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1.
Phys Rev Lett ; 126(10): 106601, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33784124

RESUMO

We propose a novel approach to achieve a giant anomalous Hall effect (AHE) in materials with flat bands (FBs). FBs are accompanied by small electronic bandwidths, which consequently increases the momentum separation (K) within pair of Weyl points and, thus, the integrated Berry curvature. Starting from a simple model with a single pair of Weyl nodes, we demonstrated the increase of K and the AHE by decreasing the bandwidth. It is further expanded to a realistic pyrochlore lattice model with characteristic double-degenerated FBs, where we discovered a giant AHE while maximizing the K with nearly vanishing band dispersion of FBs. We identify that such a model system can be realized and modulated through strain engineering in both pyrochlore and spinel compounds based on first-principles calculations, validating our theoretical model and providing a feasible platform for experimental exploration.

2.
ACS Appl Mater Interfaces ; 13(7): 7966-7976, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33566573

RESUMO

Nowadays, there is an increasing demand for more accessible routine diagnostics for patients with respect to high accuracy, ease of use, and low cost. However, the quantitative and high accuracy bioassays in large hospitals and laboratories usually require trained technicians and equipment that is both bulky and expensive. In addition, the multistep bioassays and long turnaround time could severely affect the disease surveillance and control especially in pandemics such as influenza and COVID-19. In view of this, a portable, quantitative bioassay device will be valuable in regions with scarce medical resources and help relieve burden on local healthcare systems. Herein, we introduce the MagiCoil diagnostic device, an inexpensive, portable, quantitative, and rapid bioassay platform based on the magnetic particle spectrometer (MPS) technique. MPS detects the dynamic magnetic responses of magnetic nanoparticles (MNPs) and uses the harmonics from oscillating MNPs as metrics for sensitive and quantitative bioassays. This device does not require trained technicians to operate and employs a fully automatic, one-step, and wash-free assay with a user friendly smartphone interface. Using a streptavidin-biotin binding system as a model, we show that the detection limit of the current portable device for streptavidin is 64 nM (equal to 5.12 pmole). In addition, this MPS technique is very versatile and allows for the detection of different diseases just by changing the surface modifications on MNPs. Although MPS-based bioassays show high sensitivities as reported in many literatures, at the current stage, this portable device faces insufficient sensitivity and needs further improvements. It is foreseen that this kind of portable device can transform the multistep, laboratory-based bioassays to one-step field testing in nonclinical settings such as schools, homes, offices, etc.


Assuntos
Bioensaio , Nanopartículas de Magnetita/química , Smartphone , Estreptavidina/análise , Bioensaio/instrumentação , Humanos , Hidrodinâmica , Influenza Humana/diagnóstico , Fenômenos Magnéticos , Tamanho da Partícula , Propriedades de Superfície
3.
Phys Chem Chem Phys ; 23(3): 2186-2192, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33438686

RESUMO

Subtle changes in molecular structure often lead to significant differences in host-guest interactions, which result in different host-guest recognition capabilities and dynamics behaviours in complex formation. Herein, we reveal the influence of the guest substituents on host-guest molecular recognition by molecular dynamics (MD) simulation and density functional theory (DFT) approaches. The results suggest that the binding energy barrier of acyclic cucurbit[4]uril (ACB[4]) with opiate metabolites gradually decreases. The methyl group in morphine (MOR) and morphine-3-glucuronide (M3G) strengthens the hydrophobicity of the guest, while depressing the energy loss of the desolvation of polar groups (e.g. hydroxyl) inside the ACB[4] cavity. However, in M3G, the 3-glucuronide group located outside the ACB[4] host cavity effectively alleviates the unfavourable desolvation effect of the hydroxyl and increases the binding constant by two orders of magnitude (compared with normorphine (NMOR)). Our findings stressed the essentiality of the binding mode and intermolecular noncovalent interactions in the host-guest selective binding ability.

