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1.
Ann Oncol ; 28(6): 1274-1279, 2017 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-28398524

RESUMEN

BACKGROUND: Rare ovarian tumors represent >20% of all ovarian cancers. Given the rarity of these tumors, natural history, prognostic factors are not clearly identified. The extreme variability of patients (age, histological subtypes, stage) induces multiple and complex therapeutic strategies. METHODS: Since 2011, a national network with a dedicated system for referral, up to 22 regional and three national reference centers (RC) has been supported by the French National Cancer Institute (INCa). The network aims to prospectively monitor the management of rare ovarian tumors and provide an equal access to medical expertise and innovative treatments to all French patients through a dedicated website, www.ovaire-rare.org. RESULTS: Over a 5-year activity, 4612 patients have been included. Patients' inclusions increased from 553 in 2011 to 1202 in 2015. Expert pathology review and patients' files discussion in dedicated multidisciplinary tumor boards increased from 166 cases in 2011 (25%) to 538 (45%) in 2015. Pathology review consistently modified the medical strategy in 5-9% every year. The rate of patients' files discussed in RC similarly increased from 294 (53%) to 789 (66%). An increasing number (357 in 5 years) of gynecologic (non-ovarian) rare tumors were also registered by physicians seeking for pathological or medical advice from expert tumor boards. CONCLUSION: Such a nation-wide organization for rare gynecological tumors has invaluable benefits, not only for patients, but also for epidemiological, clinical and biological research.


Asunto(s)
Manejo de la Enfermedad , Neoplasias Ováricas/terapia , Femenino , Humanos , Incidencia
2.
Immunogenetics ; 53(6): 490-500, 2001 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-11685460

RESUMEN

A segment comprising 307,078 nucleotides of the pig major histocompatibility complex (SLA) was completely sequenced. The segment corresponded to the entire SLA classical class I-containing region of the serologically defined SLA H01 haplotype. In all, 11 genes were characterized, comprising 7 class I genes located on the centromeric part of the sequence (SLA-1, 2, 3, 4, 5, 9, and 11) and 4 ring finger-related family genes located on its telomeric part. No member of one family was intermingled with a member of the other or with any third-party gene. All class I genes except SLA-11 were similarly orientated. The SLA-1, 2, and 3 genes displayed both promoter and overall coding regions compatible with normal functions. The SLA-4, 11, and 9 genes were considered pseudogenes because they exhibited marked anomalies. Although the SLA-5 gene had a complete coding region, it displayed mutations in promoter elements which could modify its expression. The great molecular similarity observed among the class I genes extended far outside them, and resulted from segmental duplications. The ring finger genes exhibited great homology with their human counterparts. In pig, one of these genes appeared to correspond to a complete gene which in humans is probably a pseudogene. In all, the 11 genes characterized span about 20% of the total sequence. The remaining 80% consists of interspersed repeat elements. The present results, together with the sequence previously reported involving the SLA class I-related genes, open the way for a better understanding of pig MHC organization.


Asunto(s)
Genes MHC Clase I , Porcinos/genética , Alelos , Animales , Secuencia de Bases , Centrómero/genética , Proteínas de Unión al ADN/genética , Haplotipos , Antígenos de Histocompatibilidad Clase I/inmunología , Prueba de Histocompatibilidad , Humanos , Datos de Secuencia Molecular , Regiones Promotoras Genéticas , Secuencias Reguladoras de Ácidos Nucleicos , Homología de Secuencia de Ácido Nucleico , Telómero/genética , Regiones no Traducidas , Dedos de Zinc
3.
Science ; 282(5389): 744-6, 1998 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-9784132

RESUMEN

A map of 30,181 human gene-based markers was assembled and integrated with the current genetic map by radiation hybrid mapping. The new gene map contains nearly twice as many genes as the previous release, includes most genes that encode proteins of known function, and is twofold to threefold more accurate than the previous version. A redesigned, more informative and functional World Wide Web site (www.ncbi.nlm.nih.gov/genemap) provides the mapping information and associated data and annotations. This resource constitutes an important infrastructure and tool for the study of complex genetic traits, the positional cloning of disease genes, the cross-referencing of mammalian genomes, and validated human transcribed sequences for large-scale studies of gene expression.


