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1.
Anticancer Res ; 40(1): 213-220, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892569

RESUMO

BACKGROUND/AIM: Kisspeptin produced from the KISS1 gene is secreted from the living cells, binds to endogenous receptor KISS1R (also called G protein-coupled receptor 54, GPR54), and has various functions in normal physiological conditions. Although an anti-metastatic role of kisspeptin in cancer is well known in several cancer types, its role in brain tumors is not yet understood. Herein, we investigated a the role of kisspeptin in glioblastoma cells. MATERIALS AND METHODS: Glioblastoma cells were treated with kisspeptin and subjected to proliferation, migration, and invasion assays. KISS1R dependency was tested by KISS1R silencing with KISS1R siRNAs. RESULTS: Kisspeptin inhibited migratory and invasive abilities of U87-MG, U-251-MG and U373-MG glioblastoma cells with no effect on cell viability. KISS1R gene silencing with KISS1R siRNAs blocked kisspeptin-induced glioblastoma cell invasiveness. Moreover, chemical inhibitors against Gq, PLC or PKC blocked kisspeptin-induced glioblastoma cell invasiveness. CONCLUSION: Kisspeptin induces glioblastoma cell invasiveness via the KISS1R-Gq-PLC-PKC signaling pathway.


Assuntos
Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Glioblastoma/metabolismo , Glioblastoma/patologia , Kisspeptinas/metabolismo , Proteína Quinase C/metabolismo , Transdução de Sinais , Fosfolipases Tipo C/metabolismo , Linhagem Celular Tumoral , Ativação Enzimática , Humanos , Invasividade Neoplásica , Metástase Neoplásica
2.
Anticancer Res ; 40(1): 229-238, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892571

RESUMO

BACKGROUND/AIM: We previously reported the potential of aminonaphthoquinone derivatives as therapeutic agents against breast and other oestrogen-responsive tumours when combined with curcumin. This study aimed at screening of novel aminonaphthoquinone derivatives (Rau 008, Rau 010, Rau 015 and Rau 018) combined with curcumin for cytotoxic, anti-angiogenic and anti-metastatic effects on MCF-7 and MDA-MB-231 breast cancer cells. MATERIALS AND METHODS: Cytotoxic and anti-angiogenic effects were analysed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and enzyme-linked immunosorbent assay; while anti-metastatic effects were measured using adhesion assay, Boyden chambers and Matrigel. RESULTS: Curcumin combined with Rau 008 elicited marked cytotoxic effects in MCF-7 cells compared with the individual treatments, whereas when it was combined with Rau 015 and with Rau 018, it displayed similar effects in MDA-MB-231 cells. The anti-angiogenic effect of Rau 015 plus curcumin in MCF-7 cells and Rau 018 plus curcumin in MDA-MB-231 cells was more effective than individual treatments, while the metastatic capability of MDA-MB-231 cells was significantly reduced after treatment with the aminonaphthoquinone-curcumin combinations. CONCLUSION: Aminonaphthoquinones may offer significant promise as therapeutic agents against breast cancer, particularly when combined with curcumin.


Assuntos
Neoplasias da Mama/patologia , Curcumina/farmacologia , Progressão da Doença , Naftoquinonas/farmacologia , Neoplasias da Mama/irrigação sanguínea , Neoplasias da Mama/tratamento farmacológico , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Curcumina/química , Curcumina/uso terapêutico , Matriz Extracelular/metabolismo , Feminino , Humanos , Células MCF-7 , Naftoquinonas/química , Invasividade Neoplásica , Neovascularização Patológica/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/metabolismo
3.
Anticancer Res ; 40(1): 143-151, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892562

RESUMO

BACKGROUND/AIM: Adiponectin protects from metabolic disease and cancer. Accordingly, serum adiponectin was reduced in patients with colorectal cancer (CRC). This hepatoprotective factor was definitely increased in hepatocellular carcinoma (HCC). CRC metastases to the liver are common and the aim of the present study was to evaluate whether serum adiponectin discriminates primary from secondary liver cancers. MATERIALS AND METHODS: Adiponectin was measured by ELISA in the serum of 36 patients with colorectal liver metastases, 32 patients with HCC and 49 patients without cancer. RESULTS: Serum adiponectin levels were higher in cancer than non-tumor patients. Adiponectin was not related to TNM stage in HCC nor to the levels of serum tumor markers. Moreover, hepatic inflammation and liver fibrosis were not correlated with serum adiponectin levels. Metabolic diseases are associated with low adiponectin and a higher risk of cancer. In HCC, but not in CRC serum, adiponectin was increased in patients with hypertension and hyperuricemia. In this cohort, adiponectin positively correlated with chemerin, an adipokine supposed to contribute to metabolic disturbances. CONCLUSION: Serum adiponectin cannot discriminate primary from secondary liver tumors.


