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2. Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition

Author

Mateo, F, Arenas, EJ, Aguilar, H, Serra-Musach, J, Garibay, GR, Boni, J, Maicas, M, Du, S, Iorio, F, Herranz-Ors, C, Islam, A, Prado, X, Llorente, A, Petit, A, Vidal, A, Catala, I, Soler, T, Venturas, G, Rojo-Sebastian, A, Serra, H, Cuadras, D, Blanco, I, Lozano, J, Canals, F, Sieuwerts, Anieta, Weerd, Vanja, Look, MP, Puertas, S, Garcia, N, Perkins, AS, Bonifaci, N, Skowron, M, Gomez-Baldo, L, Hernandez, V, Martinez-Aranda, A, Martinez-Iniesta, M, Serrat, X, Ceron, J, Brunet, J, Barretina, MP, Gil, M, Falo, C, Fernandez, A, Morilla, I, Pernas, S, Pla, MJ, Andreu, X, Segui, MA, Ballester, R, Castella, E, Nellist, Mark, Morales, S, Valls, J, Velasco, A, Matias-Guiu, X, Figueras, A, Sanchez-Mut, JV, Sanchez-Cespedes, M, Cordero, A, Gomez-Miragaya, J, Palomero, L, Gomez, A, Gajewski, TF, Cohen, EEW, Jesiotr, M, Bodnar, L, Quintela-Fandino, M, Lopez-Bigas, N, Valdes-Mas, R, Puente, XS, Vinals, F, Casanovas, O, Graupera, M, Hernandez-Losa, J, Cajal, SRY, Garcia-Alonso, L, Saez-Rodriguez, J, Esteller, M, Sierra, A, Martin-Martin, N, Matheu, A, Carracedo, A, Gonzalez-Suarez, E, Nanjundan, M, Cortes, J, Lazaro, C (Conxi), Odero, MD, Martens, John, Moreno-Bueno, G, Barcellos-Hoff, MH, Villanueva, A, Gomis, RR, Pujana, MA, Mateo, F, Arenas, EJ, Aguilar, H, Serra-Musach, J, Garibay, GR, Boni, J, Maicas, M, Du, S, Iorio, F, Herranz-Ors, C, Islam, A, Prado, X, Llorente, A, Petit, A, Vidal, A, Catala, I, Soler, T, Venturas, G, Rojo-Sebastian, A, Serra, H, Cuadras, D, Blanco, I, Lozano, J, Canals, F, Sieuwerts, Anieta, Weerd, Vanja, Look, MP, Puertas, S, Garcia, N, Perkins, AS, Bonifaci, N, Skowron, M, Gomez-Baldo, L, Hernandez, V, Martinez-Aranda, A, Martinez-Iniesta, M, Serrat, X, Ceron, J, Brunet, J, Barretina, MP, Gil, M, Falo, C, Fernandez, A, Morilla, I, Pernas, S, Pla, MJ, Andreu, X, Segui, MA, Ballester, R, Castella, E, Nellist, Mark, Morales, S, Valls, J, Velasco, A, Matias-Guiu, X, Figueras, A, Sanchez-Mut, JV, Sanchez-Cespedes, M, Cordero, A, Gomez-Miragaya, J, Palomero, L, Gomez, A, Gajewski, TF, Cohen, EEW, Jesiotr, M, Bodnar, L, Quintela-Fandino, M, Lopez-Bigas, N, Valdes-Mas, R, Puente, XS, Vinals, F, Casanovas, O, Graupera, M, Hernandez-Losa, J, Cajal, SRY, Garcia-Alonso, L, Saez-Rodriguez, J, Esteller, M, Sierra, A, Martin-Martin, N, Matheu, A, Carracedo, A, Gonzalez-Suarez, E, Nanjundan, M, Cortes, J, Lazaro, C (Conxi), Odero, MD, Martens, John, Moreno-Bueno, G, Barcellos-Hoff, MH, Villanueva, A, Gomis, RR, and Pujana, MA

