ORCID Profile
0000-0001-6934-298X
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Publisher: Wiley
Date: 02-12-2019
DOI: 10.1002/JCB.28196
Abstract: Considering the complex nature of gastrointestinal cancer, different methods including surgery, radiotherapy, and chemotherapy are considered for the treatment. Novel strategies including silencing of oncogenes using safe delivery systems could be considered as a novel approach in colorectal cancer treatment. The aim of this study was to investigate the silencing effect of high mobility group A2 (HMGA2) small interfering RNA (siRNA)-loaded nanoliposomes on gastrointestinal cancers. The siRNA-lipoplexes were prepared using dioleoyl trimethylammonium propane (DOTAP)/cholesterol (Chol)/1, 2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) through the freeze-drying of a monophase solution method. The size, polydispersity index (PDI), and zeta-potential of nanoliposomes were determined using Zetasizer analyzer. The morphology of the nanoliposomes was determined by transmission electron microscopy (TEM). The agarose gel-retardation assay was carried out to confirm the loading of siRNAs into liposome. The silencing of the HMGA2 in cancer cells was evaluated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The effect of liposomes on cell cytotoxicity was studied by MTT assay. The inhibitory effect of siRNA-loaded liposomes was evaluated by a wound-healing assay. The apoptosis induction was investigated via the annexin V ropidium iodide assay. The size, PDI, and zeta-potential of the prepared liposomes were found to be 350 nm, 0.67, and 86.3 mV, respectively. They were spherical in shape and could efficiently associate with siRNA. The results of gene silencing showed that the optimum condition of HMGA2 silencing was 80 pmol HMGA2 and 24 hours after treatment in each cancer cell lines. MTT assays indicated that silencing of HMGA2 in optimal condition could reduce the viability of the cancer cells more than 60% in the three cell lines. The result of the apoptosis assay showed more than 50% of the cell deaths related to the apoptosis in all three cell lines. The gene expression evaluation confirmed that apoptosis was induced via the intrinsic pathway inducing both caspase-3 and -9 expressions. Also, the reduction in Bcl2 expression confirmed the activation apoptosis pathway in the treated cancer cells. The wound-healing assay showed the suppression of cancer cell migration after treatment with the prepared nanoliposomes. The results of this study showed the HMGA2 siRNA-loaded nanoliposomes could be effective in the treatment of gastrointestinal cancers.
Publisher: Springer Science and Business Media LLC
Date: 28-07-2021
DOI: 10.1007/S13346-021-01034-0
Abstract: We aimed to develop a simple yet novel method to prepare plasmid DNA-loaded nanoliposomes for cancer gene therapy. Murine interleukin-12 (mIL-12) pDNA-loaded nanoliposomes were prepared via novel freeze-drying of a monophase solution method. The physicochemical characteristics, cytotoxicity, and transfection efficiency of the prepared nanoliposomes in murine CT-26 colon carcinoma cells were evaluated. Furthermore, tumor progression and survival rate in CT-26 colon carcinoma-bearing BALB/c mice subsequent to direct intratumoral injections were investigated over a period of 40 days. Using this preparation method, nanoliposomes with particle size of around 300 nm and zeta potential of 96.5 mV were obtained. The transmission electron microscope results showed that the liposomes were nano-sized and almost spherical. The agarose gel retardation assay revealed the pDNA encapsulation in the nanoliposomes. The nanoliposomes with 72.4% encapsulation efficiency and low cell toxicity could significantly improve mIL-12 expression by approximately 25-fold relative to the naked mIL-12 pDNA. There was a significant tumor growth inhibition after repeated injections of mIL-12 pDNA-loaded nanoliposomes. This is the first study on the freeze-drying of a monophase solution method as a simple yet novel technique for the preparation of pDNA-loaded nanoliposomes. Given the ease of preparation method and promising in vitro and in vivo characteristics, this investigation demonstrates advances in pDNA lipid formulation for cancer gene therapy.
Publisher: Springer Science and Business Media LLC
Date: 30-01-2022
Publisher: JMIR Publications Inc.
