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1.
Chem Soc Rev ; 53(12): 6244-6294, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38743011

RESUMO

This comprehensive review explores the diverse applications of defective zirconium-based metal-organic frameworks (Zr-MOFs) in energy and environmental remediation. Zr-MOFs have gained significant attention due to their unique properties, and deliberate introduction of defects further enhances their functionality. The review encompasses several areas where defective Zr-MOFs exhibit promise, including environmental remediation, detoxification of chemical warfare agents, photocatalytic energy conversions, and electrochemical applications. Defects play a pivotal role by creating open sites within the framework, facilitating effective adsorption and remediation of pollutants. They also contribute to the catalytic activity of Zr-MOFs, enabling efficient energy conversion processes such as hydrogen production and CO2 reduction. The review underscores the importance of defect manipulation, including control over their distribution and type, to optimize the performance of Zr-MOFs. Through tailored defect engineering and precise selection of functional groups, researchers can enhance the selectivity and efficiency of Zr-MOFs for specific applications. Additionally, pore size manipulation influences the adsorption capacity and transport properties of Zr-MOFs, further expanding their potential in environmental remediation and energy conversion. Defective Zr-MOFs exhibit remarkable stability and synthetic versatility, making them suitable for diverse environmental conditions and allowing for the introduction of missing linkers, cluster defects, or post-synthetic modifications to precisely tailor their properties. Overall, this review highlights the promising prospects of defective Zr-MOFs in addressing energy and environmental challenges, positioning them as versatile tools for sustainable solutions and paving the way for advancements in various sectors toward a cleaner and more sustainable future.

2.
Chem Soc Rev ; 53(12): 6625, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38805351

RESUMO

Correction for 'Defect-enabling zirconium-based metal-organic frameworks for energy and environmental remediation applications' by Saba Daliran et al., Chem. Soc. Rev., 2024, https://doi.org/10.1039/d3cs01057k.

3.
Chem Commun (Camb) ; 59(42): 6339-6342, 2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-37186113

RESUMO

3D SERS microneedles with self-assembled AuNPs were fabricated with tannic acid (chemical glue and reductant) on polylactic acid microneedles for in-depth chemical and biomolecular analysis, with LOD values below 200 ppb for small molecules and 102 CFU cm-2 for bacteria. The MB/Au-microneedles were used for photodynamic therapy with SERS-monitored photosensitizer degradation.


Assuntos
Nanopartículas Metálicas , Fotoquimioterapia , Ouro/química , Nanopartículas Metálicas/química , Polifenóis , Análise Espectral Raman
4.
J Acute Med ; 13(1): 41-43, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37089667

RESUMO

This case involves a 41-year-old male experiencing agitation and confusion due to betel nut intoxication. The diagnosis was made by identifying the toxidrome through physical examination. Removing the residual betel nut with a finger and brushing it with water resulted in a significant improvement in consciousness and orientation within one hour. In addition to recognizing the toxidrome, prompt and effective treatment for the intoxicated patient is essential. Given the prevalence of betel nut chewing in Taiwan, emergency physicians should be particularly vigilant of arecoline toxicity.

5.
Nanomedicine ; 47: 102628, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36400317

RESUMO

Benefit for clinical melanoma treatments, the transdermal neoadjuvant therapy could reduce surgery region and increase immunotherapy efficacy. Using lipoplex (Lipo-PEG-PEI-complex, LPPC) encapsulated doxorubicin (DOX) and carrying CpG oligodeoxynucleotide; the transdermally administered nano-liposomal drug complex (LPPC-DOX-CpG) would have high cytotoxicity and immunostimulatory activity to suppress systemic metastasis of melanoma. LPPC-DOX-CpG dramatically suppressed subcutaneous melanoma growth by inducing tumor cell apoptosis and recruiting immune cells into the tumor area. Animal studies further showed that the colonization and growth of spontaneously metastatic melanoma cells in the liver and lung were suppressed by transdermal LPPC-DOX-CpG. Furthermore, NGS analysis revealed IFN-γ and NF-κB pathways were triggered to recruit and activate the antigen-presenting-cells and effecter cells, which could activate the anti-tumor responses as the major mechanism responsible for the therapeutic effect of LPPC-DOX-CpG. Finally, we have successfully proved transdermal LPPC-DOX-CpG as a promising penetrative carrier to activate systemic anti-tumor immunity against subcutaneous and metastatic tumor.


