Immunotherapy for Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma have been frustrating to treat, with slow progress made on extending survival. Immunotherapy targeting immune checkpoints, T cells, and infiltrating lymphocytes has shown promise in early studies. The efficacy of pembrolizumab and nivolumab is encouraging. Anti-chemokine receptors and oncolytic viruses are also making headway against these stubborn tumors; improved results when immune checkpoint inhibitors are combined with radiation therapy are eagerly anticipated. Adoptive T cell therapy and vaccines are also under development. The importance of a multidisciplinary approach cannot be emphasized enough

Phase effects from the general neutrino Yukawa matrix on lepton flavor violation

We examine contributions from Majorana phases to lepton flavor violating processes in the framework of the minimal supersymmetric standard model with heavy right-handed neutrinos. All phases in the complex neutrino Yukawa matrix are taken into account in our study. We find that in the scenario with universal soft-breaking terms sizable phase effects can appear on the lepton flavor violating processes such as $\mu \to e \gamma$, $\tau \to e \gamma$, and $\tau \to \mu \gamma$. In particular, the branching ratio of $\mu \to e \gamma$ can be considerably enhanced due to the Majorana phases, so that it can be much greater than that of $\tau \to \mu \gamma$.Comment: 14 pages, 4 eps figures, revtex

Safety and Antitumor Activity of the Anti–Programmed Death-1 Antibody Pembrolizumab in Patients With Advanced Esophageal Carcinoma

Purpose The anti–programmed death-1 antibody pembrolizumab was evaluated in KEYNOTE-028, a multicohort, phase IB study of patients with programmed death ligand-1 (PD-L1)–positive advanced solid tumors. Results from the esophageal carcinoma cohort are reported herein. Patients and Methods Eligible patients with squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction in whom standard therapy failed and who had PD-L1–positive tumors received pembrolizumab 10 mg/kg every 2 weeks for up to 2 years or until confirmed disease progression or intolerable toxicity. Response was assessed every 8 weeks up to 6 months and every 12 weeks thereafter. Primary end points were safety and overall response rate, determined by investigator review per Response Evaluation Criteria in Solid Tumors (version 1.1). Results Among 83 patients with esophageal carcinoma and samples evaluable for PD-L1 expression, 37 (45%) had PD-L1–positive tumors, and 23 were enrolled. Median age was 65 years; 78% had squamous histology; and 87% received ≥ two prior therapies for advanced/metastatic disease. As of the data cutoff (February 20, 2017), median follow-up was 7 months (range, 1 to 33 months). Nine patients (39%) experienced treatment-related adverse events, most commonly decreased appetite, decreased lymphocyte count, generalized rash, and rash (two patients [9%] each). No grade 4 adverse events or deaths were attributed to pembrolizumab. Overall response rate was 30% (95% CI, 13% to 53%); median duration of response was 15 months (range, 6 to 26 months). A six-gene interferon-γ gene expression signature analysis suggested that delayed progression and increased response occur among pembrolizumab-treated patients with higher interferon-γ composite scores. Conclusion Pembrolizumab demonstrated manageable toxicity and durable antitumor activity in patients with heavily pretreated, PD-L1–positive advanced esophageal carcinoma

AKARI infrared imaging of reflection nebulae IC4954 and IC4955

We present the observations of the reflection nebulae IC4954 and IC4955 region with the Infrared Camera (IRC) and the Far-Infrared Surveyor (FIS) on board the infrared astronomical satellite AKARI during its performance verification phase. We obtained 7 band images from 7 to 160um with higher spatial resolution and higher sensitivities than previous observations. The mid-infrared color of the S9W (9um) and L18W (18um) bands shows a systematic variation around the exciting sources. The spatial variation in the mid-infrared color suggests that the star-formation in IC4954/4955 is progressing from south-west to north-east. The FIS data also clearly resolve two nebulae for the first time in the far-infrared. The FIS 4-band data from 65um to 160um allow us to correctly estimate the total infrared luminosity from the region, which is about one sixth of the energy emitted from the existing stellar sources. Five candidates for young stellar objects have been detected as point sources for the first time in the 11um image. They are located in the red S9W to L18W color regions, suggesting that current star-formation has been triggered by previous star-formation activities. A wide area map of the size of about 1 x 1 (deg^2) around the IC4954/4955 region was created from the AKARI mid-infrared all-sky survey data. Together with the HI 21cm data, it suggests a large hollow structure of a degree scale, on whose edge the IC4954/4955 region has been created, indicating star formation over three generations in largely different spatial scales.Comment: 23 pages, 7 figures, accepted for publication in PASJ AKARI special issu

