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Article ; Online: Spheresomes are the main extracellular vesicles in low-grade gliomas.

Baselga, Marta / Iruzubieta, Pablo / Castiella, Tomás / Monzón, Marta / Monleón, Eva / Berga, Carmen / Schuhmacher, Alberto J / Junquera, Concepción

Scientific reports

2023 Volume 13, Issue 1, Page(s) 11180

Abstract: Cancer progression and its impact on treatment response and prognosis is deeply regulated by tumour microenvironment (TME). Cancer cells are in constant communication and modulate TME through several mechanisms, including transfer of tumour-promoting ... ...

Abstract	Cancer progression and its impact on treatment response and prognosis is deeply regulated by tumour microenvironment (TME). Cancer cells are in constant communication and modulate TME through several mechanisms, including transfer of tumour-promoting cargos through extracellular vesicles (EVs) or oncogenic signal detection by primary cilia. Spheresomes are a specific EV that arise from rough endoplasmic reticulum-Golgi vesicles. They accumulate beneath cell membrane and are released to the extracellular medium through multivesicular spheres. This study describes spheresomes in low-grade gliomas using electron microscopy. We found that spheresomes are more frequent than exosomes in these tumours and can cross the blood-brain barrier. Moreover, the distinct biogenesis processes of these EVs result in unique cargo profiles, suggesting different functional roles. We also identified primary cilia in these tumours. These findings collectively contribute to our understanding of glioma progression and metastasis.
MeSH term(s)	Humans ; Glioma ; Extracellular Vesicles ; Exosomes ; Blood-Brain Barrier ; Cell Membrane ; Tumor Microenvironment
Language	English
Publishing date	2023-07-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-38084-y
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Article ; Online: Supporting Evidence of Human Enteric Nervous System Adult Neurogenesis: Presence of Primary Cilia and Adult Neurogenesis Markers.

Iruzubieta, Pablo / Cantarero, Irene / Monzón, Marta / Lahoz, Manuel / Junquera, Concepción

Cellular and molecular neurobiology

2020 Volume 42, Issue 2, Page(s) 473–481

Abstract: Adult neurogenesis has been profusely studied in central nervous system. However, its presence in enteric nervous system remains elusive although it has been recently demonstrated in mice and intimately linked to glial cells. Moreover, primary cilium is ... ...

Abstract	Adult neurogenesis has been profusely studied in central nervous system. However, its presence in enteric nervous system remains elusive although it has been recently demonstrated in mice and intimately linked to glial cells. Moreover, primary cilium is an important organelle in central adult neurogenesis. In the present study, we analysed some parallelisms between central and enteric nervous system (ENS) in humans based on ultrastructural and immunohistochemical techniques. Thus, we described the presence of primary cilia in some subtypes of glial cells and Interstitial Cells of Cajal (ICCs) and we performed 3-D reconstructions to better characterise their features. Besides, we studied the expression of several adult neurogenesis-related proteins. Immature neuron markers were found in human ENS, supporting the existence of adult neurogenesis. However, only ICCs showed proliferation markers. Hence, we propose a new paradigm where ICCs would constitute the original neural stem cells which, through asymmetrical cell division, would generate the new-born neurons.
MeSH term(s)	Animals ; Cilia ; Enteric Nervous System/metabolism ; Humans ; Mice ; Neurogenesis/physiology ; Neuroglia ; Neurons/metabolism
Language	English
Publishing date	2020-11-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	283404-2
ISSN	1573-6830 ; 0272-4340
ISSN (online)	1573-6830
ISSN	0272-4340
DOI	10.1007/s10571-020-01017-8
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Zs.A 1727: Show issues

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Article ; Online: Primary cilia presence and implications in bladder cancer progression and invasiveness.

Iruzubieta, Pablo / Castiella, Tomás / Monleón, Eva / Berga, Carmen / Muñoz, Guillermo / Junquera, Concepción

Histochemistry and cell biology

2021 Volume 155, Issue 5, Page(s) 547–560

Abstract: Urothelial bladder cancer is the tenth most common cancer worldwide. It is divided into muscle and non-muscle invading bladder cancer. Primary cilia have been related to several cancer hallmarks such as proliferation, epithelial-to-mesenchymal transition ...