Assuntos
Adiponectina/sangue , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Biomarcadores , Comorbidade , Diagnóstico Diferencial , Feminino , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/patologia , Testes de Função Hepática , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Masculino , Invasividade Neoplásica , Estadiamento de Neoplasias
4.
J Urol ; 203(1): 62-72, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31112107

RESUMO

PURPOSE: Studies indicate that molecular subtypes in muscle invasive bladder cancer predict the clinical outcome. We evaluated whether subtyping by a simplified method and established classifications could predict the clinical outcome. MATERIALS AND METHODS: We subtyped institutional cohort 1 of 52 patients, including 39 with muscle invasive bladder cancer, an Oncomine™ data set of 151 with muscle invasive bladder cancer and TCGA (The Cancer Genome Atlas) data set of 402 with muscle invasive bladder cancer. Subtyping was done using simplified panels (MCG-1 and MCG-Ext) which included only transcripts common in published studies and were analyzed for predicting metastasis, and cancer specific, overall and recurrence-free survival. TCGA data set was further analyzed using the Lund taxonomy, the Bladder Cancer Molecular Taxonomy Group Consensus and TCGA 2017 mRNA subtype classifications. RESULTS: Muscle invasive bladder cancer specimens from cohort 1 and the Oncomine data set showed intratumor heterogeneity for transcript and protein expression. MCG-1 subtypes did not predict the outcome on univariate or Kaplan-Meier analysis. On multivariate analysis N stage (p ≤0.007), T stage (p ≤0.04), M stage (p=0.007) and/or patient age (p=0.01) predicted metastasis, cancer specific and overall survival, and/or the cisplatin based adjuvant chemotherapy response. In TCGA data set publications showed that subtypes risk stratified patients for overall survival. Consistently the MCG-1 and MCG-Ext subtypes were associated with overall but not recurrence-free survival on univariate and Kaplan-Meier analyses. TCGA data set included 21 low grade specimens of the total of 402 and subtypes associated with tumor grade (p=0.005). However, less than 1% of muscle invasive bladder cancer cases are low grade. In only high grade specimens the MCG-1 and MCG-Ext subtypes could not predict overall survival. On univariate analysis subtypes according to the Bladder Cancer Molecular Taxonomy Group Consensus, TCGA 2017 and the Lund taxonomy were associated with tumor grade (p <0.0001) and overall survival (p=0.01 to <0.0001). Regardless of classification, subtypes had about 50% to 60% sensitivity and specificity to predict overall and recurrence-free survival. On multivariate analyses N stage and lymphovascular invasion consistently predicted recurrence-free and overall survival (p=0.039 and 0.003, respectively). CONCLUSIONS: Molecular subtypes reflect bladder tumor heterogeneity and are associated with tumor grade. In multiple cohorts and subtyping classifications the clinical parameters outperformed subtypes for predicting the outcome.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Gradação de Tumores , Invasividade Neoplásica , Metástase Neoplásica , Estadiamento de Neoplasias , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco , Transcriptoma
5.
Biosci Biotechnol Biochem ; 84(1): 111-117, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31512553

RESUMO

Slow skeletal muscle troponin T (TNNT1) has been reported to be correlated with several cancers, but there are no evidences proving that TNNT1 is required in colon adenocarcinoma (COAD). TNNT1 expression in COAD tissues and its prognostic significance were acquired from TCGA database. The proliferative, migratory, and invasive abilities of COAD cells were detected by CCK-8 and transwell assays, respectively. Correlations between TNNT1 and epithelial-mesenchymal transition (EMT)-related markers were determined using western blotting and Pearson's analysis. Our results stated that TNNT1 expression was high-regulated in COAD tissues, which was related with unfavorable prognosis of COAD patients. Functional analyses suggested that TNNT1 promoted the cellular behaviors. Moreover, aberrant expression of TNNT1 affected the expression level of EMT-related proteins. And TNNT1 was negatively linked with E-cadherin. In conclusion, our findings indicated that TNNT1 may promote the progression of COAD, mediating EMT process, and thus shed a novel light on COAD therapeutic treatments.


