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2.
Oncotarget ; 8(31): 50489-50499, 2017 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-28881577

RESUMEN

Recent literature suggests that most widely used ovarian cancer (OVCA) cell models do not recapitulate the molecular features of clinical tumors. To address this limitation, we generated 18 cell lines and 3 corresponding patient-derived xenografts predominantly from high-grade serous carcinoma (HGSOC) peritoneal effusions. Comprehensive genomic characterization and comparison of each model to its parental tumor demonstrated a high degree of molecular similarity. Our characterization included whole exome-sequencing and copy number profiling for cell lines, xenografts, and matched non-malignant tissues, and DNA methylation, gene expression, and spectral karyotyping for a subset of specimens. Compared to the Cancer Genome Atlas (TCGA), our models more closely resembled HGSOC than any other tumor type, justifying their validity as OVCA models. Our meticulously characterized models provide a crucial resource for the OVCA research community that will advance translational findings and ultimately lead to clinical applications.

3.
Sci Data ; 4: 170033, 2017 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-28350380

RESUMEN

Neuroblastoma cell lines are an important and cost-effective model used to study oncogenic drivers of the disease. While many of these cell lines have been previously characterized with SNP, methylation, and/or mRNA expression microarrays, there has not been an effort to comprehensively sequence these cell lines. Here, we present raw whole transcriptome data generated by RNA sequencing of 39 commonly-used neuroblastoma cell lines. These data can be used to perform differential expression analysis based on a genetic aberration or phenotype in neuroblastoma (e.g., MYCN amplification status, ALK mutation status, chromosome arm 1p, 11q and/or 17q status, sensitivity to pharmacologic perturbation). Additionally, we designed this experiment to enable structural variant and/or long-noncoding RNA analysis across these cell lines. Finally, as more DNase/ATAC and histone/transcription factor ChIP sequencing is performed in these cell lines, our RNA-Seq data will be an important complement to inform transcriptional targets as well as regulatory (enhancer or repressor) elements in neuroblastoma.


Asunto(s)
Línea Celular Tumoral , Perfilación de la Expresión Génica , Neuroblastoma/genética , Humanos , Mutación
4.
Addict Biol ; 19(1): 87-101, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23710649

RESUMEN

Cocaine addiction is a chronic, relapsing disease characterized by an inability to regulate drug-seeking behavior. Here we investigated the role of mGluR5 in the ventral and dorsal striatum in regulating cocaine-seeking following both abstinence and extinction. Animals underwent 2 weeks of cocaine self-administration followed by 3 weeks of home-cage abstinence. Animals were then reintroduced to the operant chamber for a context-induced relapse test, followed by 7-10 days of extinction training. Once responding was extinguished, cue-primed reinstatement test was conducted. Both drug-seeking tests were conducted in the presence of either mGluR5 negative allosteric modulator, MTEP or vehicle infused into either the nucleus accumbens (NA) core or dorsolateral striatum (dSTR). We found that MTEP infused in the NA core attenuated both context-induced relapse following abstinence and cue-primed reinstatement following extinction training. Blocking dSTR mGluR5 had no effect on context- or cue-induced cocaine-seeking. However, the intra-dSTR MTEP infusion on the context-induced relapse test day attenuated extinction learning for 4 days after the infusion. Furthermore, mGluR5 surface expression was reduced and LTD was absent in dSTR slices of animals undergoing 3 weeks of abstinence from cocaine but not sucrose self-administration. LTD was restored by bath application of VU-29, a positive allosteric modulator of mGluR5. Bath application of MTEP prevented the induction of LTD in dSTR slices from sucrose animals. Taken together, this data indicates that dSTR mGluR5 plays an essential role in extinction learning but not cocaine relapse, while NA core mGluR5 modulates drug-seeking following both extinction and abstinence from cocaine self-administration.


Asunto(s)
Ganglios Basales/metabolismo , Trastornos Relacionados con Cocaína/metabolismo , Comportamiento de Búsqueda de Drogas/efectos de los fármacos , Depresión Sináptica a Largo Plazo/efectos de los fármacos , Piridinas/farmacología , Receptor del Glutamato Metabotropico 5/fisiología , Tiazoles/farmacología , Regulación Alostérica , Análisis de Varianza , Animales , Ganglios Basales/efectos de los fármacos , Ganglios Basales/fisiopatología , Biotinilación , Western Blotting , Cocaína/administración & dosificación , Trastornos Relacionados con Cocaína/fisiopatología , Señales (Psicología) , Modelos Animales de Enfermedad , Inhibidores de Captación de Dopamina/administración & dosificación , Comportamiento de Búsqueda de Drogas/fisiología , Fenómenos Electrofisiológicos , Extinción Psicológica/efectos de los fármacos , Extinción Psicológica/fisiología , Infusiones Intravenosas , Locomoción/efectos de los fármacos , Masculino , Microinyecciones , Piridinas/administración & dosificación , Ratas , Receptor del Glutamato Metabotropico 5/antagonistas & inhibidores , Recurrencia , Autoadministración , Sacarosa/administración & dosificación , Tiazoles/administración & dosificación
5.
Expert Opin Pharmacother ; 9(5): 717-30, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18345950

RESUMEN

BACKGROUND: Skin and skin structure infections are frequently encountered in clinical practice. Fortunately, these infections usually produce only mild to moderate symptoms and signs. Some, however, are severe and may even be life-threatening. OBJECTIVE: To review the approach to the evaluation and treatment of patients with complicated skin and skin structure infections and to discuss when to consider using either established antibiotics or recently licensed agents for treating these infections. METHODS: In addition to a non-systematic literature review of complicated skin and skin structure infections and necrotizing fasciitis, we identified recent articles examining the microbiology and describing recently licensed antibiotics for treating these infections. RESULTS/CONCLUSIONS: Clinicians must learn to recognize the early symptoms and signs of severe skin and skin structure infections to ensure they select appropriate empiric antibiotic therapy and, when needed, obtain prompt surgical consultation. While the recent approvals of new agents for treating these infections are welcome, particularly in light of the continued emergence of antibiotic-resistant bacteria, traditional antibiotic regimens remain appropriate for most cases.


Asunto(s)
Antibacterianos/uso terapéutico , Enfermedades Cutáneas Bacterianas/terapia , Infecciones de los Tejidos Blandos/terapia , Bacterias/efectos de los fármacos , Farmacorresistencia Bacteriana , Fascitis Necrotizante/diagnóstico , Fascitis Necrotizante/microbiología , Fascitis Necrotizante/fisiopatología , Fascitis Necrotizante/terapia , Humanos , Índice de Severidad de la Enfermedad , Enfermedades Cutáneas Bacterianas/diagnóstico , Enfermedades Cutáneas Bacterianas/microbiología , Enfermedades Cutáneas Bacterianas/fisiopatología , Infecciones de los Tejidos Blandos/diagnóstico , Infecciones de los Tejidos Blandos/microbiología , Infecciones de los Tejidos Blandos/fisiopatología
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