Asunto(s)
Cromosomas Humanos/genética , Genoma Humano , Mapeo Físico de Cromosoma , Animales , Etiquetas de Secuencia Expresada , Expresión Génica , Marcadores Genéticos , Proyecto Genoma Humano , Humanos , Internet , Ratas , Lugares Marcados de Secuencia
4.
Immunity ; 9(2): 267-76, 1998 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-9729047

RESUMEN

Homozygous targeted disruption of the mouse Caspase 8 (Casp8) gene was found to be lethal in utero. The Caspase 8 null embryos exhibited impaired heart muscle development and congested accumulation of erythrocytes. Recovery of hematopoietic colony-forming cells from the embryos was very low. In fibroblast strains derived from these embryos, the TNF receptors, Fas/Apo1, and DR3 were able to activate the Jun N-terminal kinase and to trigger IkappaB alpha phosphorylation and degradation. They failed, however, to induce cell death, while doing so effectively in wild-type fibroblasts. These findings indicate that Caspase 8 plays a necessary and nonredundant role in death induction by several receptors of the TNF/NGF family and serves a vital role in embryonal development.


Asunto(s)
Caspasas , Cisteína Endopeptidasas/genética , Cisteína Endopeptidasas/fisiología , Fibroblastos/citología , Marcación de Gen , Genes Letales/genética , Receptores del Factor de Necrosis Tumoral/fisiología , Receptor fas/fisiología , Animales , Caspasa 8 , Caspasa 9 , Muerte Celular/efectos de los fármacos , Muerte Celular/genética , Células Cultivadas/efectos de los fármacos , ADN Complementario/genética , Muerte Fetal/genética , Fibroblastos/efectos de los fármacos , Fibroblastos/fisiología , Edad Gestacional , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados/embriología , Fenotipo , Miembro 25 de Receptores de Factores de Necrosis Tumoral , Transcripción Genética/genética , Receptor fas/farmacología
5.
Genomics ; 50(2): 147-60, 1998 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-9653642

RESUMEN

Familial Mediterranean fever (FMF) is a recessively inherited disorder characterized by attacks of fever and serositis, which affects primarily non-Ashkenazi Jews, Armenians, Turks, and Arabs. We present here a transcriptional map covering the FMF locus that we constructed in the course of the positional cloning of the gene responsible for this disease. This map was established from a contig constructed with YAC, BAC, and cosmid clones and covers about 500 kb of 16p13.3. It contains nine transcriptional units corresponding to known genes or to genes belonging to known gene families, 23 gene fragments characterized by partial sequences, and an endogenous retrovirus sequence. It thus considerably increases the number of genes in this interval and improves our knowledge concerning some of the genes or gene families present in this region. Data accumulated in this region were also used in a comparative study of different methods of exon detection.


Asunto(s)
Mapeo Cromosómico , Fiebre Mediterránea Familiar/genética , Secuencia de Bases , Northern Blotting , Cromosomas Artificiales de Levadura , Proteínas del Citoesqueleto , ADN Complementario , Exones , Expresión Génica , Biblioteca Genómica , Humanos , Metaloendopeptidasas/genética , Datos de Secuencia Molecular , Proteínas/genética , Pirina , Receptores Odorantes/genética , Mapeo Restrictivo , Sensibilidad y Especificidad , Análisis de Secuencia de ADN , Programas Informáticos , Transcripción Genética , Dedos de Zinc/genética
6.
Genome Res ; 7(7): 705-15, 1997 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9253599

RESUMEN

Human genes containing triplet repeats have been demonstrated to be involved in several neurodegenerative diseases by expansion of the repeat in succeeding generations. To identify novel genes involved in such pathologies, we have isolated transcripts containing (CAG/CTG)n repeats using two approaches. First, we screened 4 x 10(6) clones representing 10 copies of a human testis cDNA library using a (CAG)14 oligonucleotide probe. Among the 910 clones identified, the 243 clones with the strongest hybridization signal were sequenced partially from 3' or 5' ends. This provided us with 251 partial sequences that grouped into clusters corresponding to 39 genes, of which 19 represent unknown species. Second, we selected 203 additional ESTs containing (CAG/CTG)n repeats representing 121 clusters from the IMAGE consortium infant brain cDNA library. From these two series of sequences, we have localized 95 genes on human chromosomes using a panel of whole genome radiation hybrid (Genebridge 4). These genes are located on all of the chromosomes except for chromosome X, the highest density being observed on chromosome 19.


