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1.
Clin Exp Pharmacol Physiol ; 50(12): 964-972, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37715611

RESUMO

Pulmonary fibrosis (PF) is one of the common manifestations of end-stage lung disease. Chronic lung failure after lung transplantation is mainly caused by bronchiolitis obliterans syndrome (BOS) and is mainly characterized by lung tissue fibrosis. Pulmonary epithelial-mesenchymal transformation (EMT) is crucial for pulmonary fibrosis. Telocytes (TCs), a new type of mesenchymal cells, play a protective role in various acute injuries. For exploring the anti-pulmonary fibrosis effect of TCs in the BOS model in vitro and the related mechanism, rat tracheal epithelial (RTE) cells were treated with transforming growth factor-ß (TGF-ß) to simulate lung tissue fibrosis in vitro. The RTE cells were then co-cultured with TCs primarily extracted from rat lung tissue. Western blot, Seahorse XF Analysers and enzyme-linked immunosorbent assay were used to detect the level of EMT and aerobic respiration of RTE cells. Furthermore, anti-hepatocyte growth factor (anti-HGF) antibody was exogenously added to the cultured cells to explore further mechanisms. Moreover, hexokinase 2 (HK2) in RTE cells was knocked down to assess whether it influences the blocking effect of the anti-HGF antibody. TGF-ß could induce lung tissue fibrosis in RTE cells in vitro. Nevertheless, TCs co-culture decreased the level of EMT, glucose metabolic indicators (lactate and ATP) and oxygen levels. Furthermore, TCs released hepatocyte growth factor (HGF). Therefore, the exogenous addition of anti-HGF antibody in the co-culture system blocked the anti-lung tissue fibrosis effect. However, HK2 knockdown attenuated the blocking effect of the anti-HGF antibody. In conclusion, TCs can protect against lung tissue fibrosis by releasing HGF, a process dependent on HK2.


Assuntos
Fibrose Pulmonar , Telócitos , Animais , Ratos , Fibrose , Fator de Crescimento de Hepatócito/metabolismo , Hexoquinase , Pulmão/metabolismo , Fibrose Pulmonar/metabolismo , Telócitos/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
2.
Acta Biochim Biophys Sin (Shanghai) ; 54(2): 179-186, 2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-35538026

RESUMO

Hypoxia-induced epigenetic regulation calls for more effective therapeutic targets for esophageal cancer. We used GEPIA and UALCAN databases to screen survival-related and cancer stage-associated genes. Eca109 and KYSE450 esophageal cancer cell lines were cultured under normoxia, hypoxia, or CoCl-induced hypoxia conditions, which were further transfected with plasmids expressing RB binding protein 7 (RBBP7), hypoxia-inducible factor 1 (HIF1)-α, or RBBP7 shRNA. Colony formation and MTT assays were used to detect cell proliferation. Tumor sphere formation and stemness marker detection were applied to assess cell stemness. RT-PCR and western blot analysis were used to detect the relative mRNA level and protein expression, respectively. Luciferase assay was utilized to detect the direct interaction between HIF1α and RBBP7. Up-regulated RBBP7 was identified as one of the most prominent survival-related genes, which is negatively correlated with the overall survival (OS), disease recurrence-free survival (DFS), and tumor stages. Hypoxia-induced HIF1α up-regulates RBBP7 expression, which promotes esophagus cancer cell viability, proliferation, and stemness with increased cyclin-dependent kinase 4 (CDK4) expression. Luciferase reporter assay verified that HIF1α transcriptionally regulates the expression of RBBP7. We conclude that hypoxia induces high expression of RBBP7 which is at least partially mediated by HIF1α, up-regulates the expression of downstream CDK4, and thereby promotes tumor progression in esophageal cancer cells.


