Zhang R.,Zhejiang University |
Hu Y.-Y.,Zhejiang University |
Yang X.-F.,Zhejiang University |
Gu D.-X.,Zhejiang University |
And 5 more authors.
European Journal of Clinical Microbiology and Infectious Diseases | Year: 2014
One hundred and thirty-six blaOXA-51-negative strains were identified from 1,067 Acinetobacter calcoaceticus-A. baumannii complex (ACB complex) isolates, which were collected during October 2010 to March 2013 from 15 general hospitals in 10 cities throughout Zhejiang Province, China. Seven of the 136 blaOXA-51-negative ACB complex isolates were New Delhi metallo-β-lactamase-1 (NDM-1)-positive, among which three were identified as A. nosocomialis and four were identified as A. pittii strains using 16S-23S rRNA gene intergenic spacer (ITS) sequencing and partial RNA polymerase β-subunit (rpoB) sequencing. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) analysis showed that the seven NDM-positive isolates belonged to three clonal strains with three novel sequence types (STs). Polymerase chain reaction (PCR) assays and DNA sequence analysis of the carbapenemase and other β-lactamase genes indicated that all the isolates harbored the blaNDM-1 gene, and that only one strain of A. nosocomialis isolates harbored both blaNDM-1 and bla OXA-23. All of them were positive for blaADC, from which three novel blaADC genes (designated as blaADC-69, blaADC-70, and blaADC-71) were detected for the first time. The presence of ISAba125 upstream of blaNDM-1 was identified through genetic environment analysis. Carbapenem resistance can be transferred from A. nosocomialis and A. pittii to Escherichia coli EC600 by the conjugation experiment. Plasmid analysis, DNA hybridization, and extraction experiments indicated that bla NDM-1 was located on a plasmid of approximately 50 kb. In conclusion, we characterized the dissemination of NDM-1-positive A. pittii strains in Zhejiang Province, China, and reported the NDM-producing A. nosocomialis for the first time. © 2013 Springer-Verlag.
Zheng S.,Hangzhou First Peoples Hospital of Zhejiang Province |
Huang K.,Zhejiang University |
Tao D.,Taizhou Hospital of Zhejiang Province |
Pan Y.,Hangzhou First Peoples Hospital of Zhejiang Province
Journal of Gastrointestinal Surgery | Year: 2011
Background: Most gastrointestinal stromal tumors (GISTs) have gain-of-function mutation of the c-kit gene, and some have mutation of the platelet-derived growth factor receptor-α (PDGFR-α) gene. Extragastrointestinal stromal tumors (EGISTs) are mesenchymal tumors that occur outside the digestive tract. But thetissues from 25 cases of EGIST were analyzed for CD117, CD34, Ki-67, S-100, smooth muscle actin, and desmin expression by immunohistochemical method. These cases of EGISTs were also evaluated for the presence of c-kit exons 9, 11, 13, and 17 mutations and PDGFR-α exons 12 and 18 mutations. Survival analysis was used to evaluate the prognostic factors. Results: c-kit mutations were detected in 44% of EGIST patients and all were exon 11 mutations. PDGFR-α mutations were found in 12% of the 25 cases and all were exon 18 mutations. Survival analysis indicated that mitotic count and Ki-67 labeling index (Ki-67 LI) were significant predictors of survival. Conclusion: The pattern of c-kit and PDGFR-α mutation in EGISTs was essentially similar to that in GISTs. From the molecular genetics aspect, EGISTs may be a special subtype of GISTs. The results also show that the combination of mitotic counts and Ki-67 LI may be useful for predicting the prognosis of EGISTs. © 2011 The Society for Surgery of the Alimentary Tract.
Zheng S.,Hangzhou Cancer Hospital |
Huang K.-E.,Zhejiang University |
Pan Y.-L.,Hangzhou Cancer Hospital |
Zhou Y.,Hangzhou Cancer Hospital |
And 5 more authors.