Abstract	Urothelial bladder cancer is the tenth most common cancer worldwide. It is divided into muscle and non-muscle invading bladder cancer. Primary cilia have been related to several cancer hallmarks such as proliferation, epithelial-to-mesenchymal transition (EMT) or tumoral progression mainly through signaling pathways as Hedgehog (Hh). In the present study, we used immunohistochemical and ultrastructural techniques in human tissues of healthy bladder, non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) to study and clarify the activation of epithelial-to-mesenchymal transition and Hedgehog signaling pathway and the presence of primary cilia. Thus, we found a clear correlation between EMT and Hedgehog activation and bladder cancer stage and progression. Moreover, we identified the presence of primary cilia in these tissues. Interestingly, we found that in NMIBC, some ciliated cells cross the basement membrane and localized in lamina propria, near blood vessels. These results show a correlation between EMT beginning from urothelial basal cells and primary cilia assembly and suggest a potential implication of this structure in tumoral migration and invasiveness (likely in a Hh-dependent way). Hence, primary cilia may play a fundamental role in urothelial bladder cancer progression and suppose a potential therapeutic target.
MeSH term(s)	Cilia/metabolism ; Cilia/pathology ; Humans ; Urinary Bladder Neoplasms/metabolism ; Urinary Bladder Neoplasms/pathology
Language	English
Publishing date	2021-01-25
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1222930-1
ISSN	1432-119X ; 0301-5564 ; 0948-6143
ISSN (online)	1432-119X
ISSN	0301-5564 ; 0948-6143
DOI	10.1007/s00418-021-01965-2
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Article ; Online: Hedgehog signalling pathway activation in gastrointestinal stromal tumours is mediated by primary cilia.

Iruzubieta, Pablo / Monzón, Marta / Castiella, Tomás / Ramírez, Teresa / Junquera, Concepción

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association

2019 Volume 23, Issue 1, Page(s) 64–72

Abstract: Background: Gastrointestinal stromal tumour (GIST) is a mesenchymal cancer which derives from interstitial cells of Cajal. To determine whether a relationship between Hedgehog (Hh) signalling pathway and primary cilia exists in GIST tumours is intended ... ...

Abstract	Background: Gastrointestinal stromal tumour (GIST) is a mesenchymal cancer which derives from interstitial cells of Cajal. To determine whether a relationship between Hedgehog (Hh) signalling pathway and primary cilia exists in GIST tumours is intended here. Methods: Immunohistochemical, immunofluorescence and ultrastructural techniques were performed in this study. Results: We show that GIST cells present primary cilia (an antenna-like structure based on microtubules). But, moreover, we prove Hedgehog signalling pathway activation in these tumours (a pathway related with tumoural features such as proliferation, migration or stemness) and we show for the first time that this signalling pathway activation in GIST is mediated by primary cilia, likely in a paracrine way. Conclusion: Thus, primary cilia and Hedgehog signalling would be fundamental in tumoural microenvironment control of GIST cells for their maintenance, differentiation and proliferation.
MeSH term(s)	Cilia/metabolism ; Cilia/pathology ; Cilia/ultrastructure ; Gastrointestinal Neoplasms/metabolism ; Gastrointestinal Neoplasms/pathology ; Gastrointestinal Stromal Tumors/metabolism ; Gastrointestinal Stromal Tumors/pathology ; Hedgehog Proteins/metabolism ; Humans ; Signal Transduction ; Zinc Finger Protein GLI1/metabolism
Chemical Substances	GLI1 protein, human ; Hedgehog Proteins ; Zinc Finger Protein GLI1
Language	English
Publishing date	2019-07-02
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1463526-4
ISSN	1436-3305 ; 1436-3291
ISSN (online)	1436-3305
ISSN	1436-3291
DOI	10.1007/s10120-019-00984-2
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Zs.A 5290: Show issues

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Article ; Online: The FGF14 GAA repeat expansion in Greek patients with late-onset cerebellar ataxia and an overview of the SCA27B phenotype across populations.

Kartanou, Chrisoula / Mitrousias, Alexandros / Pellerin, David / Kontogeorgiou, Zoi / Iruzubieta, Pablo / Dicaire, Marie-Josée / Danzi, Matt C / Koniari, Chrysoula / Athanassopoulos, Konstantinos / Panas, Marios / Stefanis, Leonidas / Zuchner, Stephan / Brais, Bernard / Houlden, Henry / Karadima, Georgia / Koutsis, Georgios

Clinical genetics

2024 Volume 105, Issue 4, Page(s) 446–452

Abstract: A pathogenic GAA repeat expansion in the first intron of the fibroblast growth factor 14 gene (FGF14) has been recently identified as the cause of spinocerebellar ataxia 27B (SCA27B). We herein screened 160 Greek index cases with late-onset cerebellar ... ...

