22 results on '"Nicolay HJ"'
Search Results
2. Seventh annual meeting of the Italian Network for Tumor Biotherapy (NIBIT), Siena, 1-3 October 2009
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Maio, M, Nicolay, Hj, Ascierto, Pa, Belardelli, F, Camerini, R, Colombo, Mp, Queirolo, P, Ridolfi, R, Russo, V, Fonsatti, E, Parmiani, G, Allavena P, N. I. B. I. T., Anichini, A, Bellone, M, Bronte, V, Calabrò, L, Camisaschi, C, Castelli, C, Danova, M, Di Giacomo AM, Di Nicola, M, Ferlazzo, G, Giovannoni, L, Hwu, P, Lehmann, F, Maccalli, C, Melero, I, Monsurro', Vladia, Montagna, D, Moschella, F, Ponzoni, M, Protti, Mp, Puccetti, P, Sangiolo, D, and Schuler, G.
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Cancer Research ,medicine.medical_specialty ,business.industry ,Immunology ,Neoplasms therapy ,Immunotherapy ,Immunomodulatory therapy ,adoptive cell therapy ,Oncology ,medicine ,Immunology and Allergy ,Medical physics ,business - Published
- 2010
3. Seventh annual meeting of the Italian Network for Tumor Biotherapy (NIBIT)
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Maio, M, Nicolay, Hj, Ascierto, Pa, Belardelli, F, Camerini, R, Colombo, Mp, Queirolo, P, Ridolfi, R, Russo, V, Fonsatti, E, Parmiani, G, Calabro', L, and Nibit, Collaborators
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Angiogenesis Inhibitors ,Cancer Vaccines ,Dendritic Cells ,Humans ,Immune Tolerance ,Immunotherapy, Adoptive ,Neoplasms ,Tumor Escape ,Vaccination ,Adoptive ,Immunotherapy ,NO - Published
- 2010
4. The Italian Network for Tumor Biotherapy (NIBIT): getting together to push the field forward.
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Maio M, Nicolay HJ, Ascierto P, Belardelli F, Camerini R, Colombo MP, Queirolo P, Ridolfi R, Russo V, Anzalone L, Fonsatti E, Parmiani G, Maio, Michele, Nicolay, Hugues Jm, Ascierto, Paolo, Belardelli, Filippo, Camerini, Roberto, Colombo, Mario P, Queirolo, Paola, and Ridolfi, Ruggero
- Abstract
As for a consolidated tradition, the 5th annual meeting of the Italian Network for Cancer Biotherapy took place in the Certosa of Pontignano, a Tuscan monastery, on September 20-22, 2007. The congress gathered more than 40 Italian leading groups representing academia, biotechnology and pharmaceutical industry. Aim of the meeting was to share new advances in cancer bio-immunotherapy and to promote their swift translation from pre-clinical research to clinical applications. Several topics were covered including: a) molecular and cellular mechanisms of tumor escape; b) therapeutic antibodies and recombinant constructs; c) clinical trials up-date and new programs; d) National Cooperative Networks and their potential interactions; e) old and new times in cancer immunology, an "amarcord". Here, we report the main issues discussed during the meeting. [ABSTRACT FROM AUTHOR]
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- 2008
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5. Eighth annual meeting of the Italian network for tumor biotherapy (NIBIT), Siena, October 7-9, 2010
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Riccardo Danielli, Vincenzo Russo, Arianna Calcinotto, Luigi Aurisicchio, Michele Maio, Licia Rivoltini, Pier Francesco Ferrucci, Michela Perego, Filippo Belardelli, Sandra Coral, Matteo Bellone, Hugues Nicolay, Pier Luigi Lollini, Sergio Bracarda, Paola Queirolo, Mario Paolo Colombo, Maio M, Nicolay HJ, Ascierto PA, Belardelli F, Camerini R, Colombo MP, Queirolo P, Ridolfi R, Russo V, Fonsatti E, Parmiani G, NIBIT [.., P.L. Lollini, and ]
