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Article ; Online: Genomic Chaos (Multiple Copy Number Variations and Structural Reorganization) Detected in Two Prenatal Cases.

Lloveras, Elisabet / Canellas, Anna / Plaja, Alberto / Barranco, Laura / Fernández, Daniel / Mendez, Begoña / Piqué, Meritxell / de la Iglesia, Cristina / Palau, Núria / Costa, Marta / Herrero, Marta / Yeste, Diana / Auge, Marc / Puig, Laia / Pérez, Cristina

Cytogenetic and genome research

2021 Volume 161, Issue 5, Page(s) 236–242

Abstract: The use of new technologies in the routine diagnosis of constitutional abnormalities, such as high-resolution chromosomal microarray and next-generation sequencing, has unmasked new mechanisms for generating structural variation of the human genome. For ... ...

Abstract	The use of new technologies in the routine diagnosis of constitutional abnormalities, such as high-resolution chromosomal microarray and next-generation sequencing, has unmasked new mechanisms for generating structural variation of the human genome. For example, complex chromosome rearrangements can originate by a chromosome catastrophe phenomenon in which numerous genomic rearrangements are apparently acquired in a single catastrophic event. This phenomenon is named chromoanagenesis (from the Greek "chromo" for chromosome and "anagenesis" for rebirth). Herein, we report 2 cases of genomic chaos detected at prenatal diagnosis. The terms "chromothripsis" and "chromoanasynthesis" and the challenge of genetic counseling are discussed.
MeSH term(s)	Abortion, Eugenic ; Adult ; Chromosome Breakpoints ; Chromothripsis ; Comparative Genomic Hybridization ; DNA Copy Number Variations ; Female ; Fetus ; Gene Rearrangement ; Genetic Counseling/ethics ; Genome, Human ; High-Throughput Nucleotide Sequencing ; Humans ; Karyotyping/methods ; Male ; Pregnancy ; Prenatal Diagnosis/methods
Language	English
Publishing date	2021-07-16
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2087824-2
ISSN	1424-859X ; 1424-8581
ISSN (online)	1424-859X
ISSN	1424-8581
DOI	10.1159/000515653
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Article ; Online: A New Case with Corpus Callosum Abnormalities, Microcephaly and Seizures Associated with a 2.3-Mb 1q43-q44 Deletion.

Lloveras, Elisabet / Canellas, Anna / Barranco, Laura / Alves, Claudia / Vila-Real, Marta / Ventura, Vania / Fernández, Daniel / Mendez, Begona / Piqué, Meritxell / Reis-Lima, Margarida / de la Iglesia, Cristina / Palau, Nuria / Costa, Marta / Yeste, Diana / Auge, Marc / Perez, Cristina

Cytogenetic and genome research

2019 Volume 159, Issue 3, Page(s) 126–129

Abstract: 1q44 deletion is a rare syndrome associated with facial dysmorphism and developmental delay, in particular related with expressive speech, seizures, and hypotonia (ORPHA:238769). Until today, the distinct genetic causes for the different symptoms remain ... ...

Abstract	1q44 deletion is a rare syndrome associated with facial dysmorphism and developmental delay, in particular related with expressive speech, seizures, and hypotonia (ORPHA:238769). Until today, the distinct genetic causes for the different symptoms remain not entirely clear. We present a patient with a 2.3-Mb 1q44 deletion, including AKT3, ZBTB18, and HNRNPU, who shows microcephaly, developmental delay, abnormal corpus callosum, and seizures. The genetic findings in this case and a review of the literature spotlight a region between 243 Mb and 245 Mb on chromosome 1q related to the genesis of the typical symptoms of 1q44 deletion.
MeSH term(s)	Child ; Chromosome Deletion ; Chromosomes, Human, Pair 1 ; Corpus Callosum/pathology ; Humans ; Male ; Microcephaly/genetics ; Seizures/genetics
Language	English
Publishing date	2019-12-13
Publishing country	Switzerland
Document type	Case Reports ; Journal Article
ZDB-ID	2087824-2
ISSN	1424-859X ; 1424-8581
ISSN (online)	1424-859X
ISSN	1424-8581
DOI	10.1159/000504424
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Article ; Online: Alanine-based spacers promote an efficient antigen processing and presentation in neoantigen polypeptide vaccines.

