1.The correlation of asymmetrical dimethylarginine level and oxidative stress to the onset of Alzheimer's disease.
Ming CHEN ; Ping JIANG ; Jun Lü ; Zhenghua XIANG ; Binghua JIAO
Acta Pharmaceutica Sinica 2010;45(8):1001-5
This study is to investigate the influence and mechanism of action of asymmetrical dimethylarginine (ADMA) and the induced oxidative stress level on Alzheimer's disease (AD) incidence. ADMA concentration, nitric oxide, Abeta(40)/Abeta(42) ratio, inducible NO synthase (iNOS) activity and the concentrations of the induced free radicals including malondialdehyde (MDA), 3-nitrotyrosine (3-NT) and peroxynitrite (ONOO-) in the cerebrospinal fluid (CSF) from 34 neurologically normal controls and 37 AD patients were quantitatively determined and statistically compared. The results showed that the ADMA concentration significantly decreased in AD patients, and it showed negative correlation with the NO, iNOS activity, and showed positive correlation with MMSE score. ADMA concentration was negatively correlated with Abeta(40)/Abeta(42) ratio (P<0.01) with the observation that Abeta(40)/Abeta(42) ratio increased while ADMA level decreased in CSF in AD patients. The concentration levels of MDA, 3-NT and ROS significantly increased compared with the control with all the P values less than 0.05. These findings suggested that the ADMA disorder and the oxidative damage effect of the induced free radicals in CSF of AD patients are an important mechanism of AD incidence, and their joint regulation may provide new idea for the prevention and clinical treatment of AD.
2.Analysis of the differential binding protein in human breast cancer cell line(MCF-7) and paclitaxel resistant cell line(MCF-7/Taxol)
Zhenghua ZHANG ; Xiaohua LIANG ; Xueyong WU ; Kaisheng HOU ; Xiaoping ZHANG ; Zhongwei Lü
Chinese Pharmacological Bulletin 2010;26(2):217-221
Aim To identify paclitaxel differential binding protein in the cells of cell line MCF-7 and MCF-7/Taxol and to find new target for antitumor agents.Methods Synthesis and activity assay of biotinylated paclitaxel was used to gain paclitaxel binding protein by semiautomatic in vitro selection using the affinity magnetic beads method.LC MS/MS analysis and Western immunoblot analysis were used to identify the differential binding protein.Results The experimentation identified paclitaxel binding protein in the cells of MCF-7 and MCF-7/Taxol.An absent strap in MCF-7/Taxol was discovered by comparing the straps of two cell lines, which contained 25 kinds of proteins, among which 3 proteins were identified by western blot techniques: Heat shock protein HSP 90,Dermcidin Precursor,Actinin.Conclusions By comparing the straps of two cell lines, the differential protein in the cells of MCF-7 and MCF-7/Taxol are discovered, implying that they may be the novel mechanism of taxane resistance and may lead to find a new approach to finding a new target for oncotherapy drugs.
3.The expression and significance of urokinase-type plasminogen activator and its receptor in squamous cell carcinoma of hypopharynx.
Zhenghua LÜ ; Xiaojie MA ; Xinliang g PAN ; Dayu LIU ; Xinyon LUAN
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2008;22(21):961-967
OBJECTIVE:
To investigate the expression of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in squamous cell carcinoma of hypopharynx and reveal the correlation of the major clinicopathological parameters and prognosis.
METHOD:
Samples of 48 hypopharyngeal carcinoma and 10 normal hypopharyngeal tissue were detected by immunohistochemistry method (SP method) for urokinase-type plasminogen activator (uPA) and its receptor (uPAR). The correlation between the expression of urokinase-type plasminogen activator and its receptor and the major clinicopathological parameters of hypopharyngeal carcinoma were analyzed by rank sum test and Spearman correlation analysis. Overall survival were analyzed according to Kaplan-Meier and log-rank statistics, the prognostic relevance of uPA and uPAR and conventional prognostic factors were analyzed by Cox analysis.
RESULT:
In 48 hypopharyngeal carcinoma specimens, positive expression rates of uPA and uPAR were 77.1% and 68.75% respectively, which were significantly higher than in normal tissues (P < 0.01). The uPA and uPAR positive expression was correlated with pathological grading, lymph node metastases and growth mode of hypopharyngeal carcinoma. The positive expression rate for uPA and uPAR in patients with lower pathological grading, lymph node metastases and invasion growth mode were significantly higher than in patients with higher pathological grading, non-lymph node metastases and non-invasion growth mode. Patients were followed-up postoperatively. The positive expression of uPA and uPAR were correlated with prognosis (P < 0.05 and P < 0.01). According to Log-rank statistics, patients with positive expression of uPA and uPAR had a significantly shorter survival time than those with negative expression of uPA and uPAR. Multivariate Cox analysis revealed that three independent prognostic factors for overall survival time were clinical stage, invasion growth mode and uPAR expression.
CONCLUSION
The positive expression of uPA and uPAR in hypopharyngeal carcinoma were significantly higher than in normal tissues. uPAR is a new independent and strong biologically prognostic factors, which positive expression may be a powerful aid in evaluating metastatic potential and High-Risk patients in early stage of hypopharynx carcinoma ryngeal carcinoma.
Adult
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Aged
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Carcinoma, Squamous Cell
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metabolism
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pathology
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Female
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Humans
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Hypopharyngeal Neoplasms
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metabolism
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pathology
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Male
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Middle Aged
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Neoplasm Staging
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Prognosis
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Receptors, Urokinase Plasminogen Activator
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metabolism
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Urokinase-Type Plasminogen Activator
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metabolism