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Prostate stem cell antigen

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https://www.readbyqxmd.com/read/29123951/characterization-of-a-switchable-chimeric-antigen-receptor-platform-in-a-pre-clinical-solid-tumor-model
#1
Elham Pishali Bejestani, Marc Cartellieri, Ralf Bergmann, Armin Ehninger, Simon Loff, Michael Kramer, Johannes Spehr, Antje Dietrich, Anja Feldmann, Susann Albert, Martin Wermke, Michael Baumann, Mechthild Krause, Martin Bornhäuser, Gerhard Ehninger, Michael Bachmann, Malte von Bonin
The universal modular chimeric antigen receptor (UniCAR) platform redirects CAR-T cells using a separated, soluble targeting module with a short half-life. This segregation allows precise controllability and flexibility. Herein we show that the UniCAR platform can be used to efficiently target solid cancers in vitro and in vivo using a pre-clinical prostate cancer model which overexpresses prostate stem cell antigen (PSCA). Short-term administration of the targeting module to tumor bearing immunocompromised mice engrafted with human UniCAR-T cells significantly delayed tumor growth and prolonged survival of recipient mice both in a low and high tumor burden model...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29089076/-screening-of-key-molecules-of-hab18g-cd147-signal-transduction-pathway-in-human-hepatoma-cells
#2
Hongwei Zhou, Yibing Yao, Yaojie Liang, Zhihong Wang, Xiaoyan Zhou, Weiping Guo, Xiangmin Yang, Jianli Jiang, Junzhong Sun, Zhinan Chen
Objective To screen the differentially expressed key molecules of HAb18G/CD147 signal transduction pathway in human hepatoma cells. Methods The total RNA was extracted from SMMC-7721 and T7721 cells, which were stably transfected and overexpressed HAb18G/CD147, and then detected by signal transduction-related microarray to identify differentially expressed key molecules. Results The microarray data indicated that there were 13 differentially expressed genes between T7721 and SMMC-7721 cells. In T7721 cell line which overexpressed HAb18G/CD147, the down-regulated genes included bone morphogenetic protein-2 (BMP-2), BMP-5, endothelin-1 (ET-1), Wnt1-induced signaling proteins-2/CCN5 (WISP-2), cysteine-rich 61/CCN1 (Cyr61), prostate stem cell antigen (PSCA), and the up-regulated genes included interleukin-10 receptor α (IL-10Rα), IL-6, IL-8, CXCL2, mitochondrial superoxide dismutase 2 (SOD2), B factor and βig-h3...
September 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28971496/psca-promotes-prostate-cancer-proliferation-and-cell-cycle-progression-by-up-regulating-c-myc
#3
Ermao Li, Luhao Liu, Futian Li, Lianmin Luo, Shankun Zhao, Jiamin Wang, Ran Kang, Jintai Luo, Zhigang Zhao
BACKGROUND: The Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI)-anchored protein. Increasing evidence has indicated PSCA plays an important role in tumorigenesis. However, its function and the underlying molecular mechanisms in prostate cancer (PCa) are still not fully elucidated. In this study, we aimed to explore the effect of PSCA on cell cycle of PCa cells and its mechanism research. METHODS: Immunohistochemistry, quantitative reverse transcription-PCR (qRT-PCR) and Western blotting were used to quantify PSCA expression pattern in PCa tissues and cell lines...
December 2017: Prostate
https://www.readbyqxmd.com/read/28967901/mobilan-a-recombinant-adenovirus-carrying-toll-like-receptor-5-self-activating-cassette-for-cancer-immunotherapy
#4
V Mett, E A Komarova, K Greene, I Bespalov, C Brackett, B Gillard, A S Gleiberman, I A Toshkov, S Aygün-Sunar, C Johnson, E Karasik, M Bapardekar-Nair, O V Kurnasov, A L Osterman, P S Stanhope-Baker, C Morrison, M T Moser, B A Foster, A V Gudkov
Toll-like receptor 5 (TLR5) is considered an attractive target for anticancer immunotherapy. TLR5 agonists, bacterial flagellin and engineered flagellin derivatives, have been shown to have potent antitumor and metastasis-suppressive effects in multiple animal models and to be safe in both animals and humans. Anticancer efficacy of TLR5 agonists stems from TLR5-dependent activation of nuclear factor-κB (NF-κB) that mediates innate and adaptive antitumor immune responses. To extend application of TLR5-targeted anticancer immunotherapy to tumors that do not naturally express TLR5, we created an adenovirus-based vector for intratumor delivery, named Mobilan that drives expression of self-activating TLR5 signaling cassette comprising of human TLR5 and a secreted derivative of Salmonella flagellin structurally analogous to a clinical stage TLR5 agonist, entolimod...
