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1.
J Hazard Mater ; 458: 131646, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37331058

RESUMO

Sufficient levels of thermal, electrical, mechanical, or electrochemical abuse can cause thermal runaway in lithium-ion batteries, leading to the release of electrolyte vapor, combustible gas mixtures, and high-temperature particles. Particle emissions due to thermal failure of batteries may cause serious pollution of the atmosphere, water sources, and soil as well as enter the human biological chain through crops, posing a potential threat to human health. Furthermore, high-temperature particle emissions may ignite the flammable gas mixtures produced during the thermal runaway process, resulting in combustion and explosions. This research focused on determining the particle size distribution, elemental composition, morphology, and crystal structure of particles released from different cathode batteries after thermal runaway. Accelerated adiabatic calorimetry tests were performed on a fully charged Li(Ni0.3Co0.3Mn0.3)O2 battery (NCM111), Li(Ni0.5Co0.2Mn0.3)O2 battery (NCM523), and Li(Ni0.6Co0.2Mn0.2)O2 battery (NCM622). Results of all three batteries indicate that particles with a diameter less than or equal to 0.85 mm exhibit an increase in volume distribution followed by a decrease in volume distribution as the diameter increases. F, S, P, Cr, Ge, and Ge were detected in particle emissions with mass percentages ranging from 6.5% to 43.3%, 0.76-1.20%, 2.41-4.83%,1.8-3.7%, and 0-0.14%, respectively. When present in high concentrations, these may have negative impacts on human health and the environment. In addition, the diffraction patterns of the particle emissions were approximately the same for NC111, NCM523, and NCM622, with emissions primarily composed of Ni/Co elemental, graphite, Li2CO3, NiO, LiF, MnO, and LiNiO2. This study can provide important insights into the potential environmental and health risks associated with particle emissions from thermal runaway in lithium-ion batteries.

2.
Ann Clin Lab Sci ; 51(3): 285-294, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34162557

RESUMO

OBJECTIVE: MicroRNAs (miRNAs) have been confirmed to play an essential role in modulating cancer cell proliferation, metastasis, and sensitivity to chemotherapy. However, the correlation between miR-132-3p expression and etoposide (VP16) induced apoptosis in human breast cancer cells remains poorly understood. METHODS: Six datasets, including three gene expression profile datasets and three microRNA (miRNA) expression profile datasets, were downloaded from the NCBI Gene Expression Omnibus (GEO) database to identify miR-132-3p and GSK3B expression in breast cancer. Kaplan-Meier and log-rank testing were performed to evaluate the effect of miR-132-3p and GSK3B on the survival of breast cancer. Flow cytometry analysis was used to determine the effects of miR-132-3p and GSK3B on breast cancer cell apoptosis. Luciferase reporter assay, Western blot, and real-time PCR were used to determine the regulatory effect of miR-132-3p on GSK3B. RESULTS: miR-132-3p was significantly downregulated in breast cancer tissues compared with normal breast epithelial cells, whereas GSK3B expression was remarkably over-expressed in breast cancer tissues. The patients with low miR-132-3p or high GSK3B expression had worse overall survival. Luciferase reporter assay, Western blot, and real-time PCR confirmed that miR-132-3p could inhibit GSK3B protein and mRNA expression via binding to the 3'-UTR of GSK3B. Furthermore, miR-132-3p enhanced VP16-induced breast cancer cell apoptosis through targeting GSK3B. CONCLUSION: Collectively, the results of this study indicated that miR-132-3p was downregulated in breast cancer tissues and directly targeted GSK3B to be implicated in the modulation of breast cancer cell apoptosis, suggesting that miR-132-3p/GSK3B might be a novel, effective therapeutic target for treating patients with breast cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Etoposídeo/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/metabolismo , MicroRNAs/genética , Neoplasias/patologia , Antineoplásicos Fitogênicos/farmacologia , Apoptose , Biomarcadores Tumorais/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Proliferação de Células , Feminino , Glicogênio Sintase Quinase 3 beta/genética , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas
3.
Medicine (Baltimore) ; 99(45): e22649, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33157920

