RESUMO
PURPOSE: Cisplatin is commonly used in non-small-cell lung cancer (NSCLC) chemotherapy; however, chemoresistance to cisplatin remains a great clinical challenge. Octamer-binding protein 4 (OCT4) has been reported to be overexpressed in NSCLC. In this study, we aimed to investigate the potential role of OCT4 in NSCLC with chemoresistance to cisplatin. METHODS: Expressions of OCT4 was detected in NSCLC tissues and cell lines. We utilized siRNA to knock down OCT4 expression in human NSCLC cells and analyzed their phenotypic changes. RESULTS: We found that the difference of OCT4 expression between NSCLC and the adjacent non-tumourous tissues was statistically significant. Knockdown of OCT4 in NSCLC cells could decrease cell proliferation, and potentiate apoptosis induced by cisplatin, suggesting OCT4 may contribute to cisplatin resistance in NSCLC. CONCLUSION: Our findings indicate that targeting OCT4 could improve cisplatin effect in NSCLC, confirming their role in modulating cisplatin sensitivity.
Assuntos
Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Pulmonares/patologia , Fator 3 de Transcrição de Octâmero/biossíntese , Apoptose/efeitos dos fármacos , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citometria de Fluxo , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise Serial de Tecidos , TransfecçãoRESUMO
Breast cancer is among the most common causes of cancer-related death in women worldwide. Previous studies have demonstrated an association between prolonged estrogen exposure and increased risk of breast cancer. Uridine 5'-diphospho-glucuronosyltransferase 1-1 (UGT1A1) plays a significant role in the detoxification of estrogens. Two major genetic polymorphisms have been identified in the UGT1A1 locus. UGT1A1*28 has been previously linked to increased risk of breast cancer. The aim of this study was to elucidate the possible correlation between UGT1A1*6, a single nucleotide polymorphism causing a Gly71Arg substitution, and breast cancer susceptibility. Forty-six women diagnosed with breast cancer, 15 patients with gastrointestinal cancer, and 13 healthy women were recruited to this study. The genotype in the polymorphic UGT1A1 locus was determined by DNA sequencing. The frequency of each genotype was compared among the three groups. The frequency of the UGT1A1*6 allele was significantly higher in breast cancer and gastrointestinal cancer patients than that in healthy females (both P < 0.05). No significant associations were observed between the UGT1A1*6 polymorphism and estrogen receptor, progesterone receptor, HER-2 expression status, menstrual status, or metastasis (all P > 0.05). Therefore, the UGT1A1*6 polymorphism was deduced to be a risk factor for breast cancer in women of Han Chinese ethnicity. UGT1A1 may serve as a therapeutic target for the prevention and treatment of breast cancer and other estrogen-related diseases.
Assuntos
Neoplasias da Mama/genética , Neoplasias Gastrointestinais/genética , Glucuronosiltransferase/genética , Substituição de Aminoácidos , Povo Asiático/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Previous research has shown that microRNA-141 (miR-141) expression levels are associated with survival in several types of cancer. In the present study, we investigated the clinical significance and prognostic value of miR-141 in gastric cancer. Paired tissue specimens (tumor and adjacent normal mucosa) from 95 patients with gastric cancer were obtained at the Department of General Surgery, Xiangya Hospital, Central South University from March 2009 to February 2014. The levels of miR-141 in cancerous and corresponding non-cancerous tissues were detected by quantitative reverse transcription-polymerase chain reaction. Associations between clinicopathological parameters and miR-141 expression were evaluated using chi-square tests. Overall survival was calculated and survival curves were plotted using the Kaplan-Meier method; differences between groups were compared using log-rank tests. Compared to the matched normal gastric mucosa, gastric cancer tissues had significantly lower miR-141 expression levels (P < 0.001). This decreased miR-141 expression was significantly associated with tumor differentiation (P = 0.044), positive lymph node metastasis (P = 0.010), distant metastasis (P < 0.001), and advanced tumor-node-metastasis (TNM) stage (P < 0.001). Furthermore, a significant relationship was found between miR-141 expression and overall survival (P = 0.012, log-rank test). Cox regression analysis revealed that lymph node metastasis (P = 0.003), distant metastasis (P = 0.001), TNM stage (P < 0.001), and miR- 141 expression (P = 0.007) were independent prognostic factors in patients with gastric cancer. Our data provide evidence that the downregulation of miR-141 may contribute to the aggressive progression and poor prognosis of human gastric cancer.
Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Adulto , Idoso , Progressão da Doença , Regulação para Baixo , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Gástricas/patologiaRESUMO
18F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is widely used to diagnose and stage non-small cell lung cancer (NSCLC). The aim of this retrospective study was to evaluate the predictive ability of different FDG standardized uptake values (SUVs) in 74 patients with newly diagnosed NSCLC. 18F-FDG PET/CT scans were performed and different SUV parameters (SUVmax, SUVavg, SUVT/L, and SUVT/A) obtained, and their relationship with clinical characteristics were investigated. Meanwhile, correlation and multiple stepwise regression analyses were performed to determine the primary predictor of SUVs for NSCLC. Age, gender, and tumor size significantly affected SUV parameters. The mean SUVs of squamous cell carcinoma were higher than those of adenocarcinoma. Poorly differentiated tumors exhibited higher SUVs than well-differentiated ones. Further analyses based on the pathologic type revealed that the SUVmax, SUVavg, and SUVT/L of poorly differentiated adenocarcinoma tumors were higher than those of moderately or well-differentiated tumors. Among these four SUV parameters, SUVT/L was the primary predictor for tumor differentiation. However, in adenocarcinoma, SUVmax was the determining factor for tumor differentiation. Our results showed that these four SUV parameters had predictive significance related to NSCLC tumor differentiation; SUVT/L appeared to be most useful overall, but SUVmax was the best index for adenocarcinoma tumor differentiation.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Silicatos de Alumínio/toxicidade , Doenças Profissionais/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Fibrose Pulmonar/induzido quimicamente , Biópsia , Evolução Fatal , Testes de Função RespiratóriaRESUMO
(18)F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is widely used to diagnose and stage non-small cell lung cancer (NSCLC). The aim of this retrospective study was to evaluate the predictive ability of different FDG standardized uptake values (SUVs) in 74 patients with newly diagnosed NSCLC. (18)F-FDG PET/CT scans were performed and different SUV parameters (SUVmax, SUVavg, SUVT/L, and SUVT/A) obtained, and their relationship with clinical characteristics were investigated. Meanwhile, correlation and multiple stepwise regression analyses were performed to determine the primary predictor of SUVs for NSCLC. Age, gender, and tumor size significantly affected SUV parameters. The mean SUVs of squamous cell carcinoma were higher than those of adenocarcinoma. Poorly differentiated tumors exhibited higher SUVs than well-differentiated ones. Further analyses based on the pathologic type revealed that the SUVmax, SUVavg, and SUVT/L of poorly differentiated adenocarcinoma tumors were higher than those of moderately or well-differentiated tumors. Among these four SUV parameters, SUVT/L was the primary predictor for tumor differentiation. However, in adenocarcinoma, SUVmax was the determining factor for tumor differentiation. Our results showed that these four SUV parameters had predictive significance related to NSCLC tumor differentiation; SUVT/L appeared to be most useful overall, but SUVmax was the best index for adenocarcinoma tumor differentiation.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Fluordesoxiglucose F18/farmacocinética , Neoplasias Pulmonares/diagnóstico por imagem , Compostos Radiofarmacêuticos/farmacocinética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Estudos RetrospectivosRESUMO
OBJECTIVE: To examine the effect of potassium supplementation on blood pressure (BP) in a Chinese population who consume a habitual high sodium and low potassium diet. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Community sample from Beijing, China. PARTICIPANTS: A total of 150 men and women aged 35-64 years with an initial systolic BP 130-159 mmHg and/or diastolic BP 80-94 mmHg. INTERVENTIONS: Participants were randomly assigned to take 60 mmol potassium chloride supplement or placebo for 12 weeks. MAIN OUTCOME MEASURE(S): BP measurements were obtained at baseline, and at 6 weeks and 12 weeks during the trial, using random-zero sphygmomanometers. RESULTS: The average baseline urinary excretion of sodium and potassium was 182 mmol/24 h and 36 mmol/24 h. Baseline BP and other measured variables were similar between the potassium supplementation and placebo groups. In the active compared to the placebo treatment group, the urinary excretion of potassium was significantly increased by 20.6 mmol/24 h (P< 0.001) during 12 weeks of intervention. Compared to placebo, active treatment was associated with a significant reduction in systolic BP (-5.00 mmHg, 95% CI: -2.13 to -7.88 mmHg, P < 0.001) but not diastolic BP (-0.63 mmHg, 95% CI: -2.49 to1.23 mmHg, P = 0.51) during 12-week intervention. CONCLUSION: These data indicate that moderate potassium supplementation resulted in a substantial reduction in systolic BP. Our findings suggest that increased potassium intake may play an important role in the prevention and treatment of hypertension in China.