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https://www.readbyqxmd.com/read/27868181/correlation-between-the-high-expression-levels-of-cancer-germline-genes-with-clinical-characteristics-in-esophageal-squamous-cell-carcinoma
#1
Xinfeng Chen, Liping Wang, Dongli Yue, Jinyan Liu, Lan Huang, Li Yang, Ling Cao, Guohui Qin, Anqi Li, Dan Wang, Meng Wang, Yu Qi, Bin Zhang, Pierre van der Bruggen, Yi Zhang
Antigens encoded by cancer-germline genes are attractive targets for cancer immunotherapy. In this study, we aimed to evaluate the mRNA expression of cancer-germline genes, expression of the encoded proteins in patients with esophageal squamous cell carcinoma (ESCC) and their correlations with clinical characteristics. In addition, the effects of downregulation cancer-germline genes on ESCC cells were assessed in vitro. Our results showed that cancer-germline genes were frequently expressed in ESCC samples...
November 21, 2016: Histology and Histopathology
https://www.readbyqxmd.com/read/27856179/exosomal-proteins-as-prognostic-biomarkers-in-non-small-cell-lung-cancer
#2
B Sandfeld-Paulsen, N Aggerholm-Pedersen, R Bæk, K R Jakobsen, P Meldgaard, B H Folkersen, T R Rasmussen, K Varming, M M Jørgensen, B S Sorensen
BACKGROUND: Use of exosomes as biomarkers in non-small cell lung cancer (NSCLC) is an intriguing approach in the liquid-biopsy era. Exosomes are nano-sized vesicles with membrane-bound proteins that reflect their originating cell. Prognostic biomarkers are needed to improve patient selection for optimal treatment. We here evaluate exosomes by protein phenotyping as a prognostic biomarker in NSCLC. METHODS: Exosomes from plasma of 276 NSCLC patients were phenotyped using the Extracellular Vesicle Array; 49 antibodies captured the proteins on the exosomes, and a cocktail of biotin-conjugated antibodies binding the general exosome markers CD9, CD81 and CD63 was used to visualise the captured exosomes...
October 21, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/27853637/vaccination-of-stage-iii-iv-melanoma-patients-with-long-ny-eso-1-peptide-and-cpg-b-elicits-robust-cd8-and-cd4-t-cell-responses-with-multiple-specificities-including-a-novel-dr7-restricted-epitope
#3
P Baumgaertner, C Costa Nunes, A Cachot, H Maby-El Hajjami, L Cagnon, M Braun, L Derré, J-P Rivals, D Rimoldi, S Gnjatic, S Abed Maillard, P Marcos Mondéjar, M P Protti, E Romano, O Michielin, P Romero, D E Speiser, C Jandus
Long synthetic peptides and CpG-containing oligodeoxynucleotides are promising components for cancer vaccines. In this phase I trial, 19 patients received a mean of 8 (range 1-12) monthly vaccines s.c. composed of the long synthetic NY-ESO-179-108 peptide and CpG-B (PF-3512676), emulsified in Montanide ISA-51. In 18/18 evaluable patients, vaccination induced antigen-specific CD8(+) and CD4(+) T-cell and antibody responses, starting early after initiation of immunotherapy and lasting at least one year. The T-cells responded antigen-specifically, with strong secretion of IFNγ and TNFα, irrespective of patients' HLAs...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27793776/case-control-study-smoking-history-affects-the-production-of-tumor-antigen-specific-antibodies-ny-eso-1-in-patients-with-lung-cancer-in-comparison-with-cancer-disease-free-group
#4
Dagmar Myšíková, Irena Adkins, Hradilová Naďa, Palata Ondřej, Jan Šimonek, Jiří Pozniak, Jan Kolařík, Anna Skallová-Fialová, Radek Špíšek, Robert Lischke
INTRODUCTION: Lung cancer is the leading cause of cancer mortality worldwide therefore understanding the biological or clinical role of tumor associated antigens and autoantibodies is of an eminent interest for designing anti-tumor immunotherapeutic strategies. METHODS: Here we prospectively analyzed the serum frequencies of NY-ESO-1, Her2/neu and MAGE-A4 antibodies and corresponding antigens expression in tumors of 121 non-small cell lung (NSCLC) patients undergoing surgery without prior neoadjuvant chemotherapy and compared them with 57 control age-matched patients with no history of a malignant disease...
