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1.
Eur Radiol ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32065283

RESUMO

OBJECTIVES: To investigate whether there was an optimal interim size reduction (iΔSPD) cutoff value that could discriminate diffuse large B cell lymphoma (DLBCL) patients with poor prognosis. METHODS: This retrospective study enrolled 265 newly diagnosed DLBCL patients with baseline and interim (after 3 cycles) contrast-enhanced computed tomographic scan (CECT) available. Two radiologists evaluated CECT images and selected target lesions according to the Lugano Response Criteria. Lymph nodes greater than 15 mm in longest diameter (LDi) and extra-nodal lesions with LDi greater than 10 mm could be chosen as target lesions and used to calculate iΔSPD. A software tool, X-Tile, was used to calculate the optimal iΔSPD cutoff value to differentiate patients with good vs. poor prognosis. Receiver operating characteristic curve analysis, Cox regression analysis, and Kaplan-Meier analyses were further used to validate the optimal cutoff value. RESULTS: The optimal cutoff value of iΔSPD calculated by X-tile was 80%. Compared with 50% and 100%, 80% cutoff value had the intermediate sensitivity and specificity (57.75% and 86.69% for overall survival (OS), 48.98% and 92.22% for progression-free survival (PFS), respectively), but the maximal Youden index (0.4744 for OS, 0.4120 for PFS, respectively) and areas under the curve (0.737 [0.680, 0.789] for OS). Cox regression analysis also revealed that iΔSPD < 80% could independently predict an inferior OS and PFS (both p < 0.001) while neither iΔSPD < 50% nor iΔSPD = 100% could. CONCLUSIONS: iΔSPD with the cutoff value 80% is an independent predictor of PFS and OS for patients with DLBCL. Results suggest that treatment should be modified for patients with iΔSPD < 80%. KEY POINTS: • The aim of interim response assessment is to identify patients whose disease has not responded to or has progressed on induction therapy. • A cutoff value of 80% in size reduction (ΔSPD) is an independent predictor of PFS and OS for DLBCL patients and is better than 50%. • In DLBCL patients with interim ΔSPD < 80%, a change to a more efficient therapy should be considered.

2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 34-39, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027250

RESUMO

OBJECTIVE: To explore the expression of miR-155 in patients with chronic lymphocytic leukemia (CLL) and its correlation with the clinical and biological features in CLL. METHODS: The expression of miR-155 was detected by quantitative real time polymerase chain reaction (qRT-PCR) in the peripheral mononuclear cells collected from 73 CLL patients and CD19 positive B cells collected from 60 healthy controls, respectively. The expression of miR-155 in CLL patients was compared with the healthy controls, and the correlation of miR-155 expression with the clinical characteristics of CLL patients such as age, sex, Binet stage, cytogenetic and molecular genetic, as well as the relationship of miR-155 expression level with time to treatment (TTT) and overall survival (OS) was further analysed. RESULTS: The expression of miR-155 was significantly elevated in CLL patients compared with the healthy controls. Further analysis showed that miR-155 expression decreased in the patients with the mutated immunoglobulin heavy chian variable region (IGHV) as compared with the patients unmutated (P<0.05), and its expression was significant higher in the IGHV-39 family (P<0.05). Fluorescence in situ hybridization (FISH) showed that the expression of miR-155 increased in patients with P53 mmutation/deletion and ATM deletion (P<0.05). However, OS and TTT were not different between the patients with high and low expression of miR-155. CONCLUSION: MiR-155 is increasingly expresses in CLL patients and correlates with poor prognosis, suggesting its important role in the genesis and progress of CLL.