Aguilar-Gurrieri, Carmen / Barajas, Ana / Rovirosa, Carla / Ortiz, Raquel / Urrea, Victor / de la Iglesia, Nuria / Clotet, Bonaventura / Blanco, Julià / Carrillo, Jorge

Cancer immunology, immunotherapy : CII

2023 Volume 72, Issue 7, Page(s) 2113–2125

Abstract: Neoantigens are tumor-specific antigens that are mostly particular for each patient. Since the immune system is able to mount a specific immune response against these neoantigens, they are a promising tool for the development of therapeutic personalized ... ...

Abstract	Neoantigens are tumor-specific antigens that are mostly particular for each patient. Since the immune system is able to mount a specific immune response against these neoantigens, they are a promising tool for the development of therapeutic personalized cancer vaccines. Neoantigens must be presented to T cells by antigen presenting cells (APC) in the context of MHC-I or MHC-II molecules. Therefore, the strategy of vaccine delivery may have a major impact on the magnitude and quality of T cell responses. Neoantigen-based vaccines are frequently administered as a pool of individual synthetic peptides that induce mainly CD4
MeSH term(s)	Humans ; Antigen Presentation ; Neoplasms ; Histocompatibility Antigens Class I ; Antigens, Neoplasm ; Peptides ; Cancer Vaccines ; Immunotherapy
Chemical Substances	Histocompatibility Antigens Class I ; Antigens, Neoplasm ; Peptides ; Cancer Vaccines
Language	English
Publishing date	2023-02-23
Publishing country	Germany
Document type	Journal Article
ZDB-ID	195342-4
ISSN	1432-0851 ; 0340-7004
ISSN (online)	1432-0851
ISSN	0340-7004
DOI	10.1007/s00262-023-03409-3
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Article ; Online: Virus-like particle-mediated delivery of structure-selected neoantigens demonstrates immunogenicity and antitumoral activity in mice.

Journal of translational medicine

2024 Volume 22, Issue 1, Page(s) 14

Abstract: ... that elicits robust de novo immune responses.: Methods: We developed a novel neoantigen selection pipeline ... platform that elicits robust de novo immune responses and bypasses central and peripheral tolerance ... the interaction with the TCR can promote the generation of de novo antitumor-specific immune responses, resulting ...

Abstract	Background: Neoantigens are patient- and tumor-specific peptides that arise from somatic mutations. They stand as promising targets for personalized therapeutic cancer vaccines. The identification process for neoantigens has evolved with the use of next-generation sequencing technologies and bioinformatic tools in tumor genomics. However, in-silico strategies for selecting immunogenic neoantigens still have very low accuracy rates, since they mainly focus on predicting peptide binding to Major Histocompatibility Complex (MHC) molecules, which is key but not the sole determinant for immunogenicity. Moreover, the therapeutic potential of neoantigen-based vaccines may be enhanced using an optimal delivery platform that elicits robust de novo immune responses. Methods: We developed a novel neoantigen selection pipeline based on existing software combined with a novel prediction method, the Neoantigen Optimization Algorithm (NOAH), which takes into account structural features of the peptide/MHC-I interaction, as well as the interaction between the peptide/MHC-I complex and the TCR, in its prediction strategy. Moreover, to maximize neoantigens' therapeutic potential, neoantigen-based vaccines should be manufactured in an optimal delivery platform that elicits robust de novo immune responses and bypasses central and peripheral tolerance. Results: We generated a highly immunogenic vaccine platform based on engineered HIV-1 Gag-based Virus-Like Particles (VLPs) expressing a high copy number of each in silico selected neoantigen. We tested different neoantigen-loaded VLPs (neoVLPs) in a B16-F10 melanoma mouse model to evaluate their capability to generate new immunogenic specificities. NeoVLPs were used in in vivo immunogenicity and tumor challenge experiments. Conclusions: Our results indicate the relevance of incorporating other immunogenic determinants beyond the binding of neoantigens to MHC-I. Thus, neoVLPs loaded with neoantigens enhancing the interaction with the TCR can promote the generation of de novo antitumor-specific immune responses, resulting in a delay in tumor growth. Vaccination with the neoVLP platform is a robust alternative to current therapeutic vaccine approaches and a promising candidate for future personalized immunotherapy.
MeSH term(s)	Humans ; Animals ; Mice ; Neoplasms/genetics ; Antigens, Neoplasm/metabolism ; Peptides ; Receptors, Antigen, T-Cell/metabolism ; Vaccines ; Cancer Vaccines ; Immunotherapy/methods
Chemical Substances	Antigens, Neoplasm ; Peptides ; Receptors, Antigen, T-Cell ; Vaccines ; Cancer Vaccines
Language	English
Publishing date	2024-01-03
Publishing country	England
Document type	Journal Article
ZDB-ID	2118570-0
ISSN	1479-5876 ; 1479-5876
ISSN (online)	1479-5876
ISSN	1479-5876
DOI	10.1186/s12967-023-04843-8
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Article: The C250T Mutation of

Cancers

2024 Volume 16, Issue 4

Abstract: The aim of this study was to determine how : Materials and methods: TERTp: Results: Overall, there were no differences in outcomes between patients with mutated : Conclusions: In our series, patients exhibiting the C250T mutation had a more ... ...