Abstract	A pathogenic GAA repeat expansion in the first intron of the fibroblast growth factor 14 gene (FGF14) has been recently identified as the cause of spinocerebellar ataxia 27B (SCA27B). We herein screened 160 Greek index cases with late-onset cerebellar ataxia (LOCA) for FGF14 repeat expansions using a combination of long-range PCR and bidirectional repeat-primed PCRs. We identified 19 index cases (12%) carrying a pathogenic FGF14 GAA expansion, a diagnostic yield higher than that of previously screened repeat-expansion ataxias in Greek LOCA patients. The age at onset of SCA27B patients was 60.5 ± 12.3 years (range, 34-80). Episodic onset (37%), downbeat nystagmus (32%) and vertigo (26%) were significantly more frequent in FGF14 expansion-positive cases compared to expansion-negative cases. Beyond typical cerebellar signs, SCA27B patients often displayed hyperreflexia (47%) and reduced vibration sense in the lower extremities (42%). The frequency and phenotypic profile of SCA27B in Greek patients was similar to most other previously studied populations. We conclude that FGF14 GAA repeat expansions are the commonest known genetic cause of LOCA in the Greek population and recommend prioritizing testing for FGF14 expansions in the diagnostic algorithm of patients with LOCA.
MeSH term(s)	Humans ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Cerebellar Ataxia/diagnosis ; Cerebellar Ataxia/genetics ; Greece/epidemiology ; Spinocerebellar Ataxias/genetics ; Spinocerebellar Degenerations/genetics ; Phenotype ; Trinucleotide Repeat Expansion/genetics
Language	English
Publishing date	2024-01-14
Publishing country	Denmark
Document type	Journal Article
ZDB-ID	221209-2
ISSN	1399-0004 ; 0009-9163
ISSN (online)	1399-0004
ISSN	0009-9163
DOI	10.1111/cge.14482
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Zs.A 413: Show issues

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Article ; Online: Cenobamate in patients with highly refractory focal epilepsy: A retrospective real-world study.

Beltrán-Corbellini, Álvaro / Romeral-Jiménez, María / Mayo, Pablo / Sánchez-Miranda Román, Irene / Iruzubieta, Pablo / Chico-García, Juan Luis / Parra-Díaz, Paloma / García-Morales, Irene / Toledano, Rafael / Aledo-Serrano, Ángel / Gil-Nagel, Antonio

Seizure

2023 Volume 111, Page(s) 71–77

Abstract: Purpose: To determine the effectiveness and safety outcomes of cenobamate in a cohort of patients with highly refractory focal epilepsy in routine clinical practice.: Methods: Observational, retrospective, phase 4 study on subjects receiving ... ...

Abstract	Purpose: To determine the effectiveness and safety outcomes of cenobamate in a cohort of patients with highly refractory focal epilepsy in routine clinical practice. Methods: Observational, retrospective, phase 4 study on subjects receiving cenobamate in three Spanish centers. The primary endpoint was the retention rate at the last follow-up. The main secondary endpoints were the 50%-responder and seizure-free rates at three months and the last follow-up. Other secondary endpoints were Global Clinical Impressions-Improvement (CGI-I) scores and treatment-emergent adverse events (TEAEs). Results: Fifty-one patients with highly refractory focal epilepsy with 24.7 years of disease evolution, ten previously tried ASM, and a 23.5% of previous epilepsy surgery were included. The retention rate at the last follow-up was 80.4%. The 50% responder rate in focal seizures at three months was 56.5% (median reduction per month 51%, 0-74.6; p < 0.0001) and in focal to bilateral tonic-clonic seizures was 63.6% (median reduction per month 89%, 0-100; p = 0.022). A total of 54.3% of subjects reported a reduction in the intensity of focal seizures, and 66% manifested clinically significant satisfaction. Cenobamate allowed a significant decrease in concomitant ASM, especially sodium channel blockers. TEAEs were reported in 43.1% of individuals, 85% of whom resolved or improved, with no new safety findings. Conclusion: In this analysis of patients with highly refractory focal epilepsy treated with cenobamate according to standard clinical practice, there was evidence of a high reduction in both seizure frequency and intensity, with a manageable safety profile.
MeSH term(s)	Humans ; Anticonvulsants/adverse effects ; Drug Resistant Epilepsy/drug therapy ; Drug Therapy, Combination ; Epilepsies, Partial/drug therapy ; Retrospective Studies ; Seizures/drug therapy ; Treatment Outcome
Chemical Substances	Anticonvulsants ; Cenobamate (P85X70RZWS)
Language	English
Publishing date	2023-08-02
Publishing country	England
Document type	Observational Study ; Journal Article
ZDB-ID	1137610-7
ISSN	1532-2688 ; 1059-1311
ISSN (online)	1532-2688
ISSN	1059-1311
DOI	10.1016/j.seizure.2023.07.026
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Zs.A 3573: Show issues

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Article ; Online: Stromal cells of giant cell tumor of bone show primary cilia in giant cell tumor of bone.

