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Article ; Online: Vasculogenesis and angiogenesis in nonseminomatous testicular germ cell tumors.

Silván, Unai / Díez-Torre, Alejandro / Bonilla, Zuriñe / Moreno, Pablo / Díaz-Núñez, María / Aréchaga, Juan

2015 Volume 33, Issue 6, Page(s) 268.e17–28

Abstract: Testicular germ cell tumors (TGCTs) comprise the vast majority of all testicular malignancies and are the most common type of cancer among young male adults. The nonseminomatous variant of TGCTs is characterized by the presence of embryonic and ... ...

Abstract	Testicular germ cell tumors (TGCTs) comprise the vast majority of all testicular malignancies and are the most common type of cancer among young male adults. The nonseminomatous variant of TGCTs is characterized by the presence of embryonic and extraembryonic tissues together with a population of pluripotent cancer stem cells, the so-called embryonal carcinoma. One of the main causes of the resistance of these tumors to therapy is their ability to invade adjacent tissues and metastasize into distant sites of the body. Both of these tumor processes are highly favored by the neovascularization of the malignant tissue. New vessels can be generated by means of angiogenesis or vasculogenesis, and both have been observed to occur during tumor vascularization. Nevertheless, the precise contribution of each process to the neoplastic vascular bed of TGCTs remains unknown. In addition, another process known as tumor-derived vasculogenesis, in which malignant cells give rise to endothelial cells, has also been reported to occur in a number of tumor types, including experimental TGCTs. The participation and cross talk of these 3 processes in tumor vascularization is of particular interest, given the embryonic origin of teratocarcinomas. Thus, in the present review, we discuss the importance of all 3 vascularization processes in the growth, invasion, and metastasis of testicular teratocarcinomas and summarize the current state of knowledge of the TGCT microenvironment and its relationship with vascularization. Finally, we discuss the importance of vascularization as a therapeutic target for this type of malignancy.
MeSH term(s)	Cell Differentiation ; Humans ; Male ; Neoplasms, Germ Cell and Embryonal/blood ; Neoplasms, Germ Cell and Embryonal/mortality ; Neoplasms, Germ Cell and Embryonal/pathology ; Neovascularization, Pathologic/pathology ; Testicular Neoplasms/blood ; Testicular Neoplasms/mortality ; Testicular Neoplasms/pathology
Language	English
Publishing date	2015-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1336505-8
ISSN	1873-2496 ; 1078-1439
ISSN (online)	1873-2496
ISSN	1078-1439
DOI	10.1016/j.urolonc.2015.01.005
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Article ; Online: Nucleoporins redistribute inside the nucleus after cell cycle arrest induced by histone deacetylases inhibition.

Pérez-Garrastachu, Miguel / Arluzea, Jon / Andrade, Ricardo / Díez-Torre, Alejandro / Urtizberea, Marta / Silió, Margarita / Aréchaga, Juan

Nucleus (Austin, Tex.)

2017 Volume 8, Issue 5, Page(s) 515–533

Abstract: Nucleoporins are the main components of the nuclear-pore complex (NPC) and were initially considered as mere structural elements embedded in the nuclear envelope, being responsible for nucleocytoplasmic transport. Nevertheless, several recent scientific ... ...