Published
2017

3. BRAF V600E and KRAS G12S mutations in peripheral nerve sheath tumours

Author

Serrano, C, Simonetti, S, Hernandez-Losa, J, Valverde, C, Carrato, C, Bague, S, Orellana, R, Somoza, R, Moline, T, Carles, J, Huguet, P, Romagosa, C, and Cajal, SRY

Subjects
acoustic neuroma, neurofibromatosis type 2, NF1, NF2, KRAS, malignant peripheral nerve sheath tumour, neurofibromatosis type 1, schwannoma, BRAF, neurofibroma
Abstract

Aims Benign (BPNST) and malignant (MPNST) peripheral nerve sheath tumours occur either sporadically or are related to neurofibromatosis (NF). The mechanisms involved are well known in NF-related tumours, but still remain unclear in sporadic cases. Somatic BRAF and KRAS mutations represent the most frequent genetic events in melanocytic neoplastic lesions. Because melanocytes and Schwann cells both derive from neural crest cells, we hypothesized that BRAF and KRAS mutations might influence BPNST and MPNST development. Methods and results BRAF exon 15 and KRAS exons 2 and 3 polymerase chain reaction (PCR) sequencing was performed in formalin-fixed/paraffin-embedded samples of 99 BPNST and MPNST, related and non-related to NF types 1 and 2. Oncogenic BRAF V600E mutations were found in four of 40 schwannomas (including one acoustic neuroma) and one of 13 MPNST, not associated with NF. A KRAS G12S mutation was also evident in one sporadic schwannoma. Conclusion Our findings suggest that RAS pathway activation due to BRAF V600E and KRAS mutations is an important event in a subset of peripheral nerve sheath tumours not related to NF.

Published
2013

4. Molecular bases of endometrial cancer: New roles for new actors in the diagnosis and the therapy of the disease

Author

Llaurado, M, Ruiz, A, Majem, B, Ertekin, T, Colas, E, Pedrola, N, Devis, L, Rigau, M, Sequeiros, T, Montes, M, Garcia, M, Cabrera, S, Gil-Moreno, A, Xercavins, J, Castellvi, J, Garcia, A, Cajal, SRY, Moreno, G, Alameda, F, Vazquez-Levin, M, Palacios, J, Prat, J, Doll, A, Matias-Guiu, X, Abal, M, and Reventos, J

Subjects
Treatment, Mice, Endometrial carcinoma, Molecular genetics, Aspirates, Target therapy
Abstract

Endometrial carcinoma (EC) is the most commonly diagnosed gynecologic malignancy in the western world. The majority of these cancers are curable, but a subset about 15-20% of endometrial tumors exhibits an aggressive phenotype. Based on clinic-pathological and molecular characteristics, EC has been classified into two groups: Type I estrogen-dependent adenocarcinomas, which have a good prognosis and an endometrioid histology, and Type II or non-estrogen-dependent EC associated with poor prognosis and non-endometrioid histology. EC develops as a result of a stepwise accumulation of alterations that seem to be specific of each histological type. However, more knowledge is needed to better understand the differences in the biology and the clinical outcome of EC. We would like to highlight the need to explore new potential biomarkers of EC as a tool for the detection and monitoring of aggressive endometria I tumors that, at the same time, will allow us to develop novel and more selective molecular targeted therapies against EC. (C) 2011 Published by Elsevier Ireland Ltd.