Assuntos
Melanoma , Humanos , Melanoma/tratamento farmacológico
6.
Front Endocrinol (Lausanne) ; 13: 924731, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35813650

RESUMO

Objectives: Quantum molecular resonance (QMR) devices have been applied as energy-based devices in many head and neck surgeries; however, research on their use in thyroid surgery is lacking. This study aimed to investigate the safety parameters of QMR devices during thyroidectomy when dissection was adjacent to the recurrent laryngeal nerve (RLN). Methods: This study included eight piglets with 16 RLNs, and real-time electromyography (EMG) signals were obtained from continuous intraoperative neuromonitoring (C-IONM). QMR bipolar scissor (BS) and monopolar unit (MU) were tested for safety parameters. In the activation study, QMR devices were activated at varying distances from the RLN. In the cooling study, QMR devices were cooled for varying time intervals, with or without muscle touch maneuver (MTM) before contacting with the RLN. Results: In the activation study, no adverse EMG change occurred when QMR BS and MU were activated at distances of 2 mm or longer from the RLNs. In the cooling study, no adverse EMG change occurred when QMR BS and MU were cooled in 2-second intervals or immediately after MTM. Conclusion: QMR devices should be carefully used when performing RLN dissection during thyroid surgery. According to the activation and cooling safety parameters in this study, surgeons can avoid RLN injury by following standard procedures when using QMR devices.


Assuntos
Traumatismos do Nervo Laríngeo Recorrente , Glândula Tireoide , Animais , Eletromiografia , Nervo Laríngeo Recorrente/cirurgia , Traumatismos do Nervo Laríngeo Recorrente/cirurgia , Suínos , Glândula Tireoide/cirurgia , Tireoidectomia/efeitos adversos , Tireoidectomia/métodos
7.
J Clin Med ; 11(12)2022 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-35743377

RESUMO

Thiazide diuretics have long been widely used as antihypertensive agents. In addition to reducing blood pressure, thiazides also control calcium homeostasis and increase bone density. We hypothesized that the use of thiazides in patients with hypertension would reduce overall fracture risk. We used the Taiwan National Health Insurance Research Database to find patients with a hypertension diagnosis who accepted antihypertensive treatment from 2000 to 2017. The patients were further classified into thiazide users and nonthiazide users. Multivariable Cox regression analysis and Kaplan-Meier survival analysis were performed to estimate the adjusted hazard ratios (aHRs) and cumulative probability of fractures. After 1:1 propensity score matching by sex, age, urbanization level of place of residence, income, comorbidities, and medications, there were 18,483 paired thiazide users and non-users, respectively. The incidence densities of fractures (per 1000 person-months) were 1.82 (95% CI: 1.76-1.89) and 1.99 (95% CI: 1.92-2.06) in the thiazide and nonthiazide groups, respectively. The results indicated a lower hazard ratio for fractures in thiazide users (aHR = 0.93, 95% CI: 0.88-0.98). Kaplan-Meier survival analysis revealed a significantly lower cumulative incidence of fractures in the thiazide group (log-rank test; p = 0.0012). In conclusion, our results reveal that thiazide use can reduce fracture risk. When antihypertensive agents are being considered, thiazide may be a better choice if the patient is at heightened risk of fracture.