Abstract	The aim of this study was to determine how Materials and methods: TERTp Results: Overall, there were no differences in outcomes between patients with mutated Conclusions: In our series, patients exhibiting the C250T mutation had a more favorable prognosis compared to those with either
Language	English
Publishing date	2024-02-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers16040735
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Article: Dual Role of Integrin Alpha-6 in Glioblastoma: Supporting Stemness in Proneural Stem-Like Cells While Inducing Radioresistance in Mesenchymal Stem-Like Cells.

Stanzani, Elisabetta / Pedrosa, Leire / Bourmeau, Guillaume / Anezo, Oceane / Noguera-Castells, Aleix / Esteve-Codina, Anna / Passoni, Lorena / Matteoli, Michela / de la Iglesia, Núria / Seano, Giorgio / Martínez-Soler, Fina / Tortosa, Avelina

Cancers

2021 Volume 13, Issue 12

Abstract: Therapeutic resistance after multimodal therapy is the most relevant cause of glioblastoma (GBM) recurrence. Extensive cellular heterogeneity, mainly driven by the presence of GBM stem-like cells (GSCs), strongly correlates with patients' prognosis and ... ...

Abstract	Therapeutic resistance after multimodal therapy is the most relevant cause of glioblastoma (GBM) recurrence. Extensive cellular heterogeneity, mainly driven by the presence of GBM stem-like cells (GSCs), strongly correlates with patients' prognosis and limited response to therapies. Defining the mechanisms that drive stemness and control responsiveness to therapy in a GSC-specific manner is therefore essential. Here we investigated the role of integrin a6 (
Language	English
Publishing date	2021-06-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13123055
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Article ; Online: Virus-like particle-mediated delivery of structure-selected neoantigens demonstrates immunogenicity and antitumoral activity in mice

Journal of Translational Medicine, Vol 22, Iss 1, Pp 1-

2024 Volume 14

Abstract: ... that elicits robust de novo immune responses. Methods We developed a novel neoantigen selection pipeline based ... platform that elicits robust de novo immune responses and bypasses central and peripheral tolerance ... with the TCR can promote the generation of de novo ... ...

Abstract	Abstract Background Neoantigens are patient- and tumor-specific peptides that arise from somatic mutations. They stand as promising targets for personalized therapeutic cancer vaccines. The identification process for neoantigens has evolved with the use of next-generation sequencing technologies and bioinformatic tools in tumor genomics. However, in-silico strategies for selecting immunogenic neoantigens still have very low accuracy rates, since they mainly focus on predicting peptide binding to Major Histocompatibility Complex (MHC) molecules, which is key but not the sole determinant for immunogenicity. Moreover, the therapeutic potential of neoantigen-based vaccines may be enhanced using an optimal delivery platform that elicits robust de novo immune responses. Methods We developed a novel neoantigen selection pipeline based on existing software combined with a novel prediction method, the Neoantigen Optimization Algorithm (NOAH), which takes into account structural features of the peptide/MHC-I interaction, as well as the interaction between the peptide/MHC-I complex and the TCR, in its prediction strategy. Moreover, to maximize neoantigens’ therapeutic potential, neoantigen-based vaccines should be manufactured in an optimal delivery platform that elicits robust de novo immune responses and bypasses central and peripheral tolerance. Results We generated a highly immunogenic vaccine platform based on engineered HIV-1 Gag-based Virus-Like Particles (VLPs) expressing a high copy number of each in silico selected neoantigen. We tested different neoantigen-loaded VLPs (neoVLPs) in a B16-F10 melanoma mouse model to evaluate their capability to generate new immunogenic specificities. NeoVLPs were used in in vivo immunogenicity and tumor challenge experiments. Conclusions Our results indicate the relevance of incorporating other immunogenic determinants beyond the binding of neoantigens to MHC-I. Thus, neoVLPs loaded with neoantigens enhancing the interaction with the TCR can promote the generation of de novo ...
Keywords	Neoantigen ; Cancer vaccine ; Virus-like particle ; Immunotherapy ; T cell response ; Medicine ; R
Subject code	570
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Via clínica para cirugía mediante técnica WALANT fuera del estándar de cirugía mayor ambulatoria

