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1.
Trends Cancer ; 8(12): 1002-1018, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35915015

RESUMO

The contributions of mitochondria to cancer have been recognized for decades. However, the focus on the metabolic role of mitochondria and the diminutive size of the mitochondrial genome compared to the nuclear genome have hindered discovery of the roles of mitochondrial genetics in cancer. This review summarizes recent data demonstrating the contributions of mitochondrial DNA (mtDNA) copy-number variants (CNVs), somatic mutations, and germline polymorphisms to cancer initiation, progression, and metastasis. The goal is to summarize accumulating data to establish a framework for exploring the contributions of mtDNA to neoplasia and metastasis.


Assuntos
Genoma Mitocondrial , Neoplasias , Humanos , DNA Mitocondrial/genética , Mitocôndrias/metabolismo , Neoplasias/patologia , Núcleo Celular/metabolismo
2.
Behav Brain Res ; 414: 113476, 2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34302878

RESUMO

Extended fear training can lead to initially low fear expression that grows over time, termed fear incubation. Conversely, a single fear conditioning session typically results in high fear initially that is sustained over time. Fear expression decreases across extended training, suggesting that a fear extinction-like process might be responsible for low fear observed soon after training. Because of the prominent role medial prefrontal cortex (mPFC) plays in fear conditioning and extinction, we decided to examine Fos expression resulting from a cued fear retrieval test to gain insight into possible mechanisms involved in extended training fear incubation. Male Long-Evans rats received 1 or 10 days of tone-shock pairings or tone-only exposure (while lever-pressing for food). Two days after the end of fear training, rats received a cued fear test, with perfusions timed to visualize Fos expression during test. As expected, the limited fear conditioning group exhibited higher fear in the test than any of the other groups (as measured with conditioned suppression of lever-pressing). Interestingly, we found that extended training animals (whether they received tone-shock pairings or tone-only exposure) expressed higher levels of Fos in both prelimbic and infralimbic cortices than limited training animals. There was no association between fear expression and mPFC Fos expression. These results suggest we may have visualized Fos expression related to operant overtraining rather than conditioned fear related processes. Further research is needed to determine the neurobiological basis of extended training fear incubation and to determine processes represented by the pattern of Fos expression we observed.


Assuntos
Condicionamento Clássico/fisiologia , Condicionamento Operante/fisiologia , Medo/fisiologia , Giro do Cíngulo/metabolismo , Córtex Pré-Frontal/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Animais , Comportamento Animal/fisiologia , Sinais (Psicologia) , Masculino , Ratos , Ratos Long-Evans
3.
Methods Mol Biol ; 1530: 13-37, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28150194

RESUMO

Targeted cancer nanotherapeutics offers numerous opportunities for the selective uptake of toxic chemotherapies within tumors and cancer cells. The unique properties of nanoparticles, such as their small size, large surface-to-volume ratios, and the ability to achieve multivalency of targeting ligands on their surface, provide superior advantages for nanoparticle-based drug delivery to a variety of cancers. This review highlights various key concepts in the design of targeted nanotherapeutics for cancer therapy, and discusses physicochemical parameters affecting nanoparticle targeting, along with recent developments for cancer-targeted nanomedicines.


Assuntos
Nanomedicina , Neoplasias/tratamento farmacológico , Antineoplásicos/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Humanos , Terapia de Alvo Molecular , Nanomedicina/métodos , Nanopartículas/química , Neoplasias/patologia , Propriedades de Superfície , Microambiente Tumoral
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