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Aim: To evaluate a liposome complex conjugated with anti-epidermal growth factor receptor (EGFR) antibodies for the treatment of pre-eclampsia (PE).Methods: In in vitro experiments, the transfection rate, silencing effect and cytotoxicity were determined. In the in vivo PE model, the siRNA distribution, mean arterial pressure, 24-h urine protein concentration, serum sFlt1 concentration, number of viable fetuses and placental weight were measured.Results: The nanomedicine effectively reduced the expression of sFIt1 and had a strong ability to target placental tissues. It could significantly reduce the symptoms of pre-eclampsia and improve pregnancy outcomes in PE model rats.Conclusion: The constructed nanomedicine can improve pregnancy outcomes in a rat model of pre-eclampsia and provides a new strategy for the treatment of pre-eclampsia.
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Assuntos
Inativação Gênica , Lipossomos , Pré-Eclâmpsia , RNA Interferente Pequeno , Receptor 1 de Fatores de Crescimento do Endotélio Vascular , Pré-Eclâmpsia/genética , Gravidez , Feminino , Animais , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , RNA Interferente Pequeno/genética , Ratos , Humanos , Lipossomos/química , Resultado da Gravidez , Placenta/metabolismo , Ratos Sprague-Dawley , Receptores ErbB/genética , Receptores ErbB/metabolismo , Modelos Animais de DoençasRESUMO
Introduction: The toxic side effects of systemic high-dose chemotherapy and poor sensitivity to radiotherapy hinder the survival rate of patients with osteosarcoma (OS). Nanotechnology offers new solutions for OS treatment; however, conventional nanocarriers suffer from inadequate targeting of tumors and short in vivo circulation time. Methods: Here, we designed a novel drug delivery system, [Dbait-ADM@ZIF-8]OPM, which uses OS-platelet hybrid membranes to encapsulate nanocarriers, to enhance the targeting and circulation time of nanocarriers, thereby enabling high enrichment of the nanocarriers in OS sites. Results: In the tumor microenvironment, the pH-sensitive nanocarrier, which is the metal-organic framework ZIF-8, dissociates to release radiosensitizer Dbait and the classical chemotherapeutic agent Adriamycin for the integrated treatment of OS via radiotherapy and chemotherapy. Benefiting from the excellent targeting ability of the hybrid membrane and the outstanding drug loading capacity of the nanocarrier, [Dbait-ADM@ZIF-8]OPM showed potent anti-tumor effects in tumor-bearing mice with almost no significant biotoxicity. Conclusion: Overall, this project is a successful exploration of the combination of radiotherapy and chemotherapy of OS treatment. Our findings solve the problems of the insensitivity of OS to radiotherapy and the toxic side effects of chemotherapy. Furthermore, this study is an expansion of the research of OS nanocarriers and provides new potential treatments for OS.
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Extrapulmonary small cell carcinoma (EPSCC) affecting the external auditory canal (EAC) is uncommon. We herein report a case involving a 56-year-old man with EPSCC of the EAC who had a 48-year history of recurrent purulent discharge in both ears and a 20-day history of right ear pain and hemorrhage followed by incomplete right eyelid closure and an askew mouth. He underwent surgical removal of middle ear granulation tissue, residual ossicles, and a right EAC mass. Postoperatively, pathomorphological examination combined with immunohistochemical staining supported a diagnosis of small cell carcinoma. Radiation therapy at a dose of 60.06 Gy in 33 daily fractions was completed 1 month after surgery, and synchronous etoposide-cisplatin regimen chemotherapy was performed for two cycles and four sequential cycles. One year postoperatively, magnetic resonance imaging showed no tumor in the ear; however, computed tomography showed multiple liver space-occupying lesions that were considered to indicate liver metastasis. Further chemotherapy was performed, but the patient died 15 months postoperatively. This case indicates that timely and accurate chemoradiotherapy is likely the most reasonable approach to EPSCC of the EAC given the aggressiveness of this tumor.