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Xinru Wei, Yunxin Lai, Jin Li, Le Qin, Youdi Xu, Ruocong Zhao, Baiheng Li, Simiao Lin, Suna Wang, Qiting Wu, Qiubin Liang, Muyun Peng, Fenglei Yu, Yangqiu Li, Xuchao Zhang, Yilong Wu, Pentao Liu, Duanqing Pei, Yao Yao, Peng Li
In recent years, immunotherapies, such as those involving chimeric antigen receptor (CAR) T cells, have become increasingly promising approaches to non-small-cell lung cancer (NSCLC) treatment. In this study, we explored the antitumor potential of prostate stem cell antigen (PSCA)-redirected CAR T and mucin 1 (MUC1)-redirected CAR T cells in tumor models of NSCLC. First, we generated patient-derived xenograft (PDX) mouse models of human NSCLC that maintained the antigenic profiles of primary tumors. Next, we demonstrated the expression of PSCA and MUC1 in NSCLC, followed by the generation and confirmation of the specificity and efficacy of PSCA- and MUC1-targeting CAR T cells against NSCLC cell lines in vitro...
2017: Oncoimmunology
Anja Feldmann, Claudia Arndt, Ralf Bergmann, Simon Loff, Marc Cartellieri, Dominik Bachmann, Roberta Aliperta, Mirjam Hetzenecker, Florian Ludwig, Susann Albert, Pauline Ziller-Walter, Alexandra Kegler, Stefanie Koristka, Sebastian Gärtner, Marc Schmitz, Armin Ehninger, Gerhard Ehninger, Jens Pietzsch, Jörg Steinbach, Michael Bachmann
New treatment options especially of solid tumors including for metastasized prostate cancer (PCa) are urgently needed. Recent treatments of leukemias with chimeric antigen receptors (CARs) underline their impressive therapeutic potential. However CARs currently applied in the clinics cannot be repeatedly turned on and off potentially leading to severe life threatening side effects. To overcome these problems, we recently described a modular CAR technology termed UniCAR: UniCAR T cells are inert but can be turned on by application of one or multiple target modules (TMs)...
February 21, 2017: Oncotarget
Le Qin, Yunxin Lai, Ruocong Zhao, Xinru Wei, Jianyu Weng, Peilong Lai, Baiheng Li, Simiao Lin, Suna Wang, Qiting Wu, Qiubin Liang, Yangqiu Li, Xuchao Zhang, Yilong Wu, Pentao Liu, Yao Yao, Duanqing Pei, Xin Du, Peng Li
BACKGROUND: Multiple iterations of chimeric antigen receptors (CARs) have been developed, mainly focusing on intracellular signaling modules. However, the effect of non-signaling extracellular modules on the expansion and therapeutic efficacy of CARs remains largely undefined. METHODS: We generated two versions of CAR vectors, with or without a hinge domain, targeting CD19, mesothelin, PSCA, MUC1, and HER2, respectively. Then, we systematically compared the effect of the hinge domains on the growth kinetics, cytokine production, and cytotoxicity of CAR T cells in vitro and in vivo...
March 13, 2017: Journal of Hematology & Oncology
Meng Cai, Shuyang Dai, Wanqing Chen, Changfa Xia, Lingeng Lu, Shuguang Dai, Jun Qi, Minjie Wang, Meilin Wang, Lanping Zhou, Fuhua Lei, Tingting Zuo, Hongmei Zeng, Xiaohang Zhao
Gene-environment interactions may increase gastric cancer (GC) risk. Seven susceptibility loci identified by genome-wide association studies (GWASs) suggest that genetic factors play a role in gastric carcinogenesis. Meanwhile, Helicobacter pylori (H. pylori) infection, smoking, and alcohol drinking are also important environmental factors for gastric cancer. However, studies to explore the role of gene-environment interactions in gastric carcinogenesis, and particularly the relationship between the seven susceptibility loci and their potential interactions with H...
