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Inês Margarida Gomes, Sandra Moreira Rocha, Carlos Gaspar, Maria Inês Alvelos, Cecília Reis Santos, Sílvia Socorro, Cláudio Jorge Maia
Six transmembrane epithelial antigen of the prostate 1 (STEAP1) is overexpressed in numerous types of tumors, especially in prostate cancer. STEAP1 is located in the plasma membrane of epithelial cells and may play an important role in inter- and intracellular communication. Several studies suggest STEAP1 as a potential biomarker and an immunotherapeutic target for prostate cancer. However, the role of STEAP1 in cell proliferation and apoptosis remains unclear. Therefore, the role of STEAP1 in prostate cancer cells proliferation and apoptosis was determined by inducing STEAP1 gene knockdown in LNCaP cells...
February 20, 2018: Medical Oncology
Seyed-Alireza Esmaeili, Foroogh Nejatollahi, Amirhossein Sahebkar
BACKGROUND: Six-Transmembrane epithelial antigen of the prostate-1 (STEAP-1) is present at the intercellular junctions of the secretory epithelium of prostate and is overexpressed in all steps of prostate cancer. STEAP-1 acts as a transporter protein or a putative channel between cancer cells while it has limited expression in normal human tissues. This protein has been suggested as an attractive target for prostate cancer immunotherapy. OBJECTIVE: This study aimed at the development of a specific single chain fragment variable (scFv) antibody against STEAP-1 epitope and testing the inhibitory effect of the selected scFv antibody in blocking gap junctions between tumor cells...
December 7, 2017: Anti-cancer Agents in Medicinal Chemistry
Jorge Barroca-Ferreira, João Pedro Pais, Margarida Maria Santos, Ana Margarida Gonçalves, Inês Margarida Gomes, Inês Margarida Sousa, Sandra Moreira Rocha, Luís António Passarinha, Cláudio Maia
Cancer is a global health issue that impairs the life quality of patients and origins thousands of deaths annually worldwide. Six-transmembrane epithelial antigen of the prostate (STEAP1) was identified to be overexpressed in several types of cancers, namely in prostate cancer (PCa). Considering its secondary structure, associated with its location in the cell membrane, has been suggested a role in intercellular communication between tumour cells. Taking into account its high specificity and overexpression in human cancers, STEAP1 is nowadays a promising candidate to be imposed as a therapeutic target...
April 26, 2017: Current Cancer Drug Targets
Yun Liang, Xianying Xing, Maria A Beamer, William R Swindell, Mrinal K Sarkar, Liza Wolterink Roberts, John J Voorhees, J Michelle Kahlenberg, Paul W Harms, Andrew Johnston, Johann E Gudjonsson
BACKGROUND: Pustular skin disorders are a category of difficult-to-treat and potentially life-threatening conditions that involve the appearance of neutrophil-rich pustules. The molecular basis of most pustular skin conditions has remained unknown. OBJECTIVE: We sought to investigate the molecular basis of 3 pustular skin disorders: generalized pustular psoriasis (GPP), palmoplantar pustulosis (PPP), and acute generalized exanthematous pustulosis (AGEP). METHODS: Microarray analyses were performed to profile genome-wide gene expression of skin biopsy specimens obtained from patients with GPP, PPP, or AGEP and healthy control subjects...
April 2017: Journal of Allergy and Clinical Immunology
Kwangsoo Kim, Sharmistha Mitra, Gang Wu, Vladimir Berka, Jinmei Song, Ye Yu, Sebastien Poget, Da-Neng Wang, Ah-Lim Tsai, Ming Zhou
STEAP1, six-transmembrane epithelial antigen of prostate member 1, is strongly expressed in several types of cancer cells, particularly in prostate cancer, and inhibition of its expression reduces the rate of tumor cell proliferation. However, the physiological function of STEAP1 remains unknown. Here for the first time, we purified a mammalian (rabbit) STEAP1 at a milligram level, permitting its high-quality biochemical and biophysical characterizations. We found that STEAP1 likely assembles as a homotrimer and forms a heterotrimer when co-expressed with STEAP2...
