2024-03-29T14:32:22Zhttps://ebuah.uah.es/oai/requestoai:ebuah.uah.es:10017/605082024-02-16T11:51:22Zcom_10017_164com_10017_17822com_10017_17761com_10017_17741col_10017_165
Novel variants in GALE cause syndromic macrothrombocytopenia by disrupting glycosylation and thrombopoiesis
Marín Quilez, Ana
Di Buduo, Christian Andrea
Diaz-Ajenjo, Lorena
Abbonante, Vittorio
Vuelta Ramos, Elena
Soprano, Paolo Maria
Miguel-Garcia, Cristina
Santos-Minguez, Sandra
Serramito-Gomez, Inmaculada
Ruiz-Sala, Pedro
Peñarrubia, M Jesus
Pardal, Emilia
Hernandez-Rivas, Jesus Maria
Gonzalez-Porras, Jose Ramon
García Tuñón Llanio, Ignacio
Benito, Rocio
Rivera, Jose
Balduini, Alessandra
Bastida, Jose Maria
Universidad de Alcalá. Departamento de Biomedicina y Biotecnología
Glycosylation is recognized as a key process for proper megakaryopoiesis and platelet formation. The enzyme uridine diphosphate (UDP)-galactose-4-epimerase, encoded by GALE, is involved in galactose metabolism and protein glycosylation. Here, we studied 3 patients from 2 unrelated families who showed lifelong severe thrombocytopenia, bleeding diathesis, mental retardation, mitral valve prolapse, and jaundice. Whole-exome sequencing revealed 4 variants that affect GALE, 3 of those previously unreported (Pedigree A, p.Lys78ValfsX32 and p.Thr150Met; Pedigree B, p.Val128Met; and p.Leu223Pro). Platelet phenotype analysis showed giant and/or grey platelets, impaired platelet aggregation, and severely reduced alpha and dense granule secretion. Enzymatic activity of the UDP-galactose-4-epimerase enzyme was severely decreased in all patients. Immunoblotting of platelet lysates revealed reduced GALE protein levels, a significant decrease in N-acetyl-lactosamine (LacNAc), showing a hypoglycosylation pattern, reduced surface expression of gylcoprotein Ib alpha-IX-V (GPIb alpha-IX-V) complex and mature beta 1 integrin, and increased apoptosis. In vitro studies performed with patients-derived megakaryocytes showed normal ploidy and maturation but decreased proplatelet formation because of the impaired glycosylation of the GPIb alpha and beta 1 integrin, and reduced externalization to megakaryocyte and platelet membranes. Altered distribution of filamin A and actin and delocalization of the von Willebrand factor were also shown. Overall, this study expands our knowledge of GALE-related thrombocytopenia and emphasizes the critical role of GALE in the physiological glycosylation of key proteins involved in platelet production and function.
2024-02-07T07:20:55Z
2024-02-07T07:20:55Z
2024-02-07T07:20:55Z
2022-11-17
info:eu-repo/semantics/article
Blood, 2022, v. 141, n. 4, p. 406-421
0006-4971
http://hdl.handle.net/10017/60508
10.1182/blood.2022016995
AR/0000041977
Blood
141
421
4
406
eng
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
oai:ebuah.uah.es:10017/596252024-01-19T01:16:04Zcom_10017_164com_10017_17822com_10017_17761com_10017_17741col_10017_165
Rapid thawing increases the fragility of the cryopreserved arterial wall
Pascual, G
Buján, J
Bellón, J M
Carrera-San Martín, A
Jurado, F
Gimeno, M J
García-Honduvilla, N
Universidad de Alcalá. Departamento Biomedicina y Biotecnología. Unidad docente Biología Celular y Genética
Rapid thawing
Cryopreservation
Apoptotic cell
Endothelial damage
Metalloproteinases
To extend present knowledge of the biomechanical and structural changes which occur in the cryopreserved, rapidly thawed arterial wall.
Minipig iliac arterial segments were cryopreserved at -196 degrees C in either minimum essential medium or Wisconsin solution. Fresh segments served as the control group. After 1 month, the specimens were rapidly thawed (37 degrees C) and processed for biomechanical, ultrastructural, morphological and immunohistochemical (MMP-1, MMP-2, MMP-3 and MMP-9) analysis. Visualisation of apoptotic cells was performed by TUNEL method. For the mechanical distension analysis, an in vitro circuit was designed.
The cryopreserved segments showed a 42% incidence of spontaneous fracture and the appearance of microfractures which affected the endoluminal third of the vessel. An accumulation of liquid in the subelastica was observed. An increased expression of wall-degradative enzymes (mainly MMP-2) was also observed following cryopreservation. No significant differences were detected in the proportional elasticity module or tensile strength of the specimen groups. No differences in mechanical distension were observed between groups after the vessel segments were subjected to the pulsatile circuit flow for 72 h. Cell damage was most intense in the specimens cryopreserved in Wisconsin solution.
Cryopreservation in both the solutions employed, followed by rapid thawing, induce changes in the permeability which increase the fragility of the cryopreserved arterial wall. Both increased expression of wall-degradative enzymes and accumulation of liquid may contribute to graft failure after implantation.
2024-01-18T12:14:33Z
2024-01-18T12:14:33Z
2024-01-18T12:14:33Z
2000-07
info:eu-repo/semantics/article
Buján, J. et al. (2000) ‘Rapid Thawing Increases the Fragility of the Cryopreserved Arterial Wall’, European journal of vascular and endovascular surgery, 20(1), pp. 13–20. doi:10.1053/ejvs.2000.1090.
1078-5884
http://hdl.handle.net/10017/59625
10.1053/ejvs.2000.1090
European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery
20
1
13
10906291
eng
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
© 2000 Harcourt Publishers Ltd.
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
oai:ebuah.uah.es:10017/596122024-01-19T01:15:53Zcom_10017_164com_10017_17822com_10017_17761com_10017_17741col_10017_165
Coating PTFE vascular prostheses with a fibroblastic matrix improves cell retention when subjected to blood flow.
Escudero, C
Bellón, J M
Buján, J
García-Honduvilla, N
Contreras, L
Gimeno, M J
San-Román, J
Universidad de Alcalá. Departamento Biomedicina y Biotecnología. Unidad docente Biología Celular y Genética
Endothelial cells
Mesothelial cells
Cell seeding
PTFE
Blood flow
An investigation was made into the effect of blood flow on endothelial cells (EC) and mesothelial cells (MC) seeded on a vascular expanded polytetrafluoroethylene (ePTFE) prosthesis coated with a fibroblastic matrix. Endothelial cells were obtained from the external jugular vein and MC from the omentum. To test the performance of prostheses, a custom designed, femoral "ex vivo" circuit was developed in mongrel dogs. Four study groups were established: a control group, A1, where prostheses were uncoated and seeded with EC; a second control group, A2, where prostheses were uncoated and seeded with MC; group B1 where prostheses were coated with a fibroblastic matrix and seeded with EC; and group B2 where coated prostheses were seeded with MC. All cells were labeled with 111Indium oxine (10 microCi/mL) before seeding. After the seeded cells had formed a monolayer on the ePTFE prostheses (which took approximately 24 h) the prostheses were placed in the "ex vivo" circuit. The rates of blood flow to which prostheses were exposed were measured at the point of inflow (117.5 +/- 12.50 mL/min, mean +/- SD) and outflow (72.6 +/- 14.3 mL/min). MC showed a greater baseline radionuclide uptake than did EC. The cells of groups B1 and B2 adhered sufficiently to the fibroblastic matrix and covered enough of the prosthetic surface to be positioned in the "ex vivo" circuit (76.90 +/- 8.24% surface covered in EC-seeded prostheses and 71.65 +/- 6.23% in MC-seeded prostheses). After exposure to blood flow the quantity of radionuclide-labeled cells and the prosthetic surface covered by them were greatly reduced though the fibroblast-coated prostheses showed greater cell retention.
2024-01-18T10:33:07Z
2024-01-18T10:33:07Z
2024-01-18T10:33:07Z
1998-01
info:eu-repo/semantics/article
Buján, J. et al. (1998) ‘Coating PTFE vascular prostheses with a fibroblastic matrix improves cell retention when subjected to blood flow’, Journal of biomedical materials research, 39(1), pp. 32–39. doi:10.1002/(SICI)1097-4636(199801)39:13.0.CO;2-J.
