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1.
Vet Comp Oncol ; 21(3): 541-550, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37337253

RESUMO

Enumeration of circulating tumour cells (CTC) has shown promise for prognostication and guidance of therapeutic decisions in human cancers. The objective of this study was to enumerate CTC over time in dogs with naturally occurring osteosarcoma (OSA), and to determine correlation with patient outcome. Twenty-six dogs with OSA and no evidence of metastatic disease at the time of amputation were enrolled. Dogs were assessed for lung metastases and CTC prior to and following amputation, and at each chemotherapy visit. Twenty-one dogs completed the study. Nineteen dogs were euthanized and two were alive and free of metastases. Overall survival time ranged from 88 to 1058 days (median survival time (MST) 374 days). Increased serum alkaline phosphatase activity, advanced age, and higher body weight were significantly associated with lower MST. Dogs with OSA had a mean of 356 (0 to 4443) CTC/106 leukocytes. In 12 of 15 dogs that developed radiographic evidence of metastasis, a pre-metastatic CTC spike was retrospectively detectable on average 36.5 (1-100 days) days prior to metastasis and was associated with significantly shorter MST (301 ± 64 vs. 626 ± 55 days; p = .0107). In a multivariable analysis, dogs with a CTC spike were 10× more likely to die compared with those without. These results suggest that a spike in CTC frequency precedes detection of metastasis in dogs with OSA and is associated with shorter survival. More frequent enumeration of CTC in a larger cohort of dogs with OSA may be warranted.


Assuntos
Neoplasias Ósseas , Doenças do Cão , Células Neoplásicas Circulantes , Osteossarcoma , Cães , Humanos , Animais , Estudos Retrospectivos , Neoplasias Ósseas/veterinária , Neoplasias Ósseas/tratamento farmacológico , Doenças do Cão/patologia , Osteossarcoma/tratamento farmacológico , Osteossarcoma/veterinária
2.
Cytometry A ; 95(9): 997-1007, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31282052

RESUMO

Osteosarcoma (OSA) is a malignant tumor of middle-aged dogs and adolescent humans. The clinical outcome of OSA has not improved over more than three decades, and dogs typically succumb to metastatic disease within 6 months despite tumor resection through limb amputation and adjuvant chemotherapy. Therefore, undetectable tumor cells with potential to form metastases are present at diagnosis. An assay to identify canine immortalized and primary OSA cells through flow cytometric detection of intracellular collagen 1 (Col I) and osteocalcin was optimized, and applied to blood samples from tumor-bearing dogs for detection of circulating tumor cells (CTCs). Spiking variable number of OSA cells into normal dog blood recovered 50-60% of Col I positive cells with high forward and variable side light scatter. An algorithm to exclude nonviable, doublet, and autofluorescent cells was applied to sequential blood samples from three dogs obtained prior to and after limb amputation, and at approximately, triweekly intervals over 121, 142, and 183 days of chemotherapy, respectively. Dogs had >100 CTC/106 leukocytes prior to amputation, variably frequent CTC during chemotherapy, and an increase up to 4,000 CTC/106 leukocytes within 4 weeks before overt metastases or death. Sorted CTCs were morphologically similar to direct tumor aspirates and positive for Col I. Although preliminary, findings suggest that CTCs are frequent in canine OSA, more numerous than carcinoma CTC in humans, and that an increase in CTC frequency may herald clinical deterioration. This assay may enable enumeration and isolation of OSA CTC for prognostic and functional studies, respectively. © 2019 International Society for Advancement of Cytometry.


Assuntos
Neoplasias Ósseas/veterinária , Doenças do Cão/diagnóstico por imagem , Citometria de Fluxo/métodos , Células Neoplásicas Circulantes/metabolismo , Osteossarcoma/veterinária , Amputação Cirúrgica , Animais , Neoplasias Ósseas/sangue , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/tratamento farmacológico , Linhagem Celular Tumoral , Colágeno/metabolismo , Doenças do Cão/sangue , Doenças do Cão/tratamento farmacológico , Cães , Processamento de Imagem Assistida por Computador , Leucócitos/metabolismo , Células Neoplásicas Circulantes/efeitos dos fármacos , Células Neoplásicas Circulantes/patologia , Osteocalcina/metabolismo , Osteossarcoma/sangue , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/tratamento farmacológico , Prognóstico
3.
Neuropsychopharmacology ; 42(12): 2344-2353, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28240292

RESUMO

The neurobiological mechanisms underlying social learning (ie, in which an animal's learning is influenced by another) are slowly being unraveled. Previous work with systemic treatments shows that dopamine (DA) D1-type receptors mediate social learning in the social transmission of food preferences (STFP) in mice. This study examines the involvement of one brain region underlying this effect. The ventral tegmental area has dopaminergic projections to many limbic structures, including the hippocampus-a site important for social learning in the STFP in rodents. In this study, adult male and female CD-1 mice received a dorsal hippocampal microinfusion of the D1-like receptor antagonist SCH23390 at 1, 2, 4, or 6 µg/µl 15 min before a 30 min social interaction with a same-sex conspecific, in which mice had the opportunity to learn a socially transmitted food preference. Results show that social learning was blocked in female mice microinfused with 6 µg/µl, and in males infused with 1, 4, or 6 µg/µl of SCH23390. This social learning impairment could not be explained by changes in total food intake, or olfactory discrimination. A detailed analysis of the social interactions also revealed that although SCH23390 did not affect oronasal investigation for either sex, drug treatments affected other social behaviors in a sex-specific manner; there was primarily a reduction in agonistic-related behaviors among males, and social investigatory-related behaviors among females. Thus, this study shows that dorsal hippocampal D1-type receptors mediate social learning and social behaviors in male and female mice.


Assuntos
Ingestão de Alimentos/fisiologia , Hipocampo/fisiologia , Relações Interpessoais , Receptores de Dopamina D1/fisiologia , Aprendizado Social/fisiologia , Animais , Benzazepinas/farmacologia , Antagonistas de Dopamina/farmacologia , Relação Dose-Resposta a Droga , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Hipocampo/efeitos dos fármacos , Masculino , Camundongos , Receptores de Dopamina D1/antagonistas & inibidores , Aprendizado Social/efeitos dos fármacos
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