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Tumour associated antigens

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https://www.readbyqxmd.com/read/28719841/risk-of-treatment-related-mortality-in-cancer-patients-treated-with-ipilimumab-a-systematic-review-and-meta-analysis
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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...
July 7, 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
#8
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
#9
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
https://www.readbyqxmd.com/read/28656248/nestin-positive-microvessel-density-is-an-independent-prognostic-factor-in-breast-cancer
#10
Aleksandra Nowak, Jedrzej Grzegrzolka, Maria Paprocka, Aleksandra Piotrowska, Janusz Rys, Rafal Matkowski, Piotr Dziegiel
The process of angiogenesis based on new vessel formation within the tumour area plays a significant role in the progression of breast cancer. Nestin is an intermediate filament protein and participates in the cytoskeleton organization. Nestin expression in the endothelium of blood vessels is mainly limited to newly forming vessels, thus being a more specific marker of angiogenesis than the commonly used vascular antigens. The aim of this study was to determine the prognostic value of nestin-positive microvessel density (Nes+MVD) in breast cancer patients and to confirm that nestin expression is related to newly forming tumour vessels...
June 26, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28640739/hepatitis-b-virus-core-antigen-mutations-predict-post-operative-prognosis-of-patients-with-primary-hepatocellular-carcinoma
#11
Jian'an Jia, Huiming Li, Hui Wang, Shipeng Chen, Mengmeng Wang, Huijuan Feng, Yuzhen Gao, Yunjiu Wang, Meng Fang, Chunfang Gao
The aim of this study was to explore the relationship between hepatitis B virus (HBV) core antigen (HBc) mutations and the post-operative prognosis of HBV-related hepatocellular carcinoma (HCC). In total, 98 patients suffering from HBV-related HCC and treated with surgery were enrolled, with a 48 month follow-up. The preCore/Core region of the HBV genome from tumour tissue (TT) and paired adjacent non-tumour tissue (ANTT) of these patients was sequenced, and a phylogenetic tree was reconstructed. The correlations between the viral features and evolutionary divergence of preCore/Core amino acid sequences from 67 paired TTs and ANTTs were analysed...
June 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28635677/t-cell-manipulation-strategies-to-prevent-graft-versus-host-disease-in-haploidentical-stem-cell-transplantation
#12
REVIEW
Jayakumar Vadakekolathu, Sergio Rutella
Allogeneic haematopoietic stem cell transplantation (HSCT) from an human leukocyte antigen (HLA)-identical donor can be curative for eligible patients with non-malignant and malignant haematological disorders. HSCT from alternative donor sources, such as HLA-mismatched haploidentical donors, is increasingly considered as a viable therapeutic option for patients lacking HLA-matched donors. Initial attempts at haploidentical HSCT were associated with vigorous bidirectional alloreactivity, leading to unacceptably high rates of graft rejection and graft-versus-host disease (GVHD)...
June 21, 2017: Biomedicines
https://www.readbyqxmd.com/read/28634106/biology-evolution-and-medical-importance-of-polyomaviruses-an-update
#13
REVIEW
Ugo Moens, Andi Krumbholz, Bernhard Ehlers, Roland Zell, Reimar Johne, Sébastien Calvignac-Spencer, Chris Lauber
The family Polyomaviridae encompasses non-enveloped viruses with a circular dsDNA genome that is typically approximately 5000bp in length. Originally isolated from mammals, polyomavirus sequences have now been detected in invertebrates, fish, amphibians, reptiles and birds, although it remains to be determined whether all these animals are genuine hosts. The genomes of all polyomaviruses encode at least two regulatory proteins (large and small tumour antigen) and two structural proteins (capsid proteins VP1 and VP2) whose functions have been defined...
June 17, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28632300/chemo-bacterial-synthesis-of-a-sialyl-tn-cyclopeptide-vaccine-candidate
#14
Emeline Richard, C Pifferi, M Fiore, Eric Samain, Audrey Le Gouellec, Sébastien Fort, Olivier Renaudet, Bernard Priem
A conjugatable form of the tumour-associated carbohydrate antigen sialyl-Tn (Neu5Ac-alfa-2,6-GalNAc) was efficiently produced in Escherichia coli. Metabolically engineered E. coli strains overexpressing the 6-sialyl-transferase gene of Photobacterium sp. and CMP-Neu5Ac synthetase genes of Neisseria meningitidis were cultivated at high density in presence of GalNAc-alfa-propargyl as the exogeneous acceptor. The target disaccharides, which were produced on the scale of several hundred milligrams, were then conjugated using CuAAC click chemistry to a fully synthetic and immunogenic scaffold with the aim to create a candidate anticancer vaccine...