Assuntos
Adenocarcinoma/patologia , Movimento Celular , Proliferação de Células , Neoplasias do Colo/patologia , Transição Epitelial-Mesenquimal , Troponina T/genética , Troponina T/metabolismo , Antígenos CD/metabolismo , Caderinas/metabolismo , Bases de Dados Genéticas , Expressão Gênica , Técnicas de Silenciamento de Genes , Células HCT116 , Humanos , Invasividade Neoplásica , Prognóstico , Transfecção
6.
Biosci Biotechnol Biochem ; 84(1): 103-110, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31559912

RESUMO

We previously reported that MDA-MB-231 and MCF-7 cells, which are breast cancer cell lines and have cancer and cancer-initiating cells (CICs), were killed following normothermic microwave irradiation in which the cellular temperature was maintained at 37°C. In this study, we investigated the percentages of live or dead cells among CD44+/CD24- cells, which were defined as CICs among MDA-MB-231 and MCF-7 cells, and other types of cells in response to microwave irradiation. CD44+/CD24- cells among MDA-MB-231 cells were killed, thereby decreasing the number of cells, whereas the number of live CD44+/CD24- MCF-7 cells was increased following microwave irradiation. Moreover, adhesion, invasion, and migration were decreased in MDA-MB-231 cells, and the activation of matrix metalloproteinase-2 (MMP-2) in MDA-MB-231 cells was increased following microwave irradiation. These decreased cell activities might have been caused by MMP-2 activation and population changes in CD44+/CD24- in MDA-MB-231 cells.Abbreviations: APC: allophecocyanin; CBB: coomassie Brilliant Blue; CD: cluster of differentiation; CICs: cancer-initiating cells; FACS: fluorescence-activated cell sorting; FBS: fetal bovine serum; FITC: fluorescein isothiocyanate; FTDT: finite-difference time domain; HER2: human epidermal growth factor receptor type 2; PI: propidium iodide.


Assuntos
Antígeno CD24/metabolismo , Adesão Celular/efeitos da radiação , Movimento Celular/efeitos da radiação , Receptores de Hialuronatos/metabolismo , Micro-Ondas , Neoplasias de Mama Triplo Negativas/patologia , Apoptose/efeitos da radiação , Contagem de Células , Corantes/metabolismo , Feminino , Citometria de Fluxo , Humanos , Células MCF-7 , Metaloproteinase 2 da Matriz/metabolismo , Invasividade Neoplásica , Propídio/metabolismo , Temperatura Ambiente
7.
J Urol ; 203(1): 159-163, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31441673

RESUMO

PURPOSE: Patients who undergo cystectomy due to bladder cancer can elect an ileal conduit or a neobladder for urinary diversion. Decision regret related to this choice is an important and undesirable patient reported outcome. Our objective was to compare the severity of decision regret experienced by patients with a neobladder vs an ileal conduit. MATERIALS AND METHODS: We analyzed data from a longitudinal cohort study of patients who underwent cystectomy from 2013 to 2015. We applied multivariable linear regression to examine associations of the urinary diversion method (neobladder vs ileal conduit) with decision regret measured with the DRS (Decision Regret Scale) 6 and 18 months after cystectomy. Covariates included demographic and clinical characteristics, health care utilization and complications after cystectomy, quality of life and factors related to the decision making process, including informed and shared decision making, and goal concordance. RESULTS: Of the 192 patients in our cohort 141 received an ileal conduit and 51 received a neobladder. We observed no significant difference in the DRS score in patients with a neobladder vs an ileal conduit at 6 or 18 months (b=-1.28, 95% CI -9.07-6.53, vs b=-1.55, 95% CI -12.48-9.38). However, informed decision making was negatively related to decision regret at 6 and 18 months (b=-13.08, 95% CI -17.05--9.11, and b=-8.54, 95% CI -4.26--2.63, respectively). Quality of life was negatively associated with decision regret at 18 months (b=-5.50, 95% CI -8.95--2.03). CONCLUSIONS: Patients treated with cystectomy who were more informed about bladder reconstruction options experienced less regret independent of the method selected. Efforts to inform and prepare patients for the bladder reconstruction decision may help prevent decision regret.


