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1.
Lung Cancer ; 137: 100-107, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31568886

RESUMO

OBJECTIVES: Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare subtype of primary lung cancer. Due to the lack of prospective studies, the optimal first-line chemotherapy regimens and survival outcomes remain unclear. MATERIALS AND METHODS: This real-world, retrospective study enrolled consecutive patients with unresectable pulmonary LELC. The survival outcomes, prognosis, and comparative efficacy of different chemotherapy regimens were investigated. RESULTS: In total, 127 patients were included in the analyses. The first-line chemotherapy regimens included gemcitabine plus platinum (GP, n = 19 [15.0%]), taxanes plus platinum (TP, n = 70 [55.1%]) and pemetrexed plus platinum (AP, n = 38 [30.0%]). 25 (19.7%) patients underwent palliative thoracic radiotherapy. 60 (47.2%) patients had detectable baseline Epstein-Barr virus (EBV) DNA. For the entire cohort, objective response was obtained in 41 patients (32.3%). Median progression-free survival (PFS) and overall survival (OS) were 7.7 months (95% CI, 6.6-8.8) and 36.7 months (95% CI, 30.9-42.5), respectively. Among the three chemotherapy regimens, GP achieved the highest response rate (GP, 63.2% vs. TP, 30.0% vs. AP, 21.1%; p = 0.005). Median PFS in the GP group (8.8 months) was also significantly longer than that in the TP group (7.9 months) and AP group (6.4 months) (p = 0.031). In the multivariate model, cycles of first-line chemotherapy (p < 0.001), palliative thoracic radiotherapy (p < 0.001), and chemotherapy regimens (p = 0.031) remained independent prognostic factors for PFS; while cycles of first-line chemotherapy (p = 0.002), baseline EBV DNA (p = 0.033) and palliative thoracic radiotherapy (p = 0.041) were significantly associated with OS. CONCLUSION: Gemcitabine-based chemotherapy and palliative thoracic radiotherapy are active in pulmonary LELC. These data provide added evidence for the similarity between pulmonary LELC and nasopharyngeal carcinoma in endemic area. Randomized controlled studies are needed to further define the standard-of-care for patients with advanced pulmonary LELC.

2.
J Immunother Cancer ; 7(1): 120, 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31053172

RESUMO

Pembrolizumab monotherapy has become the preferred treatment for patients with advanced non-small cell lung carcinoma (NSCLC) and a programmed cell death-ligand 1 (PD-L1) tumor proportion score (TPS) of at least 50%. However, little is known about the value of adding chemotherapy to pembrolizumab in this setting. Therefore, we performed an indirect comparison for pembrolizumab plus chemotherapy versus pembrolizumab, using the frequentist methods. The primary outcomes were overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). Data were retrieved from randomized trials comparing pembrolizumab plus chemotherapy or pembrolizumab monotherapy against chemotherapy. Five trials involving 1289 patients were included. Direct meta-analysis showed that both pembrolizumab plus chemotherapy (ORR: relative risk (RR) 2.16; PFS: hazard ratio (HR) 0.36; OS: HR 0.51) and pembrolizumab alone (ORR: RR 1.33; PFS: HR, 0.65; OS: HR 0.67) improved clinical outcomes compared with chemotherapy. Indirect comparison showed that pembrolizumab plus chemotherapy was superior to pembrolizumab alone, in terms of ORR (RR 1.62, 1.18-2.23) and PFS (HR 0.55, 0.32-0.97). A trend towards improved OS was also observed (HR 0.76, 0.51-1.14). In conclusion, the addition of chemotherapy to pembrolizumab further improves the outcomes of patients with advanced NSCLC and a PD-L1 TPS of at least 50%.

