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1.
Cancer Med ; 13(11): e7347, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38845476

RESUMO

BACKGROUND: With the increasing use of daratumumab (DARA)-containing regimens for multiple myeloma (MM) patients in China, the standard infusion time of DARA is long, with the potential for infusion-related reactions (IRRs) and increased hospitalization and use of resources. Shortening the duration of DARA infusion helps to optimize the hospital stay and enhance the patient treatment experience. The current, commonly used 90-min rapid DARA infusion regimen may not be applicable to Chinese MM patients, and therefore, we explored a new 110-min rapid DARA infusion regimen aimed at reducing the treatment burden on patients to guarantee therapeutic safety. METHODS: MM inpatients treated with the DARA regimen were divided into two groups according to the number of times the DARA regimen was used: a standard infusion regimen for patients treated with the first two doses of DARA and a 110-min rapid infusion regimen for patients treated with more than two doses of DARA. Anti-allergy medications were routinely administered prior to the start of DARA infusion, patient consent, and authorization was obtained for all treatments, and statistical evaluation of the results was conducted via descriptive analyses, one-way ANOVA and chi-square tests. RESULTS: A total of 129 patients were included in this study: 68 in the standard infusion group, with 121 DARA infusions, and 129 in the rapid infusion group (patients who participated in the standard infusion subsequently participated in the rapid infusion), with 738 DARA infusions. The incidence of IRRs was 27.27% (36/121) in the standard infusion group and 1.35% (10/738) in the rapid infusion group, which were significantly different (p < 0.001). The incidence of IRRs after rapid infusion in other studies was <6%. The incidence of grade 1 IRRs in the rapid infusion group was 0.81% (6/738), the incidence of grade 2 IRRs was 0.54% (4/738), and there were no IRRs above grade 3; age, sex, and underlying disease had no effect on the choice of infusion method (p > 0.05). The mean infusion time after the occurrence of IRRs was also shorter in the rapid infusion group than in the standard infusion group (F = 24.781, p < 0.001). CONCLUSION: The 110-min rapid infusion DARA regimen is feasible and safe for use in Chinese MM patients.


Assuntos
Anticorpos Monoclonais , Estudos de Viabilidade , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Infusões Intravenosas , Idoso , China , Adulto , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Fatores de Tempo , Idoso de 80 Anos ou mais , Resultado do Tratamento , População do Leste Asiático
2.
J Inflamm Res ; 17: 2119-2135, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38595338

RESUMO

Purpose: Immune microenvironment plays an important role in aortic dissection (AD). Therefore, novel immune biomarkers may facilitate AD prevention, diagnosis, and treatment. This study aimed at mining key immune-related genes and relevant mechanisms involved in AD pathogenesis. Patients and Methods: Key immune cells in AD were identified by ssGESA algorithm. Next, genes associated with key immune cells were screened by weighted gene coexpression network analysis (WGCNA). Then hub immune genes were picked from protein-protein interaction network of overlapped genes from differential expression and WGCNA analyses by cytohubba plug-in. Their diagnostic potential was evaluated in two independent cohorts from GEO database. In addition, the expressions of hub immune genes were determined by quantitative RT-PCR, immunohistochemistry, and Western blotting in dissected and normal aortic tissues. Results: Activated B cells, CD56dim natural killer cells, eosinophils, gamma delta T cells, immature B cells, natural killer cells and type 17 T helper cells were identified as key immune cells in AD. Thereafter, a gene module significantly correlated with key immune cells were found by WGCNA method. Subsequently, KDR, IGF1, NOS3, PECAM1, GAPDH, FLT1, DLL4, CDH5, VWF, and TEK were identified as hub immune cell related genes by PPI network analysis, which may be potential diagnostic markers for AD, as evidenced by ROC curves. Moreover, the decreased expression of VWF in AD was validated at both mRNA and protein levels, and its expression was significantly positive correlated with the marker of smooth muscle cells, ACTA2, in AD. Further immunofluorescent results showed that VWF was colocalized with ACTA2 in aortic tissues. Conclusion: We identified key immune cells and hub immune cell-related genes involved in AD. Moreover, we found that VWF was co-expressed with the smooth muscle cell marker ACTA2, indicating the important role of VWF in smooth muscle cell loss in AD pathogenesis.

