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Tumour associated antigens

Edward Johnston, Hayley Pye, Elisenda Bonet-Carne, Eleftheria Panagiotaki, Dominic Patel, Myria Galazi, Susan Heavey, Lina Carmona, Alexander Freeman, Giorgia Trevisan, Clare Allen, Alexander Kirkham, Keith Burling, Nicola Stevens, David Hawkes, Mark Emberton, Caroline Moore, Hashim U Ahmed, David Atkinson, Manuel Rodriguez-Justo, Tony Ng, Daniel Alexander, Hayley Whitaker, Shonit Punwani
BACKGROUND: Whilst multi-parametric magnetic resonance imaging (mp-MRI) has been a significant advance in the diagnosis of prostate cancer, scanning all patients with elevated prostate specific antigen (PSA) levels is considered too costly for widespread National Health Service (NHS) use, as the predictive value of PSA levels for significant disease is poor. Despite the fact that novel blood and urine tests are available which may predict aggressive disease better than PSA, they are not routinely employed due to a lack of clinical validity studies...
October 21, 2016: BMC Cancer
Qian Chen, Ligeng Xu, Chao Liang, Chao Wang, Rui Peng, Zhuang Liu
A therapeutic strategy that can eliminate primary tumours, inhibit metastases, and prevent tumour relapses is developed herein by combining adjuvant nanoparticle-based photothermal therapy with checkpoint-blockade immunotherapy. Indocyanine green (ICG), a photothermal agent, and imiquimod (R837), a Toll-like-receptor-7 agonist, are co-encapsulated by poly(lactic-co-glycolic) acid (PLGA). The formed PLGA-ICG-R837 nanoparticles composed purely by three clinically approved components can be used for near-infrared laser-triggered photothermal ablation of primary tumours, generating tumour-associated antigens, which in the presence of R837-containing nanoparticles as the adjuvant can show vaccine-like functions...
October 21, 2016: Nature Communications
Peter L Stern, Richard Harrop
The natural history of a patient's cancer is often characterised by genetic diversity and sequential sweeps of clonal dominance. It is therefore not surprising that identifying the most appropriate tumour-associated antigen for targeted intervention is challenging. The 5T4 oncofoetal antigen was identified by searching for surface molecules shared between human trophoblast and cancer cells with the rationale that they may function to allow survival of the foetus as a semi-allograft in the mother or a tumour in its host...
October 18, 2016: Cancer Immunology, Immunotherapy: CII
Amanda Tivnan, Tatjana Heilinger, Ed C Lavelle, Jochen H M Prehn
Glioblastoma (GBM) is an aggressive brain tumour, associated with extremely poor prognosis and although there have been therapeutic advances, treatment options remain limited. This review focuses on the use of immunotherapy, harnessing the power of the host's immune system to reject cancer cells. Key challenges in glioma specific immunotherapy as with many other cancers are the limited immunogenicity of the cancer cells and the immunosuppressive environment of the tumour. Although specific antigens have been identified in several cancers; brain tumours, such as GBM, are considered poorly immunogenic...
October 14, 2016: Journal of Neuro-oncology
Peter Haahr, Saskia Hoffmann, Maxim A X Tollenaere, Teresa Ho, Luis Ignacio Toledo, Matthias Mann, Simon Bekker-Jensen, Markus Räschle, Niels Mailand
Activation of the ATR kinase following perturbations to DNA replication relies on a complex mechanism involving ATR recruitment to RPA-coated single-stranded DNA via its binding partner ATRIP and stimulation of ATR kinase activity by TopBP1. Here, we discovered an independent ATR activation pathway in vertebrates, mediated by the uncharacterized protein ETAA1 (Ewing's tumour-associated antigen 1). Human ETAA1 accumulates at DNA damage sites via dual RPA-binding motifs and promotes replication fork progression and integrity, ATR signalling and cell survival after genotoxic insults...
