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1.
Small ; : e1901718, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31515944

RESUMO

2D transition metal dichalcogenides (TMDs) have received widespread interest by virtue of their excellent electrical, optical, and electrochemical characteristics. Recent studies on TMDs have revealed their versatile utilization as electrocatalysts, supercapacitors, battery materials, and sensors, etc. In this study, MoS2 nanosheets are successfully assembled on the porous VS2 (P-VS2 ) scaffold to form a MoS2 /VS2 heterostructure. Their gas-sensing features, such as sensitivity and selectivity, are investigated by using a quartz crystal microbalance (QCM) technique. The QCM results and density functional theory (DFT) calculations reveal the impressive affinity of the MoS2 /VS2 heterostructure sensor toward ammonia with a higher adsorption uptake than the pristine MoS2 or P-VS2 sensor. Furthermore, the adsorption kinetics of the MoS2 /VS2 heterostructure sensor toward ammonia follow the pseudo-first-order kinetics model. The excellent sensing features of the MoS2 /VS2 heterostructure render it attractive for high-performance ammonia sensors in diverse applications.

2.
Oncogene ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511648

RESUMO

Epstein-Barr virus (EBV) immortalizes human B-lymphocytes and is implicated in the pathogenesis of lymphoid and epithelial cell malignancies. The EBV nuclear antigen (EBNA)-1 induces the accumulation of reactive oxygen species (ROS), which enables B-cell immortalization but causes oxidative DNA damage and triggers antiproliferative DNA damage responses. By comparing pairs of EBV-negative and -positive tumor cell lines we found that, while associated with the accumulation of oxidized nucleotides, EBV carriage promotes the concomitant activation of oxo-dNTP sanitization and purging pathways, including upregulation of the nucleoside triphosphatase mut-T homolog 1 (MTH1) and the DNA glycosylases 8-oxoguanine-glycosylase-1 (OGG1) and mut-Y homolog (MUTYH). Expression of EBNA1 was reversibly associated with transcriptional activation of this cellular response. DNA damage and apoptosis were preferentially induced in EBNA1-positive cell lines by treatment with MTH1 inhibitors, suggesting that virus carriage is linked to enhanced vulnerability to oxidative stress. MTH1, OGG1, and MUTYH were upregulated upon EBV infection in primary B-cells and treatment with MTH1 inhibitors prevented B-cell immortalization. These findings highlight an important role of the cellular antioxidant response in sustaining EBV infection, and suggests that targeting this cellular defense may offer a novel approach to antiviral therapy and could reduce the burden of EBV associated cancer.

3.
Synapse ; : e22134, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31562782

RESUMO

Synapse impairment is associated with post-traumatic stress disorder (PTSD), which is characterized by enhanced apoptosis in the hippocampus, amygdala, and other brain regions. However, there are no detailed studies on the relationship between apoptosis and synaptic connectivity in PTSD. In this review, we discuss results from various studies describing the synaptic changes observed in the PTSD brain. A decreased number of dendrites/spines or increased number of immature spines in the hippocampus, medial prefrontal cortex, and other brain regions has been reported. Studies on axon guidance, myelination, and the cytoskeleton suggest that PTSD may involve axon overgrowth and overbranching. Apoptosis affects synapse formation; low levels of caspase maintain the balance between growth cone attraction and repulsion and inhibit axon elongation. PTSD enhances neuronal apoptosis through caspase activation, which disrupts the balance between growth cone attraction and repulsion and alters growth cone trajectory, leading to axon mistargeting. Meanwhile, caspase activation induces dendritic pruning and dendrite degeneration. These events contribute to the formation of fewer and aberrant synapses, which is associated with enhanced apoptosis in PTSD.

4.
Biomacromolecules ; 20(9): 3385-3391, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31424203

RESUMO

Some synthetic polymers can block cell death when applied following an injury that would otherwise kill the cell. This cellular rescue occurs through interactions of the polymers with cell membranes. However, general principles for designing synthetic polymers to ensure strong, but nondisruptive, cell membrane targeting are not fully elucidated. Here, we tailored biomimetic phosphorylcholine-containing block copolymers to interact with cell membranes and determined their efficacy in blocking neuronal death following oxygen-glucose deprivation. By adjusting the hydrophilicity and membrane affinity of poly(2-methacryloyloxyethyl phosphorylcholine) (polyMPC)-based triblock copolymers, the surface active regime in which the copolymers function effectively as membrane-targeting cellular rescue agents was determined. We identified nonintrusive interactions between the polymer and the cell membrane that alter the collective dynamics of the membrane by inducing rigidification without disrupting lipid packing or membrane thickness. In general, our results open new avenues for biological applications of polyMPC-based polymers and provide an approach to designing membrane-targeting agents to block cell death after injury.