8.
Mar Drugs ; 20(4)2022 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-35447934

RESUMO

Freshwater clam extract (FCE) is a functional food that regulates the immune system and has been demonstrated in numerous studies to display desirable anti-tumor necrosis factor-alpha (TNF-α) responses. In addition, excess TNF-α production is positively associated with type 2 diabetes. However, few longitudinal clinical studies evaluating the efficiency and toxicity of FCE are available. This article reports that patients with prediabetes who received FCE had a desirable outcome of a reduction in serum TNF-α for a long period. This was a double-blind, randomized, parallel clinical trial conducted using FCE intervention and placebo groups, and 36 patients with prediabetes were enrolled. Two grams of FCE or placebo was consumed daily for 180 consecutive days. The serum of the participants was collected at four time points (0M: before the intervention; 3M: after 3 months of intervention; 6M: after 6 months of intervention; 12M: 6 months after cessation of intervention at 6M). A serum TNF-α concentration higher than 4.05 pg/mL was defined as a cut-off value. FCE reduced serum TNF-α in all participants at 6M and 12M. Moreover, FCE significantly suppressed serum TNF-α concentrations at 6M and 12M and inhibited TNF-α release with time series in subjects with elevated TNF-α values. FCE intervention effectively reduced serum TNF-α and persistently sustained the effects for half a year in patients with prediabetes. Gas chromatography-mass spectrometry (GS-MS) analysis revealed that the major components of FCE were phytosterols and fatty acids, which exerted anti-inflammatory and anti-TNF-α abilities. Hence, FCE has the potential to be developed as a natural treatment for prediabetic patients in Taiwan.


Assuntos
Corbicula , Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Animais , Corbicula/química , Diabetes Mellitus Tipo 2/tratamento farmacológico , Água Doce , Humanos , Extratos Vegetais , Estado Pré-Diabético/tratamento farmacológico , Taiwan , Inibidores do Fator de Necrose Tumoral , Fator de Necrose Tumoral alfa
9.
J Clin Med ; 11(5)2022 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-35268389

RESUMO

Total thyroidectomy (TT) in patients with Graves' disease is challenging even for an experienced thyroid surgeon. This study aimed to investigate the accumulation of experience and applying newly developed devices on major complications and voice outcomes after surgery of a single surgeon over 30 years. This study retrospectively reviewed 90 patients with Graves' disease who received TT. Forty-six patients received surgery during 1990-1999 (Group A), and 44 patients received surgery during 2010-2019 (Group B). Major complications rates were compared between Group A/B, and objective voice parameters were compared between the usage of energy-based devices (EBDs) within Group B. Compared to Group B, Group A patients had higher rates of recurrent laryngeal nerve palsy (13.0%/1.1%, p = 0.001), postoperative hypocalcemia (47.8%/18.2%, p = 0.002), and postoperative hematoma (10.9%/2.3%, p = 0.108). Additionally, Group A had one permanent vocal cord palsy, four permanent hypocalcemia, and one thyroid storm, whereas none of Group B had these complications. Group B patients with EBDs had a significantly better pitch range (p = 0.015) and jitter (p = 0.035) than those without EBDs. To reduce the major complications rate, inexperienced thyroid surgeons should remain vigilant when performing TT for Graves' disease. Updates on surgical concepts and the effective use of operative adjuncts are necessary to improve patient safety and voice outcome.

10.
Phlebology ; 37(4): 267-278, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35099328

RESUMO

BACKGROUND: The aim was to compare the genetic information of varicose vein patients with that of a healthy population attempting to identify certain significant genetic associations. METHOD: Patients' clinical characteristics and demographics were collected, and their genetic samples were examined. The results were compared to the genetic information of one thousand sex-matched healthy controls from Taiwan Biobank database. The Clinical-Etiology-Anatomy-Pathophysiology classification was applied for further subgroup analysis. RESULTS: After comparison of genetic information of ninety-six patients to that of healthy controls, two significant single nucleotide polymorphisms (SNPs) were identified. One was in DPYSL2 gene, and the other was in VSTM2L gene. A further comparison between C2-3 patient subgroup and C4-6 subgroup identified another four significant SNPs, which were located in ZNF664-FAM101A, PHF2, ACOT11, and TOM1L1 genes. CONCLUSION: Our preliminary result identified six significant SNPs located in six different genes. All of them and their genetic products may warrant further investigations.