October 25, 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27792920/t-cell-inflammation-profile-after-surgical-resection-may-predict-tumor-recurrence-in-hbv-related-hepatocellular-carcinoma
#5
Bin Song, Shoumei Zhen, Fanzhi Meng
The most effective treatment for HBV-related hepatocellular carcinoma (HCC) is surgical removal of the tumor in early stage patients. But many such patients will develop recurrent tumor within the first 24months, which is the major cause of death. To enable the prevention and earlier detection of recurrent HCC, we investigated the T cell responses that were potentially involved in HCC recurrence. We found that patients with recurrent HCC presented significantly lower frequencies of interferon gamma (IFNγ)-expressing Th1 cells and Tc1 cells, as well as significantly elevated Foxp3(+) Treg cells, in the peripheral blood and the resected primary tumor...
October 25, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27626061/lv305-a-dendritic-cell-targeting-integration-deficient-zvex-tm-based-lentiviral-vector-encoding-ny-eso-1-induces-potent-anti-tumor-immune-response
#6
Tina Chang Albershardt, David James Campbell, Andrea Jean Parsons, Megan Merrill Slough, Jan Ter Meulen, Peter Berglund
We have engineered an integration-deficient lentiviral vector, LV305, to deliver the tumor antigen NY-ESO-1 to human dendritic cells in vivo through pseudotyping with a modified Sindbis virus envelop protein. Mice immunized once with LV305 developed strong, dose-dependent, multifunctional, and cytotoxic NY-ESO-1-specific cluster of differentiation 8 (CD8) T cells within 14 days post-immunization and could be boosted with LV305 at least twice to recall peak-level CD8 T-cell responses. Immunization with LV305 protected mice against tumor growth in an NY-ESO-1-expressing CT26 lung metastasis model, with the protective effect abrogated upon depletion of CD8 T cells...
2016: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/27533084/frequency-of-expression-and-generation-of-t-cell-responses-against-antigens-on-multiple-myeloma-cells-in-patients-included-in-the-gmmg-mm5-trial
#7
Michael Schmitt, Angela G Hückelhoven, Michael Hundemer, Anita Schmitt, Susanne Lipp, Martina Emde, Hans Salwender, Mathias Hänel, Katja Weisel, Uta Bertsch, Jan Dürig, Anthony D Ho, Igor Wolfgang Blau, Hartmut Goldschmidt, Anja Seckinger, Dirk Hose
BACKGROUND: Raising T-cell response against antigens either expressed on normal and malignant plasma cells (e.g. HM1.24) or aberrantly on myeloma cells only (e.g. cancer testis antigens, CTA) by vaccination is a potential treatment approach for multiple myeloma. RESULTS: Expression by GEP is found for HM1.24 in all, HMMR in 318/458 (69.4%), MAGE-A3 in 209/458 (45.6%), NY-ESO-1/2 in 40/458 (8.7%), and WT-1 in 4/458 (0.8%) of samples with the pattern being confirmed by RNA-sequencing...
August 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27504122/diversification-of-antitumour-immunity-in-a-patient-with-metastatic-melanoma-treated-with-ipilimumab-and-an-ido-silenced-dendritic-cell-vaccine
#8
Mouldy Sioud, Marta Nyakas, Stein Sæbøe-Larssen, Anne Mobergslien, Steinar Aamdal, Gunnar Kvalheim
Indoleamine 2,3-dioxygenase (IDO) expression in dendritic cells (DCs) inhibits T-cell activation and promotes T-cell differentiation into regulatory T-cells. Moreover, IDO expression promotes resistance to immunotherapies targeting immune checkpoints such as the cytotoxic T lymphocyte antigen-4 (CTLA-4). Here, a patient with metastatic melanoma pretreated with ipilimumab, an anti-CTLA-4 blocking antibody, was vaccinated with IDO-silenced DCs cotransfected with mRNA for survivin or hTERT tumour antigens. During vaccination, T-cell responses to survivin and hTERT tumour antigens were generated, and a certain degree of clinical benefit was achieved, with a significant reduction in lung, liver, and skin metastases, along with a better performance status...
