Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 459
Filtrar
1.
J Prosthet Dent ; 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31672425

RESUMO

STATEMENT OF PROBLEM: Although different preparation designs have been proposed for onlays fabricated by computer-aided design and computer-aided manufacturing (CAD-CAM), their effect on marginal adaptation is unclear. PURPOSE: The purpose of this in vitro study was to investigate the effect of tooth preparation designs on the marginal and internal adaptation of ceramic-reinforced composite resin CAD-CAM onlays. MATERIAL AND METHODS: A traditional preparation with a heavy chamfer on the functional cusp and a contrabevel on the nonfunctional cusp and a shoulder preparation with equal reduction on all cusps were used for mesial-occlusal-distal (MOD) onlay preparations. Ceramic-reinforced composite resin onlays were designed and milled based on the scanned prepared teeth. A digital silicone replica technique was used to determine marginal discrepancies between preparations and onlay restorations. A total of 100 numeric distances (representations of the fit in each region) were measured in 3 distinct regions: the buccal margin, lingual margin, and internal area. Independent Student t tests were used to determine significant differences (α=.05). RESULTS: Traditional preparation designs resulted in significantly smaller overall discrepancies (50.9 ±0.5 µm and 139.1 ±5.4 µm, P<.001) and smaller marginal discrepancies in the buccal (49.7 ±1.4 µm and 135.8 ±2.2 µm, P<.001) and lingual areas (47.1 ±1.0 µm and 133.4 ±1.1 µm, P<.001). CONCLUSIONS: The marginal adaptation of ceramic-reinforced composite resin CAD-CAM onlays was affected by the preparation design. The traditional preparation design offered better marginal adaptation; therefore, it is recommended in clinical practice.

4.
J Exp Clin Cancer Res ; 38(1): 415, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615580

RESUMO

In the original publication of this manuscript [1], Fig. 5E lower panel was incorrect due to an error in the preparation of these figures for publication. It was noticed that in the lower panel of Fig. 5E, one mouse image of ApoE-/- + PBS group (upper) was a photograph coming from ApoE-/- + BAPN pre-treatment group (lower). The corrected figure appears below. We apologize for any confusion this may have caused.

5.
J Immunother Cancer ; 7(1): 271, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31640816

RESUMO

BACKGROUND: Chimeric antigen receptor-modified (CAR) T-cell immunotherapy is a novel promising therapy for treatment of B-cell malignancy. Cytokine release syndrome (CRS) and infection are the most common adverse events during CAR T-cell therapy. Similar clinical presentation of concurrent CRS and infection makes it difficult to differentially diagnose and timely treat the condition. METHODS: We analyzed the features of infection events during the first 30 days after CAR T-cell infusion (CTI) in 109 patients from three clinical trials (ChiCTR-OPN-16008526, ChiCTR-OPC-16009113, ChiCTR-OPN-16009847). Based on the dynamic changes of interleukin (IL)-6 and ferritin, we proposed the "double peaks of IL-6" pattern as a feature of life-threatening infection during the first 30 days after CTI. Meanwhile, we screened candidate biomarkers from 70-biomarker panel to establish a prediction model for life-threatening infection. RESULTS: In this study, 19 patients (17.4%) experienced a total of 19 infection events during the first 30 days after CAR T-cell infusion. Eleven patients (10.1%) had grade 4-5 infection, which were all bacterial infection and predominantly sepsis (N = 9). "Double peaks of IL-6" appeared in 9 out of 11 patients with life-threatening infection. The prediction model of three-cytokines (IL-8, IL-1ß and interferon-γ) could predict life-threatening infection with high sensitivity (training: 100.0%; validation: 100.0%) and specificity (training: 97.6%; validation: 82.8%). On base of the aforementioned methods, we proposed a workflow for quick identification of life-threatening infection during CAR T-cell therapy. CONCLUSIONS: In this study, we worked out two diagnostic methods for life-threatening infection during CAR T-cell therapy by analyzing inflammatory signatures, which contributed to reducing risks of infection-induced death.

