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8 results on '"MESH : Tumor Suppressor Proteins"'

1. Aberrant DNA methylation distinguishes hepatocellular carcinoma associated with HBV and HCV infection and alcohol intake

Author

Fabien Zoulim, Marie-Pierre Lambert, Massimo Tommasino, Zdenko Herceg, Jörg Tost, Jean-Yves Scoazec, Anupam Paliwal, Pierre Hainaut, Thomas Vaissière, Bakary S. Sylla, Isabelle Chemin, Centre de Recherche en Cancérologie de Lyon (CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Interactions Bactéries-Cellules (UIBC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), International Agency for Cancer Research (IACR), Equipe 16, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Service d'hépatologie et de gastroentérologie, Hospices Civils de Lyon (HCL)-Hôtel-Dieu-Hospices Civils de Lyon (HCL)-Hôtel-Dieu-Centre de Recherche en Cancérologie de Lyon (CRCL), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Sect Mech Carcinogenesis, equipe 4, Laboratoire Central d'Anatomie et de Cytologie Pathologiques [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de Recherche en Cancérologie de Lyon (CRCL), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Interactions Bactéries-Cellules ( UIBC ), Institut National de la Recherche Agronomique ( INRA ) -Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), International Agency for Cancer Research ( IACR ), International Agency for Cancer Research, Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Hospices Civils de Lyon ( HCL ) -Hôtel-Dieu-Hospices Civils de Lyon ( HCL ) -Hôtel-Dieu-Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer ( CIRC - IARC ), Organisation mondiale de la santé (OMS/WHO), international Agency for Research on Cancer - IARC, Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ) -Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre National de Génotypage ( CNG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Hospices Civils de Lyon (HCL)-Hôtel-Dieu-Hospices Civils de Lyon (HCL)-Hôtel-Dieu-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), and Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, MESH : Liver Neoplasms, MESH : Aged, Receptors, Nicotinic, MESH: Base Sequence, medicine.disease_cause, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: DNA Methylation, 0302 clinical medicine, Risk Factors, MESH: Liver Neoplasms, MESH: Risk Factors, MESH : Female, MESH: Gene Silencing, MESH: Carcinoma, Hepatocellular, MESH: Glutathione S-Transferase pi, MESH: Aged, 0303 health sciences, MESH: Middle Aged, MESH : Tumor Suppressor Proteins, Liver Neoplasms, RNA-Binding Proteins, DNA, Neoplasm, Hepatitis C, Methylation, Middle Aged, MESH : Adult, Hepatitis B, MESH : Risk Factors, 3. Good health, DNA-Binding Proteins, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, DNA methylation, MESH: Receptors, Nicotinic, Female, MESH : DNA Primers, MESH : DNA, Neoplasm, MESH : DNA-Binding Proteins, Adult, MESH : Carcinoma, Hepatocellular, MESH: DNA Primers, Carcinoma, Hepatocellular, Alcohol Drinking, MESH : Male, Hepatitis C virus, MESH : RNA-Binding Proteins, MESH: DNA, Neoplasm, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, MESH: Phosphoproteins, 03 medical and health sciences, MESH : Gene Silencing, medicine, Humans, MESH : Middle Aged, MESH: Tumor Suppressor Proteins, Gene Silencing, neoplasms, Aged, DNA Primers, 030304 developmental biology, MESH: Hepatitis C, Hepatitis B virus, MESH: Humans, Base Sequence, MESH : Receptors, Nicotinic, MESH: Hepatitis B, Hepatology, Tumor Suppressor Proteins, MESH : Humans, MESH : Hepatitis B, Cancer, MESH: Adult, DNA Methylation, MESH : Hepatitis C, Phosphoproteins, medicine.disease, MESH: Male, digestive system diseases, MESH : Alcohol Drinking, MESH: RNA-Binding Proteins, Glutathione S-Transferase pi, MESH : Glutathione S-Transferase pi, Immunology, MESH : Base Sequence, MESH : Phosphoproteins, MESH : DNA Methylation, MESH: Female, MESH: Alcohol Drinking, MESH: DNA-Binding Proteins
Abstract

