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Academic literature on the topic 'Antigeni tumore associati'

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Published: 10 March 2023

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Journal articles on the topic "Antigeni tumore associati"

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Polito, M., L. Possati, G. Muzzonigro, and V. Beatrici. "Identificazione Di Antigeni Tumore Associati Con La Tecnica Dell'Immunofluorescenza Su Cellule Uroteliali Neoplastiche." Urologia Journal 57, no. 5 (October 1990): 546–48. http://dx.doi.org/10.1177/039156039005700516.

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Krishnan, Lakshmi, Lise Deschatelets, Felicity C. Stark, Komal Gurnani, and G. Dennis Sprott. "Archaeosome Adjuvant Overcomes Tolerance to Tumor-Associated Melanoma Antigens Inducing Protective CD8+T Cell Responses." Clinical and Developmental Immunology 2010 (2010): 1–13. http://dx.doi.org/10.1155/2010/578432.

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Vesicles comprised of the ether glycerolipids of the archaeonMethanobrevibacter smithii(archaeosomes) are potent adjuvants for evoking CD8+T cell responses. We therefore explored the ability of archaeosomes to overcome immunologic tolerance to self-antigens. Priming and boosting of mice with archaeosome-antigen evoked comparable CD8+T cell response and tumor protection to an alternate boosting strategy utilizing live bacterial vectors for antigen delivery. Vaccination with melanoma antigenic peptides TRP181-189and Gp10025-33delivered in archaeosomes resulted in IFN-γproducing antigen-specific CD8+T cells with strong cytolytic capability and protection against subcutaneous B16 melanoma. Targeting responses against multiple antigens afforded prolonged median survival against melanoma challenge. Entrapment of multiple peptides within the same vesicle or admixed formulations were both effective at evoking CD8+T cells against each antigen. Melanoma-antigen archaeosome formulations also afforded therapeutic protection against established B16 tumors when combined with depletion of T-regulatory cells. Overall, we demonstrate that archaeosome adjuvants constitute an effective choice for formulating cancer vaccines.
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Yang, Changlin, Kyle Dyson, Oleg Yegorov, and Duane Mitchell. "IMMU-24. A COMPREHENSIVE IN SILICO APPROACH TO DISCOVERING TUMOR REJECTION ANTIGENS IN MALIGNANT BRAIN TUMORS." Neuro-Oncology 21, Supplement_6 (November 2019): vi124. http://dx.doi.org/10.1093/neuonc/noz175.517.

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Abstract BACKGROUND Proteins that can serve as effective tumor rejection antigens within brain tumors are poorly characterized. Current prediction algorithms relying on identification of mutated epitopes as neoantigens are limited in low mutational burden tumors. We have developed a multi-faceted computer algorighm for identifying tumor rejection antigens called the Open Reading Frame Antigen Network (ORAN). This pipeline provides a comprehensive solution for predicting brain tumor immunogenic targetable epitopes/transcripts. METHODS Human and murine RNASeq and WES data were QCed. Patients individual HLA-I and HLA-II haplotypes were predicted by highly customized Optitype and Phlat Algorithms. SNPs and Indels were called from tumors WES and read through matched RNASeq data. 19,131 transcripts expression were counted per TOIL algorithm. Tumor associate antigens(TAA) of individual patient or murine tumors were selected by setting a cutoff of Transcripts Per Million (TPM) > 1 on individual patient’s tumor, while RNA Seq data from 7000 normal tissues was used to identify tumor unique transcripts. Actual sequence of HLA and SNPed Consenses TAA(CTAA) were called. Only expressed mutations and personalized TAAs were used for antigenic epitope predictions. All neoepitopes were screened against a human reference proteomic library to guarantee that epitopes were not shared by other expressed isoforms or genes. In silico validation were preformed to cross validate predictions made by ORAN. RESULTS In medullobastoma (N=121 samples), ORAN gives an average of 15.6 MHC class I restricted neoepitopes,11.9 epitopes encoded by Indels and with 33.2 MHC class II restricted neoepitopes and 16.2 Indel antigens per patient. The TAAs of each patient reaches average 256 antigenic epitopes per patient. ORAN also predicts the exact HLA and neo-antigens from a validated neoantigens vaccine dataset (Gros A Nat Med 2016). CONCLUSION ORAN accurately identifies validated neoantigens and provides a comprehensive list of potential tumor rejection antigens within human and murine brain tumors.
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Zhao, Jiaxuan, Guangsheng Du, and Xun Sun. "Tumor Antigen-Based Nanovaccines for Cancer Immunotherapy: A Review." Journal of Biomedical Nanotechnology 17, no. 11 (November 1, 2021): 2099–113. http://dx.doi.org/10.1166/jbn.2021.3178.

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As an important means of tumor immunotherapy, tumor vaccines have achieved exciting results in the past few decades. However, there are still many obstacles that hinder tumor vaccines from achieving maximum efficacy, including lack of tumor antigens, low antigen immunogenicity and poor delivery efficiency. To overcome these challenges, researchers have developed and investigated various new types of tumor antigens with higher antigenic specificity and broader antigen spectrum, such as tumor-specific peptide antigens, tumor lysates, tumor cell membrane, tumor associated exosomes, etc. At the same time, different nanoparticulate delivery platforms have been developed to increase the immunogenicity of the tumor antigens, for example by increasing their targeting efficiency of antigen-presenting cells and lymph nodes, and by co-delivering antigens with adjuvants. In this review, we summarized different types of the tumor antigens that have been reported, and introduced several nanovaccine strategies for increasing the immunogenicity of tumor antigens. The review of recent progress in these fields may provide reference for the follow-up studies of tumor antigen-based cancer immunotherapy.
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Haupt, Katharina, Michael Roggendorf, and Klauss Mann. "The Potential of DNA Vaccination against Tumor-Associated Antigens for Antitumor Therapy." Experimental Biology and Medicine 227, no. 4 (April 2002): 227–37. http://dx.doi.org/10.1177/153537020222700403.