Assuntos
Leucemia Linfocítica Crônica de Células B , MicroRNAs/genética , Humanos , Região Variável de Imunoglobulina , Hibridização in Situ Fluorescente , Leucemia Linfocítica Crônica de Células B/genética , Mutação , Prognóstico
3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 196-201, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027276

RESUMO

OBJECTIVE: To investigate the distribution of peripheral blood lymphocytes and natural killer (NK) cells, and its influence on the prognosis of patients with myelodysplastic syndromes (MDS). METHODS: The lymphocytes proportion, absolute lymphocyte counts (ALC), NK cell proportion and absolute NK cell counts (ANKC) as well as the related data of 95 MDS patients diagnosed between 2013 and 2017 analyzed retrospectively. The correlation of ALC and ANKC with prognosis was also analyzed. RESULTS: As compared with low ALC patients, MDS patients with ALC≥0.885×109/L had a higher overall response rate (66.7% vs 35.8%) (P<0.01). The ALC of effective patients after treatment significatitly increased in compaison of ALC at diagnosis. Multivariate analysis indicated that patients with ALC≥0.885×109/L had long overall survival (OS) time in comparison with patients with low level (16.4 vs 12.4 months) (P<0.05). The OS time of patients with ANKC≥0.110×109/L was shorter in comparison with patients with low level (10.9 vs 16.3 months) (P<0.01). Otherwise, blast, cytogenetic risks and treatment response were also independent risk factors of MDS (P<0.05). Revised International Prognostic Scoring System (IPSS-R) combined with ANKC could improve predictive accuracy of IPSS-R alone (AUC 0.718 vs 0.674) (P<0.05). CONCLUSION: Lymphocytes and NK cells are important for the prognosis evaluation of MDS patients.


Assuntos
Células Matadoras Naturais , Síndromes Mielodisplásicas , Humanos , Contagem de Linfócitos , Prognóstico , Estudos Retrospectivos
4.
Artigo em Inglês | MEDLINE | ID: mdl-31915915

RESUMO

INTRODUCTION: Mantle cell lymphoma (MCL) is a subtype of B-cell non-Hodgkin lymphoma (NHL), and the purpose of this study was to evaluate the prognostic value of 25-hydroxy vitamin D [25-(OH)D] deficiency among patients with MCL. MATERIALS AND METHODS: Seventy MCL patients with serum 25-(OH)D were enrolled in this study. 25-(OH)D deficiency was defined as a 25-(OH)D level lower than 50 nmol/L, according to International standard of 25-(OH)D classification. The univariate and multivariate Cox regression analyses were used to define the prognostic factors associated with progression-free survival (PFS) and overall survival (OS). Receiver operator characteristic (ROC) curves and the areas under the curve (AUC) were calculated to evaluate the accuracy of combined MIPI-c with 25-(OH)D deficiency. RESULTS: The results showed that 40 patients had 25-OH vitamin D deficiency, with a median follow-up of 25.5 months (range 3.4-65.7 months). Univariate Cox regression analysis showed that 25-(OH)D deficiency group demonstrated unfavorable PFS (P = 0.003) and OS (P = 0.006). Multivariate Cox regression analysis revealed that 25-(OH)D deficiency was an independent prognosis factor for PFS [hazard ratio (HR) 3.713; 95% confidence interval (CI) 1.822-7.565; P < 0.001], and OS (HR 8.305; 95% CI 2.060-33.481; P = 0.003). 25-(OH)D deficiency combined with MIPI-c showed an improved prognostic capacity. CONCLUSION: In summary, 25-(OH)D deficiency was a promising prognostic predictor for MCL.

5.
Leuk Lymphoma ; : 1-7, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31928271

RESUMO

Waldenström Macroglobulinemia (WM) is a rare form of non-Hodgkin lymphoma with great heterogeneity, and data on the role of D-dimer in the progression of WM are limited. We retrospectively searched medical records for 110 newly diagnosed WM patients who were admitted to the department of hematology of the First Affiliated Hospital of Nanjing Medical University from January 2009 to December 2018. Univariate and multivariate analyses were used to assess prognostic factors for overall survival (OS) and progression-free survival (PFS). Characteristics associated with elevated D-dimer level in WM patients were high serum beta-2 macroglobulin, elevated serum lactic dehydrogenase, cytogenetic abnormalities and late stage of the international stage system of WM. Patients with D-dimer >0.55 mg/L had worse OS and PFS. In conclusion, high level of D-dimer was associated with poor survival and acted as a negative predictor for untreated WM patients.

