RESUMO
PURPOSE: The significance of the Risk of Ovarian Malignancy Algorithm (ROMA) in differentiating benign and malignant ovarian lesions has been evidenced. In our clinical work, we found that advanced ovarian cancer were accompanied commonly with high ROMA scores. Thus, this study aimed to clarify the performance of ROMA in different disease stage of epithelial ovarian cancer (EOC) prior to surgery. METHODS: Carbohydrate antigen (CA125) and human epididymis protein 4 (HE4) levels and ROMA scores in 221 patients with FIGO stage I, II or III/IV stage EOC were analyzed. The positive rates of CA125, HE4 and ROMA at each disease stage were calculated. Their cutoff values, sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) for distinguishing patients with FIGO stage I/II from those with FIGO stage III/IV were estimated via ROC curves. RESULTS: Serum CA125 and HE4 levels and ROMA scores rose significantly with advancing stage. ROMA and CA125 were significantly elevated more frequently in comparing with HE4 in EOC patients at with the same stage. Based on ROC curves, the cutoff values for FIGO stage III/IV EOC were 110 IU/mL, 126 pmol/L, 78 and 68% for CA125, HE4, premenopausal and postmenopausal ROMA, respectively. ROMA was the strongest predictor of FIGO stage, with the highest specificity, accuracy, and PPV, which were 84.4, 82.5, and 87.0% for postmenopausal patients, 89.3, 85.6, and 74.3% for premenopausal patients. CONCLUSIONS: Our data suggest high ROMA scores correlated with advanced ovarian cancer prior to surgery. These observations suggest potential utility of ROMA in the comprehensively preoperative evaluation of EOC patients.
Assuntos
Adenocarcinoma de Células Claras/patologia , Adenocarcinoma Mucinoso/patologia , Biomarcadores Tumorais/sangue , Cistadenocarcinoma Seroso/patologia , Neoplasias do Endométrio/patologia , Neoplasias Ovarianas/patologia , Adenocarcinoma de Células Claras/sangue , Adenocarcinoma de Células Claras/cirurgia , Adenocarcinoma Mucinoso/sangue , Adenocarcinoma Mucinoso/cirurgia , Adulto , Idoso , Algoritmos , Antígeno Ca-125/sangue , Cistadenocarcinoma Seroso/sangue , Cistadenocarcinoma Seroso/cirurgia , Neoplasias do Endométrio/sangue , Neoplasias do Endométrio/cirurgia , Feminino , Seguimentos , Humanos , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/cirurgia , Cuidados Pré-Operatórios , Proteínas/análise , Curva ROC , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos , Adulto JovemRESUMO
The stigma exertion rate is a polygenic inherited trait that is important for increased seed yield in hybrid rice breeding. To identify quantitative trait loci (QTL) associated with high stigma exertion rate, we conducted QTL mapping using 134 recombinant inbred lines derived from XieqingzaoB and Zhonghui9308, which have high and low stigma exertion rates, respectively. A total of eight QTLs (qSES6, qSSE11, qDSE1a, qDSE1b, qDSE10, qDSE11, qTSE1, and qTSE11) for single stigma exertion, double stigma exertion, and total stigma exertion were detected. The locations of qSSE11 and qTSE11 have not been previously reported, and the qDSE11 allele from parent XQZB exhibited a positive additive effect. In addition, three QTLs (qSNP1, qSNP3a, and qSNP3b), for spikelet number per panicle were identified. Of note, one QTL (qSNP1) was detected in two different environments (Hainan and Zhejiang). To evaluate the advantage of exerted stigma for cross-pollination, single, dual, and total stigma exertion should be considered separately for future genetic improvement in the production of rice hybrid seeds. In addition, this study provides information for fine mapping, gene cloning, and marker assisted selection, with emphasis on the latter.
