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1.
Comput Methods Programs Biomed ; 250: 108176, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38677081

RESUMO

BACKGROUND AND OBJECTIVE: Interleukin-6 (IL-6) is the critical factor of early warning, monitoring, and prognosis in the inflammatory storm of COVID-19 cases. IL-6 inducing peptides, which can induce cytokine IL-6 production, are very important for the development of diagnosis and immunotherapy. Although the existing methods have some success in predicting IL-6 inducing peptides, there is still room for improvement in the performance of these models in practical application. METHODS: In this study, we proposed UsIL-6, a high-performance bioinformatics tool for identifying IL-6 inducing peptides. First, we extracted five groups of physicochemical properties and sequence structural information from IL-6 inducing peptide sequences, and obtained a 636-dimensional feature vector, we also employed NearMiss3 undersampling method and normalization method StandardScaler to process the data. Then, a 40-dimensional optimal feature vector was obtained by Boruta feature selection method. Finally, we combined this feature vector with extreme randomization tree classifier to build the final model UsIL-6. RESULTS: The AUC value of UsIL-6 on the independent test dataset was 0.87, and the BACC value was 0.808, which indicated that UsIL-6 had better performance than the existing methods in IL-6 inducing peptide recognition. CONCLUSIONS: The performance comparison on independent test dataset confirmed that UsIL-6 could achieve the highest performance, best robustness, and most excellent generalization ability. We hope that UsIL-6 will become a valuable method to identify, annotate and characterize new IL-6 inducing peptides.


Assuntos
Biologia Computacional , Interleucina-6 , Peptídeos , Humanos , Peptídeos/química , Biologia Computacional/métodos , COVID-19 , Algoritmos , Aprendizado de Máquina , SARS-CoV-2
2.
Updates Surg ; 76(3): 899-910, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38526694

RESUMO

Therapeutic options for large or locally advanced hepatocellular carcinoma (HCC) have limited efficacy. This study investigated the efficacy and safety of drug-eluting beads trans-arterial chemo-embolization (dTACE), portal vein embolization (PVE), tyrosine kinase inhibitor (TKI), and immune checkpoint inhibitors (ICI) compared to Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) for large or locally advanced HCC.Data regarding clinicopathological details, safety, and oncological outcomes were reviewed for the quadruple therapy (dTACE-PVE-TKI-ICI) and compared with ALPPS.From 2019 to 2020, 10 patients with large or locally advanced HCC underwent future remnant liver (FRL) modulation (dTACE-PVE-TKI-ICI: 5; ALPPS: 5). All five dTACE-PVE-TKI-ICI cases responded well, with patients #4 and #5 achieving complete tumor necrosis. The overall response rate (ORR) was 5/5. Patients #1-4 underwent hepatectomy, while #5 declined surgery due to complete tumor necrosis. Mean FRL volume increased by 75.3% (range 60.0%-89.4%) in 2-4 months, compared to 104.6% (range 51.3%-160.8%) in 21-37 days for ALPPS (P = 0.032). Major postoperative complications occurred in 1/5 ALPPS patients. Resection rates were 4/4 for quadruple therapy and 5/5 for ALPPS. 2-year progression free survival for dTACE-PVE-TKI-ICI and ALPPS were 5/5 and 3/5, respectively.Quadruple therapy is a feasible, effective strategy for enhancing resectability by downsizing tumors and inducing FRL hypertrophy, with manageable complications and improved long-term prognosis. In addition, it provokes the re-examination of the application of ALPPS in an era of molecular and immune treatments.