Asunto(s)
Encéfalo , Cromosomas Humanos Par 19 , Genoma Humano , Testículo , Repeticiones de Trinucleótidos/genética , Cromosoma X , Mapeo Cromosómico , Humanos , Masculino , Datos de Secuencia Molecular , Familia de Multigenes
8.
Science ; 274(5287): 540-6, 1996 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-8849440

RESUMEN

The human genome is thought to harbor 50,000 to 100,000 genes, of which about half have been sampled to date in the form of expressed sequence tags. An international consortium was organized to develop and map gene-based sequence tagged site markers on a set of two radiation hybrid panels and a yeast artificial chromosome library. More than 16,000 human genes have been mapped relative to a framework map that contains about 1000 polymorphic genetic markers. The gene map unifies the existing genetic and physical maps with the nucleotide and protein sequence databases in a fashion that should speed the discovery of genes underlying inherited human disease. The integrated resource is available through a site on the World Wide Web at http://www.ncbi.nlm.nih.gov/SCIENCE96/.


Asunto(s)
Mapeo Cromosómico , Genoma Humano , Proyecto Genoma Humano , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Línea Celular , Cromosomas Artificiales de Levadura , Redes de Comunicación de Computadores , ADN Complementario/genética , Bases de Datos Factuales , Expresión Génica , Marcadores Genéticos , Humanos , Familia de Multigenes , ARN Mensajero/genética , Homología de Secuencia de Ácido Nucleico , Lugares Marcados de Secuencia
10.
Am J Hum Genet ; 56(6): 1417-30, 1995 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-7762565

RESUMEN

A gene for a recessive form of limb-girdle muscular dystrophy (LGMD2A) has been localized to chromosome 15. A physical map of the 7-cM candidate 15q15.1-q21.1 region has been constructed by means of a 10-12-Mb continuum of overlapping YAC clones. New microsatellite markers developed from these YACs were genotyped on large, consanguineous LGMD2A pedigrees from different origins. The identification of recombination events in these families allowed the restriction of the LGMD2A region to an estimated 1-cM interval, equivalent to approximately 3-4 Mb. Linkage disequilibrium data on genetic isolates from the island of Réunion and from the Amish community suggest a preferential location of the LGMD2A gene in the proximal part of this region. Analysis of the interrelated pedigrees from Réunion revealed the existence of at least six different carrier haplotypes. This allelic heterogeneity is incompatible with the presumed existence of a founder effect and suggests that multiple LGMD2A mutations may segregate in this population.


Asunto(s)
Cromosomas Humanos Par 15/genética , Distrofias Musculares/genética , Secuencia de Bases , Mapeo Cromosómico , Consanguinidad , ADN Satélite , Femenino , Marcadores Genéticos , Genotipo , Haplotipos , Heterocigoto , Homocigoto , Humanos , Escala de Lod , Masculino , Datos de Secuencia Molecular , Distrofias Musculares/epidemiología , Linaje , Polimorfismo Genético , Recombinación Genética , Reunión/epidemiología
11.
Cell ; 81(1): 27-40, 1995 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-7720071

RESUMEN

Limb-girdle muscular dystrophies (LGMDs) are a group of inherited diseases whose genetic etiology has yet to be elucidated. The autosomal recessive forms (LGMD2) constitute a genetically heterogeneous group with LGMD2A mapping to chromosome 15q15.1-q21.1. The gene encoding the muscle-specific calcium-activated neutral protease 3 (CANP3) large subunit is located in this region. This cysteine protease belongs to the family of intracellular calpains. Fifteen nonsense, splice site, frameshift, or missense calpain mutations cosegregate with the disease in LGMD2A families, six of which were found within La Réunion island patients. A digenic inheritance model is proposed to account for the unexpected presence of multiple independent mutations in this small inbred population. Finally, these results demonstrate an enzymatic rather than a structural protein defect causing a muscular dystrophy, a defect that may have regulatory consequences, perhaps in signal transduction.


Asunto(s)
Calpaína/genética , Distrofias Musculares/genética , Mutación/genética , Secuencia de Aminoácidos , Secuencia de Bases , Cromosomas Humanos Par 15 , ADN/sangre , Análisis Mutacional de ADN , Exones/genética , Expresión Génica , Pruebas Genéticas , Humanos , Modelos Genéticos , Datos de Secuencia Molecular , Distrofias Musculares/enzimología , Distrofias Musculares/etnología , Ácidos Nucleicos Heterodúplex , Reacción en Cadena de la Polimerasa/métodos , Mapeo Restrictivo , Alineación de Secuencia
12.
Hum Mol Genet ; 4(4): 717-25, 1995 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-7633422

