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Article ; Online: Association between an elevated inter-arm systolic blood pressure difference, the ankle-brachial index, and mortality in patients with diabetes mellitus.

Ena, Javier / Pérez-Martín, Santiago / Argente, Carlos R / Lozano, Teresa

Clinica e investigacion en arteriosclerosis : publicacion oficial de la Sociedad Espanola de Arteriosclerosis

2020 Volume 32, Issue 3, Page(s) 94–100

Abstract: Objectives: To estimate the prevalence of an inter-arm blood pressure difference greater than 10mmHg in patients with type 2 diabetes, and the association of this measurement with the presence of a low ankle-brachial index and mortality at 5-year follow- ...

Abstract	Objectives: To estimate the prevalence of an inter-arm blood pressure difference greater than 10mmHg in patients with type 2 diabetes, and the association of this measurement with the presence of a low ankle-brachial index and mortality at 5-year follow-up. Method: A validated blood pressure measurement protocol was used. The blood pressure was calculated for each arm to obtain mean systolic differences. Peripheral arterial disease was confirmed by an ankle-arm index less than 0.9. The medical history of the patient was reviewed in the computerized clinical notes after 5 years of follow-up. Results: The study included 139 patients with a mean age of 70.1 years (49% male), and a mean duration of diabetes mellitus of 10.8 years. A total of 50 (36%) patients had an inter-arm systolic blood pressure difference greater than 10mmHg. Patients with an inter-arm systolic blood pressure greater than 10mmHg had lower ankle-arm index (0.91±0.30 vs. 1.04±0.28, P=0.005), and higher mortality rates from all causes (48.0% vs. 28.9%; hazard ratio 1.64; 95% confidence interval: 1.06-2.53; P=0.03), compared with those with lower inter-arm systolic blood pressure difference. Conclusion: A high proportion of patients with type 2 diabetes have an elevated systolic blood pressure difference between arms. A significant relationship was found between elevated inter-arm systolic blood pressure difference, lower ankle-brachial index and greater all-cause mortality.
MeSH term(s)	Aged ; Aged, 80 and over ; Ankle Brachial Index/methods ; Arm ; Blood Pressure/physiology ; Blood Pressure Determination/methods ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/mortality ; Female ; Follow-Up Studies ; Humans ; Hypertension/diagnosis ; Hypertension/epidemiology ; Male ; Middle Aged ; Prospective Studies
Language	Spanish
Publishing date	2020-02-07
Publishing country	Spain
Document type	Journal Article
ISSN	1578-1879
ISSN (online)	1578-1879
DOI	10.1016/j.arteri.2019.11.003
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Article: Intratumoral electroporation of a self-amplifying RNA expressing IL-12 induces antitumor effects in mouse models of cancer.

Silva-Pilipich, Noelia / Lasarte-Cía, Aritz / Lozano, Teresa / Martín-Otal, Celia / Lasarte, Juan José / Smerdou, Cristian

Molecular therapy. Nucleic acids

2022 Volume 29, Page(s) 387–399

Abstract: Alphavirus vectors based on self-amplifying RNA (saRNA) generate high and transient levels of transgene expression and induce innate immune responses, making them an interesting tool for antitumor therapy. These vectors are usually delivered as viral ... ...

Abstract	Alphavirus vectors based on self-amplifying RNA (saRNA) generate high and transient levels of transgene expression and induce innate immune responses, making them an interesting tool for antitumor therapy. These vectors are usually delivered as viral particles, but it is also possible to administer them as RNA. We evaluated this possibility by
Language	English
Publishing date	2022-07-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2662631-7
ISSN	2162-2531
ISSN	2162-2531
DOI	10.1016/j.omtn.2022.07.020
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Article ; Online: An intracoronary honeycomb: a case report.

