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1.
Histopathology ; 69(2): 276-87, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26799253

RESUMO

AIMS: As one of the only two isoforms of the eukaryotic initiation factor (EIF)5A family, EIF5A2 plays an important role in tumour progression and prognosis evaluation. The aim of this study was to investigate EIF5A2 expression in International Federation of Gynecology and Obstetrics (FIGO) stage I-II cervical cancer and to evaluate its clinical significance. METHODS AND RESULTS: The mRNA and protein expression levels of EIF5A2 were analysed in 20 tissue samples of FIGO stage I-II cervical cancer and paired surrounding non-tumour cervical tissues by real-time polymerase chain reaction and western blot analysis. Immunohistochemistry was performed to examine EIF5A2 protein expression in paraffin-embedded tissues from 314 patients with cervical cancer. The mRNA and protein expression levels of EIF5A2 were significantly elevated in tumour tissues. The increased EIF5A2 expression was correlated with higher FIGO stage (P < 0.001), deep cervical stromal invasion (P = 0.026), lymphovascular space involvement (P = 0.002), pelvic lymph node metastasis (P < 0.001) and postoperative recurrence (P < 0.001) in patients with cervical cancer. Patients with tumours showing high EIF5A2 expression had a poorer survival time than those with normal EIF5A2 expression, especially the patients with negative pelvic lymph nodes and FIGO stage II. In addition, multivariate Cox analysis showed that high EIF5A2 expression was an independent prognostic factor for overall survival [hazard ratio 1.949; 95% confidence interval (CI) 1.116-3.404; P = 0.019] and disease-free survival (hazard ratio 1.980; 95% CI 1.189-3.297; P = 0.009). CONCLUSIONS: EIF5A2 overexpression may contribute to cancer progression and poor prognosis. Therefore, EIF5A2 could be a novel potential prognostic marker for FIGO stage I-II cervical cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Fatores de Iniciação de Peptídeos/metabolismo , Proteínas de Ligação a RNA/metabolismo , Neoplasias do Colo do Útero/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/genética , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Linfonodos/metabolismo , Linfonodos/patologia , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fatores de Iniciação de Peptídeos/genética , Prognóstico , RNA Mensageiro/genética , Proteínas de Ligação a RNA/genética , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Fator de Iniciação de Tradução Eucariótico 5A
2.
Cancer Res Treat ; 52(3): 798-814, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32124583

RESUMO

PURPOSE: Colon cancer-associated transcript 1 (CCAT1) was identified as an oncogenic long non-coding RNA (lncRNA) in a variety of cancers. However, there was a lack of understanding of the mechanism by which CCAT1 conferred cisplatin (also known as DDP) resistance in ovarian cancer cells. MATERIALS AND METHODS: Cell viability of A2780, SKOV3, A2780/DDP, and SKOV3/DDP cells upon cisplatin treatment was monitored by MTT assay. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) detected the expression levels of CCAT1 and miR-454. The effect of sh-CCAT1 on cisplatin response was investigated in xenografts study. Bioinformatic analysis, luciferase reporter assay and qRT-PCR were conducted to validate the direct interaction among CCAT1, miR-454, and survivin. Apoptosis was determined by flow cytometry after dual staining of Annexin-V-FITC/propidium iodide, and the expression of apoptosis-related proteins Bcl-2, Bax and survivin were detected by qRT-PCR and Western blotting. Xenograft study was conducted to monitor in vivo tumor formation. RESULTS: CCAT1 was highly expressed in cisplatin-resistant ovarian cancer cell line A2780/DDP and SKOV3/DDP. Knockdown of CCAT1 restored sensitivity to cisplatin in vitro and in vivo. Our data revealed that silencing of CCAT1 promoted cisplatin-induced apoptosis via modulating the expression of pro- or anti-apoptotic proteins Bax, Bcl-2, and survivin. CCAT1 directly interacted with miR-454, and miR-454 overexpression potentiated cisplatin-induced apoptosis. Survivin was identified as a functional target of miR-454, restoration of survivin attenuated the effect of miR-454 on cisplatin response. In addition, miR-454 inhibitor or overexpression of survivin was found to abolish sh-CCAT1-induced apoptosis upon cisplatin treatment. CONCLUSION: CCAT1/miR-454/survivin axis conferred cisplatin resistance in ovarian cancer cells.