Assuntos
Carcinoma Hepatocelular , Hepatectomia , Imunoterapia , Neoplasias Hepáticas , Veia Porta , Humanos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Hepatectomia/métodos , Imunoterapia/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Ligadura/métodos , Idoso , Resultado do Tratamento , Inibidores de Checkpoint Imunológico/uso terapêutico , Quimioembolização Terapêutica/métodos , Terapia Combinada , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/administração & dosagem , Adulto
3.
Hepatobiliary Surg Nutr ; 13(1): 3-15, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38322199

RESUMO

Background: We aim to investigate the prevalence, patterns, risk factors, and outcomes of peritoneal metastases (PM) after curative laparoscopic hepatectomy (LH) for hepatocellular carcinoma (HCC). Methods: A multicenter cohort of 2,138 HCC patients who underwent curative LH from August 2010 to December 2016 from seven hospitals in China was retrospectively analyzed. The incidence of PM following LH was evaluated and compared with that in open hepatectomy (OH) after 1:1 propensity score matching (PSM). Results: PM prevalence was 5.1% (15/295) in the early period [2010-2013], 2.6% (47/1,843) in the later period [2014-2016], and 2.9% (62/2,138) in all LH patients, which was similar to 4.0% (59/1,490) in the OH patients. The recurrence patterns, timing, and treatment did not significantly vary between the LH and OH patients (P>0.05). Multivariate logistic regression revealed that tumor diameter >5 cm, non-anatomical resection, presence of microvascular invasion, and lesions <2 cm from major blood vessels were independent risk factors of PM after LH. Of the 62 cases with PM, 26 (41.9%) had PM only, 34 (54.9%) had intrahepatic recurrence (IHR) and PM, and 2 (3.2%) had synchronous extraperitoneal metastases (EPM). Patients with resectable PM had a 5-year overall survival (OS) of 65.0% compared to 9.0% for unresectable PM (P=0.001). Conclusions: The prevalence, patterns and independent risk factors of PM were identified for HCC patients after LH. LH was not associated with increased incidence of PM in HCC patients for experienced surgeons. Surgical re-excision of PM was associated with prolonged survival.

4.
Cell Death Differ ; 30(7): 1648-1665, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37117273

RESUMO

Cancer stem cells (CSCs) are a minority population of cancer cells with stemness and multiple differentiation potentials, leading to cancer progression and therapeutic resistance. However, the concrete mechanism of CSCs in hepatocellular carcinoma (HCC) remains obscure. We found that in advanced HCC tissues, collagen I was upregulated, which is consistent with the expression of its receptor DDR1. Accordingly, high collagen I levels accompanied by high DDR1 expression are associated with poor prognoses in patients with HCC. Collagen I-induced DDR1 activation enhanced HCC cell stemness in vitro and in vivo. Mechanistically, DDR1 interacts with CD44, which acts as a co-receptor that amplifies collagen I-induced DDR1 signaling, and collagen I-DDR1 signaling antagonized Hippo signaling by facilitating the recruitment of PP2AA to MST1, leading to exaggerated YAP activation. The combined inhibition of DDR1 and YAP synergistically abrogated HCC cell stemness in vitro and tumorigenesis in vivo. A radiomic model based on T2 weighted images can noninvasively predict collagen I expression. These findings reveal the molecular basis of collagen I-DDR1 signaling inhibiting Hippo signaling and highlight the role of CD44/DDR1/YAP axis in promoting cancer cell stemness, suggesting that DDR1 and YAP may serve as novel prognostic biomarkers and therapeutic targets in HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/metabolismo , Via de Sinalização Hippo , Neoplasias Hepáticas/metabolismo , Linhagem Celular Tumoral , Colágeno/uso terapêutico , Receptor com Domínio Discoidina 1/metabolismo
5.
BMC Bioinformatics ; 22(Suppl 3): 457, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34560840

RESUMO

BACKGROUND: As one of the deadliest diseases in the world, cancer is driven by a few somatic mutations that disrupt the normal growth of cells, and leads to abnormal proliferation and tumor development. The vast majority of somatic mutations did not affect the occurrence and development of cancer; thus, identifying the mutations responsible for tumor occurrence and development is one of the main targets of current cancer treatments. RESULTS: To effectively identify driver genes, we adopted a semi-local centrality measure and gene mutation effect function to assess the effect of gene mutations on changes in gene expression patterns. Firstly, we calculated the mutation score for each gene. Secondly, we identified differentially expressed genes (DEGs) in the cohort by comparing the expression profiles of tumor samples and normal samples, and then constructed a local network for each mutation gene using DEGs and mutant genes according to the protein-protein interaction network. Finally, we calculated the score of each mutant gene according to the objective function. The top-ranking mutant genes were selected as driver genes. We name the proposed method as mutations effect and network centrality. CONCLUSIONS: Four types of cancer data in The Cancer Genome Atlas were tested. The experimental data proved that our method was superior to the existing network-centric method, as it was able to quickly and easily identify driver genes and rare driver factors.