7.
Cancer Res Treat ; 52(1): 189-206, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31291713

RESUMO

PURPOSE: Diabetes mellitus (DM) is associated with elevated cancer risk and poor survival outcome in malignancies. The objective of this study was to evaluate the prognostic value of preexisting DM in chronic lymphocytic leukemia (CLL). Materials and Methods: Six hundred and thirty-three subjects with newly-diagnosed CLL between 2007 and 2016 were recruited. Propensity score-matched method was performed to balance baseline characteristics and eliminate possible bias. Univariate and multivariate Cox regression analyses screened the independent risk indicators for time-to-first-treatment (TTFT) and cancer-specific survival (CSS) of CLL. Receiver operator characteristic curves and the corresponding areas under the curve assessed the predictive accuracy of CLL-International Prognostic Index (IPI) together with DM. RESULTS: The results showed that 111 patients had pre-existing DM. In the propensity-matched cohort, DM was correlated with inferior TTFT and CSS in CLL patients, and it was an independent prognostic factor for both CSS and TTFT. Pre-diabetics also shared undesirable prognostic outcome compared with patients with no diabetic tendency, and a positive association between longer diabetic duration and poorer prognosis of CLL was identified. DM as one additional point to CLL-IPI had larger area under the curve compared with CLL-IPI alone in CSS prediction and could improve the prognostic capacity of CLL-IPI. CONCLUSION: Pre-existing DM was found to be a valuable prognostic predictor and could help predict life expectancy and build refined prognostication models for CLL.

8.
Acta Physiol (Oxf) ; 228(1): e13351, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31344326

RESUMO

Oxidative stress is recognized as free radical dyshomeostasis, which has damaging effects on proteins, lipids and DNA. However, during cell differentiation and proliferation and other normal physiological processes, free radicals play a pivotal role in message transmission and are considered important messengers. Organisms maintain free radical homeostasis through a sophisticated regulatory system in which these "2-faced" molecules play appropriate roles under physiological and pathological conditions. Reactive oxygen species (ROS), including a large number of free radicals, act as redox signalling molecules in essential cellular signalling pathways, including cell differentiation and proliferation. However, excessive ROS levels can induce oxidative stress, which is an important risk factor for diabetes, cancer and cardiovascular disease. An overall comprehensive understanding of ROS is beneficial for understanding the pathogenesis of certain diseases and finding new therapeutic treatments. This review primarily focuses on ROS cellular localization, sources, chemistry and molecular targets to determine how to distinguish between the roles of ROS as messengers and in oxidative stress.

9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(6): 1876-1880, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31839053

RESUMO

OBJECTIVE: To investigate the expression level of T lymphocyte subsets in elderly patients with newly diagnosed multiple myeloma (NDMM), and to evaluated the prognostic value of T lymphocytic abnormalities in elderly NDMM patients. METHODS: Pretreated peripheral blood of 39 newly diagnosed elder patients with MM was tested by multi-parameter flow cytometry (MFC) to quantitatively detect T lymphocyte subsets, including CD4+T cell, CD8+T cell, and CD4/CD8 ratio. The prognostic values T-lymphocyte subset were evaluated in newly diagnosed elderly patients with MM. RESULTS: The median follow-up time was 21.5 (range, 3.0-66.0) months. Absolute counts of CD4+T cell and CD4/CD8 ratio positively correlated with prognosis. In the multivariate COX analysis, lower CD4/CD8 ratio and CD4+T cell counts were identified to be independent adverse prognostic factors for OS. CONCLUSION: Lower CD4/CD8 ratio and CD4+T cell counts at initial diagnosis are independent unfavorable prognostic factors for elderly patients with MM, and T lymphocyte subsets are crucial indicators for MM patients' prognosis.


Assuntos
Mieloma Múltiplo , Idoso , Relação CD4-CD8 , Citometria de Fluxo , Humanos , Contagem de Linfócitos , Subpopulações de Linfócitos , Prognóstico , Subpopulações de Linfócitos T
10.
Clin Lab ; 65(12)2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31850699

RESUMO

BACKGROUND: Changes of glycoprotein are hallmarks for various malignancies; however, the prognostic impact in diffuse large B-cell lymphoma (DLBCL) has not been well elucidated. METHODS: Here we used serum tumor abnormal protein (TAP) level, a lectin-based agglutination assay, to investigate the clinical value of circulating glycoprotein level in DLBCL. One hundred and thirty-one newly diagnosed DLBCL patients treated by rituximab combined chemotherapy were retrospectively enrolled, all with data available for TAP level at initial diagnosis. Additionally, TAP levels during and after initial treatments were measured in 97 cases. RESULTS: Our results showed elevated pre-treatment TAP level was significantly associated with shorter progression-free survival (PFS, p = 0.019) and overall survival (OS, p = 0.025), especially in the high-risk subgroups. In the multivariate Cox regression analyses, pre-treatment TAP level was an independent predictive factor for PFS (p = 0.048). Moreover, ≥ 25% decrease of TAP level indicated superior PFS (p = 0.006) and OS (p = 0.024) in patients with elevated TAP levels at diagnosis. In cases which achieved complete or partial remission, TAP levels were significantly reduced during treatment, but not in non-responsive or progressed patients. CONCLUSIONS: TAP level is a strong prognostic tool for predicting disease progression and monitoring individual response for DLBCL in the rituximab era.

12.
Cancer Res Treat ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31671936

RESUMO

Purpose: To investigate the prognostic impact of EBV-miR-BHRF1-1 with chronic lymphocytic leukemia (CLL) as well as role of EBV-miR-BHRF1-1 in p53 gene. Materials and Methods: Quantitative reverse transcription-PCR (qRT-PCR) and western blotting (WB) were used to quantify EBV-miR-BHRF1-1 and p53 expression in cultured CLL. Results: p53 aberration was associated with higher expression level of Epstein-Barr virus (EBV)-microRNA (miRNA, miR)-BHRF1-1 (p<0.001) which was also an independent prognostic marker for overall survival (OS) (p=0.028; HR 5.335 [1.193, 23.846]) in 97 newly-diagnosed CLL patients after adjusted with CLL-international prognostic index (CLL-IPI). We identified EBV-miR-BHRF1-1 as a viral miRNA regulator of p53. EBV-miR-BHRF1-1 repressed luciferase reporter activity by specific interaction with the seed region within the p53 3' untranslated region. Discordance of p53 messenger RNA and protein expression was associated with high EBV-miR-BHRF1-1 levels in CLL patients and cell lines. EBV-miR-BHRF1-1 inhibition upregulated p53 protein expression, induced cell cycle arrest and apoptosis and decreased cell proliferation in cell lines. EBV-miR-BHRF1-1 mimics downregulated p53 protein expression, decreased cell cycle arrest and apoptosis, and induced cell proliferation in cell lines. Conclusion: This study supported a role of EBV-miR-BHRF1-1 in p53 regulation in vitro. Our results support the potential of EBV-miR-BHRF1-1 as a therapeutic target in EBV-associated CLL with p53 gene aberration.

13.
J Cancer ; 10(23): 5805-5811, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737117

RESUMO

Objectives: The aim of this study is to investigate the prognostic significance of baseline maximum standard uptake value (SUVmax), whole body SUVmax (WBSUVmax), whole body metabolic tumor volume (WBMTV) and whole body total lesion glycolysis (WBTLG) in patients with peripheral T-cell lymphoma (PTCL). Methods: Eighty patients with PTCL who underwent pretreatment 18F-PET/CT were enrolled in this study. WBMTV and WBTLG were computed by using the margin threshold of SUV>3.0. WBSUVmax was obtained by summing of SUVmax of the whole-body SUVmax of 11 nodal and 10 extra-nodal lesions. Results: Median SUVmax was 13.8 (range, 4.6-35.5), median WBSUVmax was 24.6 (range, 4.6-153.4), median WBMTV was 149 cm3 (range, 4-4545 cm3) and median WBTLG was 1017 (range, 16.5-23739). Six patients with anaplastic large cell lymphoma, ALK positive were excluded in the following statistical analysis for their unique pathological types and good prognosis. The receiver operating curve (ROC) analysis showed that the optimal cut-off values of WBSUVmax, WBMTV and WBTLG with overall survival (OS) were 22.2, 169.5 cm3 and 746.1, respectively. Patients with high WBSUVmax, WBMTV and WBTLG had a poor prognosis. WBSUVmax, WBMTV and WBTLG were associated with international prognostic index (IPI) and prognostic index for T-cell lymphoma (PIT). In multivariate analysis, WBTLG and PIT were independent prognostic factors of both progression free survival (PFS) and OS. Conclusions: Our study shows that high WBTLG, WBMTV and WBSUVmax could predict a relatively poor prognosis, and has a highly significant association with PIT and IPI.WBTLG could be an independent predictive factor for survival outcomes in patients with PTCL.

14.
Oxid Med Cell Longev ; 2019: 8098135, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31583045

RESUMO

The oxidative stress of vessel endothelium is a major risk factor of cardiovascular disorders. Antioxidative stress drugs are widely used in cardiovascular therapy. Aspirin eugenol ester (AEE) is a new pharmaceutical compound synthesized by esterification reaction of aspirin with eugenols and possesses antioxidative activity. The present study was designed to investigate the mechanism how AEE protects human umbilical vein endothelial cells (HUVECs) from H2O2-induced oxidative stress. H2O2 was given to the HUVECs with or without AEE pretreatment. Changes in the oxidative stress-related factors, including those related to the mitochondria-lysosome axis, were determined with Western blotting, cellular immunofluorescence, and enzyme activity test. The results showed that, in the HUVECs, 300 µM H2O2 treatment significantly increased the apoptosis rate, MDA concentration, reactive oxygen species (ROS) production, mitochondrial membrane potential, expression of Bax and mature cathepsin D (CTSD), and activity of CTSD and Caspase3 (Cas3) but decreased the expression of Bcl2 and lysosomal membrane stability, while in the HUVECs pretreated with AEE, the above changes caused by either the stimulatory or the inhibitory effect of H2O2 on the relevant factors were significantly reduced. AEE pretreatment significantly enhanced the activity of cellular superoxide dismutase and glutathione peroxidase in the HUVECs. Our findings suggest that AEE effectively reduced H2O2-induced oxidative stress in the HUVECs via mitochondria-lysosome axis.

15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1530-1539, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607308

RESUMO

OBJECTIVE: To retrospectively analyze the cases of multiple myeloma treated with chemotherapeatic regimens based on thalidomide, and to investigate the factors affecting MM patients treated using chemotherapeutic regimens with or without bortezomib. METHODS: The clinical, laboratorial and survival data of 200 patients with newly diagnosed MM from October 2007 to December 2015 were collected, and the correlation of clinical and laboratorial indicators with the clinical characteristics and prognosis of MM patients was analyzed by using χ2 test, COX regression analysis, Kaplan-Meier method and Log-rank test. RESULTS: Multivariable analysis showed that age (≥65 years old), ISS staging (Ⅲ), complex karyotypes and no-complete remission were the independent prognostic factors for OS in bortezomib-treated group, while the ß2-MG (≥8.95 mg/L), no-complete remission were the independent prognostic factros for OS in traditional therapy group. In addition, the MPI-1 myeloma prognostic index 1, consisted of age, complex karyotypes and complete remission in bortezomib-treated group, and MPI-2 consisted of ß2-MG (≥8.95 mg/L), complex karyotypes, complete remission in traditional therapy group were suitable for evaluating the pregnosis of MM patients treated with regimens contiaining bortezomib and traditional chemotherapentic regimans. CONCLUSION: The differences of prognostic factors exist in MM patients treated with different chemotherapeutic regimens, moreover, the patients with comples karyotypes and no-complete remisson have poor prognosis. The MPI as more simple and easy clinical parameter, may be come an useful and complemental method for evaluation of prognosis except ISS and R-ISS.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Bortezomib , Humanos , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
16.
Hematol Oncol ; 37(4): 392-400, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31420873

RESUMO

Ibrutinib, a first-generation Bruton's tyrosine kinase (BTK) inhibitor, could improve immunity of relapsed or refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) patients. Whether zanubrutinib, a second-generation selective BTK inhibitor, has similar effects as ibrutinib remains to be determined. Dynamics of number and immunophenotype of immune cells during zanubrutinib treatment in 25 R/R CLL/SLL patients were examined by flow cytometry and blood routine tests. The expression intensity of programmed death-1 (PD-1) on total CD4+ (P < .01), total CD8+ (P < .01), and T helper cells (P < .05) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) on total CD4+ (P = .010) and regulatory T cells (P < .05) reduced after treatment. There were significant differences in expression intensity of CD19 (P < .01), C-X-C chemokine receptor type 5 (CXCR5) (P < .01), and CD49d (P < .05) on B cells before and after treatment. Downregulation of PD-1 on T cells and CXCR5 and CD19 on B cells were observed in nearly all patients after zanubrutinib treatment. Programmed death-ligand 1 expression downregulated, especially in the female, CLL, normal spleen, normal ß2-macroglobulin (ß2-MG) and abnormal lactate dehydrogenase (LDH) subgroups, and CTLA-4 expression on CD4+ T cells tended to decrease in the male, old, CLL, splenomegaly, abnormal ß2-MG, normal LDH, IGHV-mutated and wild-type tumor protein 53 subgroups after zanubrutinib treatment. These findings suggest that zanubrutinib can regulate immunity primarily by improving T cell exhaustion, inhibiting suppressor cells and disrupting CLL cells migration through downregulation of adhesion/homing receptors. Furthermore, favorable changes in cell number and immunophenotype were preferably observed in patients without adverse prognostic factors.


Assuntos
Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Antineoplásicos/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Proteínas de Neoplasias/antagonistas & inibidores , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Adulto , Idoso , Antineoplásicos/farmacologia , Subpopulações de Linfócitos B/efeitos dos fármacos , Feminino , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Humanos , Imunofenotipagem , Células Matadoras Naturais/efeitos dos fármacos , Leucemia Linfocítica Crônica de Células B/imunologia , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Piperidinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/farmacologia , Pirimidinas/farmacologia , Receptores de Antígenos de Linfócitos B/imunologia , Subpopulações de Linfócitos T/efeitos dos fármacos
17.
Int J Mol Sci ; 20(13)2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31261711

RESUMO

Aspirin eugenol ester (AEE) possesses anti-thrombotic, anti-atherosclerotic and anti-oxidative effects. The study aims to clarify the mechanism underlying the anti-atherosclerotic effects of AEE on vascular endothelial dysfunction. Both the high-fat diet (HFD)-induced atherosclerotic rat model and the H2O2-induced human umbilical vein endothelial cells (HUVECs) model were used to investigate the effects of AEE on vascular endothelial dysfunction. UPLC/QTOF-MS coupled with a multivariate data analysis method were used to profile the variations in the metabolites of HUVECs in response to different treatments. Pretreatment of HUVECs with AEE significantly ameliorated H2O2-induced apoptosis, the overexpression of E-selectin and VCAM-1, and the adhesion of THP-1 cells. Putative endogenous biomarkers associated with the inhibition of endothelial dysfunction were identified in HUVECs pretreated with AEE in the absence or presence of H2O2, and these biomarkers were involved in important metabolic pathways, including amino acid metabolism, carbohydrate metabolism, and glutathione metabolism. Moreover, in vivo, AEE also significantly reduced vascular endothelial dysfunction and decreased the overexpression of VCAM-1 and E-selectin. Based on our findings, the mechanism underlying the anti-atherosclerotic effects of AEE might be related to a reduction in vascular endothelial dysfunction mediated by ameliorating alterations in metabolism, inhibiting oxidative stress, and decreasing the expression of adhesion molecules.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Aspirina/análogos & derivados , Endotélio Vascular/efeitos dos fármacos , Eugenol/análogos & derivados , Placa Aterosclerótica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/farmacologia , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Apoptose , Aspirina/farmacologia , Aspirina/uso terapêutico , Linhagem Celular , Células Cultivadas , Dieta Hiperlipídica/efeitos adversos , Selectina E/metabolismo , Endotélio Vascular/metabolismo , Eugenol/farmacologia , Eugenol/uso terapêutico , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Masculino , Metaboloma , Inibidores da Agregação de Plaquetas/uso terapêutico , Ratos , Ratos Sprague-Dawley , Molécula 1 de Adesão de Célula Vascular/metabolismo
18.
Ann Transl Med ; 7(8): 176, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31168457

RESUMO

Background: Splicing factor 3b subunit 1 (SF3B1), a splicing factor modulating RNA alternative splicing, is frequently mutated in multiple hematological malignancies including myelodysplastic syndromes and chronic lymphocytic leukemia (CLL). The clinical impact of SF3B1 mutation on CLL remains controversial especially for patients of Asian descent. Methods: We retrospectively analyzed the frequency of SF3B1 mutation by Sanger sequencing in 399 newly diagnosed Chinese CLL patients. Results: SF3B1 mutation was detected in 5.5% (22/399) of the studied cohort with 59.1% of them being c.A2098G (p.K700E). SF3B1 mutation was common in patients with unmutated immunoglobulin heavy chain variable region gene, positive CD38 and positive ZAP-70. Survival analysis showed that SF3B1 mutation was associated with short treatment-free survival (TFS), but not overall survival (OS). We then developed 2 new risk models, named CLL-IPI-S and CLL-PI, according to the SF3B1 mutation status and CLL-international prognostic index (CLL-IPI); CLL-PI showed greater power to predict TFS than CLL-IPI in Chinese CLL patients. Conclusions: Our data suggest a low incidence and adverse clinical significance of SF3B1 mutation in newly diagnosed Chinese CLL patients.

19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(3): 735-740, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31204924

RESUMO

OBJECTIVE: RAG1 plays important roles in lymphopoiesis and immune system, its dysfunction may result in the malignancies of hemopoietic system. The aim of this study was to investigate the characteristics of RAG1 expression in adult B-cell acute lymphoblastic leukemia (B-ALL), and to analyze the clinical significances. METHODS: Quantitative PCR (q-PCR) was performed to evaluate the expression of RAG1 in 104 newly diagnosed, 22 relapsed adult B-ALL patients and 30 normal controls, the clinical significances of RAG1 expression were analyzed. RESULTS: Compared with normal controls, newly diagnosed and relapsed adult B-ALL patients showed higher RAG1 expression level (3.94 vs 1.23) (P<0.01), (5.86 vs 1.23) (P<0.01). The analysis of paired simples from 6 cases of newly diagnosed and relapsed B-ALL showed that the expression level of RAG1 at relapse was significantly higher than that at new diagnosis (13.65 vs 2.31) (P<0.01). The RAG1 expression level in IK6 positive patients was higher than that in IK6 negative patients (5.30 vs 2.11) (P<0.05). The ratio of patients with LDH>1 000 U/L in RAG1 high expression group was higher than that in RAG1 low expression group (42.2% vs 20.5%) (P<0.05). CONCLUSION: RAG1 up-regulation may play an important role in the development of adult B-ALL especially when relapsed, which may also take part in the formation of Ik6. Monitoring RAG1 expression may provide a new method to evaluate the prognosis of adult B-ALL patients.


Assuntos
Proteínas de Homeodomínio/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras , Doença Aguda , Adulto , Linfócitos B , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Prognóstico
20.
Lancet Haematol ; 6(6): e328-e337, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31126528

RESUMO

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


Assuntos
Antraciclinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antraciclinas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Feminino , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neutropenia/etiologia , Modelos de Riscos Proporcionais , Rituximab/administração & dosagem , Taxa de Sobrevida , Resultado do Tratamento , Vincristina/administração & dosagem , Adulto Jovem
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