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1.
J Colloid Interface Sci ; 578: 338-345, 2020 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-32535416

RESUMO

HYPOTHESIS: G-quadruplex structure has raised increasing attention in supramolecular chemistry as an effective template for ordered functional materials. Thus, it is of practical significance to advance our understanding regarding G-quadruplex structures. Typically, G-quadruplex structures are formed in the presence of suitable metal ions. New methods to construct such structures need to be explored. EXPERIMENTS: The supramolecular assembly between CTAB and a guanosine derivative at different molar ratios was systematically studied, including assembly mechanisms, morphology, and macroscopic properties. Cationic surfactants with different alkyl chains were studied as control experiments. FINDINGS: A novel strategy to construct G-quadruplex with the promotion of the cationic surfactant CTAB is presented in this work. The structure-property relationships of G-quadruplex gels are characterized by rheology and shrinkage ratio experiments. MacKintosh's theory was used to rationalize the relationship between gel elasticity and water content. The transition of G-quadruplex structures could be easily enabled by modulating CTAB concentration, which promotes the phase transition from gel/sol biphase to homogeneous sol phase. This work will provide a new viewpoint for the construction and modulation of G-quadruplex structures.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32554494

RESUMO

The anthracycline doxorubicin (Doxo) and its analogs daunorubicin (Daun), epirubicin (Epi), and idarubicin (Ida) have been cornerstones of anticancer therapy for nearly five decades. However, their clinical application is limited by severe side effects, especially dose-dependent irreversible cardiotoxicity. Other detrimental side effects of anthracyclines include therapy-related malignancies and infertility. It is unclear whether these side effects are coupled to the chemotherapeutic efficacy. Doxo, Daun, Epi, and Ida execute two cellular activities: DNA damage, causing double-strand breaks (DSBs) following poisoning of topoisomerase II (Topo II), and chromatin damage, mediated through histone eviction at selected sites in the genome. Here we report that anthracycline-induced cardiotoxicity requires the combination of both cellular activities. Topo II poisons with either one of the activities fail to induce cardiotoxicity in mice and human cardiac microtissues, as observed for aclarubicin (Acla) and etoposide (Etop). Further, we show that Doxo can be detoxified by chemically separating these two activities. Anthracycline variants that induce chromatin damage without causing DSBs maintain similar anticancer potency in cell lines, mice, and human acute myeloid leukemia patients, implying that chromatin damage constitutes a major cytotoxic mechanism of anthracyclines. With these anthracyclines abstained from cardiotoxicity and therapy-related tumors, we thus uncoupled the side effects from anticancer efficacy. These results suggest that anthracycline variants acting primarily via chromatin damage may allow prolonged treatment of cancer patients and will improve the quality of life of cancer survivors.

3.
Clin Lung Cancer ; 2020 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-32505632

RESUMO

BACKGROUND: Reliable prediction of progression patterns and failure sites for patients with stage IV lung adenocarcinoma is valuable for physicians to deliver personalized tyrosine kinase inhibitor (TKI) treatment. PATIENTS AND METHODS: We retrospectively enrolled 266 patients who had stage IV lung adenocarcinoma and received first-line TKI treatment from 2013 to 2017 in Shanghai Chest Hospital. The clinical characteristics at initial diagnosis, progression patterns, and failure sites were analyzed with the attempt to identify some predictive factors for progression patterns and failure sites. RESULTS: Among all patients, 62.4% developed systemic progression, and 37.6% developed oligoprogression. Both cohorts had a median progression-free survival (PFS) of 9 months. The percentage of patients who developed original and distant failure was 39.1% and 60.9%, respectively. Patients with oligometastasis at initial diagnosis were more prone to develop oligoprogression (odds ratio [OR], 4.370; 95% confidence interval [CI], 1.881-10.151; P = .001), whereas pulmonary metastasis was negatively correlated with oligoprogression (OR, 0.567; 95% CI, 0.330-0.974; P = .04). Both oligometastasis diagnosis (OR, 2.959; 95% CI, 1.347-6.500; P = .007) and the maximum diameter of the primary lung lesion (threshold 3.25 cm: OR, 3.646; 95% CI, 2.041-6.515; P = .0001) were strong predictive factors for original failures. Osseous metastasis at initial diagnosis might be an indication for distant failure (OR, 0.536; 95% CI, 0.316-0.909; P = .021). CONCLUSION: Over one-half of patients with stage IV lung adenocarcinoma receiving first-line TKI treatment developed systemic progression and distant failure. Metastasis patterns at initial diagnosis was the most important predictive factor for progression patterns and failure sites. The maximum diameter of the primary lung lesion and evidence of osseous metastasis were also found to be significant indicative factors for failure sites.