6.
EBioMedicine ; 2019 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-31636012

RESUMO

BACKGROUND: Understanding how cells respond to mitotic poisons is of great biomedical and clinical significance. However, it remains unknown how cell-death or survival is determined during exposure to anti-mitotic drugs. METHODS: The biological effects of SLC39A6 (LIV-1) and GrpE-like 1 (GRPEL1) on mitotic exit and apoptosis were evaluated both in vitro and in vivo using flow cytometry, western blotting, xenografts and time-lapse imaging. The interactions between proteins and the ubiquitination of GRPEL1 were assessed by GST pull down, immunoprecipitation and mass spectrometry analysis. The expression of LIV-1 in cancers was assessed by immunohistochemistry. FINDINGS: Overexpression of LIV-1 led to direct apoptosis. Depleted for LIV-1 evade anti-mitotic agent-induced killing through a rapid exit from arrested mitosis. LIV-1 interacts with GRPEL1 and Stabilizes GRPEL1 Protein by Preventing Ubiquitylation of GRPEL1. LIV-1-GRPEL1 axis depletion works to reduce the mitotic arrest by inducing PP2A-B55α phosphates activity, while inhibit apoptosis by banding AIF and preventing the latter's release into the nucleus. Loss of function in this axis was frequent in multiple types of human epithelial cancer. INTERPRETATION: These data demonstrate that LIV-1-GRPEL1 axis dually regulates mitotic exit as well as apoptosis by interacting with PP2A B55α and AIF. Its discovery constitutes a conceptual advance for the decisive mechanism of cell fate during damaged mitosis. FUND: National Clinical Research Center for Obstetric and Gynecologic Diseases, the National Natural Science Foundation of China.

7.
Leukemia ; 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31520078

RESUMO

Prognosis is poor for patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) after failure of or who are ineligible for autologous stem cell transplant. We evaluated the efficacy and safety of tislelizumab, an investigational anti-PD-1 monoclonal antibody, in phase 2, single-arm study in Chinese patients with R/R cHL. The primary endpoint was overall response rate as assessed by an independent review committee, according to the Lugano 2014 Classification. Seventy patients were enrolled in the study and received at least one dose of tislelizumab. After median follow-up of 9.8 months, 61 (87.1%) patients achieved an objective response, with 44 (62.9%) achieving a complete response (CR). The estimated 9-month progression-free survival rate was 74.5%. Most common grade ≥3 adverse events (AEs) were upper respiratory tract infection and pneumonitis. Infusion-related reactions occurred in 27 (38.6%) patients, and 27 patients (38.6%) experienced an immune-related AE, the most common of which was thyroid dysfunction. Eleven (15.7%) patients experienced at least one treatment-emergent AE leading to dose interruption or delay. No deaths occurred due to AEs. Treatment of patients with R/R cHL with tislelizumab was generally well tolerated and resulted in high overall response and CR rates, potentially translating into more durable responses for these patients.

8.
Cell Death Dis ; 10(10): 707, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31548594

RESUMO

Following publication of this article [1], the authors became aware of an error in Fig. 7e which requires correction. The images do not currently match the correct treatment and/or control conditions. Specifically, the images of siNC+AD-ctr (the top left panel) and siPDK4+AD-PDK4 (the bottom right panel) were incorrect. The error does not impact the conclusions of the article. They sincerely apologize for the mistakes in the article and any inconvenience caused.

10.
Dent Mater J ; 38(5): 756-763, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31341144

RESUMO

This study was to evaluate whether UV light irradiation and He plasma treatment of zirconia disks enhances its biocompatibility with human gingival fibroblasts (HGFs), and to compare the difference of two methods. Zirconia disks were prepared and divided into three groups: UVC light treatment (Group UV), He plasma (Group P), and control group. The surface morphology, wettability were analyzed. The cultured HGFs' adhesive density, morphology, proliferation and collagen synthesis were measured. After UV light and plasma treatment, contact angles decreased. HGFs' adhesion and proliferation in Group P was the highest (p<0.05) at each time point. HGFs on Group P also released the highest level of Col-1 after 3 and 7 days. Our study demonstrated that plasma and UV light treatment on smooth zirconia improved the hydrophilic property of surface in different mechanism and He plasma had the better effect on cells adhesion, proliferation, and especially on collagen synthesis.


Assuntos
Gengiva , Raios Ultravioleta , Células Cultivadas , Fibroblastos , Humanos , Masculino , Propriedades de Superfície , Zircônio
11.
Clin Oral Implants Res ; 30(10): 1049-1058, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31357237

RESUMO

OBJECTIVE: To evaluate the clinical outcomes of an early loading protocol of splinted implants with a fluoride-modified nanostructure surface and a tapered apex design for the therapy of posterior partial edentulism of mandible. MATERIALS AND METHODS: One hundred and seven implants were placed in the mandible of 45 subjects at three centres in China. A minimum of two and a maximum of three implants were placed in an edentulous region using a one-stage protocol. Each subject received a screw-retained, splinted and fixed permanent prosthesis 6-8 weeks after surgery. Marginal bone level (MBL) change, implant survival and soft tissue health were assessed at 6, 12, 24 and 36 months after loading. A total of 92 implants from 40 subjects were recalled and investigated in this clinical trial. RESULTS: After three-year loading, the survival rate of implant was 100%. On a subject level, there was a mean (±SD) marginal bone gain of 0.23 ± 0.48 mm at 36-month recall and the change in MBL was statistically significant (p = .00061) compared with time of loading. On an implant level, the change in MBL was statistically significant (p = .03914, p = .01494, p = .00000) at 12, 24 and 36 months of loading compared with time of loading. CONCLUSION: Three-year data indicate that early loading protocol of splinted implants with a fluoride-modified nanostructure surface and a tapered apex design is feasible and safe for the therapy of partial edentulism in posterior mandible, which may contribute to bone gain when the suitable occlusal load and oral hygiene maintenance are kept.


Assuntos
Perda do Osso Alveolar , Implantes Dentários , China , Implantação Dentária Endo-Óssea , Planejamento de Prótese Dentária , Prótese Dentária Fixada por Implante , Falha de Restauração Dentária , Humanos , Mandíbula , Estudos Prospectivos , Resultado do Tratamento
12.
Environ Sci Technol ; 53(13): 7504-7512, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31184870

RESUMO

Waterborne diseases related to unsafe water are still major threats to public health in some developing countries and rural areas. Providing affordable and safe drinking water globally remains a great challenge in the coming decades. In this study, we develop a high-throughput and conductive silver nanowire (AgNW)-modified composite filter via depositing thin and ultralong AgNWs on a macroporous substrate. An electrochemical filtration cell (EFC) equipped with the composite filter achieves controllable Ag+ release at a µg L-1 level and superior bacterial inactivation performance (>6-log inactivation efficiency) with an operation voltage of only 1 V at a high flux of 100 m3 h-1 m-2. Under such operation conditions, each composite filter (effective area: 0.79 cm2) can treat at least 750 mL of the bacterial suspension (∼107 CFU mL-1 of Escherichia coli) with a low effluent Ag+ concentration below 50 µg L-1 and almost negligible energy consumption of only ∼70 J m-3.


Assuntos
Nanofios , Purificação da Água , Desinfecção , Filtração , Prata
13.
Sensors (Basel) ; 19(12)2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31200576