3.
Arthritis Rheumatol ; 71(6): 941-951, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30618213

RESUMO

OBJECTIVE: The autoimmune etiology in psoriasis remains to be clarified. We therefore undertook this study to identify novel pathogenic autoantigens and autoantibodies in patients with psoriasis, with the aim of shedding light on the molecular and cellular basis of the pathogenesis of psoriasis and psoriatic arthritis (PsA). METHODS: In this study, we developed an autoantigen array system that harbors a variety of antigens, including typical autoantigens in rheumatic diseases as well as skin antigens, inflammatory mediators, and putative autoantigens in psoriasis. Serum samples from patients with psoriasis (n = 73) were used to interrogate the antigens on the array. In addition, enzyme-linked immunosorbent assays of individual autoantibodies were used in validation studies. RESULTS: Levels of several autoantibodies were found to be elevated in the serum of patients with psoriasis compared to healthy controls; in particular, IgG autoantibodies against 2 novel antigens, LL-37 and ADAMTS-L5, were significantly increased in patients with psoriasis. Importantly, serum levels of IgG autoantibodies against LL-37 and ADAMTS-L5 were correlated with the Psoriasis Area and Severity Index, and reflected disease progression in longitudinally collected serum samples from patients with psoriasis. Importantly, both anti-ADAMTS-L5 and anti-LL-37 autoantibody levels were also significantly elevated in psoriasis patients with PsA compared to those without PsA, suggesting that these molecules may be involved in the pathogenesis of PsA. CONCLUSION: Our findings indicate that these identified autoantibodies may be useful biomarkers and may serve as therapeutic targets in psoriasis and PsA.

4.
Biosensors (Basel) ; 8(3)2018 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-30011807

RESUMO

Breast cancer is a major cause of mortality in women; however, technologies for early stage screening and diagnosis (e.g., mammography and other imaging technologies) are not optimal for the accurate detection of cancer. This creates demand for a more effective diagnostic means to replace or be complementary to existing technologies for early discovery of breast cancer. Cancer neoantigens could reflect tumorigenesis, but they are hardly detectable at the early stage. Autoantibodies, however, are biologically amplified and hence may be measurable early on, making them promising biomarkers to discriminate breast cancer from healthy tissue accurately. In this review, we summarized the recent findings of breast cancer specific antigens and autoantibodies, which may be useful in early detection, disease stratification, and monitoring of treatment responses of breast cancer.


Assuntos
Autoanticorpos/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico , Técnicas Biossensoriais , Neoplasias da Mama/terapia , Detecção Precoce de Câncer , Feminino , Humanos , Imunoensaio , Proteoma/análise
5.
Exp Dermatol ; 27(9): 1053-1057, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29957828

RESUMO

To discover novel biomarkers of psoriasis, a target-specific antibody array screening of serum samples from psoriasis patients was initially performed. The results revealed that vascular endothelial growth factor receptor 3 (VEGFR-3) was significantly elevated in the sera of psoriasis patients, compared to healthy controls. Next, ELISA validation studies in a larger cohort of psoriasis patients (N = 73) were conducted, which confirmed that serum VEGFR-3 was indeed significantly increased in patients with psoriasis compared to healthy controls (P < 0.001). Furthermore, receiver operating characteristic curve analysis demonstrated that serum VEGFR-3 exhibited potential in distinguishing healthy controls from psoriasis patients: area under the curve = 0.85, P < 0.001. In addition, serum levels of VEGFR-3 were correlated with Psoriasis Area Severity Index scores (R = 0.32, P = 0.008) in psoriasis patients. Interestingly, serum VEGFR-3 levels were significantly elevated in psoriatic arthritis compared to non-psoriatic arthritis (P = 0.026). A pilot longitudinal study demonstrated that serum levels of VEGFR-3 could reflect disease progression in psoriasis. Collectively, serum VEGFR-3 may have a clinical value in monitoring disease activity of psoriasis.

