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1.
BMC Immunol ; 25(1): 3, 2024 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-38184521

RESUMO

OBJECTIVE: Lung cancer with the highest incidence and mortality in the world. Immune checkpoint inhibitors (ICIs), can bring long-term survival benefits to patients, but also can bring immune-related adverse events (irAEs) in some patients during therapy. Therefore, the aim of this study was to investigate the predictive effect of peripheral blood WBC, NLR, sATPCD4 and nATPCD4 on irAEs in advanced non-small cell lung cancer (NSCLC). METHODS: Clinical data of 112 patients with advanced NSCLC who were treated with PD -1/PD -L1 inhibitor in the Fifth Affiliated Hospital of Guangzhou Medical University from December 15, 2019 to April 30, 2023 were retrospectively analyzed. These patients were divided into the irAEs group (n = 27) and non-irAEs group (n = 85). The clinical data of the two groups were compared. Receiver operating characteristic (ROC) curves were drawn to determine the threshold value of baseline peripheral blood parameters to predict the occurrence of irAEs. Multivariate logistic regression analysis was used to explore the relationship between peripheral blood markers and the incidence of irAEs. RESULTS: The patient characteristics have no significant difference between irAEs and non-irAEs group. But the baseline peripheral blood WBC, sATPCD4 and nATPCD4 of patients in the irAEs group were higher than those in the non-irAEs group (p < 0.05), and the NLR in irAEs group was similar to in the non-irAEs group (p = 0.639).Univariate analysis showed that high WBC, sATPCD4 and nATPCD4 may the risk factors for the occurrence of irAEs (p < 0.05). Multivariate logistic regression analysis showed that high sATPCD4 and nATPCD4 were independent risk factors for the occurrence of irAEs (p < 0.05). The best critical values of WBC, sATPCD4 and nATPCD4 before treatment for predicting the occurrence of irAEs were 8.165 × 109cells/L (AUC = 0.705) ,484.5 ng/mL (AUC = 0.777), and 156 ng/mL (AUC = 0.840), respectively. CONCLUSIONS: sATPCD4 and nATPCD4 were independent risk factors for the occurrence of irAEs in advanced NSCLC patients. This discovery provides a new method to predict the occurrence of irAEs in patients. Based on the prediction results, corresponding treatment measures can be taken to reduce the incidence of adverse events.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Estudos Retrospectivos , Inibidores de Checkpoint Imunológico , Trifosfato de Adenosina
2.
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
3.
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
4.
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
5.
J Transl Med ; 14(1): 122, 2016 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-27150195

RESUMO

BACKGROUND: Hepatitis B virus (HBV) X protein (HBx) is a type of oncogenic protein involved in the progression of hepatocellular carcinoma (HCC) via interacting with host genes. Dysregulation of microRNAs (miRNAs) has been observed in HCC. This study aimed to investigate the role of HBx protein in the regulation of miR-19a, miR-122 and miR-223, and examine if these miRNAs involve in progression of malignant hepatocytes. METHODS: Quantitative real time PCR (qRT-PCR) was used to measure the expression of miR-19a, miR-122 and miR-223 in patient samples and in HepG2 cells transfected with HBx or 1.3 fold HBV genome and also in HepG2.2.15 cells, which stably produces HBV. Their target mRNAs and proteins-PTEN, cyclin G1 and c-myc were measured by qRT-PCR and western blot, respectively. The effect of miR-19a, miR-122 and miR-223, and their respective target genes, on cell proliferation was analyzed using 5-ethynyl-2-deoxyuridine incorporation and MTT assay. RESULTS: MiR-19a showed an up-regulation in HBV-positive HCC patients compared to healthy controls and HBV-negative HCC patients, while miR-122 and miR-223 showed a down-regulation compared to healthy controls, and miR-122 in HBV-positive HCC patients was also down-regulated when compared to HBV-negative HCC patients. MiR-19a was found to be up-regulated in HepG2 cells transfected with HBx or 1.3 fold HBV genome, but down-regulated in HepG2.2.15 cells. MiR-122 and miR-223 were down-regulated in HBx or 1.3 fold HBV transfected HepG2 cells as well as in HepG2.2.15 cell. Their target mRNAs and corresponding proteins-PTEN was down-regulated, while cyclin G1 and c-myc were found to be up-regulated. Modulated expression of miR-19a, miR-122 and miR-223 enhanced cell proliferation of HBx-transfected HepG2 cells, and rescue experiment further showed that their target genes-PTEN, cyclin G1and c-myc involved in cell proliferation of HBx-transfected HepG2 cells. CONCLUSIONS: The expression of miR-19a, miR-122 and miR-223 were differentially regulated by HBx protein, the differential expression of miR-19a, miR-122 and miR-223 plays an important role in cell proliferation of HCC. This study provides new insight into understanding how HBx protein interacts with miRNAs and subsequently regulates host function.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/metabolismo , Transativadores/metabolismo , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Proliferação de Células/genética , Ciclina G1/metabolismo , Células Hep G2 , Vírus da Hepatite B/fisiologia , Humanos , Neoplasias Hepáticas/virologia , MicroRNAs/genética , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transfecção , Proteínas Virais Reguladoras e Acessórias
6.
Cancer Cell Int ; 15: 116, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26692822

RESUMO

BACKGROUND: Multidrug resistance is one of the major reasons chemotherapy-based treatments failed in hepatitis B virus (HBV) related hepatocellular carcinoma (HCC). Hypoxia is generally associated with tumor chemo-resistance. The aim of the study was to investigate the effect of Arsenic trioxide (As2O3) on the hypoxia-induced chemo-resistance to 5-FU or cisplatin and explored its underlying mechanism in the HBx-HepG2 cells. METHODS: MTT assay was used to examine the cell viability. Mitochondrial membrane potential (MMP) and cell cycle was examined by flow cytometry. qRT-PCR was employed to observe the mRNA expression level; and western blot assay was used to determine the protein expression level. RESULTS: Our results showed that transfection of HBx plasmid established the HBx-HepG2 cells expressing HBx, and the expression of HBx was confirmed by qRT-PCR and western blot. Exposure of HBx-HepG2 cells to hypoxia (5 % O2, 3 % O2, 1 % O2) for 48 h increased the chemo-resistance to 5-fluorouracil (5-FU) (50-1600 µM) and cisplatin (25-800 µM), reduced MMP, and caused the cell cycle arrest at G0/G1 phase in a concentration-dependent manner. Hypoxia also concentration-dependently (5 % O2, 3 % O2, 1 % O2) reduced mRNA expression level of P-glycoprotein (P-gp), multidrug resistance protein (MRP1), lung resistance protein (LRP), and decreased the protein expression level of hypoxia-inducible factor-1α (HIF-1α), P-gp MRP1, and LRP. Following pretreatment with As2O3 at a non-cytotoxic concentration re-sensitized the hypoxia (1 % O2)-induced chemo-resistance to 5-FU and cisplatin in HBx-HepG2 cells. As2O3 pretreatment also prevented MMP reduction and G0/G1 arrest induced by hypoxia. Meanwhile, As2O3 antagonized increase of HIF-1α protein induced by hypoxia, and it also suppresses the increase in expression levels of P-gp, MRP1, and LRP mRNA and proteins. In addition, As2O3 in combination with 5-FU treatment caused up-regulation of DR5, caspase 3, caspase 8, and caspase 9, and down-regulation of BCL-2, but had no effect of DR4. CONCLUSIONS: Our results may suggest that As2O3 re-sensitizes hypoxia-induced chemo-resistance in HBx-HepG2 via complex pathways, and As2O3 may be a potential agent that given in combination with other anti-drugs for the treatment of HBV related HCC, which is resistant to chemotherapy.

7.
Oncol Lett ; 28(2): 369, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38933807

RESUMO

Introducing the exploration of stimulated CD4+ cells adenosine triphosphate (sATPCD4) levels for immune monitoring post non-small cell lung cancer (NSCLC) chemotherapy, the present study aimed to investigate its efficacy in gauging the potential risk of disease progression (PD) in patients with NSCLC. Therefore, a total of 89 patients with advanced NSCLC, who underwent chemotherapy between August 15 2022 and August 30 2023 at the Fifth Affiliated Hospital of Guangzhou Medical University (Guangzhou, China), were retrospectively studied. Patients were divided into the PD (n=21) and disease stability (non-PD; n=68) groups and their clinical data were compared. The thresholds for predicting PD were identified using receiver operating characteristics (ROC) curves. Multivariate logistic regression analysis was carried out to assess the association between peripheral blood markers and the incidence of PD. Therefore, post-chemotherapy, significant differences in white blood cell count, non-stimulated CD4+ cells ATP and sATPCD4 levels were obtained between patients in the PD and non-PD groups (P<0.05). In addition, sATPCD4 levels were notably decreased in the PD group compared with the non-PD group. Furthermore, ROC analysis revealed that the predictive threshold for PD was 224.5 ng/ml [area under the curve=0.887; 95% confidence interval, 0.811-0.963]. Additionally, patients with low immunity (ATP <224.5 ng/ml) exhibited a higher risk of PD compared with the high-immunity group (ATP >224.5 ng/ml; P<0.0001). Finally, multivariate logistic regression analysis suggested that sATPCD4 could serve as an independent factor for predicting NSCLC progression. Overall, the current study predicted that immune function could be possibly associated with the risk of PD in patients with NSCLC.

8.
Technol Cancer Res Treat ; 20: 1533033820986826, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33522433

RESUMO

BACKGROUND: ADAMTS5 has different roles in multiple types of cancers and participates in various molecular mechanisms. However, the prognostic value of ADAMTS5 in patients with hepatocellular carcinoma (HCC) still remains unclear. We carried the study to evaluate the prognostic value and identified underlying molecular mechanisms in HCC. METHODS: Firstly, the association of ADAMTS5 expression and clinicopathological parameters was evaluated by in GSE14520. Next, ADAMTS5 expression in HCC was performed using GSE14520, GSE36376, GSE76427 and The Cancer Genome Atlas (TCGA) profile. Furthermore, Kaplan-Meier analysis, Univariate and Multivariate Cox regression analysis, subgroup analysis was performed to evaluate the prognostic value of ADAMTS5 in HCC. Finally, GO enrichment analysis, gene set enrichment analysis (GSEA) and weighted gene co-expression network analysis (WGCNA) were performed to revealed underlying molecular mechanisms. RESULT: The expression of ADAMTS5 was positively correlated with the development of HCC. Next, high ADAMTS5 expression was significantly associated with poorer survival (all P < 0.05) and the impact of ADAMTS5 on all overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), disease specific survival (DSS) and progression free interval (PFI) was specific for HCC among other 29 cancer types. Subgroup analysis showed that ADAMTS5 overexpression was significantly associated with poorer OS in patients with HCC. Finally, ADAMTS5 might participate in the status conversion from metabolic-dominant to extracellular matrix-dominant, and the activation of ECM-related biological process might contribute to high higher mortality risk for patients with HCC. CONCLUSION: ADAMTS5 may play an important role in the progression of HCC, and may be considered as a novel and effective biomarker for predicting prognosis for patients with HCC.


Assuntos
Proteína ADAMTS5/genética , Carcinoma Hepatocelular/etiologia , Biologia Computacional , Suscetibilidade a Doenças , Neoplasias Hepáticas/etiologia , Proteína ADAMTS5/metabolismo , Adulto , Idoso , Biomarcadores Tumorais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Biologia Computacional/métodos , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica , Hepatite B/complicações , Hepatite B/virologia , Humanos , Estimativa de Kaplan-Meier , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico
9.
Biosci Rep ; 41(1)2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33350431

RESUMO

Breast carcinoma (BRCA) is the most common carcinoma among women worldwide. Despite the great progress achieved in early detection and treatment, morbidity and mortality rates remain high. In the present study, we make a systematic analysis of BRCA using TCGA database by applying CIBERSORT and ESTIMATE computational methods, uncovered CD3D as a prognostic biomarker by intersection analysis of univariate COX and protein-protein interaction (PPI). It revealed that high CD3D expression was strongly associated with poor survival of BRCA, based on The Cancer Genome Atlas (TCGA) database and online websites. Gene Set Enrichment Analysis (GSEA) revealed that the high CD3D expression group was mainly enriched for the immune-related pathways and the low CD3D expression group was mainly enriched for metabolic-related activities. Based on CIBERSORT analysis, the difference test and correlation test suggested that CD3D had a strong correlation with T cells, particularly CD8 + T cells, which indicated that CD3D up-regulation may increase T cell immune infiltration in the TME and induce antitumor immunity by activating T lymphocytes. Furthermore, the correlation analysis showed that CD3D expression had a strongly positive correlation with immune checkpoints, which indicating that the underlying mechanism involves CD3D mediated regulation of T cell functions in BRCA, and single cell RNA-seq analysis revealed that CD3D correlate with CD8 + T cells and it is itself highly expressed in CD8 + T cells. In summary, we identified a prognostic biomarker CD3D in BRCA, which was associated with lymphocyte infiltration, immune checkpoints and could be developed for innovative therapeutics of BRCA.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Complexo CD3/metabolismo , Microambiente Tumoral , Neoplasias da Mama/imunologia , Neoplasias da Mama/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Prognóstico
10.
Onco Targets Ther ; 14: 623-636, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33519210

RESUMO

BACKGROUND: Cisplatin is a vital chemotherapy regimen for gastric cancer (GC), while partial response is observed (approximately 40%) because of drug resistance. Thus, it is urgent to improve drug sensitivity to improve the therapeutic effect of cisplatin on GC. PURPOSE: The study was performed to explore the synergistic effect of decitabine and cisplatin in GC. MATERIALS AND METHODS: Cancer and matched adjacent tissues from patients with GC were obtained and quantitative real-time PCR (qRT-PCR), Western blot and immunohistochemistry were performed to evaluate Sox2 expression level. Methylation-specific PCR (MSP) was performed to assess the effect of 5-aza-2'-deoxycytidine (5-Aza-CdR) on Sox2 promoter. Cell proliferation assay, scratch-wound migration assay and Transwell invasion ability were performed to assess the effect of 5-Aza-CdR on proliferation, migration and invasion ability. Meantime, the effect of 5-Aza-CdR was also investigated in gastric cell lines BGC-823 and nude mouse xenograft tumor model. Finally, the anti-cancer effect of decitabine, cisplatin and their combination treatment were investigated in a BGC-823 and nude mouse xenograft tumor model, Sox2 methylation level, Sox2 expression of BGC-823 and xenograft tumors were analyzed by MSP, qRT-PCR and Western blot. RESULTS: Sox2 expression was significantly associated with different differentiated degrees, depth of invasion (0.0011), lymph node metastasis (0.0013), and TNM stage (0.0002). Next, methylation inhibitor 5-Aza-CdR restored Sox2 expression to promote proliferation, migration and invasion in vitro and in vivo. Finally, cisplatin and decitabine was found to be synergistic to inhibit proliferation of xenograft tumors. Likewise, cisplatin and decitabine were also synergistic to induce Sox2 DNA demethylation to promote Sox2 mRNA and protein expression in BGC-823 and xenograft tumors. CONCLUSION: Cisplatin and decitabine could be synergistic to induce Sox2 DNA demethylation to promote expression of the Sox2 gene, which exerted an anti-tumor effect on GC. It may suggest an insight for innovative therapeutics of GC.

11.
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.

12.
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.

13.
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.

14.
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
15.
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
16.
Gastroenterol Res Pract ; 2016: 7682387, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27073394

RESUMO

Smoking is a well-known major risk factor in development of esophageal cancer, but few studies have reported the association between smoking status and prognosis of these patients. We conduct the present study to summarize current evidence. A computerized search of the PubMed and EMBASE was performed up to April 30, 2015. Eight studies, containing 4,286 patients, were analyzed. In the grouping analysis, among esophageal squamous-cell carcinoma patients, current and former smokers, compared to those who have never smoked, seemed to have a poorer prognosis (HR = 1.41, 95% CI 1.22-1.64, and HR = 1.35, 95% CI 0.92-1.97, resp.). In the subgroup analysis, adverse effects on current smoker compared with never smoker were also observed in China and the other countries (HR = 1.5, 95% CI 1.18-1.92, and HR = 1.36, 95% CI 1.12-1.65, resp.). In the group that ever smoked, we could not get a similar result. No significantly increased risk was found in esophageal adenocarcinoma patients compared to the squamous-cell histology ones. In the smoking intensity analysis, heavy smoking was associated with poor survival in esophageal squamous-cell carcinoma. Our pooled results supported the existence of harmful effects of smoking on survival after esophagus cancer diagnosis.

17.
Dalton Trans ; 43(4): 1583-8, 2014 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-24217856

RESUMO

A water-soluble "turn-on" fluorescent probe (RD1) for Fe(3+) based on rhodamine B was designed and synthesized. The fluorescent probe showed "turn-on" fluorescent and colorimetric responses to Fe(3+) with a high selectivity in water containing less than 1% organic cosolvent. Furthermore, bioimaging investigations indicated that the new probe was cell permeable and suitable for monitoring intracellular Fe(3+) in living cells by confocal microscopy with low cytotoxicity.


Assuntos
Compostos Férricos/química , Corantes Fluorescentes/química , Rodaminas/química , Cristalografia por Raios X , Concentração de Íons de Hidrogênio , Espectroscopia de Ressonância Magnética , Magnetismo , Microscopia de Fluorescência , Modelos Moleculares , Soluções , Espectrometria de Fluorescência , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrofotometria Ultravioleta , Água/química
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