Zhong R.,Huazhong University of Science and Technology |
Liu L.,Huazhong University of Science and Technology |
Zou L.,Huazhong University of Science and Technology |
Sheng W.,Huazhong University of Science and Technology |
And 16 more authors.
Carcinogenesis | Year: 2013
Recent genome-wide association studies (GWAS) have reported multiple risk loci associated with risk of colorectal cancer (CRC), some of which are involved in the transforming growth factor beta (TGFβ) signaling pathway. We systematically examined associations of common genetic variations in the TGFβ signaling pathway and environmental factors with CRC risk using a two-staged case-control study in a Chinese population. A set of 77 single-nucleotide polymorphisms (SNPs) in 10 candidate genes involved in the TGFβ signaling pathway and several environmental factors including sex, age, smoking and drinking were examined by random forest (RF) to capture the potential gene-gene and gene-environment interactions in stage 1 of the study with 443 CRC patients and 480 controls. Three promising SNPs (SMAD7 rs11874392, TGFBR1 rs10988706 and rs6478972) selected by the RF method were genotyped in stage 2 comprising 351 cases and 360 controls for validation. SMAD7 rs11874392 presented consistently significant associations with a risk of CRC at both stages, with odds ratio = 1.41 (95% confidence interval = 1.21-1.63) using additive modes in combined analyses. Moreover, the potential interactions between SMAD7 rs11874392, TGFBR1 rs10988706 and rs6478972 were indicated consistently in both stages of the study by using pair-wise interaction and multilocus genotype pattern analysis. Additionally, gene-smoking interactions for rs11874392, rs10988706 and rs6478972 were also found to enhance the risk of CRC at both stages, with P for multiplicative interaction equal to 1.162×106, 8.574×108 and 9.410×108 in combined analyses, respectively. This study emphasized the substantial role of the TGFβ signaling pathway in CRC, especially in interaction with smoking. © The Author 2012. Published by Oxford University Press. All rights reserved.
Liu M.,Renmin University of China |
Luo X.-J.,Taihe Hospital |
Liao F.,Renmin University of China |
Lei X.-F.,Renmin University of China |
Dong W.-G.,Renmin University of China
Cancer Chemotherapy and Pharmacology | Year: 2011
Purpose: Noscapine plays an important role in the regulation of cell growth and death. It has been reported to potentiate the anti-tumor effect by inducing apoptosis in various malignant cells. However, the mechanism of inducing apoptosis in gastric cancer cells by this agent remains to be clarified. Methods: In the study, we investigated the signaling pathways by which noscapine induces apoptosis in gastric cancer cell lines. Apoptosis of four human gastric cancer cell lines was induced by treatment with noscapine. Results: Our results indicate that noscapine induced a dose-dependent apoptosis of these cells. The treatment with noscapine upregulated Bax and Cytochrome c (Cyt-c) protein, downregulated Bcl-2 protein. Caspase-3 and caspase-9 were activated, suggesting that the apoptosis is mediated by mitochondrial pathways. Moreover, in xenograft tumor mouse model, noscapine injection successfully inhibited the tumor growth via apoptosis induction which was demonstrated by TUNEL assay. Conclusions: These data of the study suggest that noscapine induces apoptosis in gastric cancer cells via mitochondrial pathways. © 2010 Springer-Verlag.
Zhan J.,Hubei University |
Liu Y.,Taihe Hospital |
Zhang Z.,Hubei University |
Chen C.,Hubei University |
And 2 more authors.
Molecular Biology Reports | Year: 2011
Penehyclidine hydrochloride (PHC) is a new anticholinergic drug. PHC has been shown to have a good curative effect for sepsis. Mitogen-activated protein kinase (MAPK) has recently been considered to play an important role in sepsis. In this study, the role of MAPK signal pathways in protective effects of PHC preconditioning on acute lung injury in cecal ligation and puncture (CLP)-induced sepsis was investigated. Healthy female mice were randomly divided into 4 groups: sham control, CLP, and 0.3 or 0.45 mg/kg PHC. At 12 h after surgery, arterial blood was drawn for blood gas analysis, and lung tissue samples were collected to examine pulmonary microvascular permeability, IL-6 levels and myeloperoxidase (MPO) activity. MAPK protein expressions were measured using western blot technique. Compared with sham control mice, acute lung injury was induced in CLP group, which was indicated by decreased PaO 2/FiO2, increased pulmonary microvascular permeability, IL-6 levels and MPO activity. Furthermore, mice' exposure to CLP induced the increased protein levels of MAPK. Treatment of 0.45 mg/kg PHC markedly improved PaO2/FiO2, decreased pulmonary microvascular permeability, IL-6 levels and MPO activity, and inhibited expressions of extracellular signal-regulated kinase (ERK1/2) and p38 MAPK. Taken together, these results suggest that PHC ameliorated acute lung injury through the inhibition of extracellular signal-regulated kinase (ERK1/2) and p38 MAPK activation in septic mice. © 2010 Springer Science+Business Media B.V.