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Conventional treatment approaches for malignant tumors are highly invasive and sometimes have only a palliative effect. Therefore, there is an increasing demand to develop novel, more efficient treatment options. Increased efforts have been made to apply immunomodulatory strategies in antitumor treatment. In recent years, immunizations with naked plasmid DNA encoding tumor-associated antigens have revealed a number of advantages. By DNA vaccination, antigen-specific cellular as well as humoral immune responses can be generated. The induction of specific immune responses directed against antigens expressed in tumor cells and displayed e.g., by MHC class I complexes can inhibit tumor growth and lead to tumor rejection. The improvement of vaccine efficacy has become a critical goal in the development of DNA vaccination as antitumor therapy. The use of different DNA delivery techniques and coadministration of adjuvants including cytokine genes may influence the pattern of specific immune responses induced. This brief review describes recent developments to optimize DNA vaccination against tumor-associated antigens. The prerequisite for a successful antitumor vaccination is breaking tolerance to tumor-associated antigens, which represent “self-antigens.” Currently, immunization with xenogeneic DNA to induce immune responses against self-molecules is under intensive investigation. Tumor cells can develop immune escape mechanisms by generation of antigen loss variants, therefore, it may be necessary that DNA vaccines contain more than one tumor antigen. Polyimmunization with a mixture of tumor-associated antigen genes may have a synergistic effect in tumor treatment. The identification of tumor antigens that may serve as targets for DNA immunization has proceeded rapidly. Preclinical studies in animal models are promising that DNA immunization is a potent strategy for mediating antitumor effects in vivo. Thus, DNA vaccines may offer a novel treatment for tumor patients. DNA vaccines may also be useful in the prevention of tumors with genetic predisposition. By DNA vaccination preventing infections, the development of viral-induced tumors may be avoided.
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Fischer, Duncan K., Terence L. Chen, and Raj K. Narayan. "Immunological and biochemical strategies for the identification of brain tumor-associated antigens." Journal of Neurosurgery 68, no. 2 (February 1988): 165–80. http://dx.doi.org/10.3171/jns.1988.68.2.0165.

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✓ Various strategies have been used to identify and characterize the antigens associated with human brain tumors. These approaches have included the raising of polyclonal and monoclonal antibodies against tumor antigens and, more recently, efforts toward the direct biochemical identification of such proteins. This review summarizes the progress made in this area, suggests reasons for the broad antigenic cross-reactivity and heterogeneity revealed by these studies, and proposes additional methods for deciphering the complex antigenic composition of human brain tumors.
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Craig, Vanessa J., Isabelle Arnold, Christiane Gerke, Minh Q. Huynh, Thomas Wündisch, Andreas Neubauer, Christoph Renner, Stanley Falkow, and Anne Müller. "Gastric MALT lymphoma B cells express polyreactive, somatically mutated immunoglobulins." Blood 115, no. 3 (January 21, 2010): 581–91. http://dx.doi.org/10.1182/blood-2009-06-228015.

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Abstract Gastric B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) arises against a background of chronic inflammation caused by persistent Helicobacter pylori infection. The clinical and histopathologic features of the human tumor can be reproduced by Helicobacter infection of BALB/c mice. In this study, we have analyzed the antibody sequences and antigen specificity of a panel of murine and human MALT lymphoma–derived antibodies. We find that a majority of tumors in patients as well as experimentally infected mice are monoclonal. The tumor immunoglobulin heavy chain genes have undergone somatic hypermutation, and approximately half of all tumors show evidence of intraclonal variation and positive and/or negative selective pressure. Recombinantly expressed MALT lymphoma antibodies bind with intermediate affinity to various unrelated self- and foreign antigens, including Helicobacter sonicate, immunoglobulin G (IgG), DNA, and stomach extract; antigen binding is blocked in a dose-dependent manner in competitive enzyme-linked immunosorbent assays. A strong bias toward the use of VH gene segments previously linked to autoantibodies and/or polyreactive antibodies in B-cell malignancies or autoimmune pathologies supports the experimental finding of polyreactivity. Our results suggest that MALT lymphoma development may be facilitated by an array of local self- and foreign antigens, providing direct antigenic stimulation of the tumor cells via their B-cell receptor.
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Fu, C., H. Zhao, Y. Wang, H. Cai, Y. Xiao, Y. Zeng, and H. Chen. "Tumor-associated antigens: Tn antigen, sTn antigen, and T antigen." HLA 88, no. 6 (September 28, 2016): 275–86. http://dx.doi.org/10.1111/tan.12900.

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Karan, Dev, Seema Dubey, and Brantley Thrasher. "Dual antigen target based immunotherapy for prostate cancer eliminates the growth of established tumors in mice (155.3)." Journal of Immunology 186, no. 1_Supplement (April 1, 2011): 155.3. http://dx.doi.org/10.4049/jimmunol.186.supp.155.3.

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Abstract Generation of antigen-specific CD8 T cells is considered optimal for an effective immunotherapy against cancer. Knowing that heterogeneity of prostate cancer limits the therapeutic benefit, we developed a recombinant adenovirus type 5 (rAd5) co-expressing a fusion of PSA (prostate-specific antigen) and PSCA (prostate stem cell antigen) genes. The selection of these genes is based on their restricted distribution within the prostate and their association with the development and progression of prostate cancer. Immunization of mice with rAd5 vector co-expressing PSA and PSCA antigens (Ad5-PSPA) simultaneously induces the expansion of anti-PSA, and anti-PSCA T cells as measured by intracellular cytokine staining for IFN-y. To analyze the impact on therapeutic efficacy of Ad5-PSPA vaccine against the tumor cells co-expressing cognate antigens (RM11-PSA/PSCA cells), injection of mice with Ad5-PSPA vaccine inhibited the growth of established tumors. Initially, the mice developed slow growing tumors and eventually upto 80% of the mice remain tumor free following immunization with Ad5-PSPA vaccine. These data provide useful information that antigen-specific effector T cells can be generated simultaneously and their additive anti-tumor effect has the ability to eliminate the growth of established tumors. Therefore, the immunotherapy approach of using the simultaneous targeting of dual antigens associated with prostate cancer may have important implications for human clinical trials.
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Dyson, Kyle, Changlin Yang, Vrunda Trivedi, Tyler Wildes, Adam Grippin, and Duane Mitchell. "IMMU-49. PREDICTING PATIENT-SPECIFIC ANTIGENS FOR MEDULLOBLASTOMA IMMUNOTHERAPY." Neuro-Oncology 22, Supplement_2 (November 2020): ii115. http://dx.doi.org/10.1093/neuonc/noaa215.479.

