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Near-infrared fluorescent probe for fast track of cyclooxygenase-2 in Golgi apparatus in cancer cells

Bhaskar Gurram, Miao Li, Jiangli Fan, Jingyun Wang, Xiaojun Peng

《化学科学与工程前沿（英文）》 2020年第14卷第1期页码 41-52 doi: 10.1007/s11705-019-1796-1

摘要： Cyclooxygenase-2 (COX-2) has been used as an excellent traceable biomarker, and exists maximally in Golgi apparatus (Cancer cells). Celecoxib (CCB) is a selective inhibitor for COX-2, and has been used as one of non-steroidal anti-inflammatory drug. Herein we report the conjugation of nile blue (NB) with CCB via a six-carbon linkage to form a fluorescence probe NB-C6-CCB for the detection of COX-2. NB-C6-CCB displays strong fluorescence with the emission peak centered at near-infrared wavelength (700 nm) in tumor cells or tumor tissues with high expression of COX-2. Importantly, NB-C6-CCB can discriminate cancer cells (MCF-7) fluorescence intensity from normal ones (COS-7) in the co-culture medium under confocal microscope. Subcellular localization of the NB-C6-CCB preferentially points to the Golgi apparatus and increases the fluorescent intensity. The competitive analysis (with CCB) and Native-PAGE analysis confirmed that NB-C6-CCB shows selective binding affinity towards COX-2 enzyme. Competitive analysis with CCB (flow cytometry assay) revealed the fluorescence intensity fluctuation due to pretreatment of CCB with different concentrations, indicating that the NB-C6-CCB is a precise or sensitive probe for the COX-2. Tumor tissue (depth: 500 µm), organs and mice imaging tests show excellent near-infrared visualization, specific localization and identification of tumors.

关键词： cyclooxygenase-2 nile blue CCB Golgi apparatus NIR imaging

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Cyclooxygenase-2 gene-1195G/A genotype is associated with the risk of HBV-induced HCC: A case-control

Li-Feng LIU MD, PhD, Qiong CHEN MD, PhD, Ying CHANG MD, PhD, Ju-Sheng LIN MD, PhD, Jin-Liang ZHANG MM,

《医学前沿（英文）》 2010年第4卷第1期页码 90-95 doi: 10.1007/s11684-010-0021-x

摘要： This study aimed to identify functional single nucleotide polymorphisms in the cyclooxygenase-2 gene promoter and evaluate their effects on the risk of primary hepatocellular carcinoma (HCC) with hepatitis B virus (HBV) infection. We conducted a population-based, case-control study enrolling 630 Han Chinese people in Hubei province. Subjects included primary HCC patients with HBV infection (=210), chronic hepatitis B cases (=210) and healthy Han Chinese (=210). -1195G/A polymorphism was analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing analysis. We found-1195A allele carriers had a higher risk of HCC with HBV infection (OR, 0.72; 95% CI, 0.548–0.946). The-1195A allele might be used as a marker in screening individuals at high risk of HCC with HBV infection.

关键词： cyclooxygenase-2 gene single nucleotide polymorphisms susceptibility primary hepatocellular carcinoma hepatitis B virus infection

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metastasis is related to the epithelial-mesenchymal transition and expressions of VEGF, MMP-9, and COX-2

Lihui WANG, Lianhong LI, Shen LV, Shujun FAN, Li ZHAN, Bo WANG, Zhong ZHANG

《医学前沿（英文）》 2009年第3卷第2期页码 164-170 doi: 10.1007/s11684-009-0038-1

摘要： The invasion and metastasis of breast cancer are supposed to involve several stages in which epithelial-mesenchymal transition (EMT) is regarded as the mechanistic basis for the behavior of cancer cells. A series of factors related to EMT are apparently involved in such process. The current study aimed to investigate the contributions of EMT and related factors in lymph node metastasis of breast cancer. The expressions of E-cadherin (E-Cad), N-cadherin (N-Cad), vascular endothelial cell growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), cyclooxygenase-2 (COX-2), and CD34 were examined in 74 cases of breast cancer, including 39 cases with lymph node metastasis and 35 cases without lymph node metastasis by immunohistochemistry. Multivariable Cox proportional hazards model was used to analyze the patients’ prognosis. The expressions of N-Cad, VEGF, MMP-9, and COX-2 in cases with lymph node metastasis were significantly higher than those without lymph node metastasis ( <0.05), while the E-Cad level was inversely related to status of lymph node metastasis ( <0.05). The metastasis rate of lymph node in the cases with EMT (lower E-Cad expression and higher N-Cad expression) was 78.3%, while that without EMT (higher E-Cad expression and lower N-Cad expression) was 11.1%. There was a statistical difference in the expression of COX-2 protein between histological grade I and grade II or III, respectively ( <0.05). In the cases with higher grade, the expression of E-Cad was decreased, while that of N-Cad was increased. Higher microvascular density (MVD) was also found to be significantly associated with lymphatic metastasis ( <0.05), and the cases with higher MVD had shorter survival time. This study indicates that EMT and expressions of VEGF, MMP-9 and COX-2, and MVD value are strongly correlated with lymph node metastasis in breast cancer.

关键词： epithelial-mesenchymal transition vascular endothelial cell growth factor matrix metalloproteinase-9 cyclooxygenase-2 higher microvascular density breast cancer

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Efficacy and safety of perioperative parecoxib for acute postoperative pain treatment in children: a meta-analysis

null

《医学前沿（英文）》 2015年第9卷第4期页码 496-507 doi: 10.1007/s11684-015-0414-y

摘要：

Perioperative parecoxib administration reduces postoperative pain, opioid consumption, and adverse events in adult patients. However, the efficacy and safety of parecoxib in children remain unclear. This meta-analysis included related published studies to address this concern. Eight databases in the literature until February 2015 were systematically explored to identify randomized controlled trials (RCTs) comparing perioperative parecoxib administration and placebo/standard treatments for acute postoperative pain in children. Primary outcomes were postoperative pain scores and adverse events. The Face, Legs, Activity, Crying, Consolability scale was used to score pain in children younger than 6 years, whereas the Visual Analog Scale was used in children older than 6 years. Secondary outcomes were sedation scores (measured using the Ramsay scale), agitation scores (measured using the Sedation-Agitation Scale), and opioid consumption. The methodological quality of RCTs was independently assessed in accordance with the “Risk of bias” of Cochrane Collaboration. Data were analyzed using Review Manager 5.2. Twelve RCTs involving 994 patients met the inclusion criteria. Compared with children who received placebo treatment, those who received parecoxib demonstrated lower early (2 h) and later (12 h) postoperative pain scores; lower incidence rates of postoperative nausea, vomiting, and agitation; higher early (1 h) postoperative sedation scores; and lower agitation scores. Similarly, children who received parecoxib had lower early (2 h) and later (12 h) postoperative pain scores, lower incidence rates of postoperative nausea and vomiting, and lower early (1 h) postoperative sedation scores compared with those who received standard treatments; however, these children showed no significant difference in agitation scores. Unfortunately, data on the effect of parecoxib on opioid consumption were insufficient. Overall, these results suggested that perioperative parecoxib administration was associated with less acute postoperative pain and fewer adverse events compared with placebo or standard treatments. Parecoxib administration also resulted in less emergence agitation compared with placebo treatment and less excessive sedation concern compared with standard treatments. However, the long-term effects, effects on opioid consumption, and patient satisfaction of parecoxib administration warrant further investigation.

关键词： NSAID cyclooxygenase 2 inhibitor child pain postoperative opioid placebo