RESUMO

RATIONALE: Mirizzi syndrome (MS) is an uncommon condition characterized by common hepatic duct (CHD) compression by an impacted gallbladder or cystic duct stones or adjacent inflammation. To date, a standardized therapeutic strategy for MS has not been established yet, owing to its complex clinical presentation. Thus, researchers still have to develop new optimized approaches to solve this problem. Herein, we describe a patient with refractory MS who underwent a successful treatment by novel hybrid anchoring balloon-guided direct peroral cholangioscopy (POC) using an ultraslim endoscope. PATIENT CONCERNS: A 56-year-old man with a history of biliary stone was referred to our hospital for complaints of discomfort in the right upper quadrant of the abdomen and obstructive jaundice. Endoscopic retrograde cholangiopancreatography showed an 18-mm impacted stone at the level of the cystic duct, which compressed the CHD. The CHD had local stricture, with its upstream and intrahepatic bile duct dilation. DIAGNOSES: He was diagnosed with type I MS. INTERVENTIONS: Initially, the patient received an endoscopic major sphincterotomy. However, conventional stone extraction, including mechanical lithotripsy, was unsuccessful. Then, after signing the informed consent form for further treatment, he was successfully treated with novel hybrid anchoring balloon-guided direct POC. OUTCOMES: The patient had no operative complications and was discharged with cleared ducts. At the 3-year follow-up, he was asymptomatic. LESSONS: Our novel hybrid anchoring balloon-guided direct POC may be an effective alternative treatment approach for difficult gallbladder cases, such as refractory MS.


Assuntos
Endoscopia do Sistema Digestório/instrumentação , Litotripsia/métodos , Síndrome de Mirizzi/cirurgia , Desenho de Equipamento , Humanos , Masculino , Pessoa de Meia-Idade
4.
Clin Chem Lab Med ; 59(1): 179-186, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32697751

RESUMO

Objectives: It is important to select proper quality specifications for laboratories and external quality assessment (EQA) providers for their quality control and assessment. The aim of this study is to produce new total error (TE) specifications for lymphocyte subset enumeration by analyzing the allowable TE using EQAS data and comparing them with that based on reliable biological variation (BV). Methods: A total of 54,400 results from 1,716 laboratories were collected from China National EQAS for lymphocyte subset enumeration during the period 2017-2019. The EQA data were grouped according to lower limits of reference intervals for establishing concentration-dependent specifications. The TE value that 80% of laboratories can achieve were considered as TE specifications based on state of the art. The BV studies compliant with Biological Variation Data Critical Appraisal Checklist (BIVAC) were used to calculate the three levels of TE specifications. Then these TE specifications were compared for determining the recommended TE specifications. Results: Four parameters whose quality specifications could achieve the optimum criteria were as follows: the percentages of CD3+, CD3+CD4+ (high concentration) and CD3-CD16/56+ cells, and the absolute count of CD3-CD16/56+ cells. Only the TE specifications of CD3-CD19+ cells could achieve the minimum criteria. The TE specifications of remaining parameters should reach the desirable criteria. Conclusions: New TE specifications were established by combining the EQA data and reliable BV data, which could help laboratories to apply proper criteria for continuous improvement of quality control, and EQA providers to use robust acceptance limits for better evaluation of EQAS results.


Assuntos
Confiabilidade dos Dados , Contagem de Linfócitos/normas , Subpopulações de Linfócitos , China , Humanos , Contagem de Linfócitos/estatística & dados numéricos , Controle de Qualidade
5.
Breast Cancer Res Treat ; 183(2): 429-438, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32647940

