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Article: Modelling metastasis in zebrafish unveils regulatory interactions of cancer-associated fibroblasts with circulating tumour cells.

Hurtado, Pablo / Martínez-Pena, Inés / Yepes-Rodríguez, Sabrina / Bascoy-Otero, Miguel / Abuín, Carmen / Fernández-Santiago, Cristóbal / Sánchez, Laura / López-López, Rafael / Piñeiro, Roberto

Frontiers in cell and developmental biology

2023 Volume 11, Page(s) 1076432

Abstract: The dynamic intercommunication between tumour cells and cells from the microenvironment, such as cancer-associated fibroblast (CAFs), is a key factor driving breast cancer (BC) metastasis. Clusters of circulating tumour cells (CTCs), known to bare a ... ...

Abstract	The dynamic intercommunication between tumour cells and cells from the microenvironment, such as cancer-associated fibroblast (CAFs), is a key factor driving breast cancer (BC) metastasis. Clusters of circulating tumour cells (CTCs), known to bare a higher efficiency at establishing metastases, are found in the blood of BC patients, often accompanied by CAFs in heterotypic CTC-clusters. Previously we have shown the utility of CTC-clusters models and the zebrafish embryo as a model of metastasis to understand the biology of breast cancer CTC-clusters. In this work, we use the zebrafish embryo to study the interactions between CTCs in homotypic clusters and CTC-CAFs in heterotypic CTC-clusters to identify potential pro-metastatic traits derived from CTC-CAF communication. We found that upon dissemination CAFs seem to exert a pro-survival and pro-proliferative effect on the CTCs, but only when CTCs and CAFs remain joined as cell clusters. Our data indicate that the clustering of CTC and CAF allows the establishment of physical interactions that when maintained over time favour the selection of CTCs with a higher capacity to survive and proliferate upon dissemination. Importantly, this effect seems to be dependent on the survival of disseminated CAFs and was not observed in the presence of normal fibroblasts. Moreover, we show that CAFs can exert regulatory effects on the CTCs without being involved in promoting tumour cell invasion. Lastly, we show that the physical communication between BC cells and CAFs leads to the production of soluble factors involved in BC cell survival and proliferation. These findings suggest the existence of a CAF-regulatory effect on CTC survival and proliferation sustained by cell-to-cell contacts and highlight the need to understand the molecular mechanisms that mediate the interaction between the CTCs and CAFs in clusters enhancing the metastatic capacity of CTCs.
Language	English
Publishing date	2023-03-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2023.1076432
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Dynamical characterization of antiviral effects in COVID-19.

Abuin, Pablo / Anderson, Alejandro / Ferramosca, Antonio / Hernandez-Vargas, Esteban A / Gonzalez, Alejandro H

Annual reviews in control

2021 Volume 52, Page(s) 587–601

Abstract: Mathematical models describing SARS-CoV-2 dynamics and the corresponding immune responses in patients with COVID-19 can be critical to evaluate possible clinical outcomes of antiviral treatments. In this work, based on the concept of virus spreadability ... ...

Abstract	Mathematical models describing SARS-CoV-2 dynamics and the corresponding immune responses in patients with COVID-19 can be critical to evaluate possible clinical outcomes of antiviral treatments. In this work, based on the concept of virus spreadability in the host, antiviral effectiveness thresholds are determined to establish whether or not a treatment will be able to clear the infection. In addition, the virus dynamic in the host - including the time-to-peak and the final monotonically decreasing behavior - is characterized as a function of the time to treatment initiation. Simulation results, based on nine patient data, show the potential clinical benefits of a treatment classification according to patient critical parameters. This study is aimed at paving the way for the different antivirals being developed to tackle SARS-CoV-2.
Language	English
Publishing date	2021-05-28
Publishing country	England
Document type	Journal Article
ZDB-ID	1501302-9
ISSN	1872-9088 ; 1367-5788
ISSN (online)	1872-9088
ISSN	1367-5788
DOI	10.1016/j.arcontrol.2021.05.001
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Article: Association between RNAm-Based COVID-19 Vaccines and Permanency of Menstrual Cycle Alterations in Spanish Women: A Cross-Sectional Study.

