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Tumour associated antigens

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https://www.readbyqxmd.com/read/28811834/high-risk-human-papilloma-viruses-hpvs-are-present-in-benign-prostate-tissues-before-development-of-hpv-associated-prostate-cancer
#1
Wendy K Glenn, Christopher C Ngan, Timothy G Amos, Richard J Edwards, Joshua Swift, Louise Lutze-Mann, Fei Shang, Noel J Whitaker, James S Lawson
BACKGROUND: Although high risk HPVs are associated with an increased risk of prostate cancer it is not known if they have a causal role. The purpose of this study is to investigate the potential role of human papilloma viruses (HPVs) in prostate cancer. The aims are (i) to investigate the presence and confirm the identity of high risk HPVs in benign prostate tissues prior to the development of HPV positive prostate cancer in the same patients, and (ii) to determine if HPVs are biologically active...
2017: Infectious Agents and Cancer
https://www.readbyqxmd.com/read/28804596/characterisation-of-tumour-derived-microvesicles-in-cancer-patients-blood-and-correlation-with-clinical-outcome
#2
Kerstin Menck, Annalen Bleckmann, Astrid Wachter, Bianca Hennies, Lena Ries, Matthias Schulz, Marko Balkenhol, Tobias Pukrop, Bawarjan Schatlo, Ulrike Rost, Dirk Wenzel, Florian Klemm, Claudia Binder
To evaluate whether tumour-derived microvesicles (T-MV), originating from the plasma membrane, represent suitable cancer biomarkers, we isolated MV from peripheral blood samples of cancer patients with locally advanced and/or metastatic solid tumours (n = 330, including 79 head & neck cancers, 74 lung cancers, 41 breast cancers, 28 colorectal cancers and 108 with other cancer forms) and controls (n = 103). Whole MV preparations were characterised using flow cytometry. While MV carrying the tumour-associated proteins MUC1, EGFR and EpCAM were found to be enhanced in a tumour-subtype-specific way in patients' blood, expression of the matrix metalloproteinase inducer EMMPRIN was increased independent of tumour type...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28795601/poly-glutamic-dendrimer-based-conjugates-for-cancer-vaccination-a-computational-design-for-targeted-delivery-of-antigens
#3
L I F Moura, N Martinho, L C Silva, T S Barata, S Brocchini, H F Florindo, M Zloh
Computational techniques are useful to predict interaction models and molecular properties for the design of drug delivery systems, such as dendrimers. This work evaluated the impact of surface modifications of mannosamine-conjugated multifunctional poly(glutamic acid) (PG)-dendrimers as nanocarriers of the tumour associated antigens (TAA) MART-1, gp100:44 and gp100:209. Molecular dynamics simulations and docking studies were performed. Nitrobenzoxadiazole (NBD)-PG-G4-dendrimer displayed 64 carboxylic groups, however, the Frontier Molecular Orbital Theory study evidenced that only 32 of those were available to form covalent bonds...
August 10, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28795218/atopy-and-prostate-cancer-is-there-a-link-between-circulating-levels-of-ige-and-psa-in-humans
#4
Mieke Van Hemelrijck, Sophia N Karagiannis, Sabine Rohrmann
BACKGROUND: Atopy has been investigated as a potential risk factor for prostate cancer. IgE antibodies may be major players in protective responses against tumours, through engendering antigen presentation and enhancing adaptive immune responses targeted towards a specific allergen, but potentially also against tumour-associated antigens such as prostate-specific antigen (PSA). We therefore cross-sectionally investigated associations between circulating levels of PSA and IgE in the National Health and Nutrition Examination Survey 2005-2006...
