RESUMO
Fractures of the cervical spine can cause devastating long-term effects on patients. Spinal cord injuries can occur in up to 50% of cases in association with cervical spine fractures. Therefore, it is vital and of utmost importance to recognize cervical spine injuries early on to avoid the exacerbation of an existing injury and its detrimental effects on the patients. We report a case of a C6-C7 fracture dislocation with an associated neurological insult that improved dramatically following fixation and rehabilitation. Unfortunately, patients with this presentation may have long-term neurological insults rather than regain normal function; however, our case notes the importance of prompt intervention and its effect on the outcome.
RESUMO
Metastasized cancer cells have an increased resistance to therapies leading to a drastic decrease in patient survival rates. However, our understanding of the cause for this enhanced resistance is lacking. In this study, we report that physically tight confinement during cancer cell migration triggers therapeutic resistance and induces cancer stem cell-like behavior including up-regulation in efflux proteins and in cancer stem cell related markers. Moreover, the re-localization of Yes-associated protein (YAP) to the cell nucleus indicated an elevated level of cytoskeletal tension. The increased cytoskeletal tension suggested that mechanical interactions between cancer cells and tight surroundings during metastasis is one of the factors that contributes to therapeutic resistance and acquisition of cancer stem cell (CSC) like features. With this system and supporting data, we are able to study cells with therapeutic resistance and CSC-like properties for the future purpose of developing new strategies for the treatment of metastatic cancer.
Assuntos
Proteínas de Ciclo Celular/genética , Movimento Celular/genética , Glioblastoma/genética , Células-Tronco Neoplásicas/metabolismo , Fatores de Transcrição/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Resistencia a Medicamentos Antineoplásicos/genética , Glioblastoma/patologia , Humanos , Células-Tronco Neoplásicas/patologiaRESUMO
High-throughput screening (HTS) is a well-established approach for tumor-specific drug development because of its high efficiency and customizable selection of antineoplastic drugs. However, there is still a lack of an appropriate cell-based HTS specific for migratory cancer cells. In the study presented here, we created a novel assay (mHTS): a single-cell-level screening method targeting migratory cancer cells and can be applied in a high-throughput manner. This mHTS platform is based on microchannel devices (providing physical confinement during cell migration and limit migrating cells' proliferation rate) assembled 96-well plate (fitting to HTS manner). To determine the feasibility of this assay, we quantified the anti-migratory and anti-viability effects of several molecules (Cytochalasin D, Doxorubicin and AZD-6244) on migrating (creeping inside microchannel) glioblastoma multiforme (GBM) cells. After analyzing migration screening data that was collected on a single-cell-level, we were able to compare those drug's effects on cancer cells' migration velocity and uncovered the migration inhibiting potential of AZD (500 nM and 1000 nM). Viability data based on single-cell-level screening also allowed us to further understand the same drug's different lethality toward migrating and normal 2D cultured cancer cells. The Pre-classification of subpopulations enables us to study the heterogeneity of cancer and ensures our method's feasibility for a high-throughput manner. All these results proved our mHTS platform is suitable for single-cell-level anti-migration drug screening and has potential feasibility in promoting the development of anti-migratory-cancer-drug in a high-throughput manner.