on the expression of ICAM-1 in cardiac myocytes. Recently, Seko et al[10] reported the expression of ICAM-1 on cardiac myocytes in Coxsackie B3-induced murine acute myocarditis, and demonstrated the distribution of ICAM-1 in the ventricular tissue of a patient with acute myocarditis. In our study, all 3 patients with myocarditis who had persistent cardiac dysfunction of >11 months' duration, showed the same distribution of ICAM-1 as reported by Seko et al.[10] Viral myocarditis is usually an acute and benign illness in adults, but can pursue a subacute or chronic course leading to permanent cardiac dysfunction or death.[2] Therefore, persistent expression of ICAM-1 on cardiac myocytes may lead to 'chronic' inflammation of the myocardium. Since Mason et al[11] initiated the use of immunosuppressive agents for biopsy-proven acute myocarditis, they have been used to treat patients with myocarditis based on the concept that a persistent immune response plays an important role in the development of myocarditis. However, the efficacy of these agents remains controversial. In a 1987 review of the previous studies, of the 97 patients with biopsy-proven myocarditis who received immunosuppressive therapy, 54 patients improve, a 50% success rate. However, of the 33 patients with biopsy-proven myocarditis who had not achieved immunosuppression, 16 patients (48%) improved spontaneously.[12] It is therefore difficult to determine whether improvement is due to the effects of immunosuppression or to the natural history of myocarditis. In our study, patients with myocarditis had an indistinct onset of symptoms, and presented with persistent cardiac dysfunction. Two of the 3 patients had ongoing or resolving myocarditis on follow-up biopsies. Therefore, they fit the 'chronic active myocarditis' classification proposed by Lieberman et al.[13] These patients with ongoing or resolving myocarditis demonstrated continued expression of ICAM-1 on cardiac myocytes during immunosuppressive therapy. This persistent expression of ICAM-1 may cause chronic active myocarditis, leading to dilated cardiomyopathy. Other previous studies have reported clinical and histologic relapses when immunosuppressive agents were tapered or discontinued.[11,14-16] Recently, Isobe et al[17] reported that the combination of both anti-ICAM-1 and anti-LFA-1 monoclonal antibodies might act synergistically to induce specific unresponsiveness in cardiac allografts. This therapy may be more effective than 'conventional' immunosuppressive therapy in myocarditis. Acknowledgment: We thank Yukiyoshi Kono, MD, Toshio Nagai, MD, and Yoshitake Nakamura, MD, for their technical assistance during coronary angiography. [1] Aretz HT, Billingham ME, Edwards WD, Factor SM, Fallon JT, Fenoglio JJ Jr, Olsen EGJ, Schoen FJ. Myocarditis: a histopathologic definition and classification. Am J Cardiovasc Pathol 1986;1:2-14. [2] Woodruff JF. Viral myocarditis. A review. Am J Pathol 1980;101:425-484. [3] Woodruff JF, Woodruff JJ. Involvement of T lymphocytes in the pathogenesis of Coxsackie virus B3 heart disease. J Immunol 1974;113:1726-1734. [4] Marlin SD, Springer TA. Purified intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte function-associated antigen 1 (LFA-1). Cell 1987;51:813-819. [5] Kishimoto TK, Larson RS, Corbi AL, Dustin ML, Staunton DE, Springer TA. The leukocyte integrins: LFA-1, Mac-1, and p150,95, Adv Immunol 1989;46:149-182. [6] Dustin ML, Staunton DE, Springer TA. Supergene families meet in the immune system. Immunol Today 1988;9:213-215. [7] Burow RD, Strauss HW, Singleton R, Pond M, Rehn T, Bailey IK, Griffith LC, Nicholoff E, Pitt B. Analysis of left ventricular function from multiple gated acquisition cardiac blood poll imaging: comparison to contrast angiography. Circulation 1977;56:1024-1028. [8] Makgoba MW, Sanders ME, Luce GEG, Gugel EA, Dustin ML, Springer TA, Shaw S. Functional evidence that intercellular adhesion molecule-1 (ICAM-1) is a ligand for LFA-1-dependent adhesion in T cell-mediated cytotoxicity. Eur J Immunol 1988;18:637-640. [9] Dustin ML, Rothlen R, Bhan AK, Dinarello CA, Springer TA. Induction by IL-1 and interferon, tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). J Immunol 1986;137:245-254. [10] Seko Y, Yamazaki T, Shinkai Y, Yagita H, Okumura K, Naito S, Imataka K, Fujii J, Yazaki Y. Cellular and molecular bases for the immunopathology of the myocardial cell damage involved in acute viral myocarditis with special reference to dilated cardiomyopathy. Jpn Circ J 1992;56:1062-1072. [11] Mason JW, Billingham ME, Ricci Dr. Treatment of acute inflammatory myocarditis assisted by endomyocardial biopsy. Am J Cardiol 1980;45:1037-1044. [12] O'Connell JB. The role of myocarditis in end-stage dilated cardiomyopathy Tex Heart Inst J 1987;14:268-275. [13] Lieberman EB, Hutchins GM, Herskowitz A, Rose NR, Baughman KL. Clinicopathologic description of myocarditis. J Am Coll Cardiol 1991;18:1617-1626. [14] Daly K, Richardson PJ, Olsen EGJ, Morgan-Capner P, McSorley C, Jackson G, Jewitte DE. Acute myocarditis: role of histological and virological examination in the diagnosis and assessment of immunosuppressive treatment. Br Heart J 1984;51:30-35. [15] Zee-Cheng C, Tsai CC, Palmer DC, Cogg JE, Pennington DG, Williams GA. High incidence of myocarditis by endomyocardial biopsy in patients with idiopathic congestive cardiomyopthy. J Am Coll Cardiol 1984-3:63-67. [16] Dec GW, Palacios I, Fallon JT, Aretz HT, Mills J, Lee DC, Johnson RA. Active myocarditis in the spectrum of acute dilated cardiomyopathies: clinical features, histological correlates, and clinical outcome. N Engl J Med 1985;312:885-890. [17] Isobe M, Yagita H, Okumura K, Ihara A. Specific acceptant of cardiac allograft after treatment with antibodies to ICAM-1 and LFA-1. Science 1992;255:1125-1127. Tetsuya Toyozaki, MD, Toshihiro Saito, MD, Hiroyuki Takano, MD, Kazuyuki Yorimitsu, MD, Satoru Kobayashi, MD, Haruhiko Ichikawa, MD, Ken Takeda, MD, and Yoshiaki Inagaki, MD From the Third Department of Internal Medicine, Chiba University School Medicine, Chiba, Japan.