August 9, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28791124/combining-dendritic-cells-and-b-cells-for-presentation-of-oxidised-tumour-antigens-to-cd8-t-cells
#5
Melanie L Grant, Nicholas Shields, Silke Neumann, Katrin Kramer, Andrea Bonato, Christopher Jackson, Margaret A Baird, Sarah L Young
The dendritic cell (DC) is the foremost antigen-presenting cell (APC) for ex vivo expansion of tumour-specific patient T cells. Despite marked responses in some patients following reinfusion of DC-activated autologous or HLA-matched donor T cells, overall response rates remain modest in solid tumours. Furthermore, most studies aim to generate immune responses against defined tumour-associated antigens (TAA), however, meta-analysis reveals that those approaches have less clinical success than those using whole tumour cells or their components...
July 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28779974/impact-of-early-salvage-radiation-therapy-in-patients-with-persistently-elevated-or-rising-prostate-specific-antigen-after-radical-prostatectomy
#6
Nicola Fossati, R Jeffrey Karnes, Michele Colicchia, Stephen A Boorjian, Alberto Bossi, Thomas Seisen, Nadia Di Muzio, Cesare Cozzarini, Barbara Noris Chiorda, Claudio Fiorino, Giorgio Gandaglia, Paolo Dell'Oglio, Shahrokh F Shariat, Gregor Goldner, Steven Joniau, Antonino Battaglia, Karin Haustermans, Gert De Meerleer, Valérie Fonteyne, Piet Ost, Hendrik Van Poppel, Thomas Wiegel, Francesco Montorsi, Alberto Briganti
BACKGROUND: Salvage radiation therapy (SRT) is a recommended treatment option for biochemical recurrence after radical prostatectomy (RP). However, its effectiveness may be limited to specific categories of patients. OBJECTIVE: We aimed to identify the optimal candidates for early SRT after RP. DESIGN, SETTING, AND PARTICIPANTS: The study included 925 node-negative patients treated with SRT after RP at seven institutions. Patients received SRT for either prostate-specific antigen (PSA) rising, or PSA persistence after RP that was defined as PSA level ≥0...
August 2, 2017: European Urology
https://www.readbyqxmd.com/read/28771465/ebv-epigenetically-suppresses-the-b-cell-to-plasma-cell-differentiation-pathway-while-establishing-long-term-latency
#7
Christine T Styles, Quentin Bazot, Gillian A Parker, Robert E White, Kostas Paschos, Martin J Allday
Mature human B cells infected by Epstein-Barr virus (EBV) become activated, grow, and proliferate. If the cells are infected ex vivo, they are transformed into continuously proliferating lymphoblastoid cell lines (LCLs) that carry EBV DNA as extra-chromosomal episomes, express 9 latency-associated EBV proteins, and phenotypically resemble antigen-activated B-blasts. In vivo similar B-blasts can differentiate to become memory B cells (MBC), in which EBV persistence is established. Three related latency-associated viral proteins EBNA3A, EBNA3B, and EBNA3C are transcription factors that regulate a multitude of cellular genes...
August 2017: PLoS Biology
https://www.readbyqxmd.com/read/28750922/elevation-of-ca19-9-and-cea-is-associated-with-a-poor-prognosis-in-patients-with-resectable-gallbladder-carcinoma
#8
Zhijian Wen, Anfeng Si, Jue Yang, Pinghua Yang, Xinwei Yang, Hu Liu, Xingzhou Yan, Wengang Li, Baohua Zhang
AIMS: The aim of this study was to determine whether a combination of the tumour markers carcinoembryonic (CEA) and carbohydrate antigen 19-9 (CA19-9) would be helpful in predicting the prognosis of patients with gallbladder carcinoma (GBC) who underwent resection. METHODS: A retrospective analysis of clinico-pathological features and survival of 390 patients with GBC who were treated between January 2003 and December 2013. Time-dependent receiver operating characteristic (ROC) was used to evaluate the prognostic ability of tumour markers...