4.
Environ Pollut ; 262: 114366, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32443214

RESUMO

Ground-level ozone pollution has negative impacts on human health and vegetation and has increased rapidly across China. Various factors are implicated in the formation of ozone (e.g., meteorological factors, anthropogenic emissions), but their relative individual impact and the impact of interactions between these factors remains unclear. This study quantified the influence of specific meteorological conditions and anthropogenic precursor emissions and their interactions on ozone concentrations in Chinese cities using the geographic detector model (GeoDetector). Results revealed that the impacts of meteorological and anthropogenic factors and their interactions on ozone concentrations varied significantly at different spatial and temporal scales. Temperature was the dominant driver at the annual time scale, explaining 40% (q = 0.4) of the ground-level ozone concentration. Anthropogenic precursors and meteorological conditions had comparable effects on ozone concentrations in summer and winter in northern China. Interactions between all the factors can enhance effects. The interaction between meteorological factors and anthropogenic precursors had the strongest impact in summer. The results can be used to enhance our understanding of ozone pollution, to improve ozone prediction models, and to formulate pollution control measures.

5.
J Med Chem ; 63(11): 5865-5878, 2020 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-32390424

RESUMO

Despite the availability of more than 25 antiseizure drugs on the market, approximately 30% of patients with epilepsy still suffer from seizures. Thus, the epilepsy therapy market has a great need for a breakthrough drug that will aid pharmacoresistant patients. In our previous study, we discovered a vitamin K analogue, 2h, which displayed modest antiseizure activity in zebrafish and mouse seizure models. However, there are limitations to this compound due to its pharmacokinetic profile. In this study, we develop a new series of vitamin K analogues by modifying the structure of 2h. Among these, compound 3d shows full protection in a rodent pharmacoresistant seizure model with limited rotarod motor toxicity and favorable pharmacokinetic properties. Furthermore, the brain/plasma concentration ratio of 3d indicates its excellent permeability into the brain. The resulting data shows that 3d can be further developed as a potential antiseizure drug in the clinic.

6.
Proc Natl Acad Sci U S A ; 117(18): 9832-9839, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32317383

RESUMO

G-quadruplex, assembled from a square array of guanine (G) molecules, is an important structure with crucial biological roles in vivo but also a versatile template for ordered functional materials. Although the understanding of G-quadruplex structures is the focus of numerous studies, little is known regarding the control of G-quartet stacking modes and the spontaneous orientation of G-quadruplex fibrils. Here, the effects of different metal ions and their concentrations on stacking modes of G-quartets are elucidated. Monovalent cations (typically K+) facilitate the formation of G-quadruplex hydrogels with both heteropolar and homopolar stacking modes, showing weak mechanical strength. In contrast, divalent metal ions (Ca2+, Sr2+, and Ba2+) at given concentrations can control G-quartet stacking modes and increase the mechanical rigidity of the resulting hydrogels through ionic bridge effects between divalent ions and borate. We show that for Ca2+ and Ba2+ at suitable concentrations, the assembly of G-quadruplexes results in the establishment of a mesoscopic chirality of the fibrils with a regular left-handed twist. Finally, we report the discovery of nematic tactoids self-assembled from G-quadruplex fibrils characterized by homeotropic fibril alignment with respect to the interface. We use the Frank-Oseen elastic energy and the Rapini-Papoular anisotropic surface energy to rationalize two different configurations of the tactoids. These results deepen our understanding of G-quadruplex structures and G-quadruplex fibrils, paving the way for their use in self-assembly and biomaterials.