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Cancer Research ,medicine.medical_specialty ,Immunology ,cisplatin ,interleukin 8 ,3 dioxygenase ,prostate specific antigen ,telomerase ,doxorubicin ,mitoxantrone ,NO ,asparaginylglycylarginine tumor necrosis factor ,Political science ,cetuximab ,high mobility group B1 protein ,unindexed drug ,medicine ,docetaxel ,Immunology and Allergy ,heat shock protein 70 ,ipilimumab ,antineoplastic agent ,transforming growth factor beta ,vasculotropin ,bortezomib ,Cancer ,provenge ,basic fibroblast growth factor ,thymosin alpha1 ,medicine.disease ,melphalan ,unclassified drug ,CpG oligodeoxynucleotide ,Clinical trial ,epidermal growth factor ,Hot topics ,NIBIT ,Oncology ,Family medicine ,prednisone ,Tumor immunology ,indoleamine 2 ,cyclophosphamide ,acid phosphatase prostate isoenzyme ,granulocyte macrophage colony stimulating factor ,indoleamine 2,3 dioxygenase ,monocyte chemotactic protein 1 ,tumor antigen - Abstract
NIBIT (acronym for the Network Italiano per la Bioterapia dei Tumori—Italian Network for Tumor Biotherapy) is a non-profit association created in 2004 to promote and foster scientific and operative interactions among Italian professionals involved in the field of cancer bioimmunotherapy. To date, more than 100 members representing over 40 national academic, regulatory, and industrial groups are part of the NIBIT. Aim of the annual meeting of the NIBIT is the discussion of recent preclinical and clinical results obtained by various Italian groups of the Network in the field of cancer immunology and biotherapy. Traditionally, the NIBIT meeting also hosts foreign speakers for keynote lectures on hot topics in the NIBIT field of interest. Like every year, the eighth annual meeting of the NIBIT took place in the Certosa of Pontignano, a Tuscan Carthusian monastery close to Siena. The 2010 main topics were as follows: (1) immunology of cancer stem cells; (2) prostate cancer immunotherapy; (3) immunomodulation therapy; (4) new aspects in cancer vaccines; (5) NIBIT and other Italian clinical trials.
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- 2011
6. "Cancer Bio-Immunotherapy in Siena": Thirteenth Meeting of the Network Italiano per la Bioterapia dei Tumori (NIBIT), Siena, Italy, October 8-10, 2015.
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Maio M, Bertocci E, Fazio C, Chiarucci C, Cutaia O, Scala E, Giacobini G, Lofiego MF, Fonsatti E, Maccalli C, Nicolay HJ, and Parmiani G
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- Humans, Neoplasms pathology, Immunotherapy methods, Neoplasms etiology, Neoplasms therapy
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- 2016
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7. "Cancer Bio-Immunotherapy in Siena": Eleventh Meeting of the Network Italiano per la Bioterapia dei Tumori (NIBIT), Siena, Italy, October 17-19, 2013.
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Maio M, Nicolay HJ, Cutaia O, Fonsatti E, and Parmiani G
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- Animals, Congresses as Topic, Humans, Neoplasms immunology, Biological Therapy, Immunotherapy methods, Neoplasms therapy
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- 2015
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8. Tenth annual meeting of the Italian Network for Tumor Biotherapy (NIBIT), SIENA, Italy, November 5-7, 2012.
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Maio M, Nicolay HJ, Ascierto PA, Belardelli F, Camerini R, Colombo MP, Queirolo P, Ridolfi R, Russo V, Parisi G, Cutaia O, Fonsatti E, and Parmiani G
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- Humans, Italy, Biological Therapy, Neoplasms therapy
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- 2013
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9. Immunomodulatory activity of SGI-110, a 5-aza-2'-deoxycytidine-containing demethylating dinucleotide.
