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Prostate stem cell antigen

Lena Tienken, Natascha Drude, Isabell Schau, Oliver H Winz, Achim Temme, Elmar Weinhold, Felix M Mottaghy, Agnieszka Morgenroth
In pretargeted radio-immunotherapy, the gradual administration of a non-radioactive tumor antigen-addressing antibody-construct and the subsequent application of a radioactive labeled, low molecular weight substance enable a highly effective and selective targeting of tumor tissue. We evaluated this concept in prostate stem cell antigen (PSCA)-positive cancers using the antigen-specific, biotinylated single chain antibody scFv(AM1)-P-BAP conjugated with tetrameric neutravidin. To visualize the systemic biodistribution, a radiolabeled biotin was injected to interact with scFv(AM1)-P-BAP/neutravidin conjugate...
February 28, 2018: Scientific Reports
Hiroe Ono, Hiromi Sakamoto, Teruhiko Yoshida, Norihisa Saeki
Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein and exhibits an organ-dependent expression pattern in cancer. PSCA is upregulated in prostate cancer and downregulated in gastric cancer. PSCA is expressed in a variety of human organs. Although certain studies previously demonstrated its expression in the mammalian and avian brain, its expression in the human brain has not been thoroughly elucidated. Additionally, it was previously reported that PSCA is weakly expressed in the astrocytes of the normal human brain but aberrantly expressed in glioma, suggesting that PSCA is a promising target of glioma therapy and prostate cancer therapy...
March 2018: Oncology Letters
Osamu Toyoshima, Chizu Tanikawa, Ryuta Yamamoto, Hidenobu Watanabe, Hiroharu Yamashita, Kosuke Sakitani, Shuntaro Yoshida, Michiaki Kubo, Keitaro Matsuo, Hidemi Ito, Kazuhiko Koike, Yasuyuki Seto, Koichi Matsuda
SNP rs2294008 in Prostate Stem Cell Antigen (PSCA) and decreased PSCA expression are associated with gastric cancer. The objective of this study is to investigate the role of rs2294008 and PSCA expression in the gastritis-gastric cancer carcinogenic pathway. We conducted a case-control association study of H. pylori-infected gastritis and gastric cancer. rs2294008 was associated with the progression to chronic active gastritis (P = 9.4 × 10-5; odds ratio = 3.88, TT + TC vs CC genotype), but not with H. pylori infection per se nor with the progression from active gastritis to gastric cancer...
January 9, 2018: Oncotarget
Xi Chen, Yasuhiro Nagai, Zhiqiang Zhu, Hang Ruan, Donna M Peehl, Mark I Greene, Hongtao Zhang
Prostate cancer is the most common cancer occurring in men in the United States. The monoclonal antibody F77 that was originally developed in our laboratory recognizes mainly glycolipids as well as O-linked glycosylation on proteins in prostate cancer cells. We have identified a spliced form of glycoprotein CD44 as one critical protein expressing the F77 antigen. The F77-specific glycosylation occurs on multiple potential glycosylation sites on the CD44 protein encoded by the fourteenth exon. CD44 is a tumor stem cell marker and is known to induce tumor stemness and metastasis...
January 9, 2018: Oncotarget
Xuefeng Zhang, Qin Hu, Ye Chen, Miao Li, Huming Yin, Chenchao Zhou, Gang Li, Jianquan Hou
BACKGROUND AND PURPOSE: This study explored the association between a single-nucleotide polymorphism of prostate stem cell antigen and prostate cancer in Chinese patients undergoing prostate biopsy. MATERIALS AND METHODS: DNA from 416 patients undergoing prostate biopsy was typed for the prostate stem cell antigen rs1045531 single-nucleotide polymorphism. The frequency of the rs1045531 polymorphism in patients with prostate cancer and in patients with benign prostatic hyperplasia was compared...
December 2017: Technology in Cancer Research & Treatment
Pratima Nangia-Makker, Victor Hogan, Avraham Raz
Over the last few decades galectin-3, a carbohydrate binding protein, with affinity for N-acetyllactosamine residues, has been unique due to the regulatory roles it performs in processes associated with tumor progression and metastasis such as cell proliferation, homotypic/ heterotypic aggregation, dynamic cellular transformation, migration and invasion, survival and apoptosis. Structure-function association of galectin-3 reveals that it consists of a short amino terminal motif, which regulates its nuclear-cytoplasmic shuttling; a collagen α-like domain, susceptible to cleavage by matrix metalloproteases and prostate specific antigen (PSA); accountable for its oligomerization and lattice formation, and a carbohydrate recognition/binding domain containing the anti-death motif of the Bcl2 protein family...
January 5, 2018: Glycobiology
Saul J Priceman, Ethan A Gerdts, Dileshni Tilakawardane, Kelly T Kennewick, John P Murad, Anthony K Park, Brook Jeang, Yukiko Yamaguchi, Xin Yang, Ryan Urak, Lihong Weng, Wen-Chung Chang, Sarah Wright, Sumanta Pal, Robert E Reiter, Anna M Wu, Christine E Brown, Stephen J Forman
Advancing chimeric antigen receptor (CAR)-engineered adoptive T cells for the treatment of solid cancers is a major focus in the field of immunotherapy, given impressive recent clinical responses in hematological malignancies. Prostate cancer may be amenable to T cell-based immunotherapy since several tumor antigens, including prostate stem-cell antigen (PSCA), are widely over-expressed in metastatic disease. While antigen selectivity of CARs for solid cancers is crucial, it is problematic due to the absence of truly restricted tumor antigen expression and potential safety concerns with "on-target off-tumor" activity...
2018: Oncoimmunology
Feng Li, Olga V Glinskii, Brian P Mooney, Kate Rittenhouse-Olson, Kenneth J Pienta, Vladislav V Glinsky
The tumor-associated Thomsen-Friedenreich glycoantigen (TF-Ag) plays an important role in hematogenous metastasis of multiple cancers. The LTQ Orbitrap LC-MS/MS mass spectrometry analysis of cell surface TF-Ag proteome of metastatic prostate cancer cells reveals that several cell surface glycoproteins expressing this carbohydrate antigen in prostate cancer (CD44, α2 integrin, β1 integrin, CD49f, CD133, CD59, EphA2, CD138, transferrin receptor, profilin) are either known as stem cell markers or control important cancer stem-like cell functions...
November 17, 2017: Oncotarget
Karolina S Jabbar, Liisa Arike, Caroline S Verbeke, Riadh Sadik, Gunnar C Hansson
Purpose Pancreatic cystic lesions are common incidental findings on imaging, but up to half may be forerunners of pancreatic cancer. Therefore, accurate differential diagnosis is crucial for correct patient management. Unfortunately, currently available diagnostic methods cannot robustly identify premalignant and malignant pancreatic cystic lesions. Methods Cyst fluid samples obtained by routine endoscopic ultrasound-guided aspiration were used for the analyses. In a cohort of 24 patients, eight biomarker candidates for malignant potential and high-grade dysplasia/cancer were identified by an explorative proteomic approach...
November 22, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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
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
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
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
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
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
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
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
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
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
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
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