Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 12 de 12
Filtrar
1.
BMC Cancer ; 24(1): 132, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38273254

RESUMO

BACKGROUND: Studies have revealed that acute myeloid leukemia (AML) patients are prone to combined cardiac injury. We aimed to identify hematological risk factors associated with cardiac injury in newly diagnosed AML patients before chemotherapy and develop a personalized predictive model. METHODS: The population baseline, blood test, electrocardiogram, echocardiograph, and genetic and cytogenetic data were collected from newly diagnosed AML patients. The data were subdivided into training and validation cohorts. The independent risk factors were explored by univariate and multivariate logistic regression analysis respectively, and data dimension reduction and variable selection were performed using the least absolute shrinkage and selection operator (LASSO) regression models. The nomogram was generated and the reliability and generalizability were verified by receiver operating characteristic (ROC) curves, the area under the curve (AUC) and calibration curves in an external validation cohort. RESULTS: Finally, 499 AML patients were included. After univariate logistic regression, LASSO regression and multivariate logistic regression analysis, abnormal NT-proBNP, NPM1 mutation, WBC, and RBC were independent risk factors for cardiac injury in AML patients (all P < 0.05). The nomogram was constructed based on the above four variables with high accuracy. The area under the curve was 0.742, 0.750, and 0.706 in the training, internal validation, and external validation cohort, respectively. The calibration curve indicated that the model has good testing capability. The Kaplan-Meier curve showed that the higher the risk of combined cardiac injury in AML patients, the lower their probability of survival. CONCLUSIONS: This prediction nomogram identifies hematological risk factors associated with cardiac injury in newly diagnosed AML patients and can help hematologists identify the risk and provide precise treatment options.


Assuntos
Leucemia Mieloide Aguda , Humanos , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , China/epidemiologia , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/epidemiologia , Nomogramas
2.
Blood Cancer J ; 13(1): 82, 2023 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-37193689

RESUMO

Hematologic malignancies are among the most common cancers, and understanding their incidence and death is crucial for targeting prevention, clinical practice improvement, and research resources appropriately. Here, we investigated detailed information on hematological malignancies for the period 1990-2019 from the Global Burden of Disease study. The age-standardized incidence rate (ASIR), the age-standardized death rate (ASDR), and the corresponding estimated annual percentage changes (EAPC) were calculated to assess temporal trends in 204 countries and territories over the past 30 years. Globally, incident cases of hematologic malignancies have been increasing since 1990, reaching 1343.85 thousand in 2019, but the ASDR for all types of hematologic malignancies has been declining. The ASDR for leukemia, multiple myeloma, non-Hodgkin lymphoma, and Hodgkin lymphoma were 4.26, 1.42, 3.19, and 0.34 per 100,000 population in 2019, respectively, with Hodgkin lymphoma showing the most significant decline. However, the trend varies by gender, age, region, and the country's economic situation. The burden of hematologic malignancies is generally higher in men, and this gender gap decreases after peaking at a given age. The regions with the largest increasing trend in the ASIR of leukemia, multiple myeloma, non-Hodgkin lymphoma, and Hodgkin lymphoma were Central Europe, Eastern Europe, East Asia, and Caribbean, respectively. In addition, the proportion of deaths attributed to high body-mass index continued to rise across regions, especially in regions with high socio-demographic indices (SDI). Meanwhile, the burden of leukemia from occupational exposure to benzene and formaldehyde was more widespread in areas with low SDI. Thus, hematologic malignancies remain the leading cause of the global tumor burden, with growing absolute numbers but sharp among several age-standardized measures over the past three decades. The results of the study will inform analysis of trends in the global burden of disease for specific hematologic malignancies and develop appropriate policies for these modifiable risks.