Assuntos
Quinase 4 Dependente de Ciclina , Neoplasias Esofágicas , Proteína 7 de Ligação ao Retinoblastoma , Hipóxia Celular , Linhagem Celular Tumoral , Proliferação de Células/genética , Quinase 4 Dependente de Ciclina/biossíntese , Quinase 4 Dependente de Ciclina/genética , Progressão da Doença , Epigênese Genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Proteína 7 de Ligação ao Retinoblastoma/biossíntese , Proteína 7 de Ligação ao Retinoblastoma/genética , Proteína 7 de Ligação ao Retinoblastoma/metabolismo
3.
Anal Chem ; 92(2): 1653-1657, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31809016

RESUMO

Paper spray ionization has been used as a fast sampling/ionization method for the direct mass spectrometric analysis of biological samples at ambient conditions. Here, we demonstrated that by utilizing paper spray ionization-mass spectrometry (PSI-MS) coupled with field asymmetric waveform ion mobility spectrometry (FAIMS), predictive metabolic and lipidomic profiles of routine breast core needle biopsies could be obtained effectively. By the combination of machine learning algorithms and pathological examination reports, we developed a classification model, which has an overall accuracy of 87.5% for an instantaneous differentiation between cancerous and noncancerous breast tissues utilizing metabolic and lipidomic profiles. Our results suggested that paper spray ionization-ion mobility spectrometry-mass spectrometry (PSI-IMS-MS) is a powerful approach for rapid breast cancer diagnosis based on altered metabolic and lipidomic profiles.


Assuntos
Neoplasias da Mama/diagnóstico , Aprendizado de Máquina , Papel , Algoritmos , Feminino , Humanos , Espectrometria de Mobilidade Iônica , Espectrometria de Massas por Ionização por Electrospray
4.
Int J Med Sci ; 17(13): 2040-2051, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32788883

RESUMO

Purpose: Using the gastric cancer cell line SGC7901 and gastric cancer stem cell (CSC-G), we conducted this study to investigate the role of cancer stem cells in invasion, metastasis and tumor angiogenesis. Methods: Stem cell markers (OCT4, SOX2, C-Myc and Klf4) expression was detected by RT-PCR and Western blotting. The proliferation, migration, invasion abilities, L-OHP and 5-FU resistance, angiogenesis were assessed using in vitro spherical clone formation assays, plate cloning experiments, transwell migration, transwell invasion, drug resistance, scratch-wound migration, ring formation assay, and their tumorigenic and ability were assessed using a tumor formation experiment in mice. Results: Compared with the SGC7901, the expression of Oct4, Sox2, Klf4 and CD44 mRNA was significantly higher in CSC-G, the mRNA relative expression of E-cadherin in CSC-G was lower than SGC7901, while the expression of c-Myc did not significantly change. The proliferation, drug resistance, migration, and invasion abilities were significantly higher in CSC-G, and the tumorigenic ability in mice was also significantly higher. Conclusion: The proliferation, drug resistance, migration, invasion, and tumorigenic abilities of CSC-G significantly were higher than SGC7901. CSC-G plays important roles in proliferation, migration, invasion, and tumorigenicity.


Assuntos
Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Neovascularização Patológica/patologia , Neoplasias Gástricas/patologia , Animais , Antígenos CD/genética , Antineoplásicos/farmacologia , Caderinas/genética , Linhagem Celular Tumoral , Movimento Celular , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Receptores de Hialuronatos/genética , Fator 4 Semelhante a Kruppel , Camundongos Endogâmicos NOD , Células-Tronco Neoplásicas/efeitos dos fármacos , Fator 3 de Transcrição de Octâmero/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Transcrição SOXB1/metabolismo , Neoplasias Gástricas/irrigação sanguínea , Neoplasias Gástricas/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto
5.
World J Surg Oncol ; 18(1): 126, 2020 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-32534587

RESUMO

BACKGROUND: Additional studies comparing laparoscopic gastrectomy (LG) versus open gastrectomy (OG) for advanced gastric cancer (AGC) have been published, and it is necessary to update the systematic review of this subject. OBJECTIVE: We conducted the meta-analysis to find some proof for the use of LG in AGC and evaluate whether LG is an alternative treatment for AGC. METHOD: Randomized controlled trials (RCT) and high-quality retrospective studies (NRCT) compared LG and OG for AGC, which were published in English between January 2010 and May 2019, were search in PubMed, Embase, and Web of Knowledge by three authors independently and thoroughly. Some primary endpoints were compared between the two groups, including intraoperative time, intraoperative blood loss, harvested lymph nodes, first flatus, first oral intake, first out of bed, post-operative hospital stay, postoperative morbidity and mortality, rate of disease recurrence, and 5-year over survival (5-y OS). Besides, considering for this 10-year dramatical surgical material development between 2010 and 2019, we furtherly make the same analysis based on recent studies published between 2016 and 2019. RESULT: Thirty-six studies were enrolled in this systematic review and meta-analysis, including 5714 cases in LAG and 6094 cases in OG. LG showed longer intraoperative time, less intraoperative blood loss, and quicker recovery after operations. The number of harvested lymph nodes, hospital mortality, and tumor recurrence were similar. Postoperative morbidity and 5-y OS favored LG. Furthermore, the systemic analysis of recent studies published between 2016 and 2019 revealed similar result. CONCLUSION: A positive trend was indicated towards LG. LG can be performed as an alternative to OG for AGC.


Assuntos
Gastrectomia/métodos , Recidiva Local de Neoplasia/cirurgia , Neoplasias Gástricas/cirurgia , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Mortalidade Hospitalar , Humanos , Laparoscopia/métodos , Tempo de Internação/estatística & dados numéricos , Linfonodos/patologia , Recidiva Local de Neoplasia/patologia , Período Pós-Operatório , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Resultado do Tratamento
6.
BMC Cancer ; 19(1): 635, 2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31248382

RESUMO

BACKGROUND: Zinc-finger E-box binding homeobox 1 (ZEB-1) plays crucial roles in epithelial-to-mesenchymal transition during tumor carcinogenesis. Published studies have examined the potential value of ZEB-1 as a biomarker for the prognosis of cancer. Nevertheless, the prognostic significance of ZEB-1 in human solid tumor remains inconclusive. Therefore, we performed the present meta-analysis to evaluate the prognostic value of ZEB-1 in patients with solid tumors. METHODS: The 13 included studies (1616 patients) were exact electronic searched from Web of Science, PubMed and EBSCO until September 2018. Pooled hazard ratios (HR) and the corresponding 95% confidence intervals (CI) for overall survival (OS) were analyzed through random or fixed effects models. Univariate and multivariate analyses were independently performed. Subgroup analyses, heterogeneity and publication bias were investigated to further enhance reliability. RESULTS: This research indicated that elevated expression of ZEB-1 significantly predicted worse OS in patients with solid tumors. In the univariate analysis, the pooled HR for OS was 1.66 (95% CI: 1.45-1.90; P < 0.01). Meanwhile, in multivariate analysis, the pooled HR for OS was 2.28 (95% CI: 1.58-3.30; P < 0.01). Begg's funnel plot and Begg's test did not show evidence of significant publication bias, both in univariate analysis and multivariate analysis. CONCLUSIONS: High expression of ZEB-1 was associated with poorer OS, suggesting that ZEB-1 may be a potential biomarker for the prediction of prognosis, and a novel therapeutic target in human solid tumors.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias/diagnóstico , Neoplasias/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Biomarcadores Tumorais/normas , Feminino , Humanos , Masculino , Neoplasias/mortalidade , Prognóstico , Análise de Sobrevida , Regulação para Cima
7.
BMC Infect Dis ; 18(1): 11, 2018 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-29304746

RESUMO

BACKGROUND: Acinetobacter baumannii (AB) is critical for healthcare-associated infections (HAI) with significant regional differences in the resistance rate, but its risk factors and infection trends has not been well studied. We aimed to explore the risk factors, epidemiological characteristics and resistance of multidrug-resistant Acinetobacter baumannii (MDR-AB) in intensive care unit inpatients. METHODS: Data of patients with MDR-AB (195 cases), and with antibiotic-sensitive AB infection (294 cases, control) during January to December, 2015 in three medical centers in Xiamen, China were conducted and analyzed in the present retrospective study. RESULTS: Lower respiratory tract infection with AB accounted for 68.71%. MDR-AB was detected in 39.88% of all cases. Univariate analysis suggested that mechanical ventilation, indwelling catheter, cancer patients, length of hospitalization in intensive care unit (ICU) ≥15 d, Acute Physiology and Chronic Health Evaluation (APACHE) II score, combined using antibiotic before isolation of AB and use of third-lines cephalosporins were associated with the development of MDR-AB healthcare-associated infections. Dose-response relationship analysis suggested that the age and the days of mechanical ventilation were associated with increased infection with MDR-AB. Logistic regression analysis suggested that, mechanical ventilation, combined using antibiotic before isolation of AB, and indwelling catheter, were associated with MDR-AB infection, with odds ratios (OR) and 95% confidence intervals (CI) of 3.93 (1.52-10.14), 4.11 (1.58-10.73), and 4.15 (1.32-12.99), respectively. CONCLUSIONS: MDR-AB infection was associated with mechanical ventilation, combined using antibiotic before isolation of AB, and indwelling catheter. Furthermore, the age and the days of mechanical ventilation were associated with increased infection with MDR-AB.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por Acinetobacter/epidemiologia , Acinetobacter baumannii/patogenicidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/microbiologia , Cefalosporinas/uso terapêutico , China/epidemiologia , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/epidemiologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Respiração Artificial/efeitos adversos , Estudos Retrospectivos , Fatores de Risco
8.
Oncogene ; 43(7): 511-523, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38177412

RESUMO

Leukocyte cell-derived chemotaxin 2 (LECT2) is a multifunctional cytokine that can bind to several receptors and mediate distinct molecular pathways in various cell settings. Changing levels of LECT2 have been implicated in multiple human disease states, including cancers. Here, we have demonstrated reduced serum levels of LECT2 in patients with epithelial ovarian cancer (EOC) and down-regulated circulating Lect2 as the disease progresses in a syngeneic mouse ID8 EOC model. Using the murine EOC model, we discovered that loss of Lect2 promotes EOC progression by modulating both tumor cells and the tumor microenvironment. Lect2 inhibited EOC cells' invasive phenotype and suppressed EOC's transcoelomic metastasis by targeting c-Met signaling. In addition, Lect2 downregulation induced the accumulation and activation of myeloid-derived suppressor cells (MDSCs). This fostered an immunosuppressive microenvironment in EOC by inhibiting T-cell activation and skewing macrophages toward an M2 phenotype. The therapeutic efficacy of programmed cell death-1 (PD-1)/PD-L1 pathway blockade for the ID8 model was significantly hindered. Overall, our data highlight multiple functions of Lect2 during EOC progression and reveal a rationale for synergistic immunotherapeutic strategies by targeting Lect2.


Assuntos
Neoplasias Ovarianas , Humanos , Camundongos , Animais , Feminino , Neoplasias Ovarianas/patologia , Carcinoma Epitelial do Ovário/metabolismo , Macrófagos/metabolismo , Transdução de Sinais , Imunossupressores , Modelos Animais de Doenças , Microambiente Tumoral/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo
9.
Cell Biosci ; 13(1): 118, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37381062

RESUMO

BACKGROUND: Artemisia argyi (A. argyi), also called Chinese mugwort, has been widely used to control pandemic diseases for thousands of years since ancient China due to its anti-microbial infection, anti-allergy, and anti-inflammation activities. Therefore, the potential of A. argyi and its constituents in reducing the infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was investigated in this study. RESULTS: Among the phytochemicals in A. argyi, eriodictyol and umbelliferone were identified to target transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2) proteins, the essential factors for the cellular entry of SARS-CoV-2, in both FRET-based enzymatic assays and molecular docking analyses. These two ingredients of A. argyi suppressed the infection of ACE2-expressed HEK-293 T cells with lentiviral-based pseudo-particles (Vpp) expressing wild-type and variants of SARS-CoV-2 spike (S) protein (SARS-CoV-2 S-Vpp) via interrupting the interaction between S protein and cellular receptor ACE2 and reducing the expressions of ACE2 and TMPRSS2. Oral administration with umbelliferone efficiently prevented the SARS-CoV-2 S-Vpp-induced inflammation in the lung tissues of BALB/c mice. CONCLUSIONS: Eriodictyol and umbelliferone, the phytochemicals of Artemisia argyi, potentially suppress the cellular entry of SARS-CoV-2 by preventing the protein binding activity of the S protein to ACE2.

10.
Anticancer Res ; 42(2): 845-855, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35093882

RESUMO

BACKGROUND/AIM: The poor prognosis and chemoresistance of patients with triple-negative breast cancer (TNBC) urge the development of new therapeutic strategies. Snail mucus has shown its ability against inflammation, a process closely related to tumorigenesis, suggesting a potential anti-cancer activity. MATERIALS AND METHODS: The effect and mechanisms of snail mucus on cell viability were determined by IncuCyte Live-cell analysis and molecular biological methods. The anti-cancer fractions of snail mucus were isolated and identified by medium pressure liquid chromatography (MPLC) and nuclear magnetic resonance (NMR) spectrometry analysis. RESULTS: Snail mucus significantly decreased the viability of TNBC cells with relatively lower cytotoxicity to normal breast epithelial cells and enhanced their response to chemotherapy through activation of Fas signaling by suppressing nucleolin. Two peptide fractions have been identified as the anti-cancer ingredients of the snail mucus. CONCLUSION: Snail mucus can induce programmed cell death via the extrinsic apoptotic pathway and has therapeutic potential by achieving a chemo-sensitizing effect in TNBCs.


Assuntos
Antineoplásicos/farmacologia , Muco , Transdução de Sinais/efeitos dos fármacos , Caramujos , Neoplasias de Mama Triplo Negativas/metabolismo , Receptor fas/metabolismo , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Muco/química , Muco/metabolismo , Caramujos/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia
11.
Cancers (Basel) ; 13(10)2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34069116

RESUMO

Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers, which is the second most lethal tumor worldwide. Epigenetic deregulation is a common trait observed in HCC. Recently, increasing evidence suggested that the G9a histone methyltransferase might be a novel regulator of HCC development. However, several HCC cell lines were recently noted to have HeLa cell contamination or to have been derived from non-hepatocellular origin, suggesting that functional validation of G9a in proper HCC models is still required. Herein, we first confirmed that higher G9a messenger RNA and protein expression levels were correlated with poor overall survival (OS) and disease-free survival (DFS) rates of HCC patients from The Cancer Genome Atlas (TCGA) dataset and our recruited HCC cohort. In an in vitro functional evaluation of HCC cells, HCC36 (hepatitis B virus-positive (HBV+) and Mahlavu (HBV-)) cells showed that G9a participated in promoting cell proliferation, colony formation, and migration/invasion abilities. Moreover, orthotopic inoculation of G9a-depleted Mahlavu cells in NOD-SCID mice also resulted in a significantly decreased tumor burden compared to the control group. Furthermore, after surveying microRNA (miRNA; miR) prediction databases, we identified the liver-specific miR-122 as a G9a-targeting miRNA. In various HCC cell lines, we observed that miR-122 expression levels tended to be inversely correlated to G9a expression levels. In clinical HCC specimens, a significant inverse correlation of miR-122 and G9a mRNA expression levels was also observed. Functionally, the colony formation and invasive ability were attenuated in miR-122-overexpressing HCC cells. HCC patients with low miR-122 and high G9a expression levels had the worst OS and DFS rates compared to others. Together, our results confirmed the importance of altered G9a expression during HCC progression and discovered that a novel liver-specific miR-122-G9a regulatory axis exists.

12.
Transl Cancer Res ; 9(7): 4093-4110, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35117779

RESUMO

BACKGROUND: Gastric cancer (GC) is one of the most common malignant diseases worldwide, the incidence and mortality for GC is still high, thus it is urgently important to identify the effective and reliable biomarkers to evaluate GC and the underlying molecular events. METHODS: The study integrated four Gene Expression Omnibus (GEO) profile datasets and The Cancer Genome Atlas (TCGA) dataset to screen differentially expressed genes (DEGs), screened key genes by performing the Kaplan-Meier analysis, univariate and multivariate-cox analysis. Further analysis were performed to evaluate and validate the prognostic value of the key genes based on TCGA database and online websites. In addition, mechanism analysis of the key genes was performed thought biological processes and KEGG pathway analysis. RESULTS: In the study, 192 DEGs (92 up-regulated and 100 down-regulated) were identified from the GEO and TCGA datasets. Next, gene ontology (GO) for DEGs focused primarily on cell adhesion, extracellular region and extracellular matrix structural constituent. Then four significant key genes were screened by performed the Kaplan-Meier analysis, univariate and multivariate-cox analysis. By using Kaplan-Meier plotter and OncoLnc, the expression level was associated with a worse prognosis. In addition, the area under curve (AUC) for time-dependent receiver operating characteristic (ROC) indicated a moderate diagnostic value. Furthermore, the expression of collagen triple helix repeat containing 1 (CTHRC1), serpin family E member 1 (SERPINE1), Versican (VCAN) was associated with tumor size, Uroplakin 1B (UPK1B) expression was associated with distant metastasis. Finally, multiple biological processes and signaling pathway associated with key genes revealed the underlying mechanism in GC. CONCLUSIONS: Taken together, CTHRC1, SERPINE1, VCAN, UPK1B were novel potential prognostic molecular markers for GC, which acted as oncogene to promote the development of GC.

13.
PeerJ ; 8: e9201, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32518728

RESUMO

BACKGROUND: Due to the complicated molecular and cellular heterogeneity in hepatocellular carcinoma (HCC), the morbidity and mortality still remains high level in the world. However, the number of novel metabolic biomarkers and prognostic models could be applied to predict the survival of HCC patients is still small. In this study, we constructed a metabolic gene signature by systematically analyzing the data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and International Cancer Genome Consortium (ICGC). METHODS: Differentially expressed genes (DEGs) between tumors and paired non-tumor samples of 50 patients from TCGA dataset were calculated for subsequent analysis. Univariate cox proportional hazard regression and LASSO analysis were performed to construct a gene signature. The Kaplan-Meier analysis, time-dependent receiver operating characteristic (ROC), Univariate and Multivariate Cox regression analysis, stratification analysis were used to assess the prognostic value of the gene signature. Furthermore, the reliability and validity were validated in four types of testing cohorts. Moreover, the diagnostic capability of the gene signature was investigated to further explore the clinical significance. Finally, Go enrichment analysis and Gene Set Enrichment Analysis (GSEA) have been performed to reveal the different biological processes and signaling pathways which were active in high risk or low risk group. RESULTS: Ten prognostic genes were identified and a gene signature were constructed to predict overall survival (OS). The gene signature has demonstrated an excellent ability for predicting survival prognosis. Univariate and Multivariate analysis revealed the gene signature was an independent prognostic factor. Furthermore, stratification analysis indicated the model was a clinically and statistically significant for all subgroups. Moreover, the gene signature demonstrated a high diagnostic capability in differentiating normal tissue and HCC. Finally, several significant biological processes and pathways have been identified to provide new insights into the development of HCC. CONCLUSION: The study have identified ten metabolic prognostic genes and developed a prognostic gene signature to provide more powerful prognostic information and improve the survival prediction for HCC.

14.
J Phys Chem B ; 113(35): 11800-7, 2009 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-19678632

RESUMO

A new type of acylated carboxymethyl amphiphilic chitosan (ACC) with the use of acyl chain of varying lengths, from C(2) to C(12), and various degrees of acyl substitution was successfully synthesized and has been characterized in terms of its self-assembly behavior, structural stability, and drug encapsulation. The resulting nanostructure of the ACC nanoaggregates can be well manipulated through a control of hydrophobicity. Structural evolution of the self-assembled nanoaggregates is extensively characterized via (1)H NMR, FTIR, DSC, and TEM. A critical value of the hydrophobic effect, (X(DH) x X(Cn)), i.e., a product of "degree of acyl substitution" and "carbon number of acyl chain", can be employed as an indicator for structural variation of the nanoaggregates: when (X(DH) x X(Cn)) exceeded 1.5, the architecture of the nanoaggregates underwent a structural transformation from solid nanoparticle to hollow nanocapsules. The nanoaggregates exhibited an excellent colloidal and structural stability in aqueous medium. An improved affinity toward drug encapsulation, i.e., doxorubicin, can be technically designed according to the amphiphilic nature of the resulting nanoaggregates for drug delivery.

15.
Onco Targets Ther ; 12: 4667-4682, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417271

RESUMO

Objective: Using the gastric cancer cell line SGC7901, we constructed a cell line that overexpressed octamer-binding protein 4 (Oct4) and SRY-box 2 (Sox2) to explore the stem cell oncological and biological characteristics of these cells and to elucidate the mechanisms of Oct4 and Sox2 in cancer. Methods: A lentiviral vector containing the Sox2 gene was constructed and transfected into a gastric cancer cell line overexpressing Oct4 (SGC7901-Oct4) to obtain a stably transfected cell line (SGC7901-Oct4-Sox2). Oct4 and Sox2 expression was detected by RT-PCR and Western blotting. The proliferation, drug resistance, migration, and invasion abilities of the cells were assessed using in vitro (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium), drug resistance, scratch-wound migration, transwell migration, transwell invasion, and spherical clone formation assays, and their tumorigenic ability was assessed using a tumor formation experiment in mice. Results: Compared with the control group, the expression of Oct4, Sox2, CD44, and E-cadherin was significantly higher in the group that overexpressed Oct4 and Sox2, while the expression of c-Myc and Klf4 did not significantly change. The proliferation, drug resistance, migration, and invasion abilities were significantly enhanced in the overexpression group, and the tumorigenic ability in mice was also significantly enhanced, with significantly increased tumor size and weight. Conclusion: The proliferation, drug resistance, migration, invasion, and tumorigenic abilities of SGC7901 cells overexpressing Oct4 and Sox2 were significantly improved. Oct4 and Sox2 play important roles in the proliferation, migration, invasion, and tumorigenicity of gastric cancer cells, and the two genes may be synergistic to a certain degree.

16.
Medicine (Baltimore) ; 98(14): e15115, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30946381

RESUMO

The study aimed to evaluate analgesic effects and postoperative recovery of ropivacaine wound infiltration for elderly patients in China after total laparoscopic radical gastrectomy.We retrospectively received clinical data of 132 elderly patients who received total laparoscopic gastrectomy and tracheal intubation general anesthesia from cancer center of First Affiliated Hospital of Xiamen University between September 2014 and September 2017, patients were divided into 2 groups according to local injection of drug: group I (ropivacaine group, 0.5% ropivacaine, 40 mL in total, n = 69), group II (control group, no analgesic, n = 63). The demographics, postoperative pain using numeric ratings scale (NRS), rescue analgesics as well as incidence of complications were investigated.Significantly lower pain scores were observed in group I than in group II at 6, 12, 24, and 48 h postoperatively; the use of remedy analgesia was less in group I than in group II; there was no statistical significance in the incidence of surgical-related complications between the 2 groups. The recovery time were shorter in group I than in group II, meanwhile, postoperative hospital stay, medical expenses, and anesthesia-related complications were significantly less in group I than in group II.This is a review of ropivacaine infiltration use in the elderly patients underwent total laparoscopic radical gastrectomy. This analysis describes the postoperative analgesic effect and postoperative recovery of wound infiltration with ropivacaine. Multicentered large sample prospective randomized controlled study is needed to evaluate the feasibility, security, and economic practicality.


Assuntos
Anestésicos Locais/administração & dosagem , Dor Pós-Operatória/tratamento farmacológico , Ropivacaina/administração & dosagem , Idoso , Estudos de Casos e Controles , China , Feminino , Gastrectomia , Humanos , Injeções , Laparoscópios , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia
17.
Medicine (Baltimore) ; 98(23): e15939, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31169715

RESUMO

To investigate therapeutic effect of cuff rectum drainage tube (CDT) in preventing the postoperative complications of total mesorectal excision (TME) and promoting the recovery of the patients.The clinical data of 84 cases of low rectal cancer performed TME from June 2015 to June 2017 in the First Affiliated Hospital of Xiamen University were analyzed retrospectively. All the cases were performed anus-retained operation without preventive colostomy. Patients were divided into 2 groups according to the material of the anorectal drainage tube placed in the colonic cavity. Group I (CDT group) was transanal cuff rectal drainage tube placement (Patent No. ZL 201320384337.8) (n = 48), and group II (conventional group) was transanal clinical conventional drainage tube placement (n = 36). Anastomotic fistula incidence, the time of anal exsufflation, postoperative first ambulation time, intestinal function recovery time, the incidence of interrelated complications of drainage tube and postoperative hospital stay between 2 groups were analyzed retrospectively.Both postoperative first ambulation and anal exhaust time in CDT group were shorter than those in the conventional group ([2.3 ±â€Š0.4] d vs [3.0 ±â€Š0.2] d, P < .05; [3.3 ±â€Š0.3] d vs [3.9 ±â€Š0.5] d, P < .05). Meanwhile, the postoperative hospital stay of CDT group was significantly decreased than that in the conventional group ([10.3 ±â€Š1.6] d vs [11.8 ±â€Š1.1] d, P < .05). Significant different occurrence of complications existed in anastomotic fistula (2.1% [1/48] vs 16.7% [6/36], P < .05), frequent defecation (8.3% [4/48] vs 27.8% [10/36], P < .05), defecating unfinished feeling (12.5% [6/48] vs 30.6% [11/36], P < .05), drainage tube complication (4.2% [2/48] vs 22.2% [8/36], P < .05).The cuff rectum drainage tube may reduce incidence of anastomotic fistula after TME, shorten postoperative first ambulation and anal exsufflation time, enable faster recovery with good toleration and decrease postoperative hospital stay.


Assuntos
Drenagem/métodos , Complicações Pós-Operatórias/epidemiologia , Protectomia/efeitos adversos , Neoplasias Retais/cirurgia , Reto/cirurgia , Idoso , Estudos de Casos e Controles , Defecação , Feminino , Humanos , Incidência , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Período Pós-Operatório , Protectomia/métodos , Estudos Retrospectivos , Resultado do Tratamento , Caminhada
18.
Cancers (Basel) ; 11(2)2019 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-30759864

RESUMO

Tamoxifen is the most widely used hormone therapy in estrogen receptor-positive (ER+) breast cancer, which accounts for approximately 70% of all breast cancers. Although patients who receive tamoxifen therapy benefit with respect to an improved overall prognosis, resistance and cancer recurrence still occur and remain important clinical challenges. A recent study identified TAR (HIV-1) RNA binding protein 2 (TARBP2) as an oncogene that promotes breast cancer metastasis. In this study, we showed that TARBP2 is overexpressed in hormone therapy-resistant cells and breast cancer tissues, where it enhances tamoxifen resistance. Tamoxifen-induced TARBP2 expression results in the desensitization of ER+ breast cancer cells. Mechanistically, tamoxifen post-transcriptionally stabilizes TARBP2 protein through the downregulation of Merlin, a TARBP2-interacting protein known to enhance its proteasomal degradation. Tamoxifen-induced TARBP2 further stabilizes SOX2 protein to enhance desensitization of breast cancer cells to tamoxifen, while similar to TARBP2, its induction in cancer cells was also observed in metastatic tumor cells. Our results indicate that the TARBP2-SOX2 pathway is upregulated by tamoxifen-mediated Merlin downregulation, which subsequently induces tamoxifen resistance in ER+ breast cancer.

19.
Adv Mater ; 31(7): e1806341, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30589119

RESUMO

Manipulation of light below the diffraction limit forms the basis of nanophotonics. Metals can confine light at the subwavelength scale but suffer from high loss of energy. Recent reports have theoretically demonstrated the possibility of light confinement below the diffraction limit using transparent dielectric metamaterials. Here, nanoscale light confinement (<λ/20) in transparent dielectric materials is shown experimentally through a luminescent nanosystem with rationally designed dielectric claddings. Theoretically, green light with a wavelength of 540 nm has a transmission of 98.8% when passing through an ultrathin NaYF4 /NaGdF4 superlattice cladding (thickness: 6.9 nm). Unexpectedly, the complete confinement of green emission (540 nm) by such an ultrathin dielectric cladding is directly observed. FDTD calculations are used to confirm that the ultrathin dielectric cladding has negligible influence on the transmission of propagating light, but extraordinary confinement of evanescent waves. This will provide new opportunities for nanophotonics by completely averting the use of metals.

20.
Medicine (Baltimore) ; 97(52): e13832, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30593179

RESUMO

BACKGROUND: A plenty of previous researches have reported the prognostic value of CDC20 (Cell Division Cycle Protein 20) in solid tumors. Nevertheless, these researches were restricted by the small sample databases and the results were not strongly consistent among them. METHODS: We comprehensively searched these relevant studies by PubMed, Web of Science, and EMBASE, in which publications before March 2017 were included. Pooled HR values for OS were cumulatively pooled and quantitatively analyzed in the meta-analysis. RESULTS: Hence we composed a meta-analysis based on 8 studies with 1856 patients in order to assess the potential relationship between CDC20 overexpression and OS (overall survival) in human solid tumors. There were a total of 8 studies (n = 1856) assessed in the meta-analysis. What suggested in both univariate and multivariate analysis for survival is that high level of CDC20 expression apparently pointed to poor prognosis. In the univariate analysis, the combined hazard ratio (HR) for OS was 1.75 (95% confidence interval [CI]: 1.07-2.86, P = .03). The pooled HR of multivariate analysis for OS was 2.48 (95% confidence interval [CI]: 2.10-2.94, P < .001). CONCLUSIONS: The meta-analysis indicated that high level of CDC20 expression is significantly correlated with decreased survival in most case of human solid tumors. In addition, CDC20 shows promise as a meaningful prognostic biomarker and original therapeutic target, on the basis of its expression level in solid tumors.


Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas Cdc20/metabolismo , Neoplasias/metabolismo , Neoplasias/mortalidade , Humanos , Análise Multivariada , Neoplasias/patologia , Prognóstico , Modelos de Riscos Proporcionais
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