RESUMO
Simultaneous tracking of nanoparticles and encapsulated payload is of great importance and visualizing their activity is arduous. Here we use vibrational spectroscopy to study the in vitro tracking of co-localized lipid nanoparticles and encapsulated drug employing a model system derived from doxorubicin-encapsulated deuterated phospholipid (dodecyl phosphocholine-d38) single tailed phospholipid vesicles.
Assuntos
Antibióticos Antineoplásicos/química , Doxorrubicina/química , Nanopartículas/química , Fosforilcolina/análogos & derivados , Antibióticos Antineoplásicos/metabolismo , Antibióticos Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Deutério/química , Doxorrubicina/metabolismo , Doxorrubicina/farmacologia , Humanos , Células MCF-7 , Microscopia de Força Atômica , Microscopia Eletrônica de Transmissão , Fosforilcolina/química , Análise Espectral Raman , Difração de Raios XRESUMO
We report the ability of a novel combinatorial therapy obtained from nanoparticles of hyperstar polymers encompassing drugs to selectively target triple negative breast cancer (TNBC) cell proliferation through STAT3 and topoisomerase-II pathways. This nano-cocktail was at least two to four fold better than the individual drugs and 6-20 times more selective than the parent drugs.
Assuntos
Antineoplásicos/farmacologia , Nanopartículas/química , Polímeros/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , DNA Topoisomerases Tipo II/metabolismo , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Polímeros/síntese química , Polímeros/química , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/metabolismo , Relação Estrutura-Atividade , Neoplasias de Mama Triplo Negativas/metabolismoRESUMO
Two dogs, a 14-year-old, female American Eskimo dog and a 14-year-old, male Maltese dog, were presented with thalamic syndromes, including lowered levels of consciousness, poor postural responses and presence of masses in the neck region. In both dogs, magnetic resonance imaging revealed multiple masses inside the cranium, including the pituitary gland. One dog died from status epilepticus two days after magnetic resonance imaging and the other died two months after magnetic resonance imaging from respiratory failure. These dogs were histopathologically diagnosed with multiple metastases of thyroid cancer occurring inside the cranium, including the pituitary gland. To the authors' knowledge, this is the first time this tumour pattern has been reported in dogs, but it is possible that it is not uncommon.
Assuntos
Neoplasias Encefálicas/veterinária , Doenças do Cão/diagnóstico , Neoplasias Hipofisárias/veterinária , Neoplasias da Glândula Tireoide/veterinária , Animais , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/secundário , Doenças do Cão/patologia , Cães , Evolução Fatal , Feminino , Masculino , Metástase Neoplásica , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/secundário , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologiaRESUMO
Spontaneously hyperlipidemic (SHL) mice are Japanese wild mice (KOR) with disruption of the apolipoprotein E (Apo E) gene. These mice (KOR-Apoe(shl)) are superhypercholesterolemic and develop severe xanthoma, but their atherosclerosis is relatively mild compared with Apo E knockout mice. First, we tested whether this distinction is due to additional mutation of the Apoc1 and/or Apoc2 genes in KOR-Apoe(shl). Southern blot analysis, but found no gross disruption of these genes. Next, we tested whether the phenotypic distinction is due to differences in the genetic background. To this end, we established three lines of congenic SHL mice with a genetic background of C57BL/6, BALB/c or C3H/He, and named them, respectively, C57BL/6.KOR-Apoe(shl) (B6.KOR-Apoe(shl)), BALB/c.KOR-Apoe(shl) (C.KOR-Apoe(shl)) and C3H/He.KOR-Apoe(shl) (C3.KOR-Apoe(shl)). Hypercholesterolemia was most severe in KOR-Apoe(shl) followed the by others as follows; KOR-Apoe(shl)>>C3.KOR-Apoe(shl)>C.KOR-Apoe(shl)>B6.KOR-Apoe(shl). In contrast, atherosclerosis was most severe in B6.KOR Apoe(shl) followed by the others: B6.KOR-Apoe(shl)>C.KOR-Apoe(shl)>>C3.KOR-Apoe(shl)> or =KOR-Apoe(shl). This order, however, did not match that in xanthoma, which was highly prominent in KOR-Apoe(shl) but mild in B6.KOR-Apoe(shl), C.KOR-Apoe(shl) and C3.KORApoe(shl). This order, however, did not match that in xanthoma, which was highly prominant in KOR-Apoe(shl) but mild in B6.KOR-Apoe(shl), C.KOR-Apoe(shl) and C3.KOR-Apoe(shl). These distinctions suggest that the severity of each of the phenotypes is determined by distinct genetic backgrounds which probably are composed of polymorphism of lipid metabolism-related proteins. We found that apolipoprotein A-I is decreased in each SHL strain and polymorphic between B6.KOR-Apoe(shl) and the other strains examined. This polymorphism may be related to the most severe atherosclerosis observed in B6.KOR-Apoe(shl). It is most likely that combination of such polymorphisms is due to the genetic background accountable for phenotype distinctions.