October 2, 2017: Oncogene
https://www.readbyqxmd.com/read/28939158/formulation-of-the-bivalent-prostate-cancer-vaccine-with-surgifoam-elicits-antigen-specific-effector-t-cells-in-psa-transgenic-mice
#5
Dev Karan
We previously developed and characterized an adenoviral-based prostate cancer vaccine for simultaneous targeting of prostate-specific antigen (PSA) and prostate stem cell antigen (PSCA). We also demonstrated that immunization of mice with the bivalent vaccine (Ad5-PSA+PSCA) inhibited the growth of established prostate tumors. However, there are multiple challenges hindering the success of immunological therapies in the clinic. One of the prime concerns has been to overcome the immunological tolerance and maintenance of long-term effector T cells...
October 13, 2017: Vaccine
https://www.readbyqxmd.com/read/28935568/genetically-engineered-oncolytic-newcastle-disease-virus-mediates-cytolysis-of-prostate-cancer-stem-like-cells
#6
Shobana Raghunath, Raghavendra Sumanth Pudupakam, Adria Allen, Moanaro Biswas, Nammalwar Sriranganathan
Oncolytic virotherapy is a promising novel approach that overcomes the limitations posed by radiation and chemotherapy. In this study, the oncolytic efficacy of a recombinant Newcastle disease virus (rNDV) BC-KLQL-GFP, against prostate cancer stem-like/tumor initiating cells was evaluated. Xenograft derived prostaspheres (XPS) induced tumor more efficiently than monolayer cell derived prostaspheres (MCPS) in nude mice. Primary and secondary XPS show enhanced self-renewal and clonogenic potential compared to MCPS...
September 19, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28903367/exploratory-investigation-of-psca-protein-expression-in-primary-breast-cancer-patients-reveals-a-link-to-her2-neu-overexpression
#7
Theresa Link, Friederike Kuithan, Armin Ehninger, Jan Dominik Kuhlmann, Michael Kramer, Andreas Werner, Axel Gatzweiler, Barbara Richter, Gerhard Ehninger, Gustavo Baretton, Michael Bachmann, Pauline Wimberger, Katrin Friedrich
BACKGROUND: Prostate stem cell antigen (PSCA) has been suggested as biomarker and therapeutic target for prostate cancer. Recent advances showed that PSCA is up-regulated in other cancer entities, such as bladder or pancreatic cancer. However, the clinical relevance of PSCA-expression in breast cancer patients has not yet been established and is therefore addressed by the current study. METHODS: PSCA-protein expression was assessed in 405 breast cancer patients, using immunohistochemistry (PSCA antibody MB1) and tissue microarrays...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28845520/psca-regulates-il-6-expression-through-p38-nf-%C3%AE%C2%BAb-signaling-in-prostate-cancer
#8
Luhao Liu, Ermao Li, Lianmin Luo, Shankun Zhao, Futian Li, Jiamin Wang, Jintai Luo, Zhigang Zhao
BACKGROUND: Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein. We previously reported that PSCA involved in proliferation and invasion of PCa cells, however, the underlying mechanisms are unknown. In this study, we aimed to explore the regulating role of PSCA gene expression in interleukin-6 (IL-6) autocrine of PCa cells. METHODS: The stable knockdown-PSCA and ectopically overexpressed-PSCA vector were constructed and transfected into human PCa DU145 and PC-3M cells...
October 2017: Prostate
https://www.readbyqxmd.com/read/28810652/expression-of-prostate-stem-cell-antigen-is-downregulated-during-flavonoid-induced-cytotoxicity-in-prostate-cancer-cells
#9
Qiang Zhang, Guangdong Cheng, Hongbin Qiu, Yuexin Wang, Jingtao Wang, Hui Xu, Tao Zhang, Lixin Liu, Ye Tao, Zhongjuan Ren
Prostate stem cell antigen (PSCA) is expressed in the majority of prostate cancer cases and may be a potential therapeutic target in the treatment of prostate cancer. The present study evaluated the cytotoxicity of three flavonoids (genistein, luteolin and quercetin) towards DU145 prostate cancer cells, and investigated the effect of these flavonoids on PSCA expression. The results demonstrated that genistein, luteolin and quercetin inhibited the growth of DU145 cells in a dose-dependent manner (P<0.05) and induced morphological changes characteristic of apoptosis in DU145 cells...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28808221/genetic-variation-of-the-psca-gene-rs2294008-is-not-associated-with-the-risk-of-prostate-cancer
#10
Il-Seok Lee, Sung Pil Seo, Yun Sok Ha, Pildu Jeong, Ho Won Kang, Won Tae Kim, Yong-June Kim, Seok Joong Yun, Sang Cheol Lee, Wun-Jae Kim
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 ofPSCA 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 ofPSCA was performed using PCR...
January 19, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28755148/amplification-and-overexpression-of-psca-at-8q24-in-invasive-micropapillary-carcinoma-of-breast
#11
Fanfan Meng, Bingbing Liu, Gan Xie, Yawen Song, Xia Zheng, Xiaolong Qian, Shuai Li, Hongqin Jia, Xinmin Zhang, Lanjing Zhang, Yi-Ling Yang, Li Fu
PURPOSE: Invasive micropapillary carcinoma (IMPC) of the breast has distinct histological features and molecular genetic profiles. Gains/amplifications of 8q24 are found associated with IMPC. Although the prostate stem cell antigen (PSCA) gene is located at chromosome 8q24, and found over-expressed in prior studies, its prognostic values and biological significance in IMPC have not been well studied. METHODS: Fluorescence in situ hybridization (FISH) was used to assess the frequencies of PSCA copy number gains in IMPC, invasive ductal carcinoma of no special type (IDC-NST), and invasive lobular carcinoma (ILC) samples...
July 28, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28667390/novel-psca-targeting-scfv-fusion-proteins-for-diagnosis-and-immunotherapy-of-prostate-cancer
#12
Claudia Kessler, Alessa Pardo, Mehmet K Tur, Stefan Gattenlöhner, Rainer Fischer, Katharina Kolberg, Stefan Barth
PURPOSE: Despite great progress in the diagnosis and treatment of localized prostate cancer (PCa), there remains a need for new diagnostic markers that can accurately distinguish indolent and aggressive variants. One promising approach is the antibody-based targeting of prostate stem cell antigen (PSCA), which is frequently overexpressed in PCa. Here, we show the construction of a molecular imaging probe comprising a humanized scFv fragment recognizing PSCA genetically fused to an engineered version of the human DNA repair enzyme O6-alkylguanine-DNA alkyltransferase (AGT), the SNAP-tag, enabling specific covalent coupling to various fluorophores for diagnosis of PCa...
June 30, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28643332/integrative-eqtl-analysis-of-tumor-and-host-omics-data-in-individuals-with-bladder-cancer
#13
Silvia Pineda, Kristel Van Steen, Núria Malats
Integrative analyses of several omics data are emerging. The data are usually generated from the same source material (i.e., tumor sample) representing one level of regulation. However, integrating different regulatory levels (i.e., blood) with those from tumor may also reveal important knowledge about the human genetic architecture. To model this multilevel structure, an integrative-expression quantitative trait loci (eQTL) analysis applying two-stage regression (2SR) was proposed. This approach first regressed tumor gene expression levels with tumor markers and the adjusted residuals from the previous model were then regressed with the germline genotypes measured in blood...
June 23, 2017: Genetic Epidemiology
https://www.readbyqxmd.com/read/28606732/constitutive-and-acquired-mechanisms-of-resistance-to-immune-checkpoint-blockade-in-human-cancer
#14
Matteo Bellone, Angela Rita Elia
Cancer immunotherapy with monoclonal antibodies directed against regulatory pathways in T lymphocytes has been revolutionizing medical oncology, and the clinical success of monoclonal antibodies targeting either cytotoxic T lymphocyte antigen-4 (CTLA-4) or program death-1 (PD-1) in patients affected by melanoma, Hodgkin's lymphoma, Merkel cell carcinoma, and head and neck, bladder, renal cell or non-small cell lung cancer is way beyond the most optimistic expectation. However, immune checkpoint blockade (ICB) has failed to arrest progression in a consistent amount of patients affected by those tumors, and various histological types, including breast, colon and prostate cancer, are less sensitive to this therapeutic approach...
June 2, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28602051/yes-associated-protein-expression-is-correlated-to-the-differentiation-of-prostate-adenocarcinoma
#15
Myung-Giun Noh, Sung Sun Kim, Eu Chang Hwang, Dong Deuk Kwon, Chan Choi
BACKGROUND: Yes-associated protein (YAP) in the Hippo signaling pathway is a growth control pathway that regulates cell proliferation and stem cell functions. Abnormal regulation of YAP was reported in human cancers including liver, lung, breast, skin, colon, and ovarian cancer. However, the function of YAP is not known in prostate adenocarcinoma. The purpose of this study was to investigate the role of YAP in tumorigenesis, differentiation, and prognosis of prostate adenocarcinoma. METHODS: The nuclear and cytoplasmic expression of YAP was examined in 188 cases of prostate adenocarcinoma using immunohistochemistry...
