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1.
Cytokine ; 152: 155820, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35176657

RESUMEN

Lung adenocarcinoma (LUAD) is a prevalent lung cancer histology with high morbidity and mortality. Moreover, assessment approaches for patients' prognoses are still not effective. Based on mRNA expression and clinical data from the Cancer Genome Atlas (TCGA)-LUAD data set, we utilized hypoxia-related gene set in MsigDB database to identify hypoxia-related differentially expressed genes (DEGs). On the basis of levels of hypoxia-related DEGs, K-means consensus clustering was introduced to divide LUAD patients into subgroups. After hypoxia-related DEGs were analyzed through univariate, Lasso and multivariate Cox regression analyses, 6 of them were determined to be used for evaluating LUAD patients' prognostic signature. With median risk score obtained from hypoxia-related gene signature as threshold, LUAD patients were divided into high- and low-risk groups. Besides, Kaplan-Meier curves, receiver operator characteristic (ROC) curves, univariate and multivariate Cox regression analyses verified that hypoxia-related gene signature was an important prognostic factor independent of clinical features. Gene set enrichment analysis (GSEA) displayed that pathways which showed differences between high- and low-risk groups in activation of pentose-phosphate pathway and p53 signaling pathway. CIBERSORT was utilized to assess infiltration level of each immune cell from two groups, indicating the differences in infiltration abundance of Plasma cells, T cells CD4+ memory activated and Macrophages M1 cells between high- and low-risk groups. We drew a nomogram for predicting one-, three- and five-year survival of LUAD patients following risk scores of hypoxia-related gene signature and six clinical factors. Calibration curves showed a high fit between survival predicted by nomogram and actual survival. In conclusion, hypoxia-related gene signature can be introduced for predicting LUAD patients' prognosis and assessment of the patients' immune microenvironment, guiding clinicians to make appropriate decisions during diagnosis and treatment of LUAD patients.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Biomarcadores de Tumor/genética , Humanos , Hipoxia/genética , Neoplasias Pulmonares/patología , Pronóstico , Microambiente Tumoral/genética
2.
Biol Blood Marrow Transplant ; 26(2): 242-253, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31682978

RESUMEN

Although thymus-independent donor-derived T cell expansion may determine the occurrence of graft-versus-host disease (GVHD) and relapse after transplantation, the characteristics and dynamics of the expansion process remain unclear. To address this issue, we monitored T cell receptor ß repertoire at day 0, day 28, and day 61 after transplantation in 30 patients with hematologic malignancies by next-generation sequencing. The clonality index showed an increasing clonality over time (P = .001). The top 200 clonotypes accounted for more than half of the total clonotypes (median frequency, 63.55%) at day 61, and there was a remarkable overlapping between the top 200 clonotypes of each repertoire and its former repertoire (>50%). A normalized index, called the T Cell Response Index (TCRI), was designed on the basis of rank-shift analysis to quantify antigen-driven expansion. The TCRI during the first month was not related to relapse or GVHD (P> .05), whereas the TCRI during the second month was related to relapse (P = .006). Recipients with a TCRI below 1.0 during the second month had a higher cumulative relapse rate (31.25% versus 0%, P = .0323) and had a lower 1-year survival rate (56.25% versus 78.57%, P = .281). The clonotypes with strong competitiveness in the second month in the nonrelapse group preferentially used TRBV2, TRBV12-3, TRBJ1-1 and TRBJ1-5 segments (P< .01). In conclusion, homeostatic expansion predominates in the first month due to nonspecific T cell proliferation, whereas antigen-driven expansion predominates in the second month and results in a graft-versus-tumor (GvT) effect. Moreover, TCRI could serve as a quantitative indicator of GvT against relapse within the first year. The difference in V and J segment usage reveals that T cells responsible for potent GvT effect are similar among patients.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Proliferación Celular , Humanos , Recurrencia Local de Neoplasia , Linfocitos T
3.
World J Surg Oncol ; 13: 20, 2015 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-25885214