Assuntos
Cistectomia , Tomada de Decisões , Neoplasias da Bexiga Urinária/cirurgia , Derivação Urinária/métodos , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Medidas de Resultados Relatados pelo Paciente , Satisfação do Paciente , Qualidade de Vida , Neoplasias da Bexiga Urinária/patologia
9.
Life Sci ; 241: 117171, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31843525

RESUMO

AIMS: Testis Expressed 19 (TEX19) is one of cancer/testis antigens identified in recent years and is related to the oncogenesis and progress of several cancers. This study aimed to reveal the role of TEX19 in ovarian cancer (OC) and searched for potential candidate epitope peptides of TEX19 to facilitate clinical application. MAIN METHODS: TEX19 levels were evaluated by immunohistochemistry (IHC) in 98 human ovarian tissue samples. The correlation of TEX19 levels with patients' clinicopathological features was assessed. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis were utilized to detect TEX19 levels in ovarian cell lines and TEX19-deficient cells. The level of TEX19 in OVCAR-3 and A2780 was knocked down by small interfering RNA (siRNA), and loss-of-function assays were used to determine the biological effects of TEX19 on the proliferation, migration, and invasion of OC cells. Subsequently, candidate epitope peptides from TEX19 were predicted and verified by the IEDB database, pepsite2 website, MOE software, and T2 cell binding assay. KEY FINDINGS: TEX19 was significantly upregulated in OC which correlated to higher TNM stage, lymph node involvement, and invasiveness. Knockdown of TEX19 inhibited proliferation, migration, and invasion of OC cells. Additionally, we screened four peptides derived from TEX19 and found TL to be the dominant peptide with the greatest affinity with HLA-A*0201. SIGNIFICANCE: Our data indicated a cancer-promoting effect of TEX19 in OC and demonstrated that TL could be a potential candidate for an anti-tumor epitope vaccine of OC, suggesting that TEX19 is a promising biomarker and immunotherapeutic target for OC.


Assuntos
Adenocarcinoma de Células Claras/secundário , Adenocarcinoma Mucinoso/secundário , Cistadenocarcinoma Seroso/secundário , Neoplasias do Endométrio/secundário , Epitopos/imunologia , Neoplasias Ovarianas/patologia , Proteínas de Ligação a RNA/imunologia , Proteínas de Ligação a RNA/metabolismo , Adenocarcinoma de Células Claras/imunologia , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma Mucinoso/imunologia , Adenocarcinoma Mucinoso/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Biomarcadores Tumorais/metabolismo , Estudos de Casos e Controles , Proliferação de Células , Cistadenocarcinoma Seroso/imunologia , Cistadenocarcinoma Seroso/metabolismo , Neoplasias do Endométrio/imunologia , Neoplasias do Endométrio/metabolismo , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/metabolismo , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas , Adulto Jovem
10.
Rev Med Chil ; 147(5): 557-567, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31859887

RESUMO

BACKGROUND: Breast cancer (BC) is the most common malignancy in women. AIM: To assess the impact of HER2 status on axillary lymph node (ALN) involvement in patients with invasive ductal carcinoma of no special type (IDC-NST) both at diagnosis and during the 4-year postoperative period. PATIENTS AND METHODS: We retrospectively included 375 women with an early clinical stage of non-luminal IDC-NST who between 2007 and 2013 underwent breast surgery at a clinical hospital. They were divided into phenotype-based groups: HR+HER2-, HR+HER2+, HR-HER2+ and HR-HER2-. Only patients with sentinel lymph node (SLN) macrometastases underwent ALN dissection. If > 3 ALNs were positive, radiotherapy was delivered. All patients were treated with chemotherapy, HER2+ BC patients received trastuzumab, and hormone receptor (HR)-positive BC patients received hormonal therapy. RESULTS: Larger tumor size, higher grade, HR+, HER2+ status, and lymphovascular invasion (LVI) were predictive for ALN metastases at diagnosis. The poorest overall, disease-free, and distant recurrence-free survival (OS, DFS, DRFS) were found in the HR-HER2- group, while the poorest locoregional recurrence-free survival (LRFS) was observed in HR-HER2+ and HR-HER2- groups. HER2 status was not predictor of survival. CONCLUSIONS: HER2+ status was predictive for ALN involvement at diagnosis but had no effect on 4-year LRFS in these patients.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Receptor ErbB-2/análise , Linfonodo Sentinela/patologia , Adulto , Idoso , Axila , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Antígeno Ki-67/análise , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Invasividade Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Estudos Retrospectivos , Estatísticas não Paramétricas , Fatores de Tempo , Carga Tumoral
11.
Medicine (Baltimore) ; 98(51): e14222, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31860943