October 10, 2016: Nature Cell Biology
Malay Patra, Kristof Zarschler, Hans-Jürgen Pietzsch, Holger Stephan, Gilles Gasser
Tumour pretargeting is a promising strategy for cancer diagnosis and therapy allowing for the rational use of long circulating, highly specific monoclonal antibodies (mAbs) for both non-invasive cancer radioimmunodetection (RID) and radioimmunotherapy (RIT). In contrast to conventional RID/RIT where the radionuclides and oncotropic vector molecules are delivered as presynthesised radioimmunoconjugates, the pretargeting approach is a multistep procedure that temporarily separates targeting of certain tumour-associated antigens from delivery of diagnostic or therapeutic radionuclides...
September 27, 2016: Chemical Society Reviews
E Onjukka, J Uzan, C Baker, L Howard, A Nahum, I Syndikus
AIMS: For patients with high-risk, locally bulky prostate cancer, an intra-prostatic boost to tumour volumes (dose-painting) offers a risk-adapted dose escalation. We evaluated the feasibility of hypofractionated dose-painting radiotherapy and the associated toxicity. The possibility to streamline a radiobiologically optimised planning protocol was also investigated. MATERIALS AND METHODS: Twenty-eight patients were treated using a dose-painting approach; boost volumes were identified with functional magnetic resonance imaging scans...
September 29, 2016: Clinical Oncology: a Journal of the Royal College of Radiologists
Maria Sole Chimenti, Alberto Bergamini, Paola Triggianese, Maria Domenica Guarino, Gianfranco Gigliucci, Paola Conigliaro, Carlo Perricone, Roberto Perricone
OBJECTIVES: To investigate the presence of immunoglobulin-like transcript (ILT)4 and costimulatory proteins (CD40, CD80 and CD86), as well as tumour necrosis factor (TNF)-α production in antigen-presenting cells (APCs) from patients with psoriatic arthritis, before and after treatment with the antitumour necrosis factor-α therapy, adalimumab. METHODS: Peripheral blood monocytes from patients with psoriatic arthritis and healthy controls were cultured with CD40 ligand (CD40L) to stimulate differentiation to APCs...
September 2016: Journal of International Medical Research
Lydia Dyck, Mieszko M Wilk, Mathilde Raverdeau, Alicja Misiak, Louis Boon, Kingston H G Mills
The co-inhibitory molecule PD-1 suppresses T cell responses and has been targeted in the treatment of cancer. Here, we examined the role of PD-1 in regulating the balance between regulatory and effector T cells and whether blocking PD-1 could enhance tumour vaccine-induced protective immunity. A significantly higher proportion of tumour-resident T cells expressed PD-1 and Foxp3 compared with T cells in the tumour circulation or draining lymph nodes, and this correlated with a lower frequency of IFN-γ- and TNF-secreting CD8 T cells...
September 28, 2016: Cancer Immunology, Immunotherapy: CII
N P Amdare, V K Khatri, R S P Yadav, A Tarnekar, K Goswami, M V R Reddy
Epidemiological and experimental evidence has supported the concept of using helminths as alternative bio-therapeutic agents in the treatment of type 1 diabetes (T1D). In the current study, two filarial proteins, recombinant Wuchereria bancrofti L2 (rWbL2) and Brugia malayi abundant larval transcript 2 (rBmALT-2) have been investigated, individually and in combination, for their therapeutic potential in streptozotocin (STZ)-induced T1D. The rWbL2 and rBmALT-2 proteins, when administered individually or in combination, have resulted in lowering of the blood glucose levels and reducing the incidence of T1D in mice...
