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1.
Clin Lab ; 68(6)2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35704725

RESUMO

BACKGROUND: The goal is to assess the prognosis of cytogenetic abnormality, because cytogenetic abnormality is rarely encountered in clinical practice. METHODS: We retrospectively report three cytogenetic abnormality cases with clinical, cytogenetic, and genetic characteristic. RESULTS: All cases occurred within one month of birth and had prominent hepatosplenomegaly, including acute myeloid leukemia (case 1, case 2) and acute leukemia (case 3). Moreover, case 1 appeared as leukemia cutis at birth, case 2 was born with respiratory distress, and both showed hyperleukocytosis. The R-banded karyotype detected cytogenetic abnormality in three cases, case 1 with 46,XY,t(8;12)(q21;p13), case 2 with 47,XX,+21 and case 3 with 46,XY,t(6;X)(q22:p12), respectively. Especially in case 1, reverse transcription-polymerase chain reaction analysis showed MLL-AF10 rearranged. CONCLUSIONS: In our studies, all cases had not received chemotherapy and survived about 1 - 2 months. It suggests that cytogenetic disorders are closely related to disease development and likely result in fatal outcome if untreated. Thus, we proposed that a proper treatment decision is urgently needed in congenital leukemia.


Assuntos
Leucemia Mieloide Aguda , Proteína de Leucina Linfoide-Mieloide , Aberrações Cromossômicas , Humanos , Recém-Nascido , Cariotipagem , Leucemia Mieloide Aguda/genética , Proteína de Leucina Linfoide-Mieloide/genética , Estudos Retrospectivos
2.
J Med Internet Res ; 24(11): e38108, 2022 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-36449336

RESUMO

BACKGROUND: Worldwide, mental well-being is a critical issue for public health, especially among medical staff; it affects professionalism, efficiency, quality of care delivery, and overall quality of life. Nevertheless, assessing mental well-being is a complex problem. OBJECTIVE: This study aimed to evaluate the psychometric properties of the Chinese-language version of the 14-item Warwick-Edinburgh Mental Well-being Scale (WEMWBS) in medical staff recruited mainly from 6 hospitals in China and provide a reliable measurement of positive mental well-being. METHODS: A cross-sectional online survey was conducted of medical staff from 15 provinces in China from May 15 to July 15, 2020. Confirmatory factor analysis (CFA) was conducted to test the structure of the Chinese WEMWBS. The Spearman correlations of the Chinese WEMWBS with the 5-item World Health Organization Well-Being Index (WHO-5) were used to evaluate convergent validity. The Cronbach α and split-half reliability (λ) represented internal consistency. A graded response model was adopted for an item response theory (IRT) analysis. We report discrimination, difficulty, item characteristic curves (ICCs), and item information curves (IICs). ICCs and IICs were used to estimate reliability and validity based on the IRT analysis. RESULTS: A total of 572 participants from 15 provinces in China finished the Chinese WEMWBS. The CFA showed that the 1D model was satisfactory and internal consistency reliability was excellent, with α=.965 and λ=0.947, while the item-scale correlation coefficients ranged from r=0.727 to r=0.900. The correlation coefficient between the Chinese WEMWBS and the WHO-5 was significant, at r=0.746. The average variance extraction value was 0.656, and the composite reliability value was 0.964, with good aggregation validity. The discrimination of the Chinese WEMWBS items ranged from 2.026 to 5.098. The ICCs illustrated that the orders of the category thresholds for the 14 items were satisfactory. CONCLUSIONS: The Chinese WEMWBS showed good psychometric properties and can measure well-being in medical staff.


