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ABSTRACT: To investigate the clinical value of combination of human epididymis protein 4 (HE4), CA125 and the Risk of Ovarian Malignancy Algorithm (ROMA) in diagnosis of ovarian carcinoma.
To detect the serum concentration of HE4 using ELISA and CA125 using ECL in patients of ovarian carcinoma group (n = 119), borderline ovarian tumor group (n = 36), benign ovarian neoplasm group (n = 96) and female healthy control group (n = 53). The ROMA based on the serum level of CA125, HE4 and a woman's menopausal status was used to calculate the predicted probability (PP) and diagnostic results of ovarian cancers.
The receiver operating characteristic (ROC) analysis showed the cut-off value was 67.3 pmol/L (the AUC was 0.906, the sensitivity was 80.7% and specificity was 94.6%). The serum levels of HE4 and CA125 in the ovarian carcinoma group were significantly higher than that in the borderline ovarian tumor group, benign ovarian neoplasm group and female healthy control group (P < 0.01). The serum levels of CA125 and HE4 showed statistically no significant difference between the borderline ovarian tumor group and benign ovarian neoplasm group (P > 0.05). The levels of HE4 and CA125 were reduced significantly in ovarian patients after surgery therapy (P < 0.01). The sensitivity and specificity of HE4 + CA125 combination was 92.7% and 72.5%. The ROMA that can classify patients into high and low risk groups was established as 9.3% in premenopausal and 27.3% in postmenopausal women.
HE4 is a helpful biomarker for ovarian carcinoma diagnosis. Biomarker combination of HE4 and CA125, and applying of the ROMA are helpful to improve the accuracy in diagnosis of ovarian cancers.
Zhonghua zhong liu za zhi [Chinese journal of oncology] 07/2011; 33(7):540-3.
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ABSTRACT: NDM-1 (New Delhi metallo-beta-lactamase) gene encodes a metallo-beta-lactamase (MBL) with high carbapenemase activity, which makes the host bacterial strain easily dispatch the last-resort antibiotics known as carbapenems and cause global concern. Here we present the bioinformatics data showing an unexpected similarity between NDM-1 and beta-lactamase II from Erythrobacter litoralis, a marine microbial isolate. We have further expressed these two mature proteins in E. coli cells, both of which present as a monomer with a molecular mass of 25 kDa. Antimicrobial susceptibility assay reveals that they share similar substrate specificities and are sensitive to aztreonam and tigecycline. The conformational change accompanied with the zinc binding visualized by nuclear magnetic resonance, Zn(2+)-bound NDM-1, adopts at least some stable tertiary structure in contrast to the metal-free protein. Our work implies a close evolutionary relationship between antibiotic resistance genes in environmental reservoir and in the clinic, challenging the antimicrobial resistance monitoring.
Protein & Cell 03/2011; 2(3):250-8.
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ABSTRACT: The scavenging ability of sufficient divalent metal ions is pivotal for pathogenic bacteria to survive in the host. ATP-binding cassette (ABC)-type metal transporters provide a considerable amount of different transition metals for bacterial growth. TroA is a substrate binding protein for uptake of multiple metal ions. However, the function and structure of the TroA homologue from the epidemic Streptococcus suis isolates (SsTroA) have not been characterized.
Here we determined the crystal structure of SsTroA from a highly pathogenic streptococcal toxic shock syndrome (STSS)-causing Streptococcus suis in complex with zinc. Inductively coupled plasma mass spectrometry (ICP-MS) analysis revealed that apo-SsTroA binds Zn(2+) and Mn(2+). Both metals bind to SsTroA with nanomolar affinity and stabilize the protein against thermal unfolding. Zn(2+) and Mn(2+) induce distinct conformational changes in SsTroA compared with the apo form as confirmed by both circular dichroism (CD) and nuclear magnetic resonance (NMR) spectra. NMR data also revealed that Zn(2+)/Mn(2+) bind to SsTroA in either the same site or an adjacent region. Finally, we found that the folding of the metal-bound protein is more compact than the corresponding apoprotein.
Our findings reveal a mechanism for uptake of metal ions in S. suis and this mechanism provides a reasonable explanation as to how SsTroA operates in metal transport.