0021-9304
http://hdl.handle.net/10017/59612
10.1002/(sici)1097-4636(199801)39:1<32::aid-jbm5>3.0.co;2-j
Journal of biomedical materials research
39
1
32
9429094
eng
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
© 1998 John Wiley & Sons, Inc.
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
oai:ebuah.uah.es:10017/590642023-12-22T01:16:03Zcom_10017_164com_10017_17822com_10017_17761com_10017_17741col_10017_165
Anti-proliferative and pro-apoptotic effects of GHRH antagonists in prostate cancer
Muñoz Moreno, Laura
Arenas Jiménez, María Isabel
Carmena Sierra, María José
Schally , Andrew V
Sánchez Chapado, Manuel
Prieto Villapún, Juan Carlos
Bajo Chueca, Ana María
Universidad de Alcalá. Departamento de Biomedicina y Biotecnología
Universidad de Alcalá. Departamento de Biología de Sistemas
GHRH
GHRH antagonists
cell proliferation
apoptosis
prostate cancer therapy
Growth hormone-releasing hormone (GHRH) and its receptors have been implicated in the progression of various tumors. In vitro and in vivo studies have demonstrated that GHRH antagonists inhibit the growth of several cancers. GHRH antagonists, JMR-132 and JV-1-38 inhibit the growth of androgen-independent prostate tumors. Here we investigated the involvement of GHRH antagonists in proliferative and apoptotic processes. We used non-tumoral RWPE-1 and tumoral LNCaP and PC3 human prostatic epithelial cells, as well as an experimental model of human tumor PC3 cells. We evaluated the effects of JMR-132 and JV-1-38 antagonists on cell viability and proliferation in the three cell lines by means of MTT and BrdU assays, respectively, as well as on cell cycle and apoptotic process in PC3 cells. The expression levels of PCNA, p53, p21, CD44, Cyclin D1, c-myc, Bax and Bcl2 were determined in both in vivo and in vitro models by means of Western-blot and RT-PCR. GHRH antagonists suppressed cell proliferation and decreased the levels of the proliferation marker, PCNA, in the three cell lines and in PC3 tumor. GHRH antagonists led to an increase of cells in S-phase and a decrease in G1 and G2/M phases, and induced S-phase arrest and increase of apoptotic cells. The effects of GHRH-antagonists on cell cycle could be due to the changes observed in the expression of p21, p53, Bax, Bcl2, CD44, Cyclin D1, c-myc and caspase 3. Present results confirm and extend the role of GHRH antagonists as anti-proliferative and pro-apoptotic molecules in prostate cancer.
2023-12-21T07:20:29Z
2023-12-21T07:20:29Z
2023-12-21T07:20:29Z
2016-07
info:eu-repo/semantics/article
Oncotarget, 2016, v. 7, n. 32, p. 52195-52206
1949-2553
http://hdl.handle.net/10017/59064
10.18632/oncotarget.10710
AR/0000024873
Oncotarget
7
52206
32
52195
eng
info:eu-repo/grantAgreement/JCCM//Grant PII10- 0189-3222/ES/
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
oai:ebuah.uah.es:10017/596202024-01-19T01:15:53Zcom_10017_164com_10017_17822com_10017_17761com_10017_17741col_10017_165
Evaluation of the smooth muscle cell component and apoptosis in the varicose vein wall
Dominguez, B
Bellón, J M
Buján, J
Jiménez-Cossio, J A
Jurado, F
Gimeno, M J
Pascual, G
García-Honduvilla, N
Universidad de Alcalá. Departamento Biomedicina y Biotecnología. Unidad docente Biología Celular y Genética
Varicose vein
Apoptosis
Smooth muscle cell
Vein wall
Proliferation
This study was designed to evaluate the role of the smooth muscle cell and the apoptosis in the pathogenesis of the varicose vein. Segments of saphenous vein were obtained from healthy subjects and from those with varicose veins. The vein specimens were subdivided according to subject age (younger or older than 50 years) and according to the varicose vein source (distal or proximal). Morphological, ultrastructural, cell proliferation (anti-PCNA method) and cell death (TUNEL method) analysis were performed. The walls of healthy, control vein specimens acquired a more collagenous and papillomatous appearance with age. A slight increase in the number of TUNEL-positive cells was also observed in specimens from older subjects. The proportion of apoptotic cells was much greater in the varicose veins than in control specimens. Most cellular alterations were seen in proximal varicose segments obtained from young subjects. These specimens showed hypertrophic areas with a high degree of cellularity (both in the media and in the thickened intima). The highest proportion of apoptotic cells and collagenisation were also observed in these areas. The enhanced number of apoptotic cells in varicose veins observed mainly in proximal/young vein specimens could be responsible, at least in part, for the acceleration of the final fibrosclerotic process characteristic of the varicose vein wall.
2024-01-18T11:42:01Z
2024-01-18T11:42:01Z
2024-01-18T11:42:01Z
2000-07
info:eu-repo/semantics/article
Bujan, J. et al. (2000) ‘Evaluation of the smooth muscle cell component and apoptosis in the varicose vein wall’, Histology and histopathology, 15(3), pp. 745–752.
0213-3911
http://hdl.handle.net/10017/59620
10.14670/HH-15.745
Histology and histopathology
15
3
745
eng
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
©The Author(s) 2000
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
oai:ebuah.uah.es:10017/604652024-02-07T01:16:41Zcom_10017_164com_10017_17822com_10017_17761com_10017_17741col_10017_165
Chronic Venous Disease during Pregnancy Is Related to Inflammation of the Umbilical Cord: Role of Allograft Inflammatory Factor 1 (AIF-1) and Interleukins 10 (IL-10), IL-12 and IL-18
Fraile Martínez, Óscar
García Montero, Cielo
García Puente, Luis M
González Guijarro, Luis Alberto
León Oliva, Diego de
Borau Borau, Diego Liviu
Gardón Alburquerque, David
Toledo Lobo, María del Val
García Tuñón Llanio, Ignacio
Royuela García, María del Mar
Rios Parra, Antonio
León Luis, Juan A. de
Bravo Arribas, Coral
Álvarez de Mon Soto, Melchor
Buján Varela, María Julia Araceli
Sáez García, Miguel Ángel
García Honduvilla, Natalio Antonio
Ortega Núñez, Miguel Ángel
Universidad de Alcalá. Departamento de Medicina y Especialidades Médicas
Universidad de Alcalá. Departamento de Biomedicina y Biotecnología
Universidad de Alcalá. Departamento de Biología de Sistemas
chronic venous disease (CVD)
pregnancy
umbilical cord
inflammation
Allograft inflammatory factor 1 (AIF-1)
Interleukin 10 (IL-10)
IL-12A
IL-18
Chronic venous disease (CVD) is a common condition that affects the veins in the lower limbs, resulting in a variety of symptoms, such as swelling, pain, and varicose veins (VVs). The plenty hormonal, hemodynamic and mechanical changes occurred in pregnancy make women especially vulnerable to suffer from this condition in this period. Previous works have identified that CVD is associated with an increased inflammatory milieu and significant damage in maternofetal tissues, such as the umbilical cord. However, the inflammatory status of this structure in these patients has not been studied yet. Thus, the aim of the present study was to examine gene and protein expression of a set of inflammatory markers?Allograft inflammatory factor 1 (AIF-1), the proinflammatory cytokines interleukin 12A (IL-12A) and IL-18 and the anti-inflammatory product IL-10?in the umbilical cord of women with CVD during pregnancy (N = 62) and healthy pregnant women (HC; N = 52) by the use of real time qPCR and immunohistochemistry (IHC). Our results demonstrate that the umbilical cord tissue from CVD women exhibit an increased expression of AIF-1, IL-12A and IL-18 along with a decrease in IL-10. Therefore, our study suggests an inflammatory status of this structure related to CVD. Further studies should be conducted to evaluate the expression of other inflammatory markers, as well as to analyze the maternofetal impact of these findings.
