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1.
Cell Signal ; 88: 110167, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34628002

RESUMO

Artesunate (ART), a water-soluble derivative of artemisinin, has been reported to exert antineoplastic effects via diverse mechanisms in various types of cancer. Therefore, understanding the underlying mechanism of action of ART in distinct cancer types is indispensable to optimizing the therapeutic application of ART for different types of cancer. The present study aimed to investigate the cellular and molecular mechanisms responsible for the antineoplastic effects of ART in diffuse large B cell lymphoma (DLBCL) cells. Cell proliferation was measured using Cell Counting Kit-8 and colony formation assays. The levels of apoptosis and cell cycle distribution were investigated using flow cytometry. In addition, western blotting was used to analyze the expression levels of ART-induced apoptosis-, autophagy- and ferroptosis-related proteins. Monodansylcadaverine staining was performed to determine the levels of autophagy. Moreover, malondialdehyde and reactive oxygen species assays were used to determine the levels of ferroptosis. The results of the present study revealed that ART inhibited proliferation, and induced apoptosis, cell cycle arrest, autophagy and ferroptosis in DLBCL cells. Pharmacological inhibition of autophagy and ferroptosis alleviated the increased levels of apoptosis induced by ART. Notably, ART was found to exert its effects via inhibition of STAT3 activation. The genetic knockdown of STAT3 enhanced ART-induced autophagy and ferroptosis, and concomitantly upregulated the expression levels of apoptosis- and cell cycle-related proteins. In conclusion, the findings of the current study suggested that ART may induce apoptosis and cell cycle arrest to inhibit cell proliferation, and regulate autophagy and ferroptosis via impairing the STAT3 signaling pathway in DLBCL cells.

3.
BMC Cancer ; 21(1): 955, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433456

RESUMO

BACKGROUND: The improved prognosis of classic Hodgkin lymphoma (cHL) has been accompanied by elevated risks of non-cancer-specific death (non-CSD). The aim of this study was to verify the occurrence of non-CSD and its effect on rates of overall survival among adult patients with cHL. METHODS: To ensure sufficient follow-up time, we analyzed retrospective data from patients aged ≥20 years with cHL that was diagnosed between 1983 and 2005 in the Surveillance, Epidemiology, and End Results (SEER) database. Logistic regression was applied to analyze the non-CSD occurrence in relation to all factors. Using Fine-Gray's method, we calculated the cumulative incidences of CSD and non-CSD. Stacked cumulative incidence plots and ratio of non-CSD to all causes of death were applied to evaluate the effect of non-CSD on rates of overall survival. Finally, we analyzed long-term mortality through Cox proportional hazard regression analysis and competing risk regression analysis to emphasize a more appropriate model of survival for patients with cHL. RESULTS: Among the 18,518 patients included, there were 3768 cases of CSD (20.3%) and 3217 of non-CSD (17.4%). Older age, earlier period, male sex, unmarried status, mixed cellularity (MC) and lymphocyte-depletion (LD) histological subtype, and patients received radiotherapy (RT) only were associated with more non-CSD according to binary logistic analysis. The cumulative incidence of non-CSD exceeded CSD after approximately 280 months follow-up. The most common causes of non-CSDs were cardiovascular disease, subsequent primary neoplasms, infectious diseases, accidents, and suicide. In a Cox proportional hazards model, patients who were black, unmarried, at an advanced stage or underwent chemotherapy (CT) alone were at greater risk of mortality than were white patients, who were married, at an early stage, and underwent combined modality; these populations were also found to be at greater risk for CSD in a competing risk model, but the risk of non-CSD did not differ significantly according to race and marital status, patients with early-stage disease and who underwent RT only were found to be at higher risk of non-CSD instead. CONCLUSIONS: Lymphoma was the cause of death in most patients who died, but non-CSD was not unusual. Patients with cHL should be monitored closely for signs of cardiovascular disease and malignant tumors. Rates of overall survival of patients were diminished by non-CSD, and a competing risk model was more suitable for establishing the prognosis than was the Cox proportional hazards model.


Assuntos
Causas de Morte/tendências , Doença de Hodgkin/mortalidade , Programa de SEER/estatística & dados numéricos , Adulto , Terapia Combinada , Feminino , Seguimentos , Doença de Hodgkin/patologia , Doença de Hodgkin/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Taxa de Sobrevida , Adulto Jovem
4.
Anticancer Drugs ; 32(8): 886-889, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34145178

RESUMO

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin's lymphoma, with certain DLBCLs affecting specific anatomic sites, such as primary cutaneous DLBCL, leg type and intravascular large B-cell lymphoma. However, the occurrence of secondary cutaneous involvement in DLBCL while patients are undergoing regular chemotherapy is rare. In this study, we reported a case of refractory diffuse large B-cell lymphoma with cutaneous involvement that achieved complete remission for more than 4 years with epigenetic regulation of chidamide in combination with chemotherapy and autologous hematopoietic stem cell transplantation including a pretreatment regimen containing chidamide.