Published
2012

14. Tumor heterogeneity: Morphological, molecular and clinical implications

Author

Lleonart, Me, Martin-Duque, P., Ricardo Sanchez-Prieto, Moreno, A., and Cajal, Sry

Subjects
Tumor, Carcinogenesis, 5 - Ciencias puras y naturales::57 - Biología::576 - Biología celular y subcelular. Citología [CDU], Radioresistance, Review, Heterogeneity
Abstract

Malignant tumors are characterized by their great heterogeneity and variability. There are hundreds of different types of malignant tumors that harbour many oncogenic alterations. The tumor heterogeneity has important morphological, molecular and clinical implications. Except for some hematopoietic and lymphoproliferative processes and small cell infant tumors, there are not specific molecular alterations for most human tumors. In this review we summarize the most important aspects of carcinogenesis and chemoradiosensitivity of malignant cells. In this regard, some oncogenes such as neu , ras and bcl-2 have been associated with cellular resistance to treatment with anticancer agents. The knowledge of oncogenic alterations involved in each tumor can be important to correlate the morphological features, the genetic background, the prognosis and the clinical response to treatment with anticancer agents. Based on the molecular background of the tumor there are new cancer gene therapy protocols. For example using adenovirus Ela in tumors with overexpression of neu oncogene, inhibitors of tirosine kinase specific for the PDGF receptor in glioma, inhibitors of farnesil transferase to prevent ras activity in tumors with mutations in the ras gene.

17. Clinical and molecular practice of European thoracic pathology laboratories during the COVID-19 pandemic. The past and the near future