Assuntos
Neoplasias , Redes Reguladoras de Genes , Humanos , Mutação , Neoplasias/genética
6.
Chin Med J (Engl) ; 133(20): 2410-2414, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32842015

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak occurred during the flu season around the world. This study aimed to analyze the impact of influenza A virus (IAV) exposure on COVID-19. METHODS: Seventy COVID-19 patients admitted to the hospital during January and February 2020 in Wuhan, China were included in this retrospective study. Serum tests including respiratory pathogen immunoglobulin M (IgM) and inflammation biomarkers were performed upon admission. Patients were divided into common, severe, and critical types according to disease severity. Symptoms, inflammation indices, disease severity, and fatality rate were compared between anti-IAV IgM-positive and anti-IAV IgM-negative groups. The effects of the empirical use of oseltamivir were also analyzed in both groups. For comparison between groups, t tests and the Mann-Whitney U test were used according to data distribution. The Chi-squared test was used to compare disease severity and fatality between groups. RESULTS: Thirty-two (45.71%) of the 70 patients had positive anti-IAV IgM. Compared with the IAV-negative group, the positive group showed significantly higher proportions of female patients (59.38% vs. 34.21%, χ = 4.43, P = 0.035) and patients with fatigue (59.38% vs. 34.21%, χ = 4.43, P = 0.035). The levels of soluble interleukin 2 receptor (median 791.00 vs. 1075.50 IU/mL, Z = -2.70, P = 0.007) and tumor necrosis factor α (median 10.75 vs. 11.50 pg/mL, Z = -2.18, P = 0.029) were significantly lower in the IAV-positive group. Furthermore, this group tended to have a higher proportion of critical patients (31.25% vs. 15.79%, P = 0.066) and a higher fatality rate (21.88% vs. 7.89%, P = 0.169). Notably, in the IAV-positive group, patients who received oseltamivir had a significantly lower fatality rate (0 vs. 36.84%, P = 0.025) compared with those not receiving oseltamivir. CONCLUSIONS: The study suggests that during the flu season, close attention should be paid to the probability of IAV exposure in COVID-19 patients. Prospective studies with larger sample sizes are needed to clarify whether IAV increases the fatality rate of COVID-19 and to elucidate any benefits of empirical usage of oseltamivir.


Assuntos
Betacoronavirus , Infecções por Coronavirus/mortalidade , Vírus da Influenza A , Influenza Humana/complicações , Pneumonia Viral/mortalidade , Adulto , Idoso , Anticorpos Antivirais/sangue , COVID-19 , Feminino , Humanos , Imunoglobulina M/sangue , Vírus da Influenza A/imunologia , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de Doença
7.
Asian J Surg ; 43(5): 603-612, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31611103

RESUMO

BACKGROUND: The impact of bile leakage (BL) on the long-term prognosis in patients with primary liver cancers after hepatectomy remains unclear. METHODS: One thousand nine hundred and seventy-one consecutive patients with primary liver cancers who underwent curative hepatectomy were enrolled. 75 patients encountered BL, including 34 long-time BL (LTBL) and 41 short-time BL (STBL) according to 4-weeks demarcation. Variables associated with BL were identified using multiple logistic regression analysis. 75 patients without BL were enrolled into the Non-BL group using a one-to-one propensity score matched analysis before assessing the impact of BL on the long-term prognosis. The levels of interleukin-6 (IL-6) and C-reactive protein (CRP) in the serum and drain fluid were detected and compared. RESULTS: The tumor size, type of liver cancer, operation time, blood loss and blood transfusion were independent risk factors for BL. The long-term survival showed no difference between the patients with and without BL (p > 0.05), while the LTBL was a significant predictor of poor long-term prognosis (p < 0.001). Compared with the patients without BL, the patients with BL had a higher level of IL-6 from postoperative day (POD) 1 to POD 60, and a higher level of CRP from POD 7 to POD 60. By POD 60, the levels of IL-6 and CRP hadn't restored to the normal level in the LTBL group. CONCLUSIONS: The LTBL has a negative impact on the long-term prognosis of patients with primary liver cancers after hepatectomy, in which the inflammatory responses may play a pivotal role.


Assuntos
Fístula Anastomótica , Bile , Hepatectomia , Neoplasias Hepáticas/cirurgia , Pontuação de Propensão , Adulto , Fístula Anastomótica/etiologia , Perda Sanguínea Cirúrgica , Transfusão de Sangue , Proteína C-Reativa , Feminino , Humanos , Interleucina-6/sangue , Neoplasias Hepáticas/mortalidade , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Prognóstico , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo
8.
J Infect Chemother ; 25(12): 1074-1077, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31401030

RESUMO

Enterovirus 71 (EV71), a newly emerging life-threatening pathogen induces hand-foot-mouth disease (HFMD), no effective vaccines or specific anti-viral treatments are currently available. In this study, the activity of hederacolchiside C (HSC) against EV71 was investigated, and the antiviral mechanism was explored. HSC displayed apparent antiviral activity in EV71-infected cells probably through activating the host innate immunity. Comparing with EV71-infected group at 24 hpi, the group pretreated with HSC dramatically increased the expression of MAVS, p-IRF3, IRF3 and IFN-ß, the innate immune effectors related to innate immunity. In addition, HSC displayed stronger antiviral activity in EV71-infected suckling mice in comparison with Ribavirin, a broad-spectrum antiviral drug. The results suggest that HSC could have potential as a pharmaceutical drug for HFMD.


Assuntos
Antivirais/farmacologia , Enterovirus Humano A/imunologia , Doença de Mão, Pé e Boca/tratamento farmacológico , Pulsatilla/química , Saponinas/farmacologia , Animais , Antivirais/uso terapêutico , Linhagem Celular Tumoral , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Enterovirus Humano A/efeitos dos fármacos , Doença de Mão, Pé e Boca/imunologia , Doença de Mão, Pé e Boca/virologia , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Camundongos , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/farmacologia , Ácido Oleanólico/uso terapêutico , Saponinas/uso terapêutico , Replicação Viral/efeitos dos fármacos , Replicação Viral/imunologia
9.
Cell Death Dis ; 10(2): 60, 2019 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-30683838

RESUMO

The authors have retracted the article [Hsa-miR-623 suppresses tumor progression in human lung adenocarcinoma, Cell Death & Disease volume 7, page e2388 (2016), doi 10.1038/cddis.2016.260] because it has recently come to their attention that the A549 cells used in this research were contaminated with Hela cells, which may have altered the outcome of their experiment. The conclusions of this article are therefore unreliable. All authors agree to this retraction.