Assuntos
Idioma , Qualidade de Vida , Humanos , Estudos Transversais , Psicometria , Reprodutibilidade dos Testes , Corpo Clínico , China
3.
Clin Lab ; 67(6)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34107624

RESUMO

BACKGROUND: Isochromosome 11q in patients with acute myeloid leukemia is rarely reported, and little is known about its main features. METHODS: The presence of isochromosome 11q was identified in four patients (three adults and one child) from screening 441 patients with an acute myeloid leukemia diagnosis between 2009 and 2018 by using R-banding and fluorescence in situ hybridization. RESULTS: The child, patient 1 with unreported isochromosome (partial 11q isochromosome), accompanied with t(1;11) translocation, initially achieved remission after receiving chemotherapy. However, 4 months later this patient experienced a relapse. While multiple treatments were tried, it had no effect and the patient survived for 16 months. The remaining patients with isochromosome 11q exhibited numerical/structural chromosomal abnormal-ities involving myelodysplastic syndrome-related chromosomes 5, 7, 8, and 20. In patients 2 and 3, we found a derivative chromosome 21. Patient 3 was newly diagnosed with acute myeloid leukemia and was treated with many chemotherapy protocols, unfortunately with no effect. The patient then received traditional Chinese medicine and survived for 10 months, although she still has not achieved complete remission. Patients 2 and 4 received chemotherapy but experienced rapid disease progression and died within 2 months. CONCLUSIONS: In summary, patients with isochromosome 11q/partial 11q isochromosome have a poorer prognosis, especially for isochromosome 11q. Furthermore, these chromosome aberrations may be risk factors for the presence of isochromosome 11q or myelodysplastic syndrome-related genes, both of them may be associated with a failure to respond to treatment and poor outcomes. Hence, these discoveries may lay a foundation to study mechanisms and explore treatments.


Assuntos
Isocromossomos , Leucemia Mieloide Aguda , Adulto , Criança , Aberrações Cromossômicas , Feminino , Humanos , Hibridização in Situ Fluorescente , Isocromossomos/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Prognóstico
4.
Health Qual Life Outcomes ; 17(1): 55, 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30922342

RESUMO

BACKGROUND: The mental well-being of patients with chronic heart failure is likely to influence their health-related quality of life and decrease the utilization of public health resources. This study assessed the mental well-being of patients with chronic heart failure and evaluated the reliability and validity of the Warwick-Edinburgh Mental Well-Being Scale. METHODS: We conducted a cross-sectional survey from July 2016 to July 2017 among 191 patients with chronic heart failure, and examined psychometric properties of the Warwick-Edinburgh Mental Well-Being Scale, such as internal consistency, reliability, test-retest reliability, and factorial validity of the Chinese version of the Warwick-Edinburgh Mental Well-Being Scale. RESULTS: One-dimensional construct validity was demonstrated by confirmatory factor analysis. The psychometric properties of the Chinese version of the Warwick-Edinburgh Mental Well-Being Scale were satisfactory in our sample of patients with chronic heart failure. The internal consistency reliability was .948 and the test-retest reliability .925. The item-total correlations ranged from .405 to .872. There was a strong correlation (r = .79) between the Chinese version of the Warwick-Edinburgh Mental Well-Being Scale and the five-item World Health Organization Well-Being Index. The Chinese version of the Warwick-Edinburgh Mental Well-Being Scale appears acceptable for use in patients with chronic heart failure, and we were able to verify its reliability and validity with our sample. CONCLUSIONS: The Chinese version of the Warwick-Edinburgh Mental Well-Being Scale is a reliable quantitative tool for evaluating mental well-being in patients with chronic heart failure in clinical settings, and this has important implications for overall assessments of mental well-being in patients with chronic heart failure.


Assuntos
Insuficiência Cardíaca/psicologia , Escalas de Graduação Psiquiátrica/normas , Qualidade de Vida , Adulto , Idoso , China , Comparação Transcultural , Estudos Transversais , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
5.
Exp Cell Res ; 369(1): 69-79, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29752949