Author

John R. Gosney, G. Troncone, W. Dietmaier, A. De Muret, P. Brest, S.R.Y. Cajal, E. Long-Mira, G. Gorkiewicz, H. Wolff, Lina Carvalho, J. Stojsic, A. Hofman, Izidor Kern, L. Chalabreysse, A. Dema, Cristian Ortiz-Villalón, R. Schiappa, Lukas Bubendorf, S. Garcia, L. Gibault, L. de Leval, M.-C. Copin, Aurélie Cazes, Hans-Ulrich Schildhaus, E. Shaw, M. Antoine, Véronique Hofman, A. Stenzinger, M. Garcia-Martos, M. Evert, V. Nakache, E. Chamorey, S. Savic-Prince, P. Boström, P. Brousset, M. Sajin, S. Lassalle, H. Begueret, Wim Timens, Mark Kriegsmann, Mauro Papotti, Peter Schirmacher, M.-P. Chenard, M. Barberis, V. Thomas de Montpreville, J. Meilleroux, P. Delongova, M. Ilié, C. Bonnetaud, C. Werlein, Keith M. Kerr, J.-F. Côté, A. Mamilos, A. Lupo, Patrick Pauwels, Frédérique Penault-Llorca, I. Serre, N. Poté, C.-H. Marquette, Paul Hofman, J.-C. Sabourin, J.-P. Berthet, Giuseppe Pelosi, A. Foulet, D. Damotte, D. Sizaret, Fabien Forest, Erik Thunnissen, A. Panizo, L. Panico, O. Pop, G. Cathomas, M. Kossai, I. Salmon, F. Calabrese, F. Bibeau, Aurelie Fabre, R. Matěj, J. Benzaquen, Danny Jonigk, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), FHU OncoAge - Pathologies liées à l’âge [CHU Nice] (OncoAge), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Université Côte d'Azur (UCA), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), European Institute of Oncology IRCCS [Milan, Italy] (EIO), CHU Bordeaux [Bordeaux], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU), Turku University Hospital (TYKS), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), University Hospital Basel [Basel], University of Coimbra [Portugal] (UC), Kantonsspital Baselland [Bruderholz] (KSBL), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Groupement Hospitalier Est [Bron], Hospices Civils de Lyon (HCL), CHU Strasbourg, CHU Lille, Université de Lille, Institut Mutualiste de Montsouris (IMM), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Lausanne (UNIL), University Hospital Ostrava, Centre chirurgical Marie Lannelongue, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Victor Babeş University of Medicine and Pharmacy (UMFT), University of Regensburg, University College Dublin [Dublin] (UCD), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Hospitalier Le Mans (CH Le Mans), Hôpital Nord AP‐MM Marseille, France (AP‐MM Marseille), Aix Marseille Université (AMU), Hospital General Universitario 'Gregorio Marañón' [Madrid], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), University of Graz, Hannover Medical School [Hannover] (MHH), Royal Liverpool University Hospital, University of Liverpool-Royal Liverpool and Broadgreen University Hospital NHS Trust, University Clinic Golnik, Aberdeen Royal Infirmary, Aberdeen, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Heidelberg University Hospital [Heidelberg], Charles University [Prague] (CU), Karolinska University Hospital [Stockholm], Monaldi-Cotugno-CTO, Complejo Hospitalario de Navarra, Università degli studi di Torino (UNITO), University of Antwerp (UA), University of Milan, University of Oradea, Romania, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Vall d'Hebron University Hospital [Barcelona], Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Université libre de Bruxelles (ULB), University of Medicine and Pharmacy 'Carol Davila' Bucharest (UMPCD), University Hospital [Essen, Germany], Hôpital Gui de Chauliac, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), University Hospital Southampton NHS Foundation Trust, University of Belgrade [Serbia], Institute of Zoology [Serbia], University of Amsterdam [Amsterdam] (UvA), University of Groningen [Groningen], Università degli studi di Napoli Federico II, Finnish Institute of Occupational Health of Helsinki, University of Padova Medical School, Université Nice Sophia Antipolis (1965 - 2019) (UNS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Université Côte d'Azur (UCA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Université de Lausanne = University of Lausanne (UNIL), Centre Chirurgical Marie Lannelongue (CCML), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Karl-Franzens-Universität Graz, Università degli studi di Torino = University of Turin (UNITO), Università degli Studi di Milano = University of Milan (UNIMI), University of Oradea, Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), University of Naples Federico II = Università degli studi di Napoli Federico II, Università degli Studi di Padova = University of Padua (Unipd), Institut Català de la Salut, [Hofman P, Ilié M, Nakache V] Laboratory of Clinical and Experimental Pathology, FHU OncoAge, BB-0033-00025, Louis Pasteur Hospital, IRCAN, Université Côte d'Azur, Nice, France. [Brest P] Team 4, IRCAN, INSERM, CNRS, Centre Antoine-Lacassagne, Université Côte d'Azur, Nice, France. [Chamorey E, Schiappa R] Epidemiology and Biostatistics Unit, Centre Antoine-Lacassagne, Université Côte d'Azur, Nice, France. [Cajal SRY] Servei d’Anatomia Patològica, Vall d'Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), COLO, Mouniati, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC), Karl-Franzens-Universität [Graz, Autriche], Hofman, P., Ilie, M., Chamorey, E., Brest, P., Schiappa, R., Nakache, V., Antoine, M., Barberis, M., Begueret, H., Bibeau, F., Bonnetaud, C., Bostrom, P., Brousset, P., Bubendorf, L., Carvalho, L., Cathomas, G., Cazes, A., Chalabreysse, L., Chenard, M. -P., Copin, M. -C., Cote, J. -F., Damotte, D., de Leval, L., Delongova, P., Thomas de Montpreville, V., de Muret, A., Dema, A., Dietmaier, W., Evert, M., Fabre, A., Forest, F., Foulet, A., Garcia, S., Garcia-Martos, M., Gibault, L., Gorkiewicz, G., Jonigk, D., Gosney, J., Hofman, A., Kern, I., Kerr, K., Kossai, M., Kriegsmann, M., Lassalle, S., Long-Mira, E., Lupo, A., Mamilos, A., Matej, R., Meilleroux, J., Ortiz-Villalon, C., Panico, L., Panizo, A., Papotti, M., Pauwels, P., Pelosi, G., Penault-Llorca, F., Pop, O., Pote, N., Cajal, S. R. Y., Sabourin, J. -C., Salmon, I., Sajin, M., Savic-Prince, S., Schildhaus, H. -U., Schirmacher, P., Serre, I., Shaw, E., Sizaret, D., Stenzinger, A., Stojsic, J., Thunnissen, E., Timens, W., Troncone, G., Werlein, C., Wolff, H., Berthet, J. -P., Benzaquen, J., Marquette, C. -H., Hofman, V., and Calabrese, F.