Construction of possible integrated predictive index based on EGFR and ANXA3 polymorphisms for chemotherapy response in fluoropyrimidine-treated Japanese gastric cancer patients using a bioinformatic method

Selected genetic and clinical parameters of gastric cancer patients. (XLS 33 kb

An efficient and generic reversible debugger using the virtual machine based approach

The reverse execution of programs is a function where pro-grams are executed backward in time. A reversible debugger is a debugger that provides such a functionality. In this pa-per, we propose a novel reversible debugger that enables reverse execution of programs written in the C language. Our approach takes the virtual machine based approach. In this approach, the target program is executed on a special virtual machine. Our contribution in this paper is two-fold. First, we propose an approach that can address problems of (1) compatibility and (2) efficiency that exist in previous works. By compatibility, we mean that previous debuggers are not generic, i.e., they support only a special language or special intermediate code. Second, our approach provides two execution modes: the native mode, where the debuggee is directly executed on a real CPU, and the virtual ma-chine mode, where the debuggee is executed on a virtual machine. Currently, our debugger provides four types of trade-off settings (designated by unit and optimization) to consider trade-offs between granularity, accuracy, overhead and memory requirement. The user can choose the appro-priate setting flexibly during debugging without finishing and restarting the debuggee

ANIR : Atacama Near-Infrared Camera for the 1.0-m miniTAO Telescope

We have developed a near-infrared camera called ANIR (Atacama Near-InfraRed camera) for the University of Tokyo Atacama Observatory 1.0m telescope (miniTAO) installed at the summit of Cerro Chajnantor (5640 m above sea level) in northern Chile. The camera provides a field of view of 5'.1 $\times$ 5'.1 with a spatial resolution of 0".298 /pixel in the wavelength range of 0.95 to 2.4 $\mu$m. Taking advantage of the dry site, the camera is capable of hydrogen Paschen-$\alpha$ (Pa$\alpha$, $\lambda=$1.8751 $\mu$m in air) narrow-band imaging observations, at which wavelength ground-based observations have been quite difficult due to deep atmospheric absorption mainly from water vapor. We have been successfully obtaining Pa$\alpha$ images of Galactic objects and nearby galaxies since the first-light observation in 2009 with ANIR. The throughputs at the narrow-band filters ($N1875$, $N191$) including the atmospheric absorption show larger dispersion (~10%) than those at broad-band filters (a few %), indicating that they are affected by temporal fluctuations in Precipitable Water Vapor (PWV) above the site. We evaluate the PWV content via the atmospheric transmittance at the narrow-band filters, and derive that the median and the dispersion of the distribution of the PWV are 0.40+/-0.30 mm for $N1875$ and 0.37+/-0.21 mm for $N191$, which are remarkably smaller (49+/-38% for $N1875$ and 59+/-26% for $N191$) than radiometry measurements at the base of Cerro Chajnantor (5100 m alt.). The decrease in PWV can be explained by the altitude of the site when we assume that the vertical distribution of the water vapor is approximated at an exponential profile with scale heights within 0.3-1.9 km (previously observed values at night). We thus conclude that miniTAO/ANIR at the summit of Cerro Chajnantor indeed provides us an excellent capability for a "ground-based" Pa$\alpha$ observation.Comment: 14 pages, 12 figures, 5 tables, Publications of the Astronomical Society of Japan (in press

Trifluridine/tipiracil versus placebo for third or later lines of treatment in metastatic gastric cancer: an exploratory subgroup analysis from the TAGS study