The purpose of this retrospective study was to investigate survival outcomes and irradiated tumor control (local control [LC]) and locoregional control (LRC) after stereotactic body radiotherapy (SBRT) for T1 or recurrent T1 (rT1) kidney cancer. Twenty-nine nonconsecutive patients with 30 tumors were included. SBRT doses of 70 Gy, 60 Gy or 50 Gy in 10 fractions were prescribed with a linear accelerator using daily image guidance. The Kaplan–Meier method was used to estimate time-to-event outcomes, and the log-rank test was used to compare survival curves between groups divided by each possible factor. The median follow-up periods for all patients and survivors were 57 months and 69.6 months, respectively. The five-year LC rate, LRC rate, progression-free survival (PFS) rate, disease-specific survival (DSS) rate and overall survival (OS) rate were 94%, 88%, 50%, 96% and 68%, respectively. No significant factor was related to OS and PFS. Three of 24 non-hemodialysis (HD) patients had new-onset-HD because of the progression of underlying kidney disease. Grade 3 or higher toxicities from SBRT did not occur. In conclusion, SBRT for kidney cancer provided a high rate of LC, LRC and DSS with minimal toxicities, but patient selection and indication for SBRT should be done carefully considering the relatively low OS rate.

We compared predictive performance between dose volume histogram (DVH) parameter addition and deformable image registration (DIR) addition for gastrointestinal (GI) toxicity in cervical cancer patients. A total of 59 patients receiving brachytherapy and external beam radiotherapy were analyzed retrospectively. The accumulative dose was calculated by three methods: conventional DVH parameter addition, full DIR addition and partial DIR addition. ${D}_{2{cm}^3}$, ${D}_{1{cm}^3}$ and ${D}_{0.1{cm}^3}$ (minimum doses to the most exposed 2 cm3, 1cm3 and 0.1 cm3 of tissue, respectively) of the rectum and sigmoid were calculated by each method. V50, V60 and V70 Gy (volume irradiated over 50, 60 and 70 Gy, respectively) were calculated in full DIR addition. The DVH parameters were compared between toxicity (≥grade1) and non-toxicity groups. The area under the curve (AUC) of the receiver operating characteristic (ROC) curves were compared to evaluate the predictive performance of each method. The differences between toxicity and non-toxicity groups in ${D}_{2{cm}^3}$ were 0.2, 5.7 and 3.1 Gy for the DVH parameter addition, full DIR addition and partial DIR addition, respectively. The AUCs of ${D}_{2{cm}^3}$ were 0.51, 0.67 and 0.57 for DVH parameter addition, full DIR addition and partial DIR addition, respectively. In full DIR addition, the difference in dose between toxicity and non-toxicity was the largest and AUC was the highest. AUCs of V50, V60 and V70 Gy were 0.51, 0.63 and 0.62, respectively, and V60 and V70 were high values close to the value of ${D}_{2{cm}^3}$ of the full DIR addition. Our results suggested that the full DIR addition may have the potential to predict toxicity more accurately than the conventional DVH parameter addition, and that it could be more effective to accumulate to all pelvic irradiation by DIR.