RESUMO

Making sure the change of nuclear LC3 distribution in the autophagy of acute myeloid leukemia (AML) cell and finding out the regulation mechanism may lead to a breakthrough for killing AML cells. Western blots were performed to assess the expression of autophagy proteins. Changes in the LC3 distribution were monitored by immunofluorescence assays together with western blots, and the expression levels of Sirt1, DOR, Beclin1, HMGB1, and AMPK mRNA were detected via fluorescent quantitative PCR. The effects of Sirt1 and DOR on cell proliferation and survival were analyzed by MTT, flow cytometry, and western blotting assays. We found that treating AML cells with Ara-c or Sorafenib resulted in autophagy enhancement, and when autophagy was enhanced, nuclear LC3 moved into the cytoplasm. Notably, when autophagy was inhibited by blocking the nuclear LC3 shift, the cytotoxicity of drugs was enhanced. Our results also identified Sirt1 and DOR as regulatory molecules for the observed nuclear LC3 shift, and these molecules further affected the expression of Beclin1, HMGB1, and AMPK. Our results suggest the distribution of nuclear LC3 can be a novel way for further studying death of AML cells,and the regulatory molecules may be new targets for treating AML.


Assuntos
Núcleo Celular/metabolismo , Leucemia Mieloide Aguda/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Transporte Ativo do Núcleo Celular , Apoptose/fisiologia , Autofagia/fisiologia , Linhagem Celular Tumoral , Núcleo Celular/patologia , Proliferação de Células , Citoplasma/metabolismo , Regulação Leucêmica da Expressão Gênica , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Transporte Proteico , Distribuição Tecidual
6.
Biochem Biophys Res Commun ; 498(1): 207-213, 2018 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-29501744

RESUMO

Multiple myeloma (MM), the second most common hematologic malignancy, is an incurable disease characterized by the accumulation of malignant plasma cells within the bone marrow. Though great progresses have been made in understanding the mechanisms of MM, metabolic plasticity and drug resistance remain largely unknown. In this study, we found lncRNA Protein disulfide isomerase family A member 3 pseudogene 1 (PDIA3P) is highly expressed in MM and is associated with the survival rate of MM patients. PDIA3P regulates MM growth and drug resistance through Glucose 6-phosphate dehydrogenase (G6PD) and the pentose phosphate pathway (PPP). Mechanistically, we revealed that PDIA3P interacts with c-Myc to enhance its transactivation activity and binding to G6PD promoter, stimulating G6PD expression and PPP flux. Our study identified PDIA3P as a novel c-Myc interacting lncRNA and elucidated crucial roles for PDIA3P in metabolic regulation of MM, providing a potential therapeutic target for MM patients.


Assuntos
Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Via de Pentose Fosfato/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Longo não Codificante/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Glucosefosfato Desidrogenase/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , RNA Longo não Codificante/genética , Taxa de Sobrevida
7.
Aging Clin Exp Res ; 29(4): 685-693, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27518815

RESUMO

BACKGROUND: Chronic heart failure (CHF), a major public health problem worldwide, seriously limits health-related quality of life (HRQOL). How to evaluate HRQOL in older patients with CHF remains a problem. AIM: To evaluate the reliability and validity of the Chinese version of the Medical Outcomes Study Short Form version 2 (SF-36v2) in CHF patients. METHODS: From September 2012 to June 2014, we assessed QOL using the SF-36v2 in 171 aging participants with CHF in four cardiology departments. Convergent and discriminant validity, factorial validity, sensitivity among different NYHA classes and between different age groups, and reliability were determined using standard measurement methods. RESULTS: A total of 150 participants completed a structured questionnaire including general information and the Chinese SF-36v2; 132 questionnaires were considered valid, while 21 patients refused to take part. 25 of the 50 participants invited to complete the 2-week test-retest questionnaires returned completed questionnaires. The internal consistency reliability (Cronbach's α) of the total SF-36v2 was 0.92 (range 0.74-0.93). All hypothesized item-subscale correlations showed satisfactory convergent and discriminant validity. Sensitivity was measured in different NYHA classes and age groups. Comparison of different NYHA classes showed statistical significance, but there was no significant difference between age groups. DISCUSSION: We confirmed the SF-36v2 as a valid instrument for evaluating HRQOL Chinese CHF patients. Both reliability and validity were strongly satisfactory, but there was divergence in understanding subscales such as "social functioning" because of differing cultural background. CONCLUSIONS: The reliability, validity, and sensitivity of SF-36v2 in aging patients with CHF were acceptable.