2024-02-06T12:25:56Z
2024-02-06T12:25:56Z
2024-02-06T12:25:56Z
2023-06-05
info:eu-repo/semantics/article
Journal of Personalized Medicine, 2023, v. 13, n. 6 (956), p. 1-14
2075-4426
http://hdl.handle.net/10017/60465
10.3390/jpm13060956
AR/0000044007
Journal of Personalized Medicine
13
14
6 (956)
1
eng
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
© The Authors
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
oai:ebuah.uah.es:10017/608802024-02-27T01:17:26Zcom_10017_164com_10017_17822com_10017_17761com_10017_17741col_10017_165
Homeostasis: apoptosis and cell cycle in normal and pathological prostate
Torrealba Abache, Norelia Rosa
Rodríguez Berriguete, Gonzalo
Vera San Martín, Raúl
Fraile Laiz, Benito
Olmedilla Arregui, Gabriel
Martínez Onsurbe, María Del Pilar
Sánchez Chapado, Manuel Vicente
Paniagua Gómez-Álvarez, Ricardo
Royuela García, María Del Mar
Universidad de Alcalá. Departamento de Cirugía, Ciencias Médicas y Sociales. Unidad docente Urología
Universidad de Alcalá. Departamento de Medicina y Especialidades Médicas
Universidad de Alcalá. Departamento de Biomedicina y Biotecnología. Unidad Docente Biología Celular y Genética
Homeostasis
Apoptosis
Cell cycle
Biochemical progression
Prostate cancer
Las enfermedades prostáticas como la hiperplasia y el cáncer son consecuencia del envejecimiento glandular debido a la pérdida de la homeostasis. La homeostasis glandular está garantizada por el delicado equilibrio entre proliferación y muerte celular. Tanto la renovación celular como la apoptosis son parte de este delicado equilibrio. Estudiaremos la capacidad predictiva de la progresión bioquímica, tras la prostatectomía, de algunos miembros de la familia Bcl-2 y de proteínas implicadas en la inhibición del ciclo celular junto con marcadores clásicos establecidos. Mediante inmunoquímica se analizó la expresión de Bcl-2, Bcl-xL, Mcl-1, Bax, Bim, Bad, PUMA,Noxa, p21, p27, Rb y p53 en 86 muestras de prostatectomía radical y se correlacionaron los resultados con los marcadores clinicopatológicos establecidos mediante test estadísticos como las curvas de Sperman, Kaplan-Meier, Cox unifactorial y multifactorial. Los resultados más relevantes son: (1) Correlación positiva entre: p27 con estadio clínico T; y PUMA con estadio T patológico; (2) Correlación negativa entre: Bcl-2 con estadio clínico T, Bcl-xL con supervivencia, Noxa y pRb con puntuación de Gleason. Nuestros resultados sugieren que la expresión de Bcl-2, Bcl-xL, PUMA, Noxa, p27 y Rb se relacionaron con algunos de los marcadores clásicos establecidos para predecir la progresión bioquímica después de la prostatectomía.
Prostatic diseases such as hyperplasia and cancer are a consequence of glandular aging due to
the loss of homeostasis. Glandular homeostasis is guaranteed by the delicate balance between
production and cell death. Both cell renewal and apoptosis are part of this delicate balance. We
will explore the predictive capacity for biochemical progression, following prostatectomy, of
some members of the Bcl-2 family and of proteins involved in cell cycle inhibition in conjunction
with established classical markers. The expression of Bcl-2, Bcl-xL, Mcl-1, Bax, Bim, Bad, PUMA,
Noxa, p21, p27, Rb and p53 were analyzed by immunochemistry in 86 samples of radical prostatectomy
and correlated with each of the markers established clinicopathological tests using statistical
tests such as Sperman, Kaplan–Meier curves, unifactorial Cox, and multifactorial. The most
relevant results are: (1) Positive correlation between: p27 with clinical T stage; and PUMA
with pathological T stage; (2) Negative correlation between: Bcl-2 with clinical T stage, Bcl-xL
with survival, Noxa and pRb with Gleason score.
Our results suggest that the expression of Bcl-2, Bcl-xL, PUMA, Noxa, p27, and Rb were related
to some of the classic markers established to predict biochemical progression after
prostatectomy.
2024-02-26T11:15:09Z
2024-02-26T11:15:09Z
2024-02-26T11:15:09Z
2020-12-01
info:eu-repo/semantics/article
Aging Male, 2020, v. 2020, n. 5, p. 335-345
1368-5538
http://hdl.handle.net/10017/60880
10.1080/13685538.2018.1470233.
AR/0000028418
Aging Male
2020
345
5
335
eng
info:eu-repo/grantAgreement/ISCIII//PI13/01801/ES//
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
2019 Informa UK Limited, trading as Taylor & Francis Group
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
oai:ebuah.uah.es:10017/604882024-02-07T01:16:47Zcom_10017_164com_10017_17822com_10017_17761com_10017_17741col_10017_165
METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer
García Vílchez , Raquel
Añazco Guenkova, Ana Macrina
Dietmann, Sabine
Lopez, Judith
Morón Calvente, Virginia
D'Ambrosi, Silvia
Nombela, Paz
Zamacola, Kepa
Mendizabal, Isabel
García Longarte, Saioa
Zabala Letona, Amaia
Astobiza, Ianire
Fernández, Sonia
Paniagua, Alejandro
Miguel López, Borja
Marchand, Virginie
Alonso López, Diego
Merkel, Angelika
García Tuñón Llanio, Ignacio
Azkargorta, Mikel
Elortza, Félix
Bárcena, Laura
Gonzalez Lopez, Monika
Aransay, Ana M
Di Domenico, Tomás
Sánchez Martín, Manuel A
Rivas, Javier de las
Guil, Sònia
Motorin, Yuri
Helm, Mark
Pandolfi, Pier Paolo
Carracedo, Arkaitz
Blanco, Sandra
Universidad de Alcalá. Departamento de Biomedicina y Biotecnología
Epitranscriptome
RNA modifications
Prostate cancer
7-methylguanosinet
RNA fragments
Tumour microenvironment (TME)
InterferonImmune checkpoint blockade
Newly growing evidence highlights the essential role that epitranscriptomic marks play in the development of many cancers; however, little is known about the role and implications of altered epitranscriptome deposition in prostate cancer. Here, we show that the transfer RNA N-7-methylguanosine (m(7)G) transferase METTL1 is highly expressed in primary and advanced prostate tumours. Mechanistically, we find that METTL1 depletion causes the loss of m(7)G tRNA methylation and promotes the biogenesis of a novel class of small non-coding RNAs derived from 5'tRNA fragments. 5'tRNA-derived small RNAs steer translation control to favour the synthesis of key regulators of tumour growth suppression, interferon pathway, and immune effectors. Knockdown of Mettl1 in prostate cancer preclinical models increases intratumoural infiltration of pro-inflammatory immune cells and enhances responses to immunotherapy. Collectively, our findings reveal a therapeutically actionable role of METTL1-directed m(7)G tRNA methylation in cancer cell translation control and tumour biology.
2024-02-06T15:08:50Z
2024-02-06T15:08:50Z
2024-02-06T15:08:50Z
2023-07-29
info:eu-repo/semantics/article
Molecular Cancer, 2023, v. 22, n. 1, p. 1-36
1476-4598
http://hdl.handle.net/10017/60488
10.1186/s12943-023-01809-8
AR/0000044506
Molecular Cancer
22
36
1
1
eng
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
© The Authors
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
oai:ebuah.uah.es:10017/596282024-01-19T01:15:54Zcom_10017_164com_10017_17822com_10017_17761com_10017_17741col_10017_165
Study of biochemical substrate and role of metalloproteinases in fascia transversalis from hernial processes
Buján, J
Bellón, J M
Lizarbe, M A
Olmo, N
Turnay, J
Gimeno, M J
Jurado, F
Honduvilla, N G
Universidad de Alcalá. Departamento Biomedicina y Biotecnología. Unidad docente Biología Celular y Genética
Extracellular matrix
Fascia transversalis
Hernia
Metalloproteinases
The aim of this study was to examine the fascia transversalis (FT) from patients with direct and indirect hernia in an attempt to identify possible differences between each type of hernia. FT samples were obtained from 36 patients presenting inguinal hernia (23 indirect hernia and 13 direct hernia) who underwent surgery. We have analysed the ultrastructure of the fascia surrounding the hernial lesions, the proline and lysine hydroxylation in the tissue, the type I-type III collagen ratio and the presence of metalloproteinases. We have not detected ultrastructural differences in the collagen fibrils from FT in direct and indirect hernias. However, the interfibrillar matrix was more abundant in direct hernias, showing abundant electron-dense particles. No differences in proline hydroxylation were observed between each type of hernia. A small decrease in lysine hydroxylation was detected in patients with direct hernia. Enzyme-linked immunosorbent assays (ELISAs) showed no statistically significant differences in the type I-type III collagen absorbance ratios. Immunohistochemistry revealed no differences in the expression of matrix metalloproteinase-1. FT from patients presenting direct hernia showed a very strong staining vs. metalloproteinase-2 when compared with that observed in indirect hernia.