Assuntos
Mapeamento Cromossômico/métodos , Oryza/anatomia & histologia , Oryza/genética , Locos de Características Quantitativas/genética , Análise de Variância , Cromossomos de Plantas/genética , Meio Ambiente , Genética Populacional , Endogamia , Modelos Genéticos , Polimorfismo de Nucleotídeo Único/genética , Característica Quantitativa Herdável , Recombinação Genética/genética , TemperaturaRESUMO
We investigated the effect of the IL-17 monoclonal antibody Secukinumab combined with IL-35 in the blockade of the Notch signaling pathway on the invasive capability of hepatoma cells. We examined the effects of IL-17 antibody or IL-35 treatment alone or in combination on cell invasion and migration capabilities with Transwell chambers. The mRNA levels of Hes1, Hes5, and Hey1 were tested using quantitative polymerase chain reaction. The protein expression of N1ICD, Snail, and E-cadherin protein expressions were measured with western blot. The expression of Hes1, Hes5, Hey1 and N1ICD were all very high in hepatoma cell lines, and were positively correlated with the invasive migration capabilities of the cells. The combination of IL-17 monoclonal antibody Secukinumab with IL-35 could effectively inhibit the Notch signaling pathway, as well as the invasive migration of the cells. Snail and E-cadherin are involved in the migration of hepatoma cells, and it has been established that Snail can regulate the expression of E-cadherin. IL-17 monoclonal antibody Secukinumab combined with IL-35 can increase E-cadherin and decrease Snail expression, which are positively correlated with cell invasive migration capabilities. Overall, treatment with both IL-17 antibody and IL-35 is more effective than each treatment alone. Notch signaling is activated in hepatoma cell lines and increases with the enhancement of cell invasive migration capabilities. IL-17 monoclonal antibody Secukinumab combined with IL-35 can block the Notch signaling pathway, simultaneously reducing the invasive migration capability of hepatoma cells.
Assuntos
Anticorpos Monoclonais/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Interleucinas/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais Humanizados , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Células Hep G2 , Humanos , Interleucina-17/imunologia , Interleucinas/administração & dosagem , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Invasividade Neoplásica , Receptores Notch/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição/biossínteseRESUMO
The aim of this study was to identify disrupted pathways related to Down syndrome (DS), and DS-associated congenital heart defects (DS-CHD). The gene expression profile and pathway data of 10 human DS patients and 5 control samples in E-GEOD-1789 were recruited and analyzed by the individualized pathway aberrance score (iPAS) method, consisting of the data processing, gene-level statistics, pathway-level statistics, and significant measurement steps. The pre-processing step identified 12,493 genes and 1022 pathways (4269 genes). The pathway significant analysis identified eight pathways (adjusted P value <0.1) that differed between the disease and control samples. The cross-presentation of particulate exogenous antigen (phagosomes) and methionine salvage pathways showed the most significant differences among these. The gene expression levels of key pathway genes, such as CYBB and ADI1, were higher in disease samples than in normal controls. Based on our results, we predicted that the cross-presentation of particulate exogenous antigens (phagosomes) and the methionine salvage pathway could be good indicators of DS-CHD.
Assuntos
Síndrome de Down/genética , Redes Reguladoras de Genes , Cardiopatias Congênitas/genética , Redes e Vias Metabólicas/genética , Estudos de Casos e Controles , Dioxigenases/genética , Dioxigenases/metabolismo , Síndrome de Down/complicações , Síndrome de Down/metabolismo , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/metabolismo , Humanos , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Metionina/metabolismo , NADPH Oxidase 2 , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Fagossomos/genética , Fagossomos/metabolismoRESUMO
Thermotherapy has been proven to be effective for the treatment of various tumors, including glioma. We determined whether tumor necrosis factor-alpha (TNF-α) is involved in the regulation of the biological processes of glioma development. Reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry were used to investigate the levels of TNF-α mRNA and heat shock factor-1 (HSF1) protein, respectively, in glioma cells. Radioimmunoassay was used to dynamically monitor the contents of TNF-α in the nutrient fluid of C6 cells after thermotherapy treatment. Crystal violet staining was used to determine glioma invasiveness. The most obvious increases in HSF1 protein and TNF-α mRNA in C6 cells were observed at 30 and 60 min after thermotherapy, respectively. In addition, the radioactivity of TNF-α in the culture fluid of the C6 cells reached a peak after 120 min of thermotherapy. In addition, glioma invasiveness decreased and the concentration of TNF-α reached a maximum after 120 min of thermotherapy. Our results show that the decrease in thermotherapy-mediated glioma invasiveness is due to the accelerated release of TNF-α, which could promote the release of HSF1 from neurospongioma cells.