3.
Environ Pollut ; 346: 123562, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38365078

RESUMO

Carbon black and cadmium (Cd) are important components of atmospheric particulate matter and cigarette smoke that are closely associated with the occurrence and development of lung diseases. Carbon black, particularly carbon black nanoparticles (CBNPs), can easily adsorbs metals and cause severe lung damage and even cell death. Therefore, this study aimed to explore the mechanisms underlying the combined toxicity of CBNPs and Cd. We found that the combined exposure to CBNPs and Cd promoted significantly greater autophagosome formation and ferroptosis (increased malonaldehyde (MDA), reactive oxygen species (ROS), and divalent iron ions (Fe2+) levels and altered ferroptosis-related proteins) compared with single exposure in both 16HBE cells (human bronchial epithelioid cells) and mouse lung tissues. The levels of ferroptosis proteins, transferrin receptor protein 1 (TFRC) and glutathione peroxidase 4 (GPX4), were restored by CBNPs-Cd exposure following treatment with a 3-MA inhibitor. Additionally, under CBNPs-Cd exposure, circPSEN1 overexpression inhibited increases in the autophagy proteins microtubule-associated protein 1 light chain 3 (LC3II/I) and sequestosome-1 (P62). Moreover, increases in TFRC and Fe2+, and decreases in GPX4were inhibited. Knockdown of circPSEN1 reversed these effects. circPSEN1 interacts with autophagy-related gene 5 (ATG5) protein and upregulates nuclear receptor coactivator 4 (NCOA4), the co-interacting protein of ATG5, thereby degrading ferritin heavy chain 1 (FTH1) and increasing Fe2+ in 16HBE cells. These results indicated that the combined exposure to CBNPs and Cd promoted the binding of circPSEN1 to ATG5, thereby increasing autophagosome synthesis and ATG5-NCOA4-FTH1 axis activation, ultimately inducing autophagy-dependent ferroptosis in 16HBE cells and mouse lung tissues. This study provides novel insights into the toxic effects of CBNPs and Cd in mixed pollutants.


Assuntos
Cádmio , Ferroptose , Humanos , Camundongos , Animais , Cádmio/toxicidade , Fuligem/toxicidade , Autofagia , Células Epiteliais
4.
Am J Med Sci ; 367(5): 296-303, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38278361

RESUMO

Traditionally, red blood cells (RBCs) have been perceived as passive entities within the fibrin network, without any significant role in the pathophysiology of venous thromboembolism (VTE). This review explores the involvement of RBCs in the VTE process, summarizing previous study findings and providing a comprehensive review of the latest theories. At first, it explores the influence of abnormal RBC counts (as seen in polycythemia vera and with erythropoietin use) and the exposure of RBCs to phosphatidylserine (Ptd-L-Ser) in the pathophysiology of VTE. The mechanisms of endothelial injury induced by RBCs and their adhesion to the endothelium under different disease models are then demonstrated. We explore the role of physical and chemical interactions between RBCs and platelets, as well as the interactions between RBCs and neutrophils - particularly the neutrophil extracellular traps (NETs) released by neutrophils - in the process of VTE. Additionally, we investigate the effect of RBCs on thrombin activation through two pathways, namely, the FXIIa-FXI-FIX pathway and the prekallikrein-dependent pathway. Lastly, we discuss the impact of RBCs on clot volume. In conclusion, we propose several potential methods aimed at unraveling the role of RBCs and their interaction with other components in the vascular system in the pathogenesis of VTE.


Assuntos
Trombose , Tromboembolia Venosa , Humanos , Trombose/metabolismo , Eritrócitos/metabolismo , Plaquetas , Neutrófilos
5.
Small ; 20(23): e2310184, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38148310

RESUMO

Aqueous potassium-ion batteries (AKIBs) are considered promising electrochemical energy storage systems owing to their high safety and cost-effectiveness. However, the structural degradation resulting from the repeated accommodation of large K-ions and the dissolution of active electrode materials in highly dielectric aqueous electrolytes often lead to unsatisfactory electrochemical performance. This study introduces a high-entropy Prussian blue analog (HEPBA) cathode material for AKIBs, demonstrating significantly enhanced structural stability and reduced dissolution. The HEPBA exhibits a highly reversible specific capacity of 102.4 mAh g-1, with 84.4% capacity retention after undergoing 3448 cycles over a duration of 270 days. Mechanistic insights derived from comprehensive experimental investigations, supported by theoretical calculations, reveal that the HEPBA features a robust structure resistant to dissolution, a solid-solution reaction pathway with negligible volume variation during charge-discharge, and efficient ion transport kinetics characterized by a reduced band gap and a low energy barrier. This study represents a measurable step forward in the development of long-lasting electrode materials for aqueous AKIBs.

6.
Foods ; 11(22)2022 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-36429218

RESUMO

Adsorption is an important technology for the separation of different tea components. The adsorption behavior of L-theanine onto adsorbents was comprehensively studied in this paper. Among tested adsorbents, cation exchange resin ZGSPC106Na and D001SD were suitable for separating L-theanine, PVPP and PA-6 for catechins and macroporous resin HPD-400 for caffeine. Adsorption of L-theanine onto the cation resins was significantly influenced by the acidity, contact time and temperature. The adsorption behavior could be described by the pseudo-second-order rate equation and fitted to Langmuir and Freundlich models. ZGSPC106Na exhibited higher adsorption capacity, while D001SD showed higher adsorption selectivity. These might be attributed to the distinctive structure of the two resins and different ionization of the adsorbates. A method for simultaneous preparation of decaffeinated polyphenols, caffeine-enriched extract and decaffeinated L-theanine was established through successive separation on the columns fulfilled with PA-6, HPD-400 and D001SD, respectively.

7.
Angew Chem Int Ed Engl ; 61(42): e202209619, 2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36036208

RESUMO

The rechargeability of contemporary lithium-ion batteries (LIBs) is challenging at low temperatures, mainly due to the hurdles faced by graphite anodes. Herein, by exploiting the Li-solvent co-intercalation into graphite, its low-temperature rechargeability is boosted. Experimental characterizations aided by theoretical calculations demonstrate that the co-intercalation process is featured by low interfacial resistance with a small charge transfer activation energy (0.23 eV atom-1 ) and an extremely low diffusion energy barrier (0.09 eV atom-1 ) which leads to nearly temperature-independent diffusion coefficients of the solvated Li-ion in graphite, enabling graphite to be stably charged-discharged at -60 °C with 73.7 % of its room-temperature capacity. Consequently, the full-cell consisting of a LiNi0.65 Co0.15 Mn0.2 O2 cathode and a graphite anode shows impressive rechargeability under -60 °C. This work provides an alternative approach to develop low-temperature rechargeable LIBs.

8.
Angew Chem Int Ed Engl ; 61(31): e202206012, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35642627

RESUMO

The high activation barrier, inferior rate performance, and short cycling life severely constrain the practical applications of the high-capacity Li2 S cathode. Herein, we fabricate a Li2 S-Cu nanocomposite with a drastically reduced activation potential, fast rate capability, and extraordinary cycling stability even under a practically relevant areal capacity of 2.96 mAh cm-2 . Detailed experimental investigations aided by theoretical calculations indicate that instead of converting to S8 via troublesome soluble lithium polysulfides, Li2 S is thermodynamically and kinetically more favorable to react with Cu by the displacement reaction, which alters the redox couple from Li2 S/S to Cu/Cu2 S, leading to the excellent electrochemical performance. Moreover, the stability of the composite is demonstrated in the full-cell configuration consisting of commercial graphite anodes. This work provides an innovative and effective approach to realize highly activated and stable Li2 S cathode materials.