Sanjuan-Cerveró, Rafael / Peña-Molina, Fernando / Sanjuan-Aragó, Aurora / Iglesia, Nicolas de la / Franco-Ferrando, Nuria

Revista Iberoamericana de Cirugía de la Mano

2022 Volume 50, Issue 02, Page(s) e084–e093

Abstract: Objetivo: Desarrollar y valorar al año una vía clínica para procedimientos de cirugía de mano utilizando anestesia local sin torniquete y con el paciente despierto, denominada técnica WALANT ( wide awake, local anesthesia, no tourniquet, en inglés).: ... ...

Abstract	Objetivo: Desarrollar y valorar al año una vía clínica para procedimientos de cirugía de mano utilizando anestesia local sin torniquete y con el paciente despierto, denominada técnica WALANT ( wide awake, local anesthesia, no tourniquet, en inglés). Materiales y Métodos: Se planificó y ejecutó una vía clínica para pacientes de cirugía de mano no compleja, y se realizó una comparativa de costes entre dotación completa del quirófano y cirugía local con la técnica WALANT. Como indicadores de la calidad, se calculó la tasa de suspensiones quirúrgicas y el número de pacientes intervenidos. Se comparó el tiempo medio de estancia hospitalaria entre los pacientes intervenidos de forma ordinaria y en el quirófano WALANT. Se valoró la reducción en la lista de espera quirúrgica en síndrome del túnel del carpo y dedo en gatillo. Resultados: Los gastos directos fueron un 48,9% menores en el procedimiento WALANT. Se valoraron 254 pacientes en 2020 y 339 en 2021. La tasa de suspensión fue del 5,1% (0,4% por motivos médicos). El tiempo de estancia en el hospital fue significativamente menor para los pacientes del grupo WALANT (z = -8,743; p = 0,000). La disminución en la lista quirúrgica fue de 113 días. Conclusiones: La cirugía mediante la técnica WALANT adecuada a esta vía clínica permite la intervención de pacientes con menos recursos, lo que disminuye los gastos directos y alivia las unidades de Cirugía Ambulatoria. ; Objective: To develop and assess after one year a clinical pathway for hand surgery procedures using the wide awake, local anesthesia, no tourniquet (WALANT) technique. Materials and Methods: We planned and executed clinical pathway for non-complex hand surgery patients and performed a comparative cost assessment between the operating room with all the necessary staff and local surgery with the WALANT technique. The rate of surgical cancellations and the number of patients operated on were calculated as indicators of quality. The mean length of hospital stay was compared between patients operated on in an ordinary fashion and in the WALANT operating room. We assessed the reduction in the surgical waiting list for carpal tunnel syndrome and trigger finger. Results: Direct costs were 48.9% lower with the WALANT technique. We evaluated 254 patients in 2020 and 339 in 2021. The rate of cancellations was of 5.1% (0.4% for medical reasons). The length of hospital stay was significantly shorter for patients in the WALANT group (z = -8.743; p = 0.000). The decrease in the surgical list was of 113 days. Conclusions: Surgery with the WALANT technique suited for this clinical pathway enables the performance of interventions in patients with less resources, which decreases the direct costs and unburdens the Outpatient Surgery Units.
Keywords	anestesia local ; WALANT ; vía clínica ; cirugía mayor ambulatoria ; local anesthesia ; WALANT ; clinical pathway ; major outpatient surgery
Language	Spanish
Publishing date	2022-11-01
Publisher	Thieme Revinter Publicações Ltda.
Publishing place	Stuttgart ; New York
Document type	Article
ZDB-ID	2874929-7
ISSN	1698-840X ; 1698-8396
ISSN (online)	1698-840X
ISSN	1698-8396
DOI	10.1055/s-0042-1756202
Database	Thieme publisher's database

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Article ; Online: Converging and evolving immuno-genomic routes toward immune escape in breast cancer.