The uptake of boron into tumor cells is a key factor in the biological effects of boron neutron capture therapy (BNCT). The uptake of boron agents is suppressed in hypoxic conditions, but the mechanism of hypoxia-induced modulation of suppression of boron uptake is not clear. Therefore, we evaluated whether hypoxia-inducible factor 1α (HIF-1α) contributes to attenuation of the antitumor effects of BNCT in hypoxic tumor cells. We also tested whether YC-1, a HIF-1α-targeting inhibitor, has therapeutic potential with BNCT. To elucidate the mechanism of attenuation of the effects of BNCT caused by hypoxia, deferoxamine (DFO) was used in experiments. Cells were incubated in normal oxygen, hypoxic conditions (1% O2) or 5 μM DFO for 24 h. Then, cells were treated with 10B-boronophenylalanine (BPA) for 2 h and boron accumulation in cells was evaluated. To clarify the relationship between HIF-1α and L-type amino acid transporter 1 (LAT1), gene expression was evaluated by a using HIF-1α gene knockdown technique. Finally, to improve attenuation of the effects of BNCT in hypoxic cells, BNCT was combined with YC-1. Boron uptake was continuously suppressed up to 2 h after administration of BPA by 5 μM DFO treatment. In cells treated with 5 μM DFO, LAT1 expression was restored in HIF-1α-knocked down samples in all cell lines, revealing that HIF-1α suppresses LAT1 expression in hypoxic cells. From the results of the surviving fraction after BNCT combined with YC-1, treatment with YC-1 sensitized the antitumor effects of BNCT in cells cultured in hypoxia.

Nanopore DNA sequencing offers a new paradigm owing to its extensive potential for long-read, high-throughput detection of nucleotide modification and direct RNA sequencing. Given the remarkable advances in protein nanopore sequencing technology, there is still a strong enthusiasm in exploring alternative nanopore-sequencing techniques, particularly those based on a solid-state nanopore using a semiconductor material. Since solid-state nanopores provide superior material robustness and large-scale integrability with on-chip electronics, they have the potential to surpass the limitations of their biological counterparts. However, there are key technical challenges to be addressed: the creation of an ultrasmall nanopore, fabrication of an ultrathin membrane, control of the ultrafast DNA speed and detection of four nucleotides. Extensive research efforts have been devoted to resolving these issues over the past two decades. In this review, we briefly introduce recent updates regarding solid-state nanopore technologies towards DNA sequencing. It can be envisioned that emerging technologies will offer a brand new future in DNA-sequencing technology.

The purpose of the study was to compare a 3D convolutional neural network (CNN) with the conventional machine learning method for predicting intensity-modulated radiation therapy (IMRT) dose distribution using only contours in prostate cancer. In this study, which included 95 IMRT-treated prostate cancer patients with available dose distributions and contours for planning target volume (PTVs) and organs at risk (OARs), a supervised-learning approach was used for training, where the dose for a voxel set in the dataset was defined as the label. The adaptive moment estimation algorithm was employed for optimizing a 3D U-net similar network. Eighty cases were used for the training and validation set in 5-fold cross-validation, and the remaining 15 cases were used as the test set. The predicted dose distributions were compared with the clinical dose distributions, and the model performance was evaluated by comparison with RapidPlan™. Dose–volume histogram (DVH) parameters were calculated for each contour as evaluation indexes. The mean absolute errors (MAE) with one standard deviation (1SD) between the clinical and CNN-predicted doses were 1.10% ± 0.64%, 2.50% ± 1.17%, 2.04% ± 1.40%, and 2.08% ± 1.99% for D2, D98in PTV-1 and V65in rectum and V65in bladder, respectively, whereas the MAEs with 1SD between the clinical and the RapidPlan™-generated doses were 1.01% ± 0.66%, 2.15% ± 1.25%, 5.34% ± 2.13% and 3.04% ± 1.79%, respectively. Our CNN model could predict dose distributions that were superior or comparable with that generated by RapidPlan™, suggesting the potential of CNN in dose distribution prediction.

We evaluated the impact of model-based dose calculation algorithms (MBDCAs) on high-dose-rate brachytherapy (HDR-BT) treatment planning for patients with cervical cancer. Seven patients with cervical cancer treated using HDR-BT were studied. Tandem and ovoid applicators were used in four patients, a vaginal cylinder in one, and interstitial needles in the remaining two patients. MBDCAs were applied to the Advanced Collapsed cone Engine (ACE; Elekta, Stockholm, Sweden). All plans, which were originally calculated using TG-43, were re-calculated using both ACE and Monte Carlo (MC) simulations. Air was used as the rectal material. The mean difference in the rectum D2cm3 between ACErec-air and MCrec-air was 8.60 ± 4.64%, whereas that in the bladder D2cm3 was -2.80 ± 1.21%. Conversely, in the small group analysis (n = 4) using water instead of air as the rectal material, the mean difference in the rectum D2cm3 between TG-43 and ACErec-air was 11.87 ± 2.65%, whereas that between TG-43 and ACErec-water was 0.81 ± 2.04%, indicating that the use of water as the rectal material reduced the difference in D2cm3 between TG-43 and ACE. Our results suggested that the differences in the dose-volume histogram (DVH) parameters of TG-43 and ACE were large for the rectum when considerable air (gas) volume was present in it, and that this difference was reduced when the air (gas) volume was reduced. Also, ACE exhibited better dose calculation accuracy than that of TG-43 in this situation. Thus, ACE may be able to calculate the dose more accurately than TG-43 for HDR-BT in treating cervical cancers, particularly for patients with considerable air (gas) volume in the rectum.