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Abstract BACKGROUND Identification of tumor rejection antigens remains a major barrier to the development of effective immunotherapeutics and their application to pediatric brain tumors. To identify candidate antigen targets for medulloblastoma adoptive cellular therapy, we performed a comprehensive immunogenomic analysis of medulloblastoma transcription profiles and in silico antigen prediction across a broad array of antigen classes. We hypothesized that medulloblastomas are immunologically heterogeneous and express genes with limited normal tissue expression that may serve as targets for immunotherapy. METHODS Immunologic heterogeneity was assessed using several published algorithms and approaches implemented within the R programming language. Patient-specific HLA haplotypes were called via customized Optitype and Phlat algorithms. Patient-specific tumor associated antigens (TAA) were selected only if expressed >1 transcript per million (TPM) in tumor and the standardized expression across a human tissue database was below 1 TPM. Patient-specific HLA and TAA sequences were extracted from RNA-seq data for prediction with eight MHC class I and four MHC class II affinity algorithms. Only expressed mutations and personalized TAAs were used for antigenic epitope predictions. All epitopes were screened against a human reference proteomic library to guarantee that epitopes were not shared by other expressed isoforms or genes. Public mass-spec data was also screened for protein-level antigen expression. RESULTS Although absolute immune cell content is predicted to be low, immune gene-signature analysis revealed subgroup-specific differences. Antigen prediction analysis revealed most patients express few candidate neoantigen targets passing all filtering criteria. Importantly, cancer testis antigens as well as previously unappreciated neurodevelopmental antigens were found expressed across all medulloblastoma subgroups and most patients. Protein level antigen expression was confirmed for some predicted TAAs. CONCLUSION Medulloblastomas are immunologically cold yet subgroups have distinct immune cell gene-signatures. Using a custom antigen prediction pipeline, we identified potential tumor rejection antigens with important implications for development of medulloblastoma cellular therapies.
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Dissertations / Theses on the topic "Antigeni tumore associati"

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DI, CRISTANZIANO VERONICA. "Caratterizzazione e valutazione del ruolo immunologico di un nuovo antigene associato all'adenocarcinoma del colon-retto: colorectal tumor-associated antigen 1 (COA-1)." Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2008. http://hdl.handle.net/2108/432.

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Recentemente è stato identificato un nuovo antigene associato al carcinoma del colon retto (CRC), denominato colorectal tumor-associated antigen-1 (COA-1), riconosciuto dai linfociti T CD4+ in associazione a specifiche molecole MHC di classe II e codificato del gene UBXD5. In questo studio abbiamo valutato se COA-1 sia in grado di evocare una risposta immunitaria mediata da linfociti T tumore-specifici nei pazienti affetti da CRC e se tale antigene possa rappresentare un nuovo mezzo per disegnare protocolli di immunoterapia e un marker di progressione della malattia. A tale scopo, i PBMC isolati dai pazienti con CRC sono stati stimolati in vitro con l’epitopo immunogenico di COA-1441-460 (FSTFPPTLYQDDTLTLQAAG) e la risposta immunitaria, sia antigene che tumore specifica, è stata analizzata mediante rilevazione del rilascio di IFN-g, tramite saggio ELISPOT. In tal modo, è stato possibile isolare linfociti T specifici per COA-1 e tumorereattivi da tutti i pazienti HLA-DRb1*0402 o *1301 con malattia in progressione (7/7, stadio C e D di Dukes), ma non dai pazienti con tumore in fase iniziale (4/4, stadio A e B di Dukes). I linfociti T TAA-specifici hanno mostrato un fenotipo CD3+, CD4+, CD69+, CD45RA+, compatibile con quello del subset dei linfociti T di tipo effettore. Inoltre, la maggior parte di queste cellule ha evidenziato un’attività citotossica diretta nei confronti delle cellule tumorali positive per COA-1 e per gli specifici elementi di restrizione di classe II. Abbiamo anche verificato se una risposta specifica nei confronti di COA-1 potesse essere isolata dai PBMC dei pazienti con CRC mediante l’impiego di cellule dendritiche (DC) autologhe caricate con il lisato tumporale. I nostri dati indicano che linfociti T CD4+ specifici per COA-1 e dotati di reattività anti-CRC possono essere isolati mediante stimolazione in vitro dei PBMC sia con le cellule tumorali intatte sia con le DC pulsate con il lisato del tumore autologo, suggerendo che tale TAA sia in grado di generare una risposta immunitaria dominante diretta contro il CRC. In conclusione, i risultati di questo studio indicano che COA-1 può essere considerato un antigene rilevante per la risposta immunitaria anti-tumorale nei pazienti con CRC, dal momento che correla con la progressione della malattia, e ne suggeriscono un possibile impiego nei protocolli di immunoterapia per i pazienti affetti da CRC.
Recently, a new colorectal cancer (CRC)-associated antigen, denominated colorectal tumorassociated antigen-1 (COA-1), recognized by CD4+ T lymphocytes in a HLA class IIrestricted way and encoded by UBXD5 gene, was identified. In this study, we evaluated whether COA-1 can evoke a specific T cell-mediated response in CRC patients and whether this antigen can represent a tool to design new protocols of immunotherapy and a marker for the progression of the disease. Peripheral blood lymphocytes isolated from CRC patients have been in vitro stimulated with the immunogenic epitope of COA-1441-460 (FSTFPPTLYQDDTLTLQAAG) and the antigen- and tumor immunological response was analyzed by IFN-g ELISPOT assay. We could isolate COA-1 specific and tumor reactive T lymphocytes from all (n= 7) HLADRb1* 0402+ or *1301+ CRC patients with progressive disease (Dukes’ C and D), but not in patients (n= 4) with early stage tumor (Dukes’ A and B). Furthermore, these T lymphocytes had a CD3+CD4+CD69+CD45RA+ phenotype, compatible with the activated effector-type T cell subset, and most of them exerted cytotoxic activity against tumor cells expressing COA-1 and the specific MHC restriction elements. In addition, we have verified whether COA-1 specific reactivity could be isolated from PBMCs of CRC patients by the usage of autologous dendritic cells loaded with tumor lysate. Tumor reactive and COA-1 specific CD4+ T cells colud be isolated by in vitro stimulation of PBMCs either with intact tumor cells and with DC pulsed with tumor lysate, suggesting that this antigen can generate a dominant immunological response against CRC. In conclusion, the results of this study indicate that COA-1 can be a relevant antigen for the anti-tumor immune response in CRC patients, correlating with the progression of the disease, and suggest that this molecule is suitable for immunotherapeutic protocols of these patients.
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Nastke, Maria-Dorothea. "T-cell epitopes from viral and tumor associated antigens induction and analysis of antigen-specific T cells /." [S.l. : s.n.], 2005. http://www.bsz-bw.de/cgi-bin/xvms.cgi?SWB12168223.

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Lotz, Carina. "Tolerance and immunity to human tumor-associated antigens." [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=970660308.

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Sheu, Fong-Shyong. "Characterizations of a tumor-associated antigen COX-1." Thesis, University of British Columbia, 1991. http://hdl.handle.net/2429/30332.