Mínguez-Esteban, Isabel / García-Ginés, Pablo / Romero-Morales, Carlos / Abuín-Porras, Vanesa / Navia, Jose A / Alonso-Pérez, Jose Luis / de la Cueva-Reguera, Mónica

Biology

2022 Volume 11, Issue 11

Abstract: Introduction: The purpose of this study was to delve more deeply into the medium and long-term relation between mRNA-based vaccines and changes in menstrual pain, cycle length, and amount of bleeding in Spanish women. Material and Methods: A total of 746 ...

Abstract	Introduction: The purpose of this study was to delve more deeply into the medium and long-term relation between mRNA-based vaccines and changes in menstrual pain, cycle length, and amount of bleeding in Spanish women. Material and Methods: A total of 746 women (63% between 18−30 and 37% between 31−45 years old) participated in the study. A numerical rating scale was used for recording pain intensity, a pictorial chart for menstrual bleeding, and data from menstrual cycle duration, type of vaccine, number of doses and time from vaccination. Results: Sixty-five per cent of the women perceived changes in their menstrual cycle after receiving the vaccines, irrespective of type of vaccine or number of doses; all p values were >0.05. Most of them (n = 316 out of 484) reported more than one alteration in their menstrual cycle. Almost half of the participants had been vaccinated over 5 months (45%), 3−4 months (15%) 2−3 months (26%), and one month or less (13%) before. The percentage of women that reported alterations remained strongly constant across time, p > 0.05, ranging from 64 to 65%. Conclusions: Reported alterations in Spanish women after COVID vaccination remained more than 5 months after the last dose.
Language	English
Publishing date	2022-10-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology11111579
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Article ; Online: Modelling metastasis in zebrafish unveils regulatory interactions of cancer-associated fibroblasts with circulating tumour cells

Pablo Hurtado / Inés Martínez-Pena / Sabrina Yepes-Rodríguez / Miguel Bascoy-Otero / Carmen Abuín / Cristóbal Fernández-Santiago / Laura Sánchez / Rafael López-López / Roberto Piñeiro

Frontiers in Cell and Developmental Biology, Vol

2023 Volume 11

Abstract	The dynamic intercommunication between tumour cells and cells from the microenvironment, such as cancer-associated fibroblast (CAFs), is a key factor driving breast cancer (BC) metastasis. Clusters of circulating tumour cells (CTCs), known to bare a higher efficiency at establishing metastases, are found in the blood of BC patients, often accompanied by CAFs in heterotypic CTC-clusters. Previously we have shown the utility of CTC-clusters models and the zebrafish embryo as a model of metastasis to understand the biology of breast cancer CTC-clusters. In this work, we use the zebrafish embryo to study the interactions between CTCs in homotypic clusters and CTC-CAFs in heterotypic CTC-clusters to identify potential pro-metastatic traits derived from CTC-CAF communication. We found that upon dissemination CAFs seem to exert a pro-survival and pro-proliferative effect on the CTCs, but only when CTCs and CAFs remain joined as cell clusters. Our data indicate that the clustering of CTC and CAF allows the establishment of physical interactions that when maintained over time favour the selection of CTCs with a higher capacity to survive and proliferate upon dissemination. Importantly, this effect seems to be dependent on the survival of disseminated CAFs and was not observed in the presence of normal fibroblasts. Moreover, we show that CAFs can exert regulatory effects on the CTCs without being involved in promoting tumour cell invasion. Lastly, we show that the physical communication between BC cells and CAFs leads to the production of soluble factors involved in BC cell survival and proliferation. These findings suggest the existence of a CAF-regulatory effect on CTC survival and proliferation sustained by cell-to-cell contacts and highlight the need to understand the molecular mechanisms that mediate the interaction between the CTCs and CAFs in clusters enhancing the metastatic capacity of CTCs.
Keywords	circulating tumour cells (CTCs) ; CTC-clusters ; cancer-associated fibroblasts (CAFs) ; metastasis ; zebrafish ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
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Article: Characterization of SARS-CoV-2 dynamics in the host.