International audience; BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is one of the most frequent human cancers and a major cause of cancer-related death worldwide. The major risk factors for developing HCC are infection by hepatitis B virus (HBV) and hepatitis C virus (HCV), chronic alcoholism, and aflatoxins; however, critical gene targets remain largely unknown. Herein, we sought to establish DNA methylation patterns in HCC and corresponding cirrhotic tissues and to identify DNA methylation changes associated with major risk factors. METHODS: We have established assays for quantitative analysis of DNA methylation levels in a panel of seven cancer-associated genes and repetitive elements, and combined these assays with a series of HCC tumors, associated with major risk factors, collected from two different geographical areas. RESULTS: We found a high frequency of aberrant hypermethylation of specific genes (RASSF1A, GSTP1, CHRNA3, and DOK1) in HCC tumors as compared to control cirrhotic or normal liver tissues, suggesting that aberrant hypermethylation exhibits non-random and tumor-specific patterns in HCC. Importantly, our analysis revealed an association between alcohol intake and the hypomethylation of MGMT and between hypermethylation of GSTP1 and HBV infection, indicating that hypermethylation of the genes analyzed in HCC tumors exhibits remarkably distinct patterns depending on associated risk factors. CONCLUSIONS: This study identifies aberrant DNA methylation of specific cellular genes in HCC and the major risk factors associated with these changes, providing information that could be exploited for biomarker discovery in clinics and molecular epidemiology.

Published
2011
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2. ARMC5 Mutations in a Large Cohort of Primary Macronodular Adrenal Hyperplasia: Clinical and Functional Consequences

Author

Xavier Bertagna, Francoise Doullay, Ludivine Drougat, E. Sonnet, Jérôme Bertherat, Joël Coste, Lionel Groussin, Rossella Libé, Françoise Borson-Chazot, Stéphanie Espiard, F. Brucker-Davis, Florence Torremocha, Guillaume Assié, Felix Beuschlein, Constantine A. Stratakis, Bruno Ragazzon, Marie-Laure Raffin-Sanson, G. Barrande, Stephanie Lopez, Karine Perlemoine, Nathalie Chabbert-Buffet, Denis Pinsard, Laurence Guignat, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional d'Orléans (CHRO), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Diabétologie-Endocrinologie (NICE - Endocrino), Centre Hospitalier Universitaire de Nice (CHU Nice), Endocrinologie, diabète, maladies métaboliques (CHU Marseille, AP-HM), Assistance Publique - Hôpitaux de Marseille (APHM), Service de Médecine interne B, Endocrinologie, Diabète, Maladies métaboliques [CHU Limoges], CHU Limoges, Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Service Endocrinologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'endocrinologie diabétologie et nutrition [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-Hôpital Anne-de-Bretagne, Gynécologie-obstétrique et médecine de la reproduction - Maternité [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d’endocrinologie et nutrition [AP-HP Ambroise-Paré], Hôpital Ambroise Paré [AP-HP], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupement hospitalier lyon Est (Hospices Civils de Lyon), Hospices Civils de Lyon (HCL), Unité d’Epidémiologie et de Biostatistiques [APHP Cochin-Broca-Hôtel Dieu], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Klinikum der Universitat Munchen, Ludwig-Maximilians-Universität München (LMU), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de référence des maladies rares de la surrénale [Cochin], Centre Hospitalier Régional d'Orléans ( CHR ), Centre méditérannéen de médecine moléculaire ( C3M ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Diabétologie-Endocrinologie ( NICE - Endocrino ), CHU Nice, Assistance Publique - Hôpitaux de Marseille ( APHM ), Hôpital de la Cavale Blanche - CHRU Brest ( CHU - BREST ), CHU de Poitiers, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -CHU Pontchaillou [Rennes]-Hôpital Anne-de-Bretagne, Service d'obstétrique gynécologie et médecine reproductive [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Service d’endocrinologie et nutrition [AP-HP Hôpital Ambroise-Paré], AP-HP Hôpital Ambroise-Paré [Boulogne-Billancourt], Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Groupement hospitalier lyon Est ( Hospices Civils de Lyon ), Hospices Civils de Lyon ( HCL ), Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Eunice Kennedy Shriver National Institute of Child Health and Human Development ( NICHD ), Klinikum Grosshadern, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 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)-Université Côte d'Azur (UCA), Université de Rennes (UR)-CHU Pontchaillou [Rennes]-Hôpital Anne-de-Bretagne, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Groupement Hospitalier Lyon-Est (GHE), CHU Cochin [AP-HP], Centre Hospitalier Régional d'Orléans (CHR), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, DNA Mutational Analysis, MESH : Aged, MESH : Adrenal Cortex Diseases, Biochemistry, Cohort Studies, MESH: Cushing Syndrome, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Adrenal Glands, Missense mutation, MESH : Female, MESH: Adrenal Glands, MESH: DNA Mutational Analysis, Cushing Syndrome, MESH: Cohort Studies, Cells, Cultured, MESH : Cushing Syndrome, Subclinical infection, MESH: Genetic Association Studies, MESH: Aged, 0303 health sciences, Aldosterone, MESH: Middle Aged, JCEM Online: Advances in Genetics, MESH : Tumor Suppressor Proteins, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Middle Aged, MESH : Adult, 3. Good health, Dexamethasone suppression test, Female, MESH: Cells, Cultured, Adrenal Cortex Diseases, Adult, medicine.medical_specialty, endocrine system, MESH : Male, Mutation, Missense, MESH : Cohort Studies, 030209 endocrinology & metabolism, Context (language use), MESH : DNA Mutational Analysis, Biology, MESH : Adrenal Glands, 03 medical and health sciences, Germline mutation, Internal medicine, MESH : Hyperplasia, Renin–angiotensin system, MESH : Cells, Cultured, medicine, Humans, MESH : HeLa Cells, MESH : Middle Aged, MESH: Tumor Suppressor Proteins, Genetic Association Studies, 030304 developmental biology, Aged, Armadillo Domain Proteins, MESH: Mutation, Missense, Hyperplasia, MESH: Humans, MESH: Hyperplasia, Tumor Suppressor Proteins, MESH: Adrenal Cortex Diseases, Biochemistry (medical), MESH : Humans, MESH: Adult, MESH : Genetic Association Studies, MESH: Male, chemistry, Macronodular Adrenal Hyperplasia, MESH: HeLa Cells, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Female, MESH : Mutation, Missense, HeLa Cells
Abstract

International audience; CONTEXT:Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of primary adrenal Cushing's syndrome (CS). ARMC5 germline mutations have been identified recently in PBMAH.OBJECTIVE:To determine the prevalence of ARMC5 mutations and analyze genotype-phenotype correlation in a large cohort of unrelated PBMAH patients with subclinical or clinical CS.PATIENTS AND METHODS:ARMC5 was sequenced in 98 unrelated PBMAH index cases. PBMAH was identified by bilateral adrenal nodular enlargement on computed tomography scan. The effect on apoptosis of ARMC5 missense mutants was tested in H295R and HeLa cells. Clinical and hormonal data were collected including midnight and urinary free cortisol levels, ACTH, androgens, renin/aldosterone ratio, cortisol after overnight dexamethasone suppression test, cortisol and 17-hydroxyprogesterone after ACTH 1-24 stimulation and illegitimate receptor responses. Computed tomography and histological reports were analyzed.RESULTS:ARMC5-damaging mutations were identified in 24 patients (26%). The missense mutants and the p.F700del deletion were unable to induce apoptosis in both H295R and HeLa cell lines, unlike the wild-type gene. ARMC5-mutated patients showed an overt CS more frequently, compared to wild-type patients: lower ACTH, higher midnight plasma cortisol, urinary free cortisol, and cortisol after dexamethasone suppression test (P = .003, .019, .006, and

Published
2015
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3. HOX11L2/TLX3 is transcriptionally activated through T-cell regulatory elements downstream of BCL11B as a result of the t(5;14)(q35;q32)

Author

Virginie Penard-Lacronique, Isabelle André-Schmutz, Xin-Ying Su, Roland Berger, Paola Ballerini, Claudie Lemercier, Véronique Della-Valle, Francine Mugneret, Serge Romana, Michel Lessard, Isabelle Radford-Weiss, Marina Lafage-Pochitaloff, Olivier Bernard, Génétique des hémopathies humaines ( EMI 210 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Developpement Normal et Pathologique du Système Immunitaire, Contrôle moléculaire de la réponse immune specifique, Université Joseph Fourier - Grenoble 1 ( UJF ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de Cytogénétique, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Service d'Hématologie Biologique, Assistance publique - Hôpitaux de Paris (AP-HP), Laboratoire d'Hématologie, CHU Strasbourg, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Laboratoire de cytogénétique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Génétique des hémopathies humaines (EMI 210), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)

Subjects
Oncogene Proteins, Fusion, Transcription, Genetic, T-Lymphocytes, BCL11B, Chromosomal translocation, MESH : Promoter Regions, Genetic, MESH : Oncogene Proteins, Fusion, Biochemistry, Jurkat cells, Translocation, Genetic, Jurkat Cells, MESH : Chromosomes, Human, Pair 5, 0302 clinical medicine, MESH : Translocation, Genetic, Transcription (biology), MESH: Jurkat Cells, Leukemia-Lymphoma, Adult T-Cell, MESH: Leukemia-Lymphoma, Adult T-Cell, MESH : Homeodomain Proteins, Promoter Regions, Genetic, MESH : Jurkat Cells, Oncogene Proteins, 0303 health sciences, MESH : Chromosomes, Human, Pair 14, MESH : Oncogene Proteins, MESH : Tumor Suppressor Proteins, Cell Differentiation, Hematology, Transfection, MESH: Translocation, Genetic, DNA-Binding Proteins, medicine.anatomical_structure, MESH: Repressor Proteins, 030220 oncology & carcinogenesis, Chromosomes, Human, Pair 5, MESH : DNA-Binding Proteins, MESH : Repressor Proteins, MESH : Cell Differentiation, MESH: Cell Differentiation, MESH: Chromosomes, Human, Pair 5, T cell, Immunology, Biology, 03 medical and health sciences, MESH: Oncogene Proteins, MESH: Promoter Regions, Genetic, MESH: Homeodomain Proteins, medicine, Humans, MESH: Tumor Suppressor Proteins, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Chromosomes, Human, Pair 14, Homeodomain Proteins, MESH : T-Lymphocytes, MESH: Humans, Recombinase activity, Tumor Suppressor Proteins, MESH: Transcription, Genetic, MESH : Humans, MESH : Transcription, Genetic, Cell Biology, T lymphocyte, Molecular biology, MESH : Leukemia-Lymphoma, Adult T-Cell, Repressor Proteins, MESH: T-Lymphocytes, MESH: Chromosomes, Human, Pair 14, MESH: DNA-Binding Proteins, MESH: Oncogene Proteins, Fusion
Abstract

International audience; The t(5;14)(q35;q32) chromosomal translocation is specifically observed in up to 20% of childhood T-cell acute lymphoblastic leukemia (T-ALL). It affects the BCL11B/CTIP2 locus on chromosome 14 and the RANBP17-TLX3/HOX11L2 region on chromosome 5. It leads to ectopic activation of TLX3/HOX11L2. To investigate the reasons of the association between t(5;14) and T-ALL, we isolated the translocation breakpoints in 8 t(5;14) patients. Sequence analyses did not involve recombinase activity in the genesis of the translocation. We used DNAse1 hypersensitive experiments to locate transcriptional regulatory elements downstream of BCL11B. By transient transfection experiments, 2 of the 6 regions demonstrated cis-activation properties in T cells and were also effective on the TLX3 promoter. Our data indicate that the basis of the specific association between t(5;14) and T-ALL lies on the juxtaposition of TLX3 to long-range cis-activating regions active during T-cell differentiation.

Published
2006
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4. [The two faces of p63, Janus of the p53 gene family]

Author

Caron De Fromentel, Claude, Aberdam, Edith, Aberdam, Daniel, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Faculté de Médecine ( UPD5 Médecine ), Université Paris Descartes - Paris 5 ( UPD5 ), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, MESH : Transcription Factors, MESH : Multigene Family, MESH: Genes, p53, MESH : Epidermis, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Models, Biological, MESH: Protein Isoforms, MESH : Genes, p53, Models, Biological, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Gene Expression Regulation, Developmental, Animals, Humans, Protein Isoforms, MESH: Animals, MESH: Tumor Suppressor Proteins, MESH: Humans, MESH : Tumor Suppressor Proteins, Tumor Suppressor Proteins, MESH : Humans, MESH: Models, Biological, Gene Expression Regulation, Developmental, MESH : Protein Isoforms, MESH: Adult, MESH: Transcription Factors, MESH : Adult, Genes, p53, Multigene Family, MESH: Multigene Family, MESH : Animals, MESH : Gene Expression Regulation, Developmental, Epidermis, MESH: Epidermis, Transcription Factors
Abstract

International audience; The TP53 family member TP63 encodes two main isoforms TAp63 and ΔNp63 with distinct, often opposite functions during development and in the adult. ΔNp63 is crucial for the formation of the ectodermal derivatives and epidermis, while TAp63 is essential for heart development. In the adult, ΔNp63 behaves as a cell survival factor, controlling cell proliferation, adhesion and cell differentiation. In contrast, TAp63 is a proapoptotic factor that protects oocytes from genotoxic insults and prevents premature aging of dermal stem cells. In agreement with these activities, TAp63 is often lost and ΔNp63 overexpressed in cancer cells. Because of their opposite and competitive effects, p63 isoforms could be viewed as Janus two faces. The review focuses on the accumulating data on the p63 functions and regulation in the last decade.

Published
2012
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5. DCC constrains tumour progression via its dependence receptor activity

Author

Loraine Jarrosson-Wuilleme, Jean-Yves Scoazec, Guillaume Chazot, Marie Castets, Laura Broutier, Yann Molin, Armelle Paquet, Patrick Mehlen, Nicolas Gadot, Laetitia Mazelin, Marie Brevet, Agnès Bernet, Puisieux, Alain, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Anipath, UFR Médecine Lyon-RTH Laennec, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), and Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
Deleted in Colorectal Cancer, MESH : Mutant Proteins, MESH : Receptors, Cell Surface, Apoptosis, Dependence receptor, law.invention, MESH : Adenocarcinoma, Mice, MESH: Mutant Proteins, 0302 clinical medicine, law, Netrin, MESH : Intestinal Neoplasms, MESH: Animals, MESH: Gene Silencing, Receptor, Cells, Cultured, Cancer, MESH: Receptors, Cell Surface, 0303 health sciences, MESH: Genes, APC, Multidisciplinary, MESH : Tumor Suppressor Proteins, Genomics, Netrin-1, DCC Receptor, 3. Good health, 030220 oncology & carcinogenesis, Caspases, MESH: HEK293 Cells, Disease Progression, MESH: Disease Progression, MESH : Mutation, MESH: Cells, Cultured, Genes, APC, MESH: Mutation, Context (language use), Receptors, Cell Surface, Biology, Adenocarcinoma, MESH : Nerve Growth Factors, 03 medical and health sciences, MESH : Mice, MESH : Cells, Cultured, MESH : Fibroblasts, MESH : Gene Silencing, Intestinal Neoplasms, Genetics, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Gene silencing, Animals, Humans, MESH: Tumor Suppressor Proteins, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Gene Silencing, Nerve Growth Factors, MESH: Intestinal Neoplasms, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, 030304 developmental biology, MESH: Humans, MESH: Caspases, MESH: Nerve Growth Factors, Tumor Suppressor Proteins, MESH: Apoptosis, MESH : Humans, fungi, MESH: Adenocarcinoma, MESH : Disease Progression, Fibroblasts, MESH : Disease Models, Animal, MESH : HEK293 Cells, Disease Models, Animal, MESH : Genes, APC, HEK293 Cells, MESH: Fibroblasts, Immunology, Mutation, Cancer research, Suppressor, Mutant Proteins, MESH : Animals, MESH : Caspases, MESH: Disease Models, Animal, MESH : Apoptosis
Abstract

International audience; The role of deleted in colorectal carcinoma (DCC) as a tumour suppressor has been a matter of debate for the past 15 years. DCC gene expression is lost or markedly reduced in the majority of advanced colorectal cancers and, by functioning as a dependence receptor, DCC has been shown to induce apoptosis unless engaged by its ligand, netrin-1 (ref. 2). However, so far no animal model has supported the view that the DCC loss-of-function is causally implicated as predisposing to aggressive cancer development. To investigate the role of DCC-induced apoptosis in the control of tumour progression, here we created a mouse model in which the pro-apoptotic activity of DCC is genetically silenced. Although the loss of DCC-induced apoptosis in this mouse model is not associated with a major disorganization of the intestines, it leads to spontaneous intestinal neoplasia at a relatively low frequency. Loss of DCC-induced apoptosis is also associated with an increase in the number and aggressiveness of intestinal tumours in a predisposing APC mutant context, resulting in the development of highly invasive adenocarcinomas. These results demonstrate that DCC functions as a tumour suppressor via its ability to trigger tumour cell apoptosis.

Published
2012
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6. The ribonucleotide reductase large subunit (RRM1) as a predictive factor in patients with cancer

Author

Pascal Sève, Olivier Tredan, Charles Dumontet, Lars Petter Jordheim, Equipe 14, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Médecine Nucléaire, Centre Léon Bérard [Lyon], Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), and Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
Pathology, medicine.medical_specialty, Ribonucleoside Diphosphate Reductase, [SDV.CAN]Life Sciences [q-bio]/Cancer, Polymorphism, Single Nucleotide, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, MESH : Tumor Markers, Biological, Pancreatic cancer, Neoplasms, Biomarkers, Tumor, Medicine, Humans, MESH: Neoplasms, MESH: Tumor Suppressor Proteins, Lung cancer, 030304 developmental biology, 0303 health sciences, MESH: Humans, business.industry, Cell growth, MESH : Tumor Suppressor Proteins, MESH: Polymorphism, Single Nucleotide, Tumor Suppressor Proteins, MESH : Humans, MESH : Polymorphism, Single Nucleotide, medicine.disease, MESH : Neoplasms, Gemcitabine, 3. Good health, Ribonucleotide reductase, Oncology, 030220 oncology & carcinogenesis, MESH: Tumor Markers, Biological, Cancer research, Biomarker (medicine), business, medicine.drug
Abstract

International audience; The large subunit of human ribonucleotide reductase, RRM1, is involved in the regulation of cell proliferation, cell migration, tumour and metastasis development, and the synthesis of deoxyribonucleotides for DNA synthesis. It is also a cellular target for the chemotherapeutic agent, gemcitabine. RRM1 has been studied in a large number of patients with different types of cancer, such as non-small-cell lung cancer, pancreatic cancer, breast cancer, and biliary tract cancer, to establish its prognostic or predictive value when patients were treated with gemcitabine, and mRNA expression and genetic variants as determined by genotyping have in some cases been associated with clinical outcome of patients with cancer. Here, we review preclinical and clinical studies of RRM1 assessment and discuss the further steps in the development of this clinically pertinent biomarker.

Published
2010
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7. Tumor Suppressor Schwannomin/Merlin Is Critical for the Organization of Schwann Cell Contacts in Peripheral Nerves

Author

Carmen Cifuentes-Diaz, Jean-Antoine Girault, Michèle Carnaud, Natalia Denisenko, Fabrice Chareyre, Marco Giovannini, Michiko Niwa-Kawakita, Laurence Goutebroze, Evelyne Benoit, Theano Irinopoulou, Institut du Fer à Moulin (IFM - Inserm U1270 - SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut du Fer à Moulin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Neurobiologie Alfred Fessard (INAF), Centre National de la Recherche Scientifique (CNRS), Laboratoire de neurobiologie cellulaire et moléculaire (NBCM), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Neurobiologie Alfred Fessard ( INAF ), Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de neurobiologie cellulaire et moléculaire ( NBCM ), Genomique Fonctionnelle des Tumeurs Solides, and Université Paris Diderot - Paris 7 ( UPD7 ) -IFR105-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )

Subjects
Cellular differentiation, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Cell Communication, MESH : Gene Deletion, Schwann cell proliferation, Mice, 0302 clinical medicine, Compact myelin, MESH : Cell Proliferation, MESH: Animals, Neurofibromatosis type 2, ComputingMilieux_MISCELLANEOUS, MESH : Neurofibromin 2, Neurofibromin 2, 0303 health sciences, MESH : Tumor Suppressor Proteins, General Neuroscience, MESH : Peripheral Nerves, MESH: Neurofibromin 2, Articles, MESH : Mice, Transgenic, Cell biology, medicine.anatomical_structure, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH : Cell Communication, Tumor suppressor gene, MESH: Mice, Transgenic, MESH : Schwann Cells, Schwann cell, Mice, Transgenic, Biology, 03 medical and health sciences, MESH: Cell Proliferation, MESH : Mice, MESH: Cell Communication, medicine, Animals, Humans, MESH: Tumor Suppressor Proteins, Peripheral Nerves, MESH: Mice, Cell Proliferation, 030304 developmental biology, MESH: Humans, Tumor Suppressor Proteins, MESH : Humans, medicine.disease, MESH: Peripheral Nerves, Merlin (protein), nervous system, Cytoplasm, MESH: Gene Deletion, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Schwann Cells, MESH : Animals, MESH: Schwann Cells, Neuroscience, Gene Deletion, 030217 neurology & neurosurgery
Abstract

Schwannomin/merlin is the product of a tumor suppressor gene mutated in neurofibromatosis type 2 (NF2). Although the consequences of NF2 mutations on Schwann cell proliferation are well established, the physiological role of schwannomin in differentiated cells is not known. To unravel this role, we studied peripheral nerves in mice overexpressing in Schwann cells schwannomin with a deletion occurring in NF2 patients (P0–SCH–Δ39–121) or a C-terminal deletion. The myelin sheath and nodes of Ranvier were essentially preserved in both lines. In contrast, the ultrastructural and molecular organization of contacts between Schwann cells and axons in paranodal and juxtaparanodal regions were altered, with irregular juxtaposition of normal and abnormal areas of contact. Similar but more severe alterations were observed in mice with conditional deletion of theNf2gene in Schwann cells. The number of Schmidt–Lanterman incisures, which are cytoplasmic channels interrupting the compact myelin and characterized by distinct autotypic contacts, was increased in the three mutant lines. P0–SCH–Δ39–121 and conditionally deleted mice displayed exuberant wrapping of nonmyelinated fibers and short internodes, an abnormality possibly related to altered control of Schwann cell proliferation. In support of this hypothesis, Schwann cell number was increased along fibers before myelination in P0–SCH–Δ39–121 mice but not in those with C-terminal deletion. Schwann cell numbers were also more numerous in mice with conditional deletion. Thus, schwannomin plays an important role in the control of Schwann cell number and is necessary for the correct organization and regulation of axoglial heterotypic and glio-glial autotypic contacts.

Published
2008
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8. Analysis of the fiber architecture of the heart by quantitative polarized light microscopy. Accuracy, limitations and contribution to the study of the fiber architecture of the ventricles during fetal and neonatal life

Author

Ayman Mourad, Gabrielle Michalowicz, Pierre-Simon Jouk, Annie Raoult, Yves Usson, Denis Caillerie, Vuk Milisic, RFMQ, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Equations aux Dérivées Partielles (EDP), Laboratoire Jean Kuntzmann (LJK), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS), Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Laboratoire sols, solides, structures - risques [Grenoble] (3SR), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications [Grenoble] ( TIMC-IMAG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Equations aux Dérivées Partielles ( EDP ), Laboratoire Jean Kuntzmann ( LJK ), Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Mathématiques Appliquées à Paris 5 ( MAP5 - UMR 8145 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National des Sciences Mathématiques et de leurs Interactions-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire sols, solides, structures - risques [Grenoble] ( 3S-R ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National Polytechnique de Grenoble ( INPG ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and Centre National de la Recherche Scientifique (CNRS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Université Joseph Fourier - Grenoble 1 (UJF)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Centre National de la Recherche Scientifique (CNRS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Université Joseph Fourier - Grenoble 1 (UJF)-Université Pierre Mendès France - Grenoble 2 (UPMF)

Subjects
MESH: Neoplasm Proteins, MESH : Transcription Factors, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, MESH : DNA, Muscle Fibers, Skeletal, MESH : Models, Biological, 030204 cardiovascular system & hematology, Tracking (particle physics), 030218 nuclear medicine & medical imaging, Section (fiber bundle), MESH : Muscle Fibers, 0302 clinical medicine, Orientation (geometry), MESH : Myocardium, Medicine, MESH : G2 Phase, Fiber, MESH : Adaptation, Physiological, [ SDV.IB.IMA ] Life Sciences [q-bio]/Bioengineering/Imaging, Polarized light microscopy, MESH : Tumor Suppressor Proteins, MESH: Infant, Newborn, MESH: Muscle Fibers, MESH: DNA, MESH : Protein Binding, General Medicine, MESH: Transcription Factors, Adaptation, Physiological, Azimuth, MESH: Reproducibility of Results, MESH: Heterochromatin, MESH: Microscopy, Polarization, Microscopy, Polarization, Cardiology and Cardiovascular Medicine, MESH : Chromosomal Proteins, Non-Histone, Pulmonary and Respiratory Medicine, MESH: Cell Line, Tumor, MESH: Myocardium, Heart Ventricles, MESH : Infant, Newborn, Models, Biological, 03 medical and health sciences, Optics, Fetal Heart, MESH : Neoplasm Proteins, MESH: Chromosomal Proteins, Non-Histone, Humans, MESH: Protein Binding, MESH: Tumor Suppressor Proteins, MESH : Microscopy, Polarization, MESH: Humans, Pixel, Plane (geometry), business.industry, MESH : Cell Line, Tumor, MESH : Heterochromatin, Myocardium, MESH : Reproducibility of Results, MESH : Humans, Infant, Newborn, MESH: Models, Biological, Reproducibility of Results, MESH : Nuclear Proteins, MESH : Fetal Heart, MESH: Adaptation, Physiological, MESH: G2 Phase, MESH: Fetal Heart, MESH : Heart Ventricles, Surgery, MESH: Heart Ventricles, business, MESH: Nuclear Proteins
Abstract

International audience; OBJECTIVE: To address the advantages and drawbacks of quantitative polarized light microscopy for the study of myocardial cell orientation and to identify its contribution in the field. METHODS: Quantitative polarized light microscopy allows to measure the orientation of myocardial fibers into the ventricular mass. For each pixel of a horizontal section, this orientation is the mean value of the directions of all myosin filaments contained in the thickness of the section for each pixel of the section and is accounted for by two angles, the azimuth angle, which is the angle of the fiber in the plane of the section, and the elevation angle, which measures the way the fiber escapes from the section. The azimuth is accurately measured, and its range of definition is complete from 0 degrees to 180 degrees . The elevation angle can be defined only in the range 0 degrees to 90 degrees . It is accurately measured between 20 degrees and 70 degrees . From 0 degrees to 20 degrees , there is a systematic bias raising the measured values, and from 70 degrees to 90 degrees , the angle is not accurately measured. RESULTS: With this method, we validated Streeter's conjecture concerning the architecture of the left ventricle. We formulated a pretzel conjecture about the fiber architecture of the whole ventricular mass during fetal period. In our model, elaborated by visual analysis of registered maps of orientation, the fibers run like geodesics on a nested set of 'pretzels'. Next, the validity of the helical ventricular myocardial band model of Torrent-Guasp has been examined. It appears that the band model does not account for the patterns observed in our data during the fetal period. However, after the major events of postnatal cardiovascular adaptation, our data can neither discard nor confirm Torrent-Guasp's model. CONCLUSIONS: Present limitations of quantitative polarized light analysis can neither confirm nor discard the existing models of fiber orientation in the whole ventricular mass after the neonatal period. However, the problems of mathematical and experimental validation of these two models have been posed in a rigorous manner. Non-ambiguous fiber tracking and demonstration of these models will require significant improvement of the definition range of the elevation angle that should be extended to 180 degrees .

Published
2007
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