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By using modified hybridoma technology, monoclonal antibodies against an ovarian tumor cell line, OC-3-VGH, were generated in Dr. Lee's laboratory. Among these antibodies, RP 215 was shown to react specifically with a tumor-associated antigen, COX-1. On SDS gel, COX-1 has a molecular weight of 60 KD and exists as an aggregate in the natural- state. A highly purified COX-1 was obtained mainly by immunoaffirtity chromatography, with RP 215 as the affinity ligand, from the shed medium of cultured tumor cells. A solid phase enzyme immunoassay was established using RP 215 as the capturing and the detecting antibody with a sensitivity of 1 AU/ml. This immunoassay kit could be used to determine the levels of COX-1 in the culture medium and in the sera of cancer patients. COX-1 was characterized under a variety of experimental conditions. At temperatures higher than 50°C or in the presence of trypsin at 37°C, COX-1 immunoactivity was found to decrease with incubation time. However, COX-1 was not affected by incubation with carbohydrate-digestive enzymes including neuraminidase, Beta-galactosidase and fucosidase or carbohydrate modifying agents such as NaIO₄. Concanavalin A had no effect on the immunoactivity of COX-1 to RP 215. Furthermore, rabbit antisera against COX-1 were raised, and these polyclonal antisera were shown to exhibitsimilar immunoactivity to that of RP 215 monoclonal antibody. Using the established sandwich enzyme immunoassay, serum levels of COX-1 among patients with ovarian or cervical cancers were determined retrospectively through interlaboratory evaluations and collaborations. Compared to those of normal individuals and benign tumors, serum levels of COX-1 were significantly elevated and can be correlated to the progression of the disease among cancer patients. Preliminary data indicated the COX-1 can complement other established tumor markers such as CA 125 for the purpose of monitoring patients with ovarian or cervical cancers.
Medicine, Faculty of
Obstetrics and Gynaecology, Department of
Graduate
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Ullenhag, Gustav. "Vaccine Therapy of Colorectal Cancer Patients with Tumor Associated Antigens." Doctoral thesis, Uppsala University, Oncology, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3399.

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In this thesis, two different vaccines were evaluated as adjuvant therapy for patients with colorectal cancer. The ability of the two candidate vaccines to generate antigen-specific cellular and humoral responses, respectively, was studied. The effectiveness of granulocyte colony stimulating factor (GM-CSF) as a cytokine adjuvant to augment the immune response was also examined.

The first vaccination strategy involved immunization with the recombinant tumor-associated protein, carcinoembryonic antigen (CEA). Recombinant CEA was administered at 4 different dose levels 7 times during one year. Peripheral blood samples were regularly analyzed during 36 months. This vaccination regimen induced a strong immunoglobulin 1 (IgG1) and IgG4 response, a moderate IgG2 response and a weak IgG3 response against CEA. GM-CSF markedly augmented the effect on IgG1 and IgG4 as well as the T cell response. In contrast, dose of rCEA had no or modest effect on induced immune responses. The response gradually increased during the 12 months immunization period. Responses of all three IgG subclasses and of T cells were protracted up to 36 months. The anti-CEA IgG titers related significantly to survival. Functional HLA-DR epitopes of CEA could be defined. These major histocompatibility class II epitopes may serve as putative components of a peptide-based vaccination strategy.

The other vaccine strategy consisted of the tumor-associated antigen epithelial cell adhesion molecule (Ep-Cam) expressed as a transgene in a viral vector, ALVAC. Patients were immunized subcutaneously/intradermally 3 times over 6 weeks and monitored for immune responses for 46 weeks. No anti-Ep-Cam specific humoral response was induced, but Ep-Cam specific type 1 T cells (interpheron-gamma production) were induced, mainly in the GM-CSF group. The cytotoxic cellular response appeared late, or a few months after the last immunization.

Both vaccines were well tolerated. Since GM-CSF was an important component for both regimens, immungenicity of this cytokine was assessed. Multiple immunizations with low dose GM-CSF were associated with a low incidence of GM-CSF antibodies that did not neutralize the biological effect of GM-CSF.

In conclusion, both vaccines are promising candidate vaccines. GM-CSF is necessary to induce a strong humoral and cellular immune response. Large clinical trials are urgently warranted to evaluate the clinical efficacy.

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Hishizawa, Masakatsu. "Identification of tumor-associated antigens in hematological malignancies by SEREX." Kyoto University, 2006. http://hdl.handle.net/2433/143835.

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Shi, Mengchao. "Design and Synthesis of a Novel Entirely Carbohydrate-Based Conjugate for Cancer Vaccine Development." University of Toledo / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1470412718.

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Dullforce, Per. "Cytotoxicity mediated by monoclonal antibodies to tumour associated antigens." Thesis, University of Nottingham, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.293660.

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Ruiz, Elena. "DNA fusion vaccines against HPV16 E7 antigen-associated cancers." Thesis, University of Southampton, 2011. https://eprints.soton.ac.uk/374745/.

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To date, the success of cancer vaccines in human clinical trials has been limited. One of the reasons for this is the immunological tolerance to tumour antigens found in cancer patients. A novel DNA fusion vaccine design which links a pathogen-derived domain (DOM) of fragment C from tetanus toxin to a peptide epitope from a tumour antigen has been developed in our laboratory. The microbial sequence is able to activate a non-tolerised pool of helper T cells, providing T-cell help for immune induction against the linked tumour-specific sequence. The main aim of this project was to produce a therapeutic DNA vaccine against human papillomavirus (HPV)-associated cancers. A number of DNA fusion vaccines against the E7 antigen from HPV16 were constructed, including pDOM.E749-57, which encodes a well described H-2Db-binding epitope from E7 fused to the DOM sequence. CD8+ T-cell responses to the vaccines were demonstrated using flow cytometry and functional assays. Importantly, these responses were stronger than those induced by a published synthetic long peptide strategy. In vivo tumour challenge experiments showed that DNA vaccines had a protective and therapeutic effect. The vaccines were then tested in transgenic mice which develop spontaneous E7-expressing tumours in a setting of tolerance. DNA vaccine-mediated E7-specific CD8 + T-cell responses were successfully induced in these mice, together with a reduction in the mass of spontaneous tumours. This is the first demonstration of pDOM-epitope DNA vaccine-mediated therapy for spontaneous tumours and bodes well for translation into the clinic. One limiting factor for DNA vaccination in humans may be the delivery system. Electroporation (EP) is one approach which may overcome this. Therefore, a secondary aim of this project was to investigate the impact of EP on immune responses to DNA vaccination in more detail. EP proved essential for generating T-cell and antibody responses to the pDOM.E7 49-57 vaccine in sub-optimal conditions. This information will be crucial for the planning of therapeutic vaccination protocols in patients.
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Schecter, Robyn Lee. "A double determinant serum assay for detecting breast tumor associated antigen /." Thesis, McGill University, 1987. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=66270.

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Books on the topic "Antigeni tumore associati"

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C, Ghosh Bimal, and Ghosh Luna, eds. Tumor markers and tumor-associated antigens. New York: McGraw-Hill, 1987.