RESUMEN

Previous genetic and physical studies of LGMD2A, an autosomal recessive form of limb-girdle muscular dystrophy, have led to the establishment of a 10-12 Mb YAC contig encompassing the morbid locus. In order to progress toward the identification of the gene involved in LGMD2A, a primary transcription map of this genomic region was generated. The direct cDNA selection strategy was used with three YACs covering the candidate region and two different muscle cDNA libraries. Seventeen transcription units were identified among 171 cDNA fragments analysed. Five sequences corresponded to known genes, and twelve to new ones. They were characterized for their sequences, physical positions within the YAC contig, and expression patterns. Among those specifically transcribed in muscle, the calpain gene is a good positional and functional candidate for LGMD2A.


Asunto(s)
Cromosomas Humanos Par 15 , Distrofias Musculares/genética , Adulto , Secuencia de Aminoácidos , Secuencia de Bases , Mapeo Cromosómico , Cromosomas Artificiales de Levadura , Clonación Molecular , ADN Complementario , Humanos , Datos de Secuencia Molecular , Músculos/metabolismo , Homología de Secuencia de Aminoácido , Transcripción Genética
13.
Genomics ; 23(3): 619-27, 1994 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-7851890

RESUMEN

One hundred forty-nine chromosome 15 loci were mapped by PCR with respect to chromosome breakpoints in three somatic cell hybrids retaining total or part of chromosome 15 and to a 10-Mb YAC contig. This chromosome was subdivided into 5 regions, yielding an average resolution of more than 1 sequence tagged site per megabase. The mapped loci included 18 genes, 60 cDNA-derived sequence tagged sites, and 69 microsatellites. In addition, the amount of chromosome 15 retained in line A15.1 has been defined. This work represents the first attempt at an integration of the human physical, expression, and genetic maps of chromosome 15.


Asunto(s)
Cromosomas Humanos Par 15 , Hominidae/genética , Alelos , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Línea Celular , Mapeo Cromosómico , Cromosomas Artificiales de Levadura , Cricetinae , Cricetulus , Cartilla de ADN , Bases de Datos Factuales , Expresión Génica , Marcadores Genéticos , Humanos , Células Híbridas , Ratones , Datos de Secuencia Molecular , Distribución de Poisson , Reacción en Cadena de la Polimerasa/métodos , Polimorfismo Genético , Homología de Secuencia de Aminoácido
14.
Hum Mol Genet ; 3(9): 1657-61, 1994 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-7833925

RESUMEN

Congenital muscular dystrophies (CMD) are autosomal recessive, heterogeneous disorders. The commonest forms are the Fukuyama CMD (FCMD), associated with mental retardation and structural brain anomalies, and classical (occidental) CMD, with pure muscle expression. FCMD has been localized to chromosome 9q31-q33. Following the discovery of merosin deficiency in some CMD cases, we have localized, by homozygosity mapping and linkage analysis (Zmax = 5.6; theta = 0.0 for marker AFM127xb2) in four merosin-negative families a CMD gene in a 16 cM region of chromosome 6q2 in the region of the laminin M chain gene. In three consanguineous, merosin-positive, CMD families there was no linkage to either chromosome 6q2 or 9q31-q33.


Asunto(s)
Mapeo Cromosómico , Cromosomas Humanos Par 6 , Laminina/deficiencia , Distrofias Musculares/congénito , Distrofias Musculares/genética , Cromosomas Humanos Par 9 , Consanguinidad , Femenino , Ligamiento Genético , Marcadores Genéticos , Homocigoto , Humanos , Laminina/genética , Masculino , Distrofias Musculares/metabolismo , Linaje
15.
Mol Gen Genet ; 239(1-2): 169-76, 1993 May.
Artículo en Inglés | MEDLINE | ID: mdl-8510644

RESUMEN

A multicopy genomic library of Saccharomyces cerevisiae (strain FL100) was screened for its ability to suppress conditionally defective mutations altering the 31 kDa subunit (rpc31-236) or the 53 kDa subunit (rpc53-254/424) of RNA polymerase III. In addition to allele-specific suppressors, we identified seven suppressor clones that acted on both mutations and also suppressed several other conditional mutations defective in RNA polymerases I or II. All these clones harbored a complete copy of the SSD1 gene. The same pleiotropic suppression pattern was found with the dominant SSD1-v allele present in some laboratory strains of S. cerevisiae. SSD1-v was previously shown to suppress mutations defective in the SIT4 gene product (a predicted protein phosphatase subunit) or in the regulatory subunit of the cyclic AMP-dependent protein kinase. We propose that the SSD1 gene product modulates the activity (or the level) of the three nuclear RNA polymerases, possibly by altering their degree of phosphorylation.