RESUMO

RATIONALE: Patients with gastrointestinal stromal tumors (GISTs) are often found to have liver metastases at their 1st presentation. Most patients need preoperative treatment to reduce the size of the liver metastases to increase the possibility of surgical resection. Currently, imatinib mesylate is the drug of 1st choice for preoperative treatment and sunitinib malate (SM) is seldom used. Here we report a case of GIST with liver metastases where SM was used as a preoperative treatment. PATIENT CONCERNS: A 56-year-old worker presented with intermittent abdominal pain and eating difficulties. DIAGNOSES: An enhanced computed tomography scan showed a 15 × 15 × 10 cm malignant mass in the upper abdomen, and 2 metastases (15.1 × 13.1 cm and 14.8 × 8.8 cm) in the liver. The postcaval and middle hepatic veins were compressed by the liver metastases, making radical resection very difficult. INTERVENTIONS: First the primary tumor in the jejunum was resected, and then SM was used as a preoperative treatment to reduce the size of the liver metastases to improve the possibility of surgical resection. OUTCOMES: Both liver metastases regressed considerably in size and it was then possible to perform a radical resection. LESSONS: The SM has the potential to be used as preoperative therapy for GIST with large liver metastases. This method provides a new option for the preoperative treatment of GIST with liver metastases.


Assuntos
Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/patologia , Neoplasias do Jejuno/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Sunitinibe/uso terapêutico , Dor Abdominal/diagnóstico , Dor Abdominal/etiologia , Seguimentos , Tumores do Estroma Gastrointestinal/cirurgia , Hepatectomia/métodos , Humanos , Neoplasias do Jejuno/patologia , Neoplasias do Jejuno/cirurgia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Cuidados Pré-Operatórios/métodos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
12.
Medicine (Baltimore) ; 98(51): e17175, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31860944

RESUMO

Annual pancreatic tumor incidence rates have been increasing. We explored pancreatic tumor incidence trends by treatment and clinicopathologic features.Data from the Surveillance, Epidemiology and End Results (SEER) was retrieved to evaluate temporal trends and pancreatic cancer rates from 2000 to 2015. Joinpoint regression analyses were carried out to examine trend differences.Overall, the incidence of pancreatic cancer was on the increase. The initial APC increased at a rate of 2.22% from 2000 to 2012, and increased from 2012 to 2015 at a rate of 9.05%. Joinpoint analyses revealed that trends within different demographics of pancreatic cancer showed different characteristics. The rate of pancreatic cancer also varied with histologic types. In addition, the trends by cancer stage showed significant increase incidences of stage I and II pancreatic cancer from 2000 to 2013 (stage I: APC: 2.71%; stage II: APC: 4.87%). Incidences of patients receiving surgery increased from 2000 to 2008 (APC: 7.55%), 2008 to 2011 (APC: 2.17%) and then there was a significant acceleration from 2011 to 2015 (APC: 10.51%). The incidence of cases in stage II receiving surgery increased significantly from 2004 to 2009 (APC: 9.28%) and 2009 to 2013 (APC: 2.57%). However, for cases in stage I, the incidence of cases with surgery decreased significantly since 2009 (APC: -4.14%). Patients undergoing surgical treatment without chemotherapy and radiotherapy had the higher rates compared with those who received other combined treatments.Pancreatic cancer has been increasing overall, but patterns differ by demographics and clinicopathologic features. Efforts to identify and treat more eligible candidates for curative therapy could be beneficial.


Assuntos
Gerenciamento Clínico , Pancreatectomia/métodos , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/terapia , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Terapia Combinada , Grupos de Populações Continentais , Demografia , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Pancreatectomia/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Fatores de Risco , Programa de SEER , Fatores Sexuais , Análise de Sobrevida , Estados Unidos/epidemiologia
13.
Medicine (Baltimore) ; 98(51): e18036, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31860954

RESUMO

Cullin 4A (CUL4A) is a protein of E3 ubiquitin ligase with many cellular processes. CUL4A could regulate cell cycle, development, apoptosis, and genome instability. This study aimed to analyze the expression of CUL4A in nasopharyngeal carcinoma (NPC) tissues and the associations of CUL4A expression with prognostic significance. A total of 115 NPC patients were collected to assess the protein expression of CUL4A by immunohistochemistry, so as to analyze the relationships between CUL4A expression and clinicopathological and prognostic parameters. All patients were followed-up until death or 5 years. The results showed that high expression of CUL4A was significantly associated with larger primary tumor size (P = .026), higher nodal status (P = .013), more distant metastasis (P = .020), and higher TNM stage (P = .005). Kaplan-Meier curves showed that patients with higher CUL4A expression had significantly shorter overall survival (OS) and progression-free survival (PFS) (both P < .001). In multivariate Cox analysis, CUL4A is an independent prognostic factor for OS (P = .016; hazard ratio [HR] = 2.770, 95% CI: 1.208-6.351) and PFS (P = .022; HR = 2.311, 95% CI: 1.126-4.743). In conclusion, high expression of CUL4A was associated with advanced disease status of NPC, and might serve as an independent prognostic factor.