Metastatic gastric cancer; Overall survival; Trifluridine/tipiracilCàncer gàstric metastàtic; Supervivència global; Trifluridina/tipiracilCáncer gástrico metastásico; Supervivencia global; Trifluridina/tipiraciloBackground Metastatic gastric cancer and cancer of the esophagogastric junction (GC/EGJ) is an aggressive disease with poor prognosis. In the TAGS study, trifluridine/tipiracil (FTD/TPI) improved overall survival (OS) compared with placebo in heavily pre-treated patients. This unplanned, exploratory subgroup analysis of the TAGS study aimed to clarify outcomes when FTD/TPI was used as third-line (3L) treatment and fourth- or later-line (4L+) treatment. Patients and methods Patients were divided into a 3L group (126 and 64 in FTD/TPI and placebo arms, respectively) and 4L+ group (211 and 106 in FTD/TPI and placebo arms, respectively). Endpoints included OS, progression-free survival (PFS), time to Eastern Cooperative Oncology Group performance status (ECOG PS) deterioration to ≥2, and safety. Results Baseline characteristics were generally well balanced between FTD/TPI and placebo for 3L and 4L+ treatment. Median OS (mOS) for FTD/TPI versus placebo was: 6.8 versus 3.2 months {hazard ratio (HR) [95% confidence interval (CI)] = 0.68 (0.47-0.97), P = 0.0318} in the 3L group; and 5.2 versus 3.7 months [0.73 (0.55-0.95), P = 0.0192] in the 4L+ group. Median PFS for FTD/TPI versus placebo was 3.1 versus 1.9 months [0.54 (0.38-0.77), P = 0.0004] in the 3L group; and 1.9 versus 1.8 months [0.57 (0.44-0.74), P < 0.0001] in the 4L+ group. Time to deterioration of ECOG PS to ≥2 for FTD/TPI versus placebo was 4.8 versus 2.0 months [HR (95% CI) = 0.60 (0.42-0.86), P = 0.0049] in the 3L group; and 4.0 versus 2.5 months [0.75 (0.57-0.98), P = 0.0329] in the 4L+ group. The safety of FTD/TPI was consistent in all subgroups. Conclusions This analysis confirms the efficacy and safety of FTD/TPI in patients with GC/EGJ in third and later lines with a survival benefit that seems slightly superior in 3L treatment. When FTD/TPI is taken in 3L as recommended in the international guidelines, physicians can expect to provide patients with an mOS of 6.8 months.The TAGS study was funded by Taiho Oncology and Taiho Pharmaceutical (no grant number). This exploratory subgroup analysis was funded by Servier (no grant number)

Model-Based Space Robot Teleoperation of ETS-VII Manipulator

application/pdf学術論文 (Article)653324 bytesjournal articl

Efficacy and safety of trifluridine/tipiracil in older and younger patients with metastatic gastric or gastroesophageal junction cancer: subgroup analysis of a randomized phase 3 study (TAGS)

Age groups; Gastrointestinal neoplasms; TrifluridineGrupos de edad; Neoplasias gastrointestinales; TrifluridinaGrups d'edat; Neoplàsies gastrointestinals; TrifluridinaBackground Trifluridine and tipiracil (FTD/TPI) demonstrated survival benefit vs placebo and manageable safety in previously treated patients with metastatic gastric/gastroesophageal junction cancer (mGC/GEJC) in the randomized, placebo-controlled, phase 3 TAGS study. This subgroup analysis of TAGS examined efficacy/safety outcomes by age. Methods In TAGS, patients with mGC/GEJC and ≥ 2 prior therapies were randomized (2:1) to receive FTD/TPI 35 mg/m2 or placebo, plus best supportive care. A preplanned subgroup analysis was performed to evaluate efficacy and safety outcomes in patients aged < 65, ≥ 65, and ≥ 75 years. Results Among 507 randomized patients (n = 337 FTD/TPI; n = 170 placebo), 55%, 45%, and 14% were aged < 65, ≥ 65, and ≥ 75 years, respectively. Overall survival hazard ratios for FTD/TPI vs placebo were 0.67 (95% CI 0.51–0.89), 0.73 (95% CI 0.52–1.02), and 0.67 (95% CI 0.33–1.37) in patients aged < 65, ≥ 65, and ≥ 75 years, respectively. Regardless of age, patients receiving FTD/TPI experienced improved progression-free survival and stayed longer on treatment than those receiving placebo. Among FTD/TPI-treated patients, frequencies of any-cause grade ≥ 3 adverse events (AEs) were similar across age subgroups (80% each), although grade ≥ 3 neutropenia was more frequent in older patients [40% (≥ 65 and ≥ 75 years); 29% (< 65 years)]; AE-related discontinuation rates did not increase with age [14% (< 65 years), 12% (≥ 65 years), and 12% (≥ 75 years)]. Conclusions The results of this subgroup analysis show the efficacy and tolerability of FTD/TPI treatment regardless of age in patients with mGC/GEJC who had received 2 or more prior treatments.This study was sponsored by Taiho Oncology, Inc., and Taiho Pharmaceuticals Co., Ltd. Professional medical writing and editorial assistance were provided by Vasupradha Vethantham, PhD, and Jennifer L. Robertson, PhD, at Ashfield MedComms, an Ashfield Health company, funded by Taiho Oncology, Inc