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Gires, Olivier, and Barbara Seliger. Tumor-associated antigens: Identification, characterization, and clinical applications. Weinheim: Wiley-VCH, 2009.

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Chuang, Hong-Yang. Synthesis and Vaccine Evaluation of the Tumor Associated Carbohydrate Antigen RM2 from Prostate Cancer. Berlin, Heidelberg: Springer Berlin Heidelberg, 2015. http://dx.doi.org/10.1007/978-3-662-46848-7.

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Hamburger Symposium über Tumormarker. (6th 1991 Hamburg, Germany). Tumor associated antigens, oncogenes, receptors, cytokines in tumor diagnosis and therapy at the beginning of the Nineties: 6th Symposium on Tumor Markers, Hamburg 1991. München: W. Zuckschwerdt Verlag, 1992.

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Gires, Olivier, and Barbara Seliger, eds. Tumor‐Associated Antigens. Wiley, 2009. http://dx.doi.org/10.1002/9783527625970.

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Tumor-Associated Antigens: Identification, Characterization, and Clinical Applications. Wiley-VCH Verlag GmbH, 2009.

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Gires, Olivier, and Barbara Seliger. Tumor-Associated Antigens: Identification, Characterization, and Clinical Applications. Wiley & Sons, Incorporated, John, 2009.

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(Editor), Dirk Nagorsen, and F. M. Marincola (Editor), eds. Analyzing T Cell Responses: How to analyze cellular immune responses against tumor associated antigens. Springer, 2005.

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Marincola, Francesco M., and Dirk Nagorsen. Analyzing T Cell Responses: How to Analyze Cellular Immune Responses Against Tumor Associated Antigens. Springer London, Limited, 2006.

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Marincola, Francesco M., and Dirk Nagorsen. Analyzing T Cell Responses: How to Analyze Cellular Immune Responses Against Tumor Associated Antigens. Springer, 2010.

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Book chapters on the topic "Antigeni tumore associati"

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Chabannon, Christian, and Chiara Bonini. "Structure of and Signalling Through Chimeric Antigen Receptor." In The EBMT/EHA CAR-T Cell Handbook, 3–5. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-030-94353-0_1.

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AbstractChimeric antigen receptor (CAR) is a synthetic transmembrane protein expressed at the surface of immune effector cells (IECs) that are reprogrammed either in vitro or in vivo (June et al. 2018; June and Sadelain 2018). Techniques for genetic engineering of autologous or allogeneic IECs are described in the next chapter. The synthetic CAR incorporates several functional domains. The extracellular domain is composed of a single chain variable fragment (ScFV) of immunoglobulin and recognizes the “tumour” antigen. The clinical relevance of the selected tumour antigen—with a view to minimize “on-target/off-tumour” side effects—is discussed in the third chapter of this section. Bispecific and trispecific CARs are currently being evaluated in preclinical and early clinical trials (Bielamowicz et al. 2018; Shah et al. 2020). The use of an immunoglobulin domain as the ligand of the target antigen means that recognition is not restricted to HLA antigens and that CAR-T cells are universally applicable as opposed to T cell receptor (TCR) transgenic T cells that recognize antigenic peptides presented in the context of a defined major histocompatibility complex (MHC), limiting clinical applications to subsets of patients with defined HLA typing. The intracellular domain is composed of the intracellular domain of the zeta chain of the CD3 component of the TCR, which will trigger signalling when the CAR engages the targeted ligand. The transmembrane region links the two extracellular and intracellular domains through the cell membrane and plays an important role in determining the conformation and flexibility of the CAR and its ability to efficiently bind the targeted antigen/epitope. Association of only these three functional domains characterized first generation CARs, as described in the original publications (Kuwana et al. 1987; Eshhar et al. 1993). However, full activation of T cells requires the addition of one (second generation CARs) or two (third generation CARs) domains from costimulatory molecules, such as CD28, 4-1BB/CD137, or OX40/CD134, that provide the T cell costimulatory signal. Currently approved CAR-T cells are second generation CAR-T cells; as an illustration, the CAR in tisagenlecleucel contains a 4-1BB domain, while the CAR in axicabtagene ciloleucel contains a CD28 domain. The nature of the costimulatory domain influences the ability of CAR-T cells to expand or persist (limit T cell exhaustion) in vivo after infusion into the patient, although it is unclear how this translates clinically and affects disease control, occurrence of adverse events, and overall survival due to the lack of head-to-head comparison between approved products. Finally, fourth generation CAR-T cells have been developed for preclinical projects. These cells, named armoured CAR cells or T cells redirected for universal cytokine-mediated killing (TRUCKS), encode not only a CAR (usually with one costimulatory domain, such as in second generation CARs) but also a cytokine, interleukin, pro-inflammatory ligand, or chemokine that will counteract the immune suppressive microenvironment that prevails in most solid tumours (Eshhar et al. 1993; Chmielewski and Abken 2015).
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Ward, Tony Milford. "Cancer Associated Antigens." In Proteins and Tumour Markers May 1995, 932–33. Dordrecht: Springer Netherlands, 1995. http://dx.doi.org/10.1007/978-94-011-0681-8_11.

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Anderson, Byron, Lyman E. Davis, and Mario Venegas. "Tumor-Associated Blood Group Antigen Expressions and Immunoglobulins Associated with Tumors." In The Molecular Immunology of Complex Carbohydrates, 601–56. Boston, MA: Springer US, 1988. http://dx.doi.org/10.1007/978-1-4613-1663-3_25.

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Paganuzzi, M., M. Onetto, P. Marroni, G. Valenti, F. Boccardo, and L. Santi. "CLINICAL EVALUATION OF NEW TUMOR-ASSOCIATED ANTIGENS." In Human Tumor Markers, edited by F. Cimino, G. D. Birkmayer, J. V. Klavins, E. Pimentel, and F. Salvatore, 643–56. Berlin, Boston: De Gruyter, 1987. http://dx.doi.org/10.1515/9783110846515-047.

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Mian, Shahid, R. Adrian Robins, Robert C. Rees, and Bernie Fox. "Immunogenicity of tumour associated antigens." In Cancer Immunology, 1–26. Dordrecht: Springer Netherlands, 2001. http://dx.doi.org/10.1007/978-94-017-0963-7_1.

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Klein, George. "Virus-Induced, Tumour-Associated Antigens." In Ciba Foundation Symposium - Strategy of the Viral Genome, 295–315. Chichester, UK: John Wiley & Sons, Ltd., 2008. http://dx.doi.org/10.1002/9780470719824.ch17.