Gastric Cancer | Year: 2015
Background and aims: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumor of the digestive tract and characterized by expression of KIT protein. Imatinib is the frontline therapy for metastatic and unresectable GIST patients showing clinical responses in 80 % of cases. Despite the often long-lasting clinical benefit seen in most patients treated with imatinib, many will eventually suffer disease progression. The most frequent mechanism of imatinib resistance in GIST is the acquisition of secondary mutations in either KIT or PDGFRA. There are also some imatinib-resistant GIST patients lacking an identifiable mechanism of treatment failure. Recently, activating BRAF mutation was detected in a small percentage of GISTs. In this study, we report a case of GIST with acquired resistance to imatinib during therapy. Methods: Histological, immunohistochemical, Western blot and mutational analyses were performed on GIST tissues before and after imatinib resistance. Results: The imatinib-resistant tumor showed not only heterogeneous mutations of KIT and BRAF besides the primary mutation, but also transdifferentiation into a rhabdomyosarcoma phenotype. According to Western blot analysis, in imatinib-resistant GIST with both KIT V559D and BRAF V600E mutations, the inhibition of KIT V559D by imatinib caused a strong decrease of AKT phosphorylation, while ERK1/2 phosphorylation was not affected. Conclusions: This finding, in combination with the loss of KIT expression, suggests the possibility of activation of RAS-RAF-MEK-ERK pathways driven by a KIT-independent oncogenic mechanism. Understanding the genetic aberrations beyond KIT and PDGFRA may lead to the identification of additional therapeutic targets for GISTs. © 2014, The International Gastric Cancer Association and The Japanese Gastric Cancer Association.
Chu X.,Fudan University |
Zhu C.-C.,Taizhou Hospital of Zhejiang Province |
Liu H.,Fudan University |
Wang J.-C.,Taizhou Hospital of Zhejiang Province
Asian Pacific Journal of Cancer Prevention | Year: 2014
Purpose: To investigate the expression of hypoxia-inducible factor prolyl hydroxylase 3 (HIFPH3) in non-small cell lung cancer (NSCLC) and explore the correlation of HIFPH3 expression with lymph node metastasis and microvessel density (MVD). Materials and Methods: A total of 73 cases of NSCLC specimens, 24 cases of paracancerous tissues, and 20 normal pulmonary tissues were collected for HIFPH3 and CD31 immunohistochmical (IHC) study. Microvessel density (MVD) of the NSCLC tissues was also determined based on the expression of CD31. Results: The expression of HIFPH3 in carcinoma tissue was statistically higher than para-cancerous and normal pulmonary tissues (χ2=48.806, p<0.05). Compared withthe negative lymph node metastasis group, the lymph node metastasis group showed significantly higher HIFPH3 expression (χ2=6.300, p<0.05). The strong HIFPH3+group displayed a significantly higher MVD than weak HIFPH3+ and HIFPH3- groups (p<0.05). No differences in positive HIFPH3 expression were noted regarding the tumor diameter, age, smoking status, gender of NSCLC patients, tumor size, histopathology, or differentiation. Conclusions: HIFPH3 expression in human NSCLC lesions is significantly higher than that in para-cancerous and normal lung tissues and is positively associated with lymph node metastasis and MVD.
Zhao X.,The Second Peoples Hospital of Yueqing |
Li J.,The Second Peoples Hospital of Yueqing |
Zhuo J.,The Second Peoples Hospital of Yueqing |
Cai L.,Taizhou Hospital of Zhejiang Province
Biochemical and Biophysical Research Communications | Year: 2010
The Ras-related tumor suppressor gene aplasia Ras homolog member I (ARHI) is frequently downregulated in many types of cancer, including hepatocellular carcinoma (HCC). In this study, we sought to explore the therapeutic implications of ARHI reconstitution in the treatment of HCC. We generated stable cell lines overexpressing ARHI in Hep3B and SK-Hep1 cells, both of which lack endogenous ARHI. The effects of ARHI reexpression on tumor growth and angiogenesis were assessed. Given the key role of mammalian target of rapamycin (mTOR) signaling in HCC progression, we also tested whether ARHI overexpression affected the mTOR pathway. Forced expression of ARHI resulted in a significant inhibition of the proliferation of both Hep3B and SK-Hep1 cells compared to control cells (P< 0.01). Cell cycle analysis revealed a G0-G1 arrest induced by ARHI reexpression. Moreover, ARHI reexpression significantly retarded Hep3B xenograft growth in vivo, and caused a marked reduction in tumor angiogenesis assessed by CD31-stained microvessel count. Western blot analysis of the xenografts showed that ARHI overexpression substantially reduced the phosphorylation of two mTOR substrates, S6K1 and 4E-BP1, indicative of an inactivation of the mTOR pathway. Accompanying with the mTOR inactivation, the angiogenic factors, hypoxia-inducible factor 1 alpha and vascular endothelial growth factor, were significantly downregulated. These data highlighted an important role for ARHI in controlling HCC growth and angiogenesis, therefore offering a possible therapeutic strategy against this malignancy. © 2010 Elsevier Inc.
Wang Z.,Taizhou Hospital of Zhejiang Province |
Zhang C.,Taizhou Hospital of Zhejiang Province |
Hong Z.,Taizhou Hospital of Zhejiang Province |
Chen H.,Taizhou Hospital of Zhejiang Province |
And 2 more authors.
Experimental and Therapeutic Medicine | Year: 2013
Spinal cord injury (SCI) is a severe health problem and the mechanism involved remains elusive. The aim of the present study was to elucidate the role of C/EBP homologous protein (CHOP), a prominent protein of the endoplasmic reticulum (ER) stress-mediated apoptosis in SCI. A total of 20 adult male Sprague-Dawley rats were divided into two groups at random, ten rats were subjected to a modified Allen's test (using a weight-drop device) to induce a SCI model and the remaining ten rats only had the corresponding vertebral lamina removed with no injury and served as the sham-operated group. Pathological changes in the spinal cord were observed 12 h after injury by hematoxylin and eosin staining and TUNEL staining was performed to visualize apoptotic cells. The expression of CHOP was also detected by immunohistochemistry and quantitative real-time reverse transcription-polymerase chain reaction. The results showed that a typical apoptotic morphology, namely the increased the number of TUNEL-positive cells in the injured spinal cord. The expression levels of CHOP in the rats with SCI were increased compared with the sham-operated rats (P<0.05). These results revealed that CHOP-mediated ER stress-induced apoptosis may be involved in SCI.
Liang J.,Taizhou Hospital of Zhejiang Province |
Chen H.,Taizhou Hospital of Zhejiang Province |
Pan W.,Taizhou Hospital of Zhejiang Province |
Xu C.,Taizhou Hospital of Zhejiang Province
Molecular Medicine Reports | Year: 2012
The aim of this study was to investigate the protective effect of puerarin on attenuating caspase-3 expression in osteoblasts of streptozotocin-induced diabetic rats and the possible mechanisms involved. Diabetic rats were treated with a puerarin injection of 100 mg/kg/day. After 6 weeks, the bone mineral density, pathological changes and expression of caspase-3 were observed. The bone mineral density in the diabetic rats was significantly lower compared to the control group, while osteoblast numbers in the cortical bone were significantly reduced, and new bone formation in the diabetic rats was rare. Caspase-3 expression in the osteoblasts of diabetic rats increased compared to the rats in the control group. These pathological changes were improved and caspase-3 expression decreased in the puerarin-treated rats compared to the diabetic rats (P<0.01). High glucose levels affect bone metabolism and increase caspase-3 expression in osteoblasts, and thus lead to diabetic osteoporosis. Puerarin may play a protective role in diabetic osteoporosis via the reduction of caspase-3 expression.
Zhang Y.,Taizhou Hospital of Zhejiang Province
Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery | Year: 2011
To study the expression of epidermal growth factor receptor (EGFR), C-erbB-2 and its relationship with cell proliferation in nasopharyngeal carcinoma. Expression of C-erbB-2, EGFR and proliferating cell nuclear antigen (PCNA) were detected with immunohistochemical staining in 32 nasopharyngeal carcinoma samples and 12 chronic inflammatory nasopharyngeal tissue samples. The positive rate of EGFR,C-erbB-2, and PCNA expression in nasopharyngeal carcinoma was 65.6%, 37.5%, and (42.5 +/- 22.6)%, respectively, which was significantly higher than that in chronic inflammatory nasopharyngeal tissue (P < 0.05). There were positive correlations between the positive rate of EGFR, C-erbB-2, and PCNA expression and histopathological stage. The co-expression of C-erbB2 and EGFR was found in 62.5% (20/32) nasopharyngeal carcinoma samples. There was a positive correlation between C-erbB-2 and EGFR expression (r = 0.38, P < 0.05). The highest percentage of PCNA expression was found in carcinoma samples with co-expression of C-erbB and EGFR. C-erbB-2, EGFR might have synergetic effect in the development and progress of nasopharyngeal carcinoma. The co-expression of C-erbB-2 and EGFR closely correlates with cell proliferation status.