Castiella, Tomás / Iruzubieta, Pablo / Monleón, Eva / Cardiel, Mª José / Gómez-Vallejo, Jesús / Monzón, Marta / Junquera, Mª Concepción

Microscopy research and technique

2021 Volume 85, Issue 3, Page(s) 1065–1074

Abstract: Giant cell tumor of bone (GCTB) is a locally aggressive primary bone neoplasm composed by tumoral stromal cells (SCs) and a reactive component that consists of monocytic/histiocytic cells that give rise by fusion to osteoclast-like multinucleated cells. ... ...

Abstract	Giant cell tumor of bone (GCTB) is a locally aggressive primary bone neoplasm composed by tumoral stromal cells (SCs) and a reactive component that consists of monocytic/histiocytic cells that give rise by fusion to osteoclast-like multinucleated cells. Recently, specific Histone 3.3 mutations have been demonstrated in SCs of GCTB. Many of the pathways related to bone proliferation and regulation depend on the primary cilium, a microtubule-based organelle that protrudes outside the cell and acts as a sensorial antenna. In the present work, we aimed to study the presence and role of primary cilia in GCTB. Ultrastructural, immunohistochemical, and immunofluorescence studies were performed in order to demonstrate, for the first time, that the primary cilium is located in spindle-shaped SCs of GCTB. Moreover, we showed Hedgehog (Hh) signaling pathway activation in these cells. Hence, primary cilia may play a relevant role in GCTB tumorogenesis through Hh signaling activation in SCs. RESEARCH HIGHLIGHTS: Transmission electron microscopy allows describing and differentiating cellular subpopulations in giant cell tumor of bone (GCTB). The primary cilium is present in some tumoral stromal cells of GCTB. Hedgehog signalling is activated in these cells.
MeSH term(s)	Bone Neoplasms/pathology ; Cilia/metabolism ; Cilia/pathology ; Giant Cell Tumor of Bone/genetics ; Giant Cell Tumor of Bone/metabolism ; Giant Cell Tumor of Bone/pathology ; Hedgehog Proteins/metabolism ; Humans ; Stromal Cells
Chemical Substances	Hedgehog Proteins
Language	English
Publishing date	2021-11-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	1099714-3
ISSN	1097-0029 ; 1059-910X
ISSN (online)	1097-0029
ISSN	1059-910X
DOI	10.1002/jemt.23976
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Article ; Online: Non-GAA Repeat Expansions in FGF14 Are Likely Not Pathogenic-Reply to: "Shaking Up Ataxia: FGF14 and RFC1 Repeat Expansions in Affected and Unaffected Members of a Chilean Family".

Pellerin, David / Iruzubieta, Pablo / Tekgül, Şeyma / Danzi, Matt C / Ashton, Catherine / Dicaire, Marie-Josée / Wandzel, Marion / Roth, Virginie / Lamont, Phillipa J / Bonnet, Céline / Renaud, Mathilde / Synofzik, Matthis / Zuchner, Stephan / Brais, Bernard / Başak, Nazlı A / Houlden, Henry

Movement disorders : official journal of the Movement Disorder Society

2023 Volume 38, Issue 8, Page(s) 1575–1577

MeSH term(s)	Humans ; Chile ; Ataxia/genetics ; Cerebellar Ataxia ; Friedreich Ataxia/genetics ; Trinucleotide Repeat Expansion
Language	English
Publishing date	2023-09-01
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	607633-6
ISSN	1531-8257 ; 0885-3185
ISSN (online)	1531-8257
ISSN	0885-3185
DOI	10.1002/mds.29552
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Zs.A 2555: 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)
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Article ; Online: Ultrastructural and immunohistochemical study of phenotypic switch in gastrointestinal smooth muscle cells.

Luesma, María José / Cantarero, Irene / Castiella, Tomás / Sánchez-Cano, Ana Isabel / Iruzubieta, Pablo / Junquera, Concepción

Microscopy research and technique

2018 Volume 81, Issue 11, Page(s) 1233–1240

Abstract: Dedifferentiation is a loss of phenotypic specialization that converts differentiated cells into adult stem cells in order to proliferate and differentiate into replacement tissue. This occurs in several tissues from various organs, such as smooth muscle ...