5.
J Integr Plant Biol ; 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31449354

RESUMO

The percentage of amylose in the endosperm of rice (Oryza sativa) largely determines grain cooking and eating qualities. Granule-bound starch synthase I (GBSSI) and GBSSII are responsible for amylose biosynthesis in the endosperm and leaf, respectively. Here, we identified OsGBP, a rice GBSS-binding protein that interacted with GBSSI and GBSSII in vitro and in vivo. The total starch and amylose contents in osgbp mutants were significantly lower than those of wild type in leaves and grains, resulting in reduced grain weight and quality. The carbohydrate-binding module 48 (CBM48) domain present in the C-terminus of OsGBP is crucial for OsGBP binding to starch. In the osgbp mutant, the extent of GBSSI and GBSSII binding to starch in the leaf and endosperm was significantly lower than wild type. Our data suggest that OsGBP plays an important role in leaf and endosperm starch biosynthesis by mediating the binding of GBSS proteins to developing starch granules. This elucidation of the function of OsGBP enhances our understanding of the molecular basis of starch biosynthesis in rice and contributes information that can be potentially used for the genetic improvement of yield and grain quality. This article is protected by copyright. All rights reserved.

6.
J Nutr Educ Behav ; 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31345673

RESUMO

OBJECTIVE: To explore the degree and predictors of and barriers to school garden integration (termed success). DESIGN: A 30-item online survey consisting of demographic, garden characteristic, and barrier questions, as well as the School Garden Integration Scale, was conducted in 266 school garden organizations (13 national, 8 regional, and 245 state or local). PARTICIPANTS: A total of 414 school gardeners from 38 states and Puerto Rico. MAIN OUTCOME MEASURES: School garden success using the GREEN Tool. ANALYSIS: Descriptive statistics were used to determine the degree of success of school garden programs and explore barriers. Multiple regression analysis was conducted to determine independent predictors of school garden success. RESULTS: The average score was 37 (range 1-53, of a possible 57 points), indicating moderate success. Operating budget (P < .001), operating time (P < .05), and planting in-ground (P < .01) had a positive significant influence on success score, whereas rural location (P < .01) and lacking community interest (P < .01) had a negative significant influence, controlling for race/ethnicity, region, total garden investment, and Community Need Index score (a proxy for socioeconomic status). CONCLUSIONS AND IMPLICATIONS: Results indicate that success of school garden programs may be more difficult for the schools located in a rural area or in the absence of school or community-at-large interest. This study found that race/ethnicity of students and socioeconomic status are not related to success score, which is promising as other research indicates that successful school gardens may be especially impactful for low-income people of color. Causal research is needed to identify strategies that increase school garden success, with a focus on engaging key stakeholders (administrators, teachers, parents, the community at large, and garden coordinators).

7.
ACS Appl Mater Interfaces ; 11(29): 26005-26016, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31294959

RESUMO

Poly(3-hexylthiophene) (P3HT)-based organic solar cells (OSCs) have been extensively studied due to unique advantages of P3HT such as roll-to-roll and large-area printing fabrication, but a poor short-circuit current density greatly limits the enhancement of power conversion efficiency (PCE). Herein, via the thiophene-fused aromatic heterocycle as a "π-bridge", two "A-π-D-π-A"-type acceptors have been designed and synthesized for P3HT-based OSCs. The aromaticity of the fused thiophene ring has effectively stabilized the quinoid population, thus strengthening the intramolecular charge transfer and further improving the current density. Owing to the weaker electron-withdrawing ability of the thiophene-fused benzotriazole unit in JC2 than the thiophene-fused benzothiadiazole unit in JC1, a blue-shifted absorption occurs for JC2 to show a better complementarity with P3HT to improve the light-harvesting efficiency and current density of the derived OSCs, and an uplifted lowest unoccupied molecular orbital energy level is also achieved for JC2 to obtain higher voltages. Thus, the P3HT:JC2-based device exhibits a PCE of 6.24% with a high JSC of 13.96 mA cm-2 and a VOC of 0.71 V, significantly exceeding those of the P3HT:JC1 device with a PCE of 2.80%, a JSC of 10.66 mA cm-2, and a VOC of 0.48 V. This indicates that the fusion of a thiophene ring onto a benzotriazole unit is an effective strategy to balance the VOC and JSC of P3HT-based OSCs to achieve excellent photovoltaic performances.