July 24, 2017: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
https://www.readbyqxmd.com/read/28740080/a-new-marine-derived-sulfoglycolipid-triggers-dendritic-cell-activation-and-immune-adjuvant-response
#9
Emiliano Manzo, Adele Cutignano, Dario Pagano, Carmela Gallo, Giusi Barra, Genoveffa Nuzzo, Clementina Sansone, Adrianna Ianora, Konrad Urbanek, Daniela Fenoglio, Francesca Ferrera, Cinzia Bernardi, Alessia Parodi, Giuseppe Pasquale, Antonio Leonardi, Gilberto Filaci, Raffaele De Palma, Angelo Fontana
Dendritic Cells (DCs) recognize infectious non-self molecules and engage the adaptive immune system thereby initiating long lasting, antigen-specific responses. As such, the ability to activate DCs is considered a key tool to enhance the efficacy and quality of vaccination. Here we report a novel immunomodulatory sulfolipid named β-SQDG18 that prototypes a class of natural-derived glycolipids able to prime human DCs by a TLR2/TLR4-independent mechanism and trigger an efficient immune response in vivo. β-SQDG18 induces maturation of DC with the upregulation of MHC II molecules and co-stimulatory proteins (CD83, CD86), as well as pro-inflammatory cytokines (IL-12 and INF-γ)...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28739142/radiation-therapy-for-oligorecurrence-in-prostate-cancer-preliminary-results-of-our-centre
#10
C González Ruiz de León, M Ramírez Backhaus, M Sobrón Bustamante, J Casaña, L Arribas, J Rubio-Briones
INTRODUCTION AND OBJECTIVE: There is growing interest in the use of more aggressive therapeutic modalities for treating metastatic prostate cancer. In this study, we examine the use of stereotactic body radiation therapy (SBRT) for patients with oligorecurrent prostate cancer. We analysed the biochemical response and toxicity of patients who underwent this therapy at our centre. MATERIAL AND METHOD: We selected patients who experienced oligorecurrence between January 2015 to December 2016 and were administered SBRT...
July 21, 2017: Actas Urologicas Españolas
https://www.readbyqxmd.com/read/28733646/prognostic-role-of-glasgow-prognostic-score-in-patients-with-colorectal-cancer-evidence-from-population-studies
#11
Yangyang Liu, Xingkang He, Jie Pan, Shujie Chen, Liangjing Wang
Glasgow prognostic score (GPS) has been reported to be an indicator of prognosis for various cancers. However, the relationship between GPS and colorectal cancers (CRC) remains unclear. A comprehensive search of Pubmed, Embase, Cochrane library, Web of Science, ChinaInfo and Chinese National Knowledge Infrastructure was performed to identify eligible studies, from which the risk of overall survival (OS) and cancer-specific survival (CSS) were extracted. A random-effect model was adopted to combine hazard ratio (HR) and 95% confidence interval (CI)...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28719841/risk-of-treatment-related-mortality-in-cancer-patients-treated-with-ipilimumab-a-systematic-review-and-meta-analysis
#12
Sheng Zhang, Fei Liang, Wenfeng Li, Qing Wang
BACKGROUND: Fatal adverse events (FAEs) have been reported in cancer patients receiving ipilimumab-a monoclonal antibody against cytotoxic T-lymphocyte antigen-4, but the risk of treatment-related mortality is unknown. We performed a systematic review and meta-analysis of randomised controlled trials (RCTs) of ipilimumab to determine the overall risk of FAEs associated with ipilimumab. METHODS: We systematically searched MEDLINE, EMBASE, Cochrane CENTRAL, ClinicalTrial...
July 15, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28716075/the-role-of-tumour-heterogeneity-and-clonal-cooperativity-in-metastasis-immune-evasion-and-clinical-outcome
#13
REVIEW
Deborah R Caswell, Charles Swanton
BACKGROUND: The advent of rapid and inexpensive sequencing technology allows scientists to decipher heterogeneity within primary tumours, between primary and metastatic sites, and between metastases. Charting the evolutionary history of individual tumours has revealed drivers of tumour heterogeneity and highlighted its impact on therapeutic outcomes. DISCUSSION: Scientists are using improved sequencing technologies to characterise and address the challenge of tumour heterogeneity, which is a major cause of resistance to therapy and relapse...