We evaluated dose-volume histogram (DVH) parameters based on deformable image registration (DIR) between brachytherapy (BT) and external beam radiotherapy (EBRT) that included a center-shielded (CS) plan. Eleven cervical cancer patients were treated with BT, and their pelvic and CS EBRT were studied. Planning CT images for EBRT and BT (except for the first BT, used as the reference image) were deformed with DIR to reference image. We used two DIR parameter settings: intensity-based and hybrid. Mean Dice similarity coefficients (DSCs) comparing EBRT with the reference for the uterus, rectum and bladder were 0.81, 0.77 and 0.83, respectively, for hybrid DIR and 0.47, 0.37 and 0.42, respectively, for intensity-based DIR (P < 0.05). D1 cm3 for hybrid DIR, intensity-based DIR and DVH addition were 75.1, 81.2 and 78.2 Gy, respectively, for the rectum, whereas they were 93.5, 92.3 and 94.3 Gy, respectively, for the bladder. D2 cm3 for hybrid DIR, intensity-based DIR and DVH addition were 70.1, 74.0 and 71.4 Gy, respectively, for the rectum, whereas they were 85.4, 82.8 and 85.4 Gy, respectively, for the bladder. Overall, hybrid DIR obtained higher DSCs than intensity-based DIR, and there were moderate differences in DVH parameters between the two DIR methods, although the results varied among patients. DIR is only experimental, and extra care should be taken when comparing DIR-based dose values with dose-effect curves established using DVH addition. Also, a true evaluation of DIR-based dose accumulation would require ground truth data (e.g. measurement with physical phantom).

This study aimed to evaluate the performance of the hybrid deformable image registration (DIR) method in comparison with intensity-based DIR for pelvic cone-beam computed tomography (CBCT) images, using intensity and anatomical information. Ten prostate cancer patients treated with intensity-modulated radiation therapy (IMRT) were studied. Nine or ten CBCT scans were performed for each patient. First, rigid registration was performed between the planning CT and all CBCT images using gold fiducial markers, and then DIR was performed. The Dice similarity coefficient (DSC) and center of mass (COM) displacement were used to evaluate the quantitative DIR accuracy. The average DSCs for intensity-based DIR for the prostate, rectum, bladder, and seminal vesicles were 0.84 ± 0.05, 0.75 ± 0.05, 0.69 ± 0.07 and 0.65 ± 0.11, respectively, whereas those values for hybrid DIR were 0.98 ± 0.00, 0.97 ± 0.01, 0.98 ± 0.00 and 0.94 ± 0.03, respectively (P < 0.05). The average COM displacements for intensity-based DIR for the prostate, rectum, bladder, and seminal vesicles were 2.0 ± 1.5, 3.7 ± 1.4, 7.8 ± 2.2 and 3.6 ± 1.2 mm, whereas those values for hybrid DIR were 0.1 ± 0.0, 0.3 ± 0.2, 0.2 ± 0.1 and 0.6 ± 0.6 mm, respectively (P < 0.05). These results showed that the DSC for hybrid DIR had a higher DSC value and smaller COM displacement for all structures and all patients, compared with intensity-based DIR. Thus, the accumulative dose based on hybrid DIR might be trusted as a high-precision dose estimation method that takes into account organ movement during treatment radiotherapy.

The aim of this study was to determine whether metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are associated with outcomes in Stage I lung cancer patients treated with stereotactic body radiation therapy (SBRT). Thirty-eight patients underwent [18F] fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) within 60 days before SBRT at our institution between January 2001 and December 2011. The maximum standardized uptake value (SUVmax), MTV2, MTV4, MTV6, TLG40%, TLG50%and TLG60%were calculated. Prognostic factors for overall survival (OS) and local control (LC) were analyzed using Cox's proportional hazards model, and survival curves were calculated using the Kaplan-Meier method. Receiver operating characteristics (ROC) curves of PET parameters for OS and LC were calculated. The median follow-up period for survivors was 37.7 months. Three-year OS and LC rates were 56.4% and 70.5%, respectively, and 5-year OS and LC rates were 36.8% and 70.5%, respectively. In univariate analyses, tumor diameter (P = 0.019), single dose ≥10 Gy (P = 0.017), MTV2(P = 0.030) and MTV4(P = 0.048) were significant predictors for OS. Tumor diameter (P < 0.001), single dose ≥10 Gy (P = 0.007), SUVmax(P = 0.035), MTV2(P < 0.001), MTV4(P = 0.003), MTV6(P = 0.017), TLG40%(P < 0.001), TLG50%(P = 0.001) and TLG60%(P = 0.003) were significant predictors for LC. SUVmax was not a significant predictor for OS. We made the ROC curves at PET parameters, and the largest area under the curve value for OS was MTV2and for LC was TLG40%Tumor diameter, single dose ≥10 Gy, MTV2 and MTV4are prognostic factors for OS and LC rates and MTV2is a better prognostic factor for OS than other PET parameters.

