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De-shen Wang,1,* Xiao-li Wei,1,* Zhi-qiang Wang,1,* Yun-xin Lu,1 Si-mei Shi,1 Niu Wang,1 Miao-zhen Qiu,1 Feng-hua Wang,1 Rong-jiao Wang,2 Yu-hong Li,1 Rui-hua Xu1 1Department of Medical Oncology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 2Oncology BU, BGI-Shenzhen, Shenzhen, China *These authors contributed equally to this work Abstract: Trastuzumab has substantial antitumor activity in metastatic gastric cancer. Onesuch mechanism by which it exerts its antitumor activity is antibody-dependent cell-mediated cytotoxicity, which has been reported to be influenced by FcγRIIA and IIIA polymorphisms. This study is the first to assess their impact on trastuzumab efficacy in patients with metastatic gastric cancer. We retrospectively examined 42 Her-2-positive patients receiving fluorouracil and platinum-based chemotherapy and trastuzumab, and 68 Her-2-negative patients receiving fluorouracil and platinum-based chemotherapy only as the first-line treatment. FcγRIIA andIIIA polymorphisms were assessed, and their associations with efficacy in both settings were analyzed. In patients treated with trastuzumab, the FcγRIIA H/H genotype was associated with significantly superior progression-free survival (PFS) (hazard ratio [HR] [95% CI]: 0.36 [0.16–0.82], adjusted HR [95% CI]: 0.18 [0.07–0.48], P=0.001). When combining FcγRIIA and IIIA polymorphisms, the FcγRIIA H/H or FcγRIIIA V/V genotype was associated with a significantly improved disease control rate (P=0.04) and PFS (HR [95% CI]: 0.29 [0.13–0.67], adjusted HR [95% CI]: 0.17 [0.07–0.45], P

Abiraterone acetate, a drug that blocks endogenous androgen synthesis, plus prednisone is indicated for metastatic castration-resistant prostate cancer. We evaluated the clinical benefit of abiraterone acetate plus prednisone with androgen-deprivation therapy in patients with newly diagnosed, metastatic, castration-sensitive prostate cancer. In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 1199 patients to receive either androgen-deprivation therapy plus abiraterone acetate (1000 mg daily, given once daily as four 250-mg tablets) plus prednisone (5 mg daily) (the abiraterone group) or androgen-deprivation therapy plus dual placebos (the placebo group). The two primary end points were overall survival and radiographic progression-free survival. After a median follow-up of 30.4 months at a planned interim analysis (after 406 patients had died), the median overall survival was significantly longer in the abiraterone group than in the placebo group (not reached vs. 34.7 months) (hazard ratio for death, 0.62; 95% confidence interval [CI], 0.51 to 0.76; P

Resolving distributed attacks benefits from collaboration between networks. We present three approaches for the same multi-domain defensive action that can be applied in such an alliance: 1) Counteract Everywhere, 2) Minimize Countermeasures, and 3) Minimize Propagation. First, we provide a formula to compute efficiency of a defense; then we use this formula to compute the efficiency of the approaches under various circumstances. Finally, we discuss how task execution order and timing influence defense efficiency. Our results show that the Minimize Propagation approach is the most efficient method when defending against the chosen attack.

Dong Qian,1 Jingjing Cheng,1 Xiaofeng Ding,1 Xiuli Chen,1 Xi Chen,1 Yong Guan,1 Bin Zhang,2 Jiefu Wang,3 Puchun Er,1 Minghan Qiu,1 Xianliang Zeng,1 Yihang Guo,1 Huanhuan Wang,1 Lujun Zhao,1 Dan Xie,4 Zhiyong Yuan,1 Ping Wang,1 Qingsong Pang1 1Department of Radiotherapy, 2Department of Lung Cancer, 3Department of Colorectal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 4State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou, People’s Republic of China Abstract: PinX1 plays positive and negative roles in the maintenance of telomerase and telomeres, as well as in tumorigenesis. The aim of the present study was to investigate the expression and clinical significance of PinX1 in colorectal carcinoma (CRC) and to determine the effect of PinX1 on CRC cell proliferation and apoptosis. A total of 86 CRC patients treated with radical resection and 5-fluorouracil-based adjuvant chemotherapy were enrolled in this study. The expression dynamics of PinX1 was detected by immunohistochemistry in the CRC patients and 25 normal colonic mucosa controls. PinX1 expression was significantly reduced in tumor tissues as compared to normal tissues, and the rate of PinX1 protein low/negative expression in CRC and normal tissues was 60% (52/86) and 24% (6/25), respectively (P=0.037). In addition, PinX1 downregulation was significantly associated with short overall survival (P=0.016) and disease-free survival (P=0.042) in CRC patients. Cox proportional hazards model further revealed that PinX1 expression was an independent factor in predicting overall survival and disease-free survival for CRC patients. Furthermore, we demonstrated that ectopic overexpression of PinX1 in CRC cells inhibited their proliferation, promoted apoptosis, repressed telomerase activity, and induced telomere shortening. These findings suggest that PinX1 may be a prognostic biomarker for CRC patients’ survival and that it inhibits cell proliferation and promotes apoptosis by repressing telomerase activity and inducing telomere shortening. Targeting PinX1 may therefore provide a novel therapeutic strategy for CRC patients. Keywords: colorectal carcinoma, PinX1, cell proliferation, apoptosis, telomerase, telomere, prognostic biomarker