Abuin, Pablo / Anderson, Alejandro / Ferramosca, Antonio / Hernandez-Vargas, Esteban A / Gonzalez, Alejandro H

Annual reviews in control

2020 Volume 50, Page(s) 457–468

Abstract: While many epidemiological models were proposed to understand and handle COVID-19 pandemic, too little has been invested to understand human viral replication and the potential use of novel antivirals to tackle the infection. In this work, using a ... ...

Abstract	While many epidemiological models were proposed to understand and handle COVID-19 pandemic, too little has been invested to understand human viral replication and the potential use of novel antivirals to tackle the infection. In this work, using a control theoretical approach, validated mathematical models of SARS-CoV-2 in humans are characterized. A complete analysis of the main dynamic characteristic is developed based on the reproduction number. The equilibrium regions of the system are fully characterized, and the stability of such regions is formally established. Mathematical analysis highlights critical conditions to decrease monotonically SARS-CoV-2 in the host, as such conditions are relevant to tailor future antiviral treatments. Simulation results show the aforementioned system characterization.
Keywords	covid19
Language	English
Publishing date	2020-10-06
Publishing country	England
Document type	Journal Article
ZDB-ID	1501302-9
ISSN	1872-9088 ; 1367-5788
ISSN (online)	1872-9088
ISSN	1367-5788
DOI	10.1016/j.arcontrol.2020.09.008
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Article ; Online: Factor Analysis and Clustering of the Movement Disorder Society-Non-Motor Rating Scale.

Martinez-Martin, Pablo / Rojo-Abuín, Jose Manuel / Weintraub, Daniel / Chaudhuri, Kallol Ray / Rodriguez-Blázquez, Carmen / Rizos, Alexandra / Schrag, Anette

Movement disorders : official journal of the Movement Disorder Society

2020 Volume 35, Issue 6, Page(s) 969–975

Abstract: Background: The primary validation of the Movement Disorder Society Non-Motor Rating Scale was recently published, but 2 important structural analyses were not included. The objective of this study was to examine the structural characteristics of the ... ...

Abstract	Background: The primary validation of the Movement Disorder Society Non-Motor Rating Scale was recently published, but 2 important structural analyses were not included. The objective of this study was to examine the structural characteristics of the Movement Disorder Society Non-Motor Rating Scale by factor and cluster analyses. Methods: Data came from the validation study, an international multicenter cross-sectional study of 402 Parkinson's disease patients. Demographic and clinical data, the Movement Disorder Society Non-Motor Rating Scale, and Hoehn and Yahr staging were used. Exploratory and confirmatory factor analysis and nonhierarchical cluster analysis were performed. Results: The exploratory factor analysis showed that all 13 domains of the Movement Disorder Society Non-Motor Rating Scale, except 1, and the Non-Motor Fluctuations subscale performed as unidimensional (variance explained: 0.36, sleep and wakefulness; -0.82, orthostatic hypotension). The confirmatory factor analysis could be carried out in 9 domains and showed that 6 of them and the Non-Motor Fluctuations subscale adjusted to the model satisfactorily according to the root mean square error of approximation. Furthermore, all domains had comparative fit index values >0.95, except depression and pain (both, 0.94) and sleep and wakefulness (0.90). The Non-Motor Fluctuations subscale showed satisfactory root mean square error of approximation (0.07), but a low comparative fit index value (0.91). A 5-cluster solution, correctly classifying 96% of the cases, was found. Conclusions: Overall, most subscales of the Movement Disorder Society Non-Motor Rating Scale are unidimensional, and although each subscale is distinct in terms of content covered, factors and clusters that are of clinical relevance are discernible and contribute to our understanding of possible nonmotor subtypes in Parkinson's disease. © 2020 International Parkinson and Movement Disorder Society.
MeSH term(s)	Cluster Analysis ; Cross-Sectional Studies ; Factor Analysis, Statistical ; Humans ; Parkinson Disease ; Severity of Illness Index
Language	English
Publishing date	2020-03-27
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; 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.28002
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Article: LuciA-15

