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Liu H.,University of Sichuan | Liu S.,University of Sichuan | Liu S.,Key Laboratory of Obstetric | Wang H.,University of Sichuan | And 8 more authors.
Diagnostic Pathology | Year: 2012

Background: Human papillomavirus (HPV) infection plays an etiological role in the development of cervical dysplasia and cancer. Amplification of human telomerase gene (hTERC) and over expression of telomerase were found to be associated with cervical tumorigenesis. This study was performed to analyze genomic amplification of hTERC gene, telomerase activity in association with HPV infection in different stages of cervical intraepithelial neoplasia (CIN) and cervical cancer. We were studying the role of hTERC in the progression of uterine cervical dysplasia to invasive cancer, and proposed an adjunct method for cervical cancer screening.Methods: Exfoliated cervical cells were collected from 114 patients with non neoplastic lesion (NNL, n=27), cervical intraepithelial neoplasia (CIN1, n=26, CIN2, n=16, CIN3, n=24) and cervical carcinoma (CA, n=21), and analyzed for amplification of hTERC with two-color fluorescence in situ hybridization (FISH) probe and HPV-DNA with Hybrid Capture 2.From these patients, 53 were taken biopsy to analyze telomerase activity by telomeric repeat amplification protocol (TRAP) and expression of human telomerase reverse transcriptase (hTERT), with immunohistochemistry (IHC). All biopsies were clinically confirmed by phathologists.Results: Amplification of hTERC was significantly associated with the histologic diagnoses (p<0.05). The positive correlation was found between the level of hTERC amplification and histologic grading of dysplasia (CIN2/3 from CIN1 or normal, P=0.03). A profounding increase in the accumulation of HPV and hTERC positive cases was observed in the CIN3 subgroup compared with the CIN2 group, 25% versus 62.96%, respectively (p=0.007).Conclusions: hTERC ampliffication can be detected with FISH technique on exfoliated cervical cells. Amplification of hTERC and HPV infection are associated with more progressive CIN3 and CA. The testing of hTERC amplification might be a supplementary to cytology screening and HPV test, especially high-risk patients.Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1857134686755648. © 2012 Liu et al.; licensee BioMed Central Ltd.

Xiong L.J.,University of Sichuan | Xiong L.J.,Key Laboratory of Obstetric | Tong Y.,University of Sichuan | Tong Y.,Key Laboratory of Obstetric | And 4 more authors.
Helicobacter | Year: 2013

Background: Helicobacter pylori infection is acquired mainly during childhood. To eradicate H. pylori, clarithromycin-based triple therapy has been recommended in children and adults by the latest Maastricht Consensus. However, the prevalence of clarithromycin-resistant H. pylori was higher in children than that in adults. Therefore, rapid, reliable and noninvasive methods for detecting clarithromycin-resistant H. pylori strains should be developed for children. Materials and Methods: Studies on evaluating stool PCR in detecting clarithromycin-resistant H. pylori and epidemiological surveys of the prevalence of clarithromycin-resistant H. pylori in children were searched in PubMed (from 1966 to December, 2011) for reviewing. Results: The average rates of primary clarithromycin-resistant H. pylori ranged from less than 10% to more than 40% in different regions. The rates of secondary resistance to clarithromycin were higher than primary resistance in the same population. In H. pylori isolated from children, the frequent point mutations that are responsible for the clarithromycin resistance included A2143G, A2142G, A2142C and A2144G, and they varied geographically. Comparing with culture-based susceptibility tests, stool PCR performed excellently for their rapidity, independence of bacterial growth, reproducibility and easy standardization. However, stool PCR showed lower sensitivity but perfect specificity in detection of clarithromycin-resistant H. pylori in children. Methodology and mixed infections of resistant H. pylori strains might contribute to the considerable discrepancies of stool PCR results. Conclusion: Detection of clarithromycin-resistant H. pylori by stool PCR for children are reliable, rapid, noninvasive methods that are worthy of further clinical promotion. However, more evaluations of stool PCR in detection of clarithromycin-resistant H. pylori in children need to be conducted. © 2012 Blackwell Publishing Ltd.