Xue J.-P.,Taihe Hospital |
Wang G.,Taihe Hospital |
Zhao Z.-B.,Taihe Hospital |
Wang Q.,Taihe Hospital |
Shi Y.,Taihe Hospital
Oncology Reports | Year: 2014
The molecular mechanisms underlying genistein-mediated reversal of chemoresistance remains unknown. In the present study, we investigated the molecular mechanisms by which genistein overcomes chemoresistance and its effect on doxorubicin-induced cytotoxicity. Consistent with previous reports, genistein combined with doxorubicin had a synergistic effect on MCF-7/Adr cells, and genistein reduced the chemo-resistance of these cells. Genistein treatment increased the intracellular accumulation of doxorubicin but did not influence P-gp function. The combination of genistein and doxorubicin significantly induced cell cycle arrest and apoptosis. Genistein treatment strongly inhibited HER2/neu but not MDR-1 expression at both the mRNA and protein levels. Therefore, our results demonstrated that genistein combined with doxorubicin had a synergistic effect on MCF-7/Adr cells, and the mechanisms likely involve an increase in the intracellular accumulation of doxorubicin and suppression of HER2/neu expression.
Feng Z.,State Key Laboratory of Oncology in South China |
Feng Z.,Sun Yat Sen University |
Xu S.,State Key Laboratory of Oncology in South China |
Xu S.,Taihe Hospital |
And 4 more authors.
Cancer Letters | Year: 2010
Nasopharyngeal carcinoma (NPC) is a malignant tumor. This type of carcinoma has a low 5-year patient survival rate. Thus, there is a need for improved therapeutics. We determined that the Chk1 inhibitor Gö6976 enhanced the sensitivity of CNE1 and CNE2 cells to ionizing radiation (IR) or cisplatin by abrogating S and G2/M arrest and subsequently promoting apoptosis. Furthermore, Gö6976 appeared to sensitize NPC xenografts in nude mice to IR or cisplatin treatment. This is the first report to show that the Chk1 inhibitor Gö6976 sensitizes NPC cells to treatment using in vitro and in vivo models. © 2010 Elsevier Ireland Ltd.
Sheng C.-F.,Taihe Hospital |
Liu B.-Y.,Taihe Hospital |
Zhang H.-M.,Taihe Hospital |
Zheng X.,Taihe Hospital
Genetics and Molecular Research | Year: 2015
This report aims to deepen the understanding of the pathogenesis, diagnosis, clinical characteristics, and treatment of overwhelming postsplenectomy infection (OPSI). A patient treated at Taihe Hospital for tuberculous OPSI is described, and relevant literature is reviewed. Broad-spectrum antibiotics, suppression of the systemic inflammatory reaction, and anti-shock measures were the keys to the successful treatment of this condition. OPSI is a life-threatening condition and has a high mortality rate. Early diagnosis, use of anti-inflammatory glucocorticoids, and administration of high-dose gamma globulin and ulinastatin for the treatment of OPSI may improve outcomes. ©FUNPEC-RP.