4.
Sci Adv ; 6(38)2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32948586

RESUMO

It is desirable to experimentally demonstrate an extremely high resonant frequency, assisted by strain-spin coupling, in technologically important perpendicular magnetic materials for device applications. Here, we directly observe the coupling of magnons and phonons in both time and frequency domains upon femtosecond laser excitation. This strain-spin coupling leads to a magnetoacoustic resonance in perpendicular magnetic [Co/Pd] n multilayers, reaching frequencies in the extremely high frequency (EHF) band, e.g., 60 GHz. We propose a theoretical model to explain the physical mechanism underlying the strain-spin interaction. Our model explains the amplitude increase of the magnetoacoustic resonance state with time and quantitatively predicts the composition of the combined strain-spin state near the resonance. We also detail its precise dependence on the magnetostriction. The results of this work offer a potential pathway to manipulating both the magnitude and timing of EHF and strongly coupled magnon-phonon excitations.

5.
World J Gastroenterol ; 26(29): 4327-4342, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32848337

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth most common type of cancer and the fourth leading cause of cancer-related death worldwide. Sarcomatoid HCC, which contains poorly differentiated carcinomatous and sarcomatous components, is a rare histological subtype of HCC that differs from conventional HCC. It is highly aggressive and has a poor prognosis. Its clinicopathological characteristics, surgical outcomes and underlying mechanisms of its highly aggressive nature have not been fully elucidated. AIM: To examine the clinicopathological characteristics and surgical outcomes of sarcomatoid HCC and explore the histogenesis of sarcomatoid HCC. METHODS: In total, 196 patients [41 sarcomatoid HCC and 155 high-grade (Edmondson-Steiner grade III or IV) HCC] who underwent surgical resection between 2007 and 2017 were retrospectively reviewed. The characteristics and surgical outcomes of sarcomatoid HCC were compared with those of patients with high-grade HCC. The histological composition of invasive and metastatic sarcomatoid HCCs was evaluated. RESULTS: Sarcomatoid HCC was more frequently diagnosed at an advanced stage with a larger tumor and higher rates of nonspecific symptom, adjacent organ invasion and lymph node metastasis than high-grade HCC (all P < 0.05). Compared with high-grade HCC patients, sarcomatoid HCC patients are less likely to have typical dynamic imaging features of HCC (44.4% vs 72.7%, P = 0.001) and elevated serum alpha-fetoprotein levels (> 20 ng/mL; 36.6% vs 78.7%, P < 0.001). The sarcomatoid group had a significantly shorter median recurrence-free survival (5.6 mo vs 16.4 mo, log-rank P < 0.0001) and overall survival (10.5 mo vs 48.1 mo, log-rank P < 0.0001) than the high-grade group. After controlling for confounding factors, the sarcomatoid subtype was identified as an independent predictor of poor prognosis. Pathological analyses indicated that invasive and metastatic lesions were mainly composed of carcinomatous components. CONCLUSION: Sarcomatoid HCC was associated with a more advanced stage, atypical dynamic imaging, lower serum alpha-fetoprotein levels and a worse prognosis. The highly aggressive nature of sarcomatoid HCC is perhaps mediated by carcinomatous components.

6.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32718848

RESUMO

BACKGROUND AND AIMS: Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the digestive tract with malignant potential. The current risk classification standard is unable to accurately evaluate the invasiveness and clinical outcomes of GISTs. Ki-67 labelling index (LI) may be an effective indicator in assessing tumour invasiveness and prognosis, however, its exact value in GISTs is still uncertain. The aims of our study were to evaluate the correlation of the Ki-67 LI and clinicopathological features of GISTs and to assess the potential value of the Ki-67 LI in GISTs classification and prognosis. METHODS: The clinical, pathological and prognostic data were collected and analysed to identify the independent influential factors of GISTs risk stratification and the predictors of GISTs prognosis. RESULTS: The Ki-67 LI was significantly associated with the clinicopathological features of tumour progression (P<0.05). It was an independent influential factor of GISTs risk classification (odds ratio: 1.322; 95% confidence interval: 1.031-1.696) (P=0.028), and the area under the curve (AUC) value of the Ki-67 LI on the discrimination ability of GISTs risk stratification was 0.906 (P<0.001). The optimal cutoff value of the Ki-67 LI was 6% (sensitivity of 87.5% and specificity of 76.2%), and patients with Ki-67 LI≥6% exhibited significantly poorer progression-free survival (PFS) than those with Ki-67 LI<6% (P<0.001). The AUC value of the Ki-67 LI for predicting PFS in postoperative patients was 0.813 (P=0.03). CONCLUSIONS: The Ki-67 LI has appreciated value to predict the risk grade and prognosis of GISTs. Patients with Ki-67 LI≥6% are prone to recurrence and metastasis after operation and may need a close follow-up.

7.
Gastroenterol Rep (Oxf) ; 8(3): 234-241, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32665855

RESUMO

Background: Preoperative fluoropyrimidine with radiotherapy was regarded as the standard of care for locally advanced rectal cancer (LARC). The model for predicting pCR in LARC patients was based on standard treatment only. This study aimed to establish a nomogram with pretherapeutic parameters and different neoadjuvant regimens for predicting pathologic complete response (pCR) and tumor downstaging or good response (ypT0-2N0M0) after receiving neoadjuvant treatment in patients with LARC based on a randomized clinical trial. Methods: Between January 2011 and February 2015, 309 patients with rectal cancer were enrolled from a prospective randomized study (NCT01211210). All pretreatment clinical parameters were collected to build a nomogram for predicting pCR and tumor downstaging. The model was subjected to bootstrap internal validation. The predictive performance of the model was assessed with concordance index (C-index) and calibration plots. Results: Of the 309 patients, 53 (17.2%) achieved pCR and 132 (42.7%) patients were classified as tumor downstaging with ypT0-2N0M0. Based on the logistic-regression analysis and clinical consideration, tumor length (P = 0.005), tumor circumferential extent (P = 0.036), distance from the anal verge (P = 0.019), and neoadjuvant treatment regimen (P < 0.001) showed independent association with pCR following neoadjuvant treatment. The tumor length (P = 0.015), tumor circumferential extent (P = 0.001), distance from the anal verge (P = 0.032), clinical T category (P = 0.012), and neoadjuvant treatment regimen (P = 0.001) were significantly associated with good tumor downstaging (ypT0-2N0M0). Nomograms were developed to predict the probability of pCR and tumor downstaging with a C-index of 0.802 (95% confidential interval [CI], 0.736-0.867) and 0.730 (95% CI, 0.672-0.784). Internal validation revealed good performance of the calibration plots. Conclusions: The nomogram provided individual prediction responses to different preoperative treatment for patients with rectal cancer. This model might help physicians in selecting an optimized treatment, but warrants further external validation.

8.
Curr Med Sci ; 40(3): 596, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32681267

RESUMO

The article "Polysubstituted Phenyl Glucosides Produced by the Fungus Metarrhizium anisopliae", written by Wen-jing WANG, Chong DAI, Jian-ping WANG, Hu-cheng ZHU, Chun-mei CHEN, Yong-hui ZHANG, was originally published electronically on the publisher's internet portal on May 2020 without open access. With the author(s)' decision to opt for Open Choice, the copyright of the article is changed to © The Author(s) 2020 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ ), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made..The original article has been corrected.

9.
Nanotechnology ; 31(37): 375501, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32492673

RESUMO

This work is a micromagnetic simulation-based study on the GHz-frequency ferromagnetic resonances (FMR) for the detection of magnetic nanoparticles (MNPs) using spin current nano-oscillator (SCNO) operating in precession mode. Capture antibody-antigen-detection antibody-MNP complex on the SCNO surface generates magnetic fields that modify the FMR peaks and generate measurable resonance peak shifts. Moreover, our results strongly indicate the position-sensitive behavior of the SCNO biosensor and demonstrate ways to eradicate this effect to facilitate improved bio-sensing. Additionally, a study has been made on how MNPs with different sizes can alter the SCNO device performance. This simulation-based study on the SCNO device shows the feasibility of a frequency-based nano-biosensor with the sensitivity of detecting a single MNP, even in presence of background noise.

10.
ACS Omega ; 5(20): 11756-11767, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32478267

RESUMO

Magnetic nanoparticles (MNPs) have been extensively used in drug/gene delivery, hyperthermia therapy, magnetic particle imaging (MPI), magnetic resonance imaging (MRI), magnetic bioassays, and so forth. With proper surface chemical modifications, physicochemically stable and nontoxic MNPs are emerging contrast agents and tracers for in vivo MRI and MPI applications. Herein, we report the high magnetic moment, irregularly shaped γ'-Fe4N nanoparticles for enhanced hyperthermia therapy and T2 contrast agent for MRI application. The static and dynamic magnetic properties of γ'-Fe4N nanoparticles are characterized by a vibrating sample magnetometer (VSM) and a magnetic particle spectroscopy (MPS) system, respectively. Compared to the γ-Fe2O3 nanoparticles, γ'-Fe4N nanoparticles show at least three times higher saturation magnetization, which, as a result, gives rise to the stronger dynamic magnetic responses as proved in the MPS measurement results. In addition, γ'-Fe4N nanoparticles are functionalized with an oleic acid layer by a wet mechanical milling process. The morphologies of as-milled nanoparticles are characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), and nanoparticle tracking analyzer (NTA). We report that with proper surface chemical modification and tuning on morphologies, γ'-Fe4N nanoparticles could be used as tiny heating sources for hyperthermia and contrast agents for MRI applications with minimum dose.

11.
Phys Rev Lett ; 124(18): 187701, 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32441982

RESUMO

We demonstrate a voltage-controlled exchange bias effect in CoFeB/MgO/CoFeB magnetic tunnel junctions that is related to the interfacial Fe(Co)O_{x} formed between the CoFeB electrodes and the MgO barrier. The unique combination of interfacial antiferromagnetism, giant tunneling magnetoresistance, and sharp switching of the perpendicularly magnetized CoFeB allows sensitive detection of the exchange bias. We find that the exchange bias field can be isothermally controlled by magnetic fields at low temperatures. More importantly, the exchange bias can also be effectively manipulated by the electric field applied to the MgO barrier due to the voltage-controlled antiferromagnetic anisotropy in this system.

12.
Curr Med Sci ; 40(2): 232-238, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32337684

RESUMO

Metarhizosides A-G (1-7), seven new polysubstituted phenyl glucosides, were isolated from the extracts of solid rice medium of a marine-derived fungus Metarrhizium anisopliae. Compounds 1-7 all contain a polysubstituted phenyl group and the sugar unit is identified as 4'-O-methyl-ß-D-glucopyranose. Their structures were elucidated by NMR spectroscopy and chemical method. These compounds were evaluated for anti-inflammatory activity by using LPS-stimulated murine macrophage RAW 264.7 cells and the cytotoxicities against four human cancer cell lines.

13.
Food Chem ; 319: 126539, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32193060

RESUMO

Two molecularly imprinted microspheres and two fluorescent tracers for benzimidazoles and pyrethroids were synthesized respectively. The two types of microspheres were coated in the wells of conventional microplate simultaneously. Then the sample extracts and the two traces were added for differential competition. The fluorescence intensities at two different emission wavelengths were excited and recorded for quantification of the two classes of drugs respectively. The optimized multiplexed fluorescence method could be used to determine 8 benzimidazoles and 10 pyrethroids in mutton and beef samples simultaneously. The limits of detection of the method for the 18 drugs were in the range of 5.2-17 ng/mL, and the recoveries from the standards fortified blank samples were in the range of 67.7%-109%. From the analysis of 60 real mutton and beef samples, this method could be used for multi-screening the residues of benzimidazoles and pyrethroids in meat samples.


Assuntos
Benzimidazóis/análise , Piretrinas/análise , Carne Vermelha/análise , Animais , Benzimidazóis/química , Fluorescência , Microesferas , Impressão Molecular , Estrutura Molecular , Piretrinas/química
14.
ACS Appl Mater Interfaces ; 12(12): 13686-13697, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32150378