Abstract	Nucleoporins are the main components of the nuclear-pore complex (NPC) and were initially considered as mere structural elements embedded in the nuclear envelope, being responsible for nucleocytoplasmic transport. Nevertheless, several recent scientific reports have revealed that some nucleoporins participate in nuclear processes such as transcription, replication, DNA repair and chromosome segregation. Thus, the interaction of NPCs with chromatin could modulate the distribution of chromosome territories relying on the epigenetic state of DNA. In particular, the nuclear basket proteins Tpr and Nup153, and the FG-nucleoporin Nup98 seem to play key roles in all these novel functions. In this work, histone deacetylase inhibitors (HDACi) were used to induce a hyperacetylated state of chromatin and the behavior of the mentioned nucleoporins was studied. Our results show that, after HDACi treatment, Tpr, Nup153 and Nup98 are translocated from the nuclear pore toward the interior of the cell nucleus, accumulating as intranuclear nucleoporin clusters. These transitory structures are highly dynamic, and are mainly present in the population of cells arrested at the G0/G1 phase of the cell cycle. Our results indicate that the redistribution of these nucleoporins from the nuclear envelope to the nuclear interior may be implicated in the early events of cell cycle initialization, particularly during the G1 phase transition.
MeSH term(s)	Acetylation/drug effects ; Active Transport, Cell Nucleus/drug effects ; Cell Cycle Checkpoints/drug effects ; Cell Line, Tumor ; Cell Nucleus/drug effects ; Cell Nucleus/metabolism ; Chromatin/metabolism ; Histone Deacetylase Inhibitors/pharmacology ; Histone Deacetylases/metabolism ; Humans ; Hydroxamic Acids/pharmacology ; Nuclear Pore Complex Proteins/metabolism
Chemical Substances	Chromatin ; Histone Deacetylase Inhibitors ; Hydroxamic Acids ; Nuclear Pore Complex Proteins ; trichostatin A (3X2S926L3Z) ; Histone Deacetylases (EC 3.5.1.98)
Language	English
Publishing date	2017-07-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2619626-8
ISSN	1949-1042 ; 1949-1034
ISSN (online)	1949-1042
ISSN	1949-1034
DOI	10.1080/19491034.2017.1320001
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Article ; Online: Histone deacetylase inhibitors induce invasion of human melanoma cells in vitro via differential regulation of N-cadherin expression and RhoA activity.

Díaz-Núñez, María / Díez-Torre, Alejandro / De Wever, Olivier / Andrade, Ricardo / Arluzea, Jon / Silió, Margarita / Aréchaga, Juan

BMC cancer

2016 Volume 16, Page(s) 667

Abstract: Background: Histone deacetylase inhibitors (HDACi) exert multiple cytotoxic actions on cancer cells. Currently, different synthetic HDACi are in clinical use or clinical trials; nevertheless, since both pro-invasive and anti-invasive activities have ... ...

Abstract	Background: Histone deacetylase inhibitors (HDACi) exert multiple cytotoxic actions on cancer cells. Currently, different synthetic HDACi are in clinical use or clinical trials; nevertheless, since both pro-invasive and anti-invasive activities have been described, there is some controversy about the effect of HDACi on melanoma cells. Methods: Matrigel and Collagen invasion assays were performed to evaluate the effect of several HDACi (Butyrate, Trichostatin A, Valproic acid and Vorinostat) on two human melanoma cell line invasion (A375 and HT-144). The expression of N- and E-Cadherin and the activity of the RhoA GTPase were analyzed to elucidate the mechanisms involved in the HDACi activity. Results: HDACi showed a pro-invasive effect on melanoma cells in vitro. This effect was accompanied by an up-regulation of N-cadherin expression and an inhibition of RhoA activity. Moreover, the down-regulation of N-cadherin through blocking antibodies or siRNA abrogated the pro-invasive effect of the HDACi and, additionally, the inhibition of the Rho/ROCK pathway led to an increase of melanoma cell invasion similar to that observed with the HDACi treatments. Conclusion: These results suggest a role of N-cadherin and RhoA in HDACi induced invasion and call into question the suitability of some HDACi as antitumor agents for melanoma patients.
MeSH term(s)	Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Butyrates/pharmacology ; Cadherins/biosynthesis ; Cadherins/genetics ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Histone Deacetylase Inhibitors/pharmacology ; Humans ; Hydroxamic Acids/pharmacology ; Melanoma/pathology ; Neoplasm Invasiveness/pathology ; RNA Interference ; RNA, Small Interfering/genetics ; Valproic Acid/pharmacology ; rhoA GTP-Binding Protein/metabolism
Chemical Substances	Antineoplastic Agents ; Butyrates ; Cadherins ; Histone Deacetylase Inhibitors ; Hydroxamic Acids ; RNA, Small Interfering ; RHOA protein, human (124671-05-2) ; trichostatin A (3X2S926L3Z) ; vorinostat (58IFB293JI) ; Valproic Acid (614OI1Z5WI) ; rhoA GTP-Binding Protein (EC 3.6.5.2)
Language	English
Publishing date	2016--22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1471-2407
ISSN (online)	1471-2407
DOI	10.1186/s12885-016-2693-3
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Article ; Online: Suicide mortality in a Spanish police force: The case of the civil guard.