March 2017: Cancer Medicine
Ghulam Hussain, Debbie S Silvester
The voltammetric detection of less than 1 ppm of ammonia gas in the room temperature ionic liquid (RTIL) 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([C2mim][NTf2]) is demonstrated using low-cost planar electrode devices. Three commercially available planar devices were employed, all with platinum (Pt) working electrodes: a thin-film electrode (TFE), a screen-printed electrode (SPE), and a microarray thin film electrode (MATFE), along with an "ideal" conventional Pt microdisk electrode for comparison...
December 20, 2016: Analytical Chemistry
Somala Mohammed, Sujita Sukumaran, Pradip Bajgain, Norihiro Watanabe, Helen E Heslop, Cliona M Rooney, Malcolm K Brenner, William E Fisher, Ann M Leen, Juan F Vera
The adoptive transfer of T cells redirected to tumor-associated antigens via transgenic expression of chimeric antigen receptors (CARs) has produced tumor responses, even in patients with refractory diseases. To target pancreatic cancer, we generated CAR T cells directed against prostate stem cell antigen (PSCA) and demonstrated specific tumor lysis. However, pancreatic tumors employ immune evasion strategies such as the production of inhibitory cytokines, which limit CAR T cell persistence and function...
January 4, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
Lee Il-Seok, Pil Seo Sung, Sok Ha Yun, Jeong Pildu, Won Kang Ho, Tae Kim Won, Kim Yong-June, Joong Yun Seok, Cheol Lee Sang, Kim Wun-Jae
Prostate stem cell antigen (PSCA) is a cell-membrane glycoprotein consisting of 123 amino acids and highly expressed in the prostate, but there have been few reports on the relationship between rs2294008 of PSCA and prostate cancer in the literature. Therefore, we evaluated the association between rs2294008 and the risk of prostate cancer. A total of 240 prostate cancer patients and 306 controls (patients with benign prostatic hyperplasia) were enrolled. Genotype analysis of rs2294008 of PSCA was performed using PCR...
January 19, 2017: Journal of Biomedical Research
Fatemeh Kaveh, Lars O Baumbusch, Daniel Nebdal, Anne-Lise Børresen-Dale, Ole Christian Lingjærde, Hege Edvardsen, Vessela N Kristensen, Hiroko K Solvang
BACKGROUND: Detection and localization of genomic alterations and breakpoints are crucial in cancer research. The purpose of this study was to investigate, in a methodological and biological perspective, different female, hormone-dependent cancers to identify common and diverse DNA aberrations, genes, and pathways. METHODS: In this work, we analyzed tissue samples from patients with breast (n = 112), ovarian (n = 74), endometrial (n = 84), or cervical (n = 76) cancer...
November 22, 2016: BMC Cancer
Noureddine Hadji
When the value of the dispersion coefficient is "greatly different from 0.5," as is the case for "free-electron" materials such as sodium (Na), the approximate expression for the volume plasmon critical wave vector (PCV) used by Hadji stops being valid and a different, more precise, expression must be used. Here a more accurate PCV formula is used to get a more accurate expression for plasmon scattering cross-section per atom (PSCA) species. This PSCA is then employed to calculate some physical quantities for several "free-electron" materials and together with the techniques from the quoted paper to determine values for physical quantities from amorphous silicon (a-Si) experimental data...
December 2016: Microscopy and Microanalysis
T J Mai, R Ma, Z Li, S C Bi
Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a negative regulator of T cell activation, which competes with CD28 for B7.1/B7.2 binding, and which has a greater affinity. Fusion of specific antigens to extracellular domain of CTLA4 represents a promising approach to increase the immunogenicity of DNA vaccines. In this study, we evaluated this interesting approach for CTLA4 enhancement on prostate stem cell antigen (PSCA)-specific immune responses and its anti-tumor effects in a prostate cancer mouse model...
October 24, 2016: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Kristine M Mayle, Kathryn R Dern, Vincent K Wong, Kevin Y Chen, Shijun Sung, Ke Ding, April R Rodriguez, Scott Knowles, Zachary Taylor, Z Hong Zhou, Warren S Grundfest, Anna M Wu, Timothy J Deming, Daniel T Kamei
Currently, there is no curative treatment for advanced metastatic prostate cancer, and options, such as chemotherapy, are often nonspecific, harming healthy cells and resulting in severe side effects. Attaching targeting ligands to agents used in anticancer therapies has been shown to improve efficacy and reduce nonspecific toxicity. Furthermore, the use of triggered therapies can enable spatial and temporal control over the treatment. Here, we combined an engineered prostate cancer-specific targeting ligand, the A11 minibody, with a novel photothermal therapy agent, polypeptide-based gold nanoshells, which generate heat in response to near-infrared light...
September 22, 2016: Journal of Laboratory Automation
Anxing Shan, Xianghua Xu, Zongmao Cheng
Sensing coverage is a fundamental problem in wireless sensor networks (WSNs), which has attracted considerable attention. Conventional research on this topic focuses on the 0/1 coverage model, which is only a coarse approximation to the practical sensing model. In this paper, we study the target coverage problem, where the objective is to find the least number of sensor nodes in randomly-deployed WSNs based on the probabilistic sensing model. We analyze the joint detection probability of target with multiple sensors...
August 27, 2016: Sensors
Sung Han Kim, Weon Seo Park, Bo Ram Park, Jungnam Joo, Jae Young Joung, Ho Kyung Seo, Jinsoo Chung, Kang Hyun Lee
Prostate cancer is the second most common male cancer, with half of all patients going on to develop metastases. To better identify patients at high risk for prostate cancer progression and reduce prostate cancer-related mortality, improved prognostic factors are required. In this study, we used immunohistochemistry (IHC) to determine the prognostic values of multiple tissue biomarkers in hormone-naοve prostatectomy specimens of prostate cancer. Using 510 prostatectomy specimens collected between 2002 and 2012, IHC analysis was performed for Cerb-2, Cyclin D1, VEGF, EGFR, Rb, PSCA, p53, Bcl-2, Cox-2, PMS2, and Ki-67 on formalin-fixed paraffin-embedded sections...
May 27, 2016: Asian Journal of Andrology
Jiajia Yuan, Yanyan Li, Tiantian Tian, Na Li, Yan Zhu, Jianling Zou, Jing Gao, Lin Shen
Recent genomewide studies have identified several germline variations associated with gastric cancer. The aim of the present study was to identify, in a Chinese Han population, the individual and combined effects of those single nucleotide polymorphisms (SNPs) that increase the risk of early-onset gastric cancer. We conducted a case-control study comprising 116 patients with gastric cancer as well as 102 sex- and age-matched controls and confirmed that the SNPs MUC1 (mucin 1) rs9841504 and ZBTB20 (zinc finger and BTB domain containing 20) rs4072037 were associated with an increased gastric cancer risk...
June 7, 2016: Oncotarget
Vienna Ludovini, Fortunato Bianconi, Annamaria Siggillino, Danilo Piobbico, Jacopo Vannucci, Giulio Metro, Rita Chiari, Guido Bellezza, Francesco Puma, Maria Agnese Della Fazia, Giuseppe Servillo, Lucio Crinò
Risk assessment and treatment choice remains a challenge in early non-small-cell lung cancer (NSCLC). The aim of this study was to identify novel genes involved in the risk of early relapse (ER) compared to no relapse (NR) in resected lung adenocarcinoma (AD) patients using a combination of high throughput technology and computational analysis. We identified 18 patients (n.13 NR and n.5 ER) with stage I AD. Frozen samples of patients in ER, NR and corresponding normal lung (NL) were subjected to Microarray technology and quantitative-PCR (Q-PCR)...
May 24, 2016: Oncotarget
Meng Wang, Xijing Wang, Sidney W Fu, Xinghan Liu, Tianbo Jin, Huafeng Kang, Xiaobin Ma, Shuai Lin, Haitao Guan, Shuqun Zhang, Kang Liu, Cong Dai, Yuyao Zhu, Zhijun Dai
This study explored the associations between common PSCA single-nucleotide polymorphisms (rs2294008, rs2978974, and rs2976392) and breast cancer among 560 breast cancer cases and 583 controls (Chinese Han women). We found rs2294008 was significantly associated with a high risk of breast cancer (homozygote model, odds ratio [OR]: 1.67, 95% confidence interval [CI]: 1.06-2.59; recessive, OR: 1.64, 95% CI: 1.06-2.53). And stratification by menopausal status revealed an association of the minor allele of rs2294008 with breast cancer risk among premenopausal (homozygote model, OR: 2...
May 10, 2016: Oncotarget
Shizhi Wang, Shenshen Wu, Haixia Zhu, Bo Ding, Yunlang Cai, Jing Ni, Qiang Wu, Qingtao Meng, Xin Zhang, Chengcheng Zhang, Xiaobo Li, Meilin Wang, Rui Chen, Hua Jin, Zhengdong Zhang
Recently, three genome-wide association studies have identified the PSCA (prostate stem cell antigen) rs2294008 polymorphism (C > T) associated with susceptibility to gastric cancer, bladder cancer, and duodenal ulcers, highlighting its critical role in disease pathogenesis. Given PSCA is reported to be overexpressed in cervical cancer and the rs2294008 can influence PSCA transcription, we aimed to determine the role of rs2294008 in susceptibility to cervical cancer. The genotyping was performed in the 1126 cases and 1237 controls...
March 22, 2016: Scientific Reports
Sung Han Kim, Weon Seo Park, Sun Ho Kim, Boram Park, Jungnam Joo, Geon Kook Lee, Jae Young Joung, Ho Kyung Seo, Jinsoo Chung, Kang Hyun Lee
We aimed to identify tissue biomarkers that predict early biochemical recurrence (BCR) in patients with high-risk prostate cancer (PC), toward the goal of increasing the benefits of neoadjuvant hormonal therapy (NHT). In 2005-2012, prostatectomy specimens were collected from 134 PC patients who had received NHT and radical prostatectomy. The expression of 13 tissue biomarkers was assessed in the specimens via immunohistochemistry. Time to BCR and factors predictive of BCR were determined by using the Cox proportional hazards model...
2016: PloS One
Ran Kang, Shankun Zhao, Luhao Liu, Futian Li, Ermao Li, Lianmin Luo, Lihua Xu, ShawPong Wan, Zhigang Zhao
BACKGROUND: Prostate stem cell antigen (PSCA) expression has been shown to correlate with prostatic carcinogenesis and prostate cancer (PCa) progression. The underlying mechanisms for these processes are currently unknown. Epithelial to mesenchymal transition (EMT) has been associated with the invasiveness and the distant metastasis of PCa. In this study, we investigated the effects of knocking down the PSCA on the cell migration, the invasiveness, and the EMT of the PCa cell line DU145 in vitro and in vivo...
2016: Cancer Cell International
Junqiao Lee, Debbie S Silvester
A robust, miniaturised electrochemical gas sensor for oxygen (O2) has been constructed using a commercially available Pt microarray thin-film electrode (MATFE) with a gellified electrolyte containing the room temperature ionic liquid (RTIL) 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([C2mim][NTf2]) and poly(methyl methacrylate) (PMMA) in a 50 : 50 mass ratio. Diffusion coefficients and solubilities for oxygen in mixtures of PMMA/RTIL at different PMMA doping concentrations (0-50% mass) were derived from potential step chronoamperometry (PSCA) on a Pt microdisk electrode...
June 21, 2016: Analyst
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