2016: Case Reports in Medicine
https://www.readbyqxmd.com/read/27485079/current-status-of-engineered-t-cell-therapy-for-synovial-sarcoma
#9
Matthew Dallos, William D Tap, Sandra P D'Angelo
Synovial sarcoma is a rare soft tissue sarcoma characterized by a t(X;18) translocation, which results in a SYT-SSX gene fusion. In the metastatic setting, chemotherapy has limited, durable efficacy prompting the necessity for new therapeutic modalities. One emerging new strategy involves T-cell-directed therapy such as tumor-infiltrating lymphocytes or the development of T cells that are genetically engineered to express a T-cell receptor against a cancer testis antigen. Of these approaches, engineered T cells that recognize NY-ESO-1 are the furthest along in development...
September 2016: Immunotherapy
https://www.readbyqxmd.com/read/27484900/chemotherapy-and-radiation-therapy-elicits-tumor-specific-t-cell-responses-in-a-breast-cancer-patient
#10
David Bernal-Estévez, Ramiro Sánchez, Rafael E Tejada, Carlos Parra-López
BACKGROUND: Experimental evidence and clinical studies in breast cancer suggest that some anti-tumor therapy regimens generate stimulation of the immune system that accounts for tumor clinical responses, however, demonstration of the immunostimulatory power of these therapies on cancer patients continues to be a formidable challenge. Here we present experimental evidence from a breast cancer patient with complete clinical response after 7 years, associated with responsiveness of tumor specific T cells...
2016: BMC Cancer
https://www.readbyqxmd.com/read/27471648/scib2-an-antibody-dna-vaccine-encoding-ny-eso-1-epitopes-induces-potent-antitumor-immunity-which-is-further-enhanced-by-checkpoint-blockade
#11
Wei Xue, Rachael L Metheringham, Victoria A Brentville, Barbara Gunn, Peter Symonds, Hideo Yagita, Judith M Ramage, Lindy G Durrant
Checkpoint blockade has demonstrated promising antitumor responses in approximately 10-40% of patients. However, the majority of patients do not make a productive immune response to their tumors and do not respond to checkpoint blockade. These patients may benefit from an effective vaccine that stimulates high-avidity T cell responses in combination with checkpoint blockade. We have previously shown that incorporating TRP-2 and gp100 epitopes into the CDR regions of a human IgG1 DNA (ImmunoBody®: IB) results in significant tumor regression both in animal models and patients...
June 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27466502/influence-of-photodynamic-therapy-on-the-expression-of-cancer-testis-antigens-in-squamous-cell-carcinoma-of-the-head-and-neck
#12
Marie-Nicole Theodoraki, Kai J Lorenz, Juliane Schneider, Julia C Thierauf, Giulio Spagnoli, Patrick J Schuler, Thomas K Hoffmann, Simon Laban
BACKGROUND: Photodynamic therapy (PDT) represents a palliative treatment resulting in induction of inflammatory reactions with importance for the development of an antitumor immunity. Cancer/testis antigens (CTAs) have been associated with poor prognosis in different types of cancer, including head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Tumor tissue samples before and after PDT were evaluated for the expression of four different CTAs by immunohistochemistry...