Subjects
Cancer Research, Pathology, [SDV]Life Sciences [q-bio], Medizin, Disease Outbreaks, varnost, Biosafety, 0302 clinical medicine, Surveys and Questionnaires, Pandemic, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], Medicine, Pathology, Molecular, COVID-19, activity, biosafety, lung cancer, pathology, biološka varnost, Health Occupations::Medicine::Pathology::Pathology, Clinical [DISCIPLINES AND OCCUPATIONS], Original Research, Biological Specimen Banks, 0303 health sciences, Pathology, Clinical, Molecular pathology, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], Workload, Clinical Laboratory Services, Containment of Biohazards, Biobank, 3. Good health, [SDV] Life Sciences [q-bio], Europe, covid-19, Oncology, 030220 oncology & carcinogenesis, Thoracic diseases, COVID-19 (Malaltia) - Europa, Laboratoris anatòmics, localizaciones geográficas::Europa (continente) [DENOMINACIONES GEOGRÁFICAS], safety, medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), lung neoplasms, pljučni rak, Geographic Locations::Europe [GEOGRAPHICALS], Specimen Handling, 03 medical and health sciences, Thoracic Diseases, udc:616.9, Humans, Pandemics, 030304 developmental biology, SARS-CoV-2, business.industry, pljučne novotvorbe, profesiones sanitarias::medicina::anatomía patológica::patología clínica [DISCIPLINAS Y OCUPACIONES], patologija, Human medicine, business, Biological Specimen Banks/organization & administration, Biological Specimen Banks/statistics & numerical data, COVID-19/epidemiology, COVID-19/prevention & control, COVID-19/virology, Clinical Laboratory Services/statistics & numerical data, Clinical Laboratory Services/trends, Containment of Biohazards/statistics & numerical data, Europe/epidemiology, Forecasting, Pathology, Clinical/methods, Pathology, Clinical/statistics & numerical data, Pathology, Clinical/trends, Pathology, Molecular/methods, Pathology, Molecular/statistics & numerical data, Pathology, Molecular/trends, SARS-CoV-2/isolation & purification, SARS-CoV-2/physiology, Specimen Handling/methods, Specimen Handling/statistics & numerical data, Thoracic Diseases/diagnosis, Thoracic Diseases/therapy
Abstract

Background This study evaluated the consequences in Europe of the COVID-19 outbreak on pathology laboratories orientated toward the diagnosis of thoracic diseases. Materials and methods A survey was sent to 71 pathology laboratories from 21 European countries. The questionnaire requested information concerning the organization of biosafety, the clinical and molecular pathology, the biobanking, the workload, the associated research into COVID-19, and the organization of education and training during the COVID-19 crisis, from 15 March to 31 May 2020, compared with the same period in 2019. Results Questionnaires were returned from 53/71 (75%) laboratories from 18 European countries. The biosafety procedures were heterogeneous. The workload in clinical and molecular pathology decreased dramatically by 31% (range, 3%-55%) and 26% (range, 7%-62%), respectively. According to the professional category, between 28% and 41% of the staff members were not present in the laboratories but did teleworking. A total of 70% of the laboratories developed virtual meetings for the training of residents and junior pathologists. During the period of study, none of the staff members with confirmed COVID-19 became infected as a result of handling samples. Conclusions The COVID-19 pandemic has had a strong impact on most of the European pathology laboratories included in this study. Urgent implementation of several changes to the organization of most of these laboratories, notably to better harmonize biosafety procedures, was noted at the onset of the pandemic and maintained in the event of a new wave of infection occurring in Europe., Highlights • Biosafety measures used in the first wave of the COVID-19 crisis were heterogeneous in 53 European pathology laboratories. • A dramatic decrease of the workload in pathology laboratories was noted. • No case of healthcare workers contaminated with SARS-CoV-2 associated with samples handling was identified.