Assuntos
Estudo de Associação Genômica Ampla , Varizes , Proteínas Adaptadoras de Transdução de Sinal/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Proteínas de Homeodomínio/genética , Humanos , Polimorfismo de Nucleotídeo Único , Varizes/epidemiologia , Varizes/genética
11.
J Med Ultrasound ; 30(4): 300-302, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36844771

RESUMO

Acute renal infarction is a rare form of vascular emergency. Although major risk factors of renal infarction are due to cardio-embolic events such as atrial fibrillation, valvular or ischemic heart disease, renal artery thrombosis/dissection, and coagulopathy, the prevalence of idiopathic acute renal infarction can be as high as 59%. Two cases that contributed to this emergency are presented. The history, physical examination, and clinical imaging findings for clinical assessment are briefly described. Point-of-Care Ultrasonography (POCUS) was used to exclude other etiology and identify the pathological changes. The role of POCUS in rapid rule in acute renal infarction has been emphasized in clinical settings.

12.
J Med Ultrasound ; 30(4): 303-305, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36844780

RESUMO

Brachial plexus injury (BPI) is regarded as one of the most devastating injuries of the upper extremity. Brachial plexus neuropathy can have a high morbidity by seriously affecting the motor function and sensation of upper limbs with loss of activities of daily living. The use of computed tomography myelogram and/or magnetic resonance imaging (MRI) assessing brachial plexus offers valuable details including the location, morphology, and severity of preganglionic and postganglionic injuries during the preoperative period. High-field-strength MRI with specific coil and specialized MRI sequences might be not available in every emergency setting and is time-consuming. Point-of-care ultrasonography (POCUS) comes in handy and offers good image resolution of muscles and nerves that makes early detection of neuromuscular injury possible. Here, we present a case report of BPI that POCUS provides indirect evidence of cervical root injury and expedite time to MRI.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34063602

RESUMO

Patients with pelvic fractures could encounter various complications during or after treatments. This cohort study investigated the risk of mortality and readmissions in patients with pelvic fractures, with or without urinary tract infections (UTIs), within 30 days following the pelvic fractures. This retrospective cohort study examined claim records from the Longitudinal Health Insurance Database 2000 (LHID2000). We selected patients hospitalized with pelvic fractures between 1997 and 2013 for study. Patients who had index data before 2000 or after 2010 (n = 963), who died before the index date (n = 64), who were aged <18 years (n = 94), or who had a pelvic injury (n = 31) were excluded. In total, the study cohort comprised 1623 adult patients; 115 had UTIs, and 1508 patients without UTIs were used as a comparison cohort. Multivariate analysis with a multiple Cox regression model and Kaplan-Meier survival analysis were performed to analyze the data. Our results showed that the 1-year mortality rate (adjusted hazard ratio [HR]: 2.32; 95% CI: 1.25-4.29) and readmission rate (adjusted HR: 1.72; 95% CI: 1.26-3.34) of the UTI group were significantly higher than those of the non-UTI group. Moreover, the Kaplan-Meier curve for the 1-year follow-up indicated that the UTI group had a higher cumulative risk of both mortality and hospital readmission compared with the non-UTI group. In conclusion, among patients with pelvic fracture, patients with UTI were associated with increased risks of mortality and readmission. Physicians must pay more attention to such patients to prevent UTIs among patients with pelvic fractures during hospitalization and conduct a follow-up after discharge within at least 1 year.