Date: 22-01-2023
Abstract: ral anticoagulation is the cornerstone treatment of several diseases. Its management is often challenging, and different telemedicine strategies have been implemented to support it. he aim of the study is to systematically review the evidence on the impact of telemedicine-based oral anticoagulation management compared to usual care on thromboembolic and bleeding events. andomized controlled trials were searched in 5 databases from inception to September 2021. Two independent reviewers performed study selection and data extraction. Total thromboembolic events, major bleeding, mortality, and time in therapeutic range were assessed. Results were pooled using random effect models. n total, 25 randomized controlled trials were included (n=25,746 patients) and classified as moderate to high risk of bias by the Cochrane tool. Telemedicine resulted in lower rates of thromboembolic events, though not statistically significant (n=13 studies, relative risk [RR] 0.75, 95% CI 0.53-1.07 i I /i sup /sup =42%), comparable rates of major bleeding (n=11 studies, RR 0.94, 95% CI 0.82-1.07 i I /i sup /sup =0%) and mortality (n=12 studies, RR 0.96, 95% CI 0.78-1.20 i I /i sup /sup =11%), and an improved time in therapeutic range (n=16 studies, mean difference 3.38, 95% CI 1.12-5.65 i I /i sup /sup =90%). In the subgroup of the multitasking intervention, telemedicine resulted in an important reduction of thromboembolic events (RR 0.20, 95% CI 0.08-0.48). elemedicine-based oral anticoagulation management resulted in similar rates of major bleeding and mortality, a trend for fewer thromboembolic events, and better anticoagulation quality compared to standard care. Given the potential benefits of telemedicine-based care, such as greater access to remote populations or people with ambulatory restrictions, these findings may encourage further implementation of eHealth strategies for anticoagulation management, particularly as part of multifaceted interventions for integrated care of chronic diseases. Meanwhile, researchers should develop higher-quality evidence focusing on hard clinical outcomes, cost-effectiveness, and quality of life. ROSPERO International Prospective Register of Systematic Reviews CRD42020159208 www.crd.york.ac.uk rospero/display_record.php?RecordID=159208
Publisher: JMIR Publications Inc.
Date: 10-07-2023
DOI: 10.2196/45922
Abstract: Oral anticoagulation is the cornerstone treatment of several diseases. Its management is often challenging, and different telemedicine strategies have been implemented to support it. The aim of the study is to systematically review the evidence on the impact of telemedicine-based oral anticoagulation management compared to usual care on thromboembolic and bleeding events. Randomized controlled trials were searched in 5 databases from inception to September 2021. Two independent reviewers performed study selection and data extraction. Total thromboembolic events, major bleeding, mortality, and time in therapeutic range were assessed. Results were pooled using random effect models. In total, 25 randomized controlled trials were included (n=25,746 patients) and classified as moderate to high risk of bias by the Cochrane tool. Telemedicine resulted in lower rates of thromboembolic events, though not statistically significant (n=13 studies, relative risk [RR] 0.75, 95% CI 0.53-1.07 I2=42%), comparable rates of major bleeding (n=11 studies, RR 0.94, 95% CI 0.82-1.07 I2=0%) and mortality (n=12 studies, RR 0.96, 95% CI 0.78-1.20 I2=11%), and an improved time in therapeutic range (n=16 studies, mean difference 3.38, 95% CI 1.12-5.65 I2=90%). In the subgroup of the multitasking intervention, telemedicine resulted in an important reduction of thromboembolic events (RR 0.20, 95% CI 0.08-0.48). Telemedicine-based oral anticoagulation management resulted in similar rates of major bleeding and mortality, a trend for fewer thromboembolic events, and better anticoagulation quality compared to standard care. Given the potential benefits of telemedicine-based care, such as greater access to remote populations or people with ambulatory restrictions, these findings may encourage further implementation of eHealth strategies for anticoagulation management, particularly as part of multifaceted interventions for integrated care of chronic diseases. Meanwhile, researchers should develop higher-quality evidence focusing on hard clinical outcomes, cost-effectiveness, and quality of life. PROSPERO International Prospective Register of Systematic Reviews CRD42020159208 www.crd.york.ac.uk rospero/display_record.php?RecordID=159208
Publisher: Springer Science and Business Media LLC
Date: 06-05-2020
Publisher: Informa UK Limited
Date: 28-10-2009
DOI: 10.3109/10611860903096540
Abstract: Gelatin is a natural, biocompatible, nontoxic, edible, and inexpensive macromolecule. These properties result in its wide application in pharmaceutical, medical, and cosmetic products. Recently, it has been used for the delivery of such gene therapeutic entities as plasmid DNA. This review discusses the in vivo and in vitro studies using gelatin for delivery of therapeutic genes to cancerous cells. Recent studies show that present cancer gene therapy using gelatin is lacking in both efficiency and specificity in comparison with viral vectors, whereas complexes of therapeutic DNA with modified gelatin possibly offer a safe and efficient strategy for systemic administration of therapeutic genes to solid tumors compared to injection of naked plasmid DNA. The future of these promising approaches lies in the development of better techniques for preparing gelatin-gene complexes with the aim of a gelatin-based cancer gene therapy with comparable efficiency to viral vectors but with the added advantage of biosafety for patients.
No related grants have been discovered for Luana Fonseca de Almeida Messias.