Mei L.,University of Sichuan | Hou Q.,University of Sichuan | Fang F.,University of Sichuan | Wang H.,University of Sichuan | Wang H.,Key Laboratory of Obstetric
European Journal of Gynaecological Oncology | Year: 2016

Objectives: To assess the effect and toxicity of CA125-targeted antibody used as maintenance therapy for advanced epithelial ovarian cancer (EOC). Materials and Methods: Two reviewers searched PubMed, Medline, Embase, VIP databases, and the references of selected articles for randomized controlled trials comparing maintenance CA125-targeted antibody treatment with placebo/observation. One -, two-, three-, and five-year overall survival (OS) and progression free survival (PFS) were collected. Incidence and severity of adverse events were extracted. Meta-analysis of combined risk ratio (RR) for OS, PFS, and toxicity were conducted. Results: Four trials including 1,259 women were identified. Meta-analysis showed the combined RR was 1.02 (95% CI, 0.85-1.22) for three-year OS and 0.98 (95% CI, 0.70-1.39) for the three-year PFS. This review found that abagovomab and oregovomab caused toxicity no more than placebo. Conclusions: CA125-targeted antibody used as maintenance therapy alone is not more effective than placebo but they were safe as maintenance therapy.

Ma J.,University of Sichuan | Yu D.,University of Sichuan | Yu D.,Key Laboratory of Obstetric | Tong Y.,University of Sichuan | And 2 more authors.
Biological Research | Year: 2012

Hypoxia-ischemia (HI) occurring in immature brains stimulates the expression of tissue-type plasminogen activator (tPA). Neuroserpin is a selected inhibitor of tPA in the central nerves system. However, the role that neuroserpin plays and the possible mechanisms involved during neonatal HI are poorly defined. In this study, an oxygen-glucose deprivation and reoxygenation (OGD/R) model was generated with cultured rat cortical neurons mimicking neonatal HI injury ex vivo, and an acute neuronal excitatory injury was induced by exposure to a high concentration of N-methyl-D-aspartic acid (NMDA). Cells received either neuroserpin or MK-801, an antagonist of the NMDA receptor, during OGD/R, and were incubated with or without neuroserpin after NMDA exposure. Cell viability and morphology were detected by a Cell Counting Kit-8 and immunohistochemical staining, respectively. TPA expression and activity were also assessed. We found that MK-801 alleviated injuries induced by OGD/R, suggesting an excitatory damage involvement. Neuroserpin provided a dosedependent neuroprotective effect in both OGD/R and acute excitatory injuries by inhibiting the activity of tPA, without affecting neuronal tPA expression. Neuroserpin protected neurons against OGD/R even after a delayed administration of 3h. Collectively, our data indicate that neuroserpin protects neurons against OGD/R. mainly by inhibiting tPA-mediated acute neuronal excitotoxicity.

Gao J.,Key Laboratory of Obstetric | Gao J.,University of Sichuan | Gao J.,Key Laboratory for Molecular Biology of Neural Development | Gao J.,CAS Shenzhen Institutes of Advanced Technology | And 6 more authors.
Acta Biochimica et Biophysica Sinica | Year: 2015

The ubiquitin ligase Parkin and autophagic adapter protein p62 are known to function in a common pathway controlling mitochondrial autophagy (mitophagy). However, the evidence supporting that p62 is directly recruited by ubiquitinated proteins remains undetermined. Here, we demonstrate that mitochondrial fission factor (Mff) associates with Parkin and carbonyl cyanide m-chlorophenyl hydrazone treatment significantly increases the affinity of Parkin with Mff. After recruitment to depolarized mitochondria, Parkin mediates poly-ubiquitination of Mff at lysine 251. Replacement of lysine 251 by arginine (K251R) totally abrogates Parkin-stimulated ubiquitination of Mff. Subsequently, the ubiquitinated Mff promotes its association with p62. Mff knockout interferes with p62 translocation to damaged mitochondria. Only re-transfection of Mff WT, but not K251R mutant, rescues this phenotype. Furthermore, loss of Mff results in failure of Parkin translocation and final clearance of damaged mitochondria. Thus, our data reveal functional links among Mff, p62, and the selective autophagy of mitochondria, which are implicated in the pathogenesis of neurodegeneration diseases. © 2015 The Author 2015. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

Yu Q.,University of Sichuan | Yu Q.,Key Laboratory of Obstetric | Liu S.-L.,University of Sichuan | Liu S.-L.,Key Laboratory of Obstetric | And 6 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2013