An Al2O3/SiO buffer layer was incorporated in a metal--insulator--semiconductor (MIS) Ta2O5capacitor for dynamic random access memory (DRAM) application. Al2O3was chosen for the buffer layer owing to its high band offset against silicon and oxidation resistance against increase in effective oxide thickness (EOT). It was clarified that post-deposition annealing in nitrogen at 800 °C for 600 s increased the band offset between Al2O3and the lower electrode and decreased leakage current by two orders of magnitude at 1 V. Furthermore, we predicted and experimentally confirmed that there was an optimized value of $y$ in (Si3N4)y(SiO2)(1-y), which is 0.58, for minimizing the leakage current and EOT of SiON. To clarify the oxidation resistance and appropriate thickness of Al2O3, a TiN/Ta2O5/Al2O3/SiON/polycrystalline-silicon capacitor was fabricated. It was confirmed that the lower electrode was not oxidized during the crystallization annealing of Ta2O5. By setting the Al2O3thickness to 3.4 nm, the leakage current is lowered below the required value with an EOT of 3.6 nm.

Abstract: It is well known that skeletal unloading induces bone loss. It has been shown that soybean isoflavones are effective in preventing bone loss in osteoporotic animals. We investigated the ability of isoflavones to protect bone loss induced by hindlimb unloading by using a tail-suspension mouse model. Eight-week-old female mice were divided into five groups: (1) normal housed group (Normal), (2) sham unloaded group fed a control diet (Sham-UL), (3) hindlimb unloaded group fed a control diet (UL-C), (4) hindlimb unloaded group fed a 0.25% isoflavone conjugates diet (UL-ISO 0.25), and (5) hindlimb unloaded group fed a 0.5% isoflavone conjugates diet (UL-ISO 0.5). After 3 weeks, bone mineral density (BMD) of the femur was significantly decreased in UL-C, and this bone loss was prevented by isoflavone treatment. Histomorphometric analysis revealed a decrease in the cancellous bone of the distal femur in the UL-C group, and isoflavone prevented this change. Serum corticosterone increased in the UL-C group, and isoflavones inhibited the elevation. These results suggest that isoflavones might be promising food components that provide protection from bone loss and normalize stress-induced serum corticosterone during skeletal unloading.

We reported previously that treatment of human myeloblastic leukemia ML‐1 cells with all‐transretinoic acid (ATRA) in combination with GM‐CSF enhances the granulocytic differentiation, which is induced only slightly by ATRA alone. To investigate the mechanism underlying this differentiation and the synergistic effect of ATRA and GM‐CSF, we used cDNA microarray to examine gene expression profiles of ML‐1 cells treated with ATRA and/or GM‐CSF. We identified 22 up‐regulated genes in ML‐1 cells treated with both reagents and examined the expression of these genes in cells treated with ATRA and/or GM‐CSF by Northen blot analysis. Comparison of cells treated with both reagents and cells treated with ATRA or GM‐CSF alone revealed that expression of nine of the 19 genes was induced synergistically by combined treatment with ATRA and GM‐CSF. Expression of most of these genes was increased only slightly by ATRA alone, and this induction was enhanced by the addition of GM‐CSF. These results indicate that GM‐CSF enhances ATRA‐induced gene expression. Moreover, studies with inhibitors of signaling molecules suggested that activation of JAK2 is associated with the synergistic induction of several genes by ATRA and GM‐CSF. JAK2 inhibitor suppressed induction of NBT‐reducing activity in ML‐1 cells treated with both reagents. It is likely that the enhancer effect of GM‐CSF on ATRA‐induced gene expression leads to the differentiation induced synergistically by ATRA combined with GM‐CSF. Further studies of the mechanism underlying this effect may identify better approaches for the treatment of RA‐insensitive leukemia.

A great variety of in vitro culture protocols for human monocyte‐derived dendritic cells (mo‐DCs) has been used to generate DCs suitable for use in immunotherapy. It is thought that activated DCs undergo one‐way differentiation into “exhausted” DCs. In the present study, we contrived an in vitro method for facilitating expression of CD70 by mature DCs. This was achieved by vigorous washing of mo‐DCs before exposure to lipopolysaccharide (LPS). Unexpectedly, these mature DCs retain expression of some interleukin (IL)‐12 family members after extended periods and maintain their ability to stimulate type 1 T cell responses. In contrast, DCs exposed to IL‐4 before LPS stimulation or LPS‐stimulated DCs not exposed to washing stress before activation failed to express CD70 and did differentiate into exhausted DCs. It is interesting that DCs expressing CD70 (CD70+DCs) induced interferon‐γ production from purified, allogeneic CD8+T cells through a direct CD27‐CD70 interaction. This is evidence for a pathway resulting in generation of CD8 T effectors by B7‐independent mechanisms. These data suggest that exposure of immature DCs to LPS stimulation contributes to their terminal differentiation into CD70+DCs, which have potent ability to prolong type 1 T cell responses through alternative pathways.