Assuntos
Neoplasias Hematológicas , Doença de Hodgkin , Leucemia , Linfoma não Hodgkin , Mieloma Múltiplo , Masculino , Humanos , Carga Global da Doença , Incidência , Neoplasias Hematológicas/epidemiologia , Doença de Hodgkin/epidemiologia , Linfoma não Hodgkin/epidemiologia
3.
Cell Oncol (Dordr) ; 46(5): 1253-1268, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37071330

RESUMO

BACKGROUND: Immunophenotyping surface molecules detected in the clinic are mainly applied in diagnostic confirmation and subtyping. However, the immunomodulatory molecules CD11b and CD64, are highly associated with leukemogenesis. Hence, the prognostic value of them and their potential biological functions merit further investigation. METHODS: Flow cytometry was operated to detect immunophenotypic molecules from AML bone marrow samples. Multivariate cox regression, Kaplan-Meier analyses, and nomogram were conducted to predict survival. Transcriptomic data, lymphocyte subsets, and immunohistochemical staining were incorporated to identify potential biological functions of prognostic immunophenotype in acute myeloid leukemia (AML). RESULTS: We classified 315 newly diagnosed AML patients of our center based on the expression of CD11b and CD64. The CD11b+CD64+ populations were identified as independent risk factors for overall survival and event-free survival of AML, exhibiting specific clinicopathological features. The predictive models based on CD11b+CD64+ showed high classification performance. In addition, the CD11b+CD64+ subset, characterized by high inhibitory immune checkpoints, M2-macrophage infiltration, low anti-tumor effector cells infiltration, as well as abnormal somatic mutation landscape, presented a distinctive tumor microenvironmental landscape. The CD11b+CD64+ population showd a higher expression of BCL2, and the drug sensitivity indicated that they presented a lower half-maximal inhibitory concentration value for BCL2 inhibitor, and could benefit more from the above medicine. CONCLUSIONS: This work might be of benefit to enhanced understanding of CD11b+CD64+ in the prognosis and leukemogenesis, and yielded novel biomarkers to guide immunotherapy and targeted therapy for AML.


Assuntos
Leucemia Mieloide Aguda , Microambiente Tumoral , Humanos , Prognóstico , Leucemia Mieloide Aguda/genética , Antígenos CD/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2
4.
Nutrients ; 16(1)2023 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-38201962

RESUMO

Dietary risk has always been a major risk factor for colorectal cancer (CRC). However, the contribution of dietary risk factors to CRC at the level of region, gender, and age has not been fully characterized. Based on the Global Burden of Disease (GBD) 2019 study, the death rates, age-standardized mortality rates (ASDRs), and estimated annual percentage changes (EAPCs) were calculated to assess the trends of CRC attributable to dietary risk factors over the past 30 years. Globally, the death cases of CRC increased to 1,085,797 in 2019, and the number of deaths attributed to dietary risk factors increased to 365,752 in 2019, representing approximately one-third of all CRC-related fatalities. Overall, the ASDR attributable to dietary risks was 4.61 per 100,000 in 2019, with a slight downward trend (EAPC = -0.29). Notably, there is a rising trend in early-onset colorectal cancer mortality associated with dietary factors. To alleviate CRC burdens, it is recommended to elevate the intake of whole grains, milk, calcium, and fiber while reducing consumption of red and processed meats. The results will improve the understanding, and provide guidance on the diet of CRC in different regions, gender, and age groups worldwide.


Assuntos
Neoplasias Colorretais , Dieta , Humanos , Dieta/efeitos adversos , Fatores de Risco , Cálcio da Dieta , Carga Global da Doença , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia
5.
Front Med (Lausanne) ; 9: 844350, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35755044

RESUMO

The relationship between newly diagnosed acute leukemia (AL) and heart-related lesions remains unclear. This study aimed to investigate baseline cardiac function and risk of cardiovascular diseases (CVDs) in patients with new-onset AL, and provide data on cardiac management strategies for patients with AL. We retrospectively collected data on baseline characteristics, echocardiography, and biochemical blood indicators (e.g., myocardial enzymes) from 408 patients, 200 with newly diagnosed AL, 103 with coronary artery disease (CAD), and 105 controls from January 1, 2015 to August 31, 2019. The creatine kinase isoenzyme myocardial band, lactate dehydrogenase, highly sensitive troponin-I, and B-type natriuretic peptide levels and left ventricular internal diameter (LVID) were significantly higher in patients with newly diagnosed AL than in the control group. The degree of cardiac damage was lower in newly diagnosed AL patients than in CAD patients. The best predictor of heart damage was LVID (AUC [area under the curve] = 0.709; 95% CI [confidence interval]: 0.637-0.781; p < 0.001), and independent prognostic risk factors were age and ejection fraction (HR [hazard ratio] = 1.636; 95% CI: 1.039-2.575; p = 0.033). The ratio of leukemia blasts among patients with AL was positively correlated with cardiac damage. Our data indicated that newly diagnosed AL patients had certain myocardial damage before treatment. Clinicians need to pay attention to these manifestations, which may be related to the prognosis.