2024-01-18T13:04:45Z
2024-01-18T13:04:45Z
2024-01-18T13:04:45Z
1997-06
info:eu-repo/semantics/article
Bellón, J.M. et al. (1997) ‘Study of biochemical substrate and role of metalloproteinases in fascia transversalis from hernial processes’, European journal of clinical investigation, 27(6), pp. 510–516. doi:10.1046/j.1365-2362.1997.1400686.x
0014-2972
http://hdl.handle.net/10017/59628
10.1046/j.1365-2362.1997.1400686.x
European journal of clinical investigation
27
6
510
9229232
eng
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
© 1997 Blackwell Science Ltd
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
oai:ebuah.uah.es:10017/596242024-01-19T01:16:04Zcom_10017_164com_10017_17822com_10017_17761com_10017_17741col_10017_165
Mesothelial versus endothelial cell seeding: evaluation of cell adherence to a fibroblastic matrix using 111In oxine
Bellón, J M
Buján, J
de Haro, J
Contreras, L
Gimeno, M J
Escudero, C
García-Honduvilla, N
Universidad de Alcalá. Departamento Biomedicina y Biotecnología. Unidad docente Biología Celular y Genética
Endothelial cell seeding
Mesothelial cell seeding
Vascular prostheses
The aim of this study was to compare the behaviour of mesothelial cells (MC) to that of endothelial cells (EC) when seeded onto a PTFE, prosthesis coated with a fibroblastic matrix.
Three study groups were examined: a control group (Control) of PTFE prostheses with a fibroblast matrix (n = 8); Group EC, PTFE prostheses seeded with EC on a fibroblastic matrix (n = 8); and Group MC, PTFE, prostheses seeded with MC on a fibroblastic matrix (n = 8). All cell types were labelled with 111In (100 microCi/ml) 24 h after seeding, when the cells had formed a monolayer on the prosthetic surface. Radioactive levels were measured at 2, 4, 6, and 24 h.
Both EC and MC showed optimal adherence. The MC had a better radioactive uptake and retention than the EC. The number of EC and MC cells that remained adherent to the matrix was large enough to ensure complete covering of the prosthetic surface.
The use of MC is therefore feasible as an optimal alternative for achieving a natural covering on vascular prostheses prepared with a fibroblastic matrix.
2024-01-18T12:04:42Z
2024-01-18T12:04:42Z
2024-01-18T12:04:42Z
1997-02
info:eu-repo/semantics/article
Bellon, J.M. et al. (1997) ‘Mesothelial versus endothelial cell seeding: Evaluation of cell adherence to a fibroblastic matrix using In oxine’, European journal of vascular and endovascular surgery, 13(2), pp. 142–148. doi:10.1016/S1078-5884(97)80010-X.
1078-5884
http://hdl.handle.net/10017/59624
10.1016/s1078-5884(97)80010-x
European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery
13
2
142
9091146
eng
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
© 1997 W. B. Saunders Company Ltd.
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
oai:ebuah.uah.es:10017/597092024-01-23T01:16:20Zcom_10017_164com_10017_17822com_10017_17761com_10017_17741col_10017_165
Fibroblasts from the transversalis fascia of young patients with direct inguinal hernias show constitutive MMP-2 overexpression
Buján, J
Ga-Honduvilla, N
Gimeno, M J
Pascual, G
Guerrero, A
Bellón, J M
Bajo, A
Universidad de Alcalá. Departamento Biomedicina y Biotecnología. Unidad docente Biología Celular y Genética
To determine the expression pattern of certain metalloproteinases (MMPs) known to be involved in the degradation of the extracellular matrix in cultured fibroblasts from the transversalis fascia (TF) of patients with inguinal hernia.
Inguinal hernia is a common pathology, the cause of which remains unknown. It is, however, clear that the TF is one of the anatomical structures that may impede the formation of hernias, and particularly the direct type of hernia. In previous studies the authors found enhanced MMP-2 expression in TF specimens in vivo. The persistence of increased expression in cultured fibroblasts might support the idea of a genetic defect as the cause for this pathology.
Fibroblasts from the TF of patients with direct and indirect inguinal hernia were cultured and compared with those obtained from control TF in terms of MMP (MMP-2 and MMP-9) expression.
Significant active MMP-2 expression was shown by TF fibroblasts from young patients with direct hernias. These findings were confirmed by immunosorbent assay, immunoblotting, and zymography of the fibroblast culture media. No MMP-9 expression was detected.
These results indicate that MMP-2 may be involved in the TF matrix degradative process in patients with direct hernia. The persistence of changes in MMP-2 levels in the cell cultures appears to suggest a genetic defect or irreversible change as the origin of this pathology rather than environmental factors, which may later participate in the development of the hernial process.
2024-01-22T09:08:18Z
2024-01-22T09:08:18Z
2024-01-22T09:08:18Z
2001-02
info:eu-repo/semantics/article
Bellon, J. et al. (2001) ‘Fibroblasts from the transversalis fascia of young patients with direct inguinal hernias show constitutive MMP-2 overexpression’, Annals of surgery, 233(2), pp. 287–291. doi:10.1097/00000658-200102000-00020.
0003-4932
http://hdl.handle.net/10017/59709
10.1097/00000658-200102000-00020
Annals of surgery
233
2
287
11176137
eng
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
© 2001 Lippincott Williams & Wilkins, Inc
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
oai:ebuah.uah.es:10017/605092024-02-08T01:16:34Zcom_10017_164com_10017_17822com_10017_17761com_10017_17741col_10017_165
Understanding HAT1: A Comprehensive Review of Noncanonical Roles and Connection with Disease
Ortega Núñez, Miguel Ángel
Buján Varela, María Julia Araceli
González Guijarro, Luis Alberto
Álvarez De Mon Soto, Melchor
Álvarez de Mon González, Miguel Ángel
Fraile Martínez, Óscar
García Montero, Cielo
Toledo Lobo, María del Val
García Tuñón Llanio, Ignacio
Royuela García, María del Mar
García Honduvilla, Natalio Antonio
Universidad de Alcalá. Departamento de Medicina y Especialidades Médicas
Universidad de Alcalá. Departamento de Biomedicina y Biotecnología
Universidad de Alcalá. Departamento de Biología de Sistemas
HAT1
acetyltransferase
epigenetics
noncanonical roles
cancerviral infections
immunoinflammatory diseases
translational opportunities
Histone acetylation plays a vital role in organizing chromatin, regulating gene expression and controlling the cell cycle. The first histone acetyltransferase to be identified was histone acetyltransferase 1 (HAT1), but it remains one of the least understood acetyltransferases. HAT1 catalyzes the acetylation of newly synthesized H4 and, to a lesser extent, H2A in the cytoplasm. However, 20 min after assembly, histones lose acetylation marks. Moreover, new noncanonical functions have been described for HAT1, revealing its complexity and complicating the understanding of its functions. Recently discovered roles include facilitating the translocation of the H3H4 dimer into the nucleus, increasing the stability of the DNA replication fork, replication-coupled chromatin assembly, coordination of histone production, DNA damage repair, telomeric silencing, epigenetic regulation of nuclear lamina-associated heterochromatin, regulation of the NF-kappa B response, succinyl transferase activity and mitochondrial protein acetylation. In addition, the functions and expression levels of HAT1 have been linked to many diseases, such as many types of cancer, viral infections (hepatitis B virus, human immunodeficiency virus and viperin synthesis) and inflammatory diseases (chronic obstructive pulmonary disease, atherosclerosis and ischemic stroke). The collective data reveal that HAT1 is a promising therapeutic target, and novel therapeutic approaches, such as RNA interference and the use of aptamers, bisubstrate inhibitors and small-molecule inhibitors, are being evaluated at the preclinical level.
