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1.
J Endod ; 46(2): 232-237, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31889584

RESUMO

INTRODUCTION: Optimum torque reverse (OTR) motion is a torque-sensitive reciprocal motion in which the motor rotates in alternating 90° counterclockwise and 180° clockwise rotation when the torque exceeds a predetermined value. This study aimed to examine whether OTR motion contributes to torque and force reduction during nickel-titanium rotary instrumentation with the crown-down or single-length technique. METHODS: Twenty-eight simulated straight canals in resin blocks were divided into 2 groups according to the type of motion (OTR or continuous rotation). The groups were further subdivided according to the preparation technique (crown-down or single-length technique, n = 7 each). Automated root canal instrumentation was performed with a torque/force analyzing device (300 rpm, up-and-down speed of 10 mm/min) and EndoWave instruments (FKG Dentaire, La-Chaux-de-Fonds, Switzerland) to size #25/0.06 taper. Maximum torque and apical force were recorded and analyzed with analysis of variance and the Bonferroni test. RESULTS: During the crown-down preparation phase (#35/0.08, #30/0.06, #25/0.06, and #20/0.06), OTR motion developed lower maximum torque and upward force (representing the screw-in force) than continuous rotation. During the apical preparation phase (#25/0.06), OTR motion generated significantly lower maximum clockwise and counterclockwise torque (P < .05) when the single-length technique was used and significantly lower maximum upward force regardless of the preparation technique (P < .05) compared with continuous rotation. CONCLUSIONS: Under the present experimental conditions, OTR motion reduced both torque and screw-in force during the crown-down preparation phase of the crown-down technique and during the apical preparation phase of the single-length technique.


Assuntos
Cavidade Pulpar , Preparo de Canal Radicular , Coroas , Ligas Dentárias , Desenho de Equipamento , Rotação , Titânio , Torque
2.
Nat Commun ; 11(1): 234, 2020 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-31932605

RESUMO

Microfold cells (M cells) are responsible for antigen uptake to initiate immune responses in the gut-associated lymphoid tissue (GALT). Receptor activator of nuclear factor-κB ligand (RANKL) is essential for M cell differentiation. Follicle-associated epithelium (FAE) covers the GALT and is continuously exposed to RANKL from stromal cells underneath the FAE, yet only a subset of FAE cells undergoes differentiation into M cells. Here, we show that M cells express osteoprotegerin (OPG), a soluble inhibitor of RANKL, which suppresses the differentiation of adjacent FAE cells into M cells. Notably, OPG deficiency increases M cell number in the GALT and enhances commensal bacterium-specific immunoglobulin production, resulting in the amelioration of disease symptoms in mice with experimental colitis. By contrast, OPG-deficient mice are highly susceptible to Salmonella infection. Thus, OPG-dependent self-regulation of M cell differentiation is essential for the balance between the infectious risk and the ability to perform immunosurveillance at the mucosal surface.

3.
Mol Pharm ; 17(1): 32-39, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31765157

RESUMO

Obesity and metabolic syndrome are threats to the health of large population worldwide as they are associated with high mortality, mainly linked to cardiovascular diseases. Recently, CPN-116 (CPN), which is an agonist peptide specific to neuromedin-U receptor 2 (NMUR2) that is expressed predominantly in the brain, has been developed as a new therapeutic candidate for the treatment of obesity and metabolic syndrome. However, treatment with CPN poses a challenge due to the limited delivery of CPN to the brain. Recent studies have clarified that the direct anatomical connection of the nasal cavity with brain allows delivery of several drugs to the brain. In this study, we confirm the nasal cavity as a promising CPN delivery route to the brain for the treatment of obesity and metabolic syndrome. According to the pharmacokinetic study, the clearance of CPN from the blood was very rapid with a half-life of 3 min. In vitro study on its stability in the serum and cerebrospinal fluid (CSF) indicates that CPN was more stable in the CSF than in the blood. The concentration of CPN in the brain was higher after nasal administration, despite its lower concentrations in the plasma than that after intravenous administration. The study on its pharmacological potency suggests the effective suppression of increased body weight in mice in a dose-dependent manner due to the direct activation of NMUR2 by CPN. This results from the higher concentration of corticosterone in blood after nasal administration of CPN as compared to nasal application of saline. In conclusion, the above findings indicate that the nasal cavity is a promising CPN delivery route to the brain to treat obesity and metabolic syndrome.

4.
AAPS PharmSciTech ; 21(1): 17, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31811523

RESUMO

Amorphous nanoparticles of curcumin (ANC) with primary particle sizes of 50 to 100 nm were prepared using a forced thin film reactor (FTFR). An ethanolic solution of curcumin and polyvinylpyrrolidone was mixed with purified water in an FTFR to precipitate the curcumin nanoparticles. In order to obtain amorphous particles, the solvent used and the operation conditions of FTFR such as the rotation speed of the disk and the flow rate of solutions were adjusted. According to powder X-ray diffraction (XRD) analysis and Fourier transform infrared spectroscopy (FT-IR), amorphous curcumin nanoparticles were obtained. To control the crystallinity, ultrasonic treatment was carried out on ANC suspended in water or hexane to which a polymer or a surfactant was added to prevent the growth of the particles. Transmission electron microscopy, XRD, and FT-IR analyses indicated that the treatment enabled the transformation of ANC to crystalline form 1 (a fundamental curcumin structure) and then to crystalline form 2 or crystalline form 3 without any change in the size of the primary particles. These findings suggest the possibility of preparing solid particles with a desired particle size and crystallinity.

5.
Int Immunol ; 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31867619

RESUMO

Gain-of-function (GOF) STAT1 mutations account for approximately one-half of patients with chronic mucocutaneous candidiasis (CMC) disease. Patients with GOF-STAT1 mutations display a broad variety of infectious and autoimmune manifestations in addition to CMC, and those with severe infections and/or autoimmunity have a poor prognosis. The establishment of safe and effective treatments based on a precise understanding of the molecular mechanisms of this disorder is required to improve patient care. To tackle this problem, we introduced the human R274Q GOF mutation into mice [GOF-Stat1 knock-in (GOF-Stat1R274Q)]. To investigate the immune responses, we focused on the small intestine, which contains abundant Th17 cells. Stat1R274Q/R274Q mice showed excess phosphorylation of STAT1 in CD4+ T cells upon IFN-γ; stimulation, consistent with the human phenotype in patients with the R274Q mutation. We identified two subpopulations of CD4+ T cells, those with "normal" or "high" level of basal STAT1 protein in Stat1R274Q/R274Q mice. Upon IFN-γ; stimulation, the "normal" level CD4+ T cells were more efficiently phosphorylated than those from WT mice, whereas the "high" level CD4+ T cells were not, suggesting that the level of STAT1 protein does not directly correlate with the level of pSTAT1 in the small intestine. Inoculation of Stat1R274Q/R274Q mice with Candida albicans elicited decreased IL-17-producing CD4+RORγ;t+ cells. Stat1R274Q/R274Q mice also excreted larger amounts of C. albicans DNA in their feces than control mice. Under these conditions, there was upregulation of T-bet in CD4+ T cells. GOF-Stat1R274Q mice thus should be a valuable model for functional analysis of this disorder.

6.
Dent Mater J ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31723092

RESUMO

This study aimed to evaluate the influence of a post-machining thermal treatment on canal-centering ability and torque/force generation of reciprocating nickel-titanium instruments. Simulated J-shaped resin canals were prepared with reciprocating instruments sharing identical geometric architecture and with/without post-machining thermal treatment (Reciproc Blue/Reciproc, VDW, Munich, Germany). Using an original automated root canal instrumentation and torque/force analyzing device, files were operated in a combination of reciprocation and up-and-down motion, and torque/force values were monitored. Canal-centering ratios were measured after superimposition of pre- and post-instrumentation images. Compared with Reciproc, Reciproc Blue showed a significantly lower canal-centering ratio (i.e., less deviation; p<0.05) at 0-1 mm from the apex and generated a significantly smaller upward maximum vertical force (p<0.05). Under standardized conditions using the automated device, Reciproc Blue showed better canal-centering ability and reduced screw-in forces than Reciproc, indicating that the post-machining thermal treatment confers superior performance to reciprocating nickel-titanium instruments.

8.
Front Immunol ; 10: 2345, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31649668

RESUMO

Microfold (M) cells are located in the epithelium covering mucosa-associated lymphoid tissues, such as the Peyer's patches (PPs) of the small intestine. M cells actively transport luminal antigens to the underlying lymphoid follicles to initiate an immune response. The molecular machinery of M-cell differentiation and function has been vigorously investigated over the last decade. Studies have shed light on the role of M cells in the mucosal immune system and have revealed that antigen uptake by M cells contributes to not only mucosal but also systemic immune responses. However, M-cell studies usually focus on infectious diseases; the contribution of M cells to autoimmune diseases has remained largely unexplored. Accumulating evidence suggests that dysbiosis of the intestinal microbiota is implicated in multiple systemic diseases, including autoimmune diseases. This implies that the uptake of microorganisms by M cells in PPs may play a role in the pathogenesis of autoimmune diseases. We provide an outline of the current understanding of M-cell biology and subsequently discuss the potential contribution of M cells and PPs to the induction of systemic autoimmunity, beyond the mucosal immune response.

9.
Odontology ; 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506734

RESUMO

This study aimed to analyze force/torque generation and canal volume changes of NiTi rotary glide path preparation using HyFlex EDM Glide Path File in comparison to manual stainless steel K-file instrumentation. Thirty extracted mandibular incisors with a minimally curved and narrow root canal were randomly divided into three groups (n = 10) according to the instrumentation kinematics: Optimum Glide Path motion (OGP) or continuous rotation (CR) with HyFlex EDM Glide Path Files using a custom-made automated-root-canal-preparation device and manual instrumentation with stainless steel K-files (SS) in watch-winding motion. Torque and force were monitored with a custom-made torque/force analyzing device. Canal volume changes and transportation values were measured on micro-computed tomographic images taken before and after the glide path preparation. The data were statistically evaluated using Kruskal-Wallis test and Mann-Whitney U test with Bonferroni correction, with a significance level set at 5%. Maximum upward apical force, representing the screw-in force, was lower in groups OGP and CR compared with that in group SS (P < 0.05). Group CR showed the highest maximum clockwise torque value and canal volume changes, followed by groups OGP and SS (P < 0.05). Canal transportation values at 1 and 3 mm from the apex were not significantly different among groups. Within the limitations of this study, rotary glide path preparation generated smaller screw-in force, larger torque and larger canal volume changes than manual preparation. OGP motion generated smaller torque and less canal volume changes than CR.

10.
Nihon Ronen Igakkai Zasshi ; 56(3): 331-335, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31366754

RESUMO

A 79-year-old woman came to us because of sudden onset of dysarthria. She had taken apixaban due to her non-valvular atrial fibrillation. A neurological examination revealed mild facial palsy of her right side, and magnetic resonance imaging showed acute brain infarction at the left frontal lobe. There were no stenotic lesions on intracranial or extracranial magnetic resonance angiography, and she was diagnosed with cardioembolic stroke. Intravenous infusion of heparin and edaravone was initiated, and her neurological symptoms improved. However, she gradually developed jaundice and anemia. Gastro-intestinal bleeding was not observed, and her blood test met the diagnostic criteria for hemolytic anemia. Because both the direct Coombs test and cold agglutinin were positive, she was diagnosed with mixed-type autoimmune hemolytic anemia. Although her serum hemoglobin level decreased to 7.0 g/dl on the 12th hospital day, her anemia gradually improved after steroidal therapy with transfusion. It was revealed that she had shown mild anemia (hemoglobin: 9.2-10.9 g/dl) and hyperbilirubinemia (total bilirubin: 1.8-2.6 mg/dl) for 6 months. Therefore, her latent autoimmune hemolytic anemia became activated with the occurrence of cardioembolic stroke. Autoimmune hemolytic anemia might have promoted cardiac thrombus formation despite the administration of an anticoagulant in this case. It should be noted that autoimmune hemolytic anemia can develop as thrombotic disease. In the present case, autoimmune hemolytic anemia was diagnosed based on the development of cardioembolic stroke.