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Zhi-Wei, Dong, Wei Shu-Min, Li Zhen-Pu, Wan Wen-Hui, and Xu Xin-Lai. "A Study of Tumor-Associated Antigens." In Cancer of the Liver, Esophagus, and Nasopharynx, 135–43. Berlin, Heidelberg: Springer Berlin Heidelberg, 1987. http://dx.doi.org/10.1007/978-3-642-71510-5_21.

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Álvarez-Fernández, Sheila María, Lucia De Monte, and Massimo Alessio. "Natural Antibodies to Tumor-Associated Antigens." In Methods in Molecular Biology, 11–25. New York, NY: Springer New York, 2016. http://dx.doi.org/10.1007/978-1-4939-3338-9_2.

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Ruiter, D. J., E.-B. Broecker, C. Vennegoor, and S. Ferrone. "Monoclonal Antibodies Recognizing Melanoma-Associated Antigens." In Application of Monoclonal Antibodies in Tumor Pathology, 131–65. Dordrecht: Springer Netherlands, 1987. http://dx.doi.org/10.1007/978-94-009-3299-9_8.

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Hounsell, E. F., H. C. Gooi, and T. Feizi. "Tumour-Associated Carbohydrate Antigens of Glycoproteins." In Investigation and Exploitation of Antibody Combining Sites, 317–22. Boston, MA: Springer US, 1985. http://dx.doi.org/10.1007/978-1-4684-5006-4_38.

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Conference papers on the topic "Antigeni tumore associati"

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Rickles, F. R., W. W. Hancock, K. Kobzik, N. Hogg, and C. O’Hara. "THE DISTRIBUTION OF CROSS-LINKED FIBRIN IN HUMAN LUNG CARCINOMA PARALLELS THAT OF ACTIVATED HOST MONONUCLEAR LEUKOCYTES: IMMUNO-HISTOLOGIC STUDIES WITH MONOCLONAL ANTIBODIES." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643669.

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Previous immunohistologic studies of human lung carcinoma, using polyclonal antibodies to antigens shared between fibrinogen (FGN) and fibrin (FB), showed that FGN/FB were associated withtumor cells. These findings were interpreted as evidence of the presence of tumor-associated procoagulant activity(PCA). Wecompared the distribution of coagulation-associated proteins in 16 casesof human carcinoma of the lungofvarying histologic types, using polyclonal antibodies to FGN/FB and monoclonal antibodies (mAb) to cross-linked fibrin (XL-FB;UC-45), fibronectin (FN;PHM13), factor VIII (vWF:Ag)and a tissue factor-related antigen(TF:RAg;A1 -3)- Host mononuclear leukocytes were identifiedusing various mAb toT cells and macrophages, and studied for their expression of receptorsfor interleukin-2 (IL-2R). Positive resultsare summarizedIn addition, studies of the mononuclearcells adjacent to tumors in 12/12 casesshowed the presence of tumor-associated macrophages, 10/11 showed T cells,mainly T8+, and A/5 showed corresponding expression of IL-2R, suggesting cell activation.The use of highly specific mAb showed that XL-FB is actually more selectively distributed than is found using polyclonal antisera to FGN/FB, and indeed XL-FB was largely confined to those areas adjacent to tumors which are rich in mononuclearcells. These findings suggest that fibrin deposits in human carcinomasof the lung may be due todevelopment of PCA by activated host mononuclear cells, rather than tumor cells.This lack of XL-FB on tumor cellsinspite of A1- 3 binding suggests that TF:RAg may not be available on the tumor cell surface for the activation of clotting. Further studies are neededto define the functional capacity of PCA molecules on tumor cells and tumor-associated mononuclear cells in situ.
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Thomas, Dhanya S., Ajit Sebastian, Vinotha Thomas, Anitha Thomas, Rachel Chandy, and Abraham Peedicayil. "Role of cancer antigen 19-9 in complex ovarian tumors." In 16th Annual International Conference RGCON. Thieme Medical and Scientific Publishers Private Ltd., 2016. http://dx.doi.org/10.1055/s-0039-1685315.

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Background: Cancer antigen 19-9 (CA 19-9) is a tumor-associated mucin glycoprotein antigen that may be elevated in healthy individuals as well as in patients with benign and malignant tumors. It is useful in the management of pancreatic and other gastrointestinal tumors. CA 19-9 is also elevated in benign and malignant ovarian tumors. Aim: To study the pattern of serum CA 19-9 in complex ovarian tumors. Methods: The study design was descriptive, based on data collected from medical records. Patients with a complex ovarian mass, who were investigated with CA 19-9 and had undergone surgery, were included in the study. The study duration was 2 years from January 2014 to December 2015. A total of 273 patients (119 benign and 154 malignant) with complex ovarian mass and elevated CA 19-9 underwent surgery during the study period. Results: CA 19-9 was elevated in 55 patients (20%). Of these, 23 patients had benign tumors while 32 had malignant tumors. Among patients with benign tumors, 21 had dermoid, 23 had mucinous tumors and 75 had other types of tumors. CA 19-9 was elevated in 10 (47.6%) of the dermoids, 7 (30.4%) of the mucinous tumors and 6 (8%) of the other benign tumors. Among patients with malignant tumors, 138 were epithelial and 16 were non epithelial tumors. Of the epithelial tumors, 31 were mucinous and 107 were nonmucinous types. Overall, 29 (21%) had elevated CA 19-9. Of the epithelial tumors, 22.6% of the mucinous type and 20.6% of the non mucinous type had elevated CA 19-9. Among the non-epithelial tumors, 3 (18.8%) had elevated CA19-9. Conclusion: CA 19-9 is elevated in several conditions but most likely to be raised in dermoid cysts and mucinous tumours. CA19-9 levels need to be interpreted along with clinical and radiological findings.
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Thomas, Dhanya S., Ajit Sebastian, Vinotha Thomas, Anitha Thomas, Rachel Chandy, and Abraham Peedicayil. "Role of CA 19-9 in complex ovarian tumors." In 16th Annual International Conference RGCON. Thieme Medical and Scientific Publishers Private Ltd., 2016. http://dx.doi.org/10.1055/s-0039-1685299.