We have recently shown that diesel exhaust particles (DEP) synergistically enhance acute lung injury related to lipopolysaccharide (LPS) in mice. The present study used cDNA microarray to elucidate the effects of DEP on the global pattern of LPS-related gene expression in the murine lung. The number of genes upregulated >2-fold as compared with their expression levels in the vehicle group was greater in the LPS group than in other groups, but treatment with DEP and LPS dramatically increased the number of the genes upregulated >6-fold. In particular, gene expression of metallothionein-1 and -2, S100 calcium-binding protein A9, lipocalin 2, and small inducible cytokine B family member 10 was higher by >20-fold in the DEP + LPS group than in the vehicle group. These results were concomitant with those obtained by real-time reverse transcription–polymerase chain reaction analysis in the overall trend. Our findings suggest that intense, focused expression of genes such as S100 calcium-binding protein A9, lipocalin 2, and small inducible cytokine B family member 10 relates to the synergistic aggravation of acute lung injury by LPS and DEP rather than weak, broad expression of various genes by exposure of LPS alone.

Active cell death, also known as apoptosis, has been implicated in the pathophysiology of diseases such as cancer, heart failure and neurodegenerative disorders. We report the anti-apoptotic function of IRAS, which was previously shown to bind imidazoline ligands. The amino acid sequence of human IRAS (hIRAS) is unrelated to known proteins, except for rat IRAS and a mouse homologue named nischarin, which binds the alpha5 integrin subunit of the fibronectin receptor. When stably transfected into PC12 cells, hIRAS localizes to the cytosol as a 167 kDa immunoreactive protein. Clonal PC12 cell lines expressing hIRAS displayed normal serum growth responses. However, hIRAS expression led to prolonged cell survival against known apoptotic stimuli: serum starvation or thapsigargin or staurosporine treatments. The apoptotic population of hIRAS-expressing cells was significantly reduced, and this protection was achieved by a decrease in caspase-3 activity, phosphatidylserine translocation, and nuclear fragmentation. Similar protective effect was obtained in COS7 cells transiently transfected with hIRAS. A partial activation of the PI3 kinase pathway is possibly implicated in the anti-apoptotic effect of IRAS. Thus, IRAS appears to represent a previously unknown anti-apoptotic protein involved in the regulation of cell survival.

Summary Miniature end-plate currents (MEPCs) and acetylcholine-induced current fluctuations were recorded in voltageclamped, glycerol-treated toad sartorius muscle fibers in control solution and in solutions with added divalent cations. In isosmotic solutions containing 20mm Ca or Mg, MEPCs had time constants of decay (tD) which were about 30% slower than normal. In isotonic Ca solutions (Na-free), greater increases in both tD and channel lifetime were seen; the null potential was -34 mV, and single-channel conductance decreased to approximately 5 pS. Zn or Ni, at concentrations of 0.1–5mm, were much more effective in increasing tD than Ca or Mg, although they did not greatly affect channel conductance. The normal temperature and voltage sensitivity of t was not significantly altered by any of the added divalent cations. Surface potential shifts arising from screening of membrane fixed charge by divalent cations cannot entirely explain the observed increases in t, especially when taken together with changes in channel conductance.

1,25-dihydroxyvitamin D3(1,25(OH)2D3) dose-dependently inhibited the cytotoxicity of tumor necrosis factor (TNF) in a human monoblastic leukemic cell line, U-937. Combination of TNF and 1,25(OH)2D3remarkably increased mitochondrial superoxide dismutase (mSOD) of U-937 cells, TNF alone increased it only slightly and 1,25(OH)2D3alone did not. The cytosolic SOD (cSOD) activity was not changed by TNF or/and 1.25(OH)2D3. The mSOD activity was not inhibited by 2 mM KCN, suggesting that mSOD should be a manganase SOD (MnSOD). These results suggest that 1,25(OH)2D3may reduce the susceptibility to TNF cytotoxicity of U-937 cells by enhancing the ability of inducing MnSOD by TNF.

The effects of dibromochloropropane (DBCP), a pesticide, on the male rat reproductive system were examined at morphological and hormonal expression levels. Changes of Leydig cells and seminiferous tubules were examined in rats treated with one subcutaneous (s.c.) injection of DBCP at doses of 10, 50, 75 and 100 mg/kg of body weight. The Leydig cells degenerated and decreased in number in those rats with an s.c. injection of DBCP at a dose of 50 mg/kg of body weight. However, these morphological changes were not significant in those rats that were treated with four separate s.c. injections of DBCP at 10 mg/kg of body weight. The expression of luteinizing hormone receptor mRNA, which is specifically expressed in Leydig cells, was decreased significantly in the DBCP-treated rats as compared with the normal-control rats. The expression of follicle-stimulating hormone receptor mRNA was decreased to a mild degree in DBCP-treated rats. At a dose of 75 mg/kg of body weight, seminiferous tubules as well as Leydig cells were severely damaged morphologically and at hormonal receptor expression levels. Multinucleated giant cells appeared at a dose of 75 mg/kg of body weight. All the rats died at a dose of 100 mg/kg of body weight. Our data indicate that DBCP had a cytotoxic effect on the male rat reproductive system in a dose-dependent manner.