6.
Front Oncol ; 12: 772015, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35372017

RESUMO

Purpose: The study aimed to assess factors associated with early infection and identify patients at high risk of developing infection in multiple myeloma. Methods: The study retrospectively analyzed patients with MM seen at two medical centers between January 2013 and June 2019. One medical center reported 745 cases, of which 540 of the cases were available for analysis and were further subdivided into training cohort and internal validation cohort. 169 cases from the other medical center served as an external validation cohort. The least absolute shrinkage and selection operator (Lasso) regression model was used for data dimension reduction, feature selection, and model building. Results: Bacteria and the respiratory tract were the most common pathogen and localization of infection, respectively. In the training cohort, PS≥2, HGB<35g/L of the lower limit of normal range, ß2MG≥6.0mg/L, and GLB≥2.1 times the upper limit of normal range were identified as factors associated with early grade ≥ 3 infections by Lasso regression. An infection risk model of MM (IRMM) was established to define high-, moderate- and low-risk groups, which showed significantly different rates of infection in the training cohort (46.5% vs. 22.1% vs. 8.8%, p<0.0001), internal validation cohort (37.9% vs. 24.1% vs. 13.0%, p=0.009) and external validation cohort (40.0% vs. 29.2% vs. 8.5%, p=0.0003). IRMM displayed good calibration (p<0.05) and discrimination with AUC values of 0.76, 0.67 and 0.71 in the three cohorts, respectively. Furthermore, IRMM still showed good classification ability in immunomodulatory (IMiD) based regimens, proteasome-inhibitors (PI) based regimens and combined IMiD and PI regimens. Conclusion: In this study, we determined risk factors for early grade ≥ 3 infection and established a predictive model to help clinicians identify MM patients with high-risk infection.

7.
J Med Virol ; 94(4): 1535-1539, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34850404

RESUMO

The novel coronavirus disease 2019 (COVID-19) has become a global health emergency. Early detection and intervention are key factors for improving outcomes in patients with COVID-19. Real-time reverse transcriptase polymerase chain reaction-based molecular assays and antibody for detecting SARS-CoV-2 in respiratory specimens are the current reference standard for COVID-19 diagnosis. Clinical implications of different specimen types for nucleic acid and antibody testing of COVID-19 in Zhongnan hospital of Wuhan University were analyzed. Compared with health groups, tumor patients had higher rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (+/-) immunoglobulin M (IgM) (+) immunoglobulin G (IgG) (+). The rate of SARS-CoV-2 (-) IgM (+) IgG (-) or SARS-CoV-2 (-) IgM (-) IgG (+) in female was significantly higher than that in male. These results can help governments to take screening measures to prevent the COVID-19 pandemic again.


Assuntos
Anticorpos Antivirais/sangue , COVID-19/epidemiologia , Neoplasias/epidemiologia , SARS-CoV-2/isolamento & purificação , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/imunologia , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/imunologia , Teste para COVID-19 , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lactente , Recém-Nascido , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , SARS-CoV-2/imunologia , Sensibilidade e Especificidade , Distribuição por Sexo , Adulto Jovem
8.
Hematology ; 26(1): 964-969, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34871540

RESUMO

PURPOSE: Multiple myeloma (MM) is a haematological malignant disease with a clonal proliferation of plasma cells, and timely surveillance is helpful to improve the survival rate of patients with MM. However, there is a lack of simple and effective biomarkers for the diagnosis, prognosis, and residual disease evaluation of MM. MATERIAL & METHODS: In the detection cohort, we used the samples from six newly diagnosed MM patients and six control subjects. Plasma proteins were labelled with dimethyl reagents and enriched by lectin AANL6, then the deglycosylated peptides were identified by LC-MS/MS. Differentially expressed proteins were used for further exploration. In the validation cohort, we used 90 newly diagnosed patients with MM and 70 cases of unrelated diseases as controls. The diagnosis performance was analysed by ROC analysis using SPSS. RESULTS: In this study, we show, using lectin blots with AANL6, that glycosylation levels were higher in MM patients than in controls. After AANL6 enrichment, we detected 58 differentially expressed proteins using quantitative proteomics. We further validated one candidate Fibulin-1 (FBLN1). Using an Elisa assay, we showed that FBLN1 expression was increased in plasma of 90 cases of MM, and which was significantly correlated with DKK1 expression. ROC analysis showed that these two markers had a 95.7% specificity for determining the diagnosis of MM. CONCLUSION: These data suggest that the MM cases display increased glycosylation after AANL6 enrichment and that the combined expression of FBLN1 and DKK1 can be used as an effective diagnostic biomarker.