6.
Methods Mol Biol ; 1654: 261-269, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28986797

RESUMO

Antibody arrays represent one of the very early protein array systems where antibodies are used to capture and detect target proteins in a high-throughput platform. The development of high-quality antibodies, nanomaterial-based novel detection probes, as well as innovative imaging technologies and computational tools has tremendously improved the sensitivity, specificity, and robustness of antibody arrays during the past decade. In this protocol we will incorporate the most updated innovations and developments of antibody arrays into the step-by-step experimental procedures. This includes antibody printing, sample preparation, array detection, as well as imaging and data analysis. Antibody array could be used for cytokine profiling or mapping of phosphorylation, glycosylation, or other post-translational modifications of target proteins.


Assuntos
Anticorpos/análise , Análise Serial de Proteínas/métodos , Anticorpos/química , Citocinas/análise , Citocinas/química , Humanos
7.
Methods Mol Biol ; 1654: 271-277, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28986798

RESUMO

Antigen arrays are fabricated using various antigens such as DNA, histones, synthetic peptides, recombinant proteins, or cell extracts to detect autoantibodies in autoimmune diseases, alloantibodies in transplantation, drug-induced antibodies or cancer-induced antibodies in blood or cell culture supernatant. In this protocol, we will provide a step-by-step executable procedure to perform antigen arrays, including antigen preparation and printing, blocking, sample loading, array detection, imaging, and data analysis.


Assuntos
Antígenos/análise , Análise Serial de Proteínas/métodos , Antígenos/química , Autoanticorpos/análise , Autoanticorpos/química , Biomarcadores/análise , Biomarcadores/química , Histonas/análise , Histonas/química
8.
Methods Mol Biol ; 1654: 279-289, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28986799

RESUMO

The reverse-phase protein array (RPPA) is to use highly specific antibodies to interrogate pan or posttranslationally modified protein targets, such as phosphorylated proteins, particularly the proteins involved in cell signaling pathways. In this protocol we will cover the preparation of cell (or tissue) lysates, sample printing, antibody validation, antibody interrogation, signal amplification steps, imaging and data analysis. In this protocol, colorimetric catalyzed signal amplification (CSA) chemistry, fluorescence and near-infrared (NIR) based detection methods will be described.


Assuntos
Anticorpos/química , Análise Serial de Proteínas/métodos , Proteínas/química , Anticorpos/análise , Processamento de Proteína Pós-Traducional , Proteínas/análise
9.
Adv Mater ; 29(31)2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28612952

RESUMO

To meet the increasing demands for ultrasensitivity in monitoring trace amounts of low-abundance early biomarkers or environmental toxins, the development of a robust sensing system is urgently needed. Here, a novel signal cascade strategy is reported via an ultrasensitive polymeric sensing system (UPSS) composed of gold nanoparticle (gNP)-decorated polymer, which enables gNP aggregation in polymeric network and electrical conductance change upon specific aptamer-based biomolecular recognition. Ultralow concentrations of thrombin (10-18 m) as well as a low molecular weight anatoxin (165 Da, 10-14 m) are detected selectively and reproducibly. The biomolecular recognition induced polymeric network shrinkage responses as well as dose-dependent responses of the UPSS are validated using in situ real-time atomic-force microscopy, representing the first instance of real-time detection of biomolecular binding-induced polymer shrinkage in soft matter. Furthermore, in situ real-time confocal laser scanning microscopy imaging reveals the dynamic process of gNP aggregation responses upon biomolecular binding.

10.
Arch Immunol Ther Exp (Warsz) ; 65(2): 111-121, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27592176

RESUMO

Autoimmune diseases occur when the immune system generates proinflammatory molecules and autoantibodies that mistakenly attack their own body. Traditional diagnosis of autoimmune disease is primarily based on physician assessment combined with core laboratory tests. However, these tests are not sensitive enough to detect early molecular events, and quite often, it is too late to control these autoimmune diseases and reverse tissue damage when conventional tests show positivity for disease. It is fortunate that during the past decade, research in nanotechnology has provided enormous opportunities for the development of ultrasensitive biosensors in detecting early biomarkers with high sensitivity. Biosensors consist of a biorecognition element and a transducer which are able to facilitate an accurate detection of proinflammatory molecules, autoantibodies and other disease-causing molecules. Apparently, novel biosensors could be superior to traditional metrics in assessing the drug efficacy in clinical trials, especially when specific biomarkers are indicative of the pathogenesis of disease. Furthermore, the portability of a biosensor enables the development of point-of-care devices. In this review, various types of biomolecule sensing systems, including electrochemical, optical and mechanical sensors, and their applications and future potentials in autoimmune disease treatment were discussed.