July 18, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28713035/intracerebral-gene-therapy-in-children-with-mucopolysaccharidosis-type-iiib-syndrome-an-uncontrolled-phase-1-2-clinical-trial
#14
Marc Tardieu, Michel Zérah, Marie-Lise Gougeon, Jérome Ausseil, Stéphanie de Bournonville, Béatrice Husson, Dimitrios Zafeiriou, Giancarlo Parenti, Philippe Bourget, Béatrice Poirier, Valérie Furlan, Cécile Artaud, Thomas Baugnon, Thomas Roujeau, Ronald G Crystal, Christian Meyer, Kumaran Deiva, Jean-Michel Heard
BACKGROUND: Mucopolysaccharidosis type IIIB syndrome (also known as Sanfilippo type B syndrome) is a lysosomal storage disease resulting in progressive deterioration of cognitive acquisition after age 2-4 years. No treatment is available for the neurological manifestations of the disease. We sought to assess the safety and efficacy of a novel intracerebral gene therapy. METHODS: Local regulatory authorities in France allowed inclusion of up to four children in this phase 1/2 study...
July 13, 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28709135/inhibition-of-lymphangiogenesis-impairs-antitumour-effects-of-photodynamic-therapy-and-checkpoint-inhibitors-in-mice
#15
Angelika Muchowicz, Malgorzata Wachowska, Joanna Stachura, Katarzyna Tonecka, Magdalena Gabrysiak, Dominika Wołosz, Zofia Pilch, Witold W Kilarski, Louis Boon, Tomasz J Klaus, Jakub Golab
Photodynamic therapy (PDT) has been shown to destroy tumour-associated lymphatic vessels. Therefore, we sought to investigate the functional outcomes of PDT-mediated damage to the lymphatic vessels. We observed that PDT with verteporfin, completely but transiently, blocks the functional lymphatic drainage in the orthotopic mammary tumour models. Sustained inhibition of lymphatic vessels regeneration induced by lenalidomide or the soluble form of vascular endothelial growth factor receptor 3 (sVEGFR3) that neutralises lymphangiogenic vascular endothelial growth factor C (VEGF-C), significantly impaired antitumour efficacy of PDT...
July 11, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28707331/epstein-barr-virus-lytic-cycle-involvement-in-diffuse-large-b-cell-lymphoma
#16
Melina Cohen, Aldana Georgina Vistarop, Fuad Huaman, Marina Narbaitz, Fernanda Metrebian, Elena De Matteo, María Victoria Preciado, Paola Andrea Chabay
Epstein-Barr virus (EBV)-mediated B cell transformation is achieved predominantly through the action of latent proteins, but recent evidence suggests that lytic EBV replication has also a certain pathogenic role in lymphomagenesis, at least in the early phases of cell transformation. Particularly, in diffuse large B cell lymphoma (DLBCL), the EBV lytic cycle is by and large unexplored, so to disclose lytic cell contribution to lymphomagenesis, our aim was to evaluate viral early and late lytic gene expression in relation to several immune response markers in a series of EBV+ DLBCL from Argentina...