Assuntos
Envelhecimento , Nível de Saúde , Insuficiência Cardíaca/psicologia , Qualidade de Vida , Inquéritos e Questionários/normas , Adulto , Idoso , Envelhecimento/fisiologia , Envelhecimento/psicologia , China , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Reprodutibilidade dos Testes , Traduções
8.
Cancer Invest ; 34(7): 340-7, 2016 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-27486812

RESUMO

The level of pre-transplantation serum ferritin (SF) is one of the factors related to outcome for patients undergoing allogeneic hematopoietic stem cell transplantation. We searched PubMed and Cochrane Library databases from 2000 to 2014. The primary efficacy outcome was overall survival rate and non-relapse mortality. Twenty clinical trials were selected from 189 studies identified. The combined hazard ratio indicated a significantly lower overall survival rate and a higher non-relapse mortality rate in patients with elevated SF before transplantation. This indicates that elevated pre-transplantation SF affects outcome in patients undergoing allogeneic hematopoietic stem cell transplantation.


Assuntos
Ferritinas/sangue , Transplante de Células-Tronco Hematopoéticas , Biomarcadores , Humanos , Avaliação de Resultados da Assistência ao Paciente , Período Pré-Operatório , Prognóstico , Modelos de Riscos Proporcionais , Viés de Publicação , Transplante Homólogo
9.
Dig Surg ; 33(3): 190-6, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26866931

RESUMO

RATIONALE AND OBJECTIVE: Recently, interest in the role of aquaporin 1 (AQP1) in human gastrointestinal carcinogenesis has developed. However, to date no studies have examined relationships between AQP1 expression and specific characteristics of gastric adenocarcinoma. METHODS: We investigated 109 specimens of primary gastric adenocarcinoma and their corresponding normal gastric mucosa using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) to determine AQP1 expression. We then evaluated disease free survival (DFS) and overall survival (OS) in these patients in association with AQP1 expression. RESULTS: Both immunohistochemical and RT-PCR analyses identified increased AQP1 expression in tumors from patients with gastric adenocarcinoma (p < 0.001). The 3-year DFS and OS rates were higher in the AQP1-negative group than in the positive group (DFS: 77.2 vs. 52.8%, p < 0.001; OS: 85.1 vs. 70.7%, p < 0.001). The 5-year DFS and OS rates exhibited a similar trend (p < 0.001). Subgroup analysis of patients with early gastric adenocarcinoma (stages I and II) revealed a total 5-year OS of 90.0%, with 5-year OS being higher in the AQP1-negative group than in the positive group (95.2 vs. 84.2%). Furthermore, incidence of tumor recurrence following surgical treatment was significantly higher in the AQP1-positive group (4/19, 21.1%) compared with the negative group (0/21, 0%). CONCLUSIONS: Our study demonstrates that AQP1 plays an important role in gastric adenocarcinoma and may therefore represent a novel therapeutic target and prognostic marker in this disease.


Assuntos
Adenocarcinoma/genética , Aquaporina 1/genética , Recidiva Local de Neoplasia/genética , Neoplasias Gástricas/genética , Adenocarcinoma/química , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose/genética , Aquaporina 1/análise , Intervalo Livre de Doença , Feminino , Mucosa Gástrica/química , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Gástricas/química , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de Sobrevida
10.
J Thromb Thrombolysis ; 38(2): 183-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24338248

RESUMO

Abnormal cellular immunity induced by deranged Th1/Th2 profile has been revealed to play a critical role in the pathogenesis of immune thrombocytopenic purpura (ITP). Correction of the shifted Th1/Th2 balance represents a potential therapeutic approach to treat ITP. Here, we investigated the effects of IL-11 on the restoration of Th1/Th2 balance in the peripheral blood mononuclear cells (PBMCs) isolated from adult ITP patients. As shown here, we observed a higher ratio of T-bet/GATA-3 gene expression by quantitative real-time PCR in the PBMCs from ITP patients, consistent with the presence of an abnormally high Th1/Th2 ratio. Remarkably, upon IL-11 treatment, a reversal of T-bet/GATA-3 ratio in ITP was achieved and was shown to be responsible for the restoration of Th1/Th2 balance, with IL-11 at 100 ng/ml demonstrating the highest efficiency. T-bet and GATA-3 are the two transcriptional factors that have been indicated to be the master regulators for Th1 and Th2 lineage commitment, respectively. In the presence of 100 ng/ml IL-11, GATA-3 transcript abundance rose up to ~85-fold of that measured in untreated cells, whereas T-bet transcripts were lowered merely to ~41%, suggesting that GATA-3 was the major contributor for the reversal of T-bet/GATA-3 ratio. Thus, our findings may very well encourage the development of novel medicines that specifically target and correct the T-bet/GATA-3 imbalance identified in ITP.


Assuntos
Fator de Transcrição GATA3/imunologia , Regulação da Expressão Gênica/efeitos dos fármacos , Interleucina-11/farmacologia , Púrpura Trombocitopênica Idiopática/imunologia , Proteínas com Domínio T/imunologia , Células Th1/imunologia , Células Th2/imunologia , Adulto , Relação Dose-Resposta a Droga , Feminino , Humanos , Interleucina-11/imunologia , Masculino , Púrpura Trombocitopênica Idiopática/patologia , Células Th1/patologia , Células Th2/patologia
11.
Chem Pharm Bull (Tokyo) ; 62(4): 343-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24695344

RESUMO

Novel hybrids 8a-j and 9a-j were designed and synthesized by coupling the carboxyl group of hydroxylcinnamic acids with tetrahydro-ß-carboline alkaloids which were linked with different substituted nitrogen-containing heterocycles at the positions-N9, and their in vitro biological activities were evaluated. It was found that most hybrids showed good to moderate anti-tumor activities. Especially, compound 9j had a great potency superior to 5-fluorouracil (5-FU) and comparable to adriamycin in human cancer cells, and could selectively inhibit tumor cells, but not inhibit non-tumor cell proliferation in vitro. More importantly, apoptosis assay indicated that 9j could significantly induce tumor cell apoptosis in a dose-dependent manner. Therefore, our novel findings may provide a new framework for the design of new hybrids for the intervention of human cancers.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Carbolinas/química , Cinamatos/química , Antineoplásicos/síntese química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Técnicas de Química Sintética , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Fluoruracila/farmacologia , Humanos , Relação Estrutura-Atividade
12.
Water Res ; 253: 121337, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38387266

RESUMO

The marine environment of the southern Bohai Sea is severely polluted by short-chain chlorinated paraffins (SCCPs). To improve understanding of how SCCPs occur and of how they migrate, are transformed, and transferred in this area, we collected seawater, sediment, and organism samples, and determined the SCCP contents using a new approach based on high-resolution mass spectrometry. The ΣSCCP concentrations in the seawater, sediment, and organism samples ranged from 57.5 to 1150.4 ng/L, 167.7-1105.9 ng/g (dry weight), and 11.4-583.0 ng/g (wet weight), respectively. Simulation of the spatial distribution of SCCPs using Kriging interpolation showed that SCCPs were markedly influenced by land-based pollution. Substantial quantities of SCCPs were transported to the marine environment via surface runoff from rivers that passed through areas of major SCCP production. Once discharged from such rivers into the Bohai Sea, these SCCPs were further dispersed under the influence of ocean currents. Furthermore, the logarithmic bioaccumulation factor that varied from 2.12 to 3.20 and the trophic magnification factor that reached 5.60 (r2 = 0.750, p < 0.01) suggest that organisms have the ability to accumulate and biomagnify SCCPs through the food chain, which could potentially present risks to both marine ecosystems and human health.


Assuntos
Ecossistema , Hidrocarbonetos Clorados , Humanos , Parafina/análise , Parafina/química , Monitoramento Ambiental , China
13.
Hematology ; 28(1): 2227491, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37367830

RESUMO

OBJECTIVE: Necroptosis has been reported to play an important role in different cancers, including leukemia. However, biomarkers of necroptosis-related genes (NRGs) that help predict the prognosis of AML are still lacking. Our research aims to build a novel signature of NRGs that could enhance our understanding of the molecular heterogeneity in leukemia. METHOD: Gene expression profiles as well as clinical features were downloaded from TCGA and GEO databases. Data analysis were executed using R software version 4.2.1 and GraphPad Prism version 9.0.0. RESULT: Univariate cox regression and lasso regression were applied to identify survival-specific genes. Four genes including FADD, PLA2G4A, PYCARD and ZBP1 were considered as independent risk factors that affect the prognosis of patients. Risk scores were calculated according to the coefficient of four genes. Then clinical characteristics and risk scores were enrolled to construct a nomogram. CellMiner was also used to screen potential drugs and analyze the correlations between genes and drug sensitivity. CONCLUSION: In general, we established a signature of four genes related to necroptosis that could be helpful for future risk stratification in patients with AML.


Assuntos
Leucemia Mieloide Aguda , Necroptose , Humanos , Necroptose/genética , Leucemia Mieloide Aguda/genética , Bases de Dados Factuais , Nomogramas , Fatores de Risco , Prognóstico
14.
Front Public Health ; 11: 1183483, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37213640

RESUMO

Objective: To investigate subgroups of health-related quality of life (HRQoL) in the Chinese medical staff and identify the demographic factors associated with these profiles. Methods: 574 Chinese medical staff were surveyed online. HRQoL was measured by using the 36-Item Short Form Health Survey, Version 2. Latent profile analysis (LPA) was used to identify the profiles of HRQoL. The associations between HRQoL profiles and covariates were assessed using multinomial logistic regression. Results: Three HRQoL profiles were developed: low HRQoL at 15.6%, moderate HRQoL at 46.9%, and high HRQoL at 37.6%. Multinomial logistic regression showed night shift times, aerobic exercise conditioning, and personality type significantly predicted the profile membership. Conclusion: Our findings develop earlier approaches that only used total scores to evaluate this group's HRQoL and help them with tailored interventions to promote better HRQoL.


Assuntos
População do Leste Asiático , Qualidade de Vida , Humanos , Exercício Físico , Modelos Logísticos , Inquéritos e Questionários , Corpo Clínico
15.
J Oncol ; 2022: 4112016, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35342415

RESUMO

Background: Cytogenetic abnormalities are considered initiating events in the pathogenesis of multiple myeloma (MM) and are assumed to be of clinical significance. Methods: Fluorescence in situ hybridization (FISH) was used to analyze chromosomal architecture in 101 patients with MM. We evaluated overall patient survival and assessed the cytotoxicity of imatinib against MM cells using a CCK8 assay. Results: ABL gene amplification was detected in 67 patients (66.3%). However, ABL gene amplification was not associated with clinical features, cytogenetic abnormalities (c-Myc amplification, IGH rearrangement, RB1 deletion, p53 deletion, or 1q21 amplification), or overall survival. ABL amplification in MM cell lines (LP-1 and U266) was revealed by FISH. Furthermore, the ABL protein was easily detectable in MM cell lines and some tumor cells by western blotting. A CCK8 assay indicated limited cytotoxicity of imatinib against MM cells. Conclusions: Our study firstly discussed ABL gene amplification was prevalent in MM cells, and we believe that the ABL gene would potentially be a useful target in the treatment of combination strategy for MM with ABL amplification in the future.

16.
Oncol Rep ; 44(2): 543-554, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32468066

RESUMO

Changes in histone H3 lysine 9 trimethylation (H3K9me3) may be related to the development of drug­resistant acute myeloid leukaemia (AML); insights into the network of H3K9me3 may improve patient prognosis. Patient data were derived from the Gene Expression Omnibus (GEO) database and data from AML cells treated with chidamide, a novel benzamide chemical class of histone deacetylase inhibitor (HDACi), in vitro were derived from ChIP­seq. Patients and AML cell data were analysed using GEO2R, GOseq, KOBAS, the STRING database and Cytoscape 3.5.1. We identified several genes related to the upregulation or downregulation of H3K9me3 in AML patients; some of these genes were related to apoptosis, autophagy, and the pathway of cell longevity. AML cells treated with chidamide in vitro showed the same gene changes. The protein interactions in the network did not have significantly more interactions than expected, suggesting the need for more research to identify these interactions. One compelling result from the protein interaction study was that sirtuin 1 (SIRT1) may have an indirect interaction with lysine­specific demethylase 4A (KDM4A). These results help explain alterations of H3K9me3 in AML that may direct further studies aimed at improving patient prognosis. These results may also provide a basis for chidamide as a treatment strategy for AML patients in the future.


Assuntos
Aminopiridinas/uso terapêutico , Benzamidas/uso terapêutico , Biologia Computacional/métodos , Inibidores de Histona Desacetilases/uso terapêutico , Histonas/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico , Apoptose , Sequenciamento de Cromatina por Imunoprecipitação , Resistencia a Medicamentos Antineoplásicos , Redes Reguladoras de Genes , Humanos , Leucemia Mieloide Aguda/genética , Mapas de Interação de Proteínas , Células THP-1
17.
Oncol Rep ; 44(1): 273-282, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32626988

RESUMO

Acute myeloid leukemia (AML) is a highly aggressive disease with high mortality and recurrence rates, for which novel therapeutic approaches are required. Hybrid anticancer agents with dual effects have been reported to possess therapeutic potential to treat AML. However, the efficacy and underlying toxicity of these hybrids in combination with other agents remain unclear. NL­101 is a novel hybrid formed by fusing the DNA damage­inducing agent bendamustine with the histone deacetylase inhibitor vorinostat. In the present study, NL­101 treatment was combined with the conventional chemotherapeutic drug daunorubicin (DNR) in AML cells, and it was revealed that these two compounds exerted synergistic anti­AML effects. In addition, NL­101 enhanced DNR­induced cell apoptosis, as assessed by flow cytometry and as indicated by the upregulation of cleaved­poly (ADP­ribose) polymerase, cleaved­caspase­3, cleaved­caspase­7, BAD and BIM. Mechanistically, the DNA double­strand breaks marker γ­H2AX, and other proteins associated with DNA damage, were investigated, and it was demonstrated that NL­101 in combination with DNR synergistically promoted the DNA damage response. In vivo, this combination significantly delayed the progression of AML and prolonged the survival time in mice. Collectively, the present results suggested that NL­101 in combination with daunorubicin could be an alternative novel therapeutic strategy for treating leukemia.


Assuntos
Cloridrato de Bendamustina/administração & dosagem , Daunorrubicina/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Vorinostat/administração & dosagem , Animais , Cloridrato de Bendamustina/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , Daunorrubicina/farmacologia , Sinergismo Farmacológico , Feminino , Células HL-60 , Humanos , Leucemia Mieloide Aguda/genética , Camundongos , Vorinostat/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Front Oncol ; 9: 1276, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31850196

RESUMO

Previous studies showed that chidamide enhances the cytotoxicity of drugs in acute myeloid leukemia (AML) cells. Therefore, we examined whether chidamide enhanced the cytotoxicity of drugs in AML cells by affecting H3K9me3 and autophagy levels. AML cells (THP-1 and MV4-11 cells) were treated with chidamide, cytarabine (Ara-c), or sorafenib alone or in combination. Cell proliferation and survival rates were analyzed by MTT, flow cytometry, and Western blotting assays. The results showed that a low dose of chidamide enhanced the cytotoxicity of Ara-c or sorafenib in AML cells, decreasing proliferation and increasing apoptosis. H3K9me3 levels as assessed by Western blotting were upregulated by chidamide treatment. Chromatin immunoprecipitation sequencing, which was used to investigate potential signaling pathways, indicated that the autophagy pathway might play a role in the effects of chidamide. The level of autophagy induced in AML cells upon treatment with Ara-c or sorafenib was inhibited by chidamide, and autophagy markers (LC3, P62) were tested by Western blotting. SIRT1 messenger RNA (mRNA) and protein levels were lower in AML cells treated with Ara-c or sorafenib in combination with chidamide than those in cells treated with these drugs alone. Additionally, the Integrative Genomics Viewer results indicate that the H3K9me3 changes were related to SIRT1-binding sites. Together, these results show that chidamide enhances the cytotoxicity of two chemotherapy drugs in AML cells by increasing the H3K9me3 level and inhibiting autophagy via decreasing the expression of SIRT1. Chidamide may be a potential treatment strategy for AML in the future, especially for refractory AML patients.