7.
Sci Total Environ ; 728: 138890, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32339844

RESUMO

A COVID-19 outbreak emerged in Wuhan, China at the end of 2019 and developed into a global pandemic during March 2020. The effects of temperature on the dynamics of the COVID-19 epidemic in China are unknown. Data on COVID-19 daily confirmed cases and daily mean temperatures were collected from 31 provincial-level regions in mainland China between Jan. 20 and Feb. 29, 2020. Locally weighted regression and smoothing scatterplot (LOESS), distributed lag nonlinear models (DLNMs), and random-effects meta-analysis were used to examine the relationship between daily confirmed cases rate of COVID-19 and temperature conditions. The daily number of new cases peaked on Feb. 12, and then decreased. The daily confirmed cases rate of COVID-19 had a biphasic relationship with temperature (with a peak at 10 °C), and the daily incidence of COVID-19 decreased at values below and above these values. The overall epidemic intensity of COVID-19 reduced slightly following days with higher temperatures with a relative risk (RR) was 0.96 (95% CI: 0.93, 0.99). A random-effect meta-analysis including 28 provinces in mainland China, we confirmed the statistically significant association between temperature and RR during the study period (Coefficient = -0.0100, 95% CI: -0.0125, -0.0074). The DLNMs in Hubei Province (outside of Wuhan) and Wuhan showed similar patterns of temperature. Additionally, a modified susceptible-exposed-infectious-recovered (M-SEIR) model, with adjustment for climatic factors, was used to provide a complete characterization of the impact of climate on the dynamics of the COVID-19 epidemic.

8.
J Med Chem ; 63(10): 5501-5525, 2020 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-32321249

RESUMO

Here, we present a new series of hydrazide-bearing class I selective HDAC inhibitors designed based on panobinostat. The cap, linker, and zinc-binding group were derivatized to improve HDAC affinity and antileukemia efficacy. Lead inhibitor 13a shows picomolar or low nanomolar IC50 values against HDAC1 and HDAC3 and exhibits differential toxicity profiles toward multiple cancer cells with different FLT3 and p53 statuses. 13a indirectly inhibits the FLT3 signaling pathway and down-regulates master antiapoptotic proteins, resulting in the activation of pro-caspase3 in wt-p53 FLT3-ITD MV4-11 cells. While in the wt-FLT3 and p53-null cells, 13a is incapable of causing apoptosis at a therapeutic concentration. The MDM2 antagonist and the proteasome inhibitor promote 13a-triggered apoptosis by preventing p53 degradation. Furthermore, we demonstrate that apoptosis rather than autophagy is the key contributing factor for 13a-triggered cell death. When compared to panobinostat, 13a is not mutagenic and displays superior in vivo bioavailability and a higher AUC0-inf value.

9.
Bioorg Chem ; 98: 103721, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32193030

RESUMO

In order to develop multitarget-directed ligands as potential treatments for Alzheimer's disease, twenty-eight new tacrine-hydroxamate derivatives were designed, synthesized, and biologically evaluated. As expected, most of the compounds exhibited inhibitory activities against cholinesterases (ChEs) and histone deacetylase (HDACs). Among the tested compounds, A10 showed not only potent and selective inhibition on AChE at sub-nanomolar potency (AChEIC50 = 0.12 nM, BChEIC50 = 361.52 nM) but also potent inhibition on HDAC (IC50 = 0.23 nM). Moreover, A10 exhibited inhibitory activity on Aß1-42 self-aggregation as well as disaggregation activity on pre-formed Aß fibrils. Furthermore, A10 exhibited antioxidant activity and metal chelating properties. Further mechanistic studies demonstrated that A10 is a pan-inhibitor of HDACs and a mixed-type inhibitor for AChE. It shown that A10 is a BBB penetrant by online prediction. Taken together, the results indicate that A10 can serve as a lead compound to develop promising candidate analogs as AD therapeutics.

