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1.
Rev Sci Instrum ; 88(10): 105113, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29092479

RESUMO

We measure the shock drive capabilities of a 30 J, nanosecond, 527 nm laser system at the matter in extreme conditions hutch of the Linac Coherent Light Source. Using a velocity interferometer system for any reflector, we ascertain the maximum instantaneous ablation pressure and characterize its dependence on a drive laser spot size, spatial profile, and temporal profile. We also examine the effects of these parameters on shock spatial and temporal uniformity. Our analysis shows the drive laser capable of generating instantaneous ablation pressures exceeding 160 GPa while maintaining a 1D shock profile. We find that slope pulses provide higher instantaneous ablation pressures than plateau pulses. Our results show instantaneous ablation pressures comparable to those measured at the Omega Laser Facility in Rochester, NY under similar optical drive parameters. Finally, we analyze how optical laser ablation pressures are compare with known scaling relations, accounting for variable laser wavelengths.

2.
Cell Rep ; 18(3): 601-610, 2017 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-28099841

RESUMO

Cancer cells exhibit increased use of nutrients, including glucose and glutamine, to support the bioenergetic and biosynthetic demands of proliferation. We tested the small-molecule inhibitor of glutaminase CB-839 in combination with erlotinib on epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) as a therapeutic strategy to simultaneously impair cancer glucose and glutamine utilization and thereby suppress tumor growth. Here, we show that CB-839 cooperates with erlotinib to drive energetic stress and activate the AMP-activated protein kinase (AMPK) pathway in EGFR (del19) lung tumors. Tumor cells undergo metabolic crisis and cell death, resulting in rapid tumor regression in vivo in mouse NSCLC xenografts. Consistently, positron emission tomography (PET) imaging with 18F-fluoro-2-deoxyglucose (18F-FDG) and 11C-glutamine (11C-Gln) of xenografts indicated reduced glucose and glutamine uptake in tumors following treatment with CB-839 + erlotinib. Therefore, PET imaging with 18F-FDG and 11C-Gln tracers can be used to non-invasively measure metabolic response to CB-839 and erlotinib combination therapy.


Assuntos
Apoptose/efeitos dos fármacos , Benzenoacetamidas/toxicidade , Receptores ErbB/antagonistas & inibidores , Cloridrato de Erlotinib/toxicidade , Glutaminase/antagonistas & inibidores , Tiadiazóis/toxicidade , Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Autofagia/efeitos dos fármacos , Benzenoacetamidas/uso terapêutico , Radioisótopos de Carbono/química , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Receptores ErbB/genética , Receptores ErbB/metabolismo , Cloridrato de Erlotinib/uso terapêutico , Fluordesoxiglucose F18/química , Glutaminase/metabolismo , Glutamina/química , Glutamina/metabolismo , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Camundongos , Camundongos SCID , Mutação , Interferência de RNA , Compostos Radiofarmacêuticos/química , Tiadiazóis/uso terapêutico , Transplante Heterólogo
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