8.
Theranostics ; 9(13): 3723-3731, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31281509

RESUMO

Single nucleotide polymorphism (SNP) is the most abundant molecular marker associated with many physiologic and pathologic phenotypes. An isothermal, accurate and cost-effective SNP detection could make a great difference in point-of-care testing (POCT) or on-site diagnosis. However, there are two challenges, the expensive instrument and labor-intensive process, faced by the development of on-site SNP detection. We reported a novel SNP typing method based on the probe-enhanced loop-mediated isothermal amplification (PE-LAMP), which combines the oligonucleotide probe with a conventional LAMP to realize the SNP discrimination by analyzing the great discrepancy in amplification efficiency. Methods: We firstly constructed the genotyping method by combining the hybridization of the specific probe with the powerful amplification of LAMP. Then we validated the method by genotyping the SNP rs3741219 and we sought to realize one-step visualized typing. Finally, we applied the method to pharmacogenomic testing by genotyping CYP2C19*2 and MDR1 C3435T. Results: The PE-LAMP was successfully constructed to detect SNP and the sensitivity of our method is as low as 1000 copies of target DNA, which is sufficient to routine diagnosis. The high specificity in detecting mutant in the presence of excess wild-type allele could be achieved. It has shown good performance in helping predict the individual response of antiplatelet drug Clopidogrel through typing simply treated saliva samples. Conclusions: The proposed method is one-step, colorimetric, specific and sensitive enough to detect crudely treated samples, showing great potential in the pharmacogenomic study and POCT use.

9.
Adv Healthc Mater ; 8(15): e1900306, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31211520

RESUMO

Poor cellular uptake and low therapeutic efficacy of small-molecule antitumor drugs limit the application of drug delivery systems (DDSs) in cancer therapy. A conformational change of the Antp mimetic peptide (AMP) in tumor microenvironments can greatly increase the cellular uptake as well as control drug release from a DDS. In this study, AMP-based nanoparticles (AMP-NPs) conjugated with tyroserleutide (YSL), an immunologically therapeutic tripeptide, are designed to encapsulate doxorubicin (Dox) and indocyanine green (ICG) to improve cellular uptake and cancer therapeutic efficacy by combining chemotherapy with photothermal therapy. In vitro studies verify that AMP-NPs can control the release of Dox and YSL at different pH values. Cell experiments show that AMP-NPs can promote the cellular uptake of Dox, and YSL can promote hepatocarcinoma cell (H22) apoptosis through downregulating Bcl-2 and cyclin D1 expression. In a mouse xenograft model using H22 cells, tumors are ablated when Dox- and ICG-loaded AMP-NPs are injected with the combination of hyperthermia effect induced by near-infrared (NIR) laser irradiation and chemotherapy from Dox and YSL. The pH-, photothermal-, and glutathione-responsive AMP-NPs with a conformational transition strategy can be utilized to synergistically enhance the cancer therapeutic efficacy with few side effects upon NIR laser irradiation.

10.
Clin Cancer Res ; 25(17): 5212-5220, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31138588

RESUMO

PURPOSE: This phase I study assessed the safety, tolerability, MTD, pharmacokinetics, antitumor activity, and predictive biomarkers of pyrotinib, an irreversible pan-ErbB inhibitor, in combination with capecitabine in patients with HER2-positive metastatic breast cancer (MBC). PATIENTS AND METHODS: Patients received oral pyrotinib 160 mg, 240 mg, 320 mg, or 400 mg once daily continually plus capecitabine 1,000 mg/m2 twice daily on days 1 to 14 of a 21-day cycle. Pharmacokinetic blood samples were collected on days 1 and 14. Next-generation sequencing was performed on circulating tumor DNA to probe for predictive biomarkers. RESULTS: A total of 28 patients were enrolled, 22 patients were treated at the two top-level doses. Among 17 (60.7%) trastuzumab-pretreated patients, 11 received trastuzumab for metastatic disease and 6 received adjuvant trastuzumab. No dose-limited toxicity was observed. Grade 3 treatment-related adverse events (AE) occurred in 12 (42.9%) patients; anemia (14.3%) and diarrhea (10.7%) were the most common grade 3 AEs. The overall response rate (ORR) was 78.6% [95% confidence interval (CI): 59.0%-91.7%], and the clinical benefit rate was 85.7% (95% CI: 67.3%-96.0%). The median progression-free survival (PFS) was 22.1 months (95% CI: 9.0-26.2 months). ORR was 70.6% (12/17) in trastuzumab-pretreated patients and 90.9% (10/11) in trastuzumab-naïve patients. Analysis of all genetic alterations in HER2-related signaling network in baseline blood samples suggested that multiple genetic alterations were significantly associated with poorer PFS compared with none or one genetic alteration (median, 16.8 vs. 29.9 months, P = 0.006). CONCLUSIONS: In a population largely naïve to HER2-targeted therapy, pyrotinib in combination with capecitabine was well-tolerated and demonstrates promising antitumor activity in patients with HER2-positive MBC.

11.
Talanta ; 201: 126-133, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31122402

RESUMO

Upconversion nanoparticle-based lateral flow assays (UCNP-LFAs) have attracted significant attention in point-of-care testing (POCT) applications, due to the long-term photostability and enhanced signal-to-background noise ratio. The existing UCNP-LFAs generally require peripheral equipment for exciting fluorescent signals and reading out fluorescence results, which are generally bulky and expensive. Herein, we developed a miniaturized and portable UCNP-LFA platform, which is composed of a LFA detection system, an UCNP-LFA reader and a smartphone-assisted UCNP-LFA analyzer. The LFA detection system is based on three types of UCNPs for multiplexed detection. The reader has a dimension of 24.0 cm × 9.4 cm × 5.4 cm (L × W × H) and weight of 0.9 kg. The analyzer based on the custom-designed software of a smartphone (termed as UCNP-LFA analyzer) can get the quantitative analysis results in a real-time manner. We demonstrated the universality of this platform by highly sensitive and quantitative detections of several kinds of targets, including small molecule (ochratoxin A, OTA), heavy metal ion (Hg2+), bacteria (salmonella, SE), nucleic acid (hepatitis B virus, HBV) and protein (growth stimulation expressed gene 2, ST-2). Our developed UCNP-LFA platform holds great promise for applications in disease diagnostics, environmental pollution monitoring and food safety at the point of care.


Assuntos
Imunoensaio/métodos , Nanopartículas/química , Testes Imediatos , Anticorpos/química , Biomarcadores/sangue , DNA/análise , DNA/química , DNA/genética , Érbio/química , Fluoretos/química , Fluoretos/efeitos da radiação , Vírus da Hepatite B/genética , Humanos , Imunoensaio/instrumentação , Proteína 1 Semelhante a Receptor de Interleucina-1/sangue , Proteína 1 Semelhante a Receptor de Interleucina-1/imunologia , Limite de Detecção , Mercúrio/análise , Nanopartículas/efeitos da radiação , Hibridização de Ácido Nucleico , Salmonella/isolamento & purificação , Smartphone , Espectrometria de Fluorescência/métodos , Itérbio/química , Ítrio/química , Ítrio/efeitos da radiação
12.
BMC Cardiovasc Disord ; 19(1): 77, 2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30940095