10.
Radiat Oncol ; 15(1): 43, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32070383

RESUMO

PURPOSE: To analyze patterns of failure in patients with LA-NSCLC who received definitive chemoradiotherapy (CRT) and to build a nomogram for predicting the failure patterns in this population of patients. MATERIALS AND METHODS: Clinicopathological data of patients with LA-NSCLC who received definitive chemoradiotherapy and follow-up between 2013 and 2016 in our hospital were collected. The endpoint was the first failure after definitive chemoradiotherapy. With using elastic net regression and 5-fold nested cross-validation, the optimal model with better generalization ability was selected. Based on the selected model and corresponding features, a nomogram prediction model was built. This model was also validated by ROC curves, calibration curve and decision curve analysis (DCA). RESULTS: With a median follow-up of 28 months, 100 patients experienced failure. There were 46 and 54 patients who experience local failure and distant failure, respectively. Predictive model including 9 factors (smoking, pathology, location, EGFR mutation, age, tumor diameter, clinical N stage, consolidation chemotherapy and radiation dose) was finally built with the best performance. The average area under the ROC curve (AUC) with 5-fold nested cross-validation was 0.719, which was better than any factors alone. The calibration curve revealed a satisfactory consistency between the predicted distant failure rates and the actual observations. DCA showed most of the threshold probabilities in this model were with good net benefits. CONCLUSION: Clinicopathological factors could collaboratively predict failure patterns in patients with LA-NSCLC who are receiving definitive chemoradiotherapy. A nomogram was built and validated based on these factors, showing a potential predictive value in clinical practice.

11.
Medicine (Baltimore) ; 99(3): e18841, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011499

RESUMO

BACKGROUND: It has been reported the rs10757274 SNP (present on locus 9p21 in the gene for CDKN2BAS1) might be associated with susceptibility to coronary artery disease (CAD). Owing to mixed and inconclusive results, we conducted a meta-analysis to investigate the association between rs10757274 polymorphism and the risk of CAD. OBJECTIVES: The present study aimed to investigate the relationship between rs10757274 polymorphism and the risk of CAD. METHODS: All studies of the rs10757274 SNP with CAD that were published between 2007 and 2018 were retrieved from the PubMed database. Meta-analysis was performed with Stata 14.0 software. The effect size of the rs10757274 SNP with CAD risk was assessed based on the odds ratios (ORs) with calculation of 95% confidence interval (CI). RESULTS: Eleven studies including 52,209 subjects (cases: 7990, controls: 44,219) were included in the final data combination. Pooled overall analyses showed that rs10757274 (allele model: P < .001; dominant model: P < .001; recessive model: P < .001; Heterozygote codominant: P = .002; Homozygote codominant: P < .001) polymorphisms were significantly associated with the likelihood of CAD. Significant heterogeneity between individual studies appears in all 5 models. Further subgroup analyses revealed that rs10757274 polymorphisms were all significantly correlated with the likelihood of CAD and no heterogeneity were observed in West Asians. CONCLUSIONS: Our findings indicated that rs10757274 polymorphisms may serve as genetic biomarkers of CAD, especially in West Asians.


Assuntos
Doença da Artéria Coronariana/genética , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante/genética , Grupo com Ancestrais do Continente Asiático/genética , Humanos
12.
Small ; 16(15): e1902751, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31468669

RESUMO

Enzyme-metal hybrid catalysts (EMHCs), which combine enzymatic and metal catalysis, provide tremendous possibilities for new chemoenzymatic cascade reactions. Here, an overview of the representative achievements in the design of EMHCs and their applications in chemoenzymatic cascade reactions are presented. The preparation of hybrid catalysts is classified into two categories: coimmobilized enzyme-metal heterogeneous catalysts and carrier-free enzyme-metal bioconjugates. Examples of one-pot chemoenzymatic cascade processes catalyzed by the hybrid catalysts are then provided as potential applications. Finally, the limitations and future perspectives of EMHCs are discussed.