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Coral S, Parisi G, Nicolay HJ, Colizzi F, Danielli R, Fratta E, Covre A, Taverna P, Sigalotti L, and Maio M
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- Antigens, Neoplasm biosynthesis, Antigens, Neoplasm genetics, Azacitidine pharmacology, Cell Line, Tumor, Cytotoxicity, Immunologic, Humans, Immunophenotyping, Melanoma immunology, Neoplasms therapy, Azacitidine analogs & derivatives, DNA Methylation, Immunomodulation drug effects, Immunotherapy methods, Neoplasms immunology
- Abstract
Purpose: Pharmacologic DNA hypomethylation holds strong promises in cancer immunotherapy due to its immunomodulatory activity on neoplastic cells. Searching for more efficient DNA hypomethylating agents to be utilized to design novel immunotherapeutic strategies in cancer, we investigated the immunomodulatory properties of the new DNA hypomethylating agent SGI-110, that is resistant to in vivo inactivation by cytidine deaminase., Experimental Design: Cutaneous melanoma, mesothelioma, renal cell carcinoma, and sarcoma cells were treated in vitro with SGI-110. RT-PCR, quantitative RT-PCR, quantitative methylation-specific PCR, and flow cytometric analyses were performed to investigate changes induced by SGI-110 in the constitutive immune profile of cancer cells. The recognition by gp100-specific CTL of gp100-positive melanoma cells, treated or not with SGI-110, was tested by LDH release assays., Results: SGI-110 induced/up-regulated the expression of investigated cancer/testis antigens (CTA) (i.e., MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A10, GAGE 1-2, GAGE 1-6, NY-ESO-1, and SSX 1-5) in all cancer cell lines studied, both at mRNA and at protein levels. Quantitative methylation-specific PCR analyses identified a hypomethylation of MAGE-A1 and NY-ESO-1 promoters in SGI-110-treated neoplastic cells, demonstrating a direct role of pharmacologic DNA demethylation in CTA induction. SGI-110 also up-regulated the expression of HLA class I antigens and of ICAM-1, resulting in an improved recognition of cancer cells by gp100-specific CTL., Conclusions: Our findings show that SGI-110 is a highly attractive therapeutic agent to comprehensively increase immunogenicity and immune recognition of neoplastic cells, and provide the scientific rationale for its clinical development to design novel chemo-immunotherapeutic approaches in cancer patients.
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- 2013
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10. Epigenetic remodelling of gene expression profiles of neoplastic and normal tissues: immunotherapeutic implications.
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Coral S, Covre A, Nicolay HJ, Parisi G, Rizzo A, Colizzi F, Dalla Santa S, Fonsatti E, Fratta E, Sigalotti L, and Maio M
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- Animals, Antigens, Neoplasm genetics, Antigens, Neoplasm immunology, Azacitidine pharmacology, Cell Line, Tumor, Cell Transformation, Neoplastic immunology, DNA Methylation, Decitabine, Epigenesis, Genetic, Epigenomics methods, Female, Gene Expression Profiling methods, Gene Expression Regulation, Neoplastic, Mammary Neoplasms, Experimental immunology, Mice, Mice, Inbred BALB C, Promoter Regions, Genetic, Receptors, G-Protein-Coupled genetics, Receptors, G-Protein-Coupled immunology, Signal Transduction drug effects, Signal Transduction genetics, Signal Transduction immunology, Azacitidine analogs & derivatives, Cell Transformation, Neoplastic drug effects, Cell Transformation, Neoplastic genetics, Immunotherapy methods, Mammary Neoplasms, Experimental genetics, Mammary Neoplasms, Experimental therapy
- Abstract
Background: Epigenetic remodelling of cancer cells is an attractive therapeutic strategy and distinct DNA hypomethylating agents (DHA) are being actively evaluated in patients with hemopoietic or solid tumours. However, no studies have investigated the modulation of gene expression profiles (GEP) induced by DHA in transformed and benign tissues. Such information is mandatory to clarify the fine molecular mechanism(s) underlying the clinical efficacy of DHA, to identify appropriate therapeutic combinations, and to address safety issues related to their demethylating potential in normal tissues. Thus, utilising a syngeneic mouse model, we investigated the remodelling of GEP of neoplastic and normal tissues induced by systemic administration of DHA., Methods: The murine mammary carcinoma cells TS/A were injected s.c. into female BALB/c mice that were treated i.p. with four cycles of the DHA 5-aza-2'-deoxycytidine (5-AZA-CdR) at a fractioned daily dose of 0.75 mg kg(-1) (q8 h × 3 days, every week). Whole mouse transcriptomes were analysed by microarrays in neoplastic and normal tissues from control and treated mice. Results were processed by bioinformatic analyses., Results: In all, 332 genes were significantly (P ≤ 0.05; FC ≥ 4) modulated (294 up and 38 downregulated) in neoplastic tissues from 5-AZA-CdR-treated mice compared with controls. In decreasing order of magnitude, changes in GEP significantly (P ≤ 0.05) affected immunologic, transport, signal transduction, spermatogenesis, and G-protein-coupled receptor protein signalling pathways. Epigenetic remodelling was essentially restricted to tumour tissues, leaving substantially unaltered normal ones., Conclusion: The ability of 5-AZA-CdR to selectively target tumour GEP and its major impact on immune-related genes, strongly support the clinical use of DHA alone or combined with immunotherapeutic agents.