RESUMO

PURPOSE: To evaluate the effect of adjuvant chemotherapy on improving the prognosis of patients with stage I triple-negative breast cancer (TNBC). METHODS: TNBC patients diagnosed in the SEER 18 database from 2010 to 2015 were included. Kaplan-Meier plots and log-rank tests were used to compare the differences in breast cancer-specific survival (BCSS) and overall survival (OS) between subgroups of variables. A Cox proportional hazard model was used to determine the prognostic factors affecting BCSS and OS. RESULTS: A total of 9256 patients were enrolled in this study. Among these patients, 380 died from breast cancer, and 703 died from all causes. Patients who received chemotherapy had significantly better BCSS and OS than those who did not receive chemotherapy for stage T1cN0M0 (BCSS, hazard ratio (HR) = 0.68, 95% confidence interval (CI) 0.51-0.90; OS, HR = 0.54, 95% CI 0.44-0.67) and stage IB (BCSS, HR = 0.39, 95% CI 0.16-0.95; OS, HR = 0.41, 95% CI 0.19-0.87) disease. Patients who received chemotherapy did not have significantly better BCSS or OS than those who did not receive chemotherapy for stage T1aN0M0 or T1bN0M0 disease. The patients who received chemotherapy in the poorly differentiated and undifferentiated groups had better BCSS (HR = 0.68, 95% CI 0.52-0.88) and OS (HR = 0.54, 95% CI 0.44-0.66) than the patients who did not receive chemotherapy. CONCLUSION: According to current clinical guidelines, patients with stage T1bN0M0 TNBC are probably overtreated. The prognosis of these patients with stage T1aN0M0 or T1bN0M0 disease is good enough that adjuvant chemotherapy cannot improve it further.


Assuntos
Quimioterapia Adjuvante/métodos , Bases de Dados Factuais/estatística & dados numéricos , Programa de SEER , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia
6.
J Cancer ; 11(4): 858-866, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31949489

RESUMO

Background: Lung cancer is the most common cause of death from cancer worldwide and recent studies have revealed that microRNAs play critical roles to regulate lung carcinogenesis. microRNA-129-5p (miR-129-5p) has been reported to regulate cell proliferation and invasion in lung cancer, but its role in lung cancer apoptosis remains unknown. Methods: The expression of miR-129-5p and YWHAB in lung cancer tissues were analyzed from data downloaded from the NCBI Gene Expression Omnibus (GEO) database. Luciferase reporter assay, Western blot and qRT-PCR were used to determine the regulatory effect of miR-129-5p on YWHAB. Cell apoptosis was detected by using the PI/Annexin V Cell Apoptosis Kit. The effect of miR-129-5p and YWHAB on the survival of lung cancer patients was also explored. Results: In this study, by combining the data derived from six GEO database, our results showed that miR-129-5p was downregulated in lung cancer tissues and YWHAB was upregulated in lung cancer patient' serum. A significant negative correlation between miR-129-5p and YWHAB was found in lung cancer tissues. Both the expression of YWHAB and miR-129-5p were associated significantly with prognosis (overall survival) in patients with lung cancer. Overexpression of miR-129-5p promotes VP16-induced lung cancer cell apoptosis and YWHAB was shown to be a direct downstream target of miR-129-5p. Conclusion: Overexpression of expression miR-129-5p contributes to etoposide-induced lung cancer apoptosis by modulating YWHAB.

7.
Cell Death Dis ; 10(6): 389, 2019 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-31101802

RESUMO

Melanoma is one of the most common skin malignancies. Both microRNAs and long non-coding RNAs (lncRNAs) have critical roles in the progression of cancers, including melanoma. However, the underlying molecular mechanism has not been fully characterized. We demonstrated that miR-34a is negatively correlated with MALAT1 in melanoma cells and tumor specimens. Interestingly, MALAT1, which contains functional sequence-specific miR-34a-binding sites, regulates miR-34a stability in melanoma cells and in vivo. Importantly, MALAT1 was significantly enriched in the Ago2 complex, but not when the MALAT1-binding site of miR-34a was mutated. Furthermore, MALAT1 could be shown to regulate c-Myc and Met expression by functioning as a miR-34a sponge. Our results reveal an unexpected mode of action for MALAT1 as an important regulator of miR-34a.


