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1.
J Extracell Vesicles ; 11(5): e12218, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35524455

RESUMO

Research on tumour cell-derived small extracellular vesicles (sEVs) that regulate tumour microenvironment (TME) has provided strategies for targeted therapy of head and neck squamous cell carcinoma (HNSCC). Herein, we demonstrated that sEVs derived from HNSCC cancer cells carried CD73 (sEVsCD73 ), which promoted malignant progression and mediated immune evasion. The sEVsCD73 phagocytosed by tumour-associated macrophages (TAMs) in the TME induced immunosuppression. Higher CD73high TAMs infiltration levels in the HNSCC microenvironment were correlated with poorer prognosis, while sEVsCD73 activated the NF-κB pathway in TAMs, thereby inhibiting immune function by increasing cytokines secretion such as IL-6, IL-10, TNF-α, and TGF-ß1. The absence of sEVsCD73 enhanced the sensitivity of anti-PD-1 therapy through reversed immunosuppression. Moreover, circulating sEVsCD73 increased the risk of lymph node metastasis and worse prognosis. Taken together, our study suggests that sEVsCD73 derived from tumour cells contributes to immunosuppression and is a potential predictor of anti-PD-1 responses for immune checkpoint therapy in HNSCC.


Assuntos
5'-Nucleotidase/imunologia , Vesículas Extracelulares , Neoplasias de Cabeça e Pescoço , Vesículas Extracelulares/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Macrófagos/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Microambiente Tumoral
3.
Front Oncol ; 12: 841179, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35296004

RESUMO

Objective: T-cell acute lymphoblastic leukemia (T-ALL) is a rare hematological malignancy with a poor prognosis. The present study aims to identify the precise risk grouping of children with T-ALL. Methods: We analyzed the outcomes for 105 consecutive patients treated using the Chinese Children's Cancer Group ALL-2015 (CCCG-ALL-2015) protocol registered with the Chinese Clinical Trial Registry (ChiCTR-IPR-14005706) between 2015 and 2020 in our center. Nine out of 21 clinical and biological indicators were selected for the new scoring system based on the analysis in this study. Results: The 5-year overall survival (OS), event-free survival (EFS), and disease-free survival (DFS) rates for the 105 patients were 83.1 ± 4.8%, 72.4 ± 5.6%, and 78.4 ± 3.6%, respectively. Based on the new scoring system, 90 evaluable children were regrouped into low-risk (n=22), intermediate-risk (n=50), and high-risk (n=18) groups. The 5-year survival (OS, EFS, and RFS) rates for all patients in the low-risk group were 100%, significantly higher than the rates for those in the intermediate-risk group (91.2 ± 5.2%, 74.4 ± 8.6%, and 82.5 ± 6.2%, respectively) and high-risk group (59.0 ± 13.2%, 51.9 ± 12.4%, and 51.9 ± 12.4%, respectively) (all P values < 0.01). Conclusion: The CCCG-ALL-2015 program significantly improved the treatment outcomes for childhood T-ALL as compared with the CCCG-ALL-2008 protocol. Our new refined risk grouping system showed better stratification among pediatric T-ALL patients and better potential in evaluating therapeutic efficacy.