RESUMEN

BACKGROUND: The atrial intramyocardial lipomas are rare benign unusual tumors of the heart. The indication and best form of treatment for cardiac lipomas remain controversial. CASE PRESENTATION: The atrial intramyocardial lipomas are rare benign unusual tumors of the heart. We report a 55-year-old Chinese female with a history of hypertension. Echocardiography and 64-slice computed tomography showed a fatty mass in the right atrium. Although she was asymptomatic, a surgical resection was indicated since the lipoma could cause an embolism and arrhythmias and its potential to enlarge. Surgery revealed an intramyocardial lipoma on the atrial free wall which was confirmed by histopathology. The patient remained asymptomatic after surgery, and no recurrence was seen after 1 year. CONCLUSIONS: Although cardiac lipomas are usually benign, tumor embolism, potential to enlarge, or intracardiac obstruction can cause a critical situation. Therefore, a surgical resection was indicated even in asymptomatic patients.


Asunto(s)
Atrios Cardíacos/cirugía , Neoplasias Cardíacas/cirugía , Lipoma/cirugía , Manejo de la Enfermedad , Ecocardiografía , Femenino , Atrios Cardíacos/patología , Neoplasias Cardíacas/patología , Humanos , Lipoma/patología , Persona de Mediana Edad , Pronóstico , Tomografía Computarizada por Rayos X
4.
Acta Biochim Biophys Sin (Shanghai) ; 46(12): 1056-65, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25377438

RESUMEN

Mesenchymal stem cells (MSCs) have been widely used in allogeneic stem cell transplantation. We compared immunologic and hematopoietic characteristics of MSCs derived from whole human umbilical cord (UC), as well as from different sections of UCs, including the amniotic membrane (AM), Wharton's jelly (WJ), and umbilical vessel (UV). Cell phenotypes were examined by flow cytometry. Lymphocyte transformation test and mixed lymphocyte reaction were performed to evaluate the immuno-modulatory activity of MSCs derived from UCs. The mRNA expression of cytokines was detected by real-time polymerase chain reaction. Hematopoietic function was studied by co-culturing MSCs with CD34(+) cells isolated from cord blood. Our results showed that MSCs separated from these four different sections including UC, WJ, UV, and AM had similar biological characteristics. All of the MSCs had multi-lineage differentiation ability and were able to differentiate into osteoblasts, adipocytes, and chondrocytes. The MSCs also inhibited the proliferation of allogeneic T cells in a dose-dependent manner. The relative mRNA expression of cytokines was examined, and the results showed that UCMSCs had higher interleukin-6 (IL6), IL11, stem cell factor, and FLT3 expression than MSCs derived from specific sections of UCs. CD34(+) cells had high propagation efficiencies when co-cultured with MSCs derived from different sections of UCs, among which UCMSCs are the most efficient feeding layer. Our study demonstrated that MSCs could be isolated from whole UC or specific sections of UC with similar immunomodulation and hematopoiesis supporting characteristics.


Asunto(s)
Hematopoyesis , Células Madre Mesenquimatosas/citología , Cordón Umbilical/citología , Secuencia de Bases , Diferenciación Celular , Células Cultivadas , Técnicas de Cocultivo , Cartilla de ADN , Humanos , Inmunofenotipificación , Células Madre Mesenquimatosas/inmunología , Cordón Umbilical/inmunología
5.
ACS Appl Mater Interfaces ; 16(7): 8518-8526, 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38335724