Valencia, José / Martín-Torres, José Miguel / Ruiz-Nodar, Juan Miguel / Lozano, Teresa

European heart journal. Case reports

2020 Volume 4, Issue 6, Page(s) 1–2

Language	English
Publishing date	2020-12-05
Publishing country	England
Document type	Journal Article
ISSN	2514-2119
ISSN (online)	2514-2119
DOI	10.1093/ehjcr/ytaa395
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Article ; Online: The transcriptional regulator Sin3A balances IL-17A and Foxp3 expression in primary CD4 T cells.

Perucho, Laura / Icardi, Laura / Di Simone, Elisabetta / Basso, Veronica / Agresti, Alessandra / Vilas Zornoza, Amaia / Lozano, Teresa / Prosper, Felipe / Lasarte, Juan José / Mondino, Anna

EMBO reports

2023 Volume 24, Issue 5, Page(s) e55326

Abstract: The Sin3 transcriptional regulator homolog A (Sin3A) is the core member of a multiprotein chromatin-modifying complex. Its inactivation at the CD4/CD8 double-negative stage halts further thymocyte development. Among various functions, Sin3A regulates ... ...

Abstract	The Sin3 transcriptional regulator homolog A (Sin3A) is the core member of a multiprotein chromatin-modifying complex. Its inactivation at the CD4/CD8 double-negative stage halts further thymocyte development. Among various functions, Sin3A regulates STAT3 transcriptional activity, central to the differentiation of Th17 cells active in inflammatory disorders and opportunistic infections. To further investigate the consequences of conditional Sin3A inactivation in more mature precursors and post-thymic T cell, we have generated CD4-Cre and CD4-CreER
MeSH term(s)	Animals ; Mice ; CD4-Positive T-Lymphocytes/metabolism ; Cell Differentiation/genetics ; Forkhead Transcription Factors/genetics ; Forkhead Transcription Factors/metabolism ; Interleukin-17/genetics ; Interleukin-17/metabolism ; Th17 Cells
Chemical Substances	Forkhead Transcription Factors ; Foxp3 protein, mouse ; Interleukin-17 ; SIN3A transcription factor
Language	English
Publishing date	2023-03-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2020896-0
ISSN	1469-3178 ; 1469-221X
ISSN (online)	1469-3178
ISSN	1469-221X
DOI	10.15252/embr.202255326
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Zs.A 5433: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 41: Show issues

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Article ; Online: Local delivery of optimized nanobodies targeting the PD-1/PD-L1 axis with a self-amplifying RNA viral vector induces potent antitumor responses.

Silva-Pilipich, Noelia / Blanco, Ester / Lozano, Teresa / Martisova, Eva / Igea, Ana / Herrador-Cañete, Guillermo / Ballesteros-Briones, María Cristina / Gorraiz, Marta / Sarrión, Patricia / González-Sapienza, Gualberto / Lasarte, Juan José / Vanrell, Lucía / Smerdou, Cristian

Cancer letters

2023 Volume 561, Page(s) 216139

Abstract: Despite the success of immune checkpoint blockade for cancer therapy, many patients do not respond adequately. We aimed to improve this therapy by optimizing both the antibodies and their delivery route, using small monodomain antibodies (nanobodies) ... ...

Abstract	Despite the success of immune checkpoint blockade for cancer therapy, many patients do not respond adequately. We aimed to improve this therapy by optimizing both the antibodies and their delivery route, using small monodomain antibodies (nanobodies) delivered locally with a self-amplifying RNA (saRNA) vector based on Semliki Forest virus (SFV). We generated nanobodies against PD-1 and PD-L1 able to inhibit both human and mouse interactions. Incorporation of a dimerization domain reduced PD-1/PD-L1 IC50 by 8- and 40-fold for anti-PD-L1 and anti-PD-1 nanobodies, respectively. SFV viral particles expressing dimeric nanobodies showed a potent antitumor response in the MC38 model, resulting in >50% complete regressions, and showed better therapeutic efficacy compared to vectors expressing conventional antibodies. These effects were also observed in the B16 melanoma model. Although a short-term expression of nanobodies was observed due to the cytopathic nature of the saRNA vector, it was enough to generate a strong proinflammatory response in tumors, increasing infiltration of NK and CD8
MeSH term(s)	Animals ; Humans ; Mice ; B7-H1 Antigen/genetics ; CD8-Positive T-Lymphocytes ; Neoplasms ; Semliki forest virus/genetics ; Single-Domain Antibodies/genetics ; Programmed Cell Death 1 Receptor/metabolism
Chemical Substances	B7-H1 Antigen ; Single-Domain Antibodies ; Programmed Cell Death 1 Receptor
Language	English
Publishing date	2023-03-29
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	195674-7
ISSN	1872-7980 ; 0304-3835
ISSN (online)	1872-7980
ISSN	0304-3835
DOI	10.1016/j.canlet.2023.216139
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Zs.A 1177: Show issues