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- 2012
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11. Ninth annual meeting of the Italian Network for Tumor Biotherapy (NIBIT), Siena, Italy, October 19-22, 2011: New perspectives in the immunotherapy of cancer.
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Maio M, Nicolay HJ, Ascierto PA, Belardelli F, Camerini R, Colombo MP, Queirolo P, Ridolfi R, Russo V, Parisi G, Fonsatti E, Papamichail M, and Parmiani G
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- Animals, Humans, Neoplasms immunology, Immunotherapy methods, Neoplasms therapy
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- 2012
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12. Eighth annual meeting of the Italian network for tumor biotherapy (NIBIT), Siena, October 7-9, 2010.
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Maio M, Nicolay HJ, Ascierto PA, Belardelli F, Camerini R, Colombo MP, Queirolo P, Ridolfi R, Russo V, Fonsatti E, and Parmiani G
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- Humans, Immunotherapy methods, Neoplasms immunology, Neoplasms therapy
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- 2011
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13. The biology of cancer testis antigens: putative function, regulation and therapeutic potential.
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Fratta E, Coral S, Covre A, Parisi G, Colizzi F, Danielli R, Nicolay HJ, Sigalotti L, and Maio M
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- DNA Methylation, Humans, Immunotherapy methods, Male, Antigens, Neoplasm genetics, Antigens, Neoplasm immunology, Gene Expression Regulation, Neoplastic, Neoplasms immunology, Neoplasms therapy
- Abstract
Cancer testis antigens (CTA) are a large family of tumor-associated antigens expressed in human tumors of different histological origin, but not in normal tissues except for testis and placenta. This tumor-restricted pattern of expression, together with their strong in vivo immunogenicity, identified CTA as ideal targets for tumor-specific immunotherapeutic approaches, and prompted the development of several clinical trials of CTA-based vaccine therapy. Driven by this practical clinical interest, a more detailed characterization of CTA biology has been recently undertaken. So far, at least 70 families of CTA, globally accounting for about 140 members, have been identified. Most of these CTA are expressed during spermatogenesis, but their function is still largely unknown. Epigenetic events, particularly DNA methylation, appear to be the primary mechanism regulating CTA expression in both normal and transformed cells, as well as in cancer stem cells. In view of the growing interest in CTA biology, the aim of this review is to provide the most recent information on their expression, regulation and function, together with a brief summary of the major clinical trials involving CTA as therapeutic agents. The pharmacologic modulation of CTA expression profiles on neoplastic cells by DNA hypomethylating drugs will also be discussed as a feasible approach to design new combination therapies potentially able to improve the clinical efficacy of currently adopted CTA-based immunotherapeutic regimens in cancer patients., (Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)
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- 2011
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14. Seventh annual meeting of the Italian Network for Tumor Biotherapy (NIBIT), Siena, 1-3 October 2009.
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Maio M, Nicolay HJ, Ascierto PA, Belardelli F, Camerini R, Colombo MP, Queirolo P, Ridolfi R, Russo V, Fonsatti E, and Parmiani G
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- Angiogenesis Inhibitors therapeutic use, Cancer Vaccines immunology, Dendritic Cells immunology, Humans, Immune Tolerance, Immunotherapy, Adoptive, Neoplasms immunology, Tumor Escape, Vaccination, Neoplasms therapy
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- 2010
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15. Epigenetics of human cutaneous melanoma: setting the stage for new therapeutic strategies.