Assuntos
Proteínas Culina/genética , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/mortalidade , Adulto , Idoso , China , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Hospitais Universitários , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/radioterapia , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida
14.
Medicine (Baltimore) ; 98(51): e18149, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31860962

RESUMO

RATIONALE: Retroperitoneal schwannomas are very rare and may grow very close to major abdominal vessels. Since the surgical approach to the retroperitoneal space may be complex due to surrounding vital organs, including major vessels, laparoscopic surgery is challenging and has only been recently adopted. Here, we report a case of laparoscopic resection of a large retroperitoneal schwannoma attached to large vital vessels. PATIENT CONCERNS: A 62-year-old woman presented with a chief complaint of pain in the lower right limb with consequent claudication, which had lasted for approximately 1 year. DIAGNOSES: Magnetic resonance imaging revealed a solid oval mass measuring 45 × 32 × 39 mm, located medially to the right iliopsoas muscle at the level of the intersomatic space between the 5th lumbar vertebra and the 1st sacral vertebra. This mass was inhomogeneously hypointense in T2 due to the presence of cystic areas, with intense and inhomogeneous contrast enhancement, compatible with the diagnosis of a schwannoma. The mass compressed the inferior caval vein near its bifurcation and the right common iliac vein, anteriorly dislocating the ipsilateral iliac arterial axis. INTERVENTIONS: A multidisciplinary team skilled in vascular and pelvic laparoscopy was involved. The patient underwent laparoscopic surgery via an anterior transperitoneal approach with right adnexectomy and radical excision of the tumor. The surgery lasted 120 minutes without intraoperative complications. Blood loss was less than 100 mL. The histologic diagnosis was a benign Schwannoma; grade I according to World Health Organization classification. OUTCOMES: The postoperative course was uneventful. At the 10-month follow-up, the patient had no recurrences and was asymptomatic. LESSONS: Laparoscopic removal of large retroperitoneal schwannomas, even if attached to major vital vessels, is feasible and safe when performed by experienced surgeons.


Assuntos
Laparoscopia/métodos , Neurilemoma/diagnóstico , Neurilemoma/cirurgia , Neoplasias Retroperitoneais/diagnóstico , Neoplasias Retroperitoneais/cirurgia , Veia Cava Inferior/patologia , Idoso , Biópsia por Agulha , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Comunicação Interdisciplinar , Extremidade Inferior , Dor Musculoesquelética/diagnóstico , Dor Musculoesquelética/etiologia , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Neurilemoma/diagnóstico por imagem , Doenças Raras , Neoplasias Retroperitoneais/diagnóstico por imagem , Medição de Risco , Resultado do Tratamento
15.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(11): 967-972, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31878991

RESUMO

Objective To examine the effect of exosomes derived from lung adenocarcinoma cells on macrophage polarization and the change of cytobiological behaviors in lung cancer cells induced by activated macrophages. Methods Exosomes derived from lung adenocarcinoma cells were extracted by exosomes extraction kit. The expression of exosomal markers including CD9 and CD63 was detected by Western blot analysis. After THP-1 cells were treated with 100 ng/mL phorbol ester (PMA) for 48 hours, the macrophage marker of CD68 was detected by real-time quantitative PCR (RT-qPCR). Following 24-hour treatment of macrophages with the exosomes (200 µg/mL), the mRNA levels of transforming growth factor ß (TGF-ß), tumor necrosis factor α (TNF-α), inducible nitric oxide synthase (iNOS) and CD163 were detected by RT-qPCR, and the protein levels of IL-6, IL-8 and IL-10 were measured by IMMULITE 1000. The macrophages after exosome treatment were co-cultured with A549 or H1299 cells. The invasion of lung adenocarcinoma cells was tested by TranswellTM assay and the mRNA levels of MMP9, MMP2 in lung adenocarcinoma cells were detected by RT-qPCR. Results CD9 and CD63 were highly expressed in exosomes. The THP-1 cells after PMA induction produced a high level of CD68. After the macrophages were treated with exosomes, the expression of iNOS decreased and the expression of CD163, TNF-α, IL-6, IL-8 and IL-10 significantly increased in the macrophages. The co-culture of macrophages with A549 and H1299 after exosome treatment enhanced significantly the invasion ability of lung adenocarcinoma cells and increased the levels of MMP2 and MMP9. Conclusion The exosomes derived from lung adenocarcinoma cells can activate macrophages to exhibit a mixed M1/M2 phenotype, thus promot the invasion of lung cancer cells.