Petracci, Fernando E / Villarreal-Garza, Cynthia / Argañaraz, Facundo / Abuin, Gonzalo Gómez / Peñaloza, José / Flores, Marcos Ariel / Piazzoni, Luciano / Riggi, Cecilia / Fabiano, Lucía / González, Lucía / Cieplinski, Belén / Rivero, Sergio / Korbenfeld, Ernesto / Mandó, Pablo

Ecancermedicalscience

2023 Volume 17, Page(s) 1634

Abstract: Background: Poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) improve progression free survival among patients with HER2 negative (HER2-ve) advanced breast cancer (ABC) and a BRCA1 or BRCA2 mutation compared to chemotherapy (CT). The ... ...

Abstract	Background: Poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) improve progression free survival among patients with HER2 negative (HER2-ve) advanced breast cancer (ABC) and a BRCA1 or BRCA2 mutation compared to chemotherapy (CT). The objective of this prospective study was to evaluate the clinical benefit of PARPi treatment in terms of response, outcomes and survival by breast cancer type and treatment in a Latin-American population. Methods: From September 2019 to April 2023, we analyzed the data of patients with HER2-ve ABC with germline and/or somatic mutation of BRCA1 or BRCA2, or in the homologous recombination repair genes, treated with olaparib or talazoparib in daily clinical practice by oncologist from Argentina and México. real-world objective response rate (rwORR), best response rate, real-world progression-free survival (rwPFS) and real-world overall survival (rwOS) were analysed with R software and RStudio version 14.0. Results: After a median follow-up of 18.07 months (95% CI 10.53-30.07), 51 patients were treated with PARPi. Mean age at starting treatment was 47.08 years. 62.7% had ER + ve/HER2-ve and 35.3% had triple negative breast cancer (TNBC). 62.7% and 37.3% of patients received talazoparib and olaparib, respectively. BRCA 1 and 2 germline mutations were the most common alterations found in 96% of patients. 37.5% of patients received platinum-based CT in the (neo)adjuvant/metastatic setting. At the time to starting PARPi treatment, 57.5% had visceral metastasis, the median number of metastatic sites was 2 (range 1-4), the median number of lines was 2 (range 0-8), and 23.5% and 31.4% received PARPi in the 1st line and 2nd line, respectively.The rwORR was 47.0%, and the median real-world progression-free survival-1 (rwPFS Conclusion: This is the first evidence in a Latin-American population that replicates the data already published in randomised clinical trials and other scanty real-world evidence studies in this field, showing positive results in rwORR and rwPFS, and encouraging data in rwOS. Notably, there was a high proportion of patients with visceral progression even with visceral crisis and need for CT. Interestingly, there were similar rwOS results among subgroups (TNBC versus ER + ve/HER2-ve, talazoparib versus olaparib, etc).
Language	English
Publishing date	2023-11-21
Publishing country	England
Document type	Journal Article
ISSN	1754-6605
ISSN	1754-6605
DOI	10.3332/ecancer.2023.1634
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Article ; Online: Association between RNAm-Based COVID-19 Vaccines and Permanency of Menstrual Cycle Alterations in Spanish Women

Isabel Mínguez-Esteban / Pablo García-Ginés / Carlos Romero-Morales / Vanesa Abuín-Porras / Jose A. Navia / Jose Luis Alonso-Pérez / Mónica de la Cueva-Reguera