Assuntos
Anemia Hemolítica Autoimune/diagnóstico , Acidente Vascular Cerebral/complicações , Idoso , Anemia Hemolítica Autoimune/complicações , Anemia Hemolítica Autoimune/tratamento farmacológico , Feminino , Humanos
11.
Int J Hematol ; 110(5): 627-634, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31401767

RESUMO

Outcomes of children treated for relapsed acute lymphoblastic leukemia (ALL) remain poor. Bortezomib (BZM), a proteasome inhibitor, has shown promising activity against lymphoid malignancies. We conducted a phase I study to evaluate the safety and tolerability of multidrug chemotherapy including BZM in Japanese children with relapsed ALL. Three of five children with relapsed ALL enrolled in the study between November 2014 and April 2016 were evaluated. BZM (1.3 mg/m2) was administered on days 8, 11, 15, and 18 of multidrug induction chemotherapy. Pharmacokinetic studies were performed. Age at study entry was 5, 7, and 7 years old, respectively. Two patients had hyperdiploid B-precursor ALL, and one had T cell ALL. Although all patients experienced grade 3-4 hematologic toxicity and grade 3 elevation of aminotransferases, no dose-limiting toxicities were observed. The maximum tolerated dose was defined as 1.3 mg/m2. Peripheral neuropathy and respiratory complications were not observed. Complete remission was achieved in all three patients. The mean maximum plasma concentration and area under the concentration-time curve was 74.0 ng/mL and 73.9 ng h/mL, respectively. Thus, adding BZM to 5-drug induction chemotherapy appears safe and well-tolerated in Japanese children with relapsed ALL.

12.
Sci Rep ; 9(1): 10842, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31346193

RESUMO

Zinc (Zn) is an essential nutrient and its deficiency causes immunodeficiency and skin disorders. Various cells including mast cells release Zn-containing granules when activated; however, the biological role of the released Zn is currently unclear. Here we report our findings that Zn transporter ZnT2 is required for the release of Zn from mast cells. In addition, we found that Zn and mast cells induce IL-6 production from inflammatory cells such as skin fibroblasts and promote wound healing, a process that involves inflammation. Zn induces the production of a variety of pro-inflammatory cytokines including IL-6 through signaling pathways mediated by the Zn receptor GPR39. Consistent with these findings, wound healing was impaired in mice lacking IL-6 or GPR39. Thus, our results show that Zn and mast cells play a critical role in wound healing through activation of the GPR39/IL-6 signaling axis.

14.
Front Immunol ; 10: 1323, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31244859

RESUMO

Microfold (M) cells residing in the follicle-associated epithelium of mucosa-associated lymphoid tissues are specialized for sampling luminal antigens to initiate mucosal immune responses. In the past decade, glycoprotein 2 (GP2) and Tnfaip2 were identified as reliable markers for M cells in the Peyer's patches of the intestine. Furthermore, RANKL-RANK signaling, as well as the canonical and non-canonical NFκB pathways downstream, is essential for M-cell differentiation from the intestinal stem cells. However, the molecular characterization and differentiation mechanisms of M cells in the lower respiratory tract, where organized lymphoid tissues exist rarely, remain to be fully elucidated. Therefore, this study aimed to explore M cells in the lower respiratory tract in terms of their specific molecular markers, differentiation mechanism, and functions. Immunofluorescence analysis revealed a small number of M cells expressing GP2, Tnfaip2, and RANK is present in the lower respiratory tract of healthy mice. The intraperitoneal administration of RANKL in mice effectively induced M cells, which have a high capacity to take up luminal substrates, in the lower respiratory epithelium. The airway M cells associated with lymphoid follicles were frequently detected in the pathologically induced bronchus-associated lymphoid tissue (iBALT) in the murine models of autoimmune disease as well as pulmonary emphysema. These findings demonstrate that RANKL is a common inducer of M cells in the airway and digestive tracts and that M cells are associated with the respiratory disease. We also established a two-dimensional culture method for airway M cells from the tracheal epithelium in the presence of RANKL successfully. This model may be useful for functional studies of M cells in the sampling of antigens at airway mucosal surfaces.