2024-02-07T07:32:31Z
2024-02-07T07:32:31Z
2024-02-07T07:32:31Z
2023-04-14
info:eu-repo/semantics/article
Genes, 2023, v. 14, n. 4 (915), p. 1-18
2073-4425
http://hdl.handle.net/10017/60509
10.3390/genes14040915
AR/0000043847
Genes
14
18
4 (915)
1
eng
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
© The Authors
Attribution 4.0 International (CC BY 4.0)
oai:ebuah.uah.es:10017/608812024-02-27T01:17:26Zcom_10017_164com_10017_17822com_10017_17761com_10017_17741col_10017_165
TGF-beta/PI3K/AKT/mTOR/NF-kB pathway. Clinicopathological features in prostate cancer
Torrealba Abache, Norelia Rosa
Vera San Martín, Raúl
Fraile Laiz, Benito
Martínez Onsurbe, María Del Pilar
Paniagua Gómez-Álvarez, Ricardo
Royuela García, María Del Mar
Universidad de Alcalá. Departamento de Medicina y Especialidades Médicas
Universidad de Alcalá. Departamento de Biomedicina y Biotecnología. Unidad docente Biología Celular
Prostate cancer
TFGB
NF-kB
Akt
mTOR
PI3k
El cáncer de próstata es uno de los cánceres más comunes en la población masculina. El objetivo de esta investigación fue estudiar la relación de los componentes de la ruta de transducción celular del factor de crecimiento transformante B (TGF-B)/ fosfatidilinositol-3? quinasa (PI3K)/AKT/diana de rapamicina en mamíferos (mTOR)/factor nuclear kappa B (NF-kB) con marcadores clínico-patológicos. Mediante métodos inmunohistoquímicos, determinamos la expresión de varios factores [TGF-B, TGFBRI, TGFBRII, PI3K, AKT-Ser, AKT-Thr, mTOR, p-mTOR, IKK, pIKK, IkB, pIkB, NF-kBp50 y NF-kBp65]. Nuestro objetivo consistió en conocer su relación con los marcadores clásicos establecidos (antígeno prostático específico sérico preoperatorio, estadio tumoral patológico, estadio tumoral clínico, puntaje de Gleason, invasión perineural, afectación ganglionar, márgenes quirúrgicos positivos, progresión bioquímica y supervivencia) y su importancia en el pronóstico y progresión bioquímica de la enfermedad. Para ello se realizó la prueba de Spearman, análisis de supervivencia, Log-rang, curvas de Kaplan-Meier, análisis de regresión de riesgo proporcional de Cox univariados y multivariados. El análisis de Spearman mostró que existía al menos correlación entre TGF-B, TGFBRI, PI3K, pAKT-Thr, p-mTOR, NF-kBp50 y marcadores clásicos. El análisis multivariado de Cox entre las variables pronósticas (estadio patológico del tumor, puntuación de Gleason y afectación ganglionar) y los parámetros inmunohistoquímicos confirmó a TGFBR1 y PI3K como marcador pronóstico e independiente de progresión bioquímica en el cáncer de próstata. Nuestros resultados sugieren que TGFBR1 y PI3K podrían usarse como biomarcadores útiles para el diagnóstico temprano y el pronóstico de recurrencia bioquímica en el cáncer de próstata después de una prostatectomía radical.
2024-02-26T11:39:41Z
2024-02-26T11:39:41Z
2024-02-26T11:39:41Z
2020-12-01
info:eu-repo/semantics/article
Aging Male, 2020, v. 23, n. 5, p. 801-811
1368-5538
http://hdl.handle.net/10017/60881
10.1080/13685538.2019.1597840
AR/0000031195
Aging Male
23
811
5
801
eng
PI13/01801
info:eu-repo/grantAgreement/ISCIII//PI13/01801/ES//
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
2019 Informa UK Limited, trading as Taylor & Francis Group
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
oai:ebuah.uah.es:10017/597162024-01-23T01:16:21Zcom_10017_164com_10017_17822com_10017_17761com_10017_17741col_10017_165
Modulation of PECAM-1 (CD31) expression in human endothelial cells: effect of IFNgamma and IL-10
Buján, J
Alvarez-Mon, M
Bellón, J M
Pascual, G
Prieto, A
Gimeno, M J
Universidad de Alcalá. Departamento Biomedicina y Biotecnología. Unidad docente Biología Celular y Genética
Intercellular contacts formed between endothelial cells (EC) permit the formation of a confluent monolayer and play a major role in the recruitment and the migration of leukocytes in the inflammatory response. It is currently accepted that cytokines are responsible for the signals involved in the induction of such endothelial alterations. The platelet EC adhesion molecule (PECAM-1), a specific component of EC junctions, is one of many molecules which participate in the regulation of EC interaction with blood components. Given that the regulatory mechanisms which affect the expression of this adhesion molecule are only partially understood, the aim of the present study was to compare the effects of two antagonistic inflammatory cytokines, interferon (IFN)-gamma and interleukin (IL)-10, on the expression of PECAM-1. Human umbilical vein EC grown to subconfluence were stimulated with IL-10 (10 ng/ml) and/or IFNgamma (100 U/ml) for 24 h. PECAM-1 expression was determined by FACScan and immunofluorescence. Morphological analysis of the cell cultures was performed by optical and scanning electron microscopy. In the presence of IL-10, no changes in cell growth and morphology or in the intensity of PECAM-1 expression were observed. However, when the cultures were treated with IFNgamma, the EC acquired a fibroblast-like appearance, growth was disorganized and PECAM-1 disappeared from cell junctions. The mean intensity expression and the percentage of EC expression of this antigen were analyzed by flow cytometry and significantly decreased after culture in the presence of IFNgamma. The simultaneous addition of IFNgamma and IL-10 to the EC cultures induced modifications similar to those observed in the presence of IFNgamma alone. Regulation of the expression of PECAM-1 with the subsequent functional implications seems to be dependent upon the IFNgamma signal and it is unaffected by IL-10. The different effects shown by IL-10 and IFNgamma on the expression of PECAM-1 in EC could reflect opposite regulatory actions of the inflammatory response induced by these cytokines.
1999
info:eu-repo/semantics/article
Buján J, Gimeno MJ, Prieto A, Pascual G, Bellón JM, Alvarez-Mon M. Modulation of PECAM-1 (CD31) expression in human endothelial cells: effect of IFNgamma and IL-10. J Vasc Res. 1999 Mar-Apr;36(2):106-13. doi: 10.1159/000025632. PMID: 10213905.
1018-1172
http://hdl.handle.net/10017/59716
10.1159/000025632
Journal of vascular research
36
2
106
10213905
eng
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
oai:ebuah.uah.es:10017/1662023-12-14T15:29:31Zcom_10017_164com_10017_17822com_10017_17761com_10017_17741col_10017_165
DAX-1 expression in human breast cancer: comparison with estrogen receptors ER-α, ER-ß and androgen receptor status
Conde Martín, María Isabel
Alfaro Sánchez, Juan María
Paniagua Gómez-Álvarez, Ricardo
Fraile Laiz, Benito
Arenas Jiménez, María Isabel
Universidad de Alcalá. Departamento de Biología Celular y Genética
Breast cancer
Androgen receptor
DAX-1
Estrogen receptor-α
Estrogen receptor-β
Cáncer de mama
So far there have been no reports on the expression pattern of DAX-1 (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1) in human breast cells and its relationship to the estrogen receptors, ER-¿ and ER-ß, and the androgen receptor (AR).In this study we evaluated, by immunohistochemistry and Western blot analysis, the presence and distribution of DAX-1 in benign breast disease (BBD), in situ carcinoma (CIS), and ductal and lobular breast carcinomas.In BBD and breast carcinomas, DAX-1 was present in both the nuclei and the cytoplasm of epithelial cells, although in infiltrative carcinomas the percentage of nuclear immunoreaction was higher than in CIS. An important relation was observed between DAX-1 and AR expression and between this orphan receptor and nodal status.DAX-1 might modify the AR and ER-ß intracellular location, and because a direct positive relation between the expression of these three receptors was found it could be assumed that the presence of DAX-1 in neoplastic cells might indicate a possible failure of endocrine therapies
2006-11-30T10:57:30Z
2006-11-30T10:57:30Z
2006-11-30T10:57:30Z
2004
info:eu-repo/semantics/article
Breast Cancer Research, 2004, v. 6, n. 3, p. R140-R148
1465-5411
http://hdl.handle.net/10017/166
10.1186/bcr766
eng
http://dx.doi.org/10.1186/bcr766
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
info:eu-repo/semantics/openAccess
Atribución-NoComercial-SinDerivadas 3.0 España
© Conde et al., licensee BioMed Central Ltd., 2004
BioMed Central Ltd.
oai:ebuah.uah.es:10017/56042023-12-14T15:29:31Zcom_10017_164com_10017_17822com_10017_17761com_10017_17741col_10017_165
Human pregnane X receptor is expressed in breast carcinomas, potential heterodimers formation between hPXR and RXR-alpha.