Assuntos
Melanoma/patologia , RNA Longo não Codificante/metabolismo , Sequência de Aminoácidos , Animais , Antagomirs/metabolismo , Proteínas Argonautas/metabolismo , Sítios de Ligação , Linhagem Celular Tumoral , Humanos , Masculino , Melanoma/genética , Melanoma/terapia , Camundongos , Camundongos Nus , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , MicroRNAs/metabolismo , Mutagênese , Proteínas Proto-Oncogênicas c-met/genética , Proteínas Proto-Oncogênicas c-met/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , RNA Interferente Pequeno/uso terapêutico , Alinhamento de Sequência , Transplante Heterólogo
8.
Cancer Lett ; 404: 44-52, 2017 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-28716524

RESUMO

Apoptosis resistance is an acquired hallmark of cancer cells and many factors can contribute to the tumor cell apoptosis resistance. In this study, we demonstrated that HECTD3, overexpressed in human esophageal squamous cell carcinoma (ESCC), confers cells resistance to cisplatin-induced apoptosis and promotes cancer cell survival. HECTD3 can bind and ubiquitinate caspase-9, which leads to inhibiting caspase-9 oligomerization and association with Apaf-1, and results in suppressing caspase-9 activation and inhibiting apoptosis. Furthermore, this antiapoptotic function of HECTD3 is dependent on its Thr-157 phosphorylation by ERK. HECTD3, but not T157A mutant, facilitates cell survival in ESCC cells in survival assay in vitro and promotes tumor growth in a xenograft mouse model in vivo. These findings establish a new mechanism of cancer cell resistance to apoptosis and provide a new potential strategy for ESCC treatment.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Proliferação de Células , Sobrevivência Celular , Neoplasias Esofágicas/metabolismo , Proteínas de Neoplasias/fisiologia , Ubiquitina-Proteína Ligases/fisiologia , Animais , Apoptose/efeitos dos fármacos , Caspase 9/metabolismo , Linhagem Celular Tumoral , Cisplatino/farmacologia , Modelos Animais de Doenças , Regulação para Baixo , Carcinoma de Células Escamosas do Esôfago , Humanos , Imuno-Histoquímica , Sistema de Sinalização das MAP Quinases/fisiologia , Camundongos , Ubiquitina-Proteína Ligases/metabolismo
9.
Oncotarget ; 7(47): 77764-77776, 2016 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-27780918

RESUMO

Histone H2AX is a tumor suppressor protein that plays an important role in apoptosis. However, the mechanism underlying the association of H2AX with apoptosis in cancer cells remains elusive. Here, we showed that H2AX knockdown in lung cancer A549 cells affected the expression of 16 microRNAs (miRNAs), resulting in the downregulation of 1 and the upregulation of 15 miRNAs. MicroRNA-3196 (miR-3196) was identified as a target of H2AX and shown to inhibit apoptosis in lung cancer cells by targeting p53 upregulated modulator of apoptosis (PUMA). Phosphorylated H2AX (γH2AX) was shown to bind to the promoter of miR-3196 and regulate its expression. In addition, H2AX phosphorylation increased H3K27 trimethylation in the promoter region of miR-3196 and inhibited the binding of RNA polymerase II to the promoter of miR-3196, leading to the inhibition of miR-3196 transcription. Taken together, these results indicated that H2AX phosphorylation regulates apoptosis in lung cancer cells via the miR-3196/PUMA pathway.