15.
Rinsho Ketsueki ; 60(5): 459-467, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31168014

RESUMO

Recent development of massive parallel-sequencing technology has revealed the genetic basis of pediatric T-cell acute lymphoblastic leukemia (T-ALL). However, epigenetic profiles of T-ALL, such as DNA methylation, have not been well characterized. To describe the epigenetic landscape of T-ALL, we investigated DNA methylation profiles of 79 cases with pediatric T-ALL by using the EPIC methylation array, which allowed us to perform more profound analyses, including the OpenSea region. Moreover, we conducted combined analyses of methylation data using our previous expression and mutation data. Based on DNA methylation profiles, pediatric T-ALL was clustered into four distinct subtypes, which exhibited remarkable association with genetic signatures and expression features, as well as profiles of normal T-cell development. Furthermore, our study revealed the importance of methylation status at binding sites of polycomb-repressive complex components and transcription factors, such as SPI1, in the classification of pediatric T-ALL based on DNA methylation status. These results might be helpful in the development of new therapeutic strategies for pediatric T-ALL.


Assuntos
Epigênese Genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Criança , Metilação de DNA , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/classificação , Linfócitos T
16.
Dent Mater J ; 38(3): 490-495, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31068550

RESUMO

This study aimed to evaluate cyclic fatigue resistance and bending properties and torque/force generation of WaveOne Gold (WOG) Primary in comparison with WaveOne (WO) Primary and Reciproc (RE) R25. A cyclic fatigue test revealed that the WOG Primary took significantly longer time to fracture compared with the WO Primary (p<0.05). The WOG Primary had the smallest load values at a deflection of 0.5 and 2 mm (p<0.05), as measured with a cantilever bending test. Torque/force measurement demonstrated that maximum upward force and maximum counterclockwise torque values in the WOG Primary were significantly lower than those in the RE R25 (p<0.05). Under the present experimental condition, the WOG Primary showed a higher cyclic fatigue resistance compared with the WO Primary, a higher flexibility compared with the WO Primary and RE R25, and generated a significantly lower maximum torque compared with the RE R25.


Assuntos
Ouro , Preparo de Canal Radicular , Desenho de Equipamento , Torque
17.
Oncol Lett ; 17(3): 3323-3329, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30867766

RESUMO

Recent genome-wide analysis of neuroblastoma (NBL) revealed amplification and heterozygous mutation of anaplastic lymphoma kinase (ALK) are responsible for oncogenicity, frequently observed during relapses. A 3-year-old girl with relapsed high-risk NBL had a heterozygous ALK F1245L mutation at diagnosis, which became homozygous due to uniparental disomy (UPD) of the entire chromosome 2, confirmed by single nucleotide polymorphism array and variant allele frequency of this mutation. The ALK inhibitor, crizotinib, failed to control the tumor and the patient died of the disease. Further genomic analysis using targeted capture sequencing for 381 genes related to pediatric cancers identified more alterations acquired at relapse, such as TSC complex subunit 2 and protein tyrosine phosphatase receptor type D. In addition to these several acquired mutations, this extremely rare duplication of ALK mutation might explain the aggressive clinical course after relapse, because acquired UPD, resulting in the duplication of an oncogenic mutation, has been reported for various neoplasms. Although a clinical benefit of ALK inhibitors in patients with NBL has not been confirmed yet, a treatment based on the ALK mutation status will be promising in future using more potent next-generation ALK inhibitors.

18.
J Exp Med ; 216(4): 831-846, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30877171

RESUMO

Microfold (M) cells residing in the follicle-associated epithelium (FAE) of the gut-associated lymphoid tissue are specialized for antigen uptake to initiate mucosal immune responses. The molecular machinery and biological significance of M cell differentiation, however, remain to be fully elucidated. Here, we demonstrate that Sox8, a member of the SRY-related HMG box transcription factor family, is specifically expressed by M cells in the intestinal epithelium. The expression of Sox8 requires activation of RANKL-RelB signaling. Chromatin immunoprecipitation and luciferase assays revealed that Sox8 directly binds the promoter region of Gp2 to increase Gp2 expression, which is the hallmark of functionally mature M cells. Furthermore, genetic deletion of Sox8 causes a marked decrease in the number of mature M cells, resulting in reduced antigen uptake in Peyer's patches. Consequently, juvenile Sox8-deficient mice showed attenuated germinal center reactions and antigen-specific IgA responses. These findings indicate that Sox8 plays an essential role in the development of M cells to establish mucosal immune responses.