Assuntos
Adenocarcinoma de Pulmão/patologia , Exossomos/metabolismo , Neoplasias Pulmonares/patologia , Macrófagos/citologia , Invasividade Neoplásica , Células A549 , Polaridade Celular , Citocinas/metabolismo , Humanos , Óxido Nítrico Sintase Tipo II/metabolismo , Células THP-1
16.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(11): 1023-1029, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31878999

RESUMO

Objective To explore the expression of vascular endothelial growth factor receptor 3 (VEGFR3) and its significance in lung adenocarcinoma and to examine the effect of VEGFR3 knockdown on the biological behaviors of A549 cells. Methods Immunohistochemistry was used to detect the expression of VEGFR3 in 78 pieces of lung adenocarcinoma tissue and 35 of paracancerous tissue. Relationships between VEGFR3 and clinicopathological indices were also analyzed. Correlations between lung adenocarcinoma patient survival and the expression of vascular endothelial growth factor-C (VEGF-C) or VEGFR3 were analyzed using the TCGA database. VEGFR3 expression was knocked down in A549 cells using RNA interference, and cell proliferation was assessed using a CCK-8 assay. Cell migration and invasion were detected using TranswellTM assays. The effect of siRNA-mediated knockdown of EGFR3 in A549 cells on AKT pathway activity was assessed by Western blot analysis. Results Expression of VEGFR3 was significantly higher in the lung adenocarcinoma tissue than in the adjacent tissue, and positively correlated with TNM stage and lymph node metastasis. The survival rate of patients with high VEGFR3 expression was significantly lower than that of patients with low VEGFR3 expression. Exogenous VEGF-C promoted the expression of VEGFR3, and activated the AKT signaling pathway. Silencing of VEGFR3 inhibited the proliferation, migration, and invasiveness of A549 cells, and reduced the activation of the AKT signaling pathway by VEGF-C. Conclusion High expression of VEGFR3 in the lung adenocarcinoma tissue is positively correlated with poor prognosis. Silencing VEGFR3 can block AKT pathway activity and inhibit the proliferation, migration, and invasion of A549 cells.


Assuntos
Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/patologia , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Células A549 , Adenocarcinoma de Pulmão/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , Invasividade Neoplásica , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Fator C de Crescimento do Endotélio Vascular/metabolismo
17.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(9): 769-775, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31750816

RESUMO

Objective To explore the functions and mechanisms of macrophages derived from PGRN gene knockout (PGRN-/- ) C57BL/6 mice in the invasion and migration of breast cancer cells. Methods Breast cancer cells were cultured in conditioned medium of macrophages derived from WT and PGRN-/- mice. TranswellTM assay and scratch assay were used to detect the invasion and migration ability of cancer cells. Western blot analysis was used to detect the expression of E-cadherin and N-cadherin in cancer cells. Cytokine array, real-time quantitative PCR and ELISA were performed to investigate the differences of cytokines secreted by macrophages derived from WT and PGRN-/- mice. Breast cancer cells were treated by the differentially expressed cytokine interleukin-6 (IL-6), and then the above methods were used to investigate its effect on cancer cells. Western blot analysis was used to verify the roles of NF-κB and JAK/STAT3 signaling pathways. Results The macrophages derived from PGRN-/- mice blocked NF-κB signaling pathway, reduced IL-6 secretion, and inhibited the invasion and migration of breast cancer cells. IL-6 activated JAK/STAT3 signaling pathway to promote the invasion and migration of breast cancer cells. Conclusion The macrophages derived from PGRN-/- mice can block the NF-κB and JAK/STAT3 signaling pathways, down-regulate IL-6 expression, and inhibit the invasion and migration of breast cancer cells.


Assuntos
Neoplasias da Mama/patologia , Peptídeos e Proteínas de Sinalização Intercelular/genética , Interleucina-6/imunologia , Macrófagos/imunologia , Transdução de Sinais , Animais , Neoplasias da Mama/imunologia , Caderinas , Movimento Celular , Meios de Cultivo Condicionados , Granulinas , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/metabolismo , Invasividade Neoplásica , Fator de Transcrição STAT3/metabolismo , Células Tumorais Cultivadas
18.
Zhonghua Yi Xue Za Zhi ; 99(42): 3303-3307, 2019 Nov 12.
Artigo em Chinês | MEDLINE | ID: mdl-31715665