RESUMO

BACKGROUND: The impact of cerebral microbleeds on the safety of antithrombotic therapy has recently received considerable attention. We investigated the safety of antithrombotic therapy in patients with cerebral microbleeds and cardiogenic cerebral embolism caused by nonvalvular atrial fibrillation. METHODS: This retrospective study enrolled patients with acute cardiogenic cerebral embolism due to nonvalvular atrial fibrillation in the stroke unit of the Department of Neurology at the Beijing Tiantan Hospital, the Capital Medical University, from January 2015 to January 2018. General clinical data, magnetic resonance imaging data, and data regarding the use of antithrombotic medications were collected. The main adverse events were cerebral hemorrhage and all-cause death. RESULTS: According to the susceptibility-weighted imaging sequence, patients were divided into a cerebral microbleeds group and a non-cerebral microbleeds group. Patients with cerebral microbleeds were more likely to be male and to have a history of hypertension and diabetes, and they were less likely to have received anticoagulant therapy (49.1% vs. 71.3%, P = 0.001). However, no significant differences were found in the event-free time, the occurrence of cerebral hemorrhage events and all-cause death. Cox regression analysis showed that the risk of all-cause death in patients with a cerebral hemorrhage history and cerebral microbleeds increased 2.773-fold (HR = 2.773, 95%CI 1.056-7.280, P = 0.019), and the risk of a cerebral hemorrhage event in patients with cerebral microbleeds and a hypertension history (HR = 3.451, 95%CI 1.947-6.119, P = 0.045) or a cerebral hemorrhage history (HR = 2.443, 1.078-5.536, P = 0.006) was increased 3.451-fold and 2.443-fold, respectively. CONCLUSIONS: Antithrombotic therapy in patients with CMBs and cardiogenic cerebral embolism due to nonvalvular atrial fibrillation did not have increased risks of a cerebral hemorrhage event and all-cause death. CMBs were probably not a crucial predictor of whether patients were prescribed antithrombotic medicine. Patients with CMBs and a hypertension history or cerebral hemorrhage history should receive a close follow-up after antithrombotic therapy.

13.
Cancer Med ; 8(5): 2074-2084, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30982232

RESUMO

Genetic testing for germline mutations in BRCA1/2 of patients with breast cancer (BC) is part of routine patient care. However, BRCA1/2 mutations account only for a fraction of familial BC. A custom panel of 22 gene sequencing was performed on each patient. Among the 481 female patients, 135 patients were detected to carry pathogenic (P)/likely pathogenic (LP) mutations (28.1%), which corresponded to 12 different cancer predisposition genes [14.6% (70/481) on BRCA1 gene, 5.0% (24/481) on BRCA2 gene, 8.5% (41/481) on non-BRCA1/2 genes]. Moreover, 24.7% (119/481) of patients had mutation of unknown significance (VUS) in these genes. The most common (8/481) pathogenic mutation is BRCA1 c.5470_5477del, while BRIP1 2392 C > T of patients was detected. All the mutations detected were mainly seen in the homologous recombinant repair pathway. Compared to BRCA2 mutation, BRCA1 mutation is higher in younger female patients (P < 0.01). Some pathogenic mutations were detected in the patients' familiy members without the past history of tumor and 92 novel mutations were detected (31 on BRCA including 2 P, 16 LP, 13 VUS; 61 on non-BRCA1/2 including 9 LP, 52 VUS). The detection rate of BRCA1/2 mutations was higher in patients with three or more cancer family members than those with one or two. However, the difference was not statistically different. The results suggest that multigene panel testing can increase mutation detection rate for high-risk BC patients. Detailed family history can help to categorize new mutations.

14.
Chem Commun (Camb) ; 55(26): 3749-3752, 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30860528

RESUMO

Herein, we provide a direct observation of the modulation of the excited state transition under mechanical and thermal stimuli in the solid state by two organic polymorphs based on a tetraphenylethene derivative (APMOB). It enriches the insight in the research of stimuli responsive luminescent materials.

15.
Environ Int ; 126: 184-192, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30798199

RESUMO

Prostatic enlargement might affect up to 30% of men and can cause signs and symptoms in the lower urinary tract in the elderly. Imbalanced estrogen and androgen secretions are important in prostatic physiopathology. Phthalates-environmental endocrine disruptors-affect androgen secretion and disrupt sexual organs, including testes and the prostate, but the underlying mechanisms are unclear. Using European Association of Urology (EAU) guidelines, we recruited from urology clinics in southern Taiwan 207 elderly men diagnosed with benign prostatic hyperplasia (BPH) and prostatic enlargement between 2015 and 2017. We took blood and urine samples from all patients on the same day. We used multivariate linear regression, associations, and potential interactions after we had measured and analyzed oxidative stress (OS) markers, steroidal hormones, and 11 urinary phthalate metabolites, and then we adjusted for confounders. Di(2-ethylhexyl) phthalate (DEHP) metabolite levels, particularly urinary mono-(2-ethylhexyl) phthalate, were positively associated with androgen, estrogen, hormone ratios, inducible nitric oxide synthetase (iNOS), 8-hydroxy-2'-deoxyguanosine (8-OHdG), prostate specific antigen (PSA), and prostate volume (PV) (p < 0.05). PV and PSA were positively associated with androgen, estrogen, hormone ratios and OS markers (p < 0.05). The estimated percentages of exposure to phthalates in prostatic enlargement mediated by androgen, estrogen, and OS markers ranged from 3.5% to 63.1%. Exposure to DEHP promoted the progress of BPH by increasing dihydrotestosterone (DHT), estradiol (E2), the converted enzymes aromatase and 5α reductase, and reactive oxygen species (ROS) (8-OHdG and iNOS) production. Sex hormones and OS might be important hyperplasia-promoters after a patient has been exposed to phthalates, especially to DEHP.