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Sigalotti L, Covre A, Fratta E, Parisi G, Colizzi F, Rizzo A, Danielli R, Nicolay HJ, Coral S, and Maio M
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- DNA Methylation drug effects, Enzyme Inhibitors pharmacology, Enzyme Inhibitors therapeutic use, Histones metabolism, Humans, Melanoma diagnosis, MicroRNAs metabolism, Prognosis, Protein Processing, Post-Translational drug effects, Skin Neoplasms diagnosis, Epigenesis, Genetic drug effects, Melanoma drug therapy, Melanoma genetics, Skin Neoplasms drug therapy, Skin Neoplasms genetics
- Abstract
Cutaneous melanoma is a very aggressive neoplasia of melanocytic origin with constantly growing incidence and mortality rates world-wide. Epigenetic modifications (i.e., alterations of genomic DNA methylation patterns, of post-translational modifications of histones, and of microRNA profiles) have been recently identified as playing an important role in melanoma development and progression by affecting key cellular pathways such as cell cycle regulation, cell signalling, differentiation, DNA repair, apoptosis, invasion and immune recognition. In this scenario, pharmacologic inhibition of DNA methyltransferases and/or of histone deacetylases were demonstrated to efficiently restore the expression of aberrantly-silenced genes, thus re-establishing pathway functions. In light of the pleiotropic activities of epigenetic drugs, their use alone or in combination therapies is being strongly suggested, and a particular clinical benefit might be expected from their synergistic activities with chemo-, radio-, and immuno-therapeutic approaches in melanoma patients. On this path, an important improvement would possibly derive from the development of new generation epigenetic drugs characterized by much reduced systemic toxicities, higher bioavailability, and more specific epigenetic effects.
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- 2010
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16. Sixth annual meeting of the Italian network for tumor biotherapy (NIBIT), Siena, 16-18 October 2008.
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Maio M, Nicolay HJ, Ascierto PA, Belardelli F, Camerini R, Colombo MP, Queirolo P, Ridolfi R, Russo V, Fonsatti E, and Parmiani G
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- Animals, Diagnostic Imaging, Humans, Immunologic Surveillance, Information Services, Italy, Neoplasms therapy, Neoplastic Stem Cells immunology, Organizations, Nonprofit, Cancer Vaccines, International Cooperation, Neoplasms immunology
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- 2010
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17. Epigenetically regulated clonal heritability of CTA expression profiles in human melanoma.
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Fratta E, Sigalotti L, Colizzi F, Covre A, Nicolay HJ, Danielli R, Fonsatti E, Altomonte M, Calabrò L, Coral S, and Maio M
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- Antimetabolites, Antineoplastic pharmacology, Azacitidine analogs & derivatives, Azacitidine pharmacology, Cell Division genetics, Clone Cells drug effects, Cloning, Molecular methods, DNA Methylation drug effects, Decitabine, Epigenesis, Genetic drug effects, Gene Expression Regulation, Neoplastic drug effects, Humans, Neoplasm Proteins genetics, Promoter Regions, Genetic genetics, Tumor Cells, Cultured, Antigens, Neoplasm genetics, Clone Cells metabolism, Epigenesis, Genetic genetics, Gene Expression Regulation, Neoplastic genetics, Inheritance Patterns genetics, Melanoma genetics, Melanoma metabolism
- Abstract
The intratumoral heterogeneity of cancer testis antigens (CTA) expression, which is driven by promoter methylation status, may hamper the effectiveness of CTA-directed vaccination of melanoma patients. Thus, we investigated whether the intratumoral heterogeneity of CTA expression is inherited at cellular level, or evolves throughout cellular replication, leading to a phenotypically unstable tumor cell population with reduced immunogenicity and/or able to escape immune control. Utilizing a previously characterized ex vivo clonal model of intratumoral heterogeneity of CTA expression in melanoma, Mel 313 MAGE-A3-low clone 5 (clone 5(M3-low)) and MAGE-A3-high clone 14 (clone 14(M3-high)) were sub-cloned and analyzed for CTA profile. Molecular assays demonstrated that levels of MAGE-A3 expression were highly conserved among generated sub-clones, as compared to parental clones. A similar behavior was identified for an extensive panel of other CTA investigated. Inherited levels of MAGE-A3 expression correlated with the extent of promoter methylation among clone 5(M3-low) and clone 14(M3-high) sub-clones analyzed. Treatment of clone 5(M3-low) with a DNA hypomethylating agent (DHA) resulted in an up-regulated expression of MAGE-A3, which was inherited at single cell level, being still detectable at day 60 in its sub-clones. Bisulfite sequencing demonstrated that also MAGE-A3 promoter methylation status was inherited among sub-clones generated from DHA-treated clone 5(M3-low) and strictly correlated with MAGE-A3 expression levels in investigated sub-clones. Similar results were obtained for additional CTA studied. Altogether our findings demonstrate that constitutive and DHA-modified CTA profiles of melanoma cells are clonally inherited throughout cellular replications, thus providing relevant insights to improve the effectiveness of CTA-based immunotherapy.