10.
Mol Brain ; 12(1): 6, 2019 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-30683131

RESUMO

Tuberous sclerosis complex (TSC) is a neurogenetic disorder associated with epilepsy, intellectual disabilities, and autistic behaviors. These neurological symptoms result from synaptic dysregulations, which shift a balance between excitation and inhibition. To decipher the synaptic substrate of hyperexcitability, we examined pan-neuronal Tsc1 knockout mouse and found a reduction in surface expression of a GABA receptor (GABAR) subunit but not AMPA receptor (AMPAR) subunit. Using electrophysiological recordings, we found a significant reduction in the frequency of GABAR-mediated miniature inhibitory postsynaptic currents (GABAR-mIPSCs) but not AMPAR-mediated miniature excitatory postsynaptic currents (AMPAR-mEPSCs) in layer 2/3 pyramidal neurons. To determine a subpopulation of interneurons that are especially vulnerable to the absence of TSC1 function, we also analyzed two strains of conditional knockout mice targeting two of the prominent interneuron subtypes that express parvalbumin (PV) or somatostatin (SST). Unlike pan-neuronal knockout mice, both interneuron-specific Tsc-1 knockout mice did not develop spontaneous seizures and grew into adults. Further, the properties of AMPAR-mEPSCs and GABAR-mIPSCs were normal in both Pv-Cre and Sst-Cre x Tsc1fl/fl knockout mice. These results indicate that removal of TSC1 from all neurons in a local cortical circuit results in hyperexcitability while connections between pyramidal neurons and interneurons expressing PV and SST are preserved in the layer 2/3 visual cortex. Our study suggests that another inhibitory cell type or a combination of multiple subtypes may be accountable for hyperexcitability in TSC.


Assuntos
Córtex Cerebral/fisiopatologia , Fenômenos Eletrofisiológicos , Rede Nervosa/fisiopatologia , Esclerose Tuberosa/fisiopatologia , Animais , Biotinilação , Células Cultivadas , Cruzamentos Genéticos , Modelos Animais de Doenças , Integrases/metabolismo , Camundongos Knockout , Neurônios/metabolismo , Células Piramidais/metabolismo , Córtex Visual/fisiopatologia
11.
Cell Death Dis ; 9(8): 829, 2018 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-30082717

RESUMO

Following publication of their article, the authors noticed that there were minor errors in Figs. 3, 7 and S5. The errors had no effect on the scientific content or conclusions. The rectified figures are given below.

12.
Chem Biodivers ; 14(10)2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28695650

RESUMO

A novel tropoloisoquinoline alkaloid, neotatarine (1), was isolated from the 95% ethanol extract of the rhizome parts of Acorus calamus L. The chemical structure was unambiguously elucidated by spectroscopic and single-crystal X-ray diffraction analysis. Neotatarine (1) exhibited significantly inhibitory activity against Aß25 - 35 induced PC12 cell death with 2, 4 and 8 µm comparing with the assay control (P < 0.01).


Assuntos
Acorus/química , Peptídeos beta-Amiloides/antagonistas & inibidores , Isoquinolinas/farmacologia , Fragmentos de Peptídeos/antagonistas & inibidores , Tropolona/análogos & derivados , Animais , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Isoquinolinas/química , Isoquinolinas/isolamento & purificação , Estrutura Molecular , Células PC12 , Ratos , Relação Estrutura-Atividade , Tropolona/química , Tropolona/isolamento & purificação , Tropolona/farmacologia
13.
Cell Death Dis ; 8(5): e2829, 2017 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-28542138

RESUMO

This corrects the article DOI: 10.1038/cddis.2016.260.

14.
J Asian Nat Prod Res ; 19(4): 402-415, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27454107

RESUMO

The present study was undertaken to investigate whether hederacochiside C (HSC) possesses antischistosomal effects and anti-inflammatory response activities in Schistosoma japonicum-infected mice. Different concentrations of HSC were administrated to the mice infected by schistosomula or adult worm by intravenous injection twice a day for five consecutive days. The total worm burden, female worm burden, and the egg burden in liver of mice treated with 400 mg/kg HSC were fewer than those in non-treated ones. Murine immune responses following HSC treatment were investigated using enzyme-linked immunosorbent assays (ELISA). Our results indicated that 200 mg/kg HSC could reduce the expression of IgG, tumor necrosis factor (TNF)-α, interleukin (IL)-4 and IL-17 in comparison to infected group, exhibiting best immunomodulatory effects. In addition, scanning electron microscopical examination revealed that male worms treated with HSC lost their normal surface architecture since its surface showed extensive swelling, erosion, and peeling in tegumental regions. Remarkable amelioration was noticed in histopathological investigations, and 200 mg/kg HSC treatment could reduce the size of granulomatous inflammatory infiltrations in the liver which was reflected in nearly normalization of liver architecture. These results suggested that HSC had potential antischistosomal activity and provided a basis for subsequent experimental.


Assuntos
Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Saponinas/isolamento & purificação , Saponinas/farmacologia , Schistosoma japonicum/efeitos dos fármacos , Esquistossomicidas/isolamento & purificação , Esquistossomicidas/farmacologia , Animais , Anti-Inflamatórios/química , Feminino , Humanos , Imunoglobulina G/efeitos dos fármacos , Interleucina-17/metabolismo , Interleucina-4/metabolismo , Fígado/patologia , Masculino , Camundongos , Estrutura Molecular , Saponinas/química , Esquistossomicidas/química , Fator de Necrose Tumoral alfa/efeitos dos fármacos
15.
J Huazhong Univ Sci Technolog Med Sci ; 36(5): 667-676, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27752888

RESUMO

The function of the spleen in tumor development has been investigated for years. The relationship of the spleen with hepatocellular carcinoma (HCC), a huge health burden worldwide, however, remains unknown. The present study aimed to examine the effect of splenectomy on the development of HCC and the possible mechanism. Mouse hepatic carcinoma lines H22 and Hepa1-6 as well as BALB/c and C57 mice were used to establish orthotopic and metastatic mouse models of liver cancer. Mice were divided into four groups, including control group, splenectomy control group (S group), tumor group (T group) and tumor plus splenectomy group (T+S group). Tumor growth, metastases and overall survival were assessed at determined time points. Meanwhile, myeloid-derived suppressor cells (MDSCs) were isolated from the peripheral blood (PB), the spleen and liver tumors, and then measured by flow cytometery. It was found that liver cancer led to splenomegaly, and increased the percentage of MDSCs in the PB and spleen in the mouse models. Splenectomy inhibited the growth and progression of liver cancer and prolonged the overall survival time of orthotopic and metastatic models, which was accompanied by decreased proportion of MDSCs in the PB and tumors of liver cancer-bearing mouse. It was suggested that splenectomy could be considered an adjuvant therapy to treat liver cancer.


Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Neoplasias Experimentais/cirurgia , Baço/cirurgia , Animais , Carcinoma Hepatocelular/fisiopatologia , Linhagem Celular Tumoral , Citometria de Fluxo , Humanos , Neoplasias Hepáticas/fisiopatologia , Camundongos , Células Supressoras Mieloides/patologia , Neoplasias Experimentais/fisiopatologia , Baço/fisiopatologia , Esplenectomia/métodos
16.
Cell Death Dis ; 7(9): e2388, 2016 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-27685632

RESUMO

Our previous study revealed that Ku80 was overexpressed in lung cancer tissues and hsa-miR-623 regulated the Ku80 expression; however, the detailed function of hsa-miR-623 in lung cancer was unclear. We identified that hsa-miR-623 bound to the 3'-UTR of Ku80 mRNA, thus significantly decreasing Ku80 expression in lung adenocarcinoma cells. Hsa-miR-623 was downregulated in lung adenocarcinoma tissues compared with corresponding non-tumorous tissues, and its expression was inversely correlated with Ku80 upregulation. Downregulation of hsa-miR-623 was associated with poor clinical outcomes of lung adenocarcinoma patients. Hsa-miR-623 suppressed lung adenocarcinoma cell proliferation, clonogenicity, migration and invasion in vitro. Hsa-miR-623 inhibited xenografts growth and metastasis of lung adenocarcinoma in vivo. Ku80 knockdown in lung adenocarcinoma cells suppressed tumor properties in vitro and in vivo similar to hsa-miR-623 overexpression. Further, hsa-miR-623 overexpression decreased matrix metalloproteinase-2 (MMP-2) and MMP-9 expression levels, with decreased ERK/JNK phosphorylation. Inhibition of hsa-miR-623 or overexpression of Ku80 promoted lung adenocarcinoma cell invasion, activated ERK/JNK phosphorylation and increased MMP-2/9 expressions, which could be reversed by ERK kinase inhibitor or JNK kinase inhibitor. In summary, our results showed that hsa-miR-623 was downregulated in lung adenocarcinoma and suppressed the invasion and metastasis targeting Ku80 through ERK/JNK inactivation mediated downregulation of MMP-2/9. These findings reveal that hsa-miR-623 may serve as an important therapeutic target in lung cancer therapy.


Assuntos
Adenocarcinoma/genética , Adenocarcinoma/patologia , Progressão da Doença , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/metabolismo , Adenocarcinoma de Pulmão , Animais , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Autoantígeno Ku/metabolismo , Sistema de Sinalização das MAP Quinases , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Lung Cancer ; 98: 43-50, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27393505

RESUMO

BACKGROUND: Severe malignant airway obstruction (SMAO) is a life-threatening form of non-small cell lung carcinoma (NSCLC). OBJECTIVES: To determine the efficacy and safety of para-toluenesulfonamide (PTS) intratumoral injection in NSCLC-SMAO. METHODS: Ninety patients with NSCLC-SAO received repeated courses of PTS intratumoral injection until tumor sizes had reduced by 50% or greater. Primary endpoint was objective alleviation rate, assessed by chest computed tomography (CT) and bronchoscopy, at day 7 and 30 following final dosing. Secondary endpoints included airway obstruction, spirometry, quality-of-life and survival time. RESULTS: In full-analysis set (N=88), using RECIST criteria, PTS treatment resulted in a significant objective alleviation rate [chest CT: 59.1% (95%CI: 48.1%-69.5%), bronchoscopy: 48.9% (95%CI: 38.1%-59.8%) at day 7; chest CT: 43.2% (95%CI: 32.7%-54.2%), bronchoscopy: 29.6% (95%CI: 20.3%-40.2%) at day 30]. There was a remarkable increase in FVC (mean difference: 0.35 liters, 95%CI: 0.16-0.53 liters), FEV1 (mean difference: 0.27 liters, 95%CI: 0.07-0.48 liters), Baseline Dyspnea Index (mean difference: 64.8%, 95%CI: 53.9-74.7%) and Functional Assessment of Cancer Therapy-Lung Cancer Subscale (mean difference: 6·9, 95%CI: 3.8-9.9) at day 7 post-treatment. We noted significantly reduced prevalence of atelectasis (by 42.9%) and Eastern Cooperative Oncology Group physical performance scale (mean difference: 7.2, 95%CI: 3.9-10.5). Median survival time was 394 days in full-analysis set and 460 days in per-protocol set. Adverse events were reported in 64.0% of subjects. Seven severe adverse events (7.9%) were reported, of which three led to death (drug-related in one case). CONCLUSION: PTS intratumoral injection is effective and well tolerated for palliative therapy of NSCLC-SMAO.


Assuntos
Obstrução das Vias Respiratórias/complicações , Antineoplásicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Sulfonamidas/administração & dosagem , Tolueno/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Obstrução das Vias Respiratórias/diagnóstico , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Injeções Intralesionais , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Sulfonamidas/efeitos adversos , Análise de Sobrevida , Tolueno/administração & dosagem , Tolueno/efeitos adversos , Resultado do Tratamento , Adulto Jovem
18.
J Cancer Res Ther ; 12(1): 277-82, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27072251

RESUMO

AIM: The present meta-nalysis investigates the prognostic value of osteopontin. (OPN) expression in patients with non-small-cell lung cancer. (NSCLC). MATERIALS AND METHODS: The Web of Science (1945 ~ 2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966 ~ 2013), EMBASE (1980 ~ 2013), CINAHL (1982 ~ 2013), and the Chinese Biomedical Database (CBM) (1982 ~ 2013) were searched, without language restrictions, to retrieve studies related to OPN and NSCLC. We compiled carefully selected data and a meta-analysis was conducted using STATA software (Version 12.0, Stata Corporation, and College Station, Texas USA). Hazard ratios (HR) with corresponding 95% confidence interval (95%CI) were calculated. RESULTS: Ten clinical cohort studies were selected for statistical analysis, representing a total of 1,133 NSCLC patients. The main findings of our meta-analysis are that patients who were OPN-positive had significantly shorter overall survival than OPN-negative patients. (HR = 1.47, 95%CI = 1.15. ~ 1.79,P< 0.001). Ethnicity.stratified analysis revealed a significant correlation between expression levels of OPN and poor prognosis of NSCLC patients among both Caucasians and Asians. (Asians: HR = 1.53, 95%CI = 0.95. ~ 2.11, P < 0.001; Caucasians: HR = 1.56, 95%CI = 1.08. ~ 2.03, P < 0.001; respectively). CONCLUSIONS: The present meta-analysis is consistent with the hypothesis that increased expression of OPN protein may be significantly associated with poor prognosis in patients with NSCLC.


Assuntos
Biomarcadores Tumorais/biossíntese , Carcinoma Pulmonar de Células não Pequenas/genética , Osteopontina/biossíntese , Prognóstico , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Osteopontina/genética , Proteômica , Análise de Sobrevida
19.
J Huazhong Univ Sci Technolog Med Sci ; 36(1): 150-152, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26838757

RESUMO

The number of smokers in Chinese rural areas is more than 200 million, which is twice that in cities. It is very significant to carry out tobacco control interventions in rural areas. We performed this community intervention study to evaluate the efficacy of village-based health education of tobacco control on the male current smoking rate in rural areas. The population of this study was the males above 15 years old from 6 villages in rural areas. The villages were randomly assigned to intervention group or control group (3 villages in each group). Self-designed smoking questionnaire was applied. The intervention group received the village-based health education of tobacco control for one year. The primary outcome measurement was the male current smoking rate. In the baseline investigation, completed surveys were returned by 814 male residents from the control group and 831 male residents from the intervention group. The male current smoking rate in the control group and the intervention group was 61.2% and 58.5%, respectively, before intervention. There was no significant difference between these two groups (P>0.05). After one-year intervention, the current smoking rate in the intervention group (51.2%) was significantly lower than that in the control group (62.8%) (P<0.001). Our study suggested that the village-based health education of tobacco control was effective in lowering the male current smoking rate in rural areas, which could be a suitable and feasible way for tobacco control in the Chinese rural areas.


Assuntos
Educação em Saúde/métodos , População Rural , Prevenção do Hábito de Fumar , Abandono do Uso de Tabaco , Adolescente , Adulto , Estudos de Casos e Controles , China , Atenção à Saúde/métodos , Humanos , Masculino , Pessoa de Meia-Idade
20.
Nat Prod Commun ; 11(7): 931-934, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30452165

RESUMO

Phytochemical investigation of the roots and rhizomes of Pileostegia viburnoides var. glabrescens led to the isolation and identification of 31 compounds (1-31), 25 of which (1-2, 4-7, 9-12, 15-18, 21-31) were isolated from the Pileostegia genus for the first time. 7α-Hydroxyfriedelan-3-one-26-ol-29-oic acid (1) is a new friedelane-type triterpene. The structure of n-butyl-ß-D-fructopyranoside (2) was determined by single-crystal X-ray diffraction. Compounds 4 and 12 displayed marginal cytotoxicity against the P388 murine leukemia cell line with IC50 values of 13.4 µM and 25.0 µM, respectively. Compound 23 exhibited marginal anti-inflammatory activity by the inhibition of lipopolysaccharide induced nitric oxide production in RAW 264.7 macrophage cells, with an IC50 value of 32.0 µM. Compounds 3, 8-10, 25, and 27 were phytotoxic to the dicot Lactuca sativa (lettuce) and/or the monocot Agrostis stolonifera (bentgrass).


Assuntos
Raízes de Plantas/química , Rizoma/química , Saxifragaceae/química , Triterpenos/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular , Biologia Computacional , Herbicidas/química , Herbicidas/farmacologia , Lactuca/efeitos dos fármacos , Camundongos , Estrutura Molecular , Sementes/efeitos dos fármacos , Triterpenos/farmacologia
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