5.
J Cancer ; 11(14): 4284-4296, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368311

RESUMO

Leukemia is a common malignant cancer of the hematopoietic system, whose pathogenesis has not been fully elucidated. Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides without protein-coding function. Recent studies report their role in cellular processes such as the regulation of gene expression, as well as in the carcinogenesis, occurrence, development, and prognosis of various tumors. Evidence indicating relationships between a variety of lncRNAs and leukemia pathophysiology has increased dramatically in the previous decade, with specific lncRNAs expected to serve as diagnostic biomarkers, novel therapeutic targets, and predictors of clinical outcomes. Furthermore, these lncRNAs might offer insight into disease pathogenesis and novel treatment options. This review summarizes progress in studies on the role(s) of lncRNAs in leukemia.

6.
Cell Signal ; 72: 109643, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32320859

RESUMO

Transient Receptor Potential Melastatin Subfamily Member 4 (TRPM4) has been demonstrated to be aberrantly expressed in several cancers but seldom reported in acute leukemia. Based on database mining and validated experiments, our present data show that TRPM4 is selectively overexpressed in AML patients and cell lines with the MLL gene rearrangement. We analyzed the correlation between TRPM4 expression and clinical parameters in a validated cohort of AML patients. Increased TRPM4 expression was associated with significant leukocytosis (p = .028), M4/M5 subtype (p = .000), FLT3-ITD mutation (p = .034), MLL status (p = .007) and a higher risk stratification (p = .001). Knockdown of TRPM4 mediated by siRNA impaired proliferation and arrested the cell cycle at the G0/G1 phase in MLL-rearranged leukemia cells. We suggested that TRPM4 may be involved in the pathogenesis of MLL-rearranged leukemia through regulating the AKT/GLI1/Cyclin D1 pathway. The transcription factor HOXA9 was found to be responsible for upregulation of TRPM4 expression by binding to its promoter. In conclusion, TRPM4 is overexpressed in MLL-rearranged AML and blockade of TRPM4 may be an alternative therapeutic approach in AML patients with high TRPM4 expression.

7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 21(1): 130-4, 2013 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-23484706

RESUMO

This study was purposed to establish a new quick and simple diagnostic method with high sensitivity and good specificity for idiopathic thrombocytopenic purpura (ITP) and to evaluate its significance. 240 platelet lysates (from patients with ITP, leukemia, MDS, and healthy adults, each of 60 cases) were randomly assigned to training set (120 cases) or validation set (120 cases), all of them were detected by surface enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS), in order to identify the differentially expressed protein, the diagnostic model was established by means of artificial neural network (ANN), and was validated by blind test with SPSS 17.0. The results showed that 5 marked proteins significantly differentially expressed (P < 0.01), m/z of highly expressed proteins were 2234.30, 3476.36, and 7526.29, m/z of low expressed proteins were 4990.02 and 5152.39, respectively. The sensitivity and specificity of diagnostic model were 80.6% and 77.3% respectively. The area under the ROC curve consisting of the output value of artificial neura1 network was 0.837. Efficacy of the model was validated by means of blinded test. It is concluded that the ANN model is useful for clinical diagnosis of ITP on the basis of platelet protein fingerprint spectrum.


Assuntos
Redes Neurais de Computação , Proteoma/análise , Púrpura Trombocitopênica Idiopática/diagnóstico , Adulto , Estudos de Casos e Controles , Humanos , Mapeamento de Peptídeos , Proteômica , Púrpura Trombocitopênica Idiopática/genética , Púrpura Trombocitopênica Idiopática/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 11(2): 197-8, 2003 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-12744747

RESUMO

In order to explore the serum level of granulocyte-macrophage colony stimulating factor (GM-CSF) in hematopathy patients, radioimmunoassay was used to detect GM-CSF level in serum from 163 cases of hematopathy, including 36 chronic aplastic anemia, 42 chronic granulocytic leukemia, 54 acute myeloid leukemia, 31 acute lymphocytic leukemia, and 40 healthy adults as control. The results showed that the serum GM-CSF level increased in chronic aplastic anemia patients, and significantly decreased in acute and chronic leukemia patients. In conclusion, these findings indicated that secreting level of GM-CSF is abnormal in patients with acute/chronic leukemias and chronic aplastic anemia.


Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , Doenças Hematológicas/sangue , Adolescente , Adulto , Idoso , Anemia Aplástica/sangue , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Leucemia Mieloide Aguda/sangue , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue
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