ObjectiveTo investigate whether the mitochondrial DNA content could predict the embryo viabilityDesignRetrospective analysis.SettingReproductive genetics laboratoryPatient(s)A total of 421 biopsied samples obtained from 129 patientsIntervention(s)Embryo biopsies samples underwent whole genome amplification (WGA) and were tested by next generation sequencing (NGS) and array Comparative Genomic Hybridization (aCGH), 30 samples were selected randomly to undergo quantitative real-time polymerase chain reaction (qPCR).Main Outcome Measure(s)Those embryos which obtained the consistent chromosome status determined both aCGH and NGS platform were further classified. We investigated the relationship of mtDNA content with several factors including female patient age, embryo morphology, chromosome status, and live birth rate of both blastocysts and blastomeres.Result(s)A total of 386 (110 blastomeres and 276 blastocysts) out of 399 embryos showed consistent chromosome status outcome. We found no statistically difference was observed in aneuploid and euploid blastocysts (p=0.14), the same phenomenon was observed in aneuploid and euploid blastomeres (p=0.89). Similarly, the mtDNA content was independent of female patient age, embryo morphology and live birth rate.Conclusion(s)The mtDNA content did not provide a reliable prediction of the viability of blastocysts to initiate a pregnancy.

Copyright © 2018 American Chemical Society. Metasurfaces offer unparalleled functionalities for controlling the propagation and properties of electromagnetic waves. But to transfer these functions to technological applications, it is critical to render them tunable and to enable fast control by external stimuli. In most cases, this has been realized by utilizing tunable materials combined with a top-down nanostructuring process, which is often complicated and time intensive. Here we present a novel strategy for fabricating a tunable metasurface comprising epitaxially grown nanobeams of a phase transition material, vanadium dioxide. Without the need for extensive nanolithographic fabrication, we prepared a large-area (>1 cm2), deep-subwavelength (thickness of ∼Λ/40) nanostructured thin film that can control light transmission with large modulation depth, exceeding 9 dB across all telecommunication wavelength bands. Furthermore, the transmission in the "on" state remains higher than 80% from near- to mid-infrared region. This renders our metasurface useful also as a phase-shifting element, which we demonstrate by carrying out cross-polarized transmission measurements. To provide insights about the relationship between metasurface morphology and its resulting optical properties, we perform full-field three-dimensional numerical simulations as a function of width, height, and edge-to-edge separation of the epitaxial VO2 nanobeams.

Qixing Mao,1–3,* Mantang Qiu,1–3,* Gaochao Dong,3 Wenjie Xia,1–3 Shuai Zhang,1,3 Youtao Xu,1,3 Jie Wang,3 Yin Rong,1,3 Lin Xu,1,3 Feng Jiang1,3 1Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Institute of Jiangsu Province, 2Fourth Clinical College of Nanjing Medical University, 3Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, People’s Republic of China *These authors contributed equally to this work Abstract: The association between polymorphic CAG repeats in the androgen receptor gene in women and breast cancer susceptibility has been studied extensively. However, the conclusions regarding this relationship remain conflicting. The purpose of this meta-analysis was to identify whether androgen receptor CAG repeat lengths were related to breast cancer susceptibility. The MEDLINE, PubMed, and EMBASE databases were searched through to December 2014 to identify eligible studies. Data and study quality were rigorously assessed by two investigators according to the Newcastle-Ottawa Quality Assessment Scale. The publication bias was assessed by the Begg’s test. Seventeen eligible studies were included in this meta-analysis. The overall analysis suggested no association between CAG polymorphisms and breast cancer risk (odds ratio [OR] 1.031, 95% confidence interval [CI] 0.855–1.245). However, in the subgroup analysis, we observed that long CAG repeats significantly increased the risk of breast cancer in the Caucasian population (OR 1.447, 95% CI 1.089–1.992). Additionally, the risk was significantly increased in Caucasian women carrying two alleles with CAG repeats ≥22 units compared with those with two shorter alleles (OR 1.315, 95% CI 1.014–1.707). These findings suggest that long CAG repeats increase the risk of breast cancer in Caucasian women. However, larger scale case-control studies are needed to validate our results. Keywords: androgen, CAG repeat polymorphism, women, breast cancer, risk, meta-analysis