Conde Martín, María Isabel
Toledo Lobo, María del Val
Zamora Romero, Javier
Pérez Márquez, Julio
Gonzalez, Francisco J.
Alba Conejo, Emilio
Fraile Laiz, Benito
Paniagua Gómez-Álvarez, Ricardo
Arenas Jiménez, María Isabel
Universidad de Alcalá. Departamento de Biología Celular y Genética
Human pregnane X receptor
Breast cancer
The human pregnane X receptor (hPXR) is an orphan nuclear receptor that induces transcription of response elements present in steroid-inducible cytochrome P 450 gene promoters. This activation requires the participation of retinoid X receptors (RXRs), needed partners of hPXR to form heterodimers. We have investigated the expression of hPXR and RXRs in normal, premalignant, and malignant breast tissues, in order to det. whether their expression profile in localized infiltrative breast cancer is assocd. with an increased risk of recurrent disease. Methods: Breast samples from 99 patients including benign breast diseases, in situ and infiltrative carcinomas were processed for immunohistochem. and Western-blot anal. Results: Cancer cells from patients that developed recurrent disease showed a high cytoplasmic location of both hPXR isoforms. Only the infiltrative carcinomas that relapsed before 48 mo showed nuclear location of hPXR isoform 2. This location was assocd. with the nuclear immunoexpression of RXR-alpha. Conclusion: Breast cancer cells can express both variants 1 and 2 of hPXR. Infiltrative carcinomas that recurred showed a nuclear location of both hPXR and RXR-alpha; therefore, the overexpression and the subcellular location changes of hPXR could be considered as a potential new prognostic indicator.
2010-02-12T13:09:53Z
2010-02-12T13:09:53Z
2010-02-12T13:09:53Z
2008
info:eu-repo/semantics/article
BMC Cancer 2008, 8:174
1471-2407
http://hdl.handle.net/10017/5604
10.1186/1471-2407-8-174
eng
http://dx.doi.org/10.1186/1471-2407-8-174
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
info:eu-repo/semantics/openAccess
Atribución-NoComercial-SinDerivadas 3.0 España
© Conde et al; licensee BioMed Central Ltd., 2008
BioMed Central
oai:ebuah.uah.es:10017/59182023-12-14T15:29:31Zcom_10017_164com_10017_17822com_10017_17761com_10017_17741col_10017_165
Influence of IFN-gamma and its receptors in human breast cancer
García Tuñón Llanio, Ignacio
Ricote Belinchón, Mónica
Ruiz A., Antonio
Fraile Laiz, Benito
Paniagua Gómez-Álvarez, Ricardo
Royuela García, María del Mar
Universidad de Alcalá. Departamento de Biología Celular y Genética
Breast cancer
Interferons
IFNγ receptors
Interferons are a group of proteins that trigger multiple responses including prevention of viral replication, inhibition of cell growth, and modulation of cell differentiation. In different mammary carcinoma cell lines IFNγ induces growth arrest at mid-G1. At the present there are no in vivo studies in human breast. The aim of this study was to investigate the expression patterns of IFNγ and its two receptors (IFNγ-Rα and IFNγ-Rβ) by Western blot and immunohistochem., in order to elucidate its role in the different types of human breast cancer (in situ and infiltrative). Methods: Immunohistochem. and semiquant. study of IFNγ, its receptors types (IFNγ-Rα and IFNγ-Rβ), cell proliferation (proliferating cell nuclear antigen, also named PCNA), and apoptosis (Tunel method) was carried between the three breast groups (fibrocystic lesions, in situ tumors and infiltrating tumors). Results: In the three groups of patients, IFNγ and IFNγ-Rα immunoreactions appeared in the cytoplasm while IFNγ-Rβ also was found in the nucleus. The optical d. of IFNγ was higher in in situ carcinoma than in benign and infiltrating tumors. When we obsd. IFNγ-Rα, the optical d. was lower in infiltrating carcinoma than in benign and in situ tumors (the higher d.). To IFNγ-Rβ, the optical d. was similar in the three group samples. In tumor samples PCNA and TUNEL index was significantly higher; than in benign diseases. PCNA index increased with the malignance. No significant differences were found between cancer types to TUNEL. IFNγ could be a potential therapeutic tool in breast cancer. However, tumor cells are able to escape from the control of this cytokine in the early tumor stages; this is probably due to a decreased expression of IFNγ, or also to an alteration of either its receptors or some transduction elements. Conclusions: We conclude that the decrease in the % pos. samples that expressed IFNγ and IFNγ-Rα together with the nuclear localization of IFNγ-Rβ, could be a tumoral cell response, although perhaps insufficient to inhibit the uncontrolled cell proliferation. Perhaps, IFNγ might be unable to activate p21 to stop the cell cycle, suggesting a possible participation in breast cancer development.
2010-03-12T12:42:08Z
2010-03-12T12:42:08Z
2010-03-12T12:42:08Z
2007
info:eu-repo/semantics/article
BMC Cancer, 2007, v. 7, p. 158
1471-2407
http://hdl.handle.net/10017/5918
10.1186/1471-2407-7-158
eng
http://dx.doi.org/10.1186/1471-2407-7-158
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
info:eu-repo/semantics/openAccess
Atribución-NoComercial-SinDerivadas 3.0 España
© García-Tuñón et al; licensee BioMed Central Ltd., 2007
BioMed Central
oai:ebuah.uah.es:10017/55992023-12-14T15:29:31Zcom_10017_164com_10017_17822com_10017_17761com_10017_17741col_10017_165
Lectin histochemistry study in the human vas deferens
Arenas Jiménez, María Isabel
Madrid Cuevas, Juan Francisco
Rodríguez Bethencourt Codes, Fermín
Fraile Laiz, Benito
Paniagua Gómez-Álvarez, Ricardo
Universidad de Alcalá. Departamento de Biología Celular y Genética
Lectins
Human vas deferens
Oligosaccharides
The oligosaccharide sequences of glycoconjugates in the normal human vas deferens and the nature of the saccharide linkage were studied by lectin histochem. The cytoplasm of all epithelial cell types (principal cells, basal cells, and mitochondria-rich cells) and luminal contents reacted pos. with WGA, MAA, PNA, DSA, LTA, UEA-I, AAA, and ConA. The reaction was more intense in the stereocilia of principal cells. Cytoplasmic staining was diffuse except for PNA and DSA labeling which was limited to the apical cytoplasm and stereocilia of columnar cells. The cytoplasm of all cell types also reacted diffusely with HPA, although staining was weak and was not obsd. in the stereocilia. Pos. reaction with SBA only was encountered in the stereocilia of principal cells. SNA, LTA, and DBA were unreactive. GNA-labeling showed a granular distribution in the supranuclear cytoplasm of columnar epithelial cells. Reactions with MAA, PNA, DSA, AAA, HPA and SBA disappeared after the β-elimination reaction. Reactions with WGA and UEA-I decreased after ß-elimination or Endo-F digestion. Reactions with ConA and GNA were suppressed by Endo-F digestion. Reactions with PNA, HPA, and SBA increased after desialylation. Of all the lectins that label the luminal contents of the vas deferens, only UEA-I was not found in the luminal contents of seminiferous tubules and epididymis and, thus, this lectin would probably bind to glycoproteins secreted by the vas deferens. The chem. treatments used suggest that this secretion contains fucose residues located in both N- and O-linked oligosaccharides. The other lectins may label secreted proteins, but also structural proteins or proteins reabsorbed from the luminal fluid. The lectin-binding pattern of mitochondria-rich cells in the vas deferens differed from that found in the epididymis.
