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The efficacy of chemotherapy for colon cancer is limited due to the development of chemoresistance. MicroRNA (miR)-188-5p is downregulated in various types of cancer. The aim of the present study was to explore the molecular role of miR-188 in oxaliplatin (OXA) resistance. An OXA-resistant colon cancer cell line, SW480/OXA, was used to examine the effects of miR-188-5p on the sensitivity of colon cancer cells to OXA. The target of miR-188-5p was identified using a luciferase assay. Cell cycle distribution was also assessed using flow cytometry. The measurement of p21 protein expression, Hoechst 33342 staining and Annexin V/propidium iodide staining was used to evaluate apoptosis. The expression of miR-188-5p significantly increased in SW480/OXA compared with wild-type SW480 cells. The luciferase assay demonstrated that miR-188-5p inhibited Ras GTPase-activating protein 1 (RASA1; also known as p120/RasGAP) luciferase activity by binding to the 3′-untranslated region of RASA1 mRNA, suggesting that miR-188-5p could target RASA1. In addition, miR-188-5p downregulation or RASA1 overexpression promoted the chemosensitivity of SW480/OXA, as evidenced by increased apoptosis and G1/S cell cycle arrest. Moreover, RASA1 silencing abrogated the increase in cell apoptosis induced by the miR-188-5p inhibitor. The findings of the present study suggested that miR-188-5p could enhance colon cancer cell chemosensitivity by promoting the expression of RASA1.  相似文献   
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Centromere proteins (CENPs) are involved in mitosis, and CENP gene expression levels are associated with chemotherapy responses in patients with breast cancer. The present study aimed to examine the roles and underlying mechanisms of the effects of CENP genes on chemotherapy responses and breast cancer prognosis. Using data obtained from the Gene Expression Omnibus (GEO) database, correlation and Cox multivariate regression analyses were used to determine the CENP genes associated with chemotherapy responses and survival in patients with breast cancer. Weighted gene co-expression network and correlation analyses were used to determine the gene modules co-expressed with the identified genes and the differential expression of gene modules associated with the pathological complete response (PCR) and residual disease (RD) subgroups. CENPA, CENPE, CENPF, CENPI, CENPJ and CENPN were associated with a high nuclear grade and low estrogen and progesterone receptor expression levels. In addition, CENPA, CENPB, CENPC and CENPO were independent factors affecting the distant relapse-free survival (DRFS) rates in patients with breast cancer. Patients with high expression levels of CENPA or CENPO exhibited poor prognoses, whereas those with high expression levels of CENPB or CENPC presented with favorable prognoses. For validation between databases, the Cancer Genome Atlas (TCGA) database analysis also revealed that CENPA, CENPB and CENPO exerted similar effects on overall survival. However, according to the multivariate analyses, only CENPA was an independent risk factor associated with DRFS in GEO database. In addition, in the RD subgroup, patients with higher CENPA expression levels had a worse prognosis compared with those with lower CENPA expression levels. Among patients with high expression levels of CENPA, the PI3K/Akt/mTOR pathway was more likely to be activated in the RD compared with the PCR subgroup. The same trend was observed in TCGA data. These results suggested that high CENPA expression levels plus upregulation of the PI3K/Akt/mTOR signaling pathway may affect DRFS in patients with breast cancer.  相似文献   
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Bisphosphonates are inhibitors of osteoclastic bone resorption with therapeutic benefit in a variety of bone disorders in both adults and children. While these agents have been routinely used in adults for the past three decades, their more recent introduction into paediatric medicine means there is a paucity of data on long‐term safety and effects on dental development. There is uncertainty regarding the dental management of children treated with bisphosphonates, particularly when invasive dental procedures, such as extractions and oral surgical procedures, are required. There are limited data with which to make recommendations about the dental management of patients treated with bisphosphonates, and there are no published recommendations that specifically address paediatric patients. This paper aims to outline paediatric uses and adverse effects of bisphosphonates and present recommendations on the dental management of children receiving bisphosphonates.  相似文献   
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OBJECTIVE: To compare the EuroQol (EQ-5D) and Short Form 6D (SF-6D) among multiethnic Asian patients with knee osteoarthritis (OA) scheduled for total knee replacement in Singapore. METHODS: Patients were asked to complete questionnaires including the EQ-5D, Short Form 36, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Lequesne knee index. EQ-5D and SF-6D utility scores were calculated using the scoring algorithms developed from the UK general population. Agreement between the 2 instruments was assessed by comparing their score distributions, means, medians, intraclass correlation coefficients (ICCs), and a Bland-Altman plot. Correlations of the EQ-5D and SF-6D with WOMAC and Lequesne knee index scores were also examined. RESULTS: A consecutive sample of 258 knee OA patients (127 English-speaking and 131 Chinese-speaking) participated. The mean +/- SD EQ-5D utility score was 0.49 +/- 0.31 (range -0.25-1.00) and the mean SF-6D utility score was 0.63 +/- 0.12 (range 0.32-0.89). In a hypothetical example, this 0.14-point difference in mean utility scores yielded a difference of $10,000/quality-adjusted life year (QALY) in cost-effectiveness ratios. The score distribution was bimodal for the EQ-5D and normal for the SF-6D. This poor agreement was also demonstrated by the Bland-Altman plot and the low ICC (range 0.18-0.54). Correlations of the WOMAC and Lequesne index with the EQ-5D were higher than with the SF-6D. CONCLUSION: Using different preference-based health-related quality of life instruments may yield different utility scores, which could have a great impact on QALY estimates. This highlights the importance of selecting appropriate instruments for economic evaluation. Additional research is needed to determine which instrument (the EQ-5D or the SF-6D) should be used in OA patients.  相似文献   
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Myocardial contrast echocardiography has the potential to accurately detect functionally significant coronary artery disease during pharmacologic stress testing. Different low-mechanical index modalities, including triggering replenishment imaging (TRI) and real-time imaging (RTI), are currently used to identify myocardial perfusion defects. We compared the ability of TRI with that of RTI for detecting and localizing perfusion abnormalities. Thirty-six patients (62 +/- 14 years old, 15 men) underwent single-photon emission computed tomography (SPECT) with technetium-99m sestamibi and myocardial contrast echocardiography at baseline and after infusion of 0.56 mg/kg of dipyridamole. Sixteen of these patients also underwent quantitative angiography. Contrast-enhanced images were obtained in 4-, 3-, and 2-chamber views after intravenous bolus injections of lipid-encapsulated microbubbles (0.1 ml of Definity). A myocardial perfusion defect was defined by myocardial contrast echocardiography as a delay of >2 seconds in contrast replenishment after high-mechanical index flash impulse. The myocardial segments were divided into 3 major coronary territories. There was agreement in detecting perfusion defects between SPECT and TRI in 26 patients (72%, kappa = 0.46) and between SPECT and RTI in 27 patients (75%, kappa = 0.50). Agreements between myocardial contrast echocardiography and SPECT for localizing coronary territories with perfusion defects were 81% for TRI (kappa = 0.43) and 85% for RTI (kappa = 0.61). Accuracy of RTI for detecting >50% diameter stenoses by quantitative angiography was 79%, that of TRI was 71%, and that of SPECT was 65%. These data indicate that the different low-mechanical index imaging schemes are equivalent to radionuclide SPECT in accurately detecting diseased coronary artery territories during vasodilator stress.  相似文献   
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