September 26, 2016: Journal of Helminthology
Cesare Gridelli, Paolo A Ascierto, Massimo C P Barberis, Enriqueta Felip, Edward B Garon, Mary O'brien, Suresh Senan, Francesca Casaluce, Assunta Sgambato, Vali Papadimitrakopoulou, Filippo De Marinis
INTRODUCTION: The potential long term survival gain, related to immune adaptability and memory, the potential activity across multiple tumour types through targeting the immune system, and the opportunity for combinations offered by the unique mechanism of actions and safety profile of these new agents, all support the role of immunotherapy in the cancer treatment pathway or paradigm. AREAS COVERED: The authors discuss the recent advances in the understanding of immunology and antitumor immune responses that have led to the development of new immunotherapies, including monoclonal antibodies that inhibit immune checkpoint pathways, such as Programmed Death-1 (PD-1) and Cytotoxic T-Lymphocyte-Associated Antigen 4 (CTLA-4)...
September 21, 2016: Expert Opinion on Biological Therapy
Ashumi Gupta, Shyama Jain, Nita Khurana, Arun Kumar Kakar
INTRODUCTION: Bcl-2 is a marker recently studied in thyroid tumours and proposed to have prognostic significance. p63 is expressed in a proportion of papillary thyroid carcinoma cases and may have a role in tumour progression. AIM: To study expression of Bcl2 and p63 in thyroid tumours and correlation of Bcl-2 with diagnostic markers including Thyroglobulin, Calcitonin and Carcinoembryonic antigen. MATERIALS AND METHODS: Cytology smears of 35 cases of thyroid cancer were studied over a period of 18 months...
July 2016: Journal of Clinical and Diagnostic Research: JCDR
Alan D Smith, Mathew Truong, Rob Bristow, Paul Yip, Michael F Milosevic, Anthony M Joshua
BACKGROUND/AIM: Carbonic anhydrase IX (CA9) catalyses the interconversion of carbon dioxide to carbonic acid and bicarbonate and is considered a putative biomarker of tumour hypoxia. We set out to evaluate the prognostic significance of CA9 in prostate cancer. PATIENTS AND METHODS: Plasma samples were assessed from 68 men with high-risk localised prostate cancer treated with radical prostatectomy (RP) or radiotherapy (RT), and 20 men with castration-resistant prostate cancer (CRPC) treated with docetaxel chemotherapy between 2010 and 2012 at the Princess Margaret Cancer Centre, Canada...
September 2016: Anticancer Research
Iryna Saranchova, Jeffrey Han, Hui Huang, Franz Fenninger, Kyung Bok Choi, Lonna Munro, Cheryl Pfeifer, Ian Welch, Alexander W Wyatt, Ladan Fazli, Martin E Gleave, Wilfred A Jefferies
A new paradigm for understanding immune-surveillance and immune escape in cancer is described here. Metastatic carcinomas express reduced levels of IL-33 and diminished levels of antigen processing machinery (APM), compared to syngeneic primary tumours. Complementation of IL-33 expression in metastatic tumours upregulates APM expression and functionality of major histocompatibility complex (MHC)-molecules, resulting in reduced tumour growth rates and a lower frequency of circulating tumour cells. Parallel studies in humans demonstrate that low tumour expression of IL-33 is an immune biomarker associated with recurrent prostate and kidney renal clear cell carcinomas...
2016: Scientific Reports
David W Greening, Hong Ji, Maoshan Chen, Bruce W S Robinson, Ian M Dick, Jenette Creaney, Richard J Simpson
Malignant mesothelioma (MM) is a highly-aggressive heterogeneous malignancy, typically diagnosed at advanced stage. An important area of mesothelioma biology and progression is understanding intercellular communication and the contribution of the secretome. Exosomes are secreted extracellular vesicles shown to shuttle cellular cargo and direct intercellular communication in the tumour microenvironment, facilitate immunoregulation and metastasis. In this study, quantitative proteomics was used to investigate MM-derived exosomes from distinct human models and identify select cargo protein networks associated with angiogenesis, metastasis, and immunoregulation...