4.
Front Oncol ; 12: 879471, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35494006

RESUMO

Background: T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) expresses on leukemic stem and progenitor populations of non-M3 acute myeloid leukemia (AML) as well as T lymphocytes. TIM-3 is thought to be involved in the self-renewal of leukemic stem cells and the immune escape of AML cells, however its correlation with AML prognosis is still controversial and worthy of further investigation. Methods: we simultaneously assessed TIM-3 expression levels of leukemic blasts and T lymphocytes in the bone marrow of de novo AML patients using flow cytometry. The correlations of TIM-3 expression between leukemic blasts and T lymphocytes and the correlations of TIM-3 expression with various patient parameters were analyzed. In addition, the Cancer Genome Atlas (TCGA) data of AML patients were acquired and analyzed to verify the results. Results: TIM-3 expression of CD34+ leukemic blasts (R2 = 0.95, p<0.0001) and CD34+CD38- leukemic stem cells (R2 = 0.75, p<0.0001) were significantly and positively correlated with that of the whole population of leukemic blasts. In addition, TIM-3 expression level of leukemic blasts correlated significantly and positively with that of CD8+ (R2 = 0.44, p<0.0001) and CD4+ (R2 = 0.16, p=0.0181) lymphocytes, and higher TIM-3 expression of leukemic blasts was significantly associated with a greater proportion of peripheral CD8+ T lymphocytes (R2 = 0.24, p=0.0092), indicating that TIM-3 on leukemic blasts might alter adaptive immunity of AML patients. Regarding clinical data, the presence of core binding factor (CBF) translocations was significantly correlated with higher TIM-3 expression of leukemic blasts (CBF versus non-CBF, median 22.78% versus 1.28%, p=0.0012), while TIM-3 expression levels of leukemic blasts were not significantly associated with the remission status after induction chemotherapy (p=0.9799), overall survival (p=0.4201) or event-free survival (p=0.9873). Similar to our results, TCGA data showed that patients with CBF translocations had significantly higher mRNA expression level of HAVCR2 (the gene encoding TIM-3) (median, 9.81 versus 8.69, p<0.0001), and as all patients in the cohort were divided into two groups based on the median HAVCR2 expression level, 5-year overall survivals were not significantly different (low versus high, 24.95% versus 24.54%, p=0.6660). Conclusion: TIM-3 expression level on AML blasts correlates with presence of CBF translocations rather than clinical outcomes.

5.
J Hazard Mater ; 422: 126930, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34449347

RESUMO

Dimetridazole (DMZ) and ornidazole (ONZ) have been widely used to treat anaerobic and protozoal infections. The residues of DMZ/ONZ persist in the water environment. The mechanisms and kinetics of hydroxyl-initiated oxidation, the primary DMZ/ONZ degradation method, were evaluated by quantum chemical methods.·OH-induced degradation of DMZ and ONZ shared many mechanistic and kinetic characteristics. The most feasible degradation pathway involved forming OH-imidazole adducts and NO2. The OH-imidazole adducts were subsequently degraded into double·OH imidazole intermediates. The rate coefficients for·OH degradation of DMZ and ONZ were 4.32 × 109 M-1 s-1 and 4.42 × 109 M-1 s-1 at 298 K, respectively. The lifetimes of DMZ and ONZ treated with·OH at concentrations of 10-9-10-18 mol L-1 at 298 K were τDMZ = 0.231-2.31 × 108 s and τONZ = 0.226-2.26 × 108 s, respectively. Toxicity assessment showed that the first degradation products of DMZ and ONZ exhibited enhanced aquatic toxicity, whereas most of the secondary degradation products were not harmful to aquatic organisms. Some of transformation products were still developmental toxicant or mutagenicity positive.


Assuntos
Dimetridazol , Ornidazol , Radical Hidroxila , Cinética , Ornidazol/toxicidade , Oxirredução , Água
6.
Front Oncol ; 11: 666470, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34422630

RESUMO

BACKGROUND: The aim of the study was to validate the diagnostic role of circulating tumor DNA (ctDNA) in genetics aberration on the basis of next-generation sequencing (NGS) in pediatric acute myeloid leukemia (AML). METHODS: Bone marrow (BM) and peripheral blood (PB) were collected from 20 AML children at the time of initial diagnosis, and a ctDNA sample was isolated from PB. Detection of mutation was performed on ctDNA, BM, and peripheral blood mononuclear cell (PBMC) by NGS based on a 185-gene panel. RESULTS: Among 185 genes sequenced by the NGS platform, a total of 82 abnormal genes were identified in 20 patients. Among them, 61 genes (74.39%) were detected in ctDNA, PBMC, and BM samples, while 11 (13.41%) genes were found only in ctDNA and 4 (4.88%) were detected only in the BM sample, and 2 (2.44%) were detected only in PBMC. A total of 239 mutations were detected in three samples, while 209 in ctDNA, 180 in bone marrow, and 184 in PBMC. One hundred sixty-four mutations in ctDNA were shared by matched BM samples, and the median variant allelic frequency (VAF) of these mutations was 41.34% (range, 0.55% to 99.96%) and 44.36% (range, 0.56% to 99.98%) in bone marrow and ctDNA. It was found that 65.79% (75/114) of mutations with clinical significance were detected in three samples, with 9 mutations detected both in ctDNA and BM, and 2 mutations detected both in PBMC and BM. The consistency of mutations with clinical significance between ctDNA and BM was 77.06% (84/109). Among the 84 mutations with clinical significance detected in both sources, the concordance of VAF assessment by both methods was high (R2 = 0.895). CONCLUSION: This study demonstrates that ctDNA was a reliable sample in pediatric AML and can be used for mutation detection. Consistency analysis showed that ctDNA can mirror the genomic information from BM. In addition, a subset of mutations was exclusively detected in ctDNA. These data support the fact that monitoring ctDNA with next-generation sequencing-based assays can provide more information about gene mutations to guide precision treatment in pediatric AML.