Assuntos
Doenças Autoimunes/diagnóstico , Doenças Autoimunes/terapia , Biomarcadores/metabolismo , Técnicas Biossensoriais , Doenças Autoimunes/metabolismo , Eletroquímica , Fluorescência , Humanos , Inflamação , Nanotecnologia , Sensibilidade e Especificidade , Análise Espectral Raman , Ressonância de Plasmônio de Superfície
11.
ACS Nano ; 10(7): 6464-73, 2016 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-27244244

RESUMO

Fungal keratitis, a severe ocular disease, is one of the leading causes of ocular morbidity and blindness, yet it is often neglected, especially in developing countries. Therapeutic efficacy of traditional treatment such as eye drops is very limited due to poor bioavailability, whereas intraocular injection might cause serious side effects. Herein, we designed and fabricated a hybrid hydrogel-based contact lens which comprises quaternized chitosan (HTCC), silver nanoparticles, and graphene oxide (GO) with a combination of antibacterial and antifungal functions. The hydrogel is cross-linked through electrostatic interactions between GO and HTCC, resulting in strong mechanical properties. Voriconazole (Vor), an antifungal drug, can be loaded onto GO which retains the drug and promotes its sustained release from the hydrogel-based contact lenses. The contact lenses also exhibited good antimicrobial functions in view of glycidyltrimethylammonium chloride and silver nanoparticles. The results from in vitro and in vivo experiments demonstrate that contact lenses loaded with Vor have excellent efficacy in antifungal activity in vitro and could significantly enhance the therapeutic effects on a fungus-infected mouse model. The results indicate that this hydrogel contact lenses-based drug delivery system might be a promising therapeutic approach for a rapid and effective treatment of fungal keratitis.


Assuntos
Lentes de Contato , Hidrogéis , Ceratite/terapia , Nanopartículas Metálicas , Nanomedicina Teranóstica , Animais , Hidrogel de Polietilenoglicol-Dimetacrilato , Camundongos , Prata
12.
Nat Nanotechnol ; 11(5): 465-71, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26828848

RESUMO

Precise control of the electronic surface states of two-dimensional (2D) materials could improve their versatility and widen their applicability in electronics and sensing. To this end, chemical surface functionalization has been used to adjust the electronic properties of 2D materials. So far, however, chemical functionalization has relied on lattice defects and physisorption methods that inevitably modify the topological characteristics of the atomic layers. Here we make use of the lone pair electrons found in most of 2D metal chalcogenides and report a functionalization method via a Lewis acid-base reaction that does not alter the host structure. Atomic layers of n-type InSe react with Ti(4+) to form planar p-type [Ti(4+)n(InSe)] coordination complexes. Using this strategy, we fabricate planar p-n junctions on 2D InSe with improved rectification and photovoltaic properties, without requiring heterostructure growth procedures or device fabrication processes. We also show that this functionalization approach works with other Lewis acids (such as B(3+), Al(3+) and Sn(4+)) and can be applied to other 2D materials (for example MoS2, MoSe2). Finally, we show that it is possible to use Lewis acid-base chemistry as a bridge to connect molecules to 2D atomic layers and fabricate a proof-of-principle dye-sensitized photosensing device.