13.
J Orthop Res ; 38(4): 902-910, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31736134

RESUMO

Osteosarcoma (OSA) is the most common primary bone malignancy overall and is responsible for considerable adolescent mortality. Approximately 850 patients are newly diagnosed with OSA in the United States each year. While the 5-year survival rate for localized OSA has improved from <20% over 40 years ago to over 65% today, progress has dwindled over the past three decades. Therapeutic stagnation has occurred, in part, as a result of limited preclinical models and the overall heterogeneity of OSA among patients. In this study, we report the establishment and characterization of a novel OSA cell line: OSA 1777. This cell line was isolated from the recurrent tumor specimen of a 19-year-old female who initially experienced 99% tumor necrosis after neoadjuvant chemotherapy and eventually had local recurrence and metastases. We present OSA 1777 growth characteristics, tumor markers, chemotherapeutic sensitivities, and oncogenic spheroid formation. In a two-dimensional (2D) monolayer culture, OSA 1777 exhibited a spindle shape and 60 h doubling time. STR DNA profiling revealed a unique genomic identity not matching any existing human cancer cell lines from the ATCC or DSMZ databases. Consistent with the mesenchymal origin, western blot was positive for vimentin and negative for the carcinoma marker cytokeratin. Within three-dimensional (3D) culture, the cells formed spheroids of similar patterning and smaller size compared with MNNG-HOS and U2OS cell lines. The chemotherapeutic drug sensitivity of OSA 1777 was evaluated in both 2D and 3D culture systems. In summary, we report OSA 1777 as a novel biological model of OSA amenable to future studies focused on OSA that recurs despite an initially strong chemotherapeutic response. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:902-910, 2020.

14.
Environ Sci Pollut Res Int ; 27(3): 3413-3427, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31845252

RESUMO

Excess sludge was loaded by 2450 MHz electromagnetic wave in this study. The mechanism of electromagnetic wave loading on the releasing of bound water before sludge flocculation dewatering was investigated through observing the changes of extracellular polymeric substances (EPS) composition, surface charge, and particle size distribution. The results showed that the 8.55 g/g total suspended solids (TSS) of bound water was reduced with 160 J/mL electromagnetic wave, and the moisture content of sludge decreased by 3.02%. The EPS structure in the sludge floc matrix was destroyed and the LB-EPS content reduced. Simultaneously, infrared spectrum analysis indicated that bound water content was correlated both to the changes of hydrophilic and hydrophobic functional groups. Moreover, protein secondary structure analysis found that looser protein structure facilitated the exposure of internal hydrophobic groups and further promoted the sludge hydrophobic properties. Additionally, electromagnetic wave disintegrated colloidal stability through dipole motion. The zeta potential increased from - 25.57 to - 14.32 mV; the medium particle size (d0.5) decreased from 119.99 to 80.41 µm. More small molecules created in the supernatant were helpful to release bound water, which could further improve flocculation dewaterability of sludge with electromagnetic wave loading.


Assuntos
Esgotos , Eliminação de Resíduos Líquidos , Radiação Eletromagnética , Floculação , Tamanho da Partícula , Água
15.
Sci Total Environ ; 700: 134360, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31629259

RESUMO

The characteristics of dissolved organic matter (DOM) in inflowing river, flowing into drinking water, have profound influences on the quality and safety of water. Here, ultraviolet-visible (UV-vis) spectroscopy and three-dimensional fluorescence (EEM) spectroscopy were combined to investigate the spatiotemporal variations of DOM in Nanfei River flowing into Chaohu Lake in China. 24 water samples and 24 surface sediments samples (including dry-to-wet transition season and wet season in 2018) were collected from different types of outlets. Parallel factor analysis (PARAFAC) model and correlation analysis were conducted to identify the primary sources of DOM. Two humic-like components (C1 235-250 nm/385-430 nm and C3 255-270 nm/455-510 nm) and one tryptophan-like component (C2 270-290 nm/320-350 nm) were effectively identified by PARAFAC model. The results showed DOM concentration presented significant spatiotemporal variations. The concentration was much lower in water than in surface sediments in dry-to-wet transition season, but higher in the wet season. Fluorescence index (FI), biological index (BIX) and humification index (HIX) were used to judge characteristic of DOM origination. These indexes indicated that, DOM in Nanfei River had both the characteristics of humus and autogenous, but neogene autogenic feature was stronger, which was largely due to mixture of water, resuspension and desorption of DOM in sediments and photochemical degradation. In addition, the characteristic parameter of molecular mass of DOM (the values of M) had an obvious linear relationship with the fluorescence intensity ratio of fulvic acid-like to humic acid-like (C1/C3), indicating that macromolecular substances could be removed by adding or improving membrane treatment. These provided technical support for improving quality and comprehensive treatment of drinking water sources.


Assuntos
Monitoramento Ambiental/métodos , Substâncias Húmicas/análise , Poluentes da Água/análise , Benzopiranos , China , Água Potável/química , Análise Fatorial , Fluorescência , Rios/química
16.
Nanoscale ; 11(45): 22108-22117, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31720641

RESUMO

Biomimetic strategies have successfully been applied to confine multiple enzymes on scaffolds to obtain higher catalytic efficiency of enzyme cascades than freely distributed enzymes. However, the origin of high efficiency is poorly understood. We developed a coarse-grained, particle-based model to understand the origin of high efficiency. We found that a reaction intermediate is the key in affecting reaction kinetics. In the case of unstable intermediates, the confinement of multiple enzymes in clusters enhanced the catalytic efficiency and a shorter distance between enzymes resulted in a higher reaction rate and yield. This understanding was verified by co-encapsulating multiple enzymes in metal-organic framework (MOF) nanocrystals as artificially confined multienzyme complexes. The activity enhancement of multiple enzymes in MOFs depended on the distance between enzymes, when the decay of intermediates existed. The finding of this study is useful for designing in vitro synthetic biology systems based on artificial multienzyme complexes.


Assuntos
Materiais Biomiméticos/química , Enzimas Imobilizadas/química , Estruturas Metalorgânicas/química , Modelos Químicos , Complexos Multienzimáticos/química , Catálise , Cinética
17.
Langmuir ; 35(49): 16275-16280, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31721586

RESUMO

The ability to keep surfaces dry is highly desired in many industrial settings, such as condensation, anti-icing, and antifogging. During those applications, phase-change processes are normally involved, and thus the superior superhydrophobic state manifested under ambient conditions is susceptible to collapse under these extreme conditions. Although the design of refined textures offers potential to maintain dry surfaces, the large-scale fabrication of these surfaces is tedious and costly. Herein, we report a facile one-step solution-immersion technique that allows for the attainment of sustained and dry condensation surfaces. Careful optimization of the synthesis procedure and surface morphology, especially the density of microflower structures, the wetting states and departure dynamics of condensate droplets can be mediated, leading to the overall enhanced performances. Our results not only provide important insight for the design of surfaces that promote efficient droplet departure but also promise a large-scale fabrication approach to increase heat transfer in many industrial applications.

18.
Nat Commun ; 10(1): 5165, 2019 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-31727883

RESUMO

Enzymatic catalysis in living cells enables the in-situ detection of cellular metabolites in single cells, which could contribute to early diagnosis of diseases. In this study, enzyme is packaged in amorphous metal-organic frameworks (MOFs) via a one-pot co-precipitation process under ambient conditions, exhibiting 5-20 times higher apparent activity than when the enzyme is encapsulated in corresponding crystalline MOFs. Molecular simulation and cryo-electron tomography (Cryo-ET) combined with other techniques demonstrate that the mesopores generated in this disordered and fuzzy structure endow the packaged enzyme with high enzyme activity. The highly active glucose oxidase delivered by the amorphous MOF nanoparticles allows the noninvasive and facile measurement of glucose in single living cells, which can be used to distinguish between cancerous and normal cells.