2010-02-11T11:52:31Z
2010-02-11T11:52:31Z
2010-02-11T11:52:31Z
1998
info:eu-repo/semantics/article
Glycoconjugate Journal, 1998, v. 15, n. 11, p. 1085-1091
0282-0080
http://hdl.handle.net/10017/5599
10.1023/A:1006905710648
eng
http://dx.doi.org/10.1023/A:1006905710648
info:eu-repo/semantics/openAccess
© Kluwer Academic Publishers, 1998
Springer Verlag
oai:ebuah.uah.es:10017/59022023-12-14T15:29:32Zcom_10017_164com_10017_17822com_10017_17761com_10017_17741col_10017_165
Interleukin-2 and its receptor complex (alpha, beta and gamma chains) in in situ and infiltrative human breast cancer: an immunohistochemical comparative study
García-Tuñón Llanio, Ignacio
Ricote Belinchón, Mónica
Ruiz, Antonio
Fraile Laiz, Benito
Paniagua Gómez-Álvarez, Ricardo
Royuela García, María del Mar
Universidad de Alcalá. Departamento de Biología Celular y Genética
Breast cancer
Interleukin-2
Interleukin-2 receptor
The presence and distribution of interleukin-2 (IL-2) and its receptor complex (Ralpha, Rbeta, Rgamma) were studied in 52 women who were clinically and histopathologically diagnosed with breast tumours ( 17 in situ and 35 infiltrating), and in 13 women with benign fibrocystic lesions in the breast. Methods. Immunohistochemistry with antibodies against IL-2, IL-2Ralpha, IL-2Rbeta and IL-2Rgamma was used. A comparative semiquantitative immunohistochemical study between the three breast groups ( fibrocystic lesions, in situ tumours and infiltrating tumours) was performed. Results. IL-2 and its three receptor chains were immunodetected in the cytoplasm of epithelial cells. The three receptor chains were also detected on the cell surface. In fibrocystic lesions, immunoreactions to IL-2 (38.5% of cases), IL-2Ralpha (53.8%) and IL-2Rbeta (30.8%) were very weak, whereas immunoreaction to IL-2Rgamma (46.1%) was somewhat more intense. In in situ tumours, the percentages of cases that immunostained positively for IL-2 and its three receptor chains were similar to those observed in fibrocystic lesions, but immunostainings of the four antibodies were more intense. In infiltrative tumours, the percentages of positively stained cases and also immunostaining intensities were approximately twice that found for in situ tumours. Within infiltrating tumours, the percentage of cases showing immunoreaction to IL-2 and their three receptor chains was higher in the patients with lymph node infiltration at the time of surgery. Conclusion. The development of breast tumour is associated with an increased expression of IL-2 and its three receptor chains, and this expression also seems to be associated with the malignancy of the tumour.
2010-03-11T12:14:39Z
2010-03-11T12:14:39Z
2010-03-11T12:14:39Z
2004
info:eu-repo/semantics/article
Breast Cancer Research, 2004, v. 6, p. R1-R7
1465-5411
http://hdl.handle.net/10017/5902
10.1186/bcr730
eng
http://dx.doi.org/10.1186/bcr730
PI020383 (Fondo de Investigaciones Sanitarias-FIS)
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
info:eu-repo/semantics/openAccess
Atribución-NoComercial-SinDerivadas 3.0 España
© García-Tuñón et al., licensee BioMed Central Ltd, 2004
BioMed Central
oai:ebuah.uah.es:10017/326782024-03-13T13:01:23Zcom_10017_164com_10017_17822com_10017_17761com_10017_17741col_10017_165
TNF-α/IL-1/NF-κB transduction pathway in human cancer prostate
Paniagua Gómez-Álvarez, Ricardo
Royuela García, María del Mar
Fraile Laiz, Benito
Rodríguez Berriguete, Gonzalo
Universidad de Alcalá. Departamento de Biomedicina y Biotecnología. Unidad docente Biología Celular y Genética
Prostate carcinoma
IL-1
TNF-α
NF-κB
NIK
p38
TNFα exerts apoptosis throughout an intracellular transduction pathway that involves the kinase proteins TRAF-2 (integration point of apoptotic and survival signals), ASK1 (pro-apoptotic protein), MEK-4 (p38 activator and metastasis suppressor gene), JNK (stress mitogen activated protein kinase) and the transcription factor AP-1. TNFα also exerts proliferation by p38 activation, or when TRAF-2 simultaneously induces the transcription factor NF-κB by NIK. NIK and p38 may also be activated by IL-1. P38 activated several transcription factors such as Elk-1, ATF-2 and NF-κB. NIK also may activate NF-κB.
The aim of the present article was to evaluate the different components of this TNFα/IL-1 transduction pathway in human prostate carcinoma (PC) in comparison with normal human prostate. In prostate cancer, pro-apoptotic TNFα/AP-1 pathway is probably inactivated by different factors such as p21 (at ASK-1 level) and bcl-2 (at JNK level), or diverted towards p38 or NIK activation. IL-1α enhances proliferation through IL-1RI that activates either NIK or p38 transduction pathway. P38 and NIK activate different transcription factors related with cell proliferation and survival such as ATF-2, Elk-1 or NF-κB.
In order to search a possible target to cancer prostate treatment we proposed that inhibition of several proinflamatory cytokines such as IL-1 and TNFα might be a possible target for PC treatment, because decrease the activity of all transduction pathway members that activate transcription factors as NF-κB, Elk-1 or ATF-2.
2018-03-12T11:59:07Z
2018-03-12T11:59:07Z
2018-03-12T11:59:07Z
2008-04-14
info:eu-repo/semantics/article
Histology and Histopathology. 2008, v. 23, n. 10, p. 1279-1290
0213-3911
http://hdl.handle.net/10017/32678
10.14670/HH-23.1279
Histology and Histopathology
23
1290
10
1279
18712680
1699-5848
eng
https://doi.org/10.14670/HH-23.1279
info:eu-repo/grantAgreement/MEC//SAF2007-61928/ES/ACTIVACIÓN DE IAPS (PROTEÍNAS INHIBIDORAS DE APOPTOSIS) Y CASPASAS EN CANCÉR DE PRÓSTATA MEDIANTE MAPKS (PROTEÍNAS QUINASAS ACTIVADAS POR MITÓGENOS) Y NF-KB. UTILIDAD PREDICTIVA DE POSIBLES RECIDIVAS
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
© Sercrisma International S.L., 2008
Sercrisma International S.L.
oai:ebuah.uah.es:10017/327202024-03-13T13:02:38Zcom_10017_164com_10017_17822com_10017_17761com_10017_17741col_10017_165
Prognostic value of inhibitors of apoptosis proteins (IAPs) and caspases in prostate cancer: caspase-3 forms and XIAP predict biochemical progression after radical prostatectomy
Rodríguez Berriguete, Gonzalo
Ortega Núñez, Miguel Ángel
Torrealba Abache, Norelia Rosa
Martínez Onsurbe, María del Pilar
Olmedilla Arregui, Gabriel
Paniagua Gómez-Álvarez, Ricardo
Guil Cid, Manuel Esteban
Fraile Laiz, Benito
Royuela García, María del Mar
Universidad de Alcalá. Departamento de Biomedicina y Biotecnología. Unidad docente Biología Celular y Genética
Apoptosis
Caspases
Biochemical progression
Inhibitors of apoptosis proteins
Prostate cancer
Background: The expression status of apoptotic regulators, such as caspases and inhibitors of apoptosis proteins (IAPs), could reflect the aggressiveness of tumors and, therefore, could be useful as prognostic markers. We explored the associations between tumor expression of caspases and IAPs and clinicopathological features of prostate cancer – clinical and pathological T stage, Gleason score, preoperative serum PSA levels, perineural invasion, lymph node involvement, surgical margin status and overall survival – and evaluated its capability to predict biochemical
progression after radical prostatectomy.
Methods: Protein expression of caspases (procaspase-8, cleaved caspase-8, procaspase-3, cleaved caspase-3,
caspase-7 and procaspase-9) and IAPs (cIAP1/2, cIAP2, NAIP, Survivin and XIAP) was analyzed by immunohistochemistry
in radical prostatectomy samples from 84 prostate cancer patients. Spearman’s test, Kaplan-Meier curves, and univariate
and multivariate Cox proportional hazard regression analysis were performed.
Results: cIAP1/2, cIAP2, Survivin, procaspase-8, cleaved caspase-8, procaspase-3 and caspase-7 expression correlated
with at least one clinicopathological feature of the disease. Patients negative for XIAP, procaspase-3 or cleaved
caspase-3 had a significantly worse prognosis. Of note, XIAP, procaspase-3 and cleaved caspase-3 were predictors
of biochemical progression independent of Gleason score and pathological T stage.
