Temperature Dependence of the FIR Reflectance of LaSrGaO4

The reflectance of single crystal LaSrGaO4 has been measured from approx 50 to 40000 cm^-1 along the "a" and "c" axis. The optical properties have been calculated from a Kramers-Kronig analysis of the reflectance for both polarizations. The reflectance curves have been fit using a product of Lorentzian oscillators.Comment: 12 pages including 5 figures and 2 tables. Latex file, Requires elsart.sty file and eps

Feasibility and Efficacy of Definitive Radiotherapy with 66 Gy and Concurrent Carboplatin-Paclitaxel Chemotherapy for Stage III Non-Small Cell Lung Cancer.

Purpose/Objectives : This study was conducted to assess the feasibility and efficacy of definitive radiotherapy (RT) with a total dose of 66 Gy and concurrent carboplatin-paclitaxel chemotherapy for patients (pts) with stage Ⅲ non-small celllung cancer. Materials/Methods : Between April 2007 and December 2013，99 pts with non-small cell lung cancer were treated using RT with concurrent carboplatin-paclitaxel chemotherapy in our hospital. Sixty-eight of them received RT with a total dose of 66 Gy. We analyzed 46 Stage Ⅲ pts who had been treated with RT using three-dimensional radiotherapy treatment planning. The prophylactic mediastinal lymph nodes were included in the clinical target volume for RT. The survival rate after the start of RT was estimated using the Kaplan-Meier method. We estimated the cumulative local failure and distant metastasis rates with the Fine-Gray method. Adverse events were evaluated according to the CTCAE (v.4.0). Results : The median age of the pts was 70.9 (52.8-78.7) years old (y.o.). The performance status (PS) of each pt was fairly good (ECOG PS 0: 25, PS 1: 20, PS 3:1), and their clinical stages (UICC 7th) were twenty-nine Ⅲ A and seventeen Ⅲ B. Diagnoses were pathologically confirmed in 32 pts. The median follow-up period was 35.7 (2.0-82.2) months among all pts, and 55.9 (40.1-82.2) months among survivors. The 3- and 5-year Kaplan-Meier overall survival rates were 52.2 and 34.0%，respectively, and the median survival time was 36.6 months. The 3- and 5-year Kaplan-Meier progression-free survival rates were 29.1 and 21.9%，respectively, and the median progression-free survival time was 9.9 months. The 5-year local failure rate was 37.6%, and the 5-year distant metastasis rate was 49.7%. Sixteen (34.8%) pts required steroid administration because of radiation pneumonitis (CTCAE Grade 2 or higher) and two of them died (Grade 5). No other severe non-hematologic toxicity (Grade 3 or higher) was observed. Conclusion : These results suggest that definitive RT with a total dose of 66 Gy and concurrent carboplatin-paclitaxel chemotherapy is feasible and may be promising for pts with Stage Ⅲ non-small cell lung cancer

Ⅲ期非小細胞肺癌に対するカルボプラチン・パクリタキセル同時併用66Gy放射線治療の安全性と有効性について

Purpose/Objectives: This study was conducted to assess the feasibility and efficacy of definitive radiotherapy (RT) with a total dose of 66Gy and concurrent carboplatin-paclitaxel chemotherapy for patients (pts) with stage Ⅲ non-small cell lung cancer. Materials/Methods: Between April 2007 and December 2013, 99 pts with non-small cell lung cancer were treated by RT with concurrent carboplatin-paclitaxel chemotherapy in our hospital. Sixty-eight of them received RT with a total dose of 66Gy. We analyzed 46 Stage Ⅲ pts who had been treated with RT using three-dimensional radiotherapy treatment planning. The prophylactic mediastinal lymph nodes were included in the clinical target volume of RT. The survival rate after the beginning of RT was estimated using the Kaplan-Meier method. We estimated the cumulative local failure and distant metastasis rates with the Fine-Gray method. Adverse events were evaluated according to the CTCAE (v.4.0). Results: The median age of the pts was 70.9 (52.8-78.7) years old (y.o.). The performance status (PS) of each pt was fairly good (ECOG PS 0: 25, PS 1: 20, PS3:1), and clinical stages (UICC 7th) consisted of twenty-nine ⅢA and seventeen ⅢB. Diagnoses were pathologically confirmed in 32　pts. The median follow-up period　was 35.7 (2.0-82.2) months among all pts, and 55.9 (40.1-82.2) months among survivors. The 3- and 5-year　Kaplan-Meier overall survival rates were 52.2 and 34.0%, respectively, and the median survival time was 36.6 months. The 3- and 5-year Kaplan-Meier progression-free survival rates were 29.1 and 21.9%, respectively, and the median progression-free survival time was 9.9 months. The 5-year local failure rate was 37.6%, and the 5-year distant metastasis rate was 49.7%. Sixteen (34.8%) pts required steroid administration because of radiation pneumonitis (CTCAE Grade 2 or higher) and two of them died (Grade 5). No other severe non-hematologic toxicity (Grade 3 or higher) was observed. Conclusion: These results suggest that definitive RT with a total dose of 66Gy and concurrent carboplatin-paclitaxel chemotherapy is feasible and may be promising for pts with Stage Ⅲ non-small cell lung cancer.博士（医学）・甲第663号・平成29年3月15