August 2016: Anticancer Research
https://www.readbyqxmd.com/read/27324616/human-leucocyte-antigen-class-i-redirected-anti-tumour-cd4-t-cells-require-a-higher-t-cell-receptor-binding-affinity-for-optimal-activity-than-cd8-t-cells
#13
M P Tan, G M Dolton, A B Gerry, J E Brewer, A D Bennett, N J Pumphrey, B K Jakobsen, A K Sewell
CD4(+) T helper cells are a valuable component of the immune response towards cancer. Unfortunately, natural tumour-specific CD4(+) T cells occur in low frequency, express relatively low-affinity T cell receptors (TCRs) and show poor reactivity towards cognate antigen. In addition, the lack of human leucocyte antigen (HLA) class II expression on most cancers dictates that these cells are often unable to respond to tumour cells directly. These deficiencies can be overcome by transducing primary CD4(+) T cells with tumour-specific HLA class I-restricted TCRs prior to adoptive transfer...
June 20, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27323861/expression-of-tumor-antigens-on-primary-ovarian-cancer-cells-compared-to-established-ovarian-cancer-cell-lines
#14
Kamila Kloudová, Hana Hromádková, Simona Partlová, Tomáš Brtnický, Lukáš Rob, Jiřina Bartůňková, Michal Hensler, Michael J Halaška, Radek Špíšek, Anna Fialová
In order to select a suitable combination of cancer cell lines as an appropriate source of antigens for dendritic cell-based immunotherapy of ovarian cancer, we analyzed the expression level of 21 tumor associated antigens (BIRC5, CA125, CEA, DDX43, EPCAM, FOLR1, Her-2/neu, MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A6, MAGE-A10, MAGE-A12, MUC-1, NY-ESO-1, PRAME, p53, TPBG, TRT, WT1) in 4 established ovarian cancer cell lines and in primary tumor cells isolated from the high-grade serous epithelial ovarian cancer tissue...
June 14, 2016: Oncotarget
https://www.readbyqxmd.com/read/27294163/adjuvant-autologous-melanoma-vaccine-for-macroscopic-stage-iii-disease-survival-biomarkers-and-improved-response-to-ctla-4-blockade
#15
Michal Lotem, Sharon Merims, Stephen Frank, Tamar Hamburger, Aviram Nissan, Luna Kadouri, Jonathan Cohen, Ravid Straussman, Galit Eisenberg, Shoshana Frankenburg, Einat Carmon, Bilal Alaiyan, Shlomo Shneibaum, Zeynep Ozge Ayyildiz, Murat Isbilen, Kerem Mert Senses, Ilan Ron, Hanna Steinberg, Yoav Smith, Eitan Shiloni, Ali Osmay Gure, Tamar Peretz
Background. There is not yet an agreed adjuvant treatment for melanoma patients with American Joint Committee on Cancer stages III B and C. We report administration of an autologous melanoma vaccine to prevent disease recurrence. Patients and Methods. 126 patients received eight doses of irradiated autologous melanoma cells conjugated to dinitrophenyl and mixed with BCG. Delayed type hypersensitivity (DTH) response to unmodified melanoma cells was determined on the vaccine days 5 and 8. Gene expression analysis was performed on 35 tumors from patients with good or poor survival...
2016: Journal of Immunology Research
https://www.readbyqxmd.com/read/27158940/the-future-of-immunotherapy-for-sarcoma
#16
Tomohide Tsukahara, Makoto Emori, Kenji Murata, Emi Mizushima, Yuji Shibayama, Terufumi Kubo, Takayuki Kanaseki, Yoshihiko Hirohashi, Toshihiko Yamashita, Noriyuki Sato, Toshihiko Torigoe
INTRODUCTION: The use of immunotherapeutic challenges for sarcoma has a long history. Despite the existence of objective responses, immunotherapy has been overshadowed by the results of chemotherapy, especially for osteosarcoma. However, the prognosis for non-responders to chemotherapy is still poor and immunotherapy is now focused on again. AREAS COVERED: We reviewed the following types of clinical trials of immunotherapy for sarcoma: (i) vaccination with autologous tumor cells, (ii) vaccination with peptides derived from tumor-associated antigens, (iii) adoptive cell transfer using engineered T cells expressing T cell receptor directed at NY-ESO-1 and (iv) immune checkpoint inhibitors targeting CTLA-4 and PD1/PDL1...