16.
World J Gastroenterol ; 25(6): 672-682, 2019 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-30783371

RESUMO

Artificial intelligence (AI), particularly deep learning algorithms, is gaining extensive attention for its excellent performance in image-recognition tasks. They can automatically make a quantitative assessment of complex medical image characteristics and achieve an increased accuracy for diagnosis with higher efficiency. AI is widely used and getting increasingly popular in the medical imaging of the liver, including radiology, ultrasound, and nuclear medicine. AI can assist physicians to make more accurate and reproductive imaging diagnosis and also reduce the physicians' workload. This article illustrates basic technical knowledge about AI, including traditional machine learning and deep learning algorithms, especially convolutional neural networks, and their clinical application in the medical imaging of liver diseases, such as detecting and evaluating focal liver lesions, facilitating treatment, and predicting liver treatment response. We conclude that machine-assisted medical services will be a promising solution for future liver medical care. Lastly, we discuss the challenges and future directions of clinical application of deep learning techniques.


Assuntos
Inteligência Artificial , Diagnóstico por Imagem/métodos , Hepatopatias/diagnóstico por imagem , Fígado/diagnóstico por imagem , Algoritmos , Aprendizado Profundo , Humanos , Aprendizado de Máquina , Redes Neurais (Computação)
17.
Cancer Commun (Lond) ; 39(1): 1, 2019 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-30606259

RESUMO

BACKGROUND: Epithelial-mesenchymal transition (EMT) is implicated in the metastatic process and presents a challenge to epithelial cell adhesion molecule-based detection of circulating tumor cells (CTCs), which have been demonstrated to be a prognostic indicator in metastatic breast cancer. Although evidence has indicated that heterogeneity of CTCs based on EMT markers is associated with disease progression, no standard recommendations have been established for clinical practice. This study aimed to evaluate the prognostic significance of dynamic CTC detection based on EMT for metastatic breast cancer patients. METHODS: We enrolled 108 human epidermal growth factor receptor 2-negative metastatic breast cancer patients from the prospective phase III CAMELLIA study and applied the CanPatrol CTC enrichment technique to identify CTC phenotypes (including epithelial CTCs, biphenotypic epithelial/mesenchymal CTCs, and mesenchymal CTCs) in peripheral blood samples. Receiver operating characteristic curve analyses of total CTC count and the proportion of mesenchymal CTCs for predicting the 1-year progression-free survival (PFS) rate were conducted to determine the optimal cut-off values, and Kaplan-Meier analysis and Cox proportional hazards regression analysis were performed to investigate the prognostic value of the cut-off values of both total CTC count and the proportion of mesenchymal CTCs in combination. RESULTS: For predicting the 1-year PFS rate, the optimal cut-off value of total CTC count was 9.5 (Area under the curve [AUC] = 0.538, 95% confidence interval [CI] = 0.418-0.657), and that of the proportion of mesenchymal CTCs was 10.7% (AUC = 0.581, 95% CI = 0.463-0.699). We used the two cut-off values in combination to forecast PFS in which the total CTC count was equaled to or exceeded 10/5 mL with the proportion of mesenchymal CTCs surpassed 10.7%. Patients who met the combined criteria had significantly shorter median PFS than did those who did not meet the criteria (6.2 vs. 9.9 months, P =0.010). A nomogram was constructed based on the criteria and significant clinicopathological characteristics with a C-index of 0.613 (P = 0.010). CONCLUSIONS: The criteria, which combine the total CTC count and the proportion of mesenchymal CTCs, may be used to monitor therapeutic resistance and predict prognosis in patients with metastatic breast cancer. Trial registration ClinicalTrials.gov. NCT01917279. Registered on 19 July 2013, https://clinicaltrials.gov/ct2/show/NCT01917279?term=NCT01917279&rank=1 .