June 20, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28622612/influence-of-age-and-comorbidity-on-prognosis-and-application-of-adjuvant-chemotherapy-in-elderly-japanese-patients-with-colorectal-cancer-a-retrospective-multicentre-study
#15
Tomoki Yamano, Shinichi Yamauchi, Kei Kimura, Akihito Babaya, Michiko Hamanaka, Masayoshi Kobayashi, Miki Fukumoto, Kiyoshi Tsukamoto, Masafumi Noda, Naohiro Tomita, Kenichi Sugihara
BACKGROUND: Adjuvant therapy for colorectal cancer (CRC) in patients aged ≥75 years is supported by inadequate evidence, although such patients are increasing in number worldwide. PATIENTS AND METHODS: We assessed the influence of age and comorbidities on the prognosis of CRC in elderly patients using pooled data by the Japanese Study Group for Postoperative Follow-up of Colorectal Cancer. In total, 4598 patients (3304 with colon cancer and 1294 with rectal cancer) who underwent curative surgery from 2004 to 2006 were analysed with respect to age, Charlson comorbidity score (CS), tumour marker positivity, adjuvant therapy and prognosis...
August 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28622526/extragastrointestinal-stromal-tumour-of-the-lesser-omentum-a-case-report-and-literature-review
#16
I E Katsoulis, A Tzortzopoulou, P Tziakou, N Arnogiannaki, I Kostoglou-Athanassiou, G Lypas, I G Karaitianos
INTRODUCTION: Extragastrointestinal stromal tumours (EGISTs) are very uncommon compared to their gastrointestinal counterparts. Most of them originate from the intestinal mesentery and the omentum. CASE REPORT: A 70 year-old Caucasian woman presented with a bulky abdominal mass which on laparotomy was found to originate from the lesser omentum and was completely resected. Histological examination revealed spindle cells with severe pleomorphism and high mitotic activity...
June 8, 2017: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/28610792/quantitative-and-qualitative-inkt-repertoire-associations-with-disease-susceptibility-and-outcome-in-macaque-tuberculosis-infection
#17
Andrew Chancellor, Andrew White, Anna S Tocheva, Joe R Fenn, Mike Dennis, Liku Tezera, Akul Singhania, Tim Elliott, Marc Tebruegge, Paul Elkington, Stephan Gadola, Sally Sharpe, Salah Mansour
Correlates of immune protection that reliably predict vaccine efficacy against Mycobacterium tuberculosis (Mtb) infection are urgently needed. Invariant NKT cells (iNKTs) are CD1d-dependent innate T cells that augment host antimicrobial immunity through production of cytokines, including interferon (IFN)-γ and tumour necrosis factor (TNF)-α. We determined peripheral blood iNKT numbers, their proliferative responses and iNKT subset proportions after in vitro antigen expansion by α-galactosylceramide (αGC) in a large cohort of mycobacteria-naïve non-human primates, and macaques from Bacillus Calmette-Guerin (BCG) vaccine and Mtb challenge studies...
July 2017: Tuberculosis
https://www.readbyqxmd.com/read/28609309/spontaneous-regression-of-malignant-melanoma-is-it-based-on-the-interplay-between-host-immune-system-and-melanoma-antigens
#18
Monika Cervinkova, Petra Kucerova, Jana Cizkova
Malignant melanoma (MM) is the most aggressive and uneasily treatable form of skin cancer. Up to 90% of deaths because of skin tumours are estimated to be caused by this malignancy. Spontaneous regression is described as a partial or complete disappearance of cancer. It can be defined if the clinical and histological diagnosis of malignancy is verified and any therapeutic intervention potentially inducing mechanisms leading to regression has not been applied. Regression occurs more frequently in melanoma than in other types of tumours; it is reported to be six times higher than in other malignancies...
June 12, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28607123/plasma-levels-of-intact-and-cleaved-urokinase-plasminogen-activator-receptor-upar-in-men-with-clinically-localised-prostate-cancer
#19
Gitte Kristensen, Kasper Drimer Berg, Solvej Lippert, Ib Jarle Christensen, Klaus Brasso, Gunilla Høyer-Hansen, Martin Andreas Røder
AIMS: Lymph node metastasis (N1) is an adverse prognostic factor for men with clinically localised prostate cancer (PCa), but the prediction of N1 disease remains difficult. Urokinase plasminogen activator receptor (uPAR) plays an important role in angiogenesis and tumorigenesis. We analysed whether plasma levels of the soluble uPAR forms uPAR(I-III), uPAR(II-III) and uPAR(I) were associated with the risk of N1 disease in men with clinically localised PCa. METHODS: The present study includes all men (n=518) who underwent radical prostatectomy (RP) for clinically localised PCa, 29 of whom had N1 disease...
June 12, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28596508/promoter-hypomethylation-of-ny-eso-1-association-with-clinicopathological-features-and-pd-l1-expression-in-non-small-cell-lung-cancer
#20
Anderly C Chüeh, Mun-Sem Liew, Prudence A Russell, Marzena Walkiewicz, Aparna Jayachandran, Maud H W Starmans, Paul C Boutros, Gavin Wright, Stephen A Barnett, John M Mariadason, Thomas John
Cancer-Testis antigens (CTA) are immunogenic molecules with normal tissue expression restricted to testes but with aberrant expression in up to 30% of non-small cell lung cancers (NSCLCs). Regulation of CTA expression is mediated in part through promoter DNA methylation. Recently, immunotherapy has altered treatment paradigms in NSCLC. Given its immunogenicity and ability to be re-expressed through demethylation, NY-ESO-1 promoter methylation, protein expression and its association with programmed death receptor ligand-1 (PD-L1) expression and clinicopathological features were investigated...
May 23, 2017: Oncotarget
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