7.
Ther Adv Med Oncol ; 13: 17588359211013626, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995600

RESUMO

BACKGROUND: Apatinib, a vascular endothelial growth factor receptor (VEGFR) blocker, has demonstrated encouraging antitumor activities and tolerable toxicities in various cancer types. Recurrent or metastatic adenoid cystic carcinoma of the head and neck (R/MACCHN) carries a poor prognosis, and treatment options are currently limited. This study was conducted to explore the antitumor activity and safety of apatinib in patients with R/MACCHN. METHODS: In this phase II single-arm, prospective study, patients aged 15-75 years with incurable R/MACCHN received apatinib at a 500 mg dose once daily until intolerance or progression occurred. The primary endpoint was the 6-month progression-free survival (PFS) rate based on RECIST version 1.1. The secondary endpoints included response rate, overall survival (OS), and safety. Efficacy was assessed in all dosed patients with at least one post-baseline tumor assessment. RESULTS: Among 68 patients treated with apatinib, 65 were evaluable for efficacy analysis, with a median follow-up time of 25.8 months. The 6-month, 12-month, and 24-month PFS rates were 92.3% [95% confidence interval (CI): 83-97.5%], 75.2% (95% CI: 61.5-84.0%) and 44.7% (95% CI: 32.3-57.5%), respectively. The objective response rate (ORR) and disease control rate (DCR), as assessed by investigators, were 46.2% (95% CI: 33.7-59.0%) and 98.5% (95% CI: 91.7-100.0%), respectively. The median duration of response was 17.7 months [interquartile range (IQR) 14.0-20.9]. The 12-month and 24-month OS rates were 92.3% (95% CI: 83.0-97.5%) and 82.3% (95% CI: 70-90.4%), respectively. The most common adverse events of grades 3-4 were hypertension (5.9%), proteinuria (9.2%), and hemorrhage (5.9%). One patient developed a fatal hemorrhage. CONCLUSION: An encouraging PFS, a high ORR, and a manageable safety profile were observed in this study. It seems that the administration of apatinib in R/MACCHN is likely to have a clinically meaningful therapeutic benefit and warrants further investigation.This study was prospectively registered in ClinicalTrials.gov (NCT02775370; date of registration: 17 May 2016; date of first patient enrollment: 25 May 2016).

8.
Transl Oncol ; 14(8): 101119, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34000643

RESUMO

Relapse of childhood AML1-ETO (AE) acute myeloid leukemia is the most common cause of treatment failure. Optimized minimal residual disease monitoring methods is required to prevent relapse. In this study, we used next-generation sequencing to identify the breakpoints in the fusion gene and the DNA-based droplet digital PCR (ddPCR) method was used for dynamic monitoring of AE-DNA. The ddPCR technique provides more sensitive and precise quantitation of the AE gene during disease progression and relapse. Quantification of the AE fusion gene by ddPCR further contributes to improved prognosis. Our study provides valuable methods for dynamic surveillance of AE fusion DNA and assistance in determining the prognosis.

9.
J Cancer ; 12(10): 3045-3056, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33854604

RESUMO

Background: Tumor-infiltrating immune cells are closely associated with tumor occurrence and progression. The present study explored the potential mechanism of tumor-infiltrating plasmacytoid dendritic cells (pDC) mediating the proliferation and metastasis of cancer cells in oral squamous cell carcinoma (OSCC). Methods: pDC distribution was detected by immunofluorescence and flow cytometry. chemotaxis cytokine receptor-4/7 (CXCR-4/7) expression was detected by quantitative polymerase chain reaction and immunohistochemistry. Cell proliferation and migration were measured by CCK-8, colony formation, wound healing and transwell assay. ELISA and western blotting were used to investigate cytokines secretion and NF-κB pathway activity. Results: Tumor-infiltrating pDC in OSCC was significantly increased and associated with tumor size, lymph node (LN) metastasis (P <0.05). Tumor-infiltrating-pDC-conditioned medium from OSCC patients significantly promoted tumor cell proliferation and invasion, which was at least partly mediated via enhancing the CXCR-4 expression of tumor cell. In addition, the activation of NF-κB pathway played a decisive role in the overexpression of CXCR-4, which was further regulated by pDC-derived TNF-α secretion. Conclusions: Tumor-infiltrating pDC promoted oral cancer proliferation and invasion via activating the TNF-α/NF-κB/CXCR-4 pathway, which may serve as a potential immunological target for the treatment of OSCC in the future.

10.
Arch Oral Biol ; 126: 105116, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33831734

RESUMO

OBJECTIVE: Herein, we aimed to identify biomarkers that affect lymphatic metastasis of oral squamous cell carcinoma (OSCC) through bioinformatic analysis, and clinicopathological and in vitro verifications. DESIGN: The OSCC-related gene expression dataset was retrieved from The Cancer Genome Atlas (TCGA) and analyzed to identify differentially expressed genes (DEGs), which were subjected to pathway analysis. Weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network analysis were performed to identify hub genes. Expression of potential biomarkers was examined using quantitative real-time polymerase chain reaction, immunohistochemistry, and western blotting. Statistical analyses were performed to determine the association between biomarker expression and clinicopathological characteristics of patients with OSCC. Effects of selected biomarkers on proliferation, migration, and invasion were evaluated using in vitro assays. RESULTS: For DEGs, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed potential lymphatic metastasis-related biological processes and signaling pathways. Eight hub genes - ALOXE3, CSTA, PLA2G4E, PPL, SPRR1A, SPRR2A, SPRR2D, and SPRR2E, were identified via WGCNA and PPI analyses. CSTA expression was markedly downregulated in primary OSCC tissues, and low CSTA expression significantly correlated with high tumor grade (P =  0.001), nodal metastasis (P =  0.028), and poor overall survival (P <  0.001). CTSA overexpression inhibited OSCC cell migration and invasion in vitro, with little effect on OSCC cell proliferation. CONCLUSIONS: Our study revealed that CSTA is a promising biomarker and therapeutic target with prognostic implications in patients with OSCC. CSTA may play an essential role in OSCC lymphatic metastasis and tumor differentiation.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Proteínas Ricas em Prolina do Estrato Córneo , Cistatina A , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Neoplasias Bucais/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética
11.
Leuk Res ; 106: 106565, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33865032

RESUMO

BACKGROUND: Numerous long non-coding RNAs (lncRNAs) are reported to affect the progression of multiple myeloma (MM). This study is aimed to explore the role and downstream mechanism of lncRNA LINC01003 in MM. MATERIALS AND METHODS: Xenograft tumor assay was used to assess the function of LINC01003 in MM in vivo. The mRNA expression levels of LINC01003, miR-33a-5p, and PIM1 were determined by quantitative real-time polymerase chain reaction. Cell viability was examined by MTT assay. Relative protein levels of apoptosis-related factors (Bcl-2 and Bax) and proviral integration site of the Moloney leukemia virus kinase 1 (PIM1) were detected via western blot. Adhesion-related proteins were measured by Enzyme-linked immunosorbent assay was used to determine the levels of adhesion-related proteins. Besides, the target relation among LINC01003, miR-33a-5p and PIM1 was tested via dual-luciferase reporter assay. RESULTS: Low expression of LINC01003 was observed in MM cell lines and peripheral blood samples of MM patients. Both LINC01003 up-regulation and miR-33a-5p down-regulation repressed cell viability and adhesion, and promoted apoptosis of MM cells. Moreover, LINC01003 suppressed the growth of xenograft tumor in mice. We then identified miR-33a-5p as a downstream target of LINC01003, and confirmed that PIM1 was a direct target gene of miR-33a-5p. Both high expression of miR-33a-5p and low expression of PIM1 reversed the suppressive effects of LINC01003 overexpression on cell adhesion and viability, and the promoting effect on apoptosis in MM cells. CONCLUSION: LINC01003 functioned as a sponge of miR-33a-5p to inhibit the development MM by regulating PIM1 expression.


Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Mieloma Múltiplo/genética , Proteínas Proto-Oncogênicas c-pim-1/genética , Interferência de RNA , RNA Longo não Codificante/genética , Apoptose/genética , Adesão Celular/genética , Linhagem Celular Tumoral , Sobrevivência Celular , Humanos , Proteínas Proto-Oncogênicas c-pim-1/metabolismo
12.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(3): 271-278, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33691921

RESUMO

OBJECTIVE: To study the clinical features and prognosis of childhood acute myeloid leukemia with myelodysplasia-related changes (AML-MRC). METHODS: A retrospective analysis was performed on the medical data of 14 children who were diagnosed with AML-MRC from June 2014 to March 2020, including clinical features, laboratory examination results, and prognosis. RESULTS: Among the 14 children with AML-MRC, there were 9 boys and 5 girls, with a median age of 11 years (range: 1-17 years), a median leukocyte count of 8.3×109/L [range: (2.0-191.0)×109/L], a median hemoglobin level of 73 g/L (range: 44-86 g/L), and a median platelet count of 75×109/L [range: (4-213)×109/L] at diagnosis. According to the FAB classification, the children with AML-M5 accounted for 71% (10/14). Among the 14 children, 4 had multi-lineage dysplasia (MLD), 2 had a history of myelodysplastic syndrome (MDS), 5 had MDS-related cytogenetic changes, 2 had MLD with MDS-related cytogenetic changes, and 1 had a history of MDS with MLD. The median follow-up time was 10.6 months (range: 0.4-54.4 months) for 14 children, among whom 2 gave up treatment immediately after diagnosis and 12 had an evaluable treatment outcome. The 2-year overall survival (OS) rate was 50%±15%, and the 2-year disease-free survival (DFS) rate was 33%±13%. Of the 12 children, 7 underwent haploidentical hematopoietic stem cell transplantation (HSCT), among whom 5 achieved DFS and 2 died, with a 2-year OS rate of 71%±17% and a 2-year DFS rate of 43%±19%; 5 children underwent chemotherapy alone, among whom 1 achieved DFS, 3 died, and 1 was lost to follow-up, with a 2-year OS rate of 40%±30% and a 2-year DFS rate of 30%±24%. There was no significant difference in the survival condition between the transplantation and chemotherapy groups (P > 0.05). CONCLUSIONS: Childhood AML-MRC is often observed in boys, and AML-M5 is the most common type based on FAB classification. Such children tend to have a poor prognosis. HSCT is expected to improve the poor prognosis of children with AML-MRC. However due to the small number of cases, it is necessary to increase the number of cases for further observation.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Masculino , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/terapia , Prognóstico , Estudos Retrospectivos
13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 38-42, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33554794

RESUMO

OBJECTIVE: To analyze the outcomes of the children suffered from philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL) treated with tyrosine kinase inhibitor (TKI) plus chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: 21 cases of firstly diagnosed Ph+ALL patients aged <12 year treated with Chinese Childhood Leukemia Group ALL 2008 (CCLG-ALL 2008) protocol form January 2008 and April 2015 were retrospectively analyzed.The patients were divided into two groups, one group was TKI+ chemotherapy group, the other group was allo-HSCT group. RESULTS: Among 21 patients, 17 were male and 4 were female with a median age of 8 years old (range, 4-12 years), the median follow-up time was 30 moths (range, 10-133 months). All the patients were treated with chemotherapy induced by the high-risk project of CCLG-ALL 2008. Among 14 patients treated with TKI plus chemotherapy, nine patients achieved complete remission. During 3 months after treatment, patients without complete molecular response or with the second complete remission and intensity desire of transplantation were treated with allo-HSCT, among 9 patients with allo-HSCT, six patients achieved long term survival. CONCLUSION: At TKI era, TKI combined with strong chemotherapy can make Ph+ ALL children achieve 5 years event-free survival as campared those treated with allo-HSCT. However, for the patients without complete molecular response persistently and relapsed they can still benefit from allo-HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Idoso , Criança , Feminino , Humanos , Lactente , Masculino , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Inibidores de Proteínas Quinases , Estudos Retrospectivos
14.
Cancer Cell Int ; 21(1): 28, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413420

RESUMO

BACKGROUND: Circular RNAs (circRNAs) is a newly discovered type of non-coding RNA, the abnormal expression of which has been demonstrated in many types of human tumors. So they have been considered as promising candidates as diagnostic and therapeutic targets in cancer. This research aimed to screen the profile of circRNA expression in salivary adenoid cystic carcinoma (SACC). METHODS: Using the threshold of FDR < 0.05 and fold change > 2 or < 0.5, 5 up-regulated and 26 down-regulated circRNAs were identified. The reliability of sequencing was verified by the expression detection of randomly selected circRNAs via qRT-PCR. RESULTS: Moreover, the circRNA-miRNA system was established by bioinformatics approaches and successfully identified an interaction between circRNA ABCA13 and a cancer-related miRNA (miR-138-5p), which was also verified by qRT-PCR. Moreover, the predicted molecular interaction proved that circRNA ABCA13 may promote SACC through inhibition of miR-138-5p. CONCLUSIONS: Collectively, this study has offered the first report about the circRNA expression profile and circRNA-miRNA network in SACC. All of the above could benefit the exploration of novel therapeutic target in SACC treatment.

15.
Ultrason Sonochem ; 72: 105466, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33476966

RESUMO

A series of CuCe-modified TiO2-ZrO2 catalysts synthesized by stepwise impregnation method and ultrasonic-assisted impregnation method were investigated to research the removal of NO in the simulated flue gas. Results showed that the CuCe/TiO2-ZrO2 catalyst prepared by ultrasonic-assisted impregnation method exhibited the superior NO conversion, in which higher than 85% NO was degraded at the temperature range of 250-400 °C and the highest NO conversion of 94% at 350 °C. It proves that ultrasonic treatment can markedly improve the performance of catalysts. The effect of ultrasonic enhancement on CuCe/TiO2-ZrO2 was comprehensively studied through being characterized by physicochemical characterization. Results reveal that the ultrasonic cavitation effect improves the distribution of active species and the synergistic interaction between Cu with Ce components (Cu+ + Ce4+ â†” Cu2+ + Ce3+) on the catalysts significantly, thus resulting in better dispersibility as well as a higher ratio of Cu2+ and Ce3+ of the catalysts. Moreover, it was found that the CuCe/TiO2-ZrO2 catalyst prepared by the ultrasonic-assisted impregnation method represented a higher degree of ultrafine metal particles and evenness. The above results were described with the generalized dimension and singularity spectra in multifractal analysis and validated by the comparative test. Therefore, it can be concluded that ultrasonic treatment facilitates the particle size and distribution of active sites on the catalysts.

16.
Ann Hematol ; 100(9): 2269-2277, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33443592

RESUMO

Variation in normal blood cells during chemotherapy has not been recognised as a risk factor guiding chemotherapy in childhood acute lymphoblastic leukaemia (ALL). This study aims to explore whether variations in normal haematopoiesis determine prognosis as well as to improve risk-stratified treatment in childhood ALL. A retrospective study of 279 cases of ALL treated with the CCCG-ALL-2015 regimen in the Division of Pediatric Blood Diseases Center, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, from May 2015 to January 2017 was performed to analyse the prognostic impact of blood cell levels on day 19 of induction therapy by Kaplan-Meier method. Patients with childhood ALL with absolute neutrophil count (ANC) ≤ 90 cells/µl, absolute monocyte count (AMC) ≤ 10 cells/µl or absolute lymphocyte count (ALC) ≤ 1000 cells/µl on day 19 of induction therapy had a lower event-free survival (EFS) rate than those with higher values (all P < 0.05). Multivariate analysis confirmed that ANC ≤ 90 cells/µl and ALC ≤ 1000 cells/µl were independent adverse prognostic factors (HR = 1.981 and 2.162, respectively, both P < 0.05). Among patients with minimal residual disease (MRD) < 1% on day 19 of induction therapy, those with ANC ≤ 90 cells/µl had lower EFS than those with ANC > 90 cells/µl (70.8 ± 6.1% vs 86.4 ± 3.1%, P = 0.001). In the subgroup with the BCR/ABL1 fusion gene, patients with ANC ≤ 90 cells/µl on day 19 of induction therapy also had lower EFS than those with ANC > 90 cells/µl (34.4 ± 25.2% vs 25.0 ± 21.7%, P = 0.041). ANC and ALC during induction therapy are independent prognostic factors for childhood ALL. ANC contributes to guiding the prognosis of patients with low-level MRD or the BCR/ABL1 fusion gene.


Assuntos
Quimioterapia de Indução , Contagem de Leucócitos , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Criança , Intervalo Livre de Doença , Feminino , Humanos , Contagem de Linfócitos , Masculino , Neoplasia Residual/sangue , Neoplasia Residual/diagnóstico , Neoplasia Residual/tratamento farmacológico , Neutrófilos/citologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Prognóstico , Estudos Retrospectivos
17.
Cancer Med ; 10(3): 956-964, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33491298

RESUMO

BACKGROUND: The preferred salvage treatment for children with relapsed/refractory acute myeloid leukemia (R/R-AML) remains unclear. The combination of cladribine/Ara-C/granulocyte-colony stimulating factor and mitoxantrone (CLAG-M) shown promising results in adult R/R-AML. We aim to investigate the efficacy and safety of CLAG-M versus mitoxantrone/etoposide/cytarabine (MEC) or idarubicin/etoposide/cytarabine (IEC) in R/R-AML children. METHODS: Fifty-five R/R-AML children were analyzed. The overall response rate (ORR), overall survival (OS), and progression-free survival (PFS) at 3-year were documented. Karyotype or mutations status were summarized as different risk groups. RESULTS: The ORR was achieved in 80% (16/20) and 51% (18/35) of patients after one-cycle of CLAG-M and MEC/IEC treatment (p < 0.001). The CLAG-M group's OS (66.8% ± 16.2% vs. 40.4% ± 10.9%, p = 0.019) and PFS (52.6% ± 13.7% vs. 34.9% ± 9.1%, p = 0.036) at 3-year was significantly higher than the MEC/IEC group. In high-risk patients, 33.3% experienced progression of disease (PD) and 22.2% dead in CLAG-M group, while 50% experienced PD and 43.8% dead in MEC/IEC. When it comes to low-risk group, none of them in CLAG-M experienced PD or death, while up to 50% of patients received MEC/IEC suffered PD, and all of them died eventually. Similar results were also found in the intermediate-risk group. Surprisingly, the presence of FLT3-ITD was associated with poor outcome in both groups. The most common adverse events were hematologic toxicities, and the incidence was similar in both group. CONCLUSIONS: CLAG-M group demonstrated effective palliation along with acceptable toxicity in R/R-AML patients. However, patients with FLT3-ITD may benefit less from CLAG-M, owing to higher PD rate and all-cause mortality than other patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Quimioterapia de Indução/mortalidade , Leucemia Mieloide Aguda/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Terapia de Salvação/mortalidade , Adolescente , Criança , Pré-Escolar , Cladribina/administração & dosagem , Citarabina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Idarubicina/administração & dosagem , Lactente , Leucemia Mieloide Aguda/patologia , Masculino , Mitoxantrona/administração & dosagem , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
18.
Exp Cell Res ; 399(1): 112424, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33340493

RESUMO

Increasing effort has been put into finding novel molecular pathways to improve the efficiency of EGFR inhibitors against head and neck squamous cell cancer (HNSCC). In this study, we performed data mining and bioinformatically analysed RNA-Seq data downloaded from TCGA and confirmed that higher expression of HPRT in HNSCC tissue was related to poor prognosis of patients. Then, we conducted in vitro and in vivo loss- and gain-of-function experiments to demonstrate the role of HPRT in HNSCC cell lines. Overexpression of HPRT increased the gene expression of epithelial mesenchymal transition markers via direct interaction with STAT3. Knocking down HPRT significantly decreased tumour growth and enhanced the anticancer effect of EGFR inhibitors against HNSCC xenografts. In conclusion, HPRT is a binding partner of STAT3 that promotes EMT and proliferation. Our findings support HPRT as a promising prognostic indicator and potential therapeutic target for HNSCC.


Assuntos
Neoplasias de Cabeça e Pescoço/patologia , Hipoxantina Fosforribosiltransferase/fisiologia , Fator de Transcrição STAT3/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Animais , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Transição Epitelial-Mesenquimal/fisiologia , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Hipoxantina Fosforribosiltransferase/genética , Hipoxantina Fosforribosiltransferase/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Metástase Neoplásica , Ligação Proteica , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Células Tumorais Cultivadas
19.
RSC Adv ; 12(1): 378-388, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-35424492

RESUMO

This study aims to investigate the enhanced low temperature denitration activity and promotional mechanism of a cerium-based catalyst through copper modification. In this paper, copper and cerium oxides were supported on TiO2-ZrO2 by an impregnation method, their catalytic activity tests of selective catalytic reduction (SCR) of NO with NH3 were carried out and their physicochemical properties were characterized. The CuCe/TiO2-ZrO2 catalyst shows obviously enhanced NH3-SCR activity at low temperature (<300 °C), which is associated with the well dispersed active ingredients and the synergistic effect between copper and cerium species (Cu2+ + Ce3+ ↔ Cu+ + Ce4+), and the increased ratios of surface chemisorbed oxygen and Cu+/Cu2+ lead to the enhanced low-temperature SCR activity. The denitration reaction mechanism over the CuCe/TiO2-ZrO2 catalyst was investigated by in situ DRIFTS and DFT studies. Results illustrate that the NH3 is inclined to adsorb on the Cu acidic sites (Lewis acid sites), and the NH2 and NH2NO species are the key intermediates in the low-temperature NH3-SCR process, which can explain the promotional effect of Cu modification on denitration activity of Ce/TiO2-ZrO2 at the molecular level. Finally, we have reasonably concluded a NH3-SCR catalytic cycle involving the Eley-Rideal mechanism and Langmuir-Hinshelwood mechanism, and the former mechanism dominates in the NH3-SCR reaction.

20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(6): 1831-1836, 2020 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-33283706

RESUMO

OBJECTIVE: To investigate the consistency between FCM and PCR on the detecting of MRD in TCF3-PBX1+ ALL, and to investigate the prognosis value of these 2 methods. METHODS: 55 cases of paediatric TCF3-PBX1+ ALL patients from April 2008 to April 2015 were enrolled and analyzed. The FCM and PCR was used to detect the MRD in 239 bone marrow samples of 55 patients. All statistical analyses were carried out by using SPSS software version 16. RESULTS: Among the 55 children with TCF3-PBX1+ ALL, there were 30 male and 25 female. The median age was 5 (1-14) years. 20 patients relapsed during follow-up. The MRD results from PCR and FCM showed a strong correlation between both methods (K=0.774, P<0.001). There was no significant difference in 5-years DFS and OS between the patients in PCR+ and PCR- groups on day 15 or day 33. The 5 year DFS rate between the patients in FCM- and FCM+ was 63.9%±7.0% and 0; the 5 year OS rate was 66.5%±7.9% and 0. Combined with the result of FCM and PCR, at the d 33 of treatment, the 5-year DFS rate in FCM-/PCR- and single positive group was 65.4%±7.2% and 25.0%±15.3% (P<0.01). CONCLUSION: The detection result of MRD in TCF3-PBX1 detect by FCM and PCR shows better consistency. MRD positivity detected by FCM at the end of induction therapy (day 33) predicts a high risk of relapse in TCF3-PBX1 ALL patients.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Medula Óssea , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Neoplasia Residual , Proteínas de Fusão Oncogênica/genética , Prognóstico , Recidiva
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