RESUMEN

We have witnessed the fast progress of cathodic photoelectrochemistry over the past decades, though its signal transduction tactic still lacks diversity. Exploring new sensing strategies for cathodic photoelectrochemistry is extremely demanding yet hugely challenging. This article puts forward a unique idea to incorporate an enzymatic reaction-invoked surface polarization effect (SPE) on the surface of BiOIO3 to implement an innovative cathodic photoelectrochemical (PEC) bioanalysis. Specifically, the thioredoxin reductase (TrxR)-mediated reaction produced the polar glutathione (GSH), which spontaneously coordinated to the surface of BiOIO3 and induced SPE by forming a polarized electric field, resulting in improved electron (e-) and hole (h+) pair separation efficiency and an enhanced photocurrent output. Correlating this phenomenon with the detection of TrxR exhibited a high performance in terms of sensitivity and selectivity, achieving a linear range of 0.007-0.5 µM and a low detection limit of 2.0 nM (S/N = 3). This study brings refreshing inspiration for the cathodic PEC signal transduction tactic through enzyme-mediated in situ reaction to introduce SPE, which enriches the diversity of available signaling molecules. Moreover, this study unveils the potential of in situ generated SPE for extended and futuristic applications.


Asunto(s)
Técnicas Biosensibles , Reductasa de Tiorredoxina-Disulfuro , Técnicas Electroquímicas/métodos , Técnicas Biosensibles/métodos , Electrodos , Electrones , Límite de Detección
6.
Anal Chim Acta ; 1301: 342467, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38553124

RESUMEN

Photoelectrochemistry represents a promising technique for bioanalysis, though its application for the detection of Flap endonuclease 1 (FEN1) has not been tapped. Herein, this work reports the exploration of creating oxygen vacancies (Ov) in situ onto the surface of Bi2O2S nanosheets via the attachment of dopamine (DA), which underlies a new anodic PEC sensing strategy for FEN1 detection in label-free, immobilization-free and high-throughput modes. In connection to the target-mediated rolling circle amplification (RCA) reaction for modulating the release of the DA aptamer to capture DA, the detection system showed good performance toward FEN1 analysis with a linear detection range of 0.001-10 U/mL and a detection limit of 1.4 × 10-4 U/mL (S/N = 3). This work features the bioreaction engineered surface vacancy effect of Bi2O2S nanosheets as a PEC sensing strategy, which allows a simple, easy to perform, sensitive and selective method for the detection of FEN1. This sensing strategy might have wide applications in versatile bioasssays, considering the diversity of a variety of biological reactions may produce the DA aptamer.


Asunto(s)
Técnicas Biosensibles , Endonucleasas de ADN Solapado , Oxígeno , Técnicas Biosensibles/métodos , Límite de Detección , Técnicas Electroquímicas/métodos
7.
Biomark Med ; 17(14): 599-612, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37843407

RESUMEN

Objective: This study intended to unravel the relationship of EVI2B expression with lung adenocarcinoma (LUAD). Methods: TIMER1.0, Gene Expression Profiling Interactive Analysis and Human Protein Atlas databases, as well as the University of Alabama at Birmingham Cancer website, were used to analyze the expression of EVI2B and its relationship with clinical features. The relationship between survival curve analysis and prognosis was analyzed. The role of EVI2B in LUAD was verified by wet experiments. Results: EVI2B was markedly downregulated in LUAD. There was a relationship between the expression of EVI2B and clinical features. Low EVI2B level was substantially implicated in low survival in LUAD. EVI2B overexpression constrained LUAD cell viability, migration and invasion. Conclusion: EVI2B was related to prognosis and immune microenvironment in LUAD, suggesting that EVI2B may be a novel prognostic marker for LUAD.


Lung adenocarcinoma (LUAD) is a type of cancer. It causes many deaths. However, there is no good treatment for it yet. Scientists found a gene called EVI2B. EVI2B can help show how bad the cancer is. EVI2B is at a low level in LUAD. When it is high, patients have a better chance of surviving. EVI2B is linked to the immune system fighting cancer. It can be used to check the progression of LUAD. EVI2B may help with new treatments in the future.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Glicoproteínas de Membrana , Humanos , Adenocarcinoma del Pulmón/diagnóstico , Adenocarcinoma del Pulmón/genética , Supervivencia Celular , Bases de Datos Factuales , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Pronóstico , Microambiente Tumoral , Glicoproteínas de Membrana/genética
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(2): 522-531, 2023 Apr.
Artículo en Zh | MEDLINE | ID: mdl-37096529

RESUMEN

OBJECTIVE: To evaluate the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with decitabine (Dec)-conditioning regimen in the treatment of myelodysplastic syndrome (MDS) and MDS transformed acute myeloid leukemia (MDS-AML). METHODS: The characteristics and efficacy data of 93 patients with MDS and MDS-AML who received allo-HSCT in our center from April 2013 to November 2021 were retrospectively analyzed. All patients were administered by myeloablative conditioning regimen containing Dec (25 mg/m2 /d×3 d). RESULTS: Among the 93 patients, 63 males and 30 females, were diagnosed as MDS(n =77), MDS-AML(n =16). The incidence of I/II grade regimen-related toxicity (RRT) was 39.8%, and III grade RRT was only found in 1 patient (1%). Neutrophil engraftment was successful in 91 (97.8%) patients after a median neutrophil engraftment time of 14 (9-27) days; Successful platelet engraftment was achieved in 87 (93.5%) patients, with a median engraftment time of 18 (9-290) days. The incidence of acute graft versus host disease(aGVHD) and grade III-IV aGVHD was 44.2% and 16.2%, respectively. The incidence of chronic graft versus host disease(cGVHD) and moderate-to-severe cGVHD was 59.5% and 37.1%, respectively. Of the 93 patients, 54 (58%) developed posttransplant infections, among which lung infection (32.3%) and bloodstream infection (12.9%) were the most common. The median follow-up after transplantation was 45 (0.1-108) months. The 5-year overall survival (OS) rate, disease-free survival (DFS) rate, treatment-related mortality, and cumulative incidence of relapse were 72.7%, 68.4%, 25.1%, and 6.5%, respectively. And the 1-year graft-versus-host disease/relapse-free survival rate was 49.3%. The patients in different group of relative high-risk prognostic scoring or low-risk prognostic scoring, with or without poor-risk mutation(s), with mutations number ≥3 or <3 had similar 5-year OS rate (more than 70%). Multivariate analysis showed that the incidence of grade III-IV aGVHD was the independent risk factor affecting OS(P =0.008)and DFS (P =0.019). CONCLUSION: Allo-HSCT with Dec-conditioning regimen is feasible and effective in the treatment of patients with MDS and MDS-AML, especially those in high prognostic risk and with poor-risk mutations.


Asunto(s)
Antimetabolitos Antineoplásicos , Decitabina , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Acondicionamiento Pretrasplante , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Femenino , Trasplante Homólogo , Síndromes Mielodisplásicos/terapia , Leucemia Mieloide Aguda/terapia , Decitabina/administración & dosificación , Antimetabolitos Antineoplásicos/administración & dosificación , Neutrófilos/inmunología , Enfermedad Injerto contra Huésped/epidemiología , Síndrome de Bronquiolitis Obliterante/epidemiología , Resultado del Tratamiento , Incidencia
9.
Cell Biochem Funct ; 30(8): 643-9, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22777760

RESUMEN

Mesenchymal stem cells (MSCs) are multipotent cells traditionally derived from bone marrow (BM). They have been demonstrated to be widely applied in tissue regeneration and cellular therapy. As an alternative to BM, an umbilical cord (UC) is considered as a potential source of MSCs. Here, we showed that human UC-MSCs were easily isolated by a single enzymatic digestion and characteristic of plastic adherence and fibroblast-like morphology. UC-MSCs isolation was successful in 15 of 15 samples. The colony-forming unit-fibroblast frequency was obtained 54 ± 1.33 from 10³ UC-MSCs at passage 3, and the doubling time was (24.15 ± 0.49) h. Almost 10¹° UC-MSCs were largely produced in about 30 days. By flow cytometry analysis, the adherent cells displayed an abundant presence of CD73, CD90 and CD105 and absence of CD34, CD45 and HLA-DR. When cultured in differentiation media, they can be differentiated into adipocytes, osteocytes and chondrocytes. RT-PCR reactions confirmed that their multidifferentiation related genes were positive. Moreover, stem cell-related transcription factors Nanog, Oct-4 and Sox-2 were positively expressed in UC-MSCs. On the basis of these findings, the single enzyme method is a good method to obtain large-scale production of MSCs from whole human UC in a short time, and the UC can be considered as a novel and convenient source of adult MSCs displaying high expansion potential and primitive pluripotent stem cells.


Asunto(s)
Diferenciación Celular , Proliferación Celular , Separación Celular/métodos , Células Madre Mesenquimatosas/citología , Cordón Umbilical/citología , 5'-Nucleotidasa/metabolismo , Adipocitos/citología , Adipocitos/metabolismo , Adulto , Antígenos CD/metabolismo , Células Cultivadas , Condrocitos/citología , Condrocitos/metabolismo , Endoglina , Femenino , Citometría de Flujo , Proteínas de Homeodominio/genética , Humanos , Células Madre Mesenquimatosas/metabolismo , Proteína Homeótica Nanog , Factor 3 de Transcripción de Unión a Octámeros/genética , Osteocitos/citología , Osteocitos/metabolismo , Células Madre Pluripotentes/citología , Células Madre Pluripotentes/metabolismo , Receptores de Superficie Celular/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Transcripción SOXB1/genética , Antígenos Thy-1/metabolismo , Cordón Umbilical/metabolismo
10.
Mitochondrial DNA B Resour ; 7(11): 1971-1974, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36386017

RESUMEN

Schizothorax eurystomus, Kessler 1872 is a unique economic fish in Xinjiang, China that is rarely seen in the market. Next-generation sequencing (NGS) was used to determine the complete mitochondrial genome of S. eurystomus collected from the Yarkand River in Xinjiang. The results showed that the mitochondrial genome is a circular, 16,488-bp-long nucleotide with the typical vertebrate genome structure of 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and a control region. The termination-associated sequence (TAS), central conserved sequence block (CSB), and conserved sequence block were detected in the control region. Phylogenetic analysis placed S. eurystomus in a fully supported clade with S. biddulphi, and that clade was sister to S. yunnanensis. To our knowledge, this is the first study on the complete mitochondrial genome of S. eurystomus from the Yarkand River in Xinjiang, and it provides baseline genetic information for future studies.

11.
Sci Data ; 9(1): 556, 2022 09 09.
Artículo en Inglés | MEDLINE | ID: mdl-36085327

RESUMEN

The big-head schizothorcin (Aspiorhynchus laticeps) is an endemic and near-extinction freshwater fish in Xinjiang, China. In this study, a chromosome-scale genome assembly of A. laticeps was generated using PacBio and Hi-C techniques. The PacBio sequencing data resulted in a 1.58 Gb assembly with a contig N50 of 1.27 Mb. Using Hi-C scaffolding approach, 88.38% of the initial assembled sequences were anchored and oriented into a chromosomal-scale assembly. The final assembly consisted of 25 pseudo-chromosomes that yielded 1.37 Gb of sequence, with a scaffold N50 of 44.02 Mb. BUSCO analysis showed a completeness score of 93.7%. The genome contained 48,537 predicted protein-coding genes and 58.31% of the assembly was annotated as repetitive sequences. Whole genome duplication events were further confirmed using 4dTv analysis. The genome assembly of A. laticeps should be valuable and important to understand the genetic adaptation and endangerment process of this species, which could lead to more effective management and conservation of the big-head schizothorcin and related freshwater fish species.