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- 2010
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18. Targeting cancer vasculature via endoglin/CD105: a novel antibody-based diagnostic and therapeutic strategy in solid tumours.
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Fonsatti E, Nicolay HJ, Altomonte M, Covre A, and Maio M
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- Antigens, CD metabolism, Biomarkers metabolism, Endoglin, Humans, Neoplasms metabolism, Neovascularization, Pathologic metabolism, Receptors, Cell Surface metabolism, Signal Transduction physiology, Antibodies, Monoclonal therapeutic use, Antigens, CD immunology, Neoplasms blood supply, Neoplasms therapy, Neovascularization, Pathologic drug therapy, Receptors, Cell Surface immunology
- Abstract
Endoglin/CD105 is well acknowledged as being the most reliable marker of proliferation of endothelial cells, and it is overexpressed on tumour neovasculature. Our current knowledge of its structure, physiological role, and tissue distribution suggests that targeting of endoglin/CD105 is a novel and powerful diagnostic and therapeutic strategy in human malignancies, through the imaging of tumour-associated angiogenesis and the inhibition of endothelial cell functions related to tumour angiogenesis. Among biotherapeutic agents, monoclonal antibodies have shown a major impact on the clinical course of human malignancies of different histotypes. Along this line, the potential efficacy of anti-endoglin/CD105 antibodies and their derivatives for clinical purposes in cancer is supported by a large body of available pre-clinical in vitro and in vivo data. In this review, the main findings supporting the translation of antibody-based endoglin/CD105 targeting from pre-clinical studies to clinical applications in human cancer are summarized and discussed.
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- 2010
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19. Cancer testis antigens and melanoma stem cells: new promises for therapeutic intervention.
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Sigalotti L, Covre A, Nicolay HJ, Coral S, and Maio M
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- Humans, Male, Antigens, Neoplasm metabolism, Melanoma immunology, Neoplastic Stem Cells immunology, Skin Neoplasms immunology, Testicular Neoplasms immunology
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- 2010
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20. Epigenetic drugs as pleiotropic agents in cancer treatment: biomolecular aspects and clinical applications.
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Sigalotti L, Fratta E, Coral S, Cortini E, Covre A, Nicolay HJ, Anzalone L, Pezzani L, Di Giacomo AM, Fonsatti E, Colizzi F, Altomonte M, Calabrò L, and Maio M
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- Acetylation, Animals, Antineoplastic Agents therapeutic use, Apoptosis drug effects, Apoptosis genetics, Cell Cycle drug effects, Cell Transformation, Neoplastic genetics, Cell Transformation, Neoplastic metabolism, Cell Transformation, Neoplastic pathology, Chromatin Assembly and Disassembly drug effects, DNA Methylation drug effects, DNA Modification Methylases antagonists & inhibitors, DNA Modification Methylases metabolism, DNA Repair drug effects, Enzyme Inhibitors therapeutic use, Histone Deacetylase Inhibitors, Histone Deacetylases metabolism, Histones metabolism, Humans, Neoplasm Invasiveness, Neoplasms enzymology, Neoplasms genetics, Neoplasms metabolism, Neoplasms pathology, Neovascularization, Pathologic drug therapy, Neovascularization, Pathologic genetics, Signal Transduction drug effects, Signal Transduction genetics, Tumor Escape drug effects, Tumor Escape genetics, Antineoplastic Agents pharmacology, Cell Transformation, Neoplastic drug effects, Enzyme Inhibitors pharmacology, Epigenesis, Genetic drug effects, Gene Expression Regulation, Neoplastic drug effects, Neoplasms drug therapy
- Abstract
In the last three decades huge efforts have been made to characterize genetic defects responsible for cancer development and progression, leading to the comprehensive identification of distinct cellular pathways affected by the alteration of specific genes. Despite the undoubtable role of genetic mechanisms in triggering neoplastic cell transformation, epigenetic modifications (i.e., heritable changes of gene expression that do not derive from alterations of the nucleotide sequence of DNA) are rapidly emerging as frequent alterations that often occur in the early phases of tumorigenesis and that play an important role in tumor development and progression. Epigenetic alterations, such as modifications in DNA methylation patterns and post-translational modifications of histone tails, behave extremely different from genetic modifications, being readily revertable by "epigenetic drugs" such as inhibitors of DNA methyl transferases and inhibitors of histone deacetylases. Since epigenetic alterations in cancer cells affect virtually all cellular pathways that have been associated to tumorigenesis, it is not surprising that epigenetic drugs display pleiotropic activities, being able to concomitantly restore the defective expression of genes involved in cell cycle control, apoptosis, cell signaling, tumor cell invasion and metastasis, angiogenesis and immune recognition. Prompted by this emerging clinical relevance of epigenetic drugs, this review will focus on the large amount of available data, deriving both from in vitro experimentations and in vivo pre-clinical and clinical studies, which clearly indicate epigenetic drugs as effective modifiers of cancer phenotype and as positive regulators of tumor cell biology with a relevant therapeutic potential in cancer patients.