PLoS ONE 01/2011; 6(5):e19510. · 4.09 Impact Factor
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ABSTRACT: pro-gastrin-releasing peptide (ProGRP) and neuron specific enolase (NSE) have become hotspot of tumor markers for small cell lung cancer (SCLC), and the aim of this study is to evaluate and compare the diagnostic value of serum ProGRP and NSE in SCLC by meta-analysis.
all the English and Chinese literatures for differential diagnosis of SCLC by serum ProGRP and NSE were collected. Sensitivity, specificity, likelihood ratio and diagnostic odds ratio were pooled using random-effect model. Summary receiver operating characteristic curve analysis was used to evaluate the diagnostic value of serum ProGRP and NSE.
ten studies were included in the meta-analysis, with a total of 2 536 cases. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of ProGRP in the diagnosis of SCLC were 0.70, 0.93, 11.57, 0.32 and 36.45, and as for NSE those were 0.61, 0.90, 5.67, 0.45 and 13.08, respectively. The Q* value of ProGRP and NSE were 0.804 2 and 0.723 2. There was no statistical significance between the two.
comparing with NSE, ProGRP has higher specificity and similar discrimination ability, so ProGRP might be a better index in the diagnosis of SCLC.
Zhongguo fei ai za zhi = Chinese journal of lung cancer 12/2010; 13(12):1094-100.
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ABSTRACT: To evaluate and compare the value of serum CK19-2G2 and Cyfra21-1 in diagnosis of lung cancer.
The serum concentration of CK19-2G2 and Cyfra21-1 was detected in 104 patients with lung cancer, 71 with benign lung diseases and 105 healthy volunteers. The value of the two parameters in the diagnosis of lung cancer was evaluated with ROC curve analysis. The mean level of CK19-2G2 in the three groups was compared with that of Cyfra21-1 by Mann-Whitney U test, and the correlation between these two parameters was calculated using Pearson coefficient correlation test.
The mean serum CK19-2G2 concentration in the lung cancer group was 2.87 mU/ml, significantly higher than that in the group with benign lung diseases (1.02 mU/ml) and healthy volunteer group (0.01 mU/ml) (P = 0.000). The serum concentration of CK19-2G2 was positively correlated with that of Cyfra21-1, with a Pearson coefficient correlation of 0.543. Furthermore, the mean serum CK19-2G2 level in squamous cell carcinoma group (8.35 mU/ml) was significantly higher than that in the other pathologic groups (P < 0.05).
CK19-2G2, with a higher specificity, may be a better tumor marker than CK19-2G2 in respect of specificity for non-small cell lung cancer (NSCLC), especially for squamous lung carcinoma, and deserves further study.
Zhonghua zhong liu za zhi [Chinese journal of oncology] 01/2009; 30(12):930-2.
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ABSTRACT: The Slit-Robo (sr) GTPase-activating protein (GAPs) are important components in the intracellular pathway mediating Slit-Robo signaling in axon guidance and cell migration. We report the first crystal structure of the srGAP1 SH3 domain at 1.8-A resolution. The unusual side chain conformation of the conserved Phe-13 in the P1 pocket renders the ligand binding pocket shallow and narrow, which contributes toward the low binding affinity. Moreover, the opposing electrostatic charge and the hydrophobic properties of the P3 specificity pocket are consistent with the observed binding characteristics of the srGAP1 SH3 domain to its ligand. Surface plasmon resonance experiments indicate that the srGAP1 SH3 domain interacts with its natural ligand inaCtoN orientation. The srGAP1 SH3 domain can bind to both the CC2 and CC3 motifs in vitro. The N-terminal two acidic residues in the CC3 motif recognition site are necessary for srGAP1 SH3 domain binding. A longer CC3 peptide (CC3-FL) binds with greater affinity than its shorter counterpart, suggesting that the residues surrounding the proline-rich core are important for protein-peptide interactions. Our study reveals previously unknown properties of the srGAP-Robo interaction. Our data provide a structural basis for the srGAP-Robo interaction, consistent with the role of the Robo intracellular domain in interacting with other downstream signaling molecules and mediating versatile and dynamic responses to axon guidance and cell migration cues.
Journal of Biological Chemistry 10/2006; 281(38):28430-7. · 4.77 Impact Factor
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ABSTRACT: The mouse betaPIX-SH3 domain, residues 8-63 of P21-activated kinase interacting exchange factor, has been characterized by X-ray diffraction. Crystals belonging to space group P3(2)21 diffracted to 2.0 A and the structure was phased by the single-wavelength anomalous diffraction method. The domain is a compact beta-barrel with an overall conformation similar to the general SH3 structure. The X-ray structure shows mouse betaPIX-SH3 domain binding the way in which the betaPIX characteristic amino acids do so for an unconventional ligand binding surface. This arrangement provides a rationale for the unusual ligand recognition motif exhibited by mouse betaPIX-SH3 domain. Comparison with another SH3/peptide complex shows that the recognition mode of the mouse betaPIX-SH3 domain should be very similar to the RXXK ligand binding mode. The unique large and planar hydrophobic pocket may contribute to the promiscuity of betaPIX-SH3 domain resulting in its multiple biological functions.
Biochemical and Biophysical Research Communications 02/2006; 339(1):407-14. · 2.48 Impact Factor
