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1.
J ISAKOS ; 6(6): 339-343, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34230066

RESUMO

Year-round intensive, single-sport training beginning at an young age is an increasingly common trend in the youth athlete population. Early sport specialisation may be ineffective for long-term athletic success and contribute to an increased risk of physical injury and burn-out. The medical community has noted that repetitive movement patterns may occur in non-diversified activity and this may contribute to overuse injury in young athletes. Studies have begun to identify an association between early sport specialisation and lower extremity injuries in the youth athlete population that is independent of training volume. Recent literature has suggested that sport diversification, not specialisation, is a better path for athletic success and minimised lower extremity injury risk.


Assuntos
Traumatismos em Atletas , Transtornos Traumáticos Cumulativos , Esportes , Adolescente , Atletas , Traumatismos em Atletas/epidemiologia , Transtornos Traumáticos Cumulativos/epidemiologia , Humanos , Incidência , Extremidade Inferior , Fatores de Risco
2.
JCO Precis Oncol ; 20182018.
Artigo em Inglês | MEDLINE | ID: mdl-30123863

RESUMO

PURPOSE: Third-generation epidermal growth factor receptor (EGFR) inhibitors like nazartinib are active against EGFR mutation-positive lung cancers with T790M-mediated acquired resistance to initial anti-EGFR treatment, but some patients have mixed responses. METHODS: Multiple serial tumor and liquid biopsies were obtained from two patients before, during, and after treatment with nazartinib. Next-generation sequencing and droplet digital polymerase chain reaction were performed to assess heterogeneity and clonal dynamics. RESULTS: We observed the simultaneous emergence of T790M-dependent and -independent clones in both patients. Serial plasma droplet digital polymerase chain reaction illustrated shifts in relative clonal abundance in response to various systemic therapies, confirming a molecular basis for the clinical mixed radiographic responses observed. CONCLUSION: Heterogeneous responses to treatment targeting a solitary resistance mechanism can be explained by coexistent tumor subclones harboring distinct genetic signatures. Serial liquid biopsies offer an opportunity to monitor clonal dynamics and the emergence of resistance and may represent a useful tool to guide therapeutic strategies.

3.
Cell Rep ; 21(11): 3298-3309, 2017 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-29241554

RESUMO

Personalized cancer therapy is based on a patient's tumor lineage, histopathology, expression analyses, and/or tumor DNA or RNA analysis. Here, we aim to develop an in vitro functional assay of a patient's living cancer cells that could complement these approaches. We present methods for developing cell cultures from tumor biopsies and identify the types of samples and culture conditions associated with higher efficiency of model establishment. Toward the application of patient-derived cell cultures for personalized care, we established an immunofluorescence-based functional assay that quantifies cancer cell responses to targeted therapy in mixed cell cultures. Assaying patient-derived lung cancer cultures with this method showed promise in modeling patient response for diagnostic use. This platform should allow for the development of co-clinical trial studies to prospectively test the value of drug profiling on tumor-biopsy-derived cultures to direct patient care.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias/tratamento farmacológico , Medicina de Precisão/métodos , Cultura Primária de Células/métodos , Acrilamidas , Aminopiridinas , Quinase do Linfoma Anaplásico , Compostos de Anilina , Biomarcadores Tumorais/metabolismo , Biópsia , Crizotinibe , Receptores ErbB/genética , Receptores ErbB/metabolismo , Cloridrato de Erlotinib/uso terapêutico , Células Alimentadoras/citologia , Imunofluorescência/métodos , Expressão Gênica , Ensaios de Triagem em Larga Escala , Humanos , Queratina-18/genética , Queratina-18/metabolismo , Queratina-8/genética , Queratina-8/metabolismo , Lactamas , Lactamas Macrocíclicas/uso terapêutico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Mutação , Neoplasias/classificação , Neoplasias/genética , Neoplasias/patologia , Piperazinas/uso terapêutico , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/metabolismo , Células Tumorais Cultivadas
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