July 14, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28698647/identification-of-fbxl4-as-a-metastasis-associated-gene-in-prostate-cancer
#17
Elzbieta Stankiewicz, Xueying Mao, D Chas Mangham, Lei Xu, Marc Yeste-Velasco, Gabrielle Fisher, Bernard North, Tracy Chaplin, Bryan Young, Yuqin Wang, Jasmin Kaur Bansal, Sakunthala Kudahetti, Lucy Spencer, Christopher S Foster, Henrik Møller, Peter Scardino, R Tim Oliver, Jonathan Shamash, Jack Cuzick, Colin S Cooper, Daniel M Berney, Yong-Jie Lu
Prostate cancer is the most common cancer among western men, with a significant mortality and morbidity reported for advanced metastatic disease. Current understanding of metastatic disease is limited due to difficulty of sampling as prostate cancer mainly metastasizes to bone. By analysing prostate cancer bone metastases using high density microarrays, we found a common genomic copy number loss at 6q16.1-16.2, containing the FBXL4 gene, which was confirmed in larger series of bone metastases by fluorescence in situ hybridisation (FISH)...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28694034/insertion-and-deletion-derived-tumour-specific-neoantigens-and-the-immunogenic-phenotype-a-pan-cancer-analysis
#18
Samra Turajlic, Kevin Litchfield, Hang Xu, Rachel Rosenthal, Nicholas McGranahan, James L Reading, Yien Ning S Wong, Andrew Rowan, Nnennaya Kanu, Maise Al Bakir, Tim Chambers, Roberto Salgado, Peter Savas, Sherene Loi, Nicolai J Birkbak, Laurent Sansregret, Martin Gore, James Larkin, Sergio A Quezada, Charles Swanton
BACKGROUND: The focus of tumour-specific antigen analyses has been on single nucleotide variants (SNVs), with the contribution of small insertions and deletions (indels) less well characterised. We investigated whether the frameshift nature of indel mutations, which create novel open reading frames and a large quantity of mutagenic peptides highly distinct from self, might contribute to the immunogenic phenotype. METHODS: We analysed whole-exome sequencing data from 5777 solid tumours, spanning 19 cancer types from The Cancer Genome Atlas...
August 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28687750/5t4-specific-chimeric-antigen-receptor-modification-promotes-the-immune-efficacy-of-cytokine-induced-killer-cells-against-nasopharyngeal-carcinoma-stem-cell-like-cells
#19
Xueyang Guo, Hang Zheng, Weiren Luo, Qianbing Zhang, Jingxian Liu, Kaitai Yao
Relapse and metastasis of nasopharyngeal carcinoma (NPC) are presumably attributed to cancer stem cells (CSCs). In recent years, chimeric antigen receptor (CAR)-modified immune effector cells have been shown to have impressive antitumour efficacy. In this study, we aimed to identify appropriate tumour-associated antigens predominantly expressed on NPC stem cells (NPCSCs) and determine their suitability for CAR-engineered cytokine-induced killer (CIK) cell therapy against NPC. By investigating the expression patterns of potential target antigens (ROR1, 5T4 and CAIX) in NPC, we found that the oncofetal antigen 5T4 was predominately expressed in NPC cell lines and tissues but absent in non-cancerous nasopharyngeal tissues...
July 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28678778/an-immunogenic-personal-neoantigen-vaccine-for-patients-with-melanoma
#20
Patrick A Ott, Zhuting Hu, Derin B Keskin, Sachet A Shukla, Jing Sun, David J Bozym, Wandi Zhang, Adrienne Luoma, Anita Giobbie-Hurder, Lauren Peter, Christina Chen, Oriol Olive, Todd A Carter, Shuqiang Li, David J Lieb, Thomas Eisenhaure, Evisa Gjini, Jonathan Stevens, William J Lane, Indu Javeri, Kaliappanadar Nellaiappan, Andres M Salazar, Heather Daley, Michael Seaman, Elizabeth I Buchbinder, Charles H Yoon, Maegan Harden, Niall Lennon, Stacey Gabriel, Scott J Rodig, Dan H Barouch, Jon C Aster, Gad Getz, Kai Wucherpfennig, Donna Neuberg, Jerome Ritz, Eric S Lander, Edward F Fritsch, Nir Hacohen, Catherine J Wu
Effective anti-tumour immunity in humans has been associated with the presence of T cells directed at cancer neoantigens, a class of HLA-bound peptides that arise from tumour-specific mutations. They are highly immunogenic because they are not present in normal tissues and hence bypass central thymic tolerance. Although neoantigens were long-envisioned as optimal targets for an anti-tumour immune response, their systematic discovery and evaluation only became feasible with the recent availability of massively parallel sequencing for detection of all coding mutations within tumours, and of machine learning approaches to reliably predict those mutated peptides with high-affinity binding of autologous human leukocyte antigen (HLA) molecules...
July 13, 2017: Nature
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