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Article: Impact of tumor microenvironment on adoptive T cell transfer activity.

Martín-Otal, Celia / Navarro, Flor / Casares, Noelia / Lasarte-Cía, Aritz / Sánchez-Moreno, Inés / Hervás-Stubbs, Sandra / Lozano, Teresa / Lasarte, Juan José

International review of cell and molecular biology

2022 Volume 370, Page(s) 1–31

Abstract: Recent advances in immunotherapy have revolutionized the treatment of cancer. The use of adoptive cell therapies (ACT) such as those based on tumor infiltrating lymphocytes (TILs) or genetically modified cells (transgenic TCR lymphocytes or CAR-T cells), ...

Abstract	Recent advances in immunotherapy have revolutionized the treatment of cancer. The use of adoptive cell therapies (ACT) such as those based on tumor infiltrating lymphocytes (TILs) or genetically modified cells (transgenic TCR lymphocytes or CAR-T cells), has shown impressive results in the treatment of several types of cancers. However, cancer cells can exploit mechanisms to escape from immunosurveillance resulting in many patients not responding to these therapies or respond only transiently. The failure of immunotherapy to achieve long-term tumor control is multifactorial. On the one hand, only a limited percentage of the transferred lymphocytes is capable of circulating through the bloodstream, interacting and crossing the tumor endothelium to infiltrate the tumor. Metabolic competition, excessive glucose consumption, the high level of lactic acid secretion and the extracellular pH acidification, the shortage of essential amino acids, the hypoxic conditions or the accumulation of fatty acids in the tumor microenvironment (TME), greatly hinder the anti-tumor activity of the immune cells in ACT therapy strategies. Therefore, there is a new trend in immunotherapy research that seeks to unravel the fundamental biology that underpins the response to therapy and identifies new approaches to better amplify the efficacy of immunotherapies. In this review we address important aspects that may significantly affect the efficacy of ACT, indicating also the therapeutic alternatives that are currently being implemented to overcome these drawbacks.
MeSH term(s)	Humans ; Immunotherapy ; Immunotherapy, Adoptive/methods ; Lymphocytes, Tumor-Infiltrating ; Neoplasms/therapy ; T-Lymphocytes ; Tumor Microenvironment
Language	English
Publishing date	2022-06-21
Publishing country	Netherlands
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2427220-6
ISSN	1937-6448 ; 0074-7696
ISSN	1937-6448 ; 0074-7696
DOI	10.1016/bs.ircmb.2022.03.002
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Uc I Zs.317: Show issues

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Article ; Online: FOXP3 expression diversifies the metabolic capacity and enhances the efficacy of CD8 T cells in adoptive immunotherapy of melanoma.

Conde, Enrique / Casares, Noelia / Mancheño, Uxua / Elizalde, Edurne / Vercher, Enric / Capozzi, Roberto / Santamaria, Eva / Rodriguez-Madoz, Juan R / Prosper, Felipe / Lasarte, Juan J / Lozano, Teresa / Hervas-Stubbs, Sandra

Molecular therapy : the journal of the American Society of Gene Therapy

2022 Volume 31, Issue 1, Page(s) 48–65

Abstract: Regulatory T cells overwhelm conventional T cells in the tumor microenvironment (TME) thanks to a FOXP3-driven metabolic program that allows them to engage different metabolic pathways. Using a melanoma model of adoptive T cell therapy (ACT), we show ... ...