Conclusions: Our results indicate that alterations in the expression of IAPs and caspases contribute to the
malignant behavior of prostate tumors and suggest that tumor expression of XIAP, procaspase-3 and cleaved
caspase-3 may help to identify prostate cancer patients at risk of progression.
2018-03-13T15:17:29Z
2018-03-13T15:17:29Z
2018-03-13T15:17:29Z
2015
info:eu-repo/semantics/article
BMC Cancer. 2015, v. 15, n. 809, p. 1-9
http://hdl.handle.net/10017/32720
10.1186/s12885-015-1839-z
BMC Cancer
15
9
809
26507126
1471-2407
eng
http://dx.doi.org/10.1186/s12885-015-1839-z
info:eu-repo/grantAgreement/ISCIII//PI13%2F1801/ES
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
© Rodríguez-Berriguete et al. Open access, 2015
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
BioMed Central
oai:ebuah.uah.es:10017/327242023-12-14T15:29:33Zcom_10017_164com_10017_17822com_10017_17761com_10017_17741col_10017_165
Glucocorticoid receptor changes its cellular location with breast cancer development.
Paniagua Gómez-Álvarez, Ricardo
Fraile Laiz, Benito
Arenas Jiménez, María Isabel
Lucio Cazaña, Francisco Javier de
Conde Martín, María Isabel
Universidad de Alcalá. Departamento de Biomedicina y Biotecnología. Unidad docente Biología Celular y Genética
GR
MR
COX-2
Breast cancer
Glucocorticoids play a major role in attenuation of the inflammatory response and they are useful in the primary combination chemotherapy of breast cancer, since in vitro studies have demonstrated an antiproliferative effect in human breast cancer cells. In contrast, it was recently shown that glucocorticoids protect against apoptotic signals evoked by cytokines, cAMP, tumour suppressors, and death genes in mammary gland epithelia. Their actions are mediated by intracellular receptor (GR) that functions as a hormone-dependent transcription factor; however, no previous studies have been focused on GR expression in different pathologies of the human breast, and the possible relationship with that of mineralocorticoid receptor (MR) and COX-2. Also, the role of these proteins on tumoral breast epithelial cells remains unclear. Therefore, we examined GR, MR and COX-2 expression by immunohistochemistry and Western blot techniques in 142 samples of human breast obtained by total or partial mastectomy. We found that the percentage of positive patients presenting nuclear immunoreaction to GR decreased with tumor development, while all samples analyzed showed cytoplasmic immunoreactions to MR. All positive samples to COX-2 antibody showed cytoplasmic location, a higher immunoreaction being observed in benign breast diseases than in carcinomatous lesions. Thus, breast cancer progression is associated with the accumulation of GR in the cytoplasm of tumoral cells and the decrease of COX-2 expression.
2018-03-14T12:52:16Z
2018-03-14T12:52:16Z
2018-03-14T12:52:16Z
2008-07-13
info:eu-repo/semantics/article
Histology and Histopathology. 2008, v. 23, n. 1, p. 77-85
0213-3911
http://hdl.handle.net/10017/32724
10.14670/HH-23.77
Histology and histopathology
23
85
1
77
17952860
1699-5848
eng
https://doi.org/10.14670/HH-23.77
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
© Sercrisma International S.L., 2008
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
Sercrisma International S.L.
oai:ebuah.uah.es:10017/605132024-02-08T01:16:35Zcom_10017_164com_10017_17822com_10017_17761com_10017_17741col_10017_165
A Potential Effect of Circadian Rhythm in the Delivery/Therapeutic Performance of Paclitaxel-Dendrimer Nanosystems
Alburquerque, Tania
Neves, Ana Raquel
Paul, Milan
Vuelta, Elena
García Tuñón Llanio, Ignacio
Sanchez Martin, Manuel
Quintela, Telma
Costa, Diana
Universidad de Alcalá. Departamento de Biomedicina y Biotecnología
apoptosis
Bmal1 silencing
cancer therapy
caspases
circadian rhythmnano-delivery systems
PAMAM
The circadian clock controls behavior and physiology. Presently, there is clear evidence of a connection between this timing system and cancer development/progression. Moreover, circadian rhythm consideration in the therapeutic action of anticancer drugs can enhance the effectiveness of cancer therapy. Nanosized drug delivery systems (DDS) have been demonstrated to be suitable engineered platforms for drug targeted/sustained release. The investigation of the chronobiology-nanotechnology relationship, i.e., timing DDS performance according to a patient's circadian rhythm, may greatly improve cancer clinical outcomes. In the present work, we synthesized nanosystems based on an octa-arginine (R8)-modified poly(amidoamine) dendrimer conjugated with the anticancer drug paclitaxel (PTX), G4-PTX-R8, and its physicochemical properties were revealed to be appropriate for in vitro delivery. The influence of the circadian rhythm on its cellular internalization efficiency and potential therapeutic effect on human cervical cancer cells (HeLa) was studied. Cell-internalized PTX and caspase activity, as a measure of induced apoptosis, were monitored for six time points. Higher levels of PTX and caspase-3/9 were detected at T8, suggesting that the internalization of G4-PTX-R8 into HeLa cells and apoptosis are time-specific/-regulated phenomena. For a deeper understanding, the clock protein Bmal1-the main regulator of rhythmic activity, was silenced by Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology. Bmal1 silencing was revealed to have an impact on both PTX release and caspase activity, evidencing a potential role for circadian rhythm on drug delivery/therapeutic effect mediated by G4-PTX-R8.
2024-02-07T08:13:28Z
2024-02-07T08:13:28Z
2024-02-07T08:13:28Z
2023-07-11
info:eu-repo/semantics/article
Journal of Functional Biomaterials, 2023, v. 14, n. 7, p. 362-382
2079-4983
http://hdl.handle.net/10017/60513
10.3390/jfb14070362
AR/0000046019
Journal of Functional Biomaterials
14
382
7
362
eng
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
© The Authors
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
oai:ebuah.uah.es:10017/597652024-01-24T01:16:07Zcom_10017_164com_10017_17822com_10017_17761com_10017_17741col_10017_165
Evaluation of the smooth muscle cell component and apoptosis in the varicose vein wall.
Gimeno, M J
García-Honduvilla, N
Buján, J
Jiménez-Cossio, J A
Jurado, F
Pascual, G
Bellón, J M
Dominguez, B
Universidad de Alcalá. Departamento Biomedicina y Biotecnología. Unidad docente Biología Celular y Genética
Varicose vein
Smooth muscle cell
Apoptosis
Vein wall
Roliferation
This study was designed to evaluate the role of the smooth muscle cell and the apoptosis in the pathogenesis of the varicose vein. Segments of saphenous vein were obtained from healthy subjects and from those with varicose veins. The vein specimens were subdivided according to subject age (younger or older than 50 years) and according to the varicose vein source (distal or proximal). Morphological, ultrastructural, cell proliferation (anti-PCNA method) and cell death (TUNEL method) analysis were performed. The walls of healthy, control vein specimens acquired a more collagenous and papillomatous appearance with age. A slight increase in the number of TUNEL-positive cells was also observed in specimens from older subjects. The proportion of apoptotic cells was much greater in the varicose veins than in control specimens. Most cellular alterations were seen in proximal varicose segments obtained from young subjects. These specimens showed hypertrophic areas with a high degree of cellularity (both in the media and in the thickened intima). The highest proportion of apoptotic cells and collagenisation were also observed in these areas. The enhanced number of apoptotic cells in varicose veins observed mainly in proximal/young vein specimens could be responsible, at least in part, for the acceleration of the final fibrosclerotic process characteristic of the varicose vein wall.
2024-01-23T08:21:20Z
2024-01-23T08:21:20Z
2024-01-23T08:21:20Z
2000-07
info:eu-repo/semantics/article
Bujan, J. et al. (2000) ‘Evaluation of the smooth muscle cell component and apoptosis in the varicose vein wall’, Histology and histopathology, 15(3), pp. 745–752.
0213-3911
http://hdl.handle.net/10017/59765
10.14670/HH-15.745
Histology and histopathology
15
3
745
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eng
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
©The Author(s) 2000
Attribution-NonCommercial-NoDerivatives 4.0 Internacional