脳幹部転移性脳腫瘍に対する寡分割定位放射線治療の治療成績

Background: To assess the neuroimaging and clinical outcomes in patients with brainstem metastasis (BSM) treated with linac-based fractionated stereotactic radiotherapy (fSRT) with a micro-multileaf collimator. Methods: Between May 2007 and January 2017, 24 patients (15 male and 9 female) with BSM (25 lesions: midbrain, 10; pons, 13; and medulla oblongata, 2) were consecutively treated with linac-based fSRT. BSM originated from the lung (n = 18, 75.0%), colon (n = 3, 12.5%), and breast (n = 3, 12.5%). The median patient age was 67.0 (range: 42-80) years. Recursive partition analysis classified 2 patients as class I, 17 as class II, and 5 as class III. Overall survival was calculated using the Kaplan-Meier method. Results: Tumor volume ranged from 0.01 to 7.49 cm3 (median: 0.233 cm3), and patients were treated with a dose of 24-40 Gy in 7-13 fractions. The median OS was 9 months after fSRT (95% confidence interval 4.104-13.896). Large tumor volume, presence of brainstem-related symptoms, poor pretreatment Karnofsky performance status, and recursive partition analysis class III were significantly associated with low overall survival. Tumor volume decreased in 18 metastatic lesions, remained stable in 6, and increased in 1. No patient exhibited permanent radiation injury. Grade 2 nausea and vomiting according to the Common Terminology Criteria for Adverse Events 4.0 occurred in 1 patient who received corticosteroids. Conclusions: Linac-based fSRT with a micro-multileaf collimator delivered in the doses of 24-40 Gy in 7-13 fractions is a safe and effective local therapy for patients with BSM.博士（医学）・乙第1450号・令和2年3月16日Copyright © 2019 Elsevier Inc. All rights reserved

Carboplatin-Paclitaxel Chemoradiotherapy With 66 Gy For Elderly Patients With Locally Advanced Non-Small-Cell Lung Cancer.

Background/ Aim: The common radiation dose administered with chemoradiotherapy for stage III non-small-cell lung cancer (NSCLC) is 60 Gy. We aimed to examine the feasibility and effectiveness of carboplatin-paclitaxel chemoradiotherapy with 66 Gy for elderly NSCLC patients. Patients and Methods: Forty-five patients with stage III NSCLC were enrolled from 2011 to 2014 at our hospital. They were divided into three groups according to their status and underwent different treatments. Overall survival (OS), progression-free survival (PFS), and local control (LC) were determined. Toxicity was evaluated with NCI-CTCAE ver. 4.0; intergroup differences were analysed statistically. Results: The group receiving carboplatin-paclitaxel chemotherapy with 66 Gy showed the longest median OS (40.4 months), PFS (17.9 months), and LC (44.3 months). Toxicity was acceptable in all groups. Conclusion: For elderly patients with stage III NSCLC, carboplatin-paclitaxel chemoradiotherapy with 66 Gy is suggested to be feasible and effective

Expression of immunoregulatory molecules by thyrocytes protects nonobese diabetic-H2h4 mice from developing autoimmune thyroiditis.