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Background: Cancer antigen 19-9 (CA 19-9) is a tumor-associated mucin glycoprotein antigen that may be elevated in healthy individuals as well as in patients with benign and malignant tumors. It is useful in the management of pancreatic and other gastrointestinal tumors. CA 19-9 is also elevated in benign and malignant ovarian tumors. Aim: To study the pattern of serum CA19-9 in complex ovarian tumors. Methods: The study design was descriptive, based on data collected from medical records. Patients with a complex ovarian mass, who were investigated with CA 19-9 and had undergone surgery, wereincluded in the study. The study duration was 2 years from January 2014 to December 2015. A total of 273 patients (119 - benign and 154 malignant) with complex ovarian mass and elevated CA 19-9 underwent surgery during the study period. Results: CA 19-9 was elevated in 55 patients (20%). Of these, 23 patients had benign tumors while 32 had malignant tumors.Among patients with benign tumors, 21 had dermoid, 23 had mucinous tumors and 75 had other types of tumors. CA 19-9 was elevated in 10 (47.6%) of the dermoids, 7 (30.4%) of the mucinous tumors and 6 (8%) of the other benign tumors. Among patients with malignant tumors, 138 were epithelial and 16 were non epithelial tumors. Of the epithelial tumors, 31 were mucinous and 107 were non mucinous types. Overall, 29 (21%) had elevated CA 19-9. Of the epithelial tumors, 22.6% of the mucinous type and 20.6% of the non mucinous type had elevated CA 19-9. Among the non-epithelial tumors, 3 (18.8%) had elevated CA19-9. Conclusion: CA 19-9 is elevated in several conditions but most likely to be raised in dermoid cysts and mucinous tumours. CA19-9 levels need to be interpreted along with clinical and radiological findings.
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Banerjee, Rupak K., Meinrad Praxmaraer, Ilhan Dilber, Peter Bungay, William van Osdol, and Cynthia Sung. "Numerical Simulation of Antibody Penetration in a Solid Tumor Nodule Using Finite Element Method." In ASME 1998 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 1998. http://dx.doi.org/10.1115/imece1998-0058.

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Abstract The high binding specificity that monoclonal antibodies exhibit has led to great interest in using them to target tumor-associated antigens. The antibody may be coupled to a radionuclide or cytotoxic drug to create a tumor-targeted reagent that can be used to identify sites of metastatic disease and/or deliver a lethal substance to the tumor cells. However, successful application of these compounds in a clinical setting has been hindered by a poor understanding of the factors that govern antibody accumulation in a tumor. We have used a finite element method to develop a pharmacokinetic model describing the uptake of systemically-administered antibody in an early, prevascular spherical tumor nodule embedded in normal tissue. The model incorporates such processes as plasma kinetics, transcapillary transport, interstitial diffusion, binding reactions, lymphatic clearance, and antigen internalization.
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Pandey, Divya, Neha Pruthi, and Sudha Salhan. "Unusually high serum Ca 19-9 in a benign ovarian tumor." In 16th Annual International Conference RGCON. Thieme Medical and Scientific Publishers Private Ltd., 2016. http://dx.doi.org/10.1055/s-0039-1685327.

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Introduction: Ovarian tumors have a varied spectrum of presentation. Tumors which look malignant clinico-biochemically can ultimately turn out to be benign. Tumor markers help in diagnosing various malignancies. Carbohydrate antigen 19-9 is one such marker seen to be elevated in some ovarian tumors. Case: A 55 year old, lean and thin postmenopausal female presented to Gynae OPD with abdominal mass, anorexia and weight loss developing over last 6 months. During workup, she was found to have unusually high Ca 19-9 along with MRI findings suggestive of ovarian tumor. Staging laparotomy followed by total abdominal hysterectomy with bilateral salpingoophorectomy was performed. Per operative findings were suggestive of benign nature of ovarian tumor of size 18× 20 cm. Patient was kept under follow up. Histopathology report showed benign mucinous cystadenoma. The serum levels of Ca19-9 returned to normal 8 weeks following surgery. This case report shows a rare and significant elevation of Ca19-9 levels with benign mucinous cystadenoma of the ovary, thus showing that women with unusually elevated tumor markers and even symptoms suggesting malignancy may actually harbour a benign disease. Conclusion: Unusually high Ca 19-9 may be associated with benign mucinous cystadenoma but thorough workup to rule out malignancy is a must in every case.
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Buonaguro, L. "P03.06 Tumor associated antigens and pathogen antigens: friends or foes." In iTOC9 – 9th Immunotherapy of Cancer Conference, September 22–24, 2022 – Munich, Germany. BMJ Publishing Group Ltd, 2022. http://dx.doi.org/10.1136/jitc-2022-itoc9.34.

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Athanassiou, P., A. Elezoglou, I. Kostoglou-Athanassiou, A. Theodorou, P. Konstantopoulou, A. Kotrotsios, P. Dimou, and G. Vezyroglou. "THU0197 Tumour-associated antigens in rheumatoid arthritis." In Annual European Congress of Rheumatology, Annals of the rheumatic diseases ARD July 2001. BMJ Publishing Group Ltd and European League Against Rheumatism, 2001. http://dx.doi.org/10.1136/annrheumdis-2001.1099.

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Barroilhet, Lisa M., Junzheng Yang, William R. Welch, Ross S. Berkowitz, and Shu-Wing Ng. "Abstract 2734: Tumor-associated antigen c-terminal binding protein-2 is overexpressed in epithelial ovarian tumors." In Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-2734.

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Toner, K., M. Stanojevic, M. Grant, R. Schore, A. Gross, D. Couriel, B. Hu, et al. "Tumor associated antigen specific T cells for Hodgkin Lymphoma." In ISCAYAHL 2020. © Georg Thieme Verlag KG, 2020. http://dx.doi.org/10.1055/s-0040-1701880.

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Lima, Beatriz Alves, Andressa da Silva Pereira, Bruna Alves Lima, Diana Gonçalves Lima, Leonardo Ferreira Pucci, Renato Moraes Ferreira, Tiago Castro Ferreira, and Henrique Ferreira Pucci. "PREDICTORS OF BREAST CANCER PROGNOSIS BASED ON TUMOR BIOMARKERS." In Abstracts from the Brazilian Breast Cancer Symposium - BBCS 2021. Mastology, 2021. http://dx.doi.org/10.29289/259453942021v31s2022.

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Objective: To analyze the tumor biological markers of breast cancer associated with the prognostic of the disease. Methodology: A systematic review was carried out on the Scielo, PubMed, and the National Cancer Institute databases on the topic. Descriptors used were: tumor biomarkers, breast cancer, and prognosis. Thus, 15 articles published between 2001 and 2020 were selected. Results: Breast cancer, characterized by the disordered multiplication of breast cells, is the most incident in women in the world, representing 24.2% of the total cases in 2018, and the most frequent cause of death in this gender. Accordingly, tumor markers are complementary tests for early diagnosis, since they are macromolecules derived from the tumor and biological fluids. The evaluation of tumor markers is of paramount importance due to the great diversity in clinical progression of breast cancer, for example, those hormone receptors (estrogen and progesterone), MIB-1, Ki-67, PCNA, p53, and c-erbB-2. Hence, about two-thirds of breast cancers are positive for hormone receptors and are related to a more favorable prognosis. PCNA (36 kDa protein perceptible in the cell nucleus from the late G1 to the S phase of the cell cycle) and MIB-1 (direct antibody against parts of the Ki-67 antigen) have a high proportion of tumor cells associated with a high-degree tumor differentiation, indicating a worse prognosis. Furthermore, mutations in the p53 and c-erbB-2 genes report low levels of estrogen and progesterone receptors, leading to a worse prognosis. Conclusion: In brief, the recognition of the main markers helps in the identification of patients with potentially aggressive tumors and in the mortality reduction of breast cancer, through treatments that can alter the course of the disease. On account of this, it is known that the tumor markers must be used in combination with the other methods such as diagnostic, prognostic, and therapeutic modifications.
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Reports on the topic "Antigeni tumore associati"

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Tiwari, Raj K. Tumor Associated Antigenic Peptides in Prostate Cancer. Fort Belvoir, VA: Defense Technical Information Center, March 2002. http://dx.doi.org/10.21236/ada406458.