Published
2021

18. Glyoxal acid-free (GAF) histological fixative is a suitable alternative to formalin: results from an open-label comparative non-inferiority study.

Author

Ryska A, Sapino A, Landolfi S, Valero IS, Cajal SRY, Oliveira P, Detillo P, Lianas L, Frexia F, Nicolosi PA, Monti T, Bussolati B, Marchiò C, and Bussolati G

Subjects
Humans, Female, Male, Formaldehyde chemistry, Fixatives chemistry, Tissue Fixation methods, Glyoxal
Abstract

Formalin, an aqueous solution of formaldehyde, has been the gold standard for fixation of histological samples for over a century. Despite its considerable advantages, growing evidence points to objective toxicity, particularly highlighting its carcinogenicity and mutagenic effects. In 2016, the European Union proposed a ban, but a temporary permission was granted in consideration of its fundamental role in the medical-diagnostic field. In the present study, we tested an innovative fixative, glyoxal acid-free (GAF) (a glyoxal solution deprived of acids), which allows optimal tissue fixation at structural and molecular level combined with the absence of toxicity and carcinogenic activity. An open-label, non-inferiority, multicentric trial was performed comparing fixation of histological specimens with GAF fixative vs standard phosphate-buffered formalin (PBF), evaluating the morphological preservation and the diagnostic value with four binary score questions answered by both the central pathology reviewer and local center reviewers. The mean of total score in the GAF vs PBF fixative groups was 3.7 ± 0.5 vs 3.9 ± 0.3 for the central reviewer and 3.8 ± 0.5 vs 4.0 ± 0.1 for the local pathologist reviewers, respectively. In terms of median value, similar results were observed between the two fixative groups, with a median value of 4.0. Data collected indicate the non-inferiority of GAF as compared to PBF for all organs tested. The present clinical performance study, performed following the international standard for performance evaluation of in vitro diagnostic medical devices, highlights the capability of GAF to ensure both structural preservation and diagnostic value of the preparations., (© 2023. The Author(s).)

Published
2024
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19. Clinical application of the HM-1000 image processing for HER2 fluorescence in situ hybridization signal quantification in breast cancer.

Author

Peg V, Moline T, Roig M, Saruta Y, and Cajal SRY

Subjects
Humans, Female, In Situ Hybridization, Fluorescence methods, Retrospective Studies, Neoplasm Recurrence, Local genetics, Receptor, ErbB-2 genetics, Receptor, ErbB-2 metabolism, Monosomy, Gene Amplification, Breast Neoplasms diagnosis
Abstract

Background: Accurate quantification of human epidermal growth factor receptor 2 (HER2) gene amplification is important for predicting treatment response and prognosis in patients with breast cancer. Fluorescence in situ hybridization (FISH) is the gold standard for the diagnosis of HER2 status, particularly in cases with equivocal status on immunohistochemistry (IHC) staining, but has some limitations of non-classical amplifications and such cases are diagnosed basing on additional IHC and FISH. This study investigated the clinical utility of a novel super-resolution fluorescence microscopy technique for the better FISH signal visualization and HER2 FISH classification., Methods: Fourteen breast cancer tissue samples were retrospectively collected between September 2018 and February 2022, and FISH HER2 signal quantification was evaluated by determining the HER2/chromosome 17 centromere (CEP17) ratio and the number of HER2 signals per nucleus in super- versus conventional-resolution images., Results: Super-resolution images maintained the same overall HER2 diagnosis from routine, but HER2 FISH amplification changed negative to monosomy in two cases. Two Letrozole non-response relapses coincided to monosomy samples. The median number of HER2 signals per nucleus was 7.5 in super-resolution images and 4.0 in conventional-resolution images in HER2-positive samples and 2.8 and 2.1 signals per nucleus, respectively, in HER2-negative samples., Conclusions: Super-resolution images improved signal visualization, including a significant difference in the number of countable HER2 and CEP17 signals in a single nucleus compared with conventional-resolution images. Increased accuracy of signal quantification by super-resolution microscopy may provide clinicians with more detailed information regarding HER2 FISH status that allows to better FISH classification such as HER2-low samples., (© 2024. The Author(s).)