2016: Scientific Reports
Lidia M Yshii, Christina M Gebauer, Béatrice Pignolet, Emilie Mauré, Clémence Quériault, Mandy Pierau, Hiromitsu Saito, Noboru Suzuki, Monika Brunner-Weinzierl, Jan Bauer, Roland Liblau
CTLA4 is an inhibitory regulator of immune responses. Therapeutic CTLA4 blockade enhances T cell responses against cancer and provides striking clinical results against advanced melanoma. However, this therapy is associated with immune-related adverse events. Paraneoplastic neurologic disorders are immune-mediated neurological diseases that develop in the setting of malignancy. The target onconeural antigens are expressed physiologically by neurons, and aberrantly by certain tumour cells. These tumour-associated antigens can be presented to T cells, generating an antigen-specific immune response that leads to autoimmunity within the nervous system...
September 6, 2016: Brain: a Journal of Neurology
Chul-Soo Ahn, Shin Hwang, Young-Joo Lee, Ki-Hun Kim, Deok-Bog Moon, Tae-Yong Ha, Gi-Won Song, Sung-Gyu Lee
BACKGROUND: Hepatitis B virus (HBV)-associated intrahepatic cholangiocarcinoma (ICC) was reported to have a favourable prognosis. We investigated the clinicopathological features of patients with HBV-associated ICC and compared post-resection survival outcomes of ICC patients with and without hepatitis B surface antigen (HBsAg) to assess the prognostic impact of HBV infection. METHODS: A single-institution cohort of 292 patients who underwent macroscopic curative resection for ICC were divided into HBV (n = 37) and non-HBV (n = 255) groups...
September 6, 2016: ANZ Journal of Surgery
Thomas Tsitsias, Levon Toufektzian, Tom Routledge, John Pilling
A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether there is a specific subgroup of patients that would benefit from pulmonary metastasectomy for colorectal carcinoma (CRC). A total of 524 papers were identified using the reported search, of which 1 meta-analysis, 1 systematic review and 17 retrospective studies represented the best evidence to answer the clinical question. The authors, date, journal, country, study type, population, outcomes and key results are tabulated...
August 29, 2016: Interactive Cardiovascular and Thoracic Surgery
Alexandros Iliadis, Triantafyllia Koletsa, Aikaterini Patsatsi, Elisavet Georgiou, Dimitrios Sotiriadis, Ioannis Kostopoulos
The cellular microenvironment has been proven to play a crucial role in solid tumours and seems to be important in haematologic malignancies, however, it has not been adequately investigated in primary cutaneous T cell lymphomas. The aim of this study was to register the composition of the cellular microenvironment in mycosis fungoides skin lesions and correlate the composing parameters with the clinical data and follow-up results. The presence of eosinophilic polymorphonuclear leukocytes, B lymphocytes, CD68(+) macrophages, and CD1a(+) epidermal Langerhans and antigen-presenting dermal dendritic cells, as well as their relation to clinicopathological parameters, were studied in 16 mycosis fungoides cases of different disease stages...
August 19, 2016: European Journal of Dermatology: EJD
Andreia Peixoto, Elisabete Fernandes, Cristiana Gaiteiro, Luís Lima, Rita Azevedo, Janine Soares, Sofia Cotton, Beatriz Parreira, Manuel Neves, Teresina Amaro, Ana Tavares, Filipe Teixeira, Carlos Palmeira, Maria Rangel, André M N Silva, Celso A Reis, Lúcio Lara Santos, Maria José Oliveira, José Alexandre Ferreira
Invasive bladder tumours express the cell-surface Sialyl-Tn (STn) antigen, which stems from a premature stop in protein O-glycosylation. The STn antigen favours invasion, immune escape, and possibly chemotherapy resistance, making it attractive for target therapeutics. However, the events leading to such deregulation in protein glycosylation are mostly unknown. Since hypoxia is a salient feature of advanced stage tumours, we searched into how it influences bladder cancer cells glycophenotype, with emphasis on STn expression...
August 12, 2016: Oncotarget
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