In cervical cancer, one of the most common malignant tumors in women worldwide, miR-126 has been reported to exhibit decreased expression. However, its role in cervical cancer cell proliferation and drug sensitivity has remained relatively unexplored. Here, we compared the expression of miR-126 in cervical cancer tissues (n = 20) with that in normal cervical tissue (n = 20) using quantitative RT-PCR. The viability of Siha cervical cancer cells was further measured by MTT assay after transfection with miR-126 mimic (Siha-miR-126 mimic) or microRNA mimic negative control (Siha-miR mimic NC) and after treatment with various concentrations of bleomycin (BLM). IC50s were calculated, and the survival rates (SRs) of Siha cells were calculated. miR-126 expression in cervical cancer tissue was significantly decreased compared with that in normal cervical tissue (P < 0.01). The relative SRs of Siha-miR-126 mimic cells were also significantly decreased compared with those of Siha-miR mimic NC cells at 24-96 h after transfection. The IC50 of BLM in Siha-miR-126 mimic cells (50.3 ± 2.02 μg/mL) was decreased compared with that in Siha-miR mimic NC cells (70.5 ± 4.33 μg/mL) at 48 h after transfection (P < 0.05). Finally, the SRs of Siha-miR-126 mimic cells were significantly lower than those of SihamiR mimic NC cells after cultured in medium containing 40 μg/mL BLM for 24-96 h (P < 0.05). These results suggest that miR-126 is expressed at low levels in cervical cancer. Upregulation of miR-126 inhibited cervical cancer cell proliferation and enhanced the sensitivity to BLM. Thus, miR-126 may represent a novel approach to cervical cancer treatment.

Hu Q.,University of Sichuan | Hu Q.,Key Laboratory of Obstetric | Peng J.,University of Sichuan | Peng J.,Key Laboratory of Obstetric | And 13 more authors.
International Journal of Clinical and Experimental Pathology | Year: 2014

Lin28B, a homologue of Lin28, represses biogenesis of let-7 microRNAs with a role in tumorigenesis and is considered a potential therapeutic target for various human cancers. The aim of the study was to identify the clinical significance of Lin28B in gastric adenocarcinoma (GAC). We examined the expression of Lin28B in 97 human gastric cancer samples with 32 samples of non-dysplastic tissues by immunohistochemistry. In the 97 GAC cases, 42 were with high Lin28B expression. The expression levels of Lin28B proteins in GAC were higher than in corresponding adjacent normal tissues (P=0.001). Significant correlations were noted between Lin28B expression and lymph node status (P=0.005), TNM stage (P < 0.001), tumor invasion (P=0.036), and differentiation (P=0.001) of GAC patients. The Kaplan-Meier estimates showed a negative correlation of overall 5-year survival rate with Lin28B expression where higher expression resulted in poorer prognosis in GAC. In univariate analysis, lymph node metastasis, TNM stage, serosal invasion, Lin28B expression as well as differentiation grade could predict the prognosis of GAC patients (P=0.002, P < 0.001, P=0.003, P < 0.001, P=0.001, respectively). Multivariate analysis revealed that the expression level of Lin28B (P < 0.001), TNM stage (P < 0.001) as well as differentiation grade (P < 0.001) were the three potential independent prognostic factors in our study [Hazard ratio (HR)=2.108 and P=0.017, HR=1.994 and P=0.018, HR=1.939 and P=0.046, respectively]. Our findings point to the prognostic role of Lin28B in GAC, and indicate Lin28B as a potential therapeutic target of GAC patients.

Hu Q.,University of Sichuan | Hu Q.,Key Laboratory of Obstetric | Peng J.,University of Sichuan | Peng J.,Key Laboratory of Obstetric | And 13 more authors.
International Journal of Clinical and Experimental Pathology | Year: 2014

Emerging evidence has indicated that apoptotic cells have a compensatory effect on the proliferation of neighboring cells. Recent studies have shown that apoptotic tumor cells stimulate the repopulation of tumors from a small number of surviving cells by cleaved caspase-3 regulation and elevated tumor cleaved (and thus activated) caspase-3 expression levels predict worse treatment outcomes in cancer patients. The prognostic significance of cleaved caspase-3 should be demonstrated in more human cancer types and larger subjects. Here, we examined the cleaved caspase-3 expression in 367 human tumor samples (gastric cancer: 97 cases, ovarian cancer: 65 cases, cervical cancer: 104 cases; colorectal cancer: 101 cases) with immunohistochemistry (IHC) and the relationship between the expression of cleaved caspase-3 and various clinicopathological factors were also detected. We found that, cleaved caspase-3 was significantly associated with pathological risk factors (P < 0.005) for the studied cancers, such as tumor stage, lymph-node metastasis, differentiation and so on. In univariate and multivariate analysis, patients with high expression of cleaved caspase-3 had a significant shorter overall survival time compared with those with low cleaved caspase-3 expression in gastric cancer (P < 0.001), ovarian cancer (P < 0.001), cervical cancer (P = 0.002), colorectal cancer (P < 0.001) individually and in the patients combined (P < 0.001). Cox regression results suggested cleaved caspase-3 as an independent prognosis predictor for the studied four cancer types. Our study showed cleaved caspase-3 was well correlated to progression, aggressive behaviors in the studied cancer, and implicated it as a potential predictive factor for the prognosis of the four cancer types. It also indicated cleaved caspase-3 as a potential therapeutic target for cancer patients.

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