Biology, Vol 11, Iss 1579, p

A Cross-Sectional Study

2022 Volume 1579

Abstract	Introduction: The purpose of this study was to delve more deeply into the medium and long-term relation between mRNA-based vaccines and changes in menstrual pain, cycle length, and amount of bleeding in Spanish women. Material and Methods: A total of 746 women (63% between 18–30 and 37% between 31–45 years old) participated in the study. A numerical rating scale was used for recording pain intensity, a pictorial chart for menstrual bleeding, and data from menstrual cycle duration, type of vaccine, number of doses and time from vaccination. Results: Sixty-five per cent of the women perceived changes in their menstrual cycle after receiving the vaccines, irrespective of type of vaccine or number of doses; all p values were >0.05. Most of them ( n = 316 out of 484) reported more than one alteration in their menstrual cycle. Almost half of the participants had been vaccinated over 5 months (45%), 3–4 months (15%) 2–3 months (26%), and one month or less (13%) before. The percentage of women that reported alterations remained strongly constant across time, p > 0.05, ranging from 64 to 65%. Conclusions: Reported alterations in Spanish women after COVID vaccination remained more than 5 months after the last dose.
Keywords	menstrual cycle alterations ; vaccination ; COVID ; women ; Biology (General) ; QH301-705.5
Subject code	300
Language	English
Publishing date	2022-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Dissecting Breast Cancer Circulating Tumor Cells Competence via Modelling Metastasis in Zebrafish.

Martínez-Pena, Inés / Hurtado, Pablo / Carmona-Ule, Nuria / Abuín, Carmen / Dávila-Ibáñez, Ana Belén / Sánchez, Laura / Abal, Miguel / Chaachou, Anas / Hernández-Losa, Javier / Cajal, Santiago Ramón Y / López-López, Rafael / Piñeiro, Roberto

International journal of molecular sciences

2021 Volume 22, Issue 17

Abstract: Background: Cancer metastasis is a deathly process, and a better understanding of the different steps is needed. The shedding of circulating tumor cells (CTCs) and CTC-cluster from the primary tumor, its survival in circulation, and homing are key ... ...

Abstract	Background: Cancer metastasis is a deathly process, and a better understanding of the different steps is needed. The shedding of circulating tumor cells (CTCs) and CTC-cluster from the primary tumor, its survival in circulation, and homing are key events of the metastasis cascade. In vitro models of CTCs and in vivo models of metastasis represent an excellent opportunity to delve into the behavior of metastatic cells, to gain understanding on how secondary tumors appear. Methods: Using the zebrafish embryo, in combination with the mouse and in vitro assays, as an in vivo model of the spatiotemporal development of metastases, we study the metastatic competency of breast cancer CTCs and CTC-clusters and the molecular mechanisms. Results: CTC-clusters disseminated at a lower frequency than single CTCs in the zebrafish and showed a reduced capacity to invade. A temporal follow-up of the behavior of disseminated CTCs showed a higher survival and proliferation capacity of CTC-clusters, supported by their increased resistance to fluid shear stress. These data were corroborated in mouse studies. In addition, a differential gene signature was observed, with CTC-clusters upregulating cell cycle and stemness related genes. Conclusions: The zebrafish embryo is a valuable model system to understand the biology of breast cancer CTCs and CTC-clusters.
MeSH term(s)	Animals ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Disease Models, Animal ; Embryo, Nonmammalian ; Female ; Humans ; MCF-7 Cells ; Mice ; Neoplasm Metastasis ; Neoplastic Cells, Circulating ; Zebrafish/embryology
Language	English
Publishing date	2021-08-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22179279
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Article ; Online: Characterization of SARS-CoV-2 dynamics in the host

Abuin, Pablo / Anderson, Alejandro / Ferramosca, Antonio / Hernandez-Vargas, Esteban A. / Gonzalez, Alejandro H.

Annual Reviews in Control ; ISSN 1367-5788

2020

Keywords	Control and Systems Engineering ; Software ; covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
DOI	10.1016/j.arcontrol.2020.09.008
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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