Assuntos
Proteínas Reguladoras de Apoptose/genética , Histonas/metabolismo , Neoplasias Pulmonares/genética , MicroRNAs/genética , Proteínas Proto-Oncogênicas/genética , Células A549 , Apoptose , Linhagem Celular Tumoral , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , Fosforilação , Regiões Promotoras Genéticas
10.
Photodiagnosis Photodyn Ther ; 14: 119-27, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26607555

RESUMO

5-Aminolaevulinic acid-based photodynamic therapy (ALA-PDT) has been used for part of squamous cell carcinoma (premalignant conditions or in situ cutaneous SCC-Bowen disease). However, mechanism of ALA-PDT is not fully understood yet on the cell apoptosis pathway. The aim of this study was to further investigate the effect and mechanism of 5-ALA-PDT on human squamous carcinoma A431cells. Apoptosis and cell viability after PDT were evaluated using Annexin V-FITC apoptosis detection kit and MTT assay. The mRNA and protein levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Our data showed that 5-ALA-PDT significantly inhibited cell proliferation (p<0.05), but there was no significant difference when the photosensitizer reached to 4.8mM. The inhibition in cell proliferation after 5-ALA-PDT treatment was correlated to more cells being arrested in the G0/G1 phase of the cell cycle (p<0.01). Immunocytochemical observations using anti-active caspase-3 antibodies showed active caspase-3 was translocated from cytoplasm to nuclear during apoptosis. STAT3 and its downstream gene Bax and BCL-2 were changed after 5-ALA-PDT treatment for the mRNA and protein expression. Our studies confirmed that 5-ALA-PDT might be an effective treatment for human squamous carcinoma by inhibiting the tumor cell A431growth and for the first time demonstrated that the expression of STAT3 was significantly reduced at 24h after 5-ALA-PDT treatment.


Assuntos
Ácido Aminolevulínico/uso terapêutico , Carcinoma de Células Escamosas/terapia , Fármacos Fotossensibilizantes/uso terapêutico , Fator de Transcrição STAT3 , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Reação em Cadeia da Polimerase , Fator de Transcrição STAT3/efeitos dos fármacos , Fator de Transcrição STAT3/efeitos da radiação , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação
11.
Mol Med Rep ; 13(1): 505-12, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26572100

RESUMO

Micro (mi)RNAs are short non­coding RNA molecules, which post­transcriptionally regulate gene expression and exert key roles in cell growth, differentiation and apoptosis. In the present study, the mechanism and the function of miR­1915­3p in the apoptotic regulation of lung cancer cell lines (NCI­H441 and NCI­H1650) were investigated. The expression analysis confirmed that the expression of miR­1915­3p was markedly decreased in the apoptotic cells. The overexpression of miR­1915­3p in the lung cancer cells prevented apoptosis induced by etoposide. Developmentally regulated GTP­binding protein 2 (DRG2) and pre­B cell leukemia homeobox 2 (PBX2) were identified as downstream targets of miR­1915­3p, which was shown to bind directly to the 3'­untranslated region of DRG2 and PBX2, subsequently lowering their mRNA and protein expression levels. Co­expression of miR­1915­3p and DRG2/PBX2 in the NCI­H441 and NCI­H1650 cells partly circumvented the effect of miR­1915­3p on apoptosis. The results in the present study revealed that miR­1915­3p functions as a silencer of apoptosis, which regulates lung cancer apoptosis via targeting DRG2/PBX2, and consequently this miRNA may be a putative therapeutic target in lung cancer.


Assuntos
Apoptose/genética , Regulação para Baixo/genética , Proteínas de Ligação ao GTP/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas/genética , Sequência de Bases , Linhagem Celular Tumoral , Proteínas de Ligação ao GTP/metabolismo , Proteínas de Homeodomínio/metabolismo , Humanos , MicroRNAs/genética , Dados de Sequência Molecular , Proteínas Proto-Oncogênicas/metabolismo
12.
Am J Cancer Res ; 5(3): 1180-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26045996

RESUMO

MicroRNAs play key roles in cell growth, differentiation, and apoptosis. In this study, we described the regulation and function of miR-1469 in apoptosis of lung cancer cells (A549 and NCI-H1650). Expression analysis verified that miR-1469 expression significantly increased in apoptotic cells. Overexpression of miR-1469 in lung cancer cells increased cell apoptosis induced by etoposide. Additionally, we identified that Stat5a is a downstream target of miR-1469, which can bind directly to the 3'-untranslated region of the Stat5a, subsequently reducing both the mRNA and protein levels of Stat5a. Finally, co-expression of miR-1469 and Stat5a in A549 and NCI-H1650 cells partially abrogated the effect of miR-1469 on cell apoptosis. Our results show that miR-1469 functions as an apoptosis enhancer to regulate lung cancer apoptosis through targeting Stat5a and may become a critical therapeutic target in lung cancer.