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Tiwari, Raj. Tumor Associated Antigenic Peptides in Prostate Cancer. Fort Belvoir, VA: Defense Technical Information Center, October 1999. http://dx.doi.org/10.21236/ada383084.

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Hampton, Tracy A. Identification and Characterization of Tumor Antigens Associated With Breast Cancer. Fort Belvoir, VA: Defense Technical Information Center, August 1998. http://dx.doi.org/10.21236/adb244675.

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Bai, Jining. Identification of Widely Applicable Tumor-Associated Antigens for Breast Cancer Immunotherapy. Fort Belvoir, VA: Defense Technical Information Center, October 2004. http://dx.doi.org/10.21236/ada432926.

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Bai, Jining. Identification of Widely Applicable Tumor-Associated Antigens for Breast Cancer Immunotherapy. Fort Belvoir, VA: Defense Technical Information Center, October 2002. http://dx.doi.org/10.21236/ada411919.

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Bai, Jining. Identification of Widely Applicable Tumor-Associated Antigens for Breast Cancer Immunotherapy. Fort Belvoir, VA: Defense Technical Information Center, January 2006. http://dx.doi.org/10.21236/ada588103.

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Kim, Hyunjin M., and Samuel Danishefshky. A Solid Support Synthesis and Novel Conjugation Methods of Breast Tumor Associated Antigen: Toward the Development of Cancer Vaccines. Fort Belvoir, VA: Defense Technical Information Center, July 1999. http://dx.doi.org/10.21236/ada373924.

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Long, Brian R., and Roland M. Tisch. The Use of Venezuelan Equine Encephalitis Encoding the Her-2/neu Tumor Associated Antigen for the Prevention and Treatment of Breast Cancer. Fort Belvoir, VA: Defense Technical Information Center, May 2003. http://dx.doi.org/10.21236/ada416667.

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Long, Brian R., and Roland M. Tisch. The Use of Venezuelan Equine Encephalitis Replicons Encoding the HER-2/neu Tumor Associated Antigen for the Prevention and Treatment of Breast Cancer. Fort Belvoir, VA: Defense Technical Information Center, May 2004. http://dx.doi.org/10.21236/ada428256.

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Evans, Donald L., Avigdor Eldar, Liliana Jaso-Friedmann, and Herve Bercovier. Streptococcus Iniae Infection in Trout and Tilapia: Host-Pathogen Interactions, the Immune Response Towards the Pathogen and Vaccine Formulation. United States Department of Agriculture, February 2005. http://dx.doi.org/10.32747/2005.7586538.bard.

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The objectives of the BARD proposal were to determine the mechanisms of nonspecific cytotoxic cells (NCC) that are necessary to provide heightened innate resistance to infection and to identify the antigenic determinants in Streptococcus iniae that are best suited for vaccine development. Our central hypothesis was that anti-bacterial immunity in trout and tilapia can only be acquired by combining "innate" NCC responses with antibody responses to polysaccharide antigens. These Objectives were accomplished by experiments delineated by the following Specific Aims: Specific aim (SA) #1 (USA) "Clone and Identify the Apoptosis Regulatory Genes in NCC"; Specific aim #2 (USA)"Identify Regulatory Factors that Control NCC Responses to S. iniae"; Specific aim #3 (Israel) "Characterize the Biological Properties of the S. iniae Capsular Polysaccharide"; and Specific aim #4 (Israel) "Development of an Acellular Vaccine". Our model of S. iniae pathogenesis encompassed two approaches, identify apoptosis regulatory genes and proteins in tilapia that affected NCC activities (USA group) and determine the participation of S.iniae capsular polysaccharides as potential immunogens for the development of an acellular vaccine (Israel group). We previously established that it was possible to immunize tilapia and trout against experimental S. difficile/iniaeinfections. However these studies indicated that antibody responses in protected fish were short lived (3-4 months). Thus available vaccines were useful for short-term protection only. To address the issues of regulation of pathogenesis and immunogens of S. iniae, we have emphasized the role of the innate immune response regarding activation of NCC and mechanisms of invasiveness. Considerable progress was made toward accomplishing SA #1. We have cloned the cDNA of the following tilapia genes: cellular apoptosis susceptibility (CAS/AF547173»; tumor necrosis factor alpha (TNF / A Y 428948); and nascent polypeptide-associated complex alpha polypeptide (NACA/ A Y168640). Similar attempts were made to sequence the tilapia FasLgene/cDNA, however these experiments were not successful. Aim #2 was to "Identify Regulatory Factors that Control NCC Responses to S. iniae." To accomplish this, a new membrane receptor has been identified that may control innate responses (including apoptosis) of NCC to S. iniae. The receptor is a membrane protein on teleost NCC. This protein (NCC cationic antimicrobial protein-1/ncamp-1/AAQ99138) has been sequenced and the cDNA cloned (A Y324398). In recombinant form, ncamp-l kills S. iniae in vitro. Specific aim 3 ("Characterize the Biological Properties of the S.iniae Capsular Polysaccharide") utilized an in- vitro model using rainbow trout primary skin epithelial cell mono layers. These experiments demonstrated colonization into epithelial cells followed by a rapid decline of viable intracellular bacteria and translocation out of the cell. This pathogenesis model suggested that the bacterium escapes the endosome and translocates through the rainbow trout skin barrier to further invade and infect the host. Specific aim #4 ("Development of an Acellular Vaccine") was not specifically addressed. These studies demonstrated that several different apoptotic regulatory genes/proteins are expressed by tilapia NCC. These are the first studies demonstrating that such factors exist in tilapia. Because tilapia NCC bind to and are activated by S. iniae bacterial DNA, we predict that the apoptotic regulatory activity of S. iniae previously demonstrated by our group may be associated with innate antibacterial responses in tilapia.
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