RESUMO

Flood has an important effect on plant growth by affecting their physiologic and biochemical properties. Soybean is one of the main cultivated crops in the world and the United States is one of the largest soybean producers. However, soybean plant is sensitive to flood stress that may cause slow growth, low yield, small crop production and result in significant economic loss. Therefore, it is critical to develop soybean cultivars that are tolerant to flood. One of the current bottlenecks in developing new crop cultivars is slow and inaccurate plant phenotyping that limits the genetic gain. This study aimed to develop a low-cost 3D imaging system to quantify the variation in the growth and biomass of soybean due to flood at its early growth stages. Two cultivars of soybeans, i.e. flood tolerant and flood sensitive, were planted in plant pots in a controlled greenhouse. A low-cost 3D imaging system was developed to take measurements of plant architecture including plant height, plant canopy width, petiole length, and petiole angle. It was found that the measurement error of the 3D imaging system was 5.8% in length and 5.0% in angle, which was sufficiently accurate and useful in plant phenotyping. Collected data were used to monitor the development of soybean after flood treatment. Dry biomass of soybean plant was measured at the end of the vegetative stage (two months after emergence). Results show that four groups had a significant difference in plant height, plant canopy width, petiole length, and petiole angle. Flood stress at early stages of soybean accelerated the growth of the flood-resistant plants in height and the petiole angle, however, restrained the development in plant canopy width and the petiole length of flood-sensitive plants. The dry biomass of flood-sensitive plants was near two to three times lower than that of resistant plants at the end of the vegetative stage. The results indicate that the developed low-cost 3D imaging system has the potential for accurate measurements in plant architecture and dry biomass that may be used to improve the accuracy of plant phenotyping.

15.
Lancet Haematol ; 6(6): e328-e337, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31126528

RESUMO

BACKGROUND: Anthracycline dose optimisation in the treatment of diffuse large B-cell lymphoma has rarely been tested. We aimed to find out whether R-CEOP70 was non-inferior to R-CHOP50 with less cardiotoxicity, and whether R-CEOP90 had a superior efficacy to R-CHOP50 or R-CEOP70 with acceptable toxic effects. METHODS: In this multicentre, phase 3, randomised, controlled study (NHL-001), patients with newly diagnosed diffuse large B-cell lymphoma or follicular lymphoma grade 3B were enrolled from 20 centres of the Multicenter Hematology-Oncology Programs Evaluation System in China. Young patients (16-60 years) were randomly assigned 1:1:1 (block size of six) to six courses of R-CHOP50, R-CEOP70, or R-CEOP90, and older patients (61-80 years) were assigned 1:1 (block size of four) to R-CHOP50 or R-CEOP70. Patients were randomly assigned using computer-assisted permuted-block randomisation. Investigators and patients were not masked to treatment assignment. In the R-CHOP50 group, patients were given rituximab 375 mg/m2 intravenously on day 0, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1·4 mg/m2 (maximum dose 2 mg) intravenously on day 1, and prednisone 60 mg/m2 (maximum dose 100 mg) orally from day 1-5; in the R-CEOP70 group, epirubicin 70 mg/m2 replaced doxorubicin; and in the R-CEOP90 group, high dose epirubicin 90 mg/m2 replaced doxorubicin. All patients received two additional courses of rituximab 375 mg/m2 intravenously every 21 days. Consolidation radiotherapy was given to patients with bulky disease at diagnosis or residual disease at the end of treatment. The primary endpoint was 2-year progression-free survival. The non-inferiority margin for R-CEOP70 versus R-CHOP50 was defined by hazard ratio [HR] as the upper limit of its 95% CI being no greater than 1·50. Analysis of efficacy and safety were of the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01852435. FINDINGS: From May 15, 2013, to March 16, 2016, a total of 648 patients were enrolled, including 404 (62%) young patients (R-CHOP50 [n=135], R-CEOP70 [n=134], or R-CEOP90 [n=135]), and 244 (38%) older patients (R-CHOP50 [n=122] or R-CEOP70 [n=122]). Four patients were excluded from the study for consent withdrawal and one patient for misdiagnosis before treatment. The 2-year progression-free survival in the R-CHOP50 group was 72·5% (95% CI 66·6-77·6) and in the R-CEOP70 group was 72·4% ([66·5-77·5]; HR 1·00 [0·73-1·38]; p=0·99). The non-inferiority was met and adverse events were similar between the two groups. Fewer patients in the R-CEOP70 group (14 [13%] of 110) presented with over 10% decrease in left ventricular ejection fraction (LVEF) than those in the R-CHOP50 group (31 [29%] of 108) at 3 years after remission. For young patients, the 2-year progression-free survival in the R-CEOP90 group was 88·8% (82·1-93·1) and was significantly improved compared with the R-CHOP50 group (75·9% [67·7-82·3]; 0·44 [0·25-0·76]; p=0·0047) and the R-CEOP70 group (77·4% [69·4-83·7%]; 0·49 [0·27-0·86]; p=0·017). Grade 3-4 neutropenia occurred more frequently in the R-CEOP90 group (97 [72%] of 134) than in the R-CHOP50 group (87 [65%] of 133) and R-CEOP70 group (84 [63%] of 133) in young patients but without further increase of clinically significant infections. Fewer patients in the R-CEOP70 group (7 [11%] of 66) and in the R-CEOP90 group (10 [13%] of 79) presented with more than 10% decrease in LVEF than those in the R-CHOP50 group (17 [26%] of 66) at 3 years after remission. INTERPRETATION: R-CEOP70 could serve as an alternative regimen to R-CHOP50 with mild long-term cardiotoxicity. Young patients with diffuse large B-cell lymphoma might benefit from high-dose epirubicin. Epirubicin is an alternative drug to doxorubicin in regular R-CHOP with mild long-term cardiotoxicity. FUNDING: National Natural Science Foundation of China, National Key Research and Development Program, Shanghai Commission of Science and Technology, Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant Support, Multicenter Clinical Research Project by Shanghai Jiao Tong University School of Medicine, Clinical Research Plan of Shanghai Hospital Development Center, and Chang Jiang Scholars Program.