Yuan Y.H.,Taihe Hospital
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2010
To evaluate the early hematopoietic reconstitution of implanted SCID mice which were transplanted with human umbilical cord blood-derived mononuclear cells (UCB-MNC) and placenta-derived mesenchymal stem cells (PMSC) by intro-bone marrow injection (IBMI). The placenta tissues were digested by collagenase IV and cultured with low-glucose DMEM supplemented with b-FGF. The adherent cells were collected and passaged. The phenotypes of the cultured cells were detected by flow cytometry. The osteogenic differentiation and adipogenic differentiation were induced and detected. SCID recipient mice conditioned with sublethal dose irradiation were transplanted with human UCB-MNC and PMSC by IBMI or intravenous injection (IV). Fifty recipient mice were divided into five groups at random: cotransplantation group A (PMSC+UCB-MNC by IBMI), single transplantation group B (UCB-MNC by IBMI), cotransplantation group C (PMSC by IBMI, UCB-MNC by IV), normal saline control group D (normal saline by IBMI), normal control group E (normal saline by IBMI). There were ten recipient mice in every group. On day 14, the bone marrow cells of every recipient mouse were flushed out from the injected tibias and contralateral tibias, respectively. The percentage of human CD34+ and CD45+ hematopoietic cells was analyzed by flow cytometry. PMSC were isolated and expanded from human placenta, which were successfully induced to osteogenic differentiation and adipogenic differentiation. FACS analyses showed that the phenotypes of PMSC were normal. On day 14 after transplantation in SCID mice, the percentages of human CD34+ and CD45+ hematopoietic cells in the tibias of group B were both significantly lower than them in the injected tibias and contralateral tibias of group A. Human PMSC could enhance the early engraftment of UCB-MNC in SCID mice.
Zhang X.L.,Taihe Hospital
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology | Year: 2011
To investigate the mechanisms of Aldosterone stimulating hepatic stellate cells(HSCs) contraction via Ca2+-independent pathways. HSC-T6 cell line was pre-disposed with Aldo 10mumol/L. The cell contraction was detected by silicone-rubber-membrane cultivation directly. The concentration variation of intracellular free calcium in rat HSC was observed by laser confocal microscopy. Besides, HSC-T6 cell line was under pre-disposal treatment with the blocking agents of Aldo receptor -antisterone, protein kinase C (PKC) special blocking agent-Stauro, Rho kinase blocking agent-Y27632 and MLCK special blocking agent-ML-7 respectively prior to stimulation with aldosterone. RT-PCR was used to detect the expression of Rock2, RhoAGTP and RhoGEF in Ca2+- independent pathways mediated by Rho-kinase. Aldo could induce HSCs contraction. The concentration of intracellular free calcium in rat HSCs had no change after pre-disposal treatment with Aldo. The mRNA expressions of Rock2, RhoAGTP and RhoGEF increased significantly after treatment with Aldo (0.770+/-0.049, 0.960+/-0.096, 0.180+/-0.006, P is less than 0.01).When inhibited with antisterone, the mRNA expressions of the three elements were (0.440+/-0.166, 0.370+/-0.180 and 0.050+/-0.001, P is less than 0.01), lower than that of Aldo group, but higher in ML-7+Stauro + Aldo groups (0.940+/-0.066, 1.330+/-0.192 and 0.160+/-0.007, P is less than 0.05) as compared to the control group (0.140+/-0.023, 0.540+/-0.111 and 0.110+/-0.012). In the Y27632 + ML-7 + Stauro+Aldo group, the mRNA expression of RhoGEF (0.290+/-0.004, P is less than 0.01)was higher than that of the ML-7 + Stauro + Aldo group (0.160+/-0.007). Aldo could induce HSCs contraction via Ca2+-independent pathways and Rho-Rock pathway involved in the process.
Wang Q.,Taihe Hospital |
Zhao Z.-B.,Taihe Hospital |
Wang G.,Taihe Hospital |
Hui Z.,Taihe Hospital |
And 3 more authors.
PLoS ONE | Year: 2013
To date, a great number of studies have demonstrated that altered expression of kinesins is associated with development and progression of various human cancers. Kinesin family member 26B (KIF26B), a member of the kinesin superfamily proteins (KIFs), is essential for kidney development. However, the role of KIF26B during tumorigenesis and progression is limited. Here, we demonstrate that both KIF26B mRNA and protein are overexpression in breast cancer tissues by RT-qPCR and western blot. Immunohistochemistry revealed that KIF26B expression significantly correlated with clinicopathological factors, including tumor size (P = 0.011), grade (P = 0.017), lymph node status (P = 0.009) and ER status (P = 0.012). Moreover, the Kaplan-Meier analysis indicated that breast cancer patients with high KIF26B expression had a shorter survival than those with low KIF26B expression. In addition, multivariate analysis indicated that KIF26B is an independent prognostic for outcome in breast cancer (HR, 2.356; 95%CI, 1.268-4.378; P = 0.007). Collectively, our study demonstrated that KIF26B was overexpression in breast cancer and could be served as a potential prognostic marker. © 2013 Wang et al.
Jing F.,Huazhong University of Science and Technology |
Jing F.,Southern Medical University |
Yuping W.,Southern Medical University |
Yong C.,Taihe Hospital |