Asunto(s)
Cyprinidae , Animales , China , Cromosomas/genética , Cyprinidae/genética , Agua Dulce , Análisis de Secuencia de ADN
12.
Front Oncol ; 12: 928324, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35924157

RESUMEN

Myelodysplastic syndrome (MDS) with TP53 mutations has a poor prognosis after transplantation, and novel therapeutic means are urgently needed. Decitabine (Dec) monotherapy has demonstrated improved overall response rates in MDS and acute myeloid leukaemia, although these responses were not durable. This study aimed to preliminary evaluate the efficacy of a Dec-containing allogeneic haematopoietic stem cell transplantation (allo-HSCT) preconditioning regimen in TP53-mutant MDS. Nine patients with TP53-mutant myelodysplastic syndromes received the decitabine-containing preconditioning regimen and subsequent myeloablative allo-HCT between April 2013 and September 2021 in different centres. At a median follow-up of 42 months (range, 5 to 61 months), the overall survival (OS) was 89% (8/9), progression-free survival (PFS) was 89% (8/9), and relapse incidence was 11.1%. The incidence of severe acute (grade III-IV) graft-versus-host disease (GVHD) was 22.2% (2/9) and that of chronic moderate-to-severe GVHD was 11.1% (1/9). The 1-year GVHD-free/relapse-free survival (GRFS) was 56% (5/9). In conclusion, we found real-world clinical data that supports the use of a Dec-containing preconditioning regimen before allo-HSCT for possible improved outcomes in TP53-mutant MDS patients; there is therefore an urgent call for an in-depth exploration of the involved mechanism to confirm these preliminary findings.

13.
Cancer Manag Res ; 13: 5177-5185, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34234561

RESUMEN

OBJECTIVE: Studies have indicated that AGR2 is crucial in many cancers. However, its methylation level in lung adenocarcinoma (LUAD) is rarely known. Hence, the effect of AGR2 methylation on LUAD was explored in the study. METHODS: qRT-PCR was adopted to detect the expression of AGR2 in LUAD cells and normal lung cells. Methylation-specific PCR (MSP) was used to detect the methylation of AGR2 promoter region in different cell lines. MTT, Transwell and wound healing assays were used to verify the progression of cells in each transfection group. RESULTS: The expression of AGR2 was significantly up-regulated in LUAD cells relative to that in normal cells. Moreover, the expression of AGR2 was inversely modulated by DNA methylation, and the hypomethylation of CpG islands would lead to the increased expression of AGR2. Finally, overexpression and hypomethylation of AGR2 facilitated the proliferation, invasion and migration of LUAD cells. CONCLUSION: These results demonstrated that hypomethylation of AGR2 promoter region promoted the expression of AGR2 in LUAD cells, thus promoting the progression of LUAD cells.

14.
J Cardiothorac Surg ; 16(1): 330, 2021 Nov 12.
Artículo en Inglés | MEDLINE | ID: mdl-34772428

RESUMEN

BACKGROUND: So far, few have concerned miR-497-5p in lung squamous cell carcinoma (LUSC). METHODS: MiR-497-5p expression in LUSC was measured by qRT-PCR. Its impacts on tumor-related cell behaviors were investigated by CCK8 assay, scratch healing assay, flow cytometry and Transwell invasion methods. In addition, interaction between miR-497-5p and CDCA4 in LUSC was also elucidated through rescue experiment, western blot, dual-luciferase, and bioinformatics analysis. RESULTS: Low level of miR-497-5p was confirmed in LUSC tissue and cells. Overexpressed miR-497-5p markedly inhibited cancer progression. miR-497-5p restrained CDCA4 expression. Rescue assay showed that overexpressing miR-497-5p eliminated effect of overexpressed CDCA4. CONCLUSION: By targeting CDCA4, miR-497-5p restrained development of LUSC.