13.
Acta Pharmacol Sin ; 36(3): 353-61, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25619392

RESUMO

AIM: The phosphorylation of histone H2AX, a novel tumor suppressor protein, is involved in regulation of cancer cell apoptosis. The aim of this study was to examine whether H2AX phosphorylation was required for resveratrol-induced apoptosis of human chronic myelogenous leukemia (CML) cells in vitro. METHODS: K562 cells were tested. Cell apoptosis was analyzed using flow cytometry, and the phosphorylation of H2AX and other signaling proteins was examined with Western blotting. To analyze the signaling pathways, the cells were transfected with lentiviral vectors encoding H2AX-wt or specific siRNAs. RESULTS: Treatment of K562 cells with resveratrol (20-100 µmol/L) induced apoptosis and phosphorylation of H2AX at Ser139 in time- and dose-dependent manners, but reduced phosphorylation of histone H3 at Ser10. Resveratrol treatment activated two MAPK family members p38 and JNK, and blocked the activation of another MAPK family member ERK. Pretreatment with the p38 inhibitor SB202190 or the JNK inhibitor SP600125 dose-dependently reduced resveratrol-induced phosphorylation of H2AX, which were also observed when the cells were transfected with p38- or JNK-specific siRNAs. Overexpression of H2AX in K562 cells markedly increased resveratrol-induced apoptosis, whereas overexpression of H2AX-139m (Ser139 was mutated to block phosphorylation) inhibited resveratrol-induced apoptosis. K562 cells transfected with H2AX-specific siRNAs were resistant to resveratrol-induced apoptosis. CONCLUSION: H2AX phosphorylation at Ser139 in human CML cells, which is regulated by p38 and JNK, is essential for resveratrol-induced apoptosis.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Histonas/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Estilbenos/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Relação Dose-Resposta a Droga , Histonas/genética , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/enzimologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Interferência de RNA , Resveratrol , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Transfecção , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores
14.
Int J Clin Exp Med ; 8(10): 17712-20, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26770361

RESUMO

A total of 440 patients from 10 studies were included in a systematic review to evaluate the association between improved survivals from multiple organ dysfunction syndromes in patients undergoing surgical operation. Health Inter Network Initiatives (HINARI), MEDLINE and EMBASE were searched. Exclusion criteria were duplicate publications, non-human experimental studies, and no mortality data. The primary endpoint was postoperative mortality. Levosimendan was found to be associated with a reduction in postoperative mortality (11/235 [4.7%] in the levosimendan group v 26/205 [12.7%] in the control, odds ratio of 0.35 [0.18-0.71], P for effect as 0.003, P for heterogeneity 0.22, and I(2) as 27.4% (440 patients included), cardiac troponin release, and atrial fibrillation. No difference was found in terms of myocardial infarction, acute renal failure, time on mechanical ventilation, intensive care unit, and hospital stay. Calcium-sensitizer for congestive heart failure; Levosimendan has cardioprotective effects that could result in a reduced operative mortality.

15.
Apoptosis ; 19(8): 1281-92, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24830786

RESUMO

Increasing evidence suggests that histone H2AX plays a critical role in regulation of tumor cell apoptosis and acts as a novel human tumor suppressor protein. However, the action of H2AX in chronic myelogenous leukemia (CML) cells is unknown. The detailed mechanism and epigenetic regulation by H2AX remain elusive in cancer cells. Here, we report that H2AX was involved in apoptosis of CML cells. Overexpression of H2AX increased apoptotic sensitivity of CML cells (K562) induced by imatinib. However, overexpression of Ser139-mutated H2AX (blocking phosphorylation) decreased sensitivity of K562 cells to apoptosis. Similarly, knockdown of H2AX made K562 cells resistant to apoptotic induction. These results revealed that the function of H2AX involved in apoptosis is strictly related to its phosphorylation (Ser139). Our data further indicated that imatinib may stimulate mitogen-activated protein kinase (MAPK) family member p38, and H2AX phosphorylation followed a similar time course, suggesting a parallel response. H2AX phosphorylation can be blocked by p38 siRNA or its inhibitor. These data demonstrated that H2AX phosphorylation was regulated by p38 MAPK pathway in K562 cells. However, the p38 MAPK downstream, mitogen- and stress-activated protein kinase-1 and -2, which phosphorylated histone H3, were not required for H2AX phosphorylation during apoptosis. Finally, we provided epigenetic evidence that H2AX phosphorylation regulated apoptosis-related gene Bim expression. Blocking of H2AX phosphorylation inhibited Bim gene expression. Taken together, these data demonstrated that H2AX phosphorylation regulated by p38 is involved in Bim expression and apoptosis in CML cells induced by imatinib.


Assuntos
Antineoplásicos/farmacologia , Proteínas Reguladoras de Apoptose/metabolismo , Apoptose/efeitos dos fármacos , Benzamidas/farmacologia , Histonas/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Proteínas de Membrana/metabolismo , Piperazinas/farmacologia , Proteínas Proto-Oncogênicas/metabolismo , Pirimidinas/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteínas Reguladoras de Apoptose/genética , Proteína 11 Semelhante a Bcl-2 , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Epigênese Genética , Humanos , Mesilato de Imatinib , Células K562/efeitos dos fármacos , Proteínas de Membrana/genética , Fosforilação , Proteínas Proto-Oncogênicas/genética
16.
Am J Cancer Res ; 4(2): 89-115, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24660101

RESUMO

S100 protein family has been implicated in multiple stages of tumorigenesis and progression. Among the S100 genes, 22 are clustered at chromosome locus 1q21, a region frequently rearranged in cancers. S100 protein possesses a wide range of intracellular and extracellular functions such as regulation of calcium homeostasis, cell proliferation, apoptosis, cell invasion and motility, cytoskeleton interactions, protein phosphorylation, regulation of transcriptional factors, autoimmunity, chemotaxis, inflammation and pluripotency. Many lines of evidence suggest that altered expression of S100 proteins was associated with tumor progression and prognosis. Therefore, S100 proteins might also represent potential tumor biomarkers and therapeutic targets. In this review, we summarize the evidence connecting S100 protein family and cancer and discuss the mechanisms by which S100 exerts its diverse functions.

17.
J Biol Chem ; 289(13): 9089-99, 2014 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-24532790

RESUMO

The S100 protein family represents the largest subgroup of calcium binding EF-hand type proteins. These proteins have been reported to be involved in a wide range of biological functions that are related to normal cell development and tumorigenesis. S100A14 is a recently identified member of the S100 protein family and differentially expressed in a number of different human malignancies. However, the transcriptional regulation of S100A14 and its role in breast cancer needs to be further investigated. Here, we determined that 12-O-tetradecanoylphorbol-13-acetate (TPA) up-regulated the expression of KLF4 and facilitated its binding directly to two conserved GC-rich DNA segments within the S100A14 promoter, which is essential for the transactivation of KLF4 induced S100A14 expression. Furthermore, stable silencing of KLF4 significantly suppressed breast cancer cell migration induced by TPA. Collectively, these results offer insights into the fact that TPA provokes cell motility through regulating the expression and function of S100A14 in a KLF4-dependent manner.