Assuntos
Neoplasias da Mama/tratamento farmacológico , Transição Epitelial-Mesenquimal , Células Neoplásicas Circulantes , Adulto , Idoso , Antígenos de Neoplasias/sangue , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Capecitabina/uso terapêutico , Antígeno Carcinoembrionário/sangue , Contagem de Células , Docetaxel/uso terapêutico , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Receptor ErbB-2 , Resultado do Tratamento
18.
Clin Breast Cancer ; 19(2): e370-e375, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30630678

RESUMO

INTRODUCTION: UGT1A4 is a major enzyme responsible for the glucuronidation of tamoxifen (TAM) and its metabolites. Genetic variations in the UGT1A4 gene could have a significant impact on the clinical efficacy of TAM. This study was performed to validate the association between UGT1A4 polymorphisms and the clinical outcomes for patients with breast cancer who received adjuvant TAM. PATIENTS AND METHODS: A total of 773 patients with breast cancer who received adjuvant TAM (n = 321) or aromatase inhibitors (n = 452) at the National Cancer Center in China were analyzed. Through a series of screenings, the single nucleotide polymorphism rs869283 (c.-1180G>A) in the promoter region of the UGT1A4 gene was selected. The associations of rs869283 genotype with disease-free survival (DFS) and clinicopathologic characteristics were analyzed. RESULTS: A total of 608 (78.7%) patients were wild-type G/G genotype, 154 (19.9%) patients were G/A genotype, and 11 (1.4%) patients were A/A genotype. In the TAM treatment group, patients with A/A or G/A genotype had a lower 5-year DFS rate than those with the wild-type G/G genotype (69.3% vs. 83.7%; P = .031). The rs869283 genotype remained an independent prognostic marker for DFS in multivariate analysis (hazard ratio, 1.74; P = .014). No association between the rs869283 genotype and DFS was found in patients who received AIs (P = .772). CONCLUSIONS: Our findings showed that patients with the UGT1A4 rs869283 G/A or A/A genotype received less benefit from adjuvant TAM treatment than those with the G/G genotype. Further studies are warranted to confirm our findings.

19.
Biomater Sci ; 7(3): 860-866, 2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30698593

RESUMO

Cancer combination therapy based on drug co-delivery systems provides an effective strategy for enhancing treatment efficacy and reducing side effects. In this work, a new strategy through co-delivery of combretastatin A4 disodium phosphate (CA4P) and cisplatin (CDDP) was developed for the local treatment of colon cancer, through an in situ thermo-gelling hydrogel (mPEG-b-PELG). The results indicated that this material possessed concentration-dependent thermogelling properties and tunable in vivo biodegradability. Also, the drug loaded gel could regulate the in vitro drug release behaviors of both CDDP and CA4P, which promoted the in vivo vessel disrupting effects of CA4P compared with a free drug after local treatment for 48 h. Although the drug co-loaded gel induced less in vitro cell death compared with the free drug co-treated group, this drug co-loaded gel depot showed the highest antitumor efficacy compared with the other experimental groups after peritumoral injection toward C26 tumor bearing mice.


Assuntos
Cisplatino/química , Hidrogéis/química , Peptídeos/química , Estilbenos/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/metabolismo , Cisplatino/uso terapêutico , Cisplatino/toxicidade , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Liberação Controlada de Fármacos , Feminino , Humanos , Hidrogéis/síntese química , Camundongos Endogâmicos BALB C , Polímeros/síntese química , Polímeros/química , Estilbenos/metabolismo , Estilbenos/uso terapêutico , Estilbenos/toxicidade , Transplante Heterólogo , Microambiente Tumoral/efeitos dos fármacos
20.
Artigo em Inglês | MEDLINE | ID: mdl-30470975

RESUMO

In the original publication of the article, the authors' affiliation was published incorrectly. The corrected affiliation is given in this correction. The author also found few corrections in the article which are given below.

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