Garcia-Ramos, Adriana / Gonzalez-Weiss, Rogelio / Lopez, Daniel J / Perez-Diez, Ivan / Fernandez-Rodrigues, Veronica / Torre-Luque, Alejandro de la

Spanish journal of psychiatry and mental health

2023 Volume 16, Issue 2, Page(s) 131–132

MeSH term(s)	Humans ; Police ; Suicide ; Suicide Prevention
Language	English
Publishing date	2023-01-21
Publishing country	Spain
Document type	Case Reports
ISSN	2950-2853
ISSN (online)	2950-2853
DOI	10.1016/j.rpsm.2023.01.002
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Article ; Online: The role of microenvironment in testicular germ cell tumors.

Díez-Torre, Alejandro / Silván, Unai / Díaz-Núñez, María / Aréchaga, Juan

Cancer biology & therapy

2010 Volume 10, Issue 6, Page(s) 529–536

Abstract: Testicular germ cell tumors (TGCTs) are the most frequent malignancies in adolescents and young adults. The incidence of TGCTs has doubled over the last few decades and the mechanisms underlying their pervasive growth are still poorly understood. Among ... ...

Abstract	Testicular germ cell tumors (TGCTs) are the most frequent malignancies in adolescents and young adults. The incidence of TGCTs has doubled over the last few decades and the mechanisms underlying their pervasive growth are still poorly understood. Among them, seminomatous and non-seminomatous tumors have carcinoma in situ of the testis (CIS) as a common precursor lesion. It is currently accepted that the acquisition of genetic alterations and/or exposure to environmental factors are involved in the transition from CIS to invasive tumors. Nevertheless, although several TGCT-associated genetic aberrations have been identified, the mechanisms mediating their effects on TGCT development are still largely unknown. The aim of this review is to analyze the potential role of testicular microenvironmental factors, such as hypoxia and stroma cell-derived factors, in the acquisition by TGCT cells of an aggressive phenotype and the importance of these factors as potential therapeutic targets.
MeSH term(s)	Carcinoma in Situ/genetics ; Carcinoma in Situ/metabolism ; Carcinoma in Situ/pathology ; Chemokine CXCL12/metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Insulin-Like Growth Factor I/metabolism ; Male ; Neoplasms, Germ Cell and Embryonal/genetics ; Neoplasms, Germ Cell and Embryonal/metabolism ; Neoplasms, Germ Cell and Embryonal/pathology ; Signal Transduction ; Testicular Neoplasms/genetics ; Testicular Neoplasms/metabolism ; Testicular Neoplasms/pathology ; Tumor Microenvironment
Chemical Substances	Chemokine CXCL12 ; Insulin-Like Growth Factor I (67763-96-6)
Language	English
Publishing date	2010-09-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2146305-0
ISSN	1555-8576 ; 1538-4047
ISSN (online)	1555-8576
ISSN	1538-4047
DOI	10.4161/cbt.10.6.13227
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Zs.A 5887: Show issues

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Article: Nucleoporins redistribute inside the nucleus after cell cycle arrest induced by histone deacetylases inhibition

Pérez-Garrastachu, Miguel / Arluzea, Jon / Andrade, Ricardo / Díez-Torre, Alejandro / Urtizberea, Marta / Silió, Margarita / Aréchaga, Juan

Nucleus. 2017 Sept. 3, v. 8, no. 5

2017

Abstract	Nucleoporins are the main components of the nuclear-pore complex (NPC) and were initially considered as mere structural elements embedded in the nuclear envelope, being responsible for nucleocytoplasmic transport. Nevertheless, several recent scientific reports have revealed that some nucleoporins participate in nuclear processes such as transcription, replication, DNA repair and chromosome segregation. Thus, the interaction of NPCs with chromatin could modulate the distribution of chromosome territories relying on the epigenetic state of DNA. In particular, the nuclear basket proteins Tpr and Nup153, and the FG-nucleoporin Nup98 seem to play key roles in all these novel functions. In this work, histone deacetylase inhibitors (HDACi) were used to induce a hyperacetylated state of chromatin and the behavior of the mentioned nucleoporins was studied. Our results show that, after HDACi treatment, Tpr, Nup153 and Nup98 are translocated from the nuclear pore toward the interior of the cell nucleus, accumulating as intranuclear nucleoporin clusters. These transitory structures are highly dynamic, and are mainly present in the population of cells arrested at the G0/G1 phase of the cell cycle. Our results indicate that the redistribution of these nucleoporins from the nuclear envelope to the nuclear interior may be implicated in the early events of cell cycle initialization, particularly during the G1 phase transition.
Keywords	DNA ; DNA repair ; cell cycle checkpoints ; chromatin ; chromosome segregation ; epigenetics ; histone deacetylase ; interphase ; nuclear pore ; nucleocytoplasmic transport ; nucleoporins ; phase transition
Language	English
Dates of publication	2017-0903
Size	p. 515-533.
Publishing place	Taylor & Francis
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	2619626-8
ISSN	1949-1042 ; 1949-1034
ISSN (online)	1949-1042
ISSN	1949-1034
DOI	10.1080/19491034.2017.1320001
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Suicide mortality in Spain during the COVID-19 pandemic: Longitudinal analysis of sociodemographic factors.