19.
J Endod ; 45(1): 68-72.e1, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30558799

RESUMO

INTRODUCTION: This study was performed to evaluate how the speed of up-and-down motion affects the canal centering ability and torque/force generation of ProTaper Next rotary instruments (Dentsply Maillefer, Ballaigues, Switzerland). METHODS: Twenty-one simulated resin canal blocks with a J-shaped canal were prepared with ProTaper Next X1, X2, and X3 instruments using an original automated root canal instrumentation and torque/force analyzing device with up-and-down speed settings of 10, 50, and 100 mm/min (low-, medium-, and high-speed groups, respectively). Pre- and postinstrumentation images were superimposed, and centering ratios were calculated at 0-3 mm from the apex. The maximum vertical force and torque were also recorded. The results were statistically analyzed using 1-way analysis of variance and the Tukey test. RESULTS: At 0, 0.5, 1, and 2 mm from the apex, the high-speed group showed the lowest centering ratio (ie, least deviation) followed by the medium-speed and low-speed groups (P < .05). Force values (downward and upward) tended to increase as the up-and-down speed increased; with the X2 and X3 instruments, the high-speed and/or medium-speed groups generated significantly larger values than the low-speed group (P < .05). With all instruments, the high-speed and/or medium-speed groups generated significantly larger clockwise torque than the low-speed group (P < .05). One and 2 X2 instruments fractured in the low- and high-speed groups, respectively. CONCLUSIONS: The up-and-down speed affected the canal centering ability and stress generation of ProTaper Next instruments. The high-speed group showed the best centering ability but tended to generate larger vertical force and torque than the medium- and low-speed groups.


Assuntos
Ligas , Desenho de Equipamento , Fenômenos Mecânicos , Movimento (Física) , Preparo de Canal Radicular/instrumentação , Rotação , Torque , Preparo de Canal Radicular/métodos
20.
Cancer Sci ; 110(2): 784-794, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30387229

RESUMO

Molecular mechanisms involved in the relapse of T-cell acute lymphoblastic leukemia (T-ALL) are not fully understood, although activating NOTCH1 signaling due to NOTCH1/FBXW7 alterations is a major oncogenic driver. To unravel the relevance of NOTCH1/FBXW7 mutations associated with relapse, we performed whole-exome sequencing in 30 pediatric T-ALL cases, among which 11 diagnosis-relapse paired cases were further investigated to track the clonal evolution of relapse using amplicon-based deep sequencing. NOTCH1/FBXW7 alterations were detected in 73.3% (diagnosis) and 72.7% (relapse) of cases. Single nucleotide variations in the heterodimerization domain were the most frequent (40.0%) at diagnosis, whereas proline, glutamic acid, serine, threonine-rich (PEST) domain alterations were the most frequent at relapse (54.5%). Comparison between non-relapsed and relapsed cases at diagnosis showed a predominance of PEST alterations in relapsed cases (P = .045), although we failed to validate this in the TARGET cohort. Based on the clonal analysis of diagnosis-relapse samples, we identified NOTCH1 "switching" characterized by different NOTCH1 mutations in a major clone between diagnosis and relapse samples in 2 out of 11 diagnosis-relapse paired cases analyzed. We found another NOTCH1 "switching" case in a previously reported Berlin-Frankfurt-Münster cohort (n = 13), indicating NOTCH1 importance in both the development and progression of T-ALL. Despite the limitations of having a small sample size and a non-minimal residual disease-based protocol, our results suggest that the presence of NOTCH1 mutations might contribute to the disease relapse of T-ALL.


Assuntos
Evolução Clonal/genética , Mutação/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Receptor Notch1/genética , Linfócitos T/patologia , Adolescente , Criança , Pré-Escolar , Proteína 7 com Repetições F-Box-WD/genética , Feminino , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética , Recidiva , Transdução de Sinais/genética
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