December 6, 2016: Biochemistry
J N Sheets, M Iwanicki, J F Liu, B E Howitt, M S Hirsch, J A A Gubbels, R Drapkin, K A Egland
The cause of death among the majority of epithelial ovarian cancer (EOC) patients involves passive dissemination of cancer cells within the peritoneal cavity and subsequent implantation of cancer spheroids into adjacent organs. Thus, it is important to identify the factors that mediate EOC metastasis and implantation, including clearance of the mesothelium. Sushi domain containing 2 (SUSD2) encodes a type I transmembrane protein containing several functional domains inherent to adhesion molecules. Immunohistochemical analysis determined the presence of SUSD2 in several subtypes of EOC, with the strongest staining observed in high-grade serous ovarian carcinomas (HGSOCs)...
October 24, 2016: Oncogenesis
Siddharth Sukumaran, Crystal Zhang, Douglas D Leipold, Ola M Saad, Keyang Xu, Kapil Gadkar, Divya Samineni, Bei Wang, Marija Milojic-Blair, Montserrat Carrasco-Triguero, Bonnee Rubinfeld, Paul Fielder, Kedan Lin, Saroja Ramanujan
Antibody drug conjugates (ADC), in which small molecule cytotoxic agents are non-specifically linked to antibodies, can enable targeted delivery of chemotherapeutics to tumor cells. ADCs are often produced and administered as a mixture of conjugated antibodies with different drug to antibody ratios (DAR) resulting in complex and heterogeneous disposition kinetics. We developed a mechanism-based platform model that can describe and predict the complex pharmacokinetic (PK) behavior of ADCs with protease-cleavable valine-citrulline (VC) linker linked to Monomethylmonomethyl auristatin F/E by incorporating known mechanisms of ADC disposition...
January 2017: AAPS Journal
David Schirmer, Thomas G P Grünewald, Richard Klar, Oxana Schmidt, Dirk Wohlleber, Rebeca Alba Rubío, Wolfgang Uckert, Uwe Thiel, Felix Bohne, Dirk H Busch, Angela M Krackhardt, Stefan Burdach, Günther H S Richter
Pediatric cancers, including Ewing sarcoma (ES), are only weakly immunogenic and the tumor-patients' immune system often is devoid of effector T cells for tumor elimination. Based on expression profiling technology, targetable tumor-associated antigens (TAA) are identified and exploited for engineered T-cell therapy. Here, the specific recognition and lytic potential of transgenic allo-restricted CD8(+) T cells, directed against the ES-associated antigen 6-transmembrane epithelial antigen of the prostate 1 (STEAP1), was examined...
June 2016: Oncoimmunology
Wenyu Wang, Yang Liu, Jingcan Hao, Shuyu Zheng, Yan Wen, Xiao Xiao, Awen He, Qianrui Fan, Feng Zhang, Ruiyu Liu
Hip cartilage destruction is consistently observed in the non-traumatic osteonecrosis of femoral head (NOFH) and accelerates its bone necrosis. The molecular mechanism underlying the cartilage damage of NOFH remains elusive. In this study, we conducted a systematically comparative study of gene expression profiles between NOFH and osteoarthritis (OA). Hip articular cartilage specimens were collected from 12 NOFH patients and 12 controls with traumatic femoral neck fracture for microarray (n=4) and quantitative real-time PCR validation experiments (n=8)...
October 10, 2016: Gene
Ching-Hsiao Lee, Sung-Lang Chen, Wen-Wei Sung, Hung-Wen Lai, Ming-Ju Hsieh, Hsu-Heng Yen, Tzu-Cheng Su, Yu-Hu Chiou, Chia-Yu Chen, Cheng-Yu Lin, Mei-Ling Chen, Chih-Jung Chen
STEAP1 (six transmembrane epithelial antigen of the prostate 1) is a transmembrane protein that functions as a potential channel or transporter protein. It is overexpressed in certain cancers and is viewed as a promising therapeutic target. However, the prognostic role of STEAP1 is still controversial, and no role for STEAP1 has yet been indicated in colorectal cancer. The aim of this study was to investigate the possible association of STEAP1 expression with colorectal cancer prognosis. STEAP1 expression was analyzed by immunohistochemical staining of a tissue array of 165 cancer specimens from primary colorectal cancer patients...
April 19, 2016: International Journal of Molecular Sciences
Federica Cappuccini, Stephen Stribbling, Emily Pollock, Adrian V S Hill, Irina Redchenko
Prostate cancer possesses several characteristics that make it a suitable candidate for immunotherapy; however, prostate cancer vaccines to date demonstrate modest efficacy and low immunogenicity. The goal of the present pre-clinical study was to explore the immunogenic properties and protective efficacy of a novel prostate cancer immunotherapy based on the heterologous prime-boost viral-vectored vaccination platform. The simian adenovirus, ChAdOx1, and modified vaccinia Ankara virus, MVA, encoding a prostate cancer-associated antigen, the six transmembrane epithelial antigen of the prostate 1 (STEAP1), induced strong sustained antigen-specific CD8+ T-cell responses in C57BL/6 and BALB/c male mice...
2016: Cancer Immunology, Immunotherapy: CII
Simon-Peter Williams, Annie Ogasawara, Jeff N Tinianow, Judith E Flores, David Kan, Jeffrey Lau, MaryAnn Go, Alexander N Vanderbilt, Herman S Gill, Li Miao, Joshua Goldsmith, Bonnee Rubinfeld, Weiguang Mao, Ron Firestein, Shang-Fan Yu, Jan Marik, Anton G T Terwisscha van Scheltinga
The efficacy of antibody-drug conjugates (ADCs) targeted to solid tumors depends on biological processes that are hard to monitor in vivo. 89Zr-immunoPET of the ADC antibodies could help understand the performance of ADCs in the clinic by confirming the necessary penetration, binding, and internalization. This work studied monomethyl auristatin E (MMAE) ADCs against two targets in metastatic castration-resistant prostate cancer, TENB2 and STEAP1, in four patient-derived tumor models (LuCaP35V, LuCaP70, LuCaP77, LuCaP96...
May 3, 2016: Oncotarget
Mark D Kleven, Mensur Dlakić, C Martin Lawrence
Six-transmembrane epithelial antigen of the prostate 3 (Steap3) is the major ferric reductase in developing erythrocytes. Steap family proteins are defined by a shared transmembrane domain that in Steap3 has been shown to function as a transmembrane electron shuttle, moving cytoplasmic electrons derived from NADPH across the lipid bilayer to the extracellular face where they are used to reduce Fe(3+) to Fe(2+) and potentially Cu(2+) to Cu(1+). Although the cytoplasmic N-terminal oxidoreductase domain of Steap3 and Steap4 are relatively well characterized, little work has been done to characterize the transmembrane domain of any member of the Steap family...
September 11, 2015: Journal of Biological Chemistry
Hubert Kübler, Birgit Scheel, Ulrike Gnad-Vogt, Kurt Miller, Wolfgang Schultze-Seemann, Frank Vom Dorp, Giorgio Parmiani, Christian Hampel, Steffen Wedel, Lutz Trojan, Dieter Jocham, Tobias Maurer, Gerd Rippin, Mariola Fotin-Mleczek, Florian von der Mülbe, Jochen Probst, Ingmar Hoerr, Karl-Josef Kallen, Thomas Lander, Arnulf Stenzl
BACKGROUND: CV9103 is a prostate-cancer vaccine containing self-adjuvanted mRNA (RNActive®) encoding the antigens PSA, PSCA, PSMA, and STEAP1. This phase I/IIa study evaluated safety and immunogenicity of CV9103 in patients with advanced castration-resistant prostate-cancer. METHODS: 44 Patients received up to 5 intra-dermal vaccinations. Three dose levels of total mRNA were tested in Phase I in cohorts of 3-6 patients to determine a recommended dose. In phase II, 32 additional patients were treated at the recommended dose...
2015: Journal for Immunotherapy of Cancer
X Zhuang, J M J Herbert, P Lodhia, J Bradford, A M Turner, P M Newby, D Thickett, U Naidu, D Blakey, S Barry, D A E Cross, R Bicknell
BACKGROUND: Lung cancer remains the leading cause of cancer-related death, largely owing to the lack of effective treatments. A tumour vascular targeting strategy presents an attractive alternative; however, the molecular signature of the vasculature in lung cancer is poorly explored. This work aimed to identify novel tumour vascular targets in lung cancer. METHODS: Enzymatic digestion of fresh tissue followed by endothelial capture with Ulex lectin-coated magnetic beads was used to isolate the endothelium from fresh tumour specimens of lung cancer patients...
February 3, 2015: British Journal of Cancer
Michael G Doran, Philip A Watson, Sarah M Cheal, Daniel E Spratt, John Wongvipat, Jeffrey M Steckler, Jorge A Carrasquillo, Michael J Evans, Jason S Lewis
UNLABELLED: Antibodies and antibody-drug conjugates targeting the cell surface protein 6 transmembrane epithelial antigen of prostate 1 (STEAP1) are in early clinical development for the treatment of castration-resistant prostate cancer (PCa). In general, antigen expression directly affects the bioactivity of therapeutic antibodies, and the biologic regulation of STEAP1 is unusually complicated in PCa. Paradoxically, STEAP1 can be induced or repressed by the androgen receptor (AR) in different human PCa models, while also expressed in AR-null PCa...
December 2014: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Siddharth Sukumaran, Kapil Gadkar, Crystal Zhang, Sunil Bhakta, Luna Liu, Keyang Xu, Helga Raab, Shang-Fan Yu, Elaine Mai, Aimee Fourie-O'Donohue, Katherine R Kozak, Saroja Ramanujan, Jagath R Junutula, Kedan Lin
PURPOSE: THIOMAB™ drug conjugates (TDCs) with engineered cysteine residues allow site-specific drug conjugation and defined Drug-to-Antibody Ratios (DAR). In order to help elucidate the impact of drug-loading, conjugation site, and subsequent deconjugation on pharmacokinetics and efficacy, we have developed an integrated mathematical model to mechanistically characterize pharmacokinetic behavior and preclinical efficacy of MMAE conjugated TDCs with different DARs. General applicability of the model structure was evaluated with two different TDCs...
June 2015: Pharmaceutical Research
Helen Whiteland, Samantha Spencer-Harty, Claire Morgan, Howard Kynaston, David Hywel Thomas, Pradeep Bose, Neil Fenn, Paul Lewis, Spencer Jenkins, Shareen H Doak
Prostate adenocarcinoma is the second most frequent cancer worldwide and is one of the leading causes of male cancer-related deaths. However, it varies greatly in its behaviour, from indolent non-progressive disease to metastatic cancers with high associated mortality. The aim of this study was to identify predictive biomarkers for patients with localised prostate tumours most likely to progress to aggressive disease, to facilitate future tailored clinical treatment and identify novel therapeutic targets. The expression of 602 genes was profiled using oligoarrays, across three prostate cancer cell lines: CA-HPV-10, LNCaP and PC3, qualitatively identifying several potential prognostic biomarkers...
December 2014: Clinical & Experimental Metastasis
Inês M Gomes, Cecília R Santos, Cláudio J Maia
STEAP1 gene is overexpressed in several kinds of tumors, particularly in prostate cancer. Besides STEAP1, there is another related gene, STEAP1B, which may encode two different transcripts. Although several studies have been pointing STEAP1 as a putative immunotherapeutic target and biomarker, the mechanisms underlying its regulation are not fully understood. In silico analysis allowed us to show that STEAP1 and STEAP1B share high homology, but with slight differences at structural level. Experiments with prostate cells showed that STEAP1B2 is overexpressed in cancer cells...
March 2014: Genes & Cancer
Bianca Altvater, Sareetha Kailayangiri, Nadine Theimann, Martina Ahlmann, Nicole Farwick, Christiane Chen, Sibylle Pscherer, Ilka Neumann, Gabriele Mrachatz, Anna Hansmeier, Jendrik Hardes, Georg Gosheger, Heribert Juergens, Claudia Rossig
Disseminated or relapsed Ewing sarcoma (EwS) has remained fatal in the majority of patients. A promising approach to preventing relapse after conventional therapy is to establish tumor antigen-specific immune control. Efficient and specific T cell memory against the tumor depends on the expansion of rare T cells with native specificity against target antigens overexpressed by the tumor. Candidate antigens in EwS include six-transmembrane epithelial antigen of the prostate-1 (STEAP1), and the human cancer/testis antigens X-antigen family member 1 (XAGE1) and preferentially expressed antigen in melanoma (PRAME)...
October 2014: Cancer Immunology, Immunotherapy: CII
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