Asunto(s)
Carcinoma de Células Escamosas , Proteínas de Ciclo Celular , Neoplasias Pulmonares , MicroARNs , Carcinoma de Células Escamosas/genética , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Humanos , Pulmón , Neoplasias Pulmonares/genética , MicroARNs/genética
15.
Front Immunol ; 12: 728962, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34691036

RESUMEN

Objectives: At present, reinfusions of chimeric antigen receptor (CAR)-T cell have exhibited limited efficacy, while their efficacy on extramedullary relapse remains to be further elucidated in B-cell acute lymphoblastic leukemia (B-ALL). Although combination with IL-15 demonstrated the potential to enhance antitumor activity of CAR-T, the efficacy of this approach remains to be validated clinically. Methods: We reported a patient with B-ALL with extramedullary relapse after allogeneic stem cell transplantation and who was resistant to chemotherapy and radiotherapy. In total, he received four treatments with CAR-T cells repeatedly under the status of disease progression. Results: First, the patient received autologous murine CAR19-CD28-CD3ζ-T cells and achieved full resolution of extramedullary leukemia lasting 8 months. After systemic disease relapse, he received autologous humanized CAR22-41BB-CD3ζ-tEGFR-T cells and achieved complete remission (CR) with incomplete blood count recovery (CRi) with minimal residual disease (MRD) negativity in the bone marrow and shrinkage of extramedullary leukemia. Over 2 months later, he experienced a relapse of the systemic disease and he received autologous murine CAR19-41BB-CD3ζ-mIL15-T cells and achieved CRiMRD- lasting 5 months with the strongest expansion and persistence of CAR. Finally, on relapse of CD19- medullary disease, he received allogeneic humanized CAR22-41BB-CD3ζ-tEGFR-T cells but only achieved a transient decrease in the number of blasts. No CAR-T-cell-related encephalopathy syndrome was observed, and all side effects were manageable. Conclusion: Our report hints the feasibility and safety of CD19 CAR-T cell expressing membrane-bound IL-15 for patient with B-ALL even if relapsed after multiple CAR-T-cell therapies.


Asunto(s)
Antígenos CD19/genética , Terapia Genética , Inmunoterapia Adoptiva , Interleucina-15/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Receptores Quiméricos de Antígenos/genética , Lectina 2 Similar a Ig de Unión al Ácido Siálico/genética , Linfocitos T/trasplante , Adulto , Antígenos CD19/metabolismo , Progresión de la Enfermedad , Humanos , Interleucina-15/metabolismo , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Receptores Quiméricos de Antígenos/metabolismo , Retratamiento , Lectina 2 Similar a Ig de Unión al Ácido Siálico/metabolismo , Linfocitos T/inmunología , Linfocitos T/metabolismo , Factores de Tiempo , Resultado del Tratamiento
16.
Front Oncol ; 11: 702239, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34504785

RESUMEN

Hypomethylating agents, decitabine (DAC) and azacitidine, can act as prophylactic and pre-emptive approaches after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and a non-intensive bridging approach before allo-HSCT. However, they are rarely used as a part of conditioning regimens in patients with relapsed or refractory acute myeloid leukemia (AML). This retrospectively study included a total of 65 patients (median, 37; range, 13-63) with relapsed or refractory AML who were treated by allo-HSCT after myeloablative conditioning regimens without or with DAC (high-dose DAC schedule, 75 mg/m2 on day -9 and 50 mg/m2 on day -8; low-dose DAC schedule, 25 mg/m2/day on day -10 to -8). DAC exerted no impact on hematopoietic reconstitution. However, patients who were treated with the high-dose DAC schedule had significantly higher incidence of overall survival (OS, 50.0%) and leukemia-free survival (LFS, 35.0%), and lower incidence of relapse (41.1%) and grade II-IV acute graft versus host disease (aGVHD, 10.0%) at 3 years, when compared with those treated with standard conditioning regimens or with the low-dose DAC schedule. In conclusion, high-dose DAC combined with standard conditioning regimens before allo-HSCT is feasible and efficient and might improve outcomes of patients with relapsed or refractory AML, which provides a potential approach to treat these patients.