Assuntos
Antraciclinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antraciclinas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Feminino , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neutropenia/etiologia , Modelos de Riscos Proporcionais , Rituximab/administração & dosagem , Taxa de Sobrevida , Resultado do Tratamento , Vincristina/administração & dosagem , Adulto Jovem
16.
Cancer Med ; 8(8): 3905-3917, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31119897

RESUMO

PRDM family proteins are dysregulated in many human diseases, especially hematological malignancies and solid cancers, and share a unique N-terminal PR domain followed by zinc fingers toward the C terminus. With a high frequency of DNA promoter hypermethylation, PRDM5 is primarily considered as a tumor suppressor in solid tumors. However, little is known about the function of PRDM5 in blood malignancies, especially acute myeloid leukemia (AML). In this study, we showed that high PRDM5 expression levels were independently correlated with poor overall survival in AML patients. PRDM5 overexpression promoted cell proliferation, colony formation, and migration in vitro and enhanced tumorigenesis in an in vivo xenograft model. Furthermore, we found that PRDM5 overexpression promoted cell cycle progression with the decreased level of cell cycle inhibitors such as p16 and p21, and regulated the expression of epithelial-mesenchymal transition markers ZO-1 and Vimentin to promote migration. Moreover, we observed that PRDM5 upregulated the Jun N-terminal kinase (JNK) signaling pathway and downregulated c-Myc expression. Pharmacological inhibition of JNK by SP600125 partially abrogated PRDM5-induced cell proliferation and migration. Taken together, our findings demonstrate that PRDM5 functions as an oncogenic driver in AML via JNK pathway, suggesting that PRDM5 is a potential therapeutic target for AML.

17.
Curr Med Sci ; 39(2): 211-216, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31016512

RESUMO

Discontinuation of tyrosine kinase inhibitor (TKI) therapy after achieving a persistent deep molecular response (DMR) is an urgently needed treatment goal for chronic myeloid leukemia (CML) patients and has been included in the National Comprehensive Cancer Network (NCCN) guidelines (version 2.2017) for CML. Indeed, various studies have confirmed the feasibility of discontinuing TKI therapy. In this study, we analyzed data from 45 CML patients who had discontinued TKI therapy. Univariate analysis was performed to predict factors that were potentially related to treatment-free remission (TFR) and identify the differences between early relapse and late relapse. Out of the 45 patients, 20 exhibited molecular relapse after a median follow-up of 18 months (range, 1-54 months), and the estimated TFR at 24 months was 40%. The univariate analysis revealed that a high Sokal score and interruptions or dose reductions during TKI treatment were the only baseline factors associated with poor outcomes. Our results indicate that TKI discontinuation could be successfully put into practice in China.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Adolescente , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
18.
FEBS Open Bio ; 9(5): 901-913, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31034165