9.
ACS Nano ; 15(11): 18419-18428, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34704750

RESUMO

Potassium-ion batteries (KIBs) are considered as low-cost electrochemical energy storage technologies because of the abundant potassium resources. However, the practical applications of KIBs are mainly hampered by the unsatisfactory electrochemical performance of anode materials which often undergo large volume variations during potassiation-depotassiation, limiting their cycling life. Here, low-cost sulfurized polyacrylonitrile (S-PAN) is reported as an attractive anode candidate for KIBs. It provides a high potassium storage capacity of 569 mAh g(S-PAN)-1 with decent rate capability and cycling stability (no capacity loss after 1500 cycles, running time ∼188 days). Detailed ex situ spectroscopic and in situ microscopic characterizations reveal that the distinguished electrochemical performance of S-PAN is attributed to the high reversibility of its covalent C-S and S-S bonds which undergo repeated cleavage-redimerization during potassiation-depotassiation concomitant with relatively small volume variation (less than 24.2%). Subsequently, a full-cell constructed by pairing high-voltage K2MnFe(CN)6 cathode with high-capacity S-PAN anode demonstrates an attractive energy density (290.9 Wh kg-1) and long-term cycling stability (1200 cycles with 95.4% capacity retention). Given the high performance and low cost of both anode and cathode materials, it is believed that the present full-cell promises it as a competitive energy storage system for the cost-sensitive grid-scale applications.

10.
ACS Nano ; 15(7): 11694-11703, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34181391

RESUMO

In this contribution, we fabricated a composite consisting of two polymorphs of FeS2, pyrite (P-FeS2) and marcasite (M-FeS2), for high-performance Li-FeS2 battery. A series of electrochemical, microscopic, and spectroscopic characterizations indicate that the introduction of metastable M-FeS2 into P-FeS2 enables the four-electron reduction between FeS2 and lithium to generate Fe and Li2S, providing a high specific capacity of 894 mAh/g with specific energy over 1300 Wh/kg. Moreover, it is verified that the electrochemical irreversibility of this composite toward lithium storage is mainly rooted in the shuttle effect, caused by the elemental sulfur which is inevitably produced during the oxidation process of Li2S and Fe. To tackle this issue, copper (Cu) current collector is adopted to chemically immobilize the soluble lithium polysulfides and fundamentally alter the reaction pathway. It is shown that compared with Fe, Li2S prefers to react with Cu current collector to generate Cu2S through the thermodynamically facile displacement reaction mechanism benefiting from the similar lattice framework between Cu2S and Li2S. Such displacement reaction without lattice reconstruction renders the composite superior rate capability (∼730 mAh/g@2 A/g) and long lifespan (89.7% capacity retention after 3200 cycles). Present work allows for the fabrication of high-performance electrodes based on metal chalcogenides.

11.
Chem Commun (Camb) ; 57(5): 565-575, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33346753

RESUMO

In-plane anisotropic two-dimensional (2D) materials possess unique in-plane anisotropic physical properties arising from their low crystal lattice symmetry. Among these low-symmetry 2D materials, anisotropic Ge-based binary materials have the advantages of simple binary and earth-abundant compositions, good stability, highly anisotropic physical properties along two principle axes, and wide coverage of bandgaps, enabling use in broadband photodetection from the infrared to ultraviolet region. Here, we review recent progress in in-plane anisotropic 2D Ge-based binary materials, focusing on their anisotropic structural, electrical and optical properties. We then discuss demonstrations of optoelectronic applications related to those anisotropic properties including polarization-sensitive photodetection and polarization-based all-optical switches. Finally, we provide further possible opportunities for this relatively new, but quickly expanding family of materials.

12.
J Agric Food Chem ; 68(47): 14071-14080, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33196171

RESUMO

Amino acids are very important for oolong tea brisk-smooth mouthfeel which is mainly associated with bruising and withering treatment (BWT). In this study, metabolome and transcriptome analyses were performed to comprehensively investigate the changes in abundance of amino acids and the expression pattern of relevant genes during BWT of oolong tea manufacturing. Levels of most amino acids increased during BWT in the leaves harvested from 4 cultivars, while expression of the relevant function genes responsible for synthesis and transformation of amino acids up-regulated accordingly. Upstream hub genes including receptor-like protein kinase IKU2, serine/threonine-protein kinase PBL11, MYB transcription factor MYB2, ethylene-responsive transcription factor ERF114, WRKY transcription factor WRKY71, aspartate aminotransferase AATC, UDP-glycosyltransferase U91D1, and 4-hydroxy-4-methyl-2-oxoglutarate aldolase 2 RRAA2, were predicted to be involved in regulation of the function genes expression and the amino acids metabolism through weighted gene coexpression network analysis. A modulation mechanism for accumulation of amino acids during BWT was also proposed. These findings give a deep insight into the metabolic reprogramming mechanism of amino acids during BWT of oolong tea.


Assuntos
Camellia sinensis , Aminoácidos , Metaboloma , Folhas de Planta , Chá
13.
Phys Chem Chem Phys ; 22(2): 914-918, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31845940

RESUMO

As a representative in-plane anisotropic two-dimensional (2D) material, germanium monoselenide (GeSe) has attracted considerable attention recently due to its various in-plane anisotropic material properties originating from the low symmetry of a puckered honeycomb structure. Although there have been plenty of reports on the in-plane anisotropic vibrational, electrical and optical properties of GeSe, the strain effect on those appealing anisotropies is still under exploration. Here we report a systematic first-principles computational investigation of strain-engineering of the anisotropic electronic properties of GeSe monolayers. We found that the anisotropic ratio of the effective mass and mobility of charge carriers (electrons and holes) of GeSe along two principle axes can be controlled by using simple strain conditions. Notably, the preferred conducting direction of GeSe can be even rotated by 90° under an appropriate uniaxial strain (>5%). Such effective strain modulation of the electronic anisotropy of GeSe monolayers provides them abundant opportunities for future mechanical-electronic devices.

14.
Chem Commun (Camb) ; 55(99): 14988-14991, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31777877

RESUMO

When tested as the cathode material for potassium-ion batteries, K2V3O8 delivers a highly reversible capacity of over 100 mA h g-1 in the voltage range of 1.5-4.5 V with 73% capacity retained after 50 cycles. Charge-discharge is achieved by a nontopotactic process between K2V3O8 and KV3O8 (ΔV ∼ -23.4%), causing the slow capacity decay.

15.
J Am Chem Soc ; 141(45): 18075-18082, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31638806

RESUMO

Defect passivation using oxygen has been identified as an efficient and convenient approach to suppress nonradiative recombination and improve the photovoltaic performance of hybrid organic-inorganic halide perovskites (HHPs). However, oxygen can seriously undermine the chemical stability of HHPs due to the reaction of superoxide with protonated organic cations such as CH3NH3+ and [(NH2)2CH]+, thus hindering the deep understanding of how oxygen affects their defect properties. Here we substitute free-proton inorganic Cs+ for organic moiety to avoid the negative effect of oxygen and then systematically investigate the oxygen passivation mechanism in all-inorganic halide perovskites (IHPs) from theory to experiment. We find that, in contrast to conventional oxygen molecule passivation just through physisorption on the surface of perovskites, the oxygen atom can provide a better passivation effect due to its stronger interaction with perovskites. The key point to achieve O-passivated perovskites rather than O2 is the dry-air processing condition, which can dissociate the O2 into O during the annealing process. O-passivated IHP solar cells exhibit enhanced power conversion efficiency (PCE) and better air stability than O2-passivated cells. These results not only provide deep insights into the passivation effect of oxygen on perovskites but also demonstrate the great potential of IHPs for high photovoltaic performance with simplified ambient processing.