One approach to prevent tissue destruction by autoimmune attack in organ-specific autoimmune diseases is to protect the target tissue from autoimmune reaction, regardless of its persistent activity. To provide proof-of-principle for the feasibility of this approach, the immunoregulatory molecules, TNF-related apoptosis-inducing ligand (TRAIL) and indoleamine 2, 3-dioxygenase, were expressed in the thyroid glands using adenovirus vector in nonobese diabetic-H2(h4) mice that spontaneously develop thyroiditis. Mice were anesthetized, and the thyroid glands were exposed by neck dissection, followed by in situ infection with adenovirus vector (5 x 10(10) particles per mouse) twice or thrice, starting 1 d or 4 wk before mice were supplied with sodium iodine (NaI) water. After 8 wk NaI provision, the extent of thyroiditis, serum titers of antithyroglobulin antibodies, and cytokine expression in the spleen were examined. In situ infection of adenovirus expressing TRAIL or indoleamine 2, 3-dioxygenase, but not green fluorescent protein, significantly suppressed thyroiditis scores. However, antithyroglobulin antibody titers and expression levels of cytokines (interferon-gamma and IL-4) in the spleen remained unaltered. Importantly, adenovirus infection 4 wk after NaI provision was also effective at suppressing thyroiditis. The suppressive effect of TRAIL appears to be mediated at least partly by accumulation of CD4(+)Foxp3(+) regulatory T cells into the thyroid glands. Thus, localized expression of immunoregulatory molecules efficiently protected the thyroid glands from autoimmune attack without changing the systemic autoimmunity in nonobese diabetic-H2(h4) mice. This kind of immunological intervention, although it does not suppress autoimmune reactivity, may have a potential for treating organ-specific autoimmune diseases

The Putative Liquid-Liquid Transition is a Liquid-Solid Transition in Atomistic Models of Water

We use numerical simulation to examine the possibility of a reversible liquid-liquid transition in supercooled water and related systems. In particular, for two atomistic models of water, we have computed free energies as functions of multiple order parameters, where one is density and another distinguishes crystal from liquid. For a range of temperatures and pressures, separate free energy basins for liquid and crystal are found, conditions of phase coexistence between these phases are demonstrated, and time scales for equilibration are determined. We find that at no range of temperatures and pressures is there more than a single liquid basin, even at conditions where amorphous behavior is unstable with respect to the crystal. We find a similar result for a related model of silicon. This result excludes the possibility of the proposed liquid-liquid critical point for the models we have studied. Further, we argue that behaviors others have attributed to a liquid-liquid transition in water and related systems are in fact reflections of transitions between liquid and crystal

Combined insulin B:9-23 self-peptide and polyinosinic-polycytidylic acid accelerate insulitis but inhibit development of diabetes by increasing the proportion of CD4+Foxp3+ regulatory T cells in the islets in non-obese diabetic mice.

Insulin peptide B:9-23 is a major autoantigen in type 1 diabetes. Combined treatment with B:9-23 peptide and polyinosinic-polycytidylic acid (poly I:C), but neither alone, induce insulitis in normal BALB/c mice. In contrast, the combined treatment accelerated insulitis, but prevented diabetes in NOD mice. Our immunofluorescence study with anti-CD4/anti-Foxp3 revealed that the proportion of Foxp3 positive CD4(+)CD25(+) regulatory T cells (Tregs) was elevated in the islets of NOD mice treated with B:9-23 peptide and poly I:C, as compared to non-treated mice. Depletion of Tregs by anti-CD25 antibody hastened spontaneous development of diabetes in non-treated NOD mice, and abolished the protective effect of the combined treatment and conversely accelerated the onset of diabetes in the treated mice. These results indicate that poly I:C combined with B:9-23 peptide promotes infiltration of both pathogenic T cells and predominantly Tregs into the islets, thereby inhibiting progression from insulitis to overt diabetes in NOD mice

The Role of Regulatory T Cells in Cancer

There has been an explosion of literature focusing on the role of regulatory T (Treg) cells in cancer immunity. It is becoming increasingly clear that Treg cells play an active and significant role in the progression of cancer, and have an important role in suppressing tumor-specific immunity. Thus, there is a clear rationale for developing clinical strategies to diminish their regulatory influences, with the ultimate goal of augmenting antitimor immunity. Therefore, manipulation of Treg cells represent new strategies for cancer treatment. In this Review, I will summarize and review the explosive recent studies demonstrating that Treg cells are increased in patients with malignancies and restoration of antitumor immunity in mice and humans by depletion or reduction of Treg cells. In addition, I will discuss both the prognostic value of Treg cells in tumor progression in tumor-bearing hosts and the rationale for strategies for therapeutic vaccination and immunotherapeutic targeting of Treg cells with drugs and microRNA