17.
Zhonghua Jie He He Hu Xi Za Zhi ; 33(10): 730-3, 2010 Oct.
Artículo en Zh | MEDLINE | ID: mdl-21176501

RESUMEN

OBJECTIVE: To study Fusarium solani infection as a complication in patients after allogeneic hematopoietic stem cell transplantation and to discuss the diagnosis and appropriate therapy. METHODS: Symptoms, physical examination, laboratory tests, computed tomographic (CT) scans, treatments and outcomes of Fusarium solani infection in a patient with acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation were retrospectively analyzed, and related literatures reviewed. RESULTS: The patient developed pulmonary infiltration and systemic multiple subcutaneous masses after allogeneic hematopoietic stem cell transplantation. Tissue biopsy smear showed a large number of hyphae and spores, and fungal culture grew Fusarium solani. The subcutaneous masses were incised and drained, while amphotericin B and voriconazole were administered, with granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) for hematopoietic recovery. The patient was discharge after full recovery. CONCLUSION: Fusarium solani infection is a rare but fatal complication after allogeneic hematopoietic stem cell transplantation. Once the skin lesions or subcutaneous masses developed, tissue smear and culture should be done as soon as possible. Early diagnosis and effective treatment to recovery of the patient after allogeneic hematopoietic stem cell transplant. Moreover, the recovery of adequate neutrophil levels is the most important factor in the resolution of fusarial infection.


Asunto(s)
Fusariosis/diagnóstico , Fusarium/patogenicidad , Trasplante de Células Madre Hematopoyéticas , Enfermedades de la Piel/microbiología , Fusariosis/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Enfermedades de la Piel/diagnóstico , Enfermedades de la Piel/tratamiento farmacológico , Trasplante Homólogo
18.
Mitochondrial DNA B Resour ; 5(1): 509-510, 2020 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-33366624

RESUMEN

The complete mitochondrial genome of the juvenile Gymnodiptychus dybowskii collected from Ili River was determined by high-throughput sequencing. The mitogenome is a circular molecule 16,657bp in length, including 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and a control region. The TAS, central CSB and CSB were detected in the control region. The gene contents of the mitogenome are identical to those observed in most bony fishes. The NJ phylogenetic tree showed that G. dybowskii clustered into one branch with the species from the same genus.

19.
Mitochondrial DNA B Resour ; 5(1): 742-743, 2020 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-33366729

RESUMEN

The complete mitochondrial genome of the wild Diptychus maculatus collected from Yeken River was determined using next generation sequencing. The mitogenome is a circular molecule 16,765 bp in length, including 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and a control region. The TAS, central CSB, and CSB were detected in the control region. The gene contents of the mitogenome are identical to those observed in most bony fishes. The NJ phylogenetic tree showed that D. maculatus clustered into one separate branch which is close to genus Gymnodiptychus from the same subfamily.

20.
J Chromatogr A ; 1632: 461598, 2020 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-33038752

RESUMEN

Enantioseparation of lysine derivatives by chiral high-performance liquid chromatography (HPLC) was accomplished using two chiral stationary phases (CSPs, Chiralpak IA and Chiralpak IC) based on polysaccharides under normal phase (NP) conditions. All analytes were completely separated. The impacts of polar modifiers, analyte structure and column temperature on chiral separation were discussed. Moreover, the relationship between structure and retention was investigated. The van't Hoff equation was employed to evaluate the thermodynamic parameters of the chiral separation process. The data suggest that the chiral separation process was enthalpy-driven. Surprisingly, two uncommon phenomena were observed: (1) high separation factors on Chiralpak IA and (2) different binding mechanisms with CSP and the two enantiomers.


Asunto(s)
Amilosa/química , Cromatografía Líquida de Alta Presión/métodos , Lisina/aislamiento & purificación , Fenilcarbamatos/química , Simulación del Acoplamiento Molecular , Dinámicas no Lineales , Estereoisomerismo , Temperatura
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