19.
Medicine (Baltimore) ; 98(39): e17147, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574817

RESUMO

The study aims to examine the treatment effect and adverse reactions of patients with newly diagnosed MM receiving different bortezomib-based regimens.This was a retrospective study of patients with newly diagnosed MM and who were treated with bortezomib-based combined chemotherapy at the Department of Hematology of the 2 affiliated hospitals of Wenzhou Medical University between July 2009 and May 2016. Cox proportion hazard multivariate analyses were carried out to assess the differences in treatment effect and adverse events between standard (1.3 mg/m on days 1, 4, 8, 11) and weekly (1.6 mg/m on days 1, 8, 15) cohorts, as well as the differences between intravenous injection and subcutaneous injection therapy. Progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier method and the log-rank test.Among the 117 patients, 78 patients were treated with bortezomib standard therapy and 39 patients were treated with bortezomib weekly therapy (all with intravenous injection). In all patients, the treatment strategy was not independently associated with PFS or OS. The patients in the weekly therapy group had less thrombocytopenia events than those in the standard therapy group. The subcutaneous route had similar treatment effect as the intravenous route, but the incidence of peripheral neuropathy was lower.The once-weekly bortezomib regimen was similar in effectiveness to standard therapy in treating patients with newly diagnosed MM, but the incidence of thrombocytopenia was lower with the weekly regimen compared with the standard regimen.


Assuntos
Antineoplásicos/administração & dosagem , Bortezomib/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Trombocitopenia/induzido quimicamente , Idoso , Antineoplásicos/efeitos adversos , Bortezomib/efeitos adversos , China , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Estudos Retrospectivos , Resultado do Tratamento
20.
Med Oncol ; 36(9): 77, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31372848

RESUMO

Acute myeloid leukemia (AML) is a devastating disease. Hybrid agents with dual activity, which have been shown to possess anti-cancer effect, are expected to potentially improve the prognosis of AML patients. EDO-S101 is a novel alkylating deacetylase inhibitor molecule synthesized by the addition of the hydroxamic acid of histone deacetylases inhibitor vorinostat into bendamustine, a DNA-damaging agent. However, the effect of EDO-S101 in combination with traditional chemotherapy drugs has not been studied in AML. In this study, we investigated the effect of EDO-S101 in combination with cytarabine in treating AML cells. The synergic activity against AML was identified by remarkable reduction of cell viability, significant apoptosis enhancement and the upregulation of the cleaved PARP, Casepase-3 and -7 proteins compared with monotherapy. To explain the drivers, we detected the DNA damage pathway including DNA double-strand breaks marker γ-H2AX and DNA damage checkpoint proteins, which was supposed to be responsible for the enhanced apoptosis activity. In summary, our data demonstrated that EDO-S101 in combination with cytarabine could synergistically induce the apoptosis of AML cells and it might be a potential regimen for treating leukemia.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Antineoplásicos Alquilantes/farmacologia , Apoptose/efeitos dos fármacos , Benzimidazóis/farmacologia , Citarabina/farmacologia , Inibidores de Histona Desacetilases/farmacologia , Leucemia Mieloide Aguda/patologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/genética , Sinergismo Farmacológico , Humanos , Leucemia Mieloide Aguda/genética , Células Tumorais Cultivadas
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