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Purpose We aimed to develop a new breast-immobilizing system for proton beam therapy (PBT) of early breast cancer (EBC) that would provide the optimum breast shape during the treatment as well as increased fixation reliability by reducing the influence of respiratory movement. Methods The breast-immobilizing system (HyBIS; hybrid breast-immobilizing system) consists of a whole body immobilization system (WBIS), position-converting device (to change patient position), photo-scanning system, breast cup (made using a three-dimensional printer), breast cup-fitting apparatus, breast cup-holding device (to ensure the breast remains lifted in the supine position), and dedicated stretcher fixed to the WBIS (to carry the patient). We conducted a phantom experiment to evaluate the effect of the HyBIS on breast immobilization during the respiratory cycle. Thirteen markers were embedded in the right breast of a female phantom that simulated respiratory thoracic movement at an amplitude of 15 mm, and their displacements on four-dimensional computed tomography were compared between conditions with and without immobilization by HyBIS. Results When immobilization was applied with the HyBIS, breast protrusion was maintained in the phantom in the supine treatment position. The mean values of the anteroposterior, superoinferior, lateral, and three-dimensional (3D) displacement of the markers were 2.7 ± 1.7, 0.3 ± 0.5, 0.9 ± 0.8, and 3.1 ± 1.6 mm with HyBIS, and 5.5 ± 2.9, 0.6 ± 0.8, 0.5 ± 0.4, and 5.6 ± 2.9 mm without HyBIS, respectively; thus, the anteroposterior ( P = 0.014) and 3D ( P = 0.007) displacements significantly improved with HyBIS. Conclusions We demonstrated that the HyBIS can help retain the protruded breast shape in the supine position during treatment and can reduce the influence of respiratory movement. Thus, the HyBIS can help to reliably and precisely perform PBT for EBC. [ABSTRACT FROM AUTHOR]

ABSTRACT In mammals, ventricular walls of the developing brain maintain a neurogenic niche, in which radial glial cells act as neural stem cells (NSCs) and generate new neurons in the embryo. In the adult brain, the neurogenic niche is maintained in the ventricular-subventricular zone (V-SVZ) of the lateral wall of lateral ventricles and the hippocampal dentate gyrus. In the neonatal V-SVZ, radial glial cells transform into astrocytic postnatal NSCs and multiciliated ependymal cells. On the other hand, in zebrafish, radial glial cells continue to cover the surface of the adult telencephalic ventricle and maintain a higher neurogenic potential in the adult brain. However, the cell composition of the neurogenic niche of the aged zebrafish brain has not been investigated. Here we show that multiciliated ependymal cells emerge in the neurogenic niche of the aged zebrafish telencephalon. These multiciliated cells appear predominantly in the dorsal part of the ventral telencephalic ventricular zone, which also contains clusters of migrating new neurons. Scanning electron microscopy and live imaging analyses indicated that these multiple cilia beat coordinately and generate constant fluid flow within the ventral telencephalic ventricle. Analysis of the cell composition by transmission electron microscopy revealed that the neurogenic niche in the aged zebrafish contains different types of cells, with ultrastructures similar to those of ependymal cells, transit-amplifying cells, and migrating new neurons in postnatal mice. These data suggest that the transformation capacity of radial glial cells is conserved but that its timing is different between fish and mice. J. Comp. Neurol. 524:2982-2992, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background Altered fractionation radiotherapy (RT) improves locoregional control in head and neck cancer without aggravation of late adverse events. To improve successful larynx-preservation rates in patients with resectable, intermediate-volume hypopharyngeal cancer, a prospective trial of chemotherapy-enhanced accelerated RT was conducted. Methods Patients with T2 to T4 hypopharyngeal cancer received 40 Gray (Gy)/4 weeks to the entire neck followed by boost RT administering 30 Gy/2 weeks (1.5 Gy twice-daily fractionation). Cisplatin and 5-fluorouracil were administered concomitantly only during boost RT. Results Thirty-five patients were enrolled in this study. All patients completed this protocol as planned. After a median follow-up period for surviving patients of 59 months (24-90 months), overall survival and local control rates at 3 years were 91% (95% confidence interval, 81% to 100%), and 88% (79% to 99%), respectively. All surviving patients maintained normalcy of diets. Conclusion This regimen was feasible with encouraging oncological and functional outcomes. © 2011 Wiley Periodicals, Inc. Head Neck, 2011 [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to develop a new calculation algorithm that is satisfactory in terms of the requirements for both accuracy and calculation time for a simulation of imaging of the proton-irradiated volume in a patient body in clinical proton therapy. Methods: The activity pencil beam algorithm (APB algorithm), which is a new technique to apply the pencil beam algorithm generally used for proton dose calculations in proton therapy to the calculation of activity distributions, was developed as a calculation algorithm of the activity distributions formed by positron emitter nuclei generated from target nuclear fragment reactions. In the APB algorithm, activity distributions are calculated using an activity pencil beam kernel. In addition, the activity pencil beam kernel is constructed using measured activity distributions in the depth direction and calculations in the lateral direction. 12C, 16O, and 40Ca nuclei were determined as the major target nuclei that constitute a human body that are of relevance for calculation of activity distributions. In this study, 'virtual positron emitter nuclei' was defined as the integral yield of various positron emitter nuclei generated from each target nucleus by target nuclear fragment reactions with irradiated proton beam. Compounds, namely, polyethylene, water (including some gelatin) and calcium oxide, which contain plenty of the target nuclei, were irradiated using a proton beam. In addition, depth activity distributions of virtual positron emitter nuclei generated in each compound from target nuclear fragment reactions were measured using a beam ON-LINE PET system mounted a rotating gantry port (BOLPs-RGp). The measured activity distributions depend on depth or, in other words, energy. The irradiated proton beam energies were 138, 179, and 223 MeV, and measurement time was about 5 h until the measured activity reached the background level. Furthermore, the activity pencil beam data were made using the activity pencil beam kernel, which was composed of the measured depth data and the lateral data including multiple Coulomb scattering approximated by the Gaussian function, and were used for calculating activity distributions. Results: The data of measured depth activity distributions for every target nucleus by proton beam energy were obtained using BOLPs-RGp. The form of the depth activity distribution was verified, and the data were made in consideration of the time-dependent change of the form. Time dependence of an activity distribution form could be represented by two half-lives. Gaussian form of the lateral distribution of the activity pencil beam kernel was decided by the effect of multiple Coulomb scattering. Thus, the data of activity pencil beam involving time dependence could be obtained in this study. Conclusions: The simulation of imaging of the proton-irradiated volume in a patient body using target nuclear fragment reactions was feasible with the developed APB algorithm taking time dependence into account. With the use of the APB algorithm, it was suggested that a system of simulation of activity distributions that has levels of both accuracy and calculation time appropriate for clinical use can be constructed. [ABSTRACT FROM AUTHOR]

The article presents research on the in vivo application of manganese ion enhanced magnetic resonance imaging (MRI). It relates that a low affinity chelate reagents was used to reduce free Mn2+ concentration. It explains that Mn-bicine showed a tendency for better contractility when employed with an isolated perfused frog heart. It concludes that Mn-bicine is a better choice for maintaining the vital conditions of experimental animals.

The aim of the present study was to determine the maximum tolerated dose (MTD) of S-1 in combination with chemoradiotherapy (CRT) in patients with unresectable locally advanced squamous cell carcinoma of the head and neck, and evaluate the difference in pharmacokinetics of S-1 when administered as a suspension via a feeding tube or orally as a capsule. Chemotherapy consisted of administration of S-1 twice daily on days 1-14 at escalating doses of 40, 60 and 80 mg/m per day, and cisplatin at 20 mg/m per day on days 8-11, repeated twice at a 5-week interval. Single daily radiation of 70 Gy in 35 fractions was given concurrently starting on day 1. Two additional cycles of chemotherapy were planned after the completion of CRT. Before starting CRT, each patient received S-1 via two different administration methods. Twenty-two patients were enrolled. The MTD was reached with S-1 at 80 mg/m per day, with two of six patients experiencing febrile neutropenia lasting more than 4 days. All four patients whose creatinine clearance was decreased to <60 mL/min after the first cycle of chemotherapy developed febrile neutropenia lasting more than 4 days. Pharmacokinetic analysis revealed that the 5-fluorouracil area under the curve did not significantly differ by the administration route. S-1 at 60 mg/m per day for 14 days was well tolerated with concurrent CRT. Administration of S-1 as a suspension or by whole capsule can be considered therapeutically interchangeable. Although these data are preliminary, activity was highly promising, and this approach warrants further investigation. ( Cancer Sci 2011; 102: 419-424) [ABSTRACT FROM AUTHOR]

Purpose: Respiration-gated irradiation for a moving target requires a longer time to deliver single fraction in proton radiotherapy (PRT). Ultrahigh dose rate (UDR) proton beam, which is 10-100 times higher than that is used in current clinical practice, has been investigated to deliver daily dose in single breath hold duration. The purpose of this study is to investigate the survival curve and relative biological effectiveness (RBE) of such an ultrahigh dose rate proton beam and their linear energy transfer (LET) dependence. Methods: HSG cells were irradiated by a spatially and temporally uniform proton beam at two different dose rates: 8 Gy/min (CDR, clinical dose rate) and 325 Gy/min (UDR, ultrahigh dose rate) at the Bragg peak and 1.75 (CDR) and 114 Gy/min (UDR) at the plateau. To study LET dependence, the cells were positioned at the Bragg peak, where the absorbed dose-averaged LET was 3.19 keV/μm, and at the plateau, where it was 0.56 keV/μm. After the cell exposure and colony assay, the measured data were fitted by the linear quadratic (LQ) model and the survival curves and RBE at 10% survival were compared. Results: No significant difference was observed in the survival curves between the two proton dose rates. The ratio of the RBE for CDR/UDR was 0.98±0.04 at the Bragg peak and 0.96±0.06 at the plateau. On the other hand, Bragg peak/plateau RBE ratio was 1.15±0.05 for UDR and 1.18±0.07 for CDR. Conclusions: Present RBE can be consistently used in treatment planning of PRT using ultrahigh dose rate radiation. Because a significant increase in RBE toward the Bragg peak was observed for both UDR and CDR, further evaluation of RBE enhancement toward the Bragg peak and beyond is required. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to verify the characteristics of the positron emitter nuclei generated at each treatment site by proton irradiation. Methods: Proton therapy using a beam on-line PET system mounted on a rotating gantry port (BOLPs-RGp), which the authors developed, is provided at the National Cancer Center Kashiwa, Japan. BOLPs-RGp is a monitoring system that can confirm the activity distribution of the proton irradiated volume by detection of a pair of annihilation gamma rays coincidentally from positron emitter nuclei generated by the target nuclear fragment reactions between irradiated proton nuclei and nuclei in the human body. Activity is measured from a start of proton irradiation to a period of 200 s after the end of the irradiation. The characteristics of the positron emitter nuclei generated in a patient’s body were verified by the measurement of the activity distribution at each treatment site using BOLPs-RGp. Results: The decay curves for measured activity were able to be approximated using two or three half-life values regardless of the treatment site. The activity of half-life value of about 2 min was important for a confirmation of the proton irradiated volume. Conclusions: In each proton treatment site, verification of the characteristics of the generated positron emitter nuclei was performed by using BOLPs-RGp. For the monitoring of the proton irradiated volume, the detection of 15O generated in a human body was important. [ABSTRACT FROM AUTHOR]

Background: The efficacy and safety of chemotherapy with irinotecan plus docetaxel were retrospectively evaluated for olfactory neuroblastoma.Methods: Twelve patients with histologically proven advanced or metastatic olfactory neuroblastoma were treated with chemotherapy with irinotecan plus docetaxel at the study institution between 2001 and 2005. Of these, 7 patients with locoregional disease and no prior radiotherapy received irinotecan plus docetaxel followed by definitive radiotherapy, 1 with photon radiotherapy and 6 with proton radiotherapy, whereas 3 patients with distant metastases and 2 with locoregional disease who had received prior radiotherapy received irinotecan plus docetaxel only.Results: The most common toxicities of >or=grade 3 among the 12 patients receiving irinotecan plus docetaxel were leukopenia (33%), neutropenia (50%), febrile neutropenia (8%), and diarrhea (25%), all of which were manageable. Partial response was achieved in 3 patients, giving an overall response rate of 25%. The response rate was higher in patients aged <50 years (3 of 4 patients) compared with those aged >50 years (0 of 8 patients) (P = .018). With a median follow-up period of 22.2 months, the median progression-free survival and overall survival were 13.6 months and 36.6 months, respectively. Of the 7 patients with locoregional disease also receiving definitive radiotherapy, the 2-year survival rate was 100% and 6 patients were alive at the time of last follow-up.Conclusions: Chemotherapy for olfactory neuroblastoma with irinotecan plus docetaxel is safe and manageable. Patients aged <50 years may be sensitive to chemotherapy. Induction chemotherapy followed by definitive radiotherapy may represent a promising option for patients with locally advanced olfactory neuroblastoma. [ABSTRACT FROM AUTHOR]

Background: Olfactory neuroblastoma is a rare sino-nasal tumor arising from the olfactory epithelium and is often characterized by local invasion or metastasis. The role of chemotherapy in the treatment of this tumor is unclear. The purpose of this study was to review our institution’s experience of chemotherapy for advanced or recurrent olfactory neuroblastoma. Methods: Twenty-one patients with histologically proven olfactory neuroblastoma were treated at our institution between 1992 and 2002. Twelve of these patients received chemotherapy in the setting of unresectable or recurrent disease and were retrospectively reviewed for clinical characteristics, treatment outcome or survival. Results: Eight patients of the 12 patients received cisplatin-based chemotherapy and the remaining four patients received chemotherapy consisting of docetaxel plus irinotecan (three patients) or cyclophosphamide, doxorubicin, and vincristine (1 patient). A partial response was achieved in five patients, with an overall response rate of 42%, although the chemotherapeutic regimens were heterogeneous. Two partial responses were obtained among the three patients who received docetaxel plus irinotecan. The response rate to chemotherapy was 83% in the younger age group (<40 years), as opposed to 0% in the older age group (≥40 years), and the difference between the two groups was statistically significant ( P = 0.02). Conclusion: Our study indicated that olfactory neuroblastoma would be sensitive to chemotherapy, especially with young patients. Docetaxel plus irinotecan has the possibility of showing favorable response, and warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy is often used to treat patients with unresectable advanced hepatocellular carcinoma (HCC). The present study examines the nature and frequency of adverse events with respect to liver function in such patients after radiotherapy. Methods: Forty-six patients with HCC who underwent radiotherapy were retrospectively examined. Radiotherapy was applied using coplanar 2–3-beam arrangements to a target dose of 50 Gy/5 weeks. The adverse hepatic events were evaluated according to the National Cancer Institute Common Toxicity Criteria and the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme during the acute phase and the late phase by following the patients for up to 1 year. The influence on survival by adverse hepatic events and other factors was analyzed. Results: The full irradiation dose of 50 Gy was given to 40 patients (87.0%). Grade 3 or 4 toxicity was observed in 18 (39.1%) within 3 months after radiotherapy and in 11 (33.3%) of 33 thereafter, respectively. The most frequent and serious adverse events were hyperbilirubinemia, hypoalbuminemia, and ascites. The independent adverse prognostic factors for survival were portal vein tumor thrombus ( P = 0.0012), tumor response ( P = 0.011), acute adverse hepatic event ( P = 0.012), and late adverse hepatic event ( P = 0.015). Conclusions: Hypoalbuminemia, hyperbilirubinemia, and ascites were important hepatic adverse events that developed after applying radiotherapy to treat advanced HCC. These adverse events seriously affected survival. [ABSTRACT FROM AUTHOR]

The 31P NMR localised method was used to study the metabolism of phospholipid and high energy phosphate in the prefrontal cortex. The spectra were taken from patients with schizophrenia (11 males) receiving neuroleptic medication, and were compared to normal controls (15 males). Their spectral intensities were analysed using a non-linear least-squares method with a prior knowledge of the fixed chemical shifts and linewidths, leading to further resolution into resonances of glycerophosphorylethanolamine (GPE), glycerophosphorylcholine (GPC), phosphorylethanolamine (PE) and phosphorylcholine (PC). The metabolite concentrations were calculated referring to the spectral intensities of phosphate phantoms with known concentrations. T1 values of phantom and cerebrum were estimated from a series of localised inversion recovery spectra to correct for the signal saturation effects. The schizophrenic patients showed an increased concentration of GPC but not GPE, PE or PC. Furthermore, no difference was observed regarding the concentration of high-energy phosphates such as phosphocreatine, inorganic phosphate and ATP. The patients did not show any differences in mitochondrial function such as phosphorylation potential and the ratio of the rate of ATP synthesis. Thus, an increase in GPC concentration in the prefrontal cortex could be characteristic of the pathophysiology of schizophrenia with mild negative symptoms. [ABSTRACT FROM AUTHOR]

The (31)P NMR localised method was used to study the metabolism of phospholipid and high energy phosphate in the prefrontal cortex. The spectra were taken from patients with schizophrenia (11 males) receiving neuroleptic medication, and were compared to normal controls (15 males). Their spectral intensities were analysed using a non-linear least-squares method with a prior knowledge of the fixed chemical shifts and linewidths, leading to further resolution into resonances of glycerophosphorylethanolamine (GPE), glycerophosphorylcholine (GPC), phosphorylethanolamine (PE) and phosphorylcholine (PC). The metabolite concentrations were calculated referring to the spectral intensities of phosphate phantoms with known concentrations. T1 values of phantom and cerebrum were estimated from a series of localised inversion recovery spectra to correct for the signal saturation effects. The schizophrenic patients showed an increased concentration of GPC but not GPE, PE or PC. Furthermore, no difference was observed regarding the concentration of high-energy phosphates such as phosphocreatine, inorganic phosphate and ATP. The patients did not show any differences in mitochondrial function such as phosphorylation potential and the ratio of the rate of ATP synthesis. Thus, an increase in GPC concentration in the prefrontal cortex could be characteristic of the pathophysiology of schizophrenia with mild negative symptoms.