Human myelogenous leukaemic cells can be induced to differentiate into the monocyte/macrophage pathway by protein inducers called differentiation inducing factors (DIF) in conditioned media of mitogen–stimulated human peripheral blood leukocytes1–8. However, human DIF has not yet been well characterized. DIF is known to be a T-cell lymphokine, as it can be obtained from the T-cell line HUT-1027and can be partially purified from medium conditioned by phytohaemagglutinin (PHA)–stimulated lymphocytes8. We found that monocytes also produce factor(s) that induce differentiation of human myelogenous leukaemia cell lines to cells with macrophage-like characteristics. This factor(s) has activity different from that of colony–stimulating factor(s) or interferons9. We have now purified a DIF to homogeneity from medium conditioned by PHA–stimulated leukocytes using a human myeloblastic leukemia cell line, ML-110, as target cells. The purified DIF has a relative molecular mass (Mr) of approximately 17,000, with an NH2-terminal sequence the same as that of human tumour necrosis factor (TNF). Recombinant human TNF (rHuTNF) induces differentiation of ML-1 cells and an anti-pDIF monoclonal antibody can neutralize both differentiation inducing activity and cytotoxic activity of DIF and rHuTNF. The findings indicate that one of the DIF(s) produced by leukocytes is probably TNF.

This paper reports novel, non-epitaxial raised source/drain (S/D) approaches to decrease the parasitic external resistance in complementary metal--oxide--semiconductor field-effect transistors (CMOSFETs) fabricated on ultrathin silicon on insulator (UTSOI). This technique utilizes a metal Schottky S/D process with dopant segregation. Selectively formed NiSi2with dopant segregation fabricated by laser-spike annealing (LSA) significantly lowered effective Shottky-barrier height and, thereby, lowered contact resistance ($\rho_{\text{c}}$). Satisfying the requirements of UTSOI MOSFETs in the 32-nm node for low stand-by power (LSTP) application, external parasitic resistance was reduced to 140 (NMOS) and 350 (PMOS) $\Omega$ μm. Our results show that $\rho_{\text{c}}$ is an important component of parasitic resistance in terms of improving device performance of UTSOI MOSFETs.

Irregular breathing can influence the outcome of 4D computed tomography imaging and cause artifacts. Visual biofeedback systems associated with a patient-specific guiding waveform are known to reduce respiratory irregularities. In Japan, abdomen and chest motion self-control devices (Abches) (representing simpler visual coaching techniques without a guiding waveform) are used instead; however, no studies have compared these two systems to date. Here, we evaluate the effectiveness of respiratory coaching in reducing respiratory irregularities by comparing two respiratory management systems. We collected data from 11 healthy volunteers. Bar and wave models were used as visual biofeedback systems. Abches consisted of a respiratory indicator indicating the end of each expiration and inspiration motion. Respiratory variations were quantified as root mean squared error (RMSE) of displacement and period of breathing cycles. All coaching techniques improved respiratory variation, compared with free-breathing. Displacement RMSEs were 1.43 ± 0.84, 1.22 ± 1.13, 1.21 ± 0.86 and 0.98 ± 0.47 mm for free-breathing, Abches, bar model and wave model, respectively. Period RMSEs were 0.48 ± 0.42, 0.33 ± 0.31, 0.23 ± 0.18 and 0.17 ± 0.05 s for free-breathing, Abches, bar model and wave model, respectively. The average reduction in displacement and period RMSE compared with the wave model were 27% and 47%, respectively. For variation in both displacement and period, wave model was superior to the other techniques. Our results showed that visual biofeedback combined with a wave model could potentially provide clinical benefits in respiratory management, although all techniques were able to reduce respiratory irregularities.

1,2-Thiazetidines 2and 3were synthesized by the reactions of anti- and syn-9,9'-bibenzonorbornenylidenes with TsNSO, followed by deimination with SmI2. Heating 2and 3neat produced a mixture containing aziridines, thiiranes, and alkenes.

Deformable image registration (DIR) is fundamental technique for adaptive radiotherapy and image-guided radiotherapy. However, further improvement of DIR is still needed. We evaluated the accuracy of B-spline transformation-based DIR implemented in elastix. This registration package is largely based on the Insight Segmentation and Registration Toolkit (ITK), and several new functions were implemented to achieve high DIR accuracy. The purpose of this study was to clarify whether new functions implemented in elastix are useful for improving DIR accuracy. Thoracic 4D computed tomography images of ten patients with esophageal or lung cancer were studied. Datasets for these patients were provided by DIR-lab (dir-lab.com) and included a coordinate list of anatomical landmarks that had been manually identified. DIR between peak-inhale and peak-exhale images was performed with four types of parameter settings. The first one represents original ITK (Parameter 1). The second employs the new function of elastix (Parameter 2), and the third was created to verify whether new functions improve DIR accuracy while keeping computational time (Parameter 3). The last one partially employs a new function (Parameter 4). Registration errors for these parameter settings were calculated using the manually determined landmark pairs. 3D registration errors with standard deviation over all cases were 1.78 (1.57), 1.28 (1.10), 1.44 (1.09) and 1.36 (1.35) mm for Parameter 1, 2, 3 and 4, respectively, indicating that the new functions are useful for improving DIR accuracy, even while maintaining the computational time, and this B-spline-based DIR could be used clinically to achieve high-accuracy adaptive radiotherapy.

We evaluated the accuracy of one commercially available and three publicly available deformable image registration (DIR) algorithms for thoracic four-dimensional (4D) computed tomography (CT) images. Five patients with esophagus cancer were studied. Datasets of the five patients were provided by DIR-lab (dir-lab.com) and consisted of thoracic 4D CT images and a coordinate list of anatomical landmarks that had been manually identified. Expert landmark correspondence was used for evaluating DIR spatial accuracy. First, the manually measured displacement vector field (mDVF) was obtained from the coordinate list of anatomical landmarks. Then the automatically calculated displacement vector field (aDVF) was calculated by using the following four DIR algorithms: B-spine implemented in Velocity AI (Velocity Medical, Atlanta, GA, USA), free-form deformation (FFD), Horn–Schunk optical flow (OF) and Demons in DIRART of MATLAB software. Registration error is defined as the difference between mDVF and aDVF. The mean 3D registration errors were 2.7 ± 0.8 mm for B-spline, 3.6 ± 1.0 mm for FFD, 2.4 ± 0.9 mm for OF and 2.4 ± 1.2 mm for Demons. The results showed that reasonable accuracy was achieved in B-spline, OF and Demons, and that these algorithms have the potential to be used for 4D dose calculation, automatic image segmentation and 4D CT ventilation imaging in patients with thoracic cancer. However, for all algorithms, the accuracy might be improved by using the optimized parameter setting. Furthermore, for B-spline in Velocity AI, the 3D registration error was small with displacements of less than ∼10 mm, indicating that this software may be useful in this range of displacements.

We evaluated radiation-induced myocardial damage using iodine-123 β-methyl-iodophenyl pentadecanoic acid (I-123 BMIPP) scintigraphy. Between May 2010 and April 2011 we performed I-123 BMIPP scintigraphy for patients who had maintained complete response to curative radiotherapy (RT) for esophageal cancer for more than six months. We compared the area of the myocardium in the RT fields with that of reduced I-123 BMIPP uptake using a 15-segment model that is based on axial computed tomography (CT) images. We classified the segments into three categories: segments receiving 40 Gy (Segment 40 Gy), segments receiving 60 Gy (Segment 60 Gy) and segments out of the radiation fields (Segment 0 Gy). A segment with reduced uptake in the RT fields was defined as positive. A total of 510 segments in 34 patients were used for analysis. The median interval from completion of RT to I-123 BMIPP scintigraphy was 22 months (range, 6–103 months). The numbers of Segment 0 Gy, Segment 40 Gy and Segment 60 Gy were 324, 133 and 53, respectively. Reduced uptake was detected in 42.9% (57/133) of Segment 40 Gy, 67.9% (36/53) of Segment 60 Gy and 13.3% (43/324) of Segment 0 Gy. The odds ratios of 40 Gy and 60 Gy compared with regions out of the RT fields were 5.2 (95% confidence interval [CI]: 3.7–7.4) and 15.4 (95% CI: 6.9–34.6), respectively. Reduced myocardial I-123 BMIPP uptake in RT fields, suggesting RT-induced myocardial damage, was frequently observed. I-123 BMIPP myocardial scintigraphy may be useful for identifying RT-induced myocardial damage.

Caution in handling ceramic nanoparticles is required by workers and consumers if they are to be used safely and profitably. The small size of nanoparticles can bestow high reactivity and unique translocational properties. Studies have shown that exposure to some types of nanoparticles affects the respiratory, cardiovascular and central nervous systems and various organs. When pregnant mice were exposed to nanoparticles, various organs of offspring are also affected. Our recent studies showed that prenatal exposure to nanoparticles (carbon black and titanium dioxide) causes long-term adverse effects on the reproductive, respiratory and central nervous systems of offspring. The effects of nanoparticles on fetuses and children and the possibility of them leading to the onset of diseases in adulthood are of concern. Thus, it is important to research the risk of unintentional exposure to nanoparticles, including ceramic nanoparticles, from the environment and to attempt to identify methods to protect against their toxicity.

Review: 42 refs.

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