16.
ACS Appl Mater Interfaces ; 11(27): 24247-24253, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31246410

RESUMO

In-plane anisotropic two-dimensional (2D) materials, especially black phosphorus and ReS2, have attracted significant interest recently as they can provide one more dimension to manipulate their physical properties when compared with isotropic 2D materials. As a representative anisotropic 2D material, germanium monosulfide (GeS) has emerged as a new research hot topic in this field because of its unique in-plane anisotropic physical properties. Despite the rapid growing progress in the study of GeS, many of their fundamental optical anisotropies are still absent. Here, we report the three-dimensional (3D) optical anisotropy of GeS from theory to experiment. The 3D optical anisotropic properties including extinction, refraction, absorption, and reflection were systematically investigated through density functional calculations. The anisotropic refraction and reflection of GeS were experimentally verified by polarization-resolved optical microscopy and azimuth-dependent reflectance difference microscopy, respectively. Finally, a GeS-based linear dichroic photodetector was demonstrated with a dichroic ratio of 1.45 because of its polarization sensitive absorption. Our results provide deep insights into the optical anisotropy of GeS, which is important for the further development of GeS-based optoelectronic and optical devices.

17.
Adv Sci (Weinh) ; 6(5): 1801810, 2019 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-30886804

RESUMO

Germanium diselenide (GeSe2) has recently emerged as a new member of in-plane anisotropic 2D materials, notable for its wide bandgap of 2.74 eV, excellent air stability, and high performance in polarization-sensitive photodetection. However, the interlayer interaction in GeSe2 has never been reported, which usually plays an important role in layer-number-dependent physical properties. Here, the interlayer coupling in GeSe2 is systematically investigated from theory to experiment. Unexpectedly, all of density functional theory (DFT) calculations about layer-dependent band structures, cleavage energy, binding energy, translation energy, and interlayer differential charge density demonstrate the much weaker interlayer interaction in GeSe2 when compared with black phosphorus (BP). Furthermore, both thickness-dependent and temperature-dependent Raman spectra of GeSe2 flakes, which exhibit no detectable changes of Raman peaks with the increase in thickness and a small first-order temperature coefficient of -0.0095 cm-1 K-1, respectively, experimentally confirm the weakly coupled layers in GeSe2. The results establish GeSe2 as an unusual member of in-plane anisotropic 2D materials with weak interlayer interaction.

18.
J Am Chem Soc ; 140(11): 4150-4156, 2018 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-29494139

RESUMO

In-plane anisotropic layered materials such as black phosphorus (BP) have emerged as an important class of two-dimensional (2D) materials that bring a new dimension to the properties of 2D materials, hence providing a wide range of opportunities for developing conceptually new device applications. However, all of recently reported anisotropic 2D materials are relatively narrow-bandgap semiconductors (<2 eV), and there has been no report about this type of materials with wide bandgap, restricting the relevant applications such as polarization-sensitive photodetection in short wave region. Here we present a new member of the family, germanium diselenide (GeSe2) with a wide bandgap of 2.74 eV, and systematically investigate the in-plane anisotropic structural, vibrational, electrical, and optical properties from theory to experiment. Photodetectors based on GeSe2 exhibit a highly polarization-sensitive photoresponse in short wave region due to the optical absorption anisotropy induced by in-plane anisotropy in crystal structure. Furthermore, exfoliated GeSe2 flakes show an outstanding stability in ambient air which originates from the high activation energy of oxygen chemisorption on GeSe2 (2.12 eV) through our theoretical calculations, about three times higher than that of BP (0.71 eV). Such unique in-plane anisotropy and wide bandgap, together with high air stability, make GeSe2 a promising candidate for future 2D optoelectronic applications in short wave region.

