RESUMEN
PURPOSE: Left ventricular non-compaction (LVNC) is considered rare; however, the use of cardiac magnetic resonance (CMR) has shown that its incidence is not uncommon, and its clinical presentation remains variable, with an uncertain prognosis. Risk stratification of major adverse cardiac events (MACE) in patients with LVNC remains complex. Therefore, this study aims to determine whether tissue heterogeneity from late gadolinium enhancement-derived entropy is associated with MACE in patients with LVNC. METHODS: This study was registered in the Clinical Trial Registry (CTR2200062045). Consecutive patients who underwent CMR imaging and were diagnosed with LVNC were followed up for MACE, which was defined by heart failure, arrhythmias, systemic embolism, and cardiac death. The patients were divided into MACE and non-MACE groups. The CMR parameters included left ventricular (LV) entropy, LV ejection fraction (LVEF), LV end-diastolic volume, LV end-systolic volume (LVESV), and LV mass (LVM). RESULTS: Eighty-six patients (age: 45.48 ± 16.64 years; female: 62.7%; LVEF: 42.58 ± 17.20%) were followed up for a median of 18 months and experienced 30 MACE events (34.9%). The MACE group showed higher LV entropy, LVESV, and LVM and lower LVEF than the non-MACE group. LV entropy [hazard ratio (HR): 1.710, 95% confidence interval (CI): 1.078-2.714, P = 0.023] and LVEF (HR: 0.961, 95% CI: 0.936-0.988, P = 0.004) were independent predictors of MACE (P <0.050) according to the Cox regression analysis. Receiver operating characteristic curve analysis revealed that the area under the curve of LV entropy was 0.789 (95% CI: 0.687-0.869, P < 0.001), LVEF was 0.804 (95% CI: 0.699-0.878, P < 0.001), and the combined model of LV entropy and LVEF was 0.845 (95% CI: 0.751-0.914, P < 0.050). CONCLUSION: LGE-derived LV entropy and LVEF are independent risk indicators of MACE in patients with LVNC. The combination of the two factors was more conducive to improving the prediction of MACE.
Asunto(s)
Medios de Contraste , Gadolinio , Adulto , Femenino , Humanos , Persona de Mediana Edad , Entropía , Imagen por Resonancia Cinemagnética/métodos , Espectroscopía de Resonancia Magnética , Valor Predictivo de las Pruebas , Pronóstico , Volumen Sistólico , MasculinoRESUMEN
BACKGROUND: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females worldwide. Among various types of breast cancer, the human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer is known to be more aggressive and often resistant to medicinal treatment, leading to an insufficient prognosis and poor susceptibility to chemotherapy and/or hormonal therapy in the current clinic. These circumstances implicate that developing an improved therapeutic strategy rather than persistently changing the anticancer drugs for trying is truly needed to successfully cure this type of breast cancer. In this study, we aimed to fabricate anti-HER2 indocyanine green (ICG)-doxorubicin (DOX)-loaded polyethyleneimine-coated perfluorocarbon double nanoemulsions (HIDPPDNEs) to explore the co-administration of phototherapy and chemotherapy for HER2-overexpressing breast cancer in vitro. RESULTS: The HIDPPDNE was first characterized as a sphere-like nanoparticle with surface charge of -57.1 ± 5.6 mV and size of 340.6 ± 4.5 nm, whereas the DOX release rates for the nanodroplets within 48 h in 4 and 37 °C were obtained by 8.13 ± 2.46% and 19.88 ± 2.75%, respectively. We then examined the target-ability of the nanostructure and found that the adhesion efficiency of the HIDPPDNEs onto HER2+ MDA-MB-453 cells was threefold higher than the nanodroplets without anti-HER2 antibody, indicating that the HIDPPDNEs are the product with HER2 binding specificity. In comparison to freely dissolved ICG, the HIDPPDNEs conferred an enhanced thermal stability to the entrapped ICG, and were able to provide a comparable hyperthermia effect and markedly increased production of singlet oxygen under near infrared irradiation (808 nm; 6 W/cm2). Based on the viability analyses, the results showed that the HIDPPDNEs were effective on cell eradication upon near infrared irradiation (808 nm; 6 W/cm2), and the resulting cell mortality was even higher than that caused by using twice amount of encapsulated DOX or ICG alone. CONCLUSIONS: This work demonstrates that the HIDPPDNEs are able to provide improved ICG stability, binding specificity, and enhanced anticancer efficacy as compared to equal dosage of free ICG and/or DOX, showing a high potential for use in HER2 breast cancer therapy with reduced chemotoxicity.
Asunto(s)
Antibióticos Antineoplásicos/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Doxorrubicina/administración & dosificación , Fluorocarburos/química , Inmunoconjugados/química , Verde de Indocianina/administración & dosificación , Polietileneimina/química , Receptor ErbB-2/metabolismo , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/farmacología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Doxorrubicina/farmacocinética , Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos , Femenino , Humanos , Hipertermia Inducida/métodos , Verde de Indocianina/farmacocinética , Verde de Indocianina/farmacología , Fotoquimioterapia/métodos , Poloxámero/análogos & derivados , Oxígeno Singlete/metabolismoRESUMEN
A new approach is presented to control cell attachment behavior on biocompatible substrates. Multiple layers of polylactic acid (PLA) were inkjet-printed on dry alginate films to create composite surfaces with rigidity variation. The printed films were submerged in cell culture medium and fibroblast 3T3-L1 cells were cultured on the printed films. 3T3-L1 cells were found to preferentially adhere on PLA surfaces with higher rigidity. The same approach was also used to create various cell attachment patterns. This study provides a new methodology to fabricate biodegradable matrix for favorable cell adhesion or patterning.