Published
2024
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20. Dissecting Breast Cancer Circulating Tumor Cells Competence via Modelling Metastasis in Zebrafish.

Author

Martínez-Pena I, Hurtado P, Carmona-Ule N, Abuín C, Dávila-Ibáñez AB, Sánchez L, Abal M, Chaachou A, Hernández-Losa J, Cajal SRY, López-López R, and Piñeiro R

Subjects
Animals, Cell Line, Tumor, Embryo, Nonmammalian, Female, Humans, MCF-7 Cells, Mice, Neoplasm Metastasis, Breast Neoplasms pathology, Disease Models, Animal, Neoplastic Cells, Circulating, Zebrafish embryology
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.

Published
2021
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21. Clinical and molecular practice of European thoracic pathology laboratories during the COVID-19 pandemic. The past and the near future.

Author

Hofman P, Ilié M, Chamorey E, Brest P, Schiappa R, Nakache V, Antoine M, Barberis M, Begueret H, Bibeau F, Bonnetaud C, Boström P, Brousset P, Bubendorf L, Carvalho L, Cathomas G, Cazes A, Chalabreysse L, Chenard MP, Copin MC, Côté JF, Damotte D, de Leval L, Delongova P, Thomas de Montpreville V, de Muret A, Dema A, Dietmaier W, Evert M, Fabre A, Forest F, Foulet A, Garcia S, Garcia-Martos M, Gibault L, Gorkiewicz G, Jonigk D, Gosney J, Hofman A, Kern I, Kerr K, Kossai M, Kriegsmann M, Lassalle S, Long-Mira E, Lupo A, Mamilos A, Matěj R, Meilleroux J, Ortiz-Villalón C, Panico L, Panizo A, Papotti M, Pauwels P, Pelosi G, Penault-Llorca F, Pop O, Poté N, Cajal SRY, Sabourin JC, Salmon I, Sajin M, Savic-Prince S, Schildhaus HU, Schirmacher P, Serre I, Shaw E, Sizaret D, Stenzinger A, Stojsic J, Thunnissen E, Timens W, Troncone G, Werlein C, Wolff H, Berthet JP, Benzaquen J, Marquette CH, Hofman V, and Calabrese F

Subjects
Biological Specimen Banks organization & administration, Biological Specimen Banks statistics & numerical data, COVID-19 epidemiology, COVID-19 virology, Clinical Laboratory Services trends, Containment of Biohazards statistics & numerical data, Disease Outbreaks, Europe epidemiology, Forecasting, Humans, Pandemics, Pathology, Clinical methods, Pathology, Clinical trends, Pathology, Molecular methods, Pathology, Molecular trends, SARS-CoV-2 isolation & purification, SARS-CoV-2 physiology, Specimen Handling methods, Specimen Handling statistics & numerical data, Thoracic Diseases therapy, COVID-19 prevention & control, Clinical Laboratory Services statistics & numerical data, Pathology, Clinical statistics & numerical data, Pathology, Molecular statistics & numerical data, Surveys and Questionnaires, Thoracic Diseases diagnosis
Abstract