Assuntos
Readmissão do Paciente , Infecções Urinárias , Adulto , Estudos de Coortes , Hospitalização , Humanos , Estudos Retrospectivos , Fatores de Risco , Infecções Urinárias/epidemiologia
14.
ACS Appl Mater Interfaces ; 13(14): 16418-16426, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33818075

RESUMO

In this study, nanocrystals of a cerium-based metal-organic framework (Ce-MOF), Ce-MOF-808, are directly grown on the surface of carboxylic acid-functionalized carbon nanotubes (CNTs) by a facile one-step solvothermal synthesis method. Ce-MOF-CNT nanocomposites with various Ce-MOF-to-CNT ratios are synthesized, and their crystallinity, morphology, porosity, and electrical conductivity are examined. The redox-hopping and electrochemical behaviors of the pristine Ce-MOF in aqueous electrolytes are investigated, suggesting that the pristine Ce-MOF is electrochemically active but possesses a limited charge-transport behavior. As a demonstration, all the Ce-MOF, CNT, and nanocomposites are used as active materials for application in aqueous-based supercapacitors. The capacitive performance of the CNT can be significantly boosted with the help of redox-active Ce-MOF-808 nanocrystals.

15.
Chemistry ; 27(10): 3560-3567, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33166095

RESUMO

In this study, a strategy that can result in the polyaniline (PANI) solely confined within the nanopores of a metal-organic framework (MOF) without forming obvious bulk PANI between MOF crystals is developed. A water-stable zirconium-based MOF, UiO-66-NH2 , is selected as the MOF material. The polymerization of aniline is initiated in the acidic suspension of UiO-66-NH2 nanocrystals in the presence of excess poly(sodium 4-styrenesulfonate) (PSS). Since the pore size of UiO-66-NH2 is too small to enable the insertion of the bulky PSS, the quick formation of pore-confined solid PANI and the slower formation of well dispersed PANI:PSS occur within the MOF crystals and in the bulk solution, respectively. By taking advantage of the resulting homogeneous PANI:PSS polymer solution, the bulk PANI:PSS can be removed from the PANI/UiO-66-NH2 solid by successive washing the sample with fresh acidic solutions through centrifugation. As this is the first time reporting the PANI solely confined in the pores of a MOF, as a demonstration, the obtained PANI/UiO-66-NH2 composite material is applied as the electrode material for supercapacitors. The PANI/UiO-66-NH2 thin films exhibit a pseudocapacitive electrochemical characteristic, and their resulting electrochemical activity and charge-storage capacities are remarkably higher than those of the bulk PANI thin films.

16.
J Leukoc Biol ; 109(6): 1089-1103, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33031589

RESUMO

DNA methylation is a comprehensively studied epigenetic modification and plays crucial roles in cancer development. In the present study, MethylCap-seq was used to characterize the genome-wide DNA methylation patterns in canine high-grade B-cell lymphoma (cHGBL). Canine methylated DNA fragments were captured and the MEDIUM-HIGH and LOW fraction of methylated DNA was obtained based on variation in CpG methylation density. In the MEDIUM-HIGH and LOW fraction, 2144 and 1987 cHGBL-specific hypermethylated genes, respectively, were identified. Functional analysis highlighted pathways strongly related to oncogenesis. The relevant signaling pathways associated with neuronal system were also revealed, echoing recent novel findings that neurogenesis plays key roles in tumor establishment. In addition, 14 genes were hypermethylated in all the cHGBL cases but not in the healthy dogs. These genes might be potential signatures for tracing cHGBL, and some of them have been reported to play roles in various types of cancers. Further, the distinct methylation pattern of cHGBL showed a concordance with the clinical outcome, suggesting that aberrant epigenetic changes may influence tumor behavior. In summary, our study characterized genome-wide DNA methylation patterns using MethylCap-seq in cHGBL; the findings suggest that specific DNA hypermethylation holds promise for dissecting tumorigenesis and uncovering biomarkers for monitoring the progression of cHGBL.