August 2016: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/27103177/hla-superfamily-assignment-is-a-predictor-of-immune-response-to-cancer-testis-antigens-and-survival-in-ovarian-cancer
#17
J Brian Szender, Kevin H Eng, Junko Matsuzaki, Anthony Miliotto, Sacha Gnjatic, Takemasa Tsuji, Kunle Odunsi
OBJECTIVES: To characterize the association between major histocompatibility complex (MHC) types and spontaneous antibody development to the cancer testis (CT) antigen NY-ESO-1. METHODS: Tumor expression of NY-ESO-1 and serum antibodies to NY-ESO-1 were characterized in addition to human leukocyte antigen (HLA) type for patients with epithelial ovarian cancer. HLA types were assigned to structure-based superfamilies and statistical associations were examined. HLA types were compared to existing reference libraries of HLA frequencies in a European-Caucasian American population...
July 2016: Gynecologic Oncology
https://www.readbyqxmd.com/read/27070449/mage-a-is-more-highly-expressed-than-ny-eso-1-in-a-systematic-immunohistochemical-analysis-of-3668-cases
#18
Sid P Kerkar, Zeng-Feng Wang, Jerzy Lasota, Tristen Park, Krishna Patel, Eric Groh, Steven A Rosenberg, Markku M Miettinen
Two cancer testis antigens, the New York esophageal squamous cell carcinoma-1 (NY-ESO-1) and the melanoma-antigen family A (MAGE-A), represent promising immunotherapy targets due to the low expression of these antigens in nonmalignant tissue. To assess overexpression patterns in various cancers, we performed a systematic immunohistochemical analysis for NY-ESO-1 and MAGE-A on tissue array samples of 3668 common epithelial carcinomas (CA) and germ cell tumors of high prevalence and mortality. Here, we find significantly higher expression of MAGE-A (>50% on tumor cells) compared with NY-ESO-1 in several CAs including cutaneous squamous cell carcinomas (SCC) (52...
May 2016: Journal of Immunotherapy
https://www.readbyqxmd.com/read/26942053/t-cells-targeting-ny-eso-1-demonstrate-efficacy-against-disseminated-neuroblastoma
#19
Nathan Singh, Irina Kulikovskaya, David M Barrett, Gwendolyn Binder-Scholl, Bent Jakobsen, Daniel Martinez, Bruce Pawel, Carl H June, Michael D Kalos, Stephan A Grupp
The cancer-testis antigen NY-ESO-1 is expressed by many solid tumors and has limited expression by mature somatic tissues, making it a highly attractive target for tumor immunotherapy. Targeting NY-ESO-1 using engineered T cells has demonstrated clinical efficacy in the treatment of some adult tumors. Neuroblastoma is a significant cause of cancer mortality in children, and is a tumor type shown to be responsive to immunotherapies. We evaluated a large panel of primarily resected neuroblastoma samples and demonstrated that 23% express NY-ESO-1...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/26911296/production-of-antigen-specific-human-iggs-by-in-vitro-immunization
#20
A Wijkhuisen, A Savatier, N Cordeiro, M Léonetti
BACKGROUND: We previously developed in vitro immunization based on a fusion protein containing the transcriptional transactivator (Tat) of human immunodeficiency virus and a double domain, called ZZ, derived from protein A of Staphylococcus aureus. In this approach, naïve human peripheral blood mononuclear cells (PBMCs) trigger a specific IgM antibody (Ab) response in the presence of ZZTat. In the present study, we attempted to raise a specific IgG Ab response. RESULTS: We found that PBMCs incubated with ZZTat and a mixture containing anti-CD40, IL4 and IL21 secrete anti-Tat IgG Abs in their supernatants, indicating that the cytokine cocktail provides an isotypic switch...
2016: BMC Biotechnology
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