de la Torre-Luque, Alejandro / Perez-Diez, Ivan / Pemau, Andres / Martinez-Ales, Gonzalo / Borges, Guilherme / Perez-Sola, Victor / Ayuso-Mateos, Jose Luis

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology

2024 Volume 82, Page(s) 29–34

Abstract: The COVID-19 pandemic has compromised public health response across the globe. Several countries reported increasing number of suicides during the pandemic. This study aimed to analyze the suicide mortality series in Spain (2000-2021), with a particular ... ...

Abstract	The COVID-19 pandemic has compromised public health response across the globe. Several countries reported increasing number of suicides during the pandemic. This study aimed to analyze the suicide mortality series in Spain (2000-2021), with a particular interest in depicting longitudinal trends during the COVID-19 pandemic. Moreover, it intended to identify sociodemographic groups with a higher increase in suicide victims during the pandemic. To do so, suicide cases from the National death index data were used. Weighted annual mortality rate was compared between pre-pandemic and pandemic years. Poisson time series models were used to analyze the trend in suicide mortality, considering sociodemographic variables (sex, age, migration status, marital status, and urbanicity). As a result, weighted mortality rate for 2020 was 8.92 (CI
Language	English
Publishing date	2024-03-14
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1082947-7
ISSN	1873-7862 ; 0924-977X
ISSN (online)	1873-7862
ISSN	0924-977X
DOI	10.1016/j.euroneuro.2024.02.006
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Zs.A 3288: 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.MO 630: Show issues

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Article ; Online: Embryonic stem cell transplantation into seminiferous tubules: a model for the study of invasive germ cell tumors of the testis.

Silván, Unai / Díez-Torre, Alejandro / Andrade, Ricardo / Arluzea, Jon / Silió, Margarita / Aréchaga, Juan

Cell transplantation

2011 Volume 20, Issue 5, Page(s) 637–642

Abstract: Over the last 15 years, cell transplantation into seminiferous tubules has become a valuable tool to study germinal cell biology and related matters. This is particularly so, because the blood-testis permeability barrier establishes a sealed compartment ... ...

Abstract	Over the last 15 years, cell transplantation into seminiferous tubules has become a valuable tool to study germinal cell biology and related matters. This is particularly so, because the blood-testis permeability barrier establishes a sealed compartment which protect against certain influences such as immunological rejection. In the light of the functional and genetic similarities between carcinoma in situ (CIS) of the testis and embryonic stem (ES) cells, our laboratory has developed a tumor assay to study cancer invasion processes in testicular germ cell tumors (TGCT) based on the transplantation of ES cells into the seminiferous tubules. Here, we describe this new tumor assay and provide additional information regarding the transplantation techniques used and their application for the study of TGCTs. Finally, we discuss the practical implications of our experimental approach and its potential application for the understanding of TGCT invasive processes and the development of new antineoplastic strategies.
MeSH term(s)	Animals ; Cell Transformation, Neoplastic ; Embryonic Stem Cells/cytology ; Embryonic Stem Cells/transplantation ; Male ; Mice ; Models, Biological ; Neoplasms, Germ Cell and Embryonal/pathology ; Seminiferous Tubules/pathology ; Testicular Neoplasms/pathology
Language	English
Publishing date	2011
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1135816-6
ISSN	1555-3892 ; 0963-6897
ISSN (online)	1555-3892
ISSN	0963-6897
DOI	10.3727/096368910X536581
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Zs.A 3556: Show issues

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Article ; Online: The spermatogonial stem cell niche in testicular germ cell tumors.

Silván, Unai / Díez-Torre, Alejandro / Moreno, Pablo / Arluzea, Jon / Andrade, Ricardo / Silió, Margarita / Aréchaga, Juan

The International journal of developmental biology

2013 Volume 57, Issue 2-4, Page(s) 185–195

Abstract: Spermatogonial stem cells (SSCs) are pluripotent elements found in the adult seminiferous epithelium between Sertoli cells and a basal lamina which covers the multilayered external wall of peritubular myoid cells. The microenvironment of this pluripotent ...

Abstract	Spermatogonial stem cells (SSCs) are pluripotent elements found in the adult seminiferous epithelium between Sertoli cells and a basal lamina which covers the multilayered external wall of peritubular myoid cells. The microenvironment of this pluripotent stem cell niche creates the complex and dynamic system that is necessary for the initiation of spermatogenesis, but this system also contains factors which can potentially collaborate in the progression of testicular germ cell tumors (TGCTs). In this review, we summarize our current knowledge about some important structural and molecular features related to the SSC niche, including growth factors, adhesion molecules, extracellular matrix, mechanical stress and vascularization. We discuss their possible collaborative effects on the generation and progression of TGCTs, which are a type of cancer representing the most frequent neoplasia among young men and whose incidence has grown very quickly during the past decades in North America and Europe. In this regard, a better understanding of the pluripotent stem cell niche where these malignancies arise will provide further insights into the origin of TGCTs and the mechanisms underlying their growth and invasion of adjacent and distant tissues.
MeSH term(s)	Animals ; Cell Differentiation ; Germ Cells/cytology ; Germ Cells/physiology ; Humans ; Male ; Neoplasms, Germ Cell and Embryonal/pathology ; Spermatogenesis/physiology ; Stem Cell Niche/physiology ; Testicular Neoplasms/pathology
Language	English
Publishing date	2013
Publishing country	Spain
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1036070-0
ISSN	1696-3547 ; 0214-6282
ISSN (online)	1696-3547
ISSN	0214-6282
DOI	10.1387/ijdb.130068ja
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Zs.A 3202: Show issues

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Article ; Online: Hypoxia and pluripotency in embryonic and embryonal carcinoma stem cell biology.

Silván, Unai / Díez-Torre, Alejandro / Arluzea, Jon / Andrade, Ricardo / Silió, Margarita / Aréchaga, Juan

Differentiation; research in biological diversity

2009 Volume 78, Issue 2-3, Page(s) 159–168

Abstract: Low oxygen availability (hypoxia) is a hallmark of rapidly proliferating tumors and has been suggested to be a characteristic of the embryonic and adult stem cell niche. The idea of relating cancer to stem cells is increasingly popular due to the ... ...

Abstract	Low oxygen availability (hypoxia) is a hallmark of rapidly proliferating tumors and has been suggested to be a characteristic of the embryonic and adult stem cell niche. The idea of relating cancer to stem cells is increasingly popular due to the identification of specific cancer stem cells sharing the typical plasticity and motility of pluripotent stem cells. Hypoxia plays a critical role in early embryonic development and in tumor progression, participating in processes such as angiogenesis, apoptosis, cell migration, invasion and metastasis. Some of the molecular pathways that have been shown to mediate these hypoxia-induced responses, such as the hypoxia inducible factor (HIF)-1alpha and Notch signaling, appear to be active in both embryonic and neoplastic pluripotent stem cells. Nevertheless, the mechanisms underlying these regulatory processes are not yet fully understood. In this review, we attempt to shed some light on the mechanisms involved in hypoxia-dependent processes related to stem cell features and tumor progression, such as the maintenance of the undifferentiated state, cell proliferation, tumor neovascularization, extra-cellular matrix degradation and motility factor up-regulation. With this purpose in mind, we summarize recent observations in embryonic, adult and cancer stem cells that demonstrate the parallelism existing in their hypoxia responses. Finally, based on the observations of our own laboratory and others, we suggest that the comparative analysis of the response to low oxygen levels of embryonic stem cells and cancer stem cells (such as embryonal carcinoma cells), may throw fresh light on our understanding of the mechanisms underlying hypoxia-induced invasiveness and the resistance to anticancer treatments, thereby stimulating the development of novel therapeutic strategies.
MeSH term(s)	Animals ; Embryonal Carcinoma Stem Cells/pathology ; Humans ; Hypoxia/pathology ; Neoplastic Stem Cells/pathology
Language	English
Publishing date	2009-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	184540-8
ISSN	1432-0436 ; 0301-4681
ISSN (online)	1432-0436
ISSN	0301-4681
DOI	10.1016/j.diff.2009.06.002
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