RESUMO

Metastasis is one of the major causes of death in colorectal cancer (CRC) patients. MiR-222 has been reported to be an oncogene in many types of cancer. However, its role in CRC cell invasion and migration as well as CRC downstream signaling pathways remains largely unknown. Our study found that miR-222 overexpression promotes the migration and invasion of CRC cell lines, and miR-222 interference results, as expected, in inhibition of migration and invasion. Bioinformatic analysis and dual luciferase reporter assay showed that mammalian STE20-like protein kinase 3 (MST3) may be the target gene of miR-222. Down-expression of MST3 in CRC cell lines enhanced their migration and invasion, but overexpression of MST3 could attenuate miR-222 overexpression in the promotion of migration and invasion in colorectal cell lines. HCT116 cell lines overexpressing miR-222 were transplanted into nude mice resulting in more lung metastases than in the control group. Further study found that MST3 may play a role in paxillin phosphorylation to reduce adhesion, or increase the invadopodia. These findings demonstrate that miR-222 modulates MST3 and therefore plays a critical role in regulating CRC cell migration and invasion. Thus, miR-222 may be a novel therapeutic target for CRC.

19.
Environ Int ; 128: 30-36, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31029977

RESUMO

Though well known for its anti-microbial property, copper is usually not considered for drinking water disinfection because of its health risk to human bodies under efficient biocidal concentration. Herein, we have rationally designed and constructed a tubular coaxial-electrode copper ionization cell (CECIC) that enables superior disinfection performance (~6-log removal of E. coli) with a very low effluent copper concentration (~200 µg/L). A non-uniform electric field with enhanced strength near the center electrode is generated in the chamber attributed to the coaxial center-outer electrode configuration. Exposure to the strong electric field subsequently increases the permeability of cell membrane, the excessive uptake of Cu ions into microbes, and thus the reinforced bacteria inactivation. The in-situ ionization results in a Cu ion concentration gradient with higher concentrations in the regions closer to the center. In addition, being driven by the electrophoresis and dielectrophoresis forces, the bacterial cells are transported to the vicinity of the center electrode, where both the electric field strength and Cu ion concentration are higher. These mechanisms in the CECIC synergistically result in the high inactivation efficiency with low Cu concentration in the effluent. The low-cost, high-efficiency, and disinfection-byproduct-free CECIC has shown significant potential in point-of-use applications.

20.
Biochem Biophys Res Commun ; 513(4): 1063-1069, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31010676

RESUMO

Acute myeloid leukemia (AML) is a heterogeneous clonal hematopoietic malignancy with poor survival and frequent relapse. Recently, a posttranslational modification of proteins with small ubiquitin-like modifiers (SUMO) has been notably implicated in a wide spectrum of diseases, especially cancers. Ubc9, as the sole E2-conjugating enzyme in SUMOylation cascade, particularly has been associated with adverse clinical outcomes. 2-D08, a small molecular agent, functions by blocking the transfer of SUMO from the Ubc9 thioester to SUMO substrates without any effects on other individual steps in this process. However, both the effects and mechanisms of 2-D08 on AML cells are still unknown. In this study, we found that 2-D08 significantly suppressed cell viability and colony formation ability. Additionally, it induced mitochondrial-mediated apoptosis with dramatic accumulation of the reactive oxygen species (ROS), which could be almost completely rescued by the ROS scavenger N-acetylcysteine (NAC). Furthermore, we confirmed that the fatal accumulation of ROS was due to its aberrant generation instead of defective scavenging. In summary, our results suggest that 2-D08, as a specific SUMOylation inhibitor, induces ROS accumulation-mediated intrinsic apoptosis of AML cells possibly through deSUMOylation of NOX2. Therefore, 2-D08 might be a promising therapeutic agent for the treatment of AML in the future.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA