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1.
Surg Endosc ; 36(7): 4780-4785, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34697678

RESUMO

OBJECTIVE: The aim of this study is to evaluate the feasibility and safety of a new single-port robotic surgical system for gynecological surgery in the porcine model. MATERIALS AND METHODS: Six female Tibetan miniature pigs underwent robot-assisted single-port laparoscopic total hysterectomy with the newly developed single-port EDGE SP1000 platform. Estimated blood loss (EBL), docking time, operative time, and intraoperative and postoperative complications were recorded. Postoperative pain was assessed by VAS (visual analog scale) score at 6 h, 12 h, 24 h, and 48 h. Then the experimental animals were observed for one week after surgery to assess their mental status, incisional infections and finally euthanized for necropsy to assess the recovery of the vaginal stump. RESULTS: Six hysterectomies of pigs were successfully completed. There were no significant intraoperative complications in the six surgeries. The average total operation time was 113.33 min (95-143 min), and the average docking time was 5.5 min (4-7 min). The average EBL was 10 ml (5 ~ 20 ml). The mean VAS scores at 6, 12, 24, and 48 h postoperatively were 6.3, 5.7, 5, 3, respectively. At 7 days postoperatively, no significant incisional infections or other complications were observed. Post-euthanasia examination of the pelvis showed no significant abnormalities in the vaginal stump. CONCLUSION: This preclinical study of a new single-port surgical system for gynecologic procedures demonstrated the safety and feasibility of the EDGE SP1000 system in porcine models. Further studies are required to assess its clinical utility in the future.


Assuntos
Ginecologia , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Animais , Feminino , Procedimentos Cirúrgicos em Ginecologia/métodos , Humanos , Histerectomia/métodos , Laparoscopia/métodos , Duração da Cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Suínos
2.
Exp Eye Res ; 203: 108427, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33383027

RESUMO

The aim of the present study was to investigate the pathogenesis of age-related macular degeneration (AMD) by constructing a regulatory circRNA-miRNA-mRNA network. By adjusting the P value to <0.05 and the absolute log value of fold change to >0.25, 2920 and 1057 differentially expressed mRNAs were identified from GSE50195 and GSE29801, respectively. Based on a literature review, Starbase database analysis, and RNA hybrid assays, we obtained 77 miRNA-mRNA and 331 circRNA-miRNA pairs. After combining these pairs, we constructed a circRNA-miRNA-mRNA network possessing 303 circRNA nodes, 4 miRNA nodes, 51 mRNA nodes, and 408 edges. By utilizing protein-protein network analysis, the MCODE algorithm, and the highest degree of circRNA node, we identified the regulatory axis of hsa_circRNA7329/hsa-miR-9/SCD. Hsa_circRNA7329 may regulate SCD through hsa-miR-9 to promote macrophage-mediated inflammation and pathologic angiogenesis, which lead to AMD development. However, the underlying details require further investigation.


Assuntos
Redes Reguladoras de Genes , Degeneração Macular/genética , MicroRNAs/genética , RNA Circular/genética , RNA Mensageiro/genética , Bases de Dados Factuais , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/fisiologia , Ontologia Genética , Humanos , Mapas de Interação de Proteínas/genética , Transdução de Sinais/genética
3.
Front Genet ; 12: 705512, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35058963

RESUMO

Background: Inhibin A (INHBA), a member of the TGF-ß superfamily, has been shown to be differentially expressed in various cancer types and is associated with prognosis. However, its role in cervical cancer remains unclear. Methods: We aimed to demonstrate the relationship between INHBA expression and pan-cancer using The Cancer Genome Atlas (TCGA) database. Next, we validated INHBA expression in cervical cancer using the Gene Expression Omnibus (GEO) database, including GSE7803, GSE63514, and GSE9750 datasets. Enrichment analysis of INHBA was performed using the R package "clusterProfiler." We analyzed the association between immune infiltration level and INHBA expression in cervical cancer using the single-sample gene set enrichment analysis (ssGSEA) method by the R package GSVA. We explored the association between INHBA expression and prognosis using the R package "survival". Results: Pan-cancer data analysis showed that INHBA expression was elevated in 19 tumor types, including cervical cancer. We further confirmed that INHBA expression was higher in cervical cancer samples from GEO database and cervical cancer cell lines than in normal cervical cells. Survival prognosis analysis indicated that higher INHBA expression was significantly associated with reduced Overall Survival (p = 0.001), disease Specific Survival (p = 0.006), and Progression Free Interval (p = 0.001) in cervical cancer and poorer prognosis in other tumors. GSEA and infiltration analysis showed that INHBA expression was significantly associated with tumor progression and some types of immune infiltrating cells. Conclusion: INHBA was highly expressed in cervical cancer and was significantly associated with poor prognosis. Meanwhile, it was correlated with immune cell infiltration and could be used as a promising prognostic target for cervical cancer.

4.
Int J Med Sci ; 17(15): 2362-2372, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922202

RESUMO

Cervical cancer is the most common gynecologic malignant tumor, with a high incidence in 50-55-year-olds. This study aims to investigate the potential molecular mechanism of RRM2 for promoting the development of cervical cancer based on The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). RRM2 was found to be significant upregulated in cervical tissue (P<0.05) by extracting the expression of RRM2 from TCGA, GSE63514, GSE7410, GSE7803 and GSE9750. Survival analysis indicated that the overall survival was significantly worse in the patients with high-expression of RRM2 (P<0.05). The top 1000 positively/negatively correlated genes with RRM2 by Pearson Correlation test were extracted. The gene co-expression network by Weighted Gene Co-Expression Network Analysis (WGCNA) with these genes and the clinical characteristics (lymphocyte infiltration, monocyte infiltration, necrosis, neutrophil infiltration, the number of normal/stromal/tumor cells and the number of tumor nuclei) was constructed. By screening the hub nodes from the co-expression network, results suggested that RRM2 may co-express with relevant genes to regulate the number of stromal/tumor cells and the process of lymphocyte infiltration to promote the progression of cervical cancer. RRM2 is likely to become a novel potential diagnostic and prognostic biomarker of cervical cancer and provide evidence to support the study of mechanisms for cervical cancer.


Assuntos
Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Ribonucleosídeo Difosfato Redutase/genética , Neoplasias do Colo do Útero/genética , Linhagem Celular Tumoral , Proliferação de Células , Colo do Útero/patologia , Conjuntos de Dados como Assunto , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas/genética , Análise de Sobrevida , Regulação para Cima , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia
5.
Front Genet ; 11: 725, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32793281

RESUMO

Cervical cancer and endometrial cancer remain serious threats to women's health. Even though some patients can be treated with surgery plus chemoradiotherapy as a conventional option, the overall efficacy is deemed unsatisfactory. As such, the development for new treatment approaches is truly necessary. In recent years, immunotherapy has been widely used in clinical practice and it is an area of great interest that researchers are keeping attention on. However, a thorough immune-related genes (IRGs) study for cervical cancer and endometrial cancer is still lacking. We therefore aim to make a comprehensive evaluation of IRGs through bioinformatics and large databases, and also investigate the relationship between the two types of cancer. We reviewed the transcriptome RNAs of IRGs and clinical data based on the TCGA database. Survival-associated IRGs in cervical/endometrial cancer were identified using univariable and multivariable Cox proportional-hazard regression analysis for developing an IRG signature model to evaluate the risk of patients. In the end, this model was validated based on the enrichment analyses through GO, KEGG, and GSEA pathways, Kaplan-Meier survival curve, ROC curves, and immune cell infiltration. Our results showed that out of 25/23 survival-associated IRGs for cervical/endometrial cancer, 13/12 warranted further examination by multivariate Cox proportional-hazard regression analysis and were selected to develop an IRGs signature model. As a result, enrichment analyses for high-risk groups indicated main enriched pathways were associated with tumor development and progression, and statistical differences were found between high-risk and low-risk groups as shown by Kaplan-Meier survival curve. This model could be used as an independent measure for risk assessment and was considered relevant to immune cell infiltration, but it had nothing to do with clinicopathological characteristics. In summary, based on comprehensive analysis, we obtained the IRGs signature model in cervical cancer (LTA, TFRC, TYK2, DLL4, CSK, JUND, NFATC4, SBDS, FLT1, IL17RD, IL3RA, SDC1, PLAU) and endometrial cancer (LTA, PSMC4, KAL1, TNF, SBDS, HDGF, LTB, HTR3E, NR2F1, NR3C1, PGR, CBLC), which can effectively evaluate the prognosis and risk of patients and provide justification in immunology for further researches.

6.
Biomed Res Int ; 2020: 5478574, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32351997

RESUMO

To reconstruct the ceRNA biological network of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) and to select an appropriate mRNA as a biomarker that could be used for CESC early diagnosis and prognosis evaluation. We downloaded CESC data from the TCGA public database, and statistical analysis was conducted with the R software to find out differential expressed genes encoding for lncRNAs, miRNAs, and mRNAs. The differentially expressed mRNAs (DEmRNAs) screened in the ceRNA network were analyzed for survival to find the mRNAs with significantly linked to the survival prognosis. These mRNAs were searched in the Pathological Atlas to identify the final appropriate mRNAs. Differential expression analysis revealed 773 lncRNAs, 94 miRNAs, and 2466 mRNAs. Survival analysis of DEmRNAs in the ceRNA network indicated that ADGRF4, ANXA8L1, HCAR3, IRF6, and PDE2A (P < 0.05) were negatively correlated with survival time. Verification of these six DEmRNAs in the Pathology Atlas indicated that PDE2A was a possible biomarker for CESC patients. PDE2A might be a biomarker for early diagnosis and prognosis evaluation of CESC patients, but due to the lack of available data, further studies may be needed for confirmation.


Assuntos
Adenocarcinoma , Biomarcadores Tumorais , Carcinoma de Células Escamosas , Bases de Dados de Ácidos Nucleicos , Proteínas de Neoplasias , RNA Neoplásico , Neoplasias do Colo do Útero , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Mineração de Dados , Feminino , Humanos , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo
7.
Oncol Lett ; 19(4): 3316-3332, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32256826

RESUMO

Cervical Cancer is one of the leading causes of cancer-associated mortality in women. The present study aimed to identify key genes and pathways involved in cervical cancer (CC) progression, via a comprehensive bioinformatics analysis. The GSE63514 dataset from the Gene Expression Omnibus database was analyzed for hub genes and cancer progression was divided into four phases (phases I-IV). Pathway enrichment, protein-protein interaction (PPI) and pathway crosstalk analyses were performed, to identify key genes and pathways using a criterion nodal degree ≥5. Gene pathway analysis was determined by mapping the key genes into the key pathways. Co-expression between key genes and their effect on overall survival (OS) time was assessed using The Cancer Genome Atlas database. A total of 3,446 differentially expressed genes with 107 hub genes were identified within the four phases. A total of 14 key genes with 11 key pathways were obtained, following extraction of ≥5 degree nodes from the PPI and pathway crosstalk networks. Gene pathway analysis revealed that CDK1 and CCNB1 regulated the cell cycle and were activated in phase I. Notably, the following terms, 'pathways in cancer', 'focal adhesion' and the 'PI3K-Akt signaling pathway' ranked the highest in phases II-IV. Furthermore, FN1, ITGB1 and MMP9 may be associated with metastasis of tumor cells. STAT1 was indicated to predominantly function at the phase IV via cancer-associated signaling pathways, including 'pathways in cancer' and 'Toll-like receptor signaling pathway'. Survival analysis revealed that high ITGB1 and FN1 expression levels resulted in significantly worse OS. CDK1 and CCNB1 were revealed to regulate proliferation and differentiation through the cell cycle and viral tumorigenesis, while FN1 and ITGB1, which may be developed as novel prognostic factors, were co-expressed to induce metastasis via cancer-associated signaling pathways, including PI3K-Art signaling pathway, and focal adhesion in CC; however, the underlying molecular mechanisms require further research.

8.
Oncol Lett ; 18(6): 5995-6007, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31788074

RESUMO

The present study aimed to identify the core genes and pathways involved in depression in patients with ovarian cancer (OC) who suffer from high or low-grade depression. The dataset GSE9116 from Gene Expression Omnibus database was analyzed to identify differentially expressed genes (DEGs) in these patients. To elucidate how certain genes could promote depression in patients with OC, pathway crosstalk, protein-protein interaction (PPI) and comprehensive gene-pathway analyses were determined using WebGestalt, ToppGene and Search Tool for the Retrieval of Interacting Genes and gene ontology analysis. Key genes and pathways were extracted from the gene-pathway network, and gene expression and survival analysis were evaluated. A total of 93 DEGs were identified from GSE9116 dataset, including 84 upregulated genes and nine downregulated genes. The PPI, pathway crosstalk and comprehensive gene-pathway analyses highlighted C-C motif chemokine ligand 2 (CCL2), Fos proto-oncogene, AP-1 transcription factor subunit (FOS), serpin family E member 1 (SERPINE1) and serpin family G member 1 (SERPING1) as core genes involved in the promotion of depression in patients with OC. These core genes were involved in the following four pathways 'Ensemble of genes encoding ECM-associated proteins including ECM-affiliated proteins', 'ECM regulators and secreted factors', 'Ensemble of genes encoding extracellular matrix and extracellular matrix-associated proteins' and 'MAPK signaling pathway and IL-17 signaling pathway'. The results from gene expression and survival analysis demonstrated that these four key genes were upregulated in patients with OC and high-grade depression and could worsen patients' survival. These results suggested that CCL2, FOS, SERPINE1 and SERPING1 may serve a crucial role in the promotion of depression in patients with OC. This finding may provide novel markers for predicting and treating depression in patients with OC; however, the underlying mechanisms remain unknown and require further investigation.

9.
Oncol Lett ; 18(1): 617-628, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31289534

RESUMO

Cervical, endometrial and vulvar cancer are three common types of gynecological tumor that threaten the health of females worldwide. Since their underlying mechanisms and associations remain unclear, a comprehensive and systematic bioinformatics analysis is required. The present study downloaded GSE63678 from the GEO database and then performed functional enrichment analyses, including gene ontology and pathway analysis. To further investigate the molecular mechanisms underlying the three types of gynecological cancer, protein-protein interaction (PPI) analysis was performed. A biological network was generated with the guidance of the Kyoto Encyclopedia of Genes and Genomes database and was presented in Cytoscape. A total of 1,219 DEGs were identified for the three types of cancer, and 25 hub genes were revealed. Pathway analysis and the PPI network indicated that four main types of pathway participate in the mechanism of gynecological cancer, including viral infections and cancer formation, tumorigenesis and development, signal transduction, and endocrinology and metabolism. A preliminary gynecological cancer biological network was constructed. Notably, following all analysis, the phosphoinositide 3-kinase (PI3K)/Akt pathway was identified as a potential biomarker pathway. Seven pivotal hub genes (CCNA2, CDK1, CCND1, FGF2, IGF1, BCL2 and VEGFA) of the three gynecological cancer types were proposed. The seven hub genes may serve as targets in gynecological cancer for prevention and early intervention. The PI3K/Akt pathway was identified as a critical biomarker of the three types of gynecological cancer, which may serve a role in the pathogenesis. In summary, the present study provided evidence that could support the treatment of gynecologic tumors in the future.

10.
Oncol Rep ; 41(4): 2209-2225, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30816541

RESUMO

The present study was performed with the aim of understanding the mechanisms of pathogenesis and providing novel biomarkers for cervical cancer by constructing a regulatory circular (circ)RNA­micro (mi)RNA­mRNA network. Using an adjusted P-value of <0.05 and an absolute log value of fold-change >1, 16 and 156 miRNAs from GSE30656 and The Cancer Genome Atlas (TCGA), 5,321 mRNAs from GSE63514, 4,076 mRNAs from cervical squamous cell carcinoma and endocervical adenocarcinoma (from TCGA) and 75 circRNAs from GSE102686 were obtained. Using RNAhybrid, Venn and UpSetR plot, 12 circRNA­miRNA pairs and 266 miRNA­mRNA pairs were obtained. Once these pairs were combined, a circRNA­miRNA­mRNA network with 11 circRNA nodes, 4 miRNA nodes, 153 mRNA nodes and 203 edges was constructed. By constructing the protein­protein interaction network using Molecular Complex Detection scores >5 and >5 nodes, 7 hubgenes (RRM2, CEP55, CHEK1, KIF23, RACGAP1, ATAD2 and KIF11) were identified. By mapping the 7 hubgenes into the preliminary circRNA­miRNA­mRNA network, a circRNA­miRNA­hubgenes network consisting of 5 circRNAs (hsa_circRNA_000596, hsa_circRNA_104315, hsa_circRNA_400068, hsa_circRNA_101958 and hsa_circRNA_103519), 2 mRNAs (hsa­miR­15b and hsa­miR­106b) and 7 mRNAs (RRM2, CEP55, CHEK1, KIF23, RACGAP1, ATAD2 and KIF11) was constructed. There were 22 circRNA­miRNA­mRNA regulatory axes identified in the subnetwork. By analyzing the overall survival for the 7 hubgenes using the Gene Expression Profiling Interactive Analysis tool, higher expression of RRM2 was demonstrated to be associated with a significantly poorer overall survival. PharmGkb analysis identified single nucleotide polymorphisms (SNPs) of rs5030743 and rs1130609 of RRM2, which can be treated with cladribine and cytarabine. RRM2 was also indicated to be involved in the gemcitabine pathway. The 5 circRNAs (hsa_circRNA_000596, hsa_circRNA_104315, hsa_circRNA_400068, hsa_circRNA_101958 and hsa_circRNA_103519) may function as competing endogenous RNAs and serve critical roles in cervical cancer. In addition, cytarabine may produce similar effects to gemcitabine and may be an optional chemotherapeutic drug for treating cervical cancer by targeting rs5030743 and rs1130609 or other similar SNPs. However, the specific mechanism of action should be confirmed by further study.


Assuntos
Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes/genética , Ribonucleosídeo Difosfato Redutase/genética , Neoplasias do Colo do Útero/genética , Biomarcadores Tumorais/metabolismo , Carcinogênese/genética , Biologia Computacional , Conjuntos de Dados como Assunto , Feminino , Perfilação da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único , Mapas de Interação de Proteínas/genética , RNA/genética , RNA/metabolismo , RNA Circular , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ribonucleosídeo Difosfato Redutase/metabolismo , Análise de Sobrevida , Neoplasias do Colo do Útero/mortalidade
11.
Cell Death Discov ; 4: 36, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30275981

RESUMO

This study aims to investigate the role of miR-106b-5p in cervical cancer by performing a comprehensive analysis on its expression and identifying its putative molecular targets and pathways based on The Cancer Genome Atlas (TCGA) dataset, Gene Expression Omnibus (GEO) dataset, and literature review. Significant upregulation of miR-106b-5p in cervical cancer is confirmed by meta-analysis with the data from TCGA, GEO, and literature. Moreover, the expression of miR-106b-5p is significantly correlated with the number of metastatic lymph nodes. Our bioinformatics analyses show that miR-106b could promote cervical cancer progression by modulating the expression of GSK3B, VEGFA, and PTK2 genes. Importantly, these three genes play a crucial role in PI3K-Akt signaling, focal adhesion, and cancer. Both the expression of miR-106b-5p and key genes are upregulated in cervical cancer. Several explanations could be implemented for this upregulation. However, the specific mechanism needs to be investigated further.

12.
Oncol Lett ; 16(1): 1003-1009, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29963176

RESUMO

The aim of the present study was to investigate the key pathways and genes in the progression of cervical cancer. The gene expression profiles GSE7803 and GSE63514 were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using GEO2R and the limma package, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using the Database for Annotation, Visualization and Integrated Discovery. The hub genes were identified using Cytoscape and protein-protein interaction (PPI) networks were constructed using the STRING database. A total of 127 and 99 DEGs were identified in the pre-invasive and invasive stages of cervical cancer, respectively. GO enrichment analysis indicated that the DEGs in pre-invasive cervical cancer were primarily associated with the 'protein binding', 'single-stranded DNA-dependent ATPase activity', 'DNA replication origin binding' and 'microtubule binding' terms, whereas the DEGs in invasive cervical cancer were associated with the 'extracellular matrix (ECM) structural constituent', 'heparin binding' and 'integrin binding'. KEGG enrichment analysis revealed that the pre-invasive DEGs were significantly enriched in the 'cell cycle', 'DNA replication' and 'p53 signaling pathway' terms, while the invasive DEGs were enriched in the 'amoebiasis', 'focal adhesion', 'ECM-receptor interaction' and 'platelet activation' terms. The PPI network identified 4 key genes (PCNA, CDK2, VEGFA and PIK3CA), which were hub genes for pre-invasive and invasive cervical cancer. In conclusion, bioinformatics analysis identified 4 key genes in cervical cancer progression (PCNA, CDK2, VEGFA and PIK3CA), which may be potential biomarkers for differentiating normal cervical epithelial tissue from cervical cancer.

13.
Chem Biol Drug Des ; 91(3): 728-734, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29068538

RESUMO

This study aimed to develop novel 1,3,5-triazine derivatives as potent anti-cervical cancer agents. The compounds were synthesized in short steps with an excellent yield and characterized via various spectroscopic and analytical methods. A structure-activity relationship study suggested that electron-withdrawing substituents showed greater anticancer activity than electron-donating groups. Compound 7p (p-fluoro) showed the highest activity against cervical cancer cells. In a nude mouse xenograft model inoculated with HeLa cells, 7p showed dose-dependent inhibition of cervical tumour growth. Histopathological examination of excised tumour-bearing tissues showed that 7p improved the microstructure in a dose-dependent manner. Compound 7p also increased the proportions of HeLa cells in G0/G1 and S-phase and significantly decreased that of G2/M-phase. The effects of 7p on C-caspase-3, C-caspase-9, Bcl-2 and Bax expression in HeLa cells were also determined.


Assuntos
Antineoplásicos , Caspase 3/biossíntese , Caspase 9/biossíntese , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Triazinas , Proteína X Associada a bcl-2/biossíntese , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Ciclo Celular/efeitos dos fármacos , Células HeLa , Humanos , Células Jurkat , Camundongos , Camundongos Nus , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Triazinas/síntese química , Triazinas/química , Triazinas/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Oncotarget ; 7(44): 72067-72075, 2016 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-27732565

RESUMO

The human cervical cancer (CC) acts as the most common one of women tumors. However, the pathological changes and molecular alterations of CC are not clear. It has been reported that miR-202 takes part in the development and progression of different tumors. The present study aims to detect the expression of miR-202 in 100 cases of CC tissues and cells, and then we continued to investigate the potential mechanisms of miR-202 in CC cells. In this work, we found that the expression of miR-202 is obviously decreased in both CC cell lines and tissues, and negatively related with the expression of cyclin D1 in SiHa, HeLa and Caski cells. In-vitro assay revealed that the ectopic expression of miR-202 suppressed the proliferation, migration and invasion of SiHa and HeLa cells. Additionally, the over-expression of miR-202 extremely affected the expression of cyclin D1 protein. Notably, the over-expression of cyclin D1 in SiHa and HeLa cells with miR-202 mimics attenuated the inhibitory effects of miR-202 on cell proliferation, migration and invasion. In conclusion, our study identified that miR-202 plays an important role in regulating cell proliferation, migration and invasion of CC by directly targeting cyclin D1, thus miR-202 may represent a potential therapeutic target for patients with cervical cancer.


Assuntos
Ciclina D1/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Neoplasias do Colo do Útero/genética , Movimento Celular , Proliferação de Células , Colo do Útero/patologia , Ciclina D1/metabolismo , Progressão da Doença , Regulação para Baixo , Feminino , Células HeLa , Humanos , Queratinócitos , Gradação de Tumores , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia
15.
Mol Neurobiol ; 53(9): 6209-6217, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-26558632

RESUMO

Proliferating cell nuclear antigen (PCNA) is reported as a famous marker in various tumors. A couple of articles have been published about the clinical function of PCNA on cancer progression; however, these results are conflicting in some degree. Thus, it is crucial to perform a systematic review and meta-analysis to identify their real actions. Here, we took cervical cancer and glioma as example and then pooled hazard ratios (HRs) or odds ratios (ORs) with 95 % confidence intervals (95 % CIs). In the present study, the PCNA expression in cervical cancer and gliomas patients was both correlated with 5-year-overall survival (OS) (HR = 4.41, 95 % CI 2.71-7.17, p = 0.000; HR = 4.40, 95 % CI 3.00-6.47, p = 0.000; respectively). In addition, a fixed effect model revealed a significant association between PCNA and FIGO stage (OR = 4.48, 95 % CI 3.48-5.77, p = 0.000) or WHO grade (OR = 5.64, 95 % CI 4.15-7.68, p = 0.000), rather than age (OR = 1.01, 95 % CI 0.71-1.43, p = 0.957; OR = 1.00, 95 % CI 0.80-1.24, p = 0.989; respectively). No heterogeneity was observed across all studies. According to funnel plot, no publication bias was reported. In conclusion, our systematic review suggests that PCNA expression is significantly associated with poor 5-year survival, advanced stage or higher WHO grade, which might be suggested as a useful prognostic and diagnostic biomarker, or an effective therapy target in cervical cancer, gliomas, or even more cancers.


Assuntos
Neoplasias/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Humanos , Prognóstico , Viés de Publicação , Fatores de Risco , Análise de Sobrevida
16.
Tumour Biol ; 36(12): 9763-7, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26156805

RESUMO

In recent years, astrocyte elevated gene-1 (AEG-1) has been recommended as an important mediator that is involved in the epithelial-to-mesenchymal transition (EMT) process. However, the mechanisms underlying the chemokine (C-C motif) ligand 20 (CCL20)/chemokine (C-C motif) receptor 6 (CCR6)-AEG-1 pathway-mediated EMT in cervical cancer (CC) have not been well featured till now. We used immunohistochemistry and immunoblotting to assess the expression of AEG-1 in 94 cervical cancer tissues and cells. Subsequently, cervical cancer SiHa cells were treated with si-AEG-1 and then subjected to in vitro assays. We observed that AEG-1 proteins were highly expressed in cervical cancer tissues and closely correlated with International Federation of Gynecology and Obstetrics (FIGO) stage and metastasis. Importantly, we validated the expression of AEG-1, p-Erk1/2, p-Akt, vimentin, N-cadherin, and matrix metalloproteinase 2 (MMP2) increased in SiHa with CCL20 treatment in a concentration-dependent manner. When cells were treated with si-AEG-1, the expression of p-Erk1/2, p-Akt, vimentin, N-cadherin, and MMP2 was also downregulated. Using the cell cycle assay, the knockdown of AEG-1 inhibited the entry of G1 into S phase. In conclusion, AEG-1 mediates CCL20/CCR6-induced EMT development via both Erk1/2 and Akt signaling pathway in cervical cancer, which indicates that CCL20/CCR6-AEG-1-EMT pathway could be suggested as a useful target to affect the progression of cervical cancer.


Assuntos
Moléculas de Adesão Celular/biossíntese , Quimiocina CCL20/genética , Transição Epitelial-Mesenquimal/genética , Receptores CCR6/genética , Neoplasias do Colo do Útero/genética , Adulto , Moléculas de Adesão Celular/genética , Linhagem Celular Tumoral , Proliferação de Células , Quimiocina CCL20/biossíntese , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas de Membrana , Pessoa de Meia-Idade , Proteínas de Neoplasias/biossíntese , Proteínas de Ligação a RNA , Transdução de Sinais , Neoplasias do Colo do Útero/patologia
17.
Tumour Biol ; 36(5): 3979-84, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25596084

RESUMO

We conducted a case-control study to estimate association between six common single nucleotide polymorphisms (SNPs) and risk of cervical cancer and evaluate the interaction between IL-17 gene polymorphisms and environmental factors in cervical cancer patients. This study included 264 consecutive primary cervical cancer patients and 264 age-matched controls. The genotypes of IL-17A rs2275913, rs3748067, and rs3819025 and IL-17A rs763780, rs9382084, and rs1266828 were analyzed using polymerase chain reaction-restriction fragment length of polymorphism (PCR-RFLP) assay. By logistic regression analysis, we found that individuals with AA genotype of rs2275913 were correlated with increased risk of cervical cancer when compared with GG genotype, and the odds ratio (OR) (95 % confidence interval (CI)) for AA genotype was 2.34 (1.24-4.49). By stratified analysis, individuals with AA genotype of rs2275913 were significantly associated with increased risk of cervical cancer in HPV-16- or HPV-18-infected patients when compared with GG genotype, and the OR (95 % CI) was 4.11 (1.14-22.33). In this case-control study, we suggest that rs2275913 may play an important role in the development of cervical cancer, especially in HPV-16- or HPV-18-infected patients.


Assuntos
Predisposição Genética para Doença , Interleucina-17/genética , Neoplasias do Colo do Útero/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Papillomavirus Humano 16/patogenicidade , Papillomavirus Humano 18/patogenicidade , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia
18.
Eur J Obstet Gynecol Reprod Biol ; 159(1): 1-18, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21664034

RESUMO

The objective of this meta-analysis was to assess whether laparoscopic-assisted vaginal hysterectomy achieves better clinical results compared with abdominal hysterectomy. Medline (PubMed), EMBASE, Web of Science, ProQuest, Cochrane Library and China Biological Medicine Database were searched to identify randomized controlled trials that compared laparoscopic-assisted vaginal hysterectomy with abdominal hysterectomy. Twenty-three trials were studied and the analysis was performed using Review Manager Version 5 and R Version 2.11.1. The results showed that laparoscopic-assisted vaginal hysterectomy was associated with a longer operation time, less blood loss, shorter hospital stay, smaller haemoglobin drop, less postoperative pain, quicker return to normal activities and fewer peri-operative complications. Quality of life is likely to be the key outcome to evaluate the approach for hysterectomy, but further research is needed. For suitable patients and surgeons, laparoscopic-assisted vaginal hysterectomy is a better choice than abdominal hysterectomy.


Assuntos
Histerectomia Vaginal/efeitos adversos , Laparoscopia/efeitos adversos , Doenças Uterinas/cirurgia , Atividades Cotidianas , Perda Sanguínea Cirúrgica/prevenção & controle , Feminino , Humanos , Histerectomia/efeitos adversos , Histerectomia/métodos , Complicações Pós-Operatórias/prevenção & controle , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo
19.
Arch Gynecol Obstet ; 283(6): 1275-89, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21234758

RESUMO

PURPOSE: To evaluate the clinical results of vaginal myomectomy and laparoscopic myomectomy (LM). METHODS: The database of PubMed, EMBASE, Web of Science, ProQuest, Cochrane library and China Biological Medicine Database (CBM), Chinese National Knowledge Infrastructure (CNKI), Wanfang (Chinese) and VIP (Chinese) were searched using the keywords "laparoscopic", "laparoscopically", "vaginal", "trasvaginal", "myomectomy", "randomized", "randomised" and "randomly" to identify randomized controlled trails which compared vaginal myomectomy and LM. Studies are also searched by hand. No language restrictions were made. RESULTS: Four trials were studied and the analysis was performed using Review Manager Version 5 and R software Version 2.11.1. The results had shown that vaginal myomectomy was associated with less operation time significantly, but reduced blood loss, hospital stay and gas recovery and more minor complications without significant difference. CONCLUSIONS: This meta-analysis was not powerful to form an accurate conclusion because of less number, low quality of included studies and no data on major complications and long-term outcomes such as recurrence and pregnancy. Hence, more studies and data should be awaited and involved for further evaluation.


Assuntos
Colposcopia , Laparoscopia , Leiomioma/cirurgia , Complicações Pós-Operatórias/etiologia , Neoplasias Uterinas/cirurgia , Adulto , Feminino , Humanos , Tempo de Internação , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos de Tempo e Movimento , Adulto Jovem
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