Wu X.M.,Taizhou Hospital of Zhejiang Province
Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] | Year: 2012
To investigate the possible association between the SNP in the 5' untranslated region (5' UTR) of the human beta defensin 1 (DEFB1) gene and the susceptibility to pulmonary tuberculosis (PTB) in Chinese Han population. In this case-control study, venous blood was collected from 102 patients with PTB and 148 healthful persons. Genomic DNA was extracted using whole blood DNA extraction kit. The -52A/G, -44C/G and -20A/G SNP were genotyped by PCR-directed sequencing. The genotypes and allele frequency were analyzed using the χ(2) test. The linkage disequilibrium and haplotype were analyzed by SHEsis software. A total of 102 patients with PTB (69 males and 33 females, (53.42 ± 20.22) years old) and 148 healthy control cases (95 males and 53 females, (50.67 ± 14.53) years old) were enrolled, with no difference in gender and age (all P values > 0.05). DEFB1 -44 CC genotype was significantly more frequently found in PTB patients than in control group (81.4% (83/102) vs 66.9% (99/148), χ(2) = 5.114, P < 0.05, OR = 2.096, 95%CI: 1.095 - 4.011), so was -44C allele (89.2% (182/204) vs 80.4% (238/296), χ(2) = 6.975, P < 0.05, OR = 1.576, 95%CI: 1.086 - 2.286). No difference in -52 A/G and -20 A/G SNP was observed between the two groups. The proportion of the GGG (-52/-44/-20) haplotype was lower in PTB patients than in the control group (0.030 vs 0.081, χ(2) = 5.629, P < 0.05, OR = 0.348, 95%CI: 0.140 - 0.863). No linkage disequilibrium was found among the SNP of the three sites (D' values were 0.132, 0.064, 0.088; r(2) values were 0.003, 0.002, 0.003; all P values > 0.05). These results suggest that the SNP of DEFB1 5' UTR is associated with susceptibility to PTB in Chinese Han population. -44 C→G SNP and the related haplotype (GGG) might play a protective role in the pathogenesis of PTB.
Zhu Y.-Y.,Taizhou Hospital of Zhejiang Province |
Mao Y.-Z.,Taizhou Hospital of Zhejiang Province |
Wu W.-L.,Taizhou Hospital of Zhejiang Province |
Cai Q.-X.,Taizhou Hospital of Zhejiang Province |
Lin X.-H.,Taizhou Hospital of Zhejiang Province
Clinical and Vaccine Immunology | Year: 2010
The objective of this work was to evaluate whether postnatal hepatitis B immunization failure in children is caused by prenatal infections. A prospective study was conducted from October 2006 to September 2008. Fetal samples from HBsAg-positive mothers were retrieved by either amniocentesis or cordocentesis (percutaneous umbilical blood sampling [PUBS]). Hepatitis B virus (HBV) serologic markers (HBVM) and quantitative HBV DNA assays were performed to assess prenatal infection. All neonates were given combined HBV immunoprophylaxis after delivery. The newborns were followed up with HBV serologic testing at 1 year old. For the 252 pregnant women recruited, 16 fetuses were found to be HBV DNA positive, with all HBV DNA levels under 10 4 copies/ml. HBsAg and HBV DNA detected in the uterus were uncommon and were expressed at low levels. In contract to the case with prenatal statuses, neonatal serologies were more similar to their mothers'. The response rate of vaccination was 95%. Six children for whom immunoprophylaxis failed were born to HBeAg-positive mothers with high HBV DNA levels (>108 copies/ml), but only one of them was found to be positive for intrauterine HBV DNA (8.5 × 102 copies/ml). The presence of intrauterine hepatitis B antigen and DNA does not indicate postnatal HBV infection and vaccination failure. Copyright © 2010, American Society for Microbiology. All Rights Reserved.