Assuntos
Neoplasias Encefálicas/terapia , Regulação Neoplásica da Expressão Gênica , Glioma/terapia , Hipertermia Induzida , Fator de Necrose Tumoral alfa/genética , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Glioma/genética , Glioma/metabolismo , Glioma/patologia , Fatores de Transcrição de Choque Térmico , Masculino , Invasividade Neoplásica , Transplante de Neoplasias , Ratos , Ratos Wistar , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
We conducted this case-control study to assess the role of the VEGF -2578C/A, +1612G/A, +936C/T and -634G/C gene polymorphisms in the development of renal cell carcinoma (RCC). A hospital-based case-control study was conducted in a 360 consecutive primary RCC patients and 360 age and gender-matched controls during January 2010 and January 2014. The polymerase chain reaction-restriction fragment length polymorphism was used for VEGF -2578C/A, +1612G/A, +936C/T and -634G/C genotyping. Multivariate conditional logistic regression analyses showed that subjects carrying the AA and the CA+AA genotypes of VEGF -2578C/A had significant association with increased risk of RCC compared to those having the CC genotype, and the ORs (95%CI) were 1.77 (1.10-2.85) and 1.37 (1.01-1.86), respectively. Using the conditional logistic regression model, CA+AA genotype of VEGF -2578C/A had a significantly increased risk of RCC in ever cigarette smokers, and individuals with hypertension, and the ORs (95%CI) were 1.93 (1.08-3.45) and 2.57 (1.06-6.57), respectively. In conclusion, our results showed that AA genotype of VEGF -2578C/A genetic variants is associated with increased risk of RCC.
Assuntos
Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , RiscoRESUMO
OBJECTIVE: To explore the differentially expressed proteins in normal cervix, cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC) tissues by differential proteomics technique. METHODS: Cervical tissues (including normal cervix, CIN and CSCC) were collected in Department of Gynecologic Oncology of Beijing Obstetrics and Gynecology Hospital. Two-dimensional fluorescence difference in gel electrophoresis (2-D DIGE) and DeCyder software were used to detect the differentially expressed proteins. Matrix-assisted laser desorption/ionization-time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS) was used to identify the differentially expressed proteins. Western blot (WB) and immunohistochemistry (IHC) were performed to validate the expressions of selected proteins among normal cervix, CIN and CSCC. RESULTS: 2-D DIGE images with high resolution and good repeatability were obtained. Forty-six differentially expressed proteins (27 up-regulated and 19 down-regulated) were differentially expressed among the normal cervix, CIN and CSCC. 26 proteins were successfully identified by MALDI-TOF/TOF MS. S100A9 (S100 calcium-binding protein A9) was the most significantly up-regulated protein. Eukaryotic elongation factor 1-alpha-1 (eEF1A1) was the most significantly down-regulated protein. Pyruvate kinase isozymes M2 (PKM2) was both up-regulated and down-regulated. The results of WB showed that with the increase in the severity of cervical lesions, the expression of S100A9 protein was significantly increased among the three groups (P = 0.010). The expression of eEF1A1 was reduced but without significant difference (P = 0.861). The expression of PKM2 was significantly reduced (P = 0.000). IHC showed that protein S100A9 was mainly expressed in the cytoplasm, and its positive expression rate was 20.0 % in normal cervix, 70.0 % in CIN and 100.0 % in CSCC, with a significant difference among them (P = 0.006). eEF1A1 was mainly expressed in the cell plasma, and its positive expression rate was 70.0 % in normal cervix, 73.3 % in CIN and 60.0 % in CSCC tissues, without significant difference among them (P = 0.758). PKM2 was mainly expressed in the cell nuclei, and its positive expression rate was 100.0 % in normal cervix, 93.3 % in CIN and 75.0 % in CSCC tissues, showing a difference close to statistical significance (P = 0.059) among them. CONCLUSIONS: There are differentially expressed proteins among normal cervix, CIN and CSCC. S100A9, eEF1A1 and PKM2 may become candidate markers for early diagnosis of cervical cancer and new targets for therapy. It also provides a basis for further studies of the mechanism for CIN developing to CSCC.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Colo do Útero/metabolismo , Displasia do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/metabolismo , Adulto , Western Blotting , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Estudos de Casos e Controles , Colo do Útero/patologia , Colo do Útero/cirurgia , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Estadiamento de Neoplasias , Prognóstico , Proteômica , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrometria de Massas em Tandem , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/cirurgiaRESUMO
PURPOSE: TGF-beta can induce G1 arrest via many mechanisms including up-regulating p21, p27, and Rb. However, as the member of Rb family, whether RBL2 is induced by TGF-beta treatment remains exclusive. METHODS: The expression of RBL2 and miR-93 after TGF-beta treatment was determined by quantitative real-time PCR and western blot. The growth of renal cancer cells was determined by CCK-8 assays and cell cycle was determined by PI staining. The binding of miR-93 on RBL2 3'-UTR was determined by double luciferase system. RESULTS: In renal cancer cells, TGF-beta treatment induced expression of RBL2 in a time- and concentration-dependent manner, and RBL2 mediated TGF-beta induced growth inhibition and cell cycle arrest in renal cancer cells. Furthermore, we found that miR-93 directly targeted RBL2 by binding to its 3'-UTR in renal cancer cells. Over-expression of miR-93 significantly reduced the expression of RBL2, whereas knock down of miR-93 up-regulated the expression of RBL2. More importantly, TGF-beta treatment inhibited miR-93 expression, which resulted in up-regulation of RBL2 after TGF-beta treatment. CONCLUSION: TGF-beta induced RBL2 expression through down-regulating miR-93 in renal cancer cells. The newly identified TGF-beta/miR-93/RBL2 signal pathway reveals a new mechanism of TGF-beta induced growth arrest in renal cancer.
Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Renais/genética , MicroRNAs/biossíntese , Proteína p130 Retinoblastoma-Like/biossíntese , Fator de Crescimento Transformador beta/metabolismo , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Humanos , Neoplasias Renais/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , TransfecçãoRESUMO
This study aimed to isolate mesenchymal stem cells from bone mesenchymal stem cells (BMSCs), determine their therapeutic potential for treating rats with acute liver failure (ALF), further explore the factors that induce liver failure mechanisms, and elucidate the role of bone marrow stem cell therapy and BMSCs on liver homing. We found that differentiation potential was present in BMSCs expressing high levels of CD29 and CD90. These cells improved liver functioning in vivo after transplantation into rat livers with D-galactosamine damage, as evidenced by the levels of alanine aminotransferase and aspartate aminotransferase returning to normal (low levels) in recipient ALF rats. A significant improvement in the liver functional test and histological findings was observed in the transplantation group after 120 and 168 h of transplantation (P < 0.05). Histological data revealed that hepatocyte cell apoptosis was lower in the transplantation group compared to the control groups (P < 0.05), and that the transplantation of BMSCs reduced liver inflammation, decreased hepatic denaturation and necrosis, and promoted liver regeneration. These ameliorations were not recorded in the control groups. The results of in situ hybridization, immunofluorescence staining, and Western blot confirmed the presence of transplanted BMSCs in recipient rat livers. Stromal cell derived factor-1 alpha and vascular endothelial growth factor were significantly upregulated after the intraportal transplantation of BMSCs, with significantly higher levels being found in the portal vein and the tail vein groups (P < 0.05). In conclusion, BMSCs have a therapeutic effect against ALF rats, evoke endogenous repair mechanisms in the liver, and may represent a novel form of therapeutic intervention for the disease. Furthermore, intraportal transplantation serves as a more effective pathway compared to tail vein transplantation.
Assuntos
Células da Medula Óssea/citologia , Falência Hepática Aguda/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Falência Hepática Aguda/sangue , Falência Hepática Aguda/fisiopatologia , Testes de Função Hepática , Regeneração Hepática , Masculino , Ratos Sprague-Dawley , Resultado do TratamentoRESUMO
We evaluated changes in levels by comparing serum proteins in senescence-accelerated mouse-prone 8 (SAMP8) mice at 2, 6, 12, and 15 months of age (SAMP8-2 m, -6 m, -12 m, -15 m) to age-matched SAM-resistant 1 (SAMR1) mice. Mice were sacrificed, and blood was analyzed by 2-dimensional electrophoresis combined with mass spectrometry. Five protein spots were present in all SAMP8 serum samples, but only appeared in SAMR1 samples at 15 months of age except for spot 3, which also showed a slight expression in SAMR1-12 m sera. Two proteins decreased in the sera from SAMP8-2 m, -6 m, and -12 m mice, and divided into 2 spots each in SAMP8-15 m sera. Thus, the total number of altered spots in SAMP8 sera was 7; of these, 4 were identified as Ig kappa chain V region (M-T413), chain A of an activity suppressing Fab fragment to cytochrome P450 aromatase (32C2_A), alpha-fetoprotein, and apolipoprotein A-II. M-T413 is a monoclonal CD4 antibody, which inhibits T cell proliferation. We found that M-T413 RNA level was significantly enhanced in splenocytes from SAMP8-2 m mice. This agreed with serum M-T413 protein alterations and a strikingly lower blood CD4+ T cell count in SAMP8 mice when compared to the age-matched SAMR1 mice, with the latter negatively correlating with serum M-T413 protein volume. Age-related changes in serum proteins favored an increase in autoantibodies and alpha-fetoprotein and a decrease of apolipoprotein A-II, which occurred in SAMP8 mice at 2 months of age and onwards. These proteins may serve as candidate biomarkers for early aging.