Assuntos
Neoplasias da Mama/patologia , Proteínas de Ligação ao Cálcio/metabolismo , Movimento Celular/efeitos dos fármacos , Fatores de Transcrição Kruppel-Like/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Animais , Sequência de Bases , Sítios de Ligação , Proteínas de Ligação ao Cálcio/deficiência , Proteínas de Ligação ao Cálcio/genética , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inativação Gênica , Humanos , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/deficiência , Fatores de Transcrição Kruppel-Like/genética , Camundongos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Tempo
18.
J Biol Chem ; 289(2): 827-37, 2014 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-24285542

RESUMO

HER2 is overexpressed in 20­25% of breast cancers. Overexpression of HER2 is an adverse prognostic factor and correlates with decreased patient survival. HER2 stimulates breast tumorigenesis via a number of intracellular signaling molecules, including PI3K/AKT and MAPK/ERK.S100A14,one member of the S100 protein family, is significantly associated with outcome of breast cancer patients. Here, for the first time, we show that S100A14 and HER2 are coexpressed in invasive breast cancer specimens,andthere is a significant correlation between the expression levels of the two proteins by immunohistochemistry. S100A14 and HER2 are colocalized in plasma membrane of breast cancer tissue cells and breast cancer cell lines BT474 and SK-BR3. We demonstrate that S100A14 binds directly to HER2 by co-immunoprecipitation and pull-down assays. Further study shows that residues 956­1154 of the HER2 intracellular domain and residue 83 of S100A14 are essential for the two proteins binding.Moreover,we observe a decrease of HER2 phosphorylation, downstream signaling, and HER2-stimulated cell proliferation in S100A14-silenced MCF-7, BT474, and SK-BR3 cells. Our findings suggest that S100A14 functions as a modulator of HER2 signaling and provide mechanistic evidence for its role in breast cancer progression.


Assuntos
Neoplasias da Mama/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Carcinoma Ductal de Mama/metabolismo , Receptor ErbB-2/metabolismo , Transdução de Sinais , Western Blotting , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Proteínas de Ligação ao Cálcio/genética , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/patologia , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Proliferação de Células , Motivos EF Hand/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Células MCF-7 , Microscopia Confocal , Pessoa de Meia-Idade , Ligação Proteica , Receptor ErbB-2/genética
19.
Mol Cancer Res ; 11(12): 1542-53, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24107296

RESUMO

UNLABELLED: Aberrant keratinocyte differentiation is a key mechanism in the initiation of cancer. Because activities regulating differentiation exhibit altered or reduced capacity in esophageal cancer cells, it is vital to pinpoint those genes that control epidermal proliferation and terminal differentiation to better understand esophageal carcinogenesis. S100A14 is a member of the S100 calcium-binding protein family and has been suggested to be involved in cell proliferation, apoptosis, and invasion. The present study used immunohistochemistry analysis of S100A14 in clinical specimens of esophageal squamous cell carcinoma (ESCC) to show that decreased S100A14 is strongly correlated with poor differentiation. Furthermore, both mRNA and protein expression of S100A14 was drastically increased upon 12-O-tetra-decanoylphorbol-13-acetate (TPA) and calcium-induced esophageal cancer cell differentiation. Overexpression of S100A14 resulted in a G1-phase cell cycle arrest and promoted calcium-inhibited cell growth. Conversely, decreasing S100A14 expression significantly promoted G1-S transition and prevented the morphologic changes associated with calcium-induced cell differentiation. Molecular investigation demonstrated that S100A14 altered the calcium-induced expression of late markers of differentiation, with the most prominent effect on involucrin (IVL) and filaggrin (FLG). Finally, it was determined that S100A14 is transcriptionally regulated by JunB and that S100A14 and JunB status significantly correlated in ESCC tissue. In summary, these data demonstrate that S100A14 is transcriptionally regulated by JunB and involved in ESCC cell differentiation. IMPLICATIONS: This study further differentiates the molecular mechanism controlling the development and progression of esophageal cancer.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Carcinoma de Células Escamosas/patologia , Transformação Celular Neoplásica , Neoplasias Esofágicas/patologia , Fatores de Transcrição/metabolismo , Cálcio/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago , Proteínas Filagrinas , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Proteínas de Filamentos Intermediários/metabolismo , Gradação de Tumores , Estadiamento de Neoplasias , Precursores de Proteínas/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo
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