July 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28600675/a-novel-capillary-nano-immunoassay-for-assessing-androgen-receptor-splice-variant-7-in-plasma-correlation-with-cd133-antigen-expression-in-circulating-tumor-cells-a-pilot-study-in-prostate-cancer-patients
#16
J L García, R Lozano, I Misiewicz-Krzeminska, J Fernández-Mateos, P Krzeminski, S Alfonso, R A Marcos, R García, F Gómez-Veiga, Á Virseda, M Herrero, D Olmos, J J Cruz-Hernández
PURPOSE: Androgen receptor (AR) splice variant 7 (AR-V7) has been related with both a higher risk of prostate cancer (PC) progression and differential responsiveness to hormonal agents versus chemotherapy. The objective of this study was to investigate the feasibility of a novel capillary nano-immunoassay in assessing AR-V7 in plasma from PC patients. METHODS: Patients with either localized or advanced PC were included in the study. Assessment of AR-V7 in plasma was performed through a capillary nano-immunoassay platform...
November 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28567040/a-unique-cellular-and-molecular-microenvironment-is-present-in-tertiary-lymphoid-organs-of-patients-with-spontaneous-prostate-cancer-regression
#17
María de la Luz García-Hernández, Norma Ofelia Uribe-Uribe, Ricardo Espinosa-González, W Martin Kast, Shabaana A Khader, Javier Rangel-Moreno
OBJECTIVE: Multiple solid cancers contain tertiary lymphoid organs (TLO). However, it is unclear whether they promote tumor rejection, facilitate tumor evasion, or simply whether they are a byproduct of chronic inflammation. We hypothesize that although chronic inflammation induces TLO formation, the tumor milieu can modulate TLO organization and functions in prostate cancer. Therefore, our study seeks to elucidate the cellular and molecular signatures in unique prostatectomy specimens from evanescent carcinoma patients to identify markers of cancer regression, which could be harnessed to modulate local immunosuppression or potentially enhance TLO function...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28512267/exploratory-investigation-of-psca-protein-expression-in-primary-breast-cancer-patients-reveals-a-link-to-her2-neu-overexpression
#18
Theresa Link, Friederike Kuithan, Armin Ehninger, Jan Dominik Kuhlmann, Michael Kramer, Andreas Werner, Axel Gatzweiler, Barbara Richter, Gerhard Ehninger, Gustavo Baretton, Michael Bachmann, Pauline Wimberger, Katrin Friedrich
BACKGROUND: Prostate stem cell antigen (PSCA) has been suggested as biomarker and therapeutic target for prostate cancer. Recent advances showed that PSCA is up-regulated in other cancer entities, such as bladder or pancreatic cancer. However, the clinical relevance of PSCA-expression in breast cancer patients has not yet been established and is therefore addressed by the current study. METHODS: PSCA-protein expression was assessed in 405 breast cancer patients, using immunohistochemistry (PSCA antibody MB1) and tissue microarrays...
April 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28439009/estrogen-receptor-%C3%AE-a-regulator-of-androgen-receptor-signaling-in-the-mouse-ventral-prostate
#19
Wan-Fu Wu, Laure Maneix, Jose Insunza, Ivan Nalvarte, Per Antonson, Juha Kere, Nancy Yiu-Lin Yu, Virpi Tohonen, Shintaro Katayama, Elisabet Einarsdottir, Kaarel Krjutskov, Yu-Bing Dai, Bo Huang, Wen Su, Margaret Warner, Jan-Åke Gustafsson
As estrogen receptor β(-/-) (ERβ(-/-)) mice age, the ventral prostate (VP) develops increased numbers of hyperplastic, fibroplastic lesions and inflammatory cells. To identify genes involved in these changes, we used RNA sequencing and immunohistochemistry to compare gene expression profiles in the VP of young (2-mo-old) and aging (18-mo-old) ERβ(-/-) mice and their WT littermates. We also treated young and old WT mice with an ERβ-selective agonist and evaluated protein expression. The most significant findings were that ERβ down-regulates androgen receptor (AR) signaling and up-regulates the tumor suppressor phosphatase and tensin homolog (PTEN)...
May 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28405515/psca-and-muc1-in-non-small-cell-lung-cancer-as-targets-of-chimeric-antigen-receptor-t-cells
#20
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
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