RESUMO

Objective: To studythe effect of lentivirus-mediated inhibition of Med19 on cell migration andinvasion in the PC3 cells, and explore the mechanism of epithelial-mesenchymal transition transformation. Methods: The lentivirus vectors containing small interferingRNA(siRNA) targeting Medl9 gene were constructed and transfected to PC3 cells.Quantitative real-time PCR(qRT-PCR) and Western blot analysis were used to detect the Medl9 expression in the siRNA group(PC3-Med 19-siRNA cells)and the NC group(PC3-Med 19-sc cells) at 72h after the transfection.The cell mobility,migration and invasion ability of PC3 cells were respectively measured by Boyden migration and woun-healing assay. The expression of E-Cadherin, N-Cadherin, Vimentin, ZEB2, Snail-1, and Snail-2 mRNA were detected by using qRT-PCR. Results: The expression of Medl9 mRNA in PC3-Med 19-siRNA cells was lower than that in PC3-Med 19-scRNA cells(P<0.01). The number of migrated cells and invaded cells were significantly decreased in PC3-Med 19-siRNA cells(P<0.01). The expression of N-Cadherin, Vimentin, ZEB2, Snail-1, and Snail-2 mRNA were remarkablylower and E-Cadherin was higher in PC3-Med 19-siRNA cells. Conclusion: Med 19 inhibitioncouldreduce migration abilityof prostate cancer PC3 cells by epithelial-mesenchymal transition.


Assuntos
Transição Epitelial-Mesenquimal , Complexo Mediador/metabolismo , Neoplasias da Próstata , Caderinas , Movimento Celular , Humanos , Masculino , Complexo Mediador/genética , Invasividade Neoplásica , Células PC-3
19.
Rev Med Suisse ; 15(673): 2190-2194, 2019 Nov 27.
Artigo em Francês | MEDLINE | ID: mdl-31778047

RESUMO

For more than 30 years, cisplatin-based neoadjuvant chemotherapy (NAC) has been administered to patients with muscle-invasive bladder cancer (MIBC). However, the benefit is modest. With the advent of modern immunotherapies, new therapeutic strategies are also opening up to bladder cancer. Unfortunately, the initial results in the neoadjuvant context show a response rate of only 20-35 %. Other therapeutic strategies, such as Pan-FGFR inhibitors, do not show better response. Due to the high genetic variability of bladder cancer, a «â€…one drug fits all ¼ concept is not an ideal solution. Patient selection based on the probability of response appears to be a promising strategy to improve this modest benefit of each treatment. In this context, the NAC will also continue to play an important role.


Assuntos
Cisplatino/uso terapêutico , Imunoterapia/tendências , Terapia Neoadjuvante/tendências , Invasividade Neoplásica , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Quimioterapia Adjuvante , Humanos , Seleção de Pacientes
20.
Zhonghua Gan Zang Bing Za Zhi ; 27(10): 766-771, 2019 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-31734990

RESUMO

Objective: To investigate the prognostic relationship between the expression levels of periostin (POSTN) in hepatocellular carcinoma (HCC) tissues as well as its effect in invasion and metastasis. Methods: The expression levels of POSTN in liver cancer tissues were detected with real-time quantitative PCR (QPCR) and immunohistochemistry (IHC). Kaplan-Meier method and Log-rank test were used to analyze the relationship between POSTN expression level and postoperative prognosis in patients with liver cancer. The expression of POSTN in hepatocellular carcinoma cells with different metastasis characteristics were detected in vitro and the overexpression of POSTN in low metastatic hepatocellular carcinoma cells was mediated through plasmid transfection techniques. The effects of POSTN on invasion and metastasis of hepatocellular carcinoma cells were determined by transwell migration and matrigel invasion assay. The comparative expression level of POSTN was analyzed by t-test. Results: The expression levels of POSTN in tissues from high to low was in the order of metastatic liver cancer tissues, non-metastatic liver cancer tissues and normal liver tissues (P = 0.006). The median survival time and 3-year survival rate in postoperative patients with hepatocellular carcinoma of high POSTN expression level were significantly lower than the low expression group (10.00 months, 44.44%; 59.00 months, 53.13%, P = 0.031 2). In in vitro testing, the expression of POSTN was highest in MHCC97H cells with high metastatic characteristics as compared with Huh7 and MHCC97L cells with low and medium metastatic characteristics. After overexpression of POSTN in MHCC97L cells, the migration and invasion capacity of MHCC97L cells was increased. Conclusion: POSTN is associated with pathological processes such as metastasis and invasion of liver cancer, which may promote the migration and invasion of liver cancer cells. It is expected to be an important prognostic biomarker of tumor recurrence and a therapeutic target for inhibiting the occurrence of metastasis in postoperative patients with hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular/patologia , Moléculas de Adesão Celular/metabolismo , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/metabolismo , Invasividade Neoplásica , Metástase Neoplásica , Recidiva Local de Neoplasia , Prognóstico
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