Abstract	Regulatory T cells overwhelm conventional T cells in the tumor microenvironment (TME) thanks to a FOXP3-driven metabolic program that allows them to engage different metabolic pathways. Using a melanoma model of adoptive T cell therapy (ACT), we show that FOXP3 overexpression in mature CD8 T cells improved their antitumor efficacy, favoring their tumor recruitment, proliferation, and cytotoxicity. FOXP3-overexpressing (Foxp3UP) CD8 T cells exhibited features of tissue-resident memory-like and effector T cells, but not suppressor activity. Transcriptomic analysis of tumor-infiltrating Foxp3UP CD8 T cells showed positive enrichment in a wide variety of metabolic pathways, such as glycolysis, fatty acid (FA) metabolism, and oxidative phosphorylation (OXPHOS). Intratumoral Foxp3UP CD8 T cells exhibited an enhanced capacity for glucose and FA uptake as well as accumulation of intracellular lipids. Interestingly, Foxp3UP CD8 T cells compensated for the loss of mitochondrial respiration-driven ATP production by activating aerobic glycolysis. Moreover, in limiting nutrient conditions these cells engaged FA oxidation to drive OXPHOS for their energy demands. Importantly, their ability to couple glycolysis and OXPHOS allowed them to sustain proliferation under glucose restriction. Our findings demonstrate a hitherto unknown role for FOXP3 in the adaptation of CD8 T cells to TME that may enhance their efficacy in ACT.
MeSH term(s)	Humans ; CD8-Positive T-Lymphocytes/immunology ; Forkhead Transcription Factors/genetics ; Forkhead Transcription Factors/metabolism ; Glucose/metabolism ; Immunotherapy, Adoptive ; Melanoma/therapy ; Tumor Microenvironment
Chemical Substances	Forkhead Transcription Factors ; FOXP3 protein, human ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2022-08-31
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2010592-7
ISSN	1525-0024 ; 1525-0016
ISSN (online)	1525-0024
ISSN	1525-0016
DOI	10.1016/j.ymthe.2022.08.017
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Zs.A 5640: Show issues

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Article: A Tomato EMS-Mutagenized Population Provides New Valuable Resources for Gene Discovery and Breeding of Developmental Traits.

Fonseca, Rocío / Capel, Carmen / Nieto-Canseco, Roberto / Ortiz-Atienza, Ana / Bretones, Sandra / López-Fábregas, Juan D / Quevedo-Colmena, Abraham S / Lebrón, Ricardo / Barragán-Lozano, Teresa / Villalobos-Ramírez, Víctor / Yuste-Lisbona, Fernando J / Angosto, Trinidad / Capel, Juan / Lozano, Rafael

Plants (Basel, Switzerland)

2022 Volume 11, Issue 19

Abstract: Tomato ( ...

Abstract	Tomato (
Language	English
Publishing date	2022-09-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704341-1
ISSN	2223-7747
ISSN	2223-7747
DOI	10.3390/plants11192453
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Article ; Online: Overcoming T cell dysfunction in acidic pH to enhance adoptive T cell transfer immunotherapy.

Navarro, Flor / Casares, Noelia / Martín-Otal, Celia / Lasarte-Cía, Aritz / Gorraiz, Marta / Sarrión, Patricia / Llopiz, Diana / Reparaz, David / Varo, Nerea / Rodriguez-Madoz, Juan Roberto / Prosper, Felipe / Hervás-Stubbs, Sandra / Lozano, Teresa / Lasarte, Juan José

Oncoimmunology

2022 Volume 11, Issue 1, Page(s) 2070337

Abstract: The high metabolic activity and insufficient perfusion of tumors leads to the acidification of the tumor microenvironment (TME) that may inhibit the antitumor T cell activity. We found that pharmacological inhibition of the acid loader chloride/ ... ...