RESUMO

Magnetic nanoparticles (MNPs) with proper surface functionalization have been extensively applied as labels for magnetic immunoassays, carriers for controlled drug/gene delivery, tracers and contrasts for magnetic imaging, etc. Here, we introduce a new biosensing scheme based on magnetic particle spectroscopy (MPS) and the self-assembly of MNPs to quantitatively detect H1N1 nucleoprotein molecules. MPS monitors the harmonics of oscillating MNPs as a metric for the freedom of rotational process, thus indicating the bound states of MNPs. These harmonics can be readily collected from nanogram quantities of iron oxide nanoparticles within 10 s. The H1N1 nucleoprotein molecule hosts multiple different epitopes that forms binding sites for many IgG polyclonal antibodies. Anchoring IgG polyclonal antibodies onto MNPs triggers the cross-linking between MNPs and H1N1 nucleoprotein molecules, thereby forming MNP self-assemblies. Using MPS and the self-assembly of MNPs, we were able to detect as low as 44 nM (4.4 pmole) H1N1 nucleoprotein. In addition, the morphologies and the hydrodynamic sizes of the MNP self-assemblies are characterized to verify the MPS results. Different MNP self-assembly models such as classical cluster, open ring tetramer, and chain model as well as multimers (from dimer to pentamer) are proposed in this paper. Herein, we claim the feasibility of using MPS and the self-assembly of MNPs as a new biosensing scheme for detecting ultralow concentrations of target biomolecules, which can be employed as rapid, sensitive, and wash-free magnetic immunoassays.

16.
Gastroenterol Rep (Oxf) ; 8(1): 36-41, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32104584

RESUMO

Background: Transanal total mesorectal excision (taTME) has recently emerged as a promising novel surgical procedure for rectal cancer. It is believed to hold the potential advantage of providing better access to mobilize the distal rectum and achieving better pathologic results. This study aimed to evaluate the feasibility of taTME for rectal cancer and summarize the preliminary experience in 10 Chinese hospitals. Methods: A total of 211 patients were enrolled in this study. Variables for evaluation of safety, feasibility, and oncologic outcomes were retrospectively collected and analysed. Results: The median distance between the tumor and the anal verge was 5.9 cm (range, 1.5-12 cm). The median operating time was 280 min (range, 70-600 min) and the median estimated intra-operative blood loss was 50 mL (range, 10-1,500 mL). The overall rate of complication was 27.9%. Among the 211 patients, 175 (82.9%) had complete TME and 33 (15.6%) had near complete TME. The circumferential resection margin was negative in 97.7% of patients. The patients were followed for a median of 35 months (range, 2-86 months). There was 7.6% (16) mortality, 6.2% (13) had local recurrence, and 12.8% (27) had systemic recurrence. Kaplan-Meier survival analysis showed that 1-, 2-, and 3-year disease-free survival rates were 94.8%, 89.3%, and 80.2%, respectively, and 1-, 2-, and 3-year OS rates were 97.4%, 95.7%, and 92.9%, respectively. Conclusions: Although limited by its retrospective nature, taTME was safe and feasible in selected patients. Future work with rigorous data recording is warranted.

17.
Luminescence ; 35(1): 120-128, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31486187

RESUMO

The residues of pyrethroids in foods of animal origin are dangerous to the consumers, so this study presented a chemiluminescence sensor for determination of pyrethroids in chicken samples. A dual-dummy-template molecularly imprinted polymer capable of recognizing 10 pyrethroids was synthesized. The results of computation simulation showed that the specific 3D conformations of the templates had important influences on the polymer' recognition ability. The polymer was used to prepare a sensor on conventional 96-well microplates, and the sample solution was added into the wells for direct absorption. The absorbed analytes were initiated with the bis(2,4,6-trichlorophenyl)oxalate-H2 O2 -imidazole system, and the chemiluminescence intensity was used for analyte quantification. Results showed that one assay was finished within 12 min, and this sensor could be reused four times. The limits of detection for the 10 analytes were in the range o0.3-6.0 pg/ml, and the recoveries from the standards of fortified blank chicken samples were in the range 70.5-99.7%.


Assuntos
Inseticidas/análise , Medições Luminescentes , Simulação de Dinâmica Molecular , Impressão Molecular , Polímeros/química , Piretrinas/análise , Estrutura Molecular
18.
Food Chem ; 311: 125966, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31862567

RESUMO

A hapten of sulfabenzamide was first synthesized to generate a monoclonal antibody that simultaneously recognized 32 sulfonamides. The computational simulation showed that the 3D conformation, molecular bend angle, molecular volume, electronic charge of core structure of these drugs all showed influences on the antibody binding. The antibody was combined with a heterologous enzyme-labeled hapten to develop a direct competitive chemiluminescence enzyme linked immunosorbent assay for determination of the 32 sulfonamides in chicken muscle sample. The CRs of the optimized method for these drugs were in the range of 7.3%-1778%, and the IC50 values were in the range of 0.038-11.2 ng/g. The limits of detection for detection of these drugs in chicken were in the range of 0.03-26 ng/g. Their recoveries from the standards fortified blank chicken samples were in the range of 60.8%-97.1%. Therefore, this method could be used as a useful tool for routine screening sulfonamides residues in meat.


Assuntos
Anticorpos Monoclonais/imunologia , Galinhas/metabolismo , Imunoensaio/métodos , Músculos/química , Sulfonamidas/análise , Animais , Contaminação de Alimentos/análise , Haptenos/química , Medições Luminescentes , Músculos/metabolismo , Sulfonamidas/química , Sulfonamidas/imunologia
19.
Aging (Albany NY) ; 11(21): 9264-9279, 2019 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-31683259

RESUMO

This study explored the influence of long non-coding RNA (lncRNA) SNHG14 on α-synuclein (α-syn) expression and Parkinson's disease (PD) pathogenesis. Firstly, we found that the expression level of SNHG14 was elevated in brain tissues of PD mice. In MN9D cells, the rotenone treatment (1µmol/L) enhanced the binding between transcriptional factor SP-1 and SNHG14 promoter, thus promoting SNHG14 expression. Interference of SNHG14 ameliorated the DA neuron injury induced by rotenone. Next, we found an interaction between SNHG14 and miR-133b. Further study showed that miR-133b down-regulated α-syn expression by targeting its 3'-UTR of mRNA and SNHG14 could reverse the negative effect of miR-133b on α-syn expression. Interference of SNHG14 reduced rotenone-induced DA neuron damage through miR-133b in MN9D cells and α-syn was responsible for the protective effect of miR-133b. Similarly, interference of SNHG14 mitigated neuron injury in PD mouse model. All in all, silence of SNHG14 mitigates dopaminergic neuron injury by down-regulating α-syn via targeting miR-133b, which contributes to improving PD.


Assuntos
Neurônios Dopaminérgicos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , MicroRNAs/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Doença de Parkinson Secundária/etiologia , alfa-Sinucleína/metabolismo , Animais , Linhagem Celular , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Doença de Parkinson Secundária/metabolismo , RNA Longo não Codificante/metabolismo , Rotenona
20.
Cancer Med ; 8(18): 7774-7780, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31670906

RESUMO

BACKGROUND: Cervical cancer is one of the most common causes of cancer-associated mortality among affected women in the world. At present, treatment with weekly cisplatin plus ionizing radiation (IR) therapy is the standard regimen for cervical cancer, especially for locally advanced cervical cancer. The purpose of this study is to determine whether FEN1 inhibitors could enhance the therapeutic effect of IR therapy. METHODS: Western blot was applied to determine the expression of FEN1- and apoptosis-related proteins. Cell growth inhibition assay and colony formation assay were used to determine the effects of FEN1 inhibitor and IR exposure for Hela cells in vitro. CRISPR technology was used to knockdown FEN1 expression level of 293T cells, and tumor xenograft in nude mice was employed to determine the effects of FEN1 inhibitor and IR exposure on tumor growth in vivo. RESULTS: Our data revealed that FEN1 is overexpressed in HeLa cell and can be upregulated further by IR. We also demonstrated that FEN1 inhibitor enhances IR sensitivity of cervical cancer in vitro and in vivo. CONCLUSION: FEN1 inhibitor SC13 could sensitize radiotherapy of cervical cancer cell.


Assuntos
Inibidores Enzimáticos/farmacologia , Endonucleases Flap/antagonistas & inibidores , Tolerância a Radiação/efeitos dos fármacos , Radiossensibilizantes/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Modelos Animais de Doenças , Feminino , Endonucleases Flap/genética , Endonucleases Flap/metabolismo , Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Células HeLa , Humanos , Camundongos , Radiação Ionizante , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
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