Assuntos
Biomarcadores Tumorais/metabolismo , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , MicroRNAs/genética , Neoplasias Ovarianas/tratamento farmacológico , RNA Longo não Codificante/genética , Survivina/metabolismo , Animais , Antineoplásicos/farmacologia , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Survivina/genética , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Zhonghua Yi Xue Za Zhi ; 85(6): 396-9, 2005 Feb 16.
Artigo em Zh | MEDLINE | ID: mdl-15854530

RESUMO

OBJECTIVE: To study the leptin receptor isoforms regulation by leptin and insulin. METHODS: Human hepatocellular carcinoma cells of the line HepG2 were cultured in DMEM containing 10% FBS in six-well plate and were incubated for 24 hours in serum-free medium containing 0, 10(-9), 10(-8), 10(-7), and 10(-6) mol/L of human leptin or insulin. Using the semi-quantitative RT-PCR technique, the mRNA expressions of long (OB-Rb) and short (OB-Ra: OB-R219.3) leptin receptor isoforms were measured. RESULTS: OB-Rb and OB-R219.3 mRNAs were expressed in this cell line. Leptin of the concentrations of 10(-7) approximately 10(-6) mol/L significantly inhibited the OB-Rb mRNA expression, with the maximum decrease (by 43%) at the concentration of 10(-6) mol/L. Similarly the mRNA expression of OB-R219.3 was also markedly reduced in cells treated with leptin of the concentrations of 10(-8) approximately 10(-6) (mol/L), with the maximum inhibition (by 49%) at the concentrations of 10(-6) mol/L. Insulin showed no effect on OB-Rb and OB-R219.3 mRNAs expression in HepG2 cell. CONCLUSION: In HepG2 cells, leptin down-regulates the expressions of OB-Rb and OB-R219.3 mRNAs, and insulin has no effect on OB-Rb and OB-R219.3 mRNAs, which contributes at least partly to an understanding of the mechanism of leptin resistance in vivo and suggests that leptin-induced receptor down-regulation may be relevant to leptin resistance at sites of peripheral action.


Assuntos
Insulina/farmacologia , Leptina/farmacologia , Neoplasias Hepáticas/metabolismo , RNA Mensageiro/biossíntese , Receptores de Superfície Celular/biossíntese , Humanos , Neoplasias Hepáticas/patologia , RNA Mensageiro/genética , Receptores de Superfície Celular/genética , Receptores para Leptina , Células Tumorais Cultivadas
4.
PLoS One ; 10(8): e0135452, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26280557

RESUMO

Plant temperature (Tp) is an important indicator of plant health. To determine the dynamics of plant temperature and self-cooling ability of the plant, we measured Tp in Artemisia ordosica in July, in the Mu Us Desert of Northwest China. Related factors were also monitored to investigate their effects on Tp, including environmental factors, such as air temperature (Ta), relative humidity, wind speed; and physiological factors, such as leaf water potential, sap flow, and water content. The results indicate that: 1) Tp generally changes in conjunction with Ta mainly, and varies with height and among the plant organs. Tp in the young branches is most constant, while it is the most sensitive in the leaves. 2) Correlations between Tp and environmental factors show that Tp is affected mainly by Ta. 3) The self-cooling ability of the plant was effective by midday, with Tp being lower than Ta. 4) Increasing sap flow and leaf water potential showed that transpiration formed part of the mechanism that supported self-cooling. Increased in water conductance and specific heat at midday may be additional factors that contribute to plant cooling ability. Therefore, our results confirmed plant self-cooling ability. The response to high temperatures is regulated by both transpiration speed and an increase in stem water conductance. This study provides quantitative data for plant management in terms of temperature control. Moreover, our findings will assist species selection with taking plant temperature as an index.


Assuntos
Artemisia/fisiologia , Transpiração Vegetal/fisiologia , Artemisia/metabolismo , Clima Desértico , Meio Ambiente , Umidade , Folhas de Planta/metabolismo , Folhas de Planta/fisiologia , Caules de Planta/metabolismo , Caules de Planta/fisiologia , Temperatura , Água/metabolismo , Vento
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