Background: This study evaluated the consequences in Europe of the COVID-19 outbreak on pathology laboratories orientated toward the diagnosis of thoracic diseases., Materials and Methods: A survey was sent to 71 pathology laboratories from 21 European countries. The questionnaire requested information concerning the organization of biosafety, the clinical and molecular pathology, the biobanking, the workload, the associated research into COVID-19, and the organization of education and training during the COVID-19 crisis, from 15 March to 31 May 2020, compared with the same period in 2019., Results: Questionnaires were returned from 53/71 (75%) laboratories from 18 European countries. The biosafety procedures were heterogeneous. The workload in clinical and molecular pathology decreased dramatically by 31% (range, 3%-55%) and 26% (range, 7%-62%), respectively. According to the professional category, between 28% and 41% of the staff members were not present in the laboratories but did teleworking. A total of 70% of the laboratories developed virtual meetings for the training of residents and junior pathologists. During the period of study, none of the staff members with confirmed COVID-19 became infected as a result of handling samples., Conclusions: The COVID-19 pandemic has had a strong impact on most of the European pathology laboratories included in this study. Urgent implementation of several changes to the organization of most of these laboratories, notably to better harmonize biosafety procedures, was noted at the onset of the pandemic and maintained in the event of a new wave of infection occurring in Europe., Competing Interests: Disclosure The authors have declared no conflicts of interest. Data sharing Anonymized participant-level data are available for investigators. Ethical approval The study complied with the law of January 1978 (78-17) relating to computing, data, and freedom known as ‘computing and freedoms’ and with rules 2016/679 of the European Parliament (of 25 May 2018) concerning the general data protection regulation (GDPR; MR004). The study was registered by the Nice University Hospital (R04-39) and filed on the Health Data Hub website (7 July 2020) (www.health-data-hub.fr/depot)., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2021
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23. Characterization of Kelch domain-containing protein 7B in breast tumours and breast cancer cell lines.

Author

Martín-Pardillos A and Cajal SRY

Abstract

Adenocarcinomas exhibit great heterogeneity, with many genetic and epigenetic alterations. The Kelch domain-containing protein 7B (KLHDC7B) has recently been identified as epigenetically modified and upregulated in breast cancer. The potential reversibility of epigenetic states offers exciting possibilities for novel cancer diagnostics and drugs. However, to properly evaluate specific inhibitors, the role of KLHDC7B in the development and progression of breast cancer should be established. With that objective in mind, the present study investigated a series of human breast tumours and correlated their clinicopathology, according to the Elston-Ellis modification of the Scarff-Bloom-Richardson (SBR) grading system, with KLHDC7B mRNA expression, analysed using quantitative PCR (qPCR). The results revealed that KLHDC7B was significantly upregulated in grade 3 tumours, and that KLHDC7B expression varied according to the tumour grade and the individual, being downregulated in well-differentiated and moderately-differentiated tumours (grade 1-2) and upregulated in poorly-differentiated tumours (grade 3). Immunohistochemical staining revealed that ductal tumours and tumours with a higher percentage of Ki67 positive cells showed the highest levels of KLHDC7B. Receptor expression, HER, p53 status, presence of metastasis, and vascular invasion showed no association with KLHDC7B expression. Previous studies have proposed KLHDC7B as an epigenetic marker of breast cancer. We propose that KLHDC7B should be used as a marker for poorly-differentiated tumours only; use of KLHDC7B without considering tumour grade could lead to an inaccurate diagnosis. Finally, we suggest the appropriate breast cancer cell lines to use to determine the functions of KLHDC7B. KLHDC7B expression was tested in the non-tumour cell line MCF-10A and in the breast cancer cell lines MCF-7, MDA-MB-231 and MDA-MB-468, using qPCR and western blotting. The results revealed that all tested cancer cell lines overexpressed KLHDC7B mRNA, but MDA-MB-468 exhibited a much lower level of protein expression relative to mRNA. Although the breast cancer cell lines used may be appropriate for studying KLHDC7B epigenetic status, MDA-MB-468 should be excluded from functional experiments.

Published
2019
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