Assuntos
Mieloma Múltiplo/sangue , Adulto , Biomarcadores Tumorais/sangue , Proteínas de Ligação ao Cálcio/sangue , Feminino , Glicosilação , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Prognóstico , Curva ROC , Espectrometria de Massas em Tandem
9.
Carbohydr Polym ; 240: 116329, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32475588

RESUMO

Acute myeloid leukemia (AML) is a difficult therapeutic hematological tumor. It is urgent to find a non-toxic natural drug to treat AML. Herein, the selenium nanoparticles (SeNPs) embedded in nanotubes consisted of triple helix ß-(1, 3)-d-glucan (BFP) from the black fungus that were wrapped to form stable inclusion complex BFP-Se, which was self-assembled and exhibited high stability in water. In vitro, the BFP-Se significantly inhibited the proliferation of AML cells and increased the cytotoxicity on AML cells. On single-cell levels, the U937 cells were gradually swelled and lysed with BFP-Se treatment on optofluidics chips. Further, the blood and bone marrow analysis indicated the anti-leukemia effects of BFP-Se in vivo. Moreover, BFP-Se increased the total antioxidant capacity of AML cells and decreased the expression of c-Jun activation domain-binding protein 1 and thioredoxin 1. Our results suggest that this biocompatible polysaccharide nanotube containing Se nanoparticles would provide a novel strategy for AML therapy.


Assuntos
Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Glucanos/farmacologia , Leucemia Mieloide Aguda/tratamento farmacológico , Nanopartículas/química , Selênio/farmacologia , Animais , Antineoplásicos/química , Antioxidantes/química , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Glucanos/química , Glutationa/antagonistas & inibidores , Humanos , Leucemia Mieloide Aguda/patologia , Camundongos , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Imagem Óptica , Tamanho da Partícula , Selênio/química , Superóxido Dismutase/antagonistas & inibidores , Superóxido Dismutase/metabolismo , Propriedades de Superfície , Células Tumorais Cultivadas
10.
Free Radic Biol Med ; 146: 275-286, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31730934

RESUMO

Chemoresistance and high incidence of relapse in acute myeloid leukemia (AML) patients are associated with thioredoxin (Trx) overexpression. Thus, targeting the Trx system has emerged as a promising approach to treating AML. Both arsenicals and azelaic acid (AZA) are thioredoxin reductase (TrxR) inhibitors and possess antileukemic effects. In this study, to exploit agents with higher potency and lower toxicity, we got some organic arsenicals and further synthesized a series of targeted compounds by binding AZA to organic arsenicals, and then screened the most effective one, N-(4-(1, 3, 2-dithiarsinan-2-yl) phenyl)-azelamide (A-Z2). A-Z2 showed a stronger inhibitory effect against TrxR activity and in AML cell lines than did AZA or arsenicals. Additionally, A-Z2 was less toxic to healthy cells compared with traditional chemotherapeutic drugs. A-Z2 induces apoptosis by collapsing of mitochondrial membrane potential, reducing ATP level, releasing of cytochrome c and TNF-α, activating of caspase 9, 8 and 3. Analysis of the mechanism revealed that A-Z2 activates the intrinsic apoptotic pathway by directly selectively targeting TrxR/Trx and indirectly inhibiting NF-κB. A-Z2's better efficacy and safety profile against arsenicals and azelaic acid were also evident in vivo. A-Z2 had better plasma stability and biological activity in rats. A-Z2-treated mice displayed significant symptom relief and prolonged survival in a patient-derived xenograft (PDX) AML model. Herein, our study provides a novel antitumor candidate and approach for treating AML.