Abstract	The high metabolic activity and insufficient perfusion of tumors leads to the acidification of the tumor microenvironment (TME) that may inhibit the antitumor T cell activity. We found that pharmacological inhibition of the acid loader chloride/bicarbonate anion exchanger 2 (Ae2), with 4,4'-diisothiocyanatostilbene-2,2'-disulfonicacid (DIDS) enhancedCD4
MeSH term(s)	4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid/metabolism ; Animals ; CD8-Positive T-Lymphocytes/metabolism ; Cell Line, Tumor ; Hydrogen-Ion Concentration ; Immunotherapy, Adoptive/methods ; Mice
Chemical Substances	4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid (Q1O6DSW23R)
Language	English
Publishing date	2022-05-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2645309-5
ISSN	2162-402X ; 2162-4011
ISSN (online)	2162-402X
ISSN	2162-4011
DOI	10.1080/2162402X.2022.2070337
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Article ; Online: Dual activity of PD-L1 targeted Doxorubicin immunoliposomes promoted an enhanced efficacy of the antitumor immune response in melanoma murine model.

Merino, María / Lozano, Teresa / Casares, Noelia / Lana, Hugo / Troconiz, Iñaki F / Ten Hagen, Timo L M / Kochan, Grazyna / Berraondo, Pedro / Zalba, Sara / Garrido, María J

Journal of nanobiotechnology

2021 Volume 19, Issue 1, Page(s) 102

Abstract: Background: The immunomodulation of the antitumor response driven by immunocheckpoint inhibitors (ICIs) such as PD-L1 (Programmed Death Ligand-1) monoclonal antibody (α-PD-L1) have shown relevant clinical outcomes in a subset of patients. This fact has ... ...

Abstract	Background: The immunomodulation of the antitumor response driven by immunocheckpoint inhibitors (ICIs) such as PD-L1 (Programmed Death Ligand-1) monoclonal antibody (α-PD-L1) have shown relevant clinical outcomes in a subset of patients. This fact has led to the search for rational combinations with other therapeutic agents such as Doxorubicin (Dox), which cytotoxicity involves an immune activation that may enhance ICI response. Therefore, this study aims to evaluate the combination of chemotherapy and ICI by developing Dox Immunoliposomes functionalized with monovalent-variable fragments (Fab') of α-PD-L1. Results: Immunoliposomes were assayed in vitro and in vivo in a B16 OVA melanoma murine cell line over-expressing PD-L1. Here, immune system activation in tumor, spleen and lymph nodes, together with the antitumor efficacy were evaluated. Results showed that immunoliposomes bound specifically to PD-L1 Conclusion: PD-L1 targeted liposomes encapsulating Dox have proved to be a rational combination able to enhance the modulation of the immune system by blocking PD-L1 and selectively internalizing Dox, thus successfully providing a dual activity offered by both, chemo and immune therapeutic strategies.
MeSH term(s)	Animals ; Antibodies, Monoclonal/pharmacology ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents, Immunological/pharmacology ; B7-H1 Antigen/metabolism ; Cell Line, Tumor ; Disease Models, Animal ; Doxorubicin/pharmacology ; Drug Liberation ; Drug Therapy ; Female ; Immunity/drug effects ; Immunotherapy/methods ; Liposomes/immunology ; Melanoma/drug therapy ; Melanoma, Experimental/drug therapy ; Mice ; Mice, Inbred C57BL
Chemical Substances	Antibodies, Monoclonal ; Antineoplastic Agents ; Antineoplastic Agents, Immunological ; B7-H1 Antigen ; Cd274 protein, mouse ; Liposomes ; Doxorubicin (80168379AG)
Language	English
Publishing date	2021-04-13
Publishing country	England
Document type	Journal Article
ISSN	1477-3155
ISSN (online)	1477-3155
DOI	10.1186/s12951-021-00846-z
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