Asunto(s)
Proteínas Fúngicas/genética , ARN Polimerasa III/genética , ARN Polimerasa II/genética , ARN Polimerasa I/genética , Saccharomyces cerevisiae/genética , Supresión Genética , Alelos , Genes Fúngicos , Mapeo Restrictivo , Saccharomyces cerevisiae/enzimología
16.
J Biol Chem ; 267(32): 23099-107, 1992 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-1429657

RESUMEN

RPC53 has previously been shown to encode an essential subunit required for tRNA gene transcription by RNA polymerase C in vivo (Mann, C., Micouin, J.-Y., Chiannilkulchai, N., Treich, I., Buhler, J.-M., and Sentenac, A. (1992) Mol. Cell. Biol. 12, in press). In this paper, we have determined that an unusual rho+ lethality associated with the rpc53::HIS3-1 disruption mutation is due to the inadvertent formation of a Pet56-C53 fusion protein. This fusion protein is missorted to mitochondria, thereby reducing the quantity of the C53 subunit available for RNA polymerase C assembly. We show that the carboxyl-terminal region of C53 contains the essential functional domain of the subunit and that a mutant RNA polymerase containing only this domain is thermolabile for its function in vivo and in vitro. The thermolability of the carboxyl-terminal C53 domain is suppressed by five different genes on multicopy plasmids, including RPC160, encoding the largest subunit of RNA polymerase C and SSD1/SRK1, which has been implicated in the activity of protein phosphatases.


Asunto(s)
Genes Fúngicos , Mitocondrias/enzimología , ARN Polimerasa III/genética , ARN Polimerasa III/metabolismo , Saccharomyces cerevisiae/enzimología , Saccharomyces cerevisiae/genética , Transcripción Genética , Alelos , Secuencia de Aminoácidos , Secuencia de Bases , ADN de Hongos/genética , ADN de Hongos/metabolismo , Estabilidad de Enzimas , Genes Letales , Prueba de Complementación Genética , Biblioteca Genómica , Cinética , Sustancias Macromoleculares , Datos de Secuencia Molecular , Mutagénesis , Oligodesoxirribonucleótidos , Plásmidos , Reacción en Cadena de la Polimerasa/métodos , ARN Polimerasa III/aislamiento & purificación , ARN de Transferencia/genética , ARN de Transferencia/metabolismo , Proteínas Recombinantes de Fusión/aislamiento & purificación , Proteínas Recombinantes de Fusión/metabolismo , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Mapeo Restrictivo , Factor Rho/genética , Eliminación de Secuencia
17.
Mol Cell Biol ; 12(10): 4314-26, 1992 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-1406624

RESUMEN

RPC53 is shown to be an essential gene encoding the C53 subunit specifically associated with yeast RNA polymerase C (III). Temperature-sensitive rpc53 mutants were generated and showed a rapid inhibition of tRNA synthesis after transfer to the restrictive temperature. Unexpectedly, the rpc53 mutants preferentially arrested their cell division in the G1 phase as large, round, unbudded cells. The RPC53 DNA sequence is predicted to code for a hydrophilic M(r)-46,916 protein enriched in charged amino acid residues. The carboxy-terminal 136 amino acids of C53 are significantly similar (25% identical amino acid residues) to the same region of the human BN51 protein. The BN51 cDNA was originally isolated by its ability to complement a temperature-sensitive hamster cell mutant that undergoes a G1 cell division arrest, as is true for the rpc53 mutants.


Asunto(s)
Fase G1/genética , ARN Polimerasa III/genética , Saccharomyces cerevisiae/genética , Secuencia de Aminoácidos , Secuencia de Bases , Clonación Molecular , ADN de Hongos , Citometría de Flujo , Genes Fúngicos , Cinética , Datos de Secuencia Molecular , Mutagénesis , ARN Polimerasa III/antagonistas & inhibidores , ARN Polimerasa III/metabolismo , ARN de Transferencia/biosíntesis , Mapeo Restrictivo , Saccharomyces cerevisiae/citología , Saccharomyces cerevisiae/enzimología , Homología de Secuencia , Temperatura , Transcripción Genética
18.
Mol Cell Biol ; 12(10): 4433-40, 1992 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-1406632

RESUMEN

RNA polymerase C (III) promotes the transcription of tRNA and 5S RNA genes. In Saccharomyces cerevisiae, the enzyme is composed of 15 subunits, ranging from 160 to about 10 kDa. Here we report the cloning of the gene encoding the 82-kDa subunit, RPC82. It maps as a single-copy gene on chromosome XVI. The UCR2 gene was found in the opposite orientation only 340 bp upstream of the RPC82 start codon, and the end of the SKI3 coding sequence was found only 117 bp downstream of the RPC82 stop codon. The RPC82 gene encodes a protein with a predicted M(r) of 73,984, having no strong sequence similarity to other known proteins. Disruption of the RPC82 gene was lethal. An rpc82 temperature-sensitive mutant, constructed by in vitro mutagenesis of the gene, showed a deficient rate of tRNA relative to rRNA synthesis. Of eight RNA polymerase C genes tested, only the RPC31 gene on a multicopy plasmid was capable of suppressing the rpc82(Ts) defect, suggesting an interaction between the polymerase C 82-kDa and 31-kDa subunits. A group of RNA polymerase C-specific subunits are proposed to form a substructure of the enzyme.


Asunto(s)
ARN Polimerasa III/genética , Saccharomyces cerevisiae/genética , Secuencia de Aminoácidos , Secuencia de Bases , Clonación Molecular , ADN de Hongos , Genes Fúngicos , Prueba de Complementación Genética , Cinética , Datos de Secuencia Molecular , ARN Polimerasa III/metabolismo , ARN de Hongos/biosíntesis , ARN de Transferencia/biosíntesis , Mapeo Restrictivo , Saccharomyces cerevisiae/enzimología , Saccharomyces cerevisiae/crecimiento & desarrollo , Supresión Genética , Temperatura
19.
Cancer Chemother Pharmacol ; 26(2): 122-6, 1990.
Artículo en Inglés | MEDLINE | ID: mdl-2189589

RESUMEN

In our previous studies, doxorubicin-loaded polyisohexylcyanoacrylate nanoparticles have been proven to increase dramatically the antitumoral activity of the cytotoxic agent in metastasis-bearing mice. The experimental model consisted of metastases induced by i.v. inoculation of reticulosarcoma M 5076 cell suspension to C57BL/6 mice. The improved efficacy of the drug was noted in terms of either metastasis count or survival. Therefore, tissue-distribution studies of this drug delivery system within the metastatic liver after i.v. administration were undertaken to gain more insight into the mechanism of action. Doxorubicin measurements in healthy hepatic or neoplastic tissue were carried out together with histological examinations using transmission electron microscopy. These results demonstrated the hepatic tissue to be an efficient reservoir of the drug when it was injected associated with nanoparticles. Accumulation of biodegradable nanoparticles with associated doxorubicin in Kupffer cells created a gradient of drug concentration for a massive and prolonged diffusion of the free drug towards the neoplastic tissue.


Asunto(s)
Doxorrubicina/farmacocinética , Neoplasias Hepáticas Experimentales/metabolismo , Hígado/metabolismo , Linfoma no Hodgkin/metabolismo , Animales , Cianoacrilatos , Doxorrubicina/administración & dosificación , Portadores de Fármacos , Inyecciones Intravenosas , Ratones , Ratones Endogámicos , Microquímica , Microscopía Electrónica , Trasplante de Neoplasias , Distribución Tisular
20.
Sel Cancer Ther ; 5(1): 1-11, 1989.
Artículo en Inglés | MEDLINE | ID: mdl-2756244

RESUMEN

Free doxorubicin and doxorubicin associated with polyisohexlycyanoacrylate were tested for their therapeutic efficiency in hepatic metastasis-bearing mice. The metastases originated from the M 5076 reticulum cell sarcoma. Irrespective of the dose and the administration schedule, the reduction of the number of metastases was much larger with the doxorubicin-loaded nanoparticles than with free doxorubicin. This was clearly confirmed by histological examination. Although pharmacological and pharmacokinetic data indicated a strong capture of the nanoparticles by the hepatic issue, the mechanism of nanoparticle therapeutic efficiency remains unclear.


Asunto(s)
Doxorrubicina/uso terapéutico , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Animales , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacocinética , Hígado/metabolismo , Neoplasias Hepáticas Experimentales/secundario , Ratones , Ratones Endogámicos C57BL , Microesferas , Trasplante de Neoplasias , Polímeros
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