Assuntos
Antineoplásicos , Leucemia Mieloide Aguda , Animais , Antineoplásicos/farmacologia , Apoptose , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Camundongos , Ratos , Tiorredoxina Dissulfeto Redutase , Tiorredoxinas
11.
Aging (Albany NY) ; 11(20): 8892-8910, 2019 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-31631064

RESUMO

Radiotherapy is used to treat gastric cancer (GC); however, radioresistance challenges the clinical outcomes of GC, and the mechanisms of radioresistance in GC remain poorly understood. Here, we report that the TGF-ß receptor inhibitor, LY2109761 (LY), is a potential radiosensitizer both in vitro and in vivo. As per the Cancer Genome Atlas database, TGF-ß overexpression is significantly related to poor overall survival in GC patients. We demonstrated that the TGF-ß/SMAD4 signaling pathway was activated in both radioresistant GC cells and radioresistant GC patients. As a TGF-ß receptor inhibitor, LY can enhance the activities of irradiation by inhibiting cell proliferation, decreasing clonogenicity and increasing apoptosis. Moreover, LY attenuated the radiation-induced migration and invasion, epithelial-mesenchymal transition (EMT), inflammatory factor activation, immunosuppression, and cancer stem cell characteristics of GC cells, thus leading to radiosensitization of the GC cells. We confirmed that LY reduced tumor growth, inhibited TGF-ß/SMAD4 pathway activation and reversed irradiation-induced EMT in a tumor xenograft model. Our findings indicate that the novel TGF-ß receptor inhibitor, LY, increases GC radiosensitivity by directly regulating the TGF-ß/SMAD4 signaling pathway. These findings provide new insight for radiotherapy in GC patients.


Assuntos
Pirazóis/farmacologia , Pirróis/farmacologia , Proteína Smad4/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/radioterapia , Fator de Crescimento Transformador beta/antagonistas & inibidores , Fator de Crescimento Transformador beta/metabolismo , Animais , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos Nus , Neoplasias Experimentais , Tolerância a Radiação , Transdução de Sinais/efeitos dos fármacos , Proteína Smad4/genética , Fator de Crescimento Transformador beta/genética
12.
J Exp Clin Cancer Res ; 37(1): 277, 2018 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-30454068

RESUMO

BACKGROUND: The increase in the levels of reactive oxygen species (ROS) in acute myeloid leukemia (AML) patients has been previously described; thus, it is important to regulate ROS levels in AML. METHODS: Flow cytometry were used to assess the in vitro effect of compound kushen injection (CKI). Quantitative proteomics were used to analyse the mechanism. The AML patient-derived xenograft (PDX) model were used to evaluate the in vivo effect of CKI. RESULTS: We found that intracellular ROS levels in AML cells were decreased, the antioxidant capacity were increased when treated with CKI. CKI inhibited the proliferation of AML cells and enhanced the cytotoxicity of AML cells, which has few toxic effects on haematopoietic stem cells (HSCs) and T cells. At the single-cell level, individual AML cells died gradually by CKI treatment on optofluidic chips. CKI promoted apoptosis and arrested cell cycle at G1/G0 phase in U937 cells. Furthermore, higher peroxiredoxin-3 (Prdx3) expression levels were identified in CKI-treated U937 cells through quantitative proteomics detection. Mechanically, the expression of Prdx3 and peroxiredoxin-2 (Prdx2) was up-regulated in CKI-treated AML cells, while thioredoxin 1 (Trx1) was reduced. Laser confocal microscopy showed that the proteins Prdx2 could be Interacted with Trx1 by CKI treatment. In vivo, the survival was longer and the disease was partially alleviated by decreased CD45+ immunophenotyping in peripheral blood in the CKI-treated group in the AML PDX model. CONCLUSIONS: Antioxidant CKI possess better clinical application against AML through the Prdxs/ROS/Trx1 signalling pathway.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Leucemia Mieloide Aguda/tratamento farmacológico , Peroxirredoxinas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Tiorredoxinas/metabolismo , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Células HL-60 , Xenoenxertos , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Camundongos , Microscopia Confocal , Transdução de Sinais/efeitos dos fármacos , Células U937
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA