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1.
Br J Haematol ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32068254

RESUMO

Dehydropeptidase-1 (DPEP1) is a zinc-dependent metalloproteinase abnormally expressed in many cancers. However, its potential role in adults with B cell acute lymphoblastic leukaemia (ALL) is unknown. We found that in adults with common B cell ALL high DPEP1, transcript levels at diagnosis were independently associated with an increased cumulative incidence of relapse (CIR) and worse relapse-free survival (RFS) compared with subjects with low transcript levels. We show an increased proliferation and prosurvival role of DPEP1 in B cell ALL cells via regulation of phosphCREB and p53, which may be the biological basis of the clinical correlation we report. Our data implicate DPEP1 expression in the biology of common B cell ALL in adults. We report clinical correlates and provide a potential biological basis for these correlations. If confirmed, analysing DPEP1 transcript levels at diagnosis could help predict therapy outcomes. Moreover, regulation of DPEP1 expression could be a therapy target in B cell ALL.

2.
Ann Hematol ; 99(2): 215-221, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31900500

RESUMO

Many studies have confirmed that overexpressed WT1 exists in leukemic cells, especially in AML. However, the immunophenotypic features of this sort of leukemic cells remain to be unclarified. We retrospectively analyzed the immunophenotype of 283 newly diagnosed AML patients with intermediated and poor cytogenetic risk to evaluate the correlation between phenotype and WT1 overexpression. EVI1 transcripts, KMT2A-PTD, FLT3-ITD, and NPM1 mutations were simultaneously assessed. Our results revealed that overexpressed WT1 was significantly associated with the expression of CD117, CD13, and CD123. Besides, leukemic cells with WT1 overexpression also lacked lymphoid and myeloid differentiation-related markers. FAB subtype M2 patients had higher WT1 levels, compared with other FAB subtype. Multivariate analysis was proved that NPM1 mutation, M2 subtype, and the expression of CD123 were independently associated with WT1 overexpression. These indicated that AML with overexpressed WT1 was proliferated and blocked in the early stage of AML development. It presumably provided some clues to detect overexpressed WT1 cells via multiparameter flow cytometry. CD123-targeted drugs might become one of the alternative treatments for patients with WT1 overexpression.


Assuntos
Regulação Leucêmica da Expressão Gênica , Leucemia Mieloide Aguda/metabolismo , Proteínas WT1/biossíntese , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/biossíntese , Antígenos CD/genética , Antígenos de Diferenciação/biossíntese , Antígenos de Diferenciação/genética , Feminino , Humanos , Imunofenotipagem , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas Nucleares/biossíntese , Proteínas Nucleares/genética , Fatores de Risco , Proteínas WT1/genética
3.
Ann Hematol ; 99(1): 73-82, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31768677

RESUMO

For acute myeloid leukemia (AML) with nucleophosmin 1 mutation (NPM1m), multiparameter flow cytometry (FCM) and real-time quantitative polymerase chain reaction (RQ-PCR) are used to monitor minimal residual disease (MRD). However, the results of the two methods are sometimes inconsistent. This study was designed to analyze how to address the discordant results of FCM and RQ-PCR in AML patients undergoing chemotherapy, especially when positive FCM (FCM+) and negative NPM1m (NPM1m-) results are detected in the same sample. Our study included 93 AML patients with NPM1m positive (NPM1m+) who received chemotherapy but did not undergo hematopoietic stem cell transplantation. We monitored NPM1m and leukemia-associated immunophenotypes (LAIPs) by RQ-PCR and FCM, respectively, to assess MRD after each chemotherapy course. After each course of chemotherapy, all patients were classified into four groups based on the results of FCM and RQ-PCR: both negative (group 1, FCM-NPM1m-), single positive (group 2, FCM-NPM1m+; group 3, FCM+NPM1m-), or both positive (group 4, FCM+NPM1m+). The results showed that there was not a significant difference in the 2-year cumulative incidence of relapse (CIR) after each course of chemotherapy between group 2 and group 3. Furthermore, patients in groups 2 and 3 had a lower 2-year CIR than those in group 4 and a significantly higher 2-year CIR than those in group 1 after the first two courses. The patients in group 4 had a significantly higher 2-year CIR than those in group 1 after the first two courses. These results suggested that in the MRD monitoring process of AML patients, when the results of FCM and RQ-PCR are inconsistent (especially when FCM is positive and NPM1m is negative), these single-positive results still have predictive significance for relapse.


Assuntos
Citometria de Fluxo , Leucemia Mieloide Aguda , Mutação , Proteínas de Neoplasias , Proteínas Nucleares , Reação em Cadeia da Polimerase em Tempo Real , Adolescente , Adulto , Idoso , Feminino , Humanos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/genética , Neoplasia Residual , Proteínas Nucleares/sangue , Proteínas Nucleares/genética , Valor Preditivo dos Testes , Estudos Retrospectivos
4.
Cytometry B Clin Cytom ; 98(1): 75-87, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31424628

RESUMO

BACKGROUND: This study aimed to determine the impact of the pre- and post-minimal residual disease (MRD) status as well as the peri-transplant MRD kinetics on clinical outcomes in pediatric ALL patients who received haploidentical allografts. METHODS: A retrospective study (n = 166) was performed. MRD was determined using multiparameter flow cytometry. RESULTS: Pediatric ALL patients with pre-MRDneg had a lower cumulative incidences of relapse (CIR) compared to those with pre-MRDpos (19.7% vs. 41.2%, P = 0.009). Compared to post-MRDneg group, patients with post-MRDpos experienced higher CIR (81.0% vs. 15.9%, P < 0.001), inferior LFS (14.3% vs. 66.9%, P < 0.001) and OS (19.1% vs. 66.9%, P < 0.001). In regard to peri-MRD kinetics, compared with the MRD-decreasing group and MRDneg/MRDneg group, MRD-increasing group had higher CIR, lower probabilities of LFS and OS (P < 0.001). Compared to pre-MRDneg/post-MRDneg group, a higher CIR was found in the pre-MRDpos/post-MRDpos group (66.7% vs. 12.5%, P < 0.001), pre-MRDpos/post-MRDneg group (32.0% vs. 12.5%, P = 0.016), and pre-MRDneg/post-MRDpos group (91.7% vs. 12.5%, P < 0.001). A lower incidence of LFS and OS were found in pre-MRDpos/post-MRDpos group and pre-MRDneg/post-MRDpos group than in pre-MRDneg/post-MRDneg group (P < 0.05). Multivariate analyses confirmed the association of pre-MRD status, post-MRD status, and peri-MRD kinetics with outcomes (P < 0.05). CONCLUSIONS: The results indicate that, in the pediatric ALL subgroup, not only pre-MRD status or post-MRD status but also peri-SCT MRD dynamics, were associated with an increased CIR after haploidentical allografts. Patients are put into different risk group based on MRD kinetics versus single time MRD status. © 2019 International Clinical Cytometry Society.

5.
Anim Biotechnol ; 31(1): 42-51, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30570383

RESUMO

Cellular retinoic acid binding protein 2 (CRABP2) is essential to myoblast differentiation. However, there was no report about the function of CRABP2 gene in cattle. This study explored the association of CRABP2 gene polymorphisms with growth traits in cattle breeds by several methods, such as DNA sequencing, PCR, PCR-RFLP and forced PCR-RFLP. Two sequence variants were determined. There were 621 individuals in six cattle breeds from China for the experiment, and three breeds were used to test validation of polymorphisms and extent of linkage disequilibrium (LD). The results showed that both SNPs (SNP1, g.2458 G > T, SNP2, g.3878 G > A) were in intron1. Two SNPs were in low linkage disequilibrium. Association analysis suggested that SNP1 had the significant difference on growth traits with body height, height at hip cross and body slanting length (P < .05), while SNP2 showed a significant difference in growth traits with body height, height at hip cross and body slanting length(P < .05). The results of this investigation displayed that the CRABP2 gene is an available candidate gene and may be used for breed selection and conservation.

6.
Blood Adv ; 3(21): 3406-3418, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31714962

RESUMO

Thrombocytopenia is associated with life-threatening bleeding and is common in myelodysplastic syndromes (MDS). Robust molecular prognostic biomarkers need to be developed to improve clinical decision making for patients with MDS with thrombocytopenia. Wilms tumor 1 (WT1) and preferentially expressed antigen in melanoma (PRAME) are promising immunogenic antigen candidates for immunotherapy, and their clinical effects on patients with MDS with thrombocytopenia are still not well understood. We performed a multicenter observational study of adult patients with MDS with thrombocytopenia from 7 different tertiary medical centers in China. We examined bone marrow samples collected at diagnosis for WT1 and PRAME transcript levels and then analyzed their prognostic effect for patients with MDS with thrombocytopenia. In total, we enrolled 1110 patients diagnosed with MDS with thrombocytopenia. Overexpression of WT1 and PRAME was associated with elevated blast percentage, worse cytogenetics, and higher Revised International Prognostic Scoring System (IPSS-R) risk. Further, both WT1 and PRAME overexpression were independent poor prognostic factors for acute myeloid leukemia evolution, overall survival, and progression-free survival. Together, the 2 genes overexpression identified a population of patients with MDS with substantially worse survival. On the basis of WT1 and PRAME transcript levels, patients with MDS with IPSS-R low risk were classified into 2 significantly divergent prognostic risk groups: a low-favorable group and a low-adverse group. The low-adverse group had survival similar to that of patients in the intermediate-risk group. Our study demonstrates that the evaluation of WT1/PRAME transcript analysis may improve the prognostication precision and better risk-stratify the patients.

7.
iScience ; 21: 549-561, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31715498

RESUMO

Multi-targeted kinase inhibitors, such as sorafenib, have been used in various malignancies, but their efficacy in clinical applications varies among individuals and lacks pretherapeutic prediction measures. We applied the concept of "click chemistry" to pathological staining and established a drug-loaded probe staining assay. We stained the cells and different types of pathological sections and demonstrated that the assay was reliable. We further verified in cells, cell-derived xenograft model, and clinical level that the staining intensity of the probe could reflect drug sensitivity. The stained samples from 300 patients who suffered from hepatocellular carcinoma and used the sorafenib probe also indicated that staining intensity was closely related to clinical information and could be used as an independent marker without undergoing sorafenib therapy for prognosis. This assay provided new ideas for multi-target drug clinical trials, pre-medication prediction, and pathological research.

8.
Ann Hematol ; 98(11): 2551-2559, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31493003

RESUMO

The prognostic significance of Wilms' tumor gene 1 (WT1) expression at diagnosis in adults with B cell precursor acute lymphoblastic leukemia (BCP-ALL) remains poorly understood. A total of 257 adults with Ph-negative BCP-ALL who were consecutively diagnosed and received at least 1 course of induction therapy at our institute were retrospectively analyzed. The WT1 expression patterns were significantly different among the molecularly and cytogenetically defined groups (E2A-PBX1, TEL-AML1, and MLL rearrangements; high hyperdiploidy and B-other). By considering the WT1 expression pattern and the relapse status, 2 cutoff values, 1.8% and 7.2%, were arbitrarily selected to place patients into WT1-low, WT1-inter, and WT1-high groups. In the B-other patients who achieved complete remission (CR), WT1-low and WT1-high patients had similar 3-year relapse-free survival (RFS), disease-free survival (DFS), and overall survival (OS) rates, which were all significantly lower than those of WT1-inter patients. The combined WT1-low/high expression group (n = 132) had significantly lower 3-year RFS, DFS, and OS rates compared with the WT1-inter group (n = 63) of B-other patients (RFS and DFS all P < 0.0001; OS P = 0.0018 and 0.0008). WT1 low/high expression as well as treating with chemotherapy only was independent poor prognostic factors for RFS, DFS, and OS in the B-other patients who achieved CR. Therefore, the molecularly and cytogenetically defined adult Ph-negative BCP-ALL groups have characteristic WT1 expression patterns, and WT1 low/high expression at diagnosis predicts poor outcome in B-other patients.


Assuntos
Regulação Leucêmica da Expressão Gênica , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidade , Proteínas WT1/biossíntese , Adolescente , Adulto , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Taxa de Sobrevida , Proteínas WT1/genética
9.
Cancer Med ; 8(12): 5459-5467, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31364309

RESUMO

Acute myeloid leukemia (AML) with t(8;21) is a heterogeneous disease. Although the detection of minimal residual disease (MRD), which is indicated by RUNX1-RUNX1T1 transcript levels, plays a key role in directing treatment, risk stratification needs to be improved, and other markers need to be assessed. A total of 66 t(8;21) AML patients were tested for aldehyde dehydrogenase (ALDH) activity by flow cytometry at diagnosis, and 52 patients were followed up for a median of 20 (1-34) months. The median percentage of CD34+ALDH+, CD34+CD38-ALDH+, and CD34+CD38+ALDH+ cells among nucleated cells were 0.028%, 0.012%, and 0.0070%, respectively. The CD34+ALDH+-H, CD34+CD38-ALDH+-H, and CD34+CD38+ALDH+-H statuses (the percentage of cells that were higher than the individual cutoffs) were all significantly associated with a lower 2-year relapse-free survival (RFS) rate in both the whole cohort and adult patients (P = .015, .016, and .049; P = .014, .018, and .032). Patients with < 3-log reduction in the RUNX1-RUNX1T1 transcript level after the second consolidation therapy (defined as MRD-H) had a significantly lower 2-year RFS rate than patients with ≥ 3-log reduction (MRD-L) (P = .017). The CD34+ALDH+ status at diagnosis was then combined with the MRD status. CD34+ALDH+-L/MRD-H patients had similar 2-year RFS rates to both CD34+ALDH+-L/MRD-L and CD34+ALDH+-H/MRD-L patients (P = .50 and 1.0); and CD34+ALDH+-H/MRD-H patients had significantly lower 2-year RFS rate compared with CD34+ALDH+-L and/or MRD-L patients (P < .0001). Multivariate analysis showed that CD34+ALDH+-H/MRD-H was an independent adverse prognostic factor for relapse. In conclusion, ALDH status at diagnosis may improve MRD-based risk stratification in t(8;21) AML, and concurrent high levels of CD34+ALDH+ at diagnosis and MRD predict relapse.

10.
Anim Biotechnol ; : 1-8, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253064

RESUMO

The study evaluated the effects of branched-chain volatile fatty acids (BCVFA) and fibrolytic enzyme (FE) on rumen development in calves. Forty Holstein male calves at the same ages (15 ± 2.5 days of age) and weights (45 ± 3.3 kg of body weight [BW]) were assigned randomly to four groups with a 2 × 2 factorial arrangement of treatments. Supplemental BCVFA (0 g/d or 18 g/d) and FE (0 g/d or 1.83 g/d) were fed to calves. Data were analyzed as a 2 × 2 factorial arrangement random design by the mixed procedure of SAS. The BCVFA × FE interaction was observed for ruminal propionate, blood growth hormone (GH) and insulin-like growth factor-1 (IGF-1), and GH receptor (GHR) and IGF-1 receptor (IGF-1R) expression in the rumen mucosa. Dry matter intake was higher for BCVFA addition. The higher average daily gain and ruminal volatile fatty acids were observed for BCVFA or FE addition. Stomach weight and the length and width of rumen papillae were higher for BCVFA addition. The higher expression of GHR, IGF-1R and 3-hydroxy-3-methylglutaryl-CoA synthase 1 in rumen mucosa, and blood GH and IGF-1 were observed with BCVFA or FE addition. Blood ß-hydroxybutyrate and acetoacetate were higher for BCVFA addition. The results indicated that rumen development was promoted by BCVFA, but was not affected with FE addition in calves.

11.
Ann Hematol ; 98(7): 1733-1742, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31053879

RESUMO

Hepatic sinusoidal obstruction syndrome (SOS) has been rarely studied after haploidentical donor (HID) allogeneic hematopoietic stem cell transplantation (allo-HSCT). We performed a retrospective multicentre study on patients with SOS after allo-HSCT in China. The incidence, risk factors, and outcomes were compared between HID HSCT and matched related donor (MRD) HSCT. SOS developed in 0.4% of patients (HIDs: 0.4%, MRDs: 0.5%, p = 0.952) at a median time of 21.50 days (range, 1-55) after allo-HSCT (HIDs: 24 days, MRDs: 20 days, p = 0.316). For patients diagnosed with SOS, the 2-year cumulative incidence of relapse was 22.7% and 22.4% in patients receiving HID and MRD transplantation, respectively (p = 0.584). Overall survival (OS) at 2 year was 10.4% and 38.5% in the two groups (p = 0.113). The transplant-related mortality (TRM) at 100 days was 60.9% in the HID group and 38.5% in the MRD group (p = 0.178). According to the multivariate analyses, significant independent risk factors for the occurrence of SOS were delayed platelet engraftment (p = 0.007) and advanced disease status at the time of HSCT (p = 0.009). The outcomes of SOS after HID HSCT are similar to those after MRD HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Hepatopatia Veno-Oclusiva , Doadores de Tecidos , Condicionamento Pré-Transplante , Adolescente , Adulto , Aloenxertos , Criança , China/epidemiologia , Feminino , Seguimentos , Hepatopatia Veno-Oclusiva/epidemiologia , Hepatopatia Veno-Oclusiva/etiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
12.
Br J Haematol ; 185(5): 836-851, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30916375

RESUMO

Refinement of risk stratification in Philadelphia chromosome (Ph)-negative B-cell acute lymphoblastic leukaemia (ALL) might aid the identification of patients who are likely to relapse. Abnormal S100 calcium binding protein A16 (S100A16) has been implicated in various cancers, but its function remains unclear. We found S100A16 transcript levels were higher in 130 adults with newly-diagnosed Ph-negative B-cell ALL compared with 33 healthy controls. In 115 of 130 patients who achieved first complete remission, those with high S100A16 transcript levels displayed a lower 3-year cumulative incidence of relapse (CIR; 34% [21, 47%] vs. 40% [48, 72%]; P = 0·012) and higher 3-year relapse-free survival (RFS; 65% [53, 78%] vs. 35% [23, 46%]; P = 0·012), especially when receiving chemotherapy only. In multivariate analysis a low S100A16 transcript level was independently-associated with a higher CIR (Hazard ratio [HR] = 3·74 [1·01-13·82]; P = 0·048) and inferior RFS (HR = 5·78 [1·91, 17·84]; P < 0·001). Function analysis indicated that knockdown of S100A16 promoted proliferation and anti-apoptosis and reduced chemosensitivity. S100A16 over-expression revealed an opposite trend, especially in a xeno-transplant mouse model. Western blotting analysis showed upregulation of PI3K/AKT and ERK1/2 in S100A16-knockdown and S100A16-overexpression B-cell ALL cell lines respectively. Inhibition assays suggested these two signalling pathways participated in the S100A16-mediated proliferation and survival effects in B-cell ALL cell lines. Trial Registration: Registered in the Chinese Clinical Trial Registry [ChiCTR-OCH-10000940]; http://www.chictr.org.cn.

13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(1): 141-148, 2019 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-30738461

RESUMO

OBJECTIVE: To study the value of flow cytometric scoring system in the diagnosis of myelodysplastic syndromes (MDS). METHODS: The phenotypes of erythroid and immature cells were analyzed retrospectively in 130 MDS patients, 19 healthy controls and 89 pathological controls, all of them were well clinically immunophenotyped. The 4-parameter scoring system reported in the literature was studied, including myeloblast-related cluster size, B-progenitor-related cluster size, lymphocyte to myeloblast CD45 ratio, and granulocyte to lymphocyte side scatter ratio. The two flow cytomatric parameters of the erythroid scoring system were analyzed, including CD36 coefficient of variation (CV) and CD71CV. According to our previous study, the percentage of CD117+CD105- myeloid progenitor cells and the proportion of CD105+ cells in CD117+ cells were selected to establish a two-parameter scoring system, and compared with the four-parameter scoring system and the erythroid scoring system. RESULTS: The sensitivity of the four-parameter scoring system and the erythroid scoring system for the diagnosis of low-risk MDS was 43.5% and 63.0%, and the specificity was 87.0% and 63.9%, respectively. After combining the two scoring systems, the sensitivity to diagnose low-risk MDS was 73.9% and the specificity was 62.0%. The sensitivity of the two-parameter scoring system for the diagnosis of low-risk MDS was 76.1% with a specificity of 81.5%. Combined with the four-parameter scoring system, the sensitivity was increased to 78.3%, but the specificity was reduced to 71.3%. After combining with the erythroid scoring system, the sensitivity reached 87.0%, but the specificity was reduced to 54.6%. CONCLUSION: Using the two-parameter scoring system alone can achieve great sensitivity and specificity in the diagnosis of low risk MDS.


Assuntos
Síndromes Mielodisplásicas , Endoglina , Citometria de Fluxo , Humanos , Imunofenotipagem , Síndromes Mielodisplásicas/diagnóstico , Proteínas Proto-Oncogênicas c-kit , Estudos Retrospectivos
14.
Leuk Lymphoma ; 60(9): 2181-2189, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30773106

RESUMO

Acute myeloid leukemia (AML) patients with biallelic CEBPA (bi CEBPA) mutations are considered prognostically favorable, but 38-58% of them still relapse. Therefore, recognizing patients with a high risk of relapse is important. We retrospectively analyzed 83 bi CEBPA AML. Minimal residual disease (MRD) was detected by multiparameter flow cytometry (MFC). Patients with MRD positivity during consolidation chemotherapy had inferior 3-year CIR (55% vs. 36.7%; p = .037) and RFS (45% vs. 63.3%; p = .037) than those with MRD negativity. In patients with adverse cytogenetics, FLT3-ITD or MRD positivity, allogeneic hematopoietic stem cell transplantation (allo-HSCT) achieved superior 3-year CIR (0% vs. 52.8%; p = .006) and RFS (88.9% vs. 47.2%; p = .027) than did consolidation chemotherapy. Consolidation chemotherapy maintained a relatively favorable outcome (3-year CIR, 29%; 3-year RFS, 71%) in patients with intermediate cytogenetics, negative FLT3-ITD, and MRD negativity. Therefore, MFC-MRD could predict relapse and was complementary to genetics for risk stratification treatment in bi CEBPA AML.

15.
PLoS One ; 14(2): e0210774, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30721238

RESUMO

With wetlands categorized as one of the three major ecosystems, the study of wetland health has global environmental implications. Multiple regression models were employed to establish relationships between Landsat-8 images, vegetation indices and field measured biomass in the Yellow River Delta Nature Reserve. These models were then used to estimate the spatial distribution of wetland vegetative biomass. The relationships between wetland vegetative biomass and soil factors (organic matter, nitrogen, phosphorus, potassium, water soluble salt, pH and moisture) were modeled. We were able to achieve higher correlations and improved model fits using vegetative indices and spectral bands 1-5 as independent variables. Several important soil factors were isolated, including soil moisture and salt concentrations, which affect wetland biomass spatial distributions. Overall, wetland biomass decreased from land to the ocean and from the river courses outward.


Assuntos
Biomassa , Modelos Biológicos , Áreas Alagadas , China
16.
Am J Hematol ; 94(5): 512-521, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30680765

RESUMO

This study evaluated the effects of pretransplantation minimal residual disease (pre-MRD) on outcomes of patients with acute lymphoblastic leukemia (ALL) who underwent unmanipulated haploidentical stem cell transplantation (haplo-SCT). A retrospective study including 543 patients with ALL was performed. MRD was determined using multiparametric flow cytometry. Both in the entire cohort of patients and in subgroup cases with T-ALL or B-ALL, patients with positive pre-MRD had a higher incidence of relapse (CIR) than those with negative pre-MRD in MSDT settings (P < 0.01 for all). Landmark analysis at 6 months showed that MRD positivity was significantly and independently associated with inferior rates of relapse (HR, 1.908; P = 0.007), leukemia-free survival (LFS) (HR, 1.559; P = 0.038), and OS (HR, 1.545; P = 0.049). The levels of pre-MRD according to a logarithmic scale were also associated with leukemia relapse, LFS, and OS, except that cases with MRD <0.01% experienced comparable CIR and LFS to those with negative pre-MRD. A risk score for CIR was developed using the variables pre-MRD, disease status, and immunophenotype of ALL. The CIR was 14%, 26%, and 59% for subjects with scores of 0, 1, and 2-3, respectively (P < 0.001). Three-year LFS was 75%, 64%, and 42%, respectively (P < 0.001). Multivariate analysis confirmed the association of the risk score with CIR and LFS. The results indicate that positive pre-MRD, except for low level one (MRD < 0.01%), is associated with poor outcomes in patients with ALL who underwent unmanipulated haplo-SCT.


Assuntos
Citometria de Fluxo , Leucemia-Linfoma Linfoblástico de Células Precursoras , Transplante de Células-Tronco , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Cuidados Pré-Operatórios , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo
17.
Oncogene ; 38(2): 228-243, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30087438

RESUMO

Hepatocellular carcinoma (HCC) is a typical hypervascular solid tumor. Vasculogenic mimicry (VM) formed by aggressive tumor cells to mimic vasculogenic networks plays an important role in the tumor malignancy of HCC. Hsp90ß promotes endothelial cell-dependent angiogenesis in HCC. However, the relationship between Hsp90ß and VM formation is unclear. In this study, we found that Hsp90ß is positively correlated with VM and EMT marker proteins in HCC tissues and promotes tube formation, cell migration, and invasion in vitro. Hsp90ß interacts with Twist1 and promotes its deubiquitination and stabilization to nuclear translocation and enhances the VE-cadherin promoter activity. Results of in vitro analysis indicate that Hsp90ß enhances the tumor VM in tumor-burdened mice, and the Hsp90 inhibitor NVP-BEP800 suppresses VM formation by releasing Hsp90ß and Twist1 interaction. This study provides a potential antitumor therapy for inhibiting VM by targeting Hsp90ß in HCC.


Assuntos
Carcinoma Hepatocelular/patologia , Transição Epitelial-Mesenquimal , Proteínas de Choque Térmico HSP90/metabolismo , Neoplasias Hepáticas/patologia , Animais , Carcinoma Hepatocelular/metabolismo , Xenoenxertos , Humanos , Neoplasias Hepáticas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neovascularização Patológica
18.
Bone Marrow Transplant ; 54(4): 567-577, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30127465

RESUMO

A retrospective study (n = 460) was performed to assess the relationship between minimal residual disease (MRD) and transplant outcomes in a haplo-stem cell transplantation (SCT) setting. Patients from the pre-MRDneg group and the pre-MRDpos group had comparable outcomes. Compared to post-MRDneg patients, post-MRDpos patients had a higher incidence of relapse (100.0% vs. 8.3%, p < 0.001), lower incidences of overall survival (OS) (16.9% vs. 78.2%, p < 0.001) and leukemia-free survival (LFS) (0% vs. 76.5%, p < 0.001), and comparable probability of NRM (13.4% vs. 16.9%, p = 0.560). In a second set of analyses, all adult AML patients undergoing haplo-SCT were classified into the MRDneg/MRDneg group, the MRD decreasing group, and the MRD increasing group according to MRD dynamics by flow cytometry peri-SCT. Compared to the other two groups, patients from the MRD increasing group had higher cumulative incidences of relapse (MRD increasing, 100.0%; MRDneg/MRDneg, 9.6%; MRD decreasing, 19.2%; p < 0.001) and worse probabilities of OS (MRD increasing, 28.5%; MRDneg/MRDneg, 76.3%; MRD decreasing, 76.0%; p < 0.001) and LFS (MRD increasing, 0.0%; MRDneg/MRDneg, 73.9%; MRD decreasing, 74.0%; p < 0.001). The results indicated that haploidentical allografts might have a beneficial anti-leukemia effect in eradicating pretransplantation MRD, and MRD assessment peri-SCT is useful for risk stratification from a practical perspective.

19.
Chin Med J (Engl) ; 131(23): 2808-2816, 2018 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-30511683

RESUMO

Background: Several studies have shown that detection of minimal residual disease (MRD) in acute myeloid leukemia (AML) is an independent prognostic factor. This study aimed to evaluate the significance of dynamic MRD pretransplantation on outcome of AML patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: We retrospectively analyzed 145 consecutive AML patients undergoing allo-HSCT in complete remission status between June 2013 and June 2016. MRD was determined with multiparameter flow cytometry after the first and second courses of chemotherapy and pre-HSCT. Results: In matched sibling donor transplantation (MSDT) settings, patients with positive MRD had higher cumulative incidence of relapse (CIR) than those without MRD after the first (32.3 ± 9.7% vs. 7.7 ± 3.1%, χ2 = 3.661, P = 0.055) or second course of chemotherapy (57.1 ± 3.6% vs. 12.5 ± 2.7%, χ2 = 8.759, P = 0.003) or pre-HSCT (50.0 ± 9.7% vs. 23.0 ± 3.2%, χ2 = 5.547, P = 0.019). In haploidentical SCT (haplo-SCT) settings, the MRD status at those timepoints had no significant impact on clinical outcomes. However, patients with persistent positive MRD from chemotherapy to pre-HSCT had higher CIR than those without persistent positive MRD both in MSDT and haplo-SCT settings. Patients with persistent positive MRD underwent MSDT had the highest relapse incidence, followed by those with persistent positive MRD underwent haplo-SCT, those without persistent MRD underwent haplo-SCT, and those without persistent MRD underwent MSDT (66.7 ± 9.2% vs. 38.5 ± 6.0% vs. 18.8 ± 8.7% vs. 12.0 ± 1.0%, χ2 = 20.763, P < 0.001). Multivariate analysis showed that persistent positive MRD before transplantation was associated with higher CIR (hazard ratio [HR] = 1.69, 95% confidence interval [CI]: 1.200-2.382, P = 0.003), worse leukemia-free survival (HR = 1.812, 95% CI: 1.168-2.812, P = 0.008), and overall survival (HR = 2.354, 95% CI: 1.528-3.627, P < 0.001). Conclusion: Our results suggest that persistent positive MRD before transplantation, rather than positive MRD at single timepoint, could predict poor outcome both in MSDT and haplo-SCT settings.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Neoplasia Residual/diagnóstico , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Transplante Homólogo , Adulto Jovem
20.
EBioMedicine ; 38: 25-36, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30396856

RESUMO

BACKGROUND: Hypoxia commonly occurs in solid tumors. The hypoxia in the center of solid tumors considerably decreases the chemosensitivity of tumor cells and induces epithelial-mesenchymal transition (EMT) as well as drug resistance of antitumor drugs. METHODS: Here, the effects of salidroside (Sal) combined with platinum drugs on human hepatocellular carcinoma were examined in vitro and in vivo. We investigated the antitumor effects of Sal by inhibiting the drug resistance and explained its mechanism in inhibiting tumor growth. FINDINGS: The results showed that Sal co-administration reverses the drug resistance of platinum drugs and suppressed metastasis induced by the hypoxic tumor microenvironment. Sal promoted the degradation of HIF-1α. In conclusion, Sal significantly increased the sensitivity to platinum drugs and inhibited hypoxia-induced EMT in hepatocellular carcinoma (HCC) through inhibiting HIF-1α signaling pathway. INTERPRETATION: Therefore, Sal may be an effective platinum drug sensitizer that can improve the chemotherapeutic efficacy in patients with HCC.


Assuntos
Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Glucosídeos/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Hipóxia/metabolismo , Fenóis/farmacologia , Transdução de Sinais/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Biologia Computacional/métodos , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Perfilação da Expressão Gênica , Glucosídeos/química , Humanos , Hipóxia/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Camundongos , Fenóis/química , Ensaios Antitumorais Modelo de Xenoenxerto
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