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- 2007
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21. Functional up-regulation of human leukocyte antigen class I antigens expression by 5-aza-2'-deoxycytidine in cutaneous melanoma: immunotherapeutic implications.
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Fonsatti E, Nicolay HJ, Sigalotti L, Calabrò L, Pezzani L, Colizzi F, Altomonte M, Guidoboni M, Marincola FM, and Maio M
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- Azacitidine pharmacology, Cell Line, Tumor, Decitabine, Fluorescent Antibody Technique, Indirect, Humans, Interferon-gamma metabolism, Membrane Glycoproteins metabolism, Reverse Transcriptase Polymerase Chain Reaction, T-Lymphocytes, Cytotoxic metabolism, Up-Regulation, gp100 Melanoma Antigen, Azacitidine analogs & derivatives, Gene Expression Regulation, Neoplastic, Histocompatibility Antigens Class I biosynthesis, Immunotherapy methods, Melanoma drug therapy, Melanoma immunology, Skin Neoplasms drug therapy, Skin Neoplasms immunology, T-Lymphocytes, Cytotoxic immunology
- Abstract
Purpose: To investigate the potential of the DNA hypomethylating agent 5-aza-2'-deoxycytidine (5-aza-CdR) to improve the effectiveness of immunotherapeutic approaches against melanocyte differentiation antigens., Experimental Design: The effect of 5-aza-CdR on the constitutive expression of gp100 was investigated in 11 human melanoma cell lines by real-time reverse transcription-PCR and indirect immunofluorescence (IIF) analyses. 5-aza-CdR-mediated changes in the levels of expression of human leukocyte antigen (HLA) class I antigens and HLA-A2 allospecificity, intercellular adhesion molecule-1 (ICAM-1), and leukocyte-function-associated antigen-3 were investigated by IIF analysis on melanoma cells under study. The recognition of gp100-positive Mel 275 melanoma cells, treated or not with 5-aza-CdR, by HLA-A2-restricted gp100((209-217))-specific CTL was investigated by (51)Cr-release assays, IFN-gamma release and IFN-gamma ELISPOT assays., Results: The constitutive expression of gp100 was not affected by 5-aza-CdR on all melanoma cells investigated. Compared with untreated cells, the exposure of Mel 275 melanoma cells to 5-aza-CdR significantly (P < 0.05) up-regulated their expression of HLA class I antigens and of ICAM-1. These phenotypic changes significantly (P < 0.05) increased the lysis of 5-aza-CdR-treated Mel 275 melanoma cells by gp100-specific CTL and increased their IFN-gamma release. 5-aza-CdR treatment of Mel 275 cells also induced a higher number of gp100-specific CTL to secrete IFN-gamma., Conclusions: Treatment with 5-aza-CdR improves the recognition of melanoma cells by gp100-specific CTL through the up-regulation of HLA class I antigens expression; ICAM-1 also contributes to this phenomenon. These findings highlight a broader range of therapeutic implications of 5-aza-CdR when used in association with active or adoptive immunotherapeutic approaches against a variety of melanoma-associated antigens.
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- 2007
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22. 5-AZA-2'-deoxycytidine in cancer immunotherapy: a mouse to man story.
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Coral S, Sigalotti L, Covre A, Nicolay HJ, Natali PG, and Maio M
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- Animals, Antigens, Neoplasm immunology, Azacitidine pharmacology, Decitabine, Humans, Immunotherapy, Adoptive, Melanoma immunology, Mice, Xenograft Model Antitumor Assays, Antimetabolites, Antineoplastic pharmacology, Azacitidine analogs & derivatives, Melanoma therapy
- Published
- 2007
- Full Text
- View/download PDF
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