Assuntos
Metilação de DNA , Doenças do Cão/genética , Doenças do Cão/patologia , Epigênese Genética , Epigenômica , Estudo de Associação Genômica Ampla , Linfoma de Células B/veterinária , Animais , Transformação Celular Neoplásica/genética , Ilhas de CpG , Cães , Epigenômica/métodos , Estudo de Associação Genômica Ampla/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Gradação de Tumores , Análise de Sequência de DNA
17.
ACS Appl Mater Interfaces ; 12(38): 42634-42643, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32845608

RESUMO

To obtain renewable and clean fuels, exploration of effective electrocatalysts is highly desirable due to the sluggish kinetics of water splitting. In this study, the oxygen plasma-activated hybrid structure of Ni-Fe Prussian blue analogue (PBA) interconnected by carbon nanotubes (O-CNT/NiFe) is reported as a highly effective electrocatalytic material for the oxygen evolution reaction (OER). The electrocatalytic performance is significantly influenced by different mass ratios of CNTs to Ni-Fe PBA. Benefiting from the conductive and oxygen plasma-activated CNTs as well as ordered and distributed metal sites in the framework, the optimized O-CNT/NiFe 1:18 exhibits a competitive overpotential of 279 mV at a current density of 10 mA cm-2 and a low Tafel slope of 42.8 mV dec-1 in 1.0 M KOH. Furthermore, the composite shows superior durability for at least 100 h. These results suggest that the O-CNT/NiFe 1:18 possesses promising potential as a highly active electrocatalyst.

18.
Theranostics ; 10(19): 8771-8789, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32754277

RESUMO

Rationale: Triple-negative breast cancer (TNBC), which has the highest recurrence rate and shortest survival time of all breast cancers, is in urgent need of a risk assessment method to determine an accurate treatment course. Recently, miRNA expression patterns have been identified as potential biomarkers for diagnosis, prognosis, and personalized therapy. Here, we investigate a combination of candidate miRNAs as a clinically applicable signature that can precisely predict relapse in TNBC patients after surgery. Methods: Four total cohorts of training (TCGA_TNBC and GEOD-40525) and validation (GSE40049 and GSE19783) datasets were analyzed with logistic regression and Gaussian mixture analyses. We established a miRNA signature risk model and identified an 8-miRNA signature for the prediction of TNBC relapse. Results: The miRNA signature risk model identified ten candidate miRNAs in the training set. By combining 8 of the 10 miRNAs (miR-139-5p, miR-10b-5p, miR-486-5p, miR-455-3p, miR-107, miR-146b-5p, miR-324-5p and miR-20a-5p), an accurate predictive model of relapse in TNBC patients was established and was highly correlated with prognosis (AUC of 0.80). Subsequently, this 8-miRNA signature prognosticated relapse in the two validation sets with AUCs of 0.89 and 0.90. Conclusion: The 8-miRNA signature predictive model may help clinicians provide a prognosis for TNBC patients with a high risk of recurrence after surgery and provide further personalized treatment to decrease the chance of relapse.


Assuntos
Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica/métodos , MicroRNAs/genética , Recidiva Local de Neoplasia/diagnóstico , Neoplasias de Mama Triplo Negativas/diagnóstico , Adulto , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Medicina de Precisão , Prognóstico , Neoplasias de Mama Triplo Negativas/genética
19.
J Nanobiotechnology ; 18(1): 58, 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32272948