Blanco-Heredia, Juan / Souza, Carla Anjos / Trincado, Juan L / Gonzalez-Cao, Maria / Gonçalves-Ribeiro, Samuel / Gil, Sara Ruiz / Pravdyvets, Dmytro / Cedeño, Samandhy / Callari, Maurizio / Marra, Antonio / Gazzo, Andrea M / Weigelt, Britta / Pareja, Fresia / Vougiouklakis, Theodore / Jungbluth, Achim A / Rosell, Rafael / Brander, Christian / Tresserra, Francesc / Reis-Filho, Jorge S /

Tiezzi, Daniel Guimarães / de la Iglesia, Nuria / Heyn, Holger / De Mattos-Arruda, Leticia

Nature communications

2024 Volume 15, Issue 1, Page(s) 1302

Abstract: The interactions between tumor and immune cells along the course of breast cancer progression remain largely unknown. Here, we extensively characterize multiple sequential and parallel multiregion tumor and blood specimens of an index patient and a ... ...

Abstract	The interactions between tumor and immune cells along the course of breast cancer progression remain largely unknown. Here, we extensively characterize multiple sequential and parallel multiregion tumor and blood specimens of an index patient and a cohort of metastatic triple-negative breast cancers. We demonstrate that a continuous increase in tumor genomic heterogeneity and distinct molecular clocks correlated with resistance to treatment, eventually allowing tumors to escape from immune control. TCR repertoire loses diversity over time, leading to convergent evolution as breast cancer progresses. Although mixed populations of effector memory and cytotoxic single T cells coexist in the peripheral blood, defects in the antigen presentation machinery coupled with subdued T cell recruitment into metastases are observed, indicating a potent immune avoidance microenvironment not compatible with an effective antitumor response in lethal metastatic disease. Our results demonstrate that the immune responses against cancer are not static, but rather follow dynamic processes that match cancer genomic progression, illustrating the complex nature of tumor and immune cell interactions.
MeSH term(s)	Humans ; Female ; Breast Neoplasms/genetics ; Triple Negative Breast Neoplasms/genetics ; Triple Negative Breast Neoplasms/pathology ; Genomics/methods ; Tumor Microenvironment
Language	English
Publishing date	2024-02-21
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-45292-1
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Article ; Online: Gal-1 Expression Analysis in the GLIOCAT Multicenter Study: Role as a Prognostic Factor and an Immune-Suppressive Biomarker.

Cells

2023 Volume 12, Issue 6

Abstract: Glioblastoma (GBM) is the most frequent primary malignant brain tumor and has a dismal prognosis. Unfortunately, despite the recent revolution of immune checkpoint inhibitors in many solid tumors, these have not shown a benefit in overall survival in GBM ...

Abstract	Glioblastoma (GBM) is the most frequent primary malignant brain tumor and has a dismal prognosis. Unfortunately, despite the recent revolution of immune checkpoint inhibitors in many solid tumors, these have not shown a benefit in overall survival in GBM patients. Therefore, new potential treatment targets as well as diagnostic, prognostic, and/or predictive biomarkers are needed to improve outcomes in this population. The β-galactoside binding protein Galectin-1 (Gal-1) is a protein with a wide range of pro-tumor functions such as proliferation, invasion, angiogenesis, and immune suppression. Here, we evaluated Gal-1 expression by immunohistochemistry in a homogenously treated cohort of GBM (the GLIOCAT project) and correlated its expression with clinical and molecular data. We observed that Gal-1 is a negative prognostic factor in GBM. Interestingly, we observed higher levels of Gal-1 expression in the mesenchymal/classical subtypes compared to the less aggressive proneural subtype. We also observed a Gal-1 expression correlation with immune suppressive signatures of CD4 T-cells and macrophages, as well as with several GBM established biomarkers, including SHC1, PD-L1, PAX2, MEOX2, YKL-40, TCIRG1, YWHAG, OLIG2, SOX2, Ki-67, and SOX11. Moreover, Gal-1 levels were significantly lower in grade 4
MeSH term(s)	Humans ; Galectin 1/genetics ; Galectin 1/metabolism ; Prognosis ; Glioblastoma/diagnosis ; Glioblastoma/genetics ; Glioblastoma/metabolism ; Astrocytoma/metabolism ; Biomarkers ; Vacuolar Proton-Translocating ATPases/metabolism ; 14-3-3 Proteins/metabolism
Chemical Substances	Galectin 1 ; Biomarkers ; TCIRG1 protein, human ; Vacuolar Proton-Translocating ATPases (EC 3.6.1.-) ; YWHAG protein, human ; 14-3-3 Proteins
Language	English
Publishing date	2023-03-08
Publishing country	Switzerland
Document type	Multicenter Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12060843
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