Assuntos
Glucose Oxidase/metabolismo , Estruturas Metalorgânicas/química , Animais , Glucose/análise , Células Hep G2 , Humanos , Células MCF-7 , Camundongos , Nanocompostos/química , Nanocompostos/ultraestrutura , Porosidade
19.
Phys Med ; 67: 77-84, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31678800

RESUMO

Using auto-planning, the dosimetric and biological differences between PET- and CT-based target delineation in LA-NSCLC were studied. Twenty-three patients with IIIA-IIIB NSCLC were included in this retrospective study. For each patient, two AP plans (Plan_PET, Plan_CT) were generated based on PET- and CT-based gross tumor volume (GTVPET, GTVCT). The volume, boundary and center of mass (COM) of GTVPET and GTVCT were compared. Dosimetric indicators such as mean lung dose (MLD) and so on were evaluated. Tumor control probability (TCP) of GTVPET and GTVCT and normal tissue complication probability (NTCP) of total lung and heart were calculated. A paired-samples t-test was used to check for significant differences (p < 0.05) between dataset. Volume of GTVPET was significantly smaller than that of GTVCT. Under the premise that GTVPET met the clinical requirements in Plan_PET, GTVCT couldn't satisfy the requirements. GTVCT met the clinical requirements in Plan_CT, and four cases of GTVPET could not satisfy the requirements. Compared with Plan_CT, Plan_PET significantly reduced MLD, V5, V10, V13, V15, V20, V30 and V40 of total lung, and MHD, V30 and V40 of heart, and MUs. No significant difference was observed with respect to Dmax of spinal cord. TCP of GTVPET in Plan_PET was significantly higher than that of GTVCT. NTCP of total lung in Plan_PET was significantly lower than that in Plan_CT. There were differences in volume, boundary, and COM of targets based on the two delineation methods. These led to differences in dosimetric and biological indicators. For LA-NSCLC, the way that most hospitals only use CT to delineate the target should be careful consideration.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Tomografia por Emissão de Pósitrons , Planejamento da Radioterapia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Órgãos em Risco/efeitos da radiação , Radiometria , Dosagem Radioterapêutica
20.
Eur J Radiol ; 121: 108708, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31704600

RESUMO

PURPOSE: To analyze radiation-induced lung injury (RIL) after stereotactic body radiotherapy (SBRT) of lung cancer and the subsequent clinical problems. METHODS: 106 lung cancer patients treated with SBRT were included, their computed tomography (CT) scans were reviewed. Late injury pattern was classified by Koening's, radiologist' diagnosis reports for RIL was reviewed. Logistic regression was used to analyze the predictive model of injury pattern, which was also validated by ROC curve. RESULTS: Radiographic late injury within at least 6 months after SBRT was concluded. The majority of late RIL was mass-like pattern, not the modified conventional pattern. 36.8% patients showed acute injury, which trend to occur late lung injury earlier than patients who were not found acute injury (p = 0.0185). 24.5% RIL cases were misdiagnosed to tumor progression by radiologists. Most misdiagnosis occurred among mass-like pattern. Per fraction dose (p < 0.0001), prescription isodose line (p = 0.027) and age (p = 0.089) trend to associate with the occurrence of mass-like injury pattern. Nomogram was established based on these parameters, ROC curve showed that area under the ROC curve (AUC) of the nomogram was 0.767 (95% CI = 0.677-0.857), which was better than any factors along. CONCLUSION: SBRT for lung cancer patients was safe, the majority of late RIL was mass-like pattern. This injury was difficult to be distinguished from tumor progression, which leaded to misdiagnosis of 24.5% patients receiving SBRT. A nomogram based on age, per fraction dose and the prescription isodose line may assist the diagnosis in clinical practice.


Assuntos
Erros de Diagnóstico/estatística & dados numéricos , Lesão Pulmonar/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Lesões por Radiação/diagnóstico por imagem , Radiocirurgia/efeitos adversos , Tomografia Computadorizada por Raios X/métodos , Idoso , Feminino , Humanos , Modelos Logísticos , Pulmão/diagnóstico por imagem , Pulmão/efeitos da radiação , Lesão Pulmonar/etiologia , Masculino , Curva ROC
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