RESUMO

BACKGROUND: The anti-angiogenic fusion protein RBDV-IgG1 Fc (RBDV), which comprises the receptor-binding domain of vascular endothelial growth factor-A (VEGF-A), has shown antitumour effects by reducing angiogenesis in vivo. This study used the cationic lipoplex lipo-PEG-PEI-complex (LPPC) to simultaneously encapsulate both the RBDV targeting protein and the RBDV plasmid (pRBDV) without covalent bonds to assess VEGFR targeting gene therapy in mice with melanoma in vivo. RESULTS: LPPC protected the therapeutic transgene from degradation by DNase, and the LPPC/RBDV complexes could specifically target VEGFR-positive B16-F10 cells both in vitro and in vivo. With or without RBDV protein-targeting direction, the pRBDV-expressing RBDV proteins were expressed and reached a maximal concentration on the 7th day in the sera after transfection in vivo and significantly elicited growth suppression against B16-F10 melanoma but not IgG1 control proteins. In particular, LPPC/pRBDV/RBDV treatment with the targeting molecules dramatically inhibited B16-F10 tumour growth in vivo to provide better therapeutic efficacy than the treatments with gene therapy with IgG1 protein targeting or administration of a protein drug with RBDV. CONCLUSIONS: The simultaneous combination of the LPPC complex with pRBDV gene therapy and RBDV protein targeting might be a potential tool to conveniently administer targeted gene therapy for cancer therapy.


Assuntos
Inibidores da Angiogênese/genética , Terapia Genética/métodos , Lipossomos/química , Melanoma Experimental/terapia , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Células 3T3 , Animais , Linhagem Celular Tumoral , Proliferação de Células , Fragmentos Fc das Imunoglobulinas/genética , Fragmentos Fc das Imunoglobulinas/metabolismo , Masculino , Melanoma Experimental/mortalidade , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Plasmídeos/química , Plasmídeos/genética , Plasmídeos/uso terapêutico , Domínios Proteicos/genética , Receptores de Fatores de Crescimento do Endotélio Vascular/genética , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/isolamento & purificação , Taxa de Sobrevida , Transplante Homólogo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
20.
Biol Proced Online ; 20: 10, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29743821

RESUMO

BACKGROUND: Gastric cancer is currently the fourth leading cause of cancer-related death worldwide. Gastric cancer is often diagnosed at advanced stages and the outcome of the treatment is often poor. Therefore, identifying new therapeutic targets for this cancer is urgently needed. Integrin alpha 2 (ITGA2) subunit and the beta 1 subunit form a heterodimer for a transmembrane receptor for extracellular matrix, is an important molecule involved in tumor cell proliferation, survival and migration. Integrin α2ß1 is over-expressed on a variety of cancer cells, but is low or absent in most normal organs and resting endothelial cells. RESULTS: In this report, we assessed the ITGA2 as the potential therapeutic target with the bioinformatics tools from the TCGA dataset in which composed of 375 gastric cancer tissues and 32 gastric normal tissues. According to the information from the Cancer Cell Line Encyclopedia (CCLE) database, the AGS cell line with ITGA2 high expression and the SUN-1 cell line with low expression were chosen for the further investigation. Interestingly, the anti-ITGA2 antibody (at 3 µg/ml) inhibited approximately 50% survival of the AGS cells (over-expressed ITGA2), but had no effect in SNU-1 cells (ITGA2 negative). The extents of antibody-mediated cancer inhibition positively correlated with the expression levels of the ITGA2. We further showed that the anti-ITGA2 antibody induced apoptosis by up-regulating the RhoA-p38 MAPK signaling to promote the expressions of Bim, Apaf-1 and Caspase-9, whereas the expressions of Ras and Bax/Bcl-2 were not affected. Moreover, blocking ITGA2 by the specific antibody at lower doses also inhibited cell migration of gastric cancer cells. Blockade of ITGA2 by a specific antibody down-regulated the expression of N-WASP, PAK and LIMK to impede actin organization and cell migration of gastric cancer cells. CONCLUSIONS: Here, we showed that the mRNA expression levels of ITGA2 comparing to normal tissues significantly increased. In addition, the results revealed that targeting integrin alpha 2 subunit by antibodies did not only inhibit cell migration, but also induce apoptosis effect on gastric cancer cells. Interestingly, higher expression level of ITGA2 led to significant effects on apoptosis progression during anti-ITGA2 antibody treatment, which indicated that ITGA2 expression levels directly correlate with their functionality. Our findings suggest that ITGA2 is a potential therapeutic target for gastric cancer.

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