Abstract	Dedifferentiation is a loss of phenotypic specialization that converts differentiated cells into adult stem cells in order to proliferate and differentiate into replacement tissue. This occurs in several tissues from various organs, such as smooth muscle cells (SMCs) of the mammalian gastrointestinal tract. The aim of this study was to describe ultrastructural and immunohistochemical changes in SMCs which could be compatible with a dedifferentiation process in human and rabbit intestinal muscles. Ultrastructural study and immunohistochemical staining (SMemb and MyoD) on human and rabbit duodenum tissue sections were performed. In both species, this dedifferentiation process is characterized by a loss of intercellular junctions, increased intercellular spaces, cytoskeletal disorganization, perinuclear accumulation of large vacuoles that tend to fuse, rupture of the vacuole membrane and release of cytoplasmic fragments. Dedifferentiated cells show the characteristic phenotype of a mesenchymal cell with scarce perinuclear cytoplasm, long cytoplasmic prolongations and finely distributed granular chromatin in the nucleus. These morphological changes are accompanied by a modulation to a less mature phenotype showing immunoreactivity for the embryonic form of the myosin heavy chain and for the myogenic regulatory factor MyoD. We suggest that SMC dedifferentiation includes the elimination of the contractile apparatus, the activation of the nucleus and the re-expression of embryonic markers. We described an ultrastructural dedifferentiation process possible in intestinal SMCs. This dedifferentiation process seems to play a key role in the homeostasis of the intestinal muscle.
MeSH term(s)	Aged ; Animals ; Biological Variation, Population ; Cell Dedifferentiation/physiology ; Duodenum/cytology ; Humans ; Immunohistochemistry ; Intestines/cytology ; Mesenchymal Stem Cells/cytology ; MyoD Protein/immunology ; Myocytes, Smooth Muscle/immunology ; Myocytes, Smooth Muscle/ultrastructure ; Myosin Heavy Chains/immunology ; Rabbits ; Tight Junctions/physiology
Chemical Substances	MyoD Protein ; MyoD1 myogenic differentiation protein ; Myosin Heavy Chains (EC 3.6.4.1)
Language	English
Publishing date	2018-11-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	1099714-3
ISSN	1097-0029 ; 1059-910X
ISSN (online)	1097-0029
ISSN	1059-910X
DOI	10.1002/jemt.23126
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Article ; Online: Impact on functional outcome of an adaptive Stroke Unit based system of care for patients undergoing endovascular treatment during pandemic times.

Equiza, Jon / de la Riva, Patricia / Angel Larrea, José / Marta-Enguita, Juan / Albájar, Inés / Lüttich, Alex / Garmendia, Eñaut / Alonso, Maitane / de Arce, Ana / Díez, Noemí / Gonzalez, Félix / Iruzubieta, Pablo / Sulibarria, Naroa / Puig, Josep / Martínez-Zabaleta, Maite

European stroke journal

2022 Volume 7, Issue 3, Page(s) 248–256

Abstract: Introduction: The COVID19 pandemic collapsed intensive care units (ICUs) all around the world, conditioning systems of care (SOC) for other critical conditions such as severe ischemic stroke requiring endovascular treatment (EVT). Our aim was to ... ...

Abstract	Introduction: The COVID19 pandemic collapsed intensive care units (ICUs) all around the world, conditioning systems of care (SOC) for other critical conditions such as severe ischemic stroke requiring endovascular treatment (EVT). Our aim was to evaluate the impact of an adaptive Stroke Unit (SU) based SOC on functional outcomes, with the goal of avoiding both general anesthesia (GA) and ICU admission in stroke patients treated with EVT. Material and methods: We performed an observational study comparing data from our traditional ICU-GA based SOC and the adaptive SU-Conscious Sedation (CS) based SOC (consecutive patients undergoing EVT 1 year prior and after onset of the pandemic). Primary outcome was 90-days modified Rankin Scale (mRS), and secondary outcomes included, among others, in-hospital complications, and hospital length of stay (LOS). Results: A total of 210 EVT were performed during the study period (107 under the traditional-SOC and 103 under the adaptive-SOC). A significantly greater proportion of patient was treated under CS (15.9% vs 57.3%; Conclusion: In our case, an adaptive SOC that combined both preference for CS and postprocedural care in SU was associated with better functional outcomes and reduced healthcare resource use for patients undergoing EVT.
Language	English
Publishing date	2022-05-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2851287-X
ISSN	2396-9881 ; 2396-9873
ISSN (online)	2396-9881
ISSN	2396-9873
DOI	10.1177/23969873221098269
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