19.
J Cell Mol Med ; 21(12): 3360-3371, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28631396

RESUMO

Pseudogenes play a crucial role in cancer progression. However, the role of pituitary tumour-transforming 3, pseudogene (PTTG3P) in gastric cancer (GC) remains unknown. Here, we showed that PTTG3P expression was abnormally up-regulated in GC tissues compared with that in normal tissues both in our 198 cases of clinical samples and the cohort from The Cancer Genome Atlas (TCGA) database. High PTTG3P expression was correlated with increased tumour size and enhanced tumour invasiveness and served as an independent negative prognostic predictor. Moreover, up-regulation of PTTG3P in GC cells stimulated cell proliferation, migration and invasion both in vitro in cell experiments and in vivo in nude mouse models, and the pseudogene functioned independently of its parent genes. Overall, these results reveal that PTTG3P is a novel prognostic biomarker with independent oncogenic functions in GC.


Assuntos
Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Pseudogenes , Securina/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Idoso , Animais , Atlas como Assunto , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Transplante de Neoplasias , Prognóstico , Estudos Retrospectivos , Securina/metabolismo , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida , Carga Tumoral
20.
Clin Cancer Res ; 23(8): 2071-2080, 2017 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-27756785

RESUMO

Purpose: The long, noncoding RNA (lncRNA) PVT1 is an important epigenetic regulator with a critical role in human tumors. Here, we aimed to investigate the clinical application and the potential molecular mechanisms of PVT1 in gastric cancer tumorigenesis and progression.Experimental Design: The expression level of PVT1 was determined by RT-qPCR analysis in 190 pairs of gastric cancer tissues and adjacent normal gastric mucosa tissues (ANT). The biologic functions of PVT1 were assessed by in vitro and in vivo functional experiments. RNA protein pull-down assays and LS/MS mass spectrometry analysis were performed to detect and identify the PVT1- interacting protein FOXM1. Protein-RNA immunoprecipitation assays were conducted to examine the interaction of FOXM1 and PVT1 Chromatin immunoprecipitation (ChIP) and luciferase analyses were utilized to identify the binding site of FOXM1 on the PVT1 promoter.Results: The lncRNA PVT1 was significantly upregulated in gastric cancer tissues compared with ANTs. High expression of PVT1 predicted poor prognosis in patients with gastric cancer. PVT1 enhanced gastric cancer cell proliferation and invasion in vitro and in vivoPVT1 directly bound FOXM1 protein and increased FOXM1 posttranslationally. Moreover, PVT1 is also a FOXM1-responsive lncRNA, and FOXM1 directly binds to the PVT1 promoter to activate its transcription. Finally, PVT1 fulfilled its oncogenic functions in a FOXM1-mediated manner.Conclusions: Our study suggests that PVT1 promotes tumor progression by interacting with FOXM1. PVT1 may be a valuable prognostic predictor for gastric cancer, and the positive feedback loop of PVT1-FOXM1 could be a therapeutic target in pharmacologic strategies. Clin Cancer Res; 23(8); 2071-80. ©2016 AACR.


Assuntos
Proteína Forkhead Box M1/biossíntese , Regulação Neoplásica da Expressão Gênica/genética , Invasividade Neoplásica/genética , RNA Longo não Codificante/genética , Neoplasias Gástricas/patologia , Western Blotting , Proliferação de Células , Imunoprecipitação da Cromatina , Intervalo Livre de Doença , Retroalimentação Fisiológica , Proteína Forkhead Box M1/genética , Humanos , Estimativa de Kaplan-Meier , Espectrometria de Massas , Invasividade Neoplásica/patologia , Modelos de Riscos Proporcionais , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Regulação para Cima
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