13.
J Transl Int Med ; 4(3): 109-113, 2016 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28191531

RESUMO

There is a high risk for the survival of patients with an end-stage renal disease for kidney transplantation. To avoid rejection by strict medication adherence is of utmost importance to avoid the failure of a kidney transplant. It is imperative to develop non-invasive biomarkers to assess immunity risk, and to ultimately provide guidance for therapeutic decision-making following kidney transplantation. Urine biomarkers may represent the promising non-invasive tools that will help in predicting risk or success rates of kidney transplantations. Furthermore, composite urinary biomarkers or urinary biomarker panel array might be critical in improving the sensitivity and specificity in reflecting various risks of kidney failure during transplantation. This review primarily focuses on the role of such biomarkers in predicting chronic kidney disease (CKD) progression and/or cardiovascular disease (CVD) risk in renal allograft.

14.
Proteomics Clin Appl ; 10(6): 625-34, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26684273

RESUMO

Lupus is one of the most common autoimmune diseases, yet many mechanisms of its pathogenesis are not fully known. Over the last few years, advances in protein array technology have accelerated rapidly, resulting in many promising insights toward the discovery of novel lupus biomarkers that may become useful in disease diagnosis and management. Still, only two types of analytical protein arrays thus far, being antibody and antigen arrays, have found notable usage toward lupus biomarker discovery. In this review, we summarize current protein array technologies being used for biomarker discoveries in lupus and associated biomarker findings, as well as protein arrays that are likely to be used for lupus biomarker discovery in the near future.


Assuntos
Autoanticorpos/sangue , Autoantígenos/sangue , Proteínas Sanguíneas/metabolismo , Lúpus Eritematoso Sistêmico/diagnóstico , Análise Serial de Proteínas/métodos , Autoimunidade , Biomarcadores/sangue , Citocinas/sangue , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/patologia , Análise Serial de Proteínas/instrumentação , Proteoma/metabolismo
15.
Int J Nanomedicine ; 10: 1155-72, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25709439

RESUMO

Magnetic resonance imaging (MRI) contrast agents based on chitosan derivatives have great potential for diagnosing diseases. However, stable tumor-targeted MRI contrast agents using micelles prepared from high molecular weight chitosan derivatives are seldom reported. In this study, we developed a novel tumor-targeted MRI vehicle via superparamagnetic iron oxide nanoparticles (SPIONs) encapsulated in self-aggregating polymeric folate-conjugated N-palmitoyl chitosan (FAPLCS) micelles. The tumor-targeting ability of FAPLCS/SPIONs was demonstrated in vitro and in vivo. The results of dynamic light scattering experiments showed that the micelles had a relatively narrow size distribution (136.60±3.90 nm) and excellent stability. FAPLCS/SPIONs showed low cytotoxicity and excellent biocompatibility in cellular toxicity tests. Both in vitro and in vivo studies demonstrated that FAPLCS/SPIONs bound specifically to folate receptor-positive HeLa cells, and that FAPLCS/SPIONs accumulated predominantly in established HeLa-derived tumors in mice. The signal intensities of T2-weighted images in established HeLa-derived tumors were reduced dramatically after intravenous micelle administration. Our study indicates that FAPLCS/SPION micelles can potentially serve as safe and effective MRI contrast agents for detecting tumors that overexpress folate receptors.


Assuntos
Quitosana/análogos & derivados , Meios de Contraste , Imagem por Ressonância Magnética/métodos , Nanopartículas de Magnetita/química , Micelas , Neoplasias/patologia , Animais , Quitosana/química , Quitosana/farmacocinética , Meios de Contraste/química , Meios de Contraste/farmacocinética , Ácido Fólico/química , Ácido Fólico/farmacocinética , Células HeLa , Humanos , Camundongos
16.
Carbohydr Polym ; 92(2): 1367-76, 2013 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-23399166

RESUMO

Phosphate rock (PHR), a traditional fertilizer, is abundant, but is hard to be utilized by plants. To improve the utilization of PHR, and to integrate water-retaining and controlled-release fertilizers, an agricultural superabsorbent polymer based on sulfonated corn starch/poly (acrylic acid) embedding phosphate rock (SCS/PAA/PHR) was prepared. PHR can be suspended and well-dispersed in SCS/PAA by sulfonated corn starch (SCS). PHR and KOH were mixed in acrylic acid solution to provide phosphorus (P) and potassium (K) nutrients, respectively. Impacts on water absorption capacity of the superabsorbent were investigated. The maximum swelling capacity in distilled water or 0.9 wt.% (weight percent) NaCl solution reached 498 g g(-1) and 65 g g(-1) (water/prepared dry superabsorbent) respectively. Moreover, release behaviours of P and K in SCS/PAA/PHR were also investigated. The results showed that SCS/PAA/PHR possessed excellent sustained-release property of plant nutrient, and the SCS/PAA could improve the P release greatly. Besides, the XPS analysis was employed to study the relationship between PHR and superabsorbent polymer.


Assuntos
Fertilizantes , Minerais/química , Fosfatos/química , Amido/química , Água/química , Absorção , Resinas Acrílicas/química , Preparações de Ação Retardada , Fósforo/química , Potássio/química , Solubilidade , Ácidos Sulfônicos/química , Zea mays/química
17.
Carbohydr Polym ; 90(2): 820-6, 2012 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-22840007

RESUMO

To improve the water-fertilizer utilization ratio and mitigate the environmental contamination, an eco-friendly superabsorbent polymer (SPA), modified sugarcane bagasse/poly (acrylic acid) embedding phosphate rock (MSB/PAA/PHR), was prepared. Ammonia, phosphate rock (PHR) and KOH were admixed in the presence of acrylic acid to provide nitrogen (N), phosphorus (P) and potassium (K) nutrients, respectively. Impacts on water absorption capacity of the superabsorbent polymer (SAP) were investigated. The maximum swelling capacity in distilled water and 0.9 wt.% (weight percent) NaCl solution reached 414 gg(-1) and 55 gg(-1) (water/prepared SAP), respectively. The available NPK contents of the combination system were 15.13 mgg(-1), 6.93 mgg(-1) and 52.05 mgg(-1), respectively. Moreover, the release behaviors of NPK in the MSB/PAA/PHR were also studied. The results showed that the MSB/PAA/PHR has outstanding sustained-release plant nutrients property.


Assuntos
Celulose/química , Fertilizantes , Fósforo/química , Polímeros/farmacocinética , Saccharum/química , Água/química , Absorção , Celulose/farmacocinética , Celulose/farmacologia , Reagentes para Ligações Cruzadas/farmacologia , Modelos Biológicos , Fósforo/farmacocinética , Fósforo/farmacologia , Polímeros/síntese química , Polímeros/química , Água/metabolismo , Molhabilidade
18.
Int J Biol Macromol ; 50(3): 707-12, 2012 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-22230613

RESUMO

Tetraethylenepentamine (TEPA) modified sugarcane bagasse (SB), a novel biosorbent (TEPA-MSB), was proved to be an effective adsorbent for anionic dyes due to the introduced functional amino groups. FTIR, TG and DSC analysis were employed to characterize the sorbent. The effects of pH, temperature, contact time and initial concentration of dye on the adsorption of eosin Y were investigated. The experimental data fit very well to the Langmuir model, giving a maximum sorption capacity of 399.04 mg/g at 25 °C. And the kinetic data were well described by the pseudo-second-order kinetic model. pH 6 was the optimal pH for eosin Y adsorption, and the maximum adsorption capacity of TEPA-MSB calculated by Langmuir model was 18 times higher than that of SB.


Assuntos
Celulose/química , Corantes/química , Corantes/isolamento & purificação , Amarelo de Eosina-(YS)/química , Amarelo de Eosina-(YS)/isolamento & purificação , Etilenodiaminas/química , Saccharum/química , Adsorção , Concentração de Íons de Hidrogênio , Fatores de Tempo , Água/química
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