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1.
Biomed Pharmacother ; 125: 109962, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32106373

RESUMO

Chemoresistance is still a major obstacle for lung cancer treatment. Increasing studies have demonstrated that microRNAs (miRNAs) are essential meditators of chemoresistance during cancer progression. MiR-451a is reported to be a tumor suppressor during cancer development. However, its effects on lung cancer and drug resistance in lung cancer are still unclear. In the study, the results showed that miR-451a exhibited a significant role in suppressing the drug resistance in lung cancer cells when treated with doxorubicin (DOX) through alleviating epithelialmesenchymal transition (EMT), as evidenced by the markedly reduced expression of N-cadherin and Vimentin, while the enhanced expression of E-cadherin. In addition, miR-451a over-expression markedly promoted the sensitivity of lung cancer cells to DOX treatments, and also disrupted the EMT of lung cancer cells. Mechanistically, miR-451a was found to directly target c-Myc to affect the EMT and drug resistance in lung cancer cells in response to DOX incubation. Furthermore, c-Myc knockdown markedly elevated the sensitivity of lung cancer cells to DOX, whereas over-expressing c-Myc markedly reversed the anti-tumor role of DOX, which was slightly diminished by miR-451a mimic. The in vivo experiments confirmed that miR-451a promoted the sensitivity of lung cancer cells-derived tumors to DOX treatment by reducing c-Myc. Therefore, our results revealed a new insight into DOX resistance of lung cancer cells and miR-451a could be considered as a potential therapeutic target to overcome drug resistance in lung cancer.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , MicroRNAs/metabolismo , Fatores de Transcrição/metabolismo , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Camundongos Nus , MicroRNAs/genética , Neoplasias Experimentais/tratamento farmacológico , Fatores de Transcrição/genética
2.
Chinese Medical Journal ; (24): 2002-2007, 2009.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-240757

RESUMO

<p><b>BACKGROUND</b>Real-time perfusion imaging (RTPI) using ultrasound contrast agents has shown good "accuracy" in detecting myocardial infarction, however its accuracy in the assessment of peri-infarct ischemia and stress echocardiography are not known. The aim of this study was to determine the accuracy of RTPI in assessment of peri-infarct ischemia during dobutamine and adenosine stress.</p><p><b>METHODS</b>We employed the RTPI modality (Agilent and ATL Philips) in a canine model (18 dogs) of distal coronary occlusion and proximal coronary stenosis. Using coronary flow probe recordings, the physiologic significance of proximal coronary stenosis was established by confirming abolition of the coronary reserve. The contrast agent Optison was given as a slow bolus injection at baseline, during prolonged distal coronary occlusion, during adenosine bolus stress and during dobutamine stress. Triphenyltetrazolium chloride (TTC) staining was used to verify a distal infarction. RTPI recordings at baseline, the distal coronary occlusion and stress protocols were randomly mixed and reviewed blindly.</p><p><b>RESULTS</b>In all but one dog, RTPI detected a distal infarct as small as 9% of the left ventricle. The sensitivity, specificity and overall diagnostic accuracy of RTPI in the detection of distal infarcts were: 94%, 89% and 92%, respectively. The sensitivity, specificity, and overall diagnostic accuracy of RTPI in the assessment of peri-infarction ischemia were 83%, 92% and 88% for adenosine stress and 95%, 86% and 91% for dobutamine stress, respectively.</p><p><b>CONCLUSIONS</b>Even small distal infarcts can be detected by RTPI; peri-infarct ischemia can be accurately recognized by RTPI during stress; adenosine and dobutamine stress appear equally reliable in the RTPI evaluation of peri-infarct ischemia.</p>


Assuntos
Animais , Cães , Feminino , Masculino , Adenosina , Toxicidade , Circulação Coronária , Dobutamina , Toxicidade , Ecocardiografia , Métodos , Hemodinâmica , Infarto do Miocárdio , Diagnóstico por Imagem
3.
Chinese Medical Journal ; (24): 179-184, 2006.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-282785

RESUMO

<p><b>BACKGROUND</b>Innovative advancements in ultrasound instrumentation present a number of imaging modalities for myocardial contrast echocardiography (MCE) in ischemic syndromes. How well they compare to each other in diagnostic accuracy in the detection of acute myocardial infarction is unclear. The purpose of this study was to assess the relative accuracy of 3 different imaging modes of MCE, low mechanical index (MI) real-time perfusion imaging (RTPI), triggered harmonic angio mode (HA), and ultraharmonic imaging mode (UH) in the detection of acute experimental myocardial infarction within the time frame suitable for potential reperfusion.</p><p><b>METHODS</b>MCE was performed in 10 open-chest dogs using RTPI, triggered HA and triggered UH modes at baseline and one hour after occlusion of left anterior descending coronary artery. Presence or absence of perfusion defects, and the perfusion defect size when present, were analyzed and compared with the infarct size delineated by triphenyltetrazolium chloride (TTC) staining.</p><p><b>RESULTS</b>The infarct area was (15.8 +/- 2.4)% by TTC staining; Perfusion defect area by MCE was similar to anatomic infarct area in all the three MCE approaches: (16.1 +/- 2.7)% by RTPI mode, (15.5 +/- 2.9)% by HA mode, and (15.5 +/- 3.0)% by UH mode. The sensitivity, specificity and overall diagnostic accuracy in the detection of myocardial infarction were 100%, 88%, and 94% for RTPI mode, 88%, 100%, and 94% for HA mode, and 100%, 75%, and 88% for UH mode.</p><p><b>CONCLUSION</b>All modes of MCE, RTPI, triggered HA mode and triggered UH mode have excellent diagnostic accuracy in the immediate hour of acute coronary occlusion within the optimal time frame suitable for reperfusion therapy.</p>


Assuntos
Animais , Cães , Meios de Contraste , Ecocardiografia , Métodos , Infarto do Miocárdio , Diagnóstico por Imagem , Coloração e Rotulagem , Sais de Tetrazólio
4.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-675950

RESUMO

Objective To investigate the influence of anti-depression therapy on cardiac function and short-term prognosis in elderly patients with congestive heart failure (CHF) and the safety and effectiveness of fluoxetine in these patients.Methods Ninety six elderly hospitalized patients with CHF accompanied with depressive disorder were randomly divided into two groups:fluoxetine (20mg once daily)and placebo treated groups based on the routine cardiac drug therapy for 3 months. Results The prevalence rate of depressive disorder in elderly patients with CHF was 31.1%.The length of stay of fluoxetine group was shorter than that of placebo group.The post-treatment depressive exponents of self-rating depression scale(SDS)in fluoxetine group (51.39%?8.63)was lower than those in pretreatment and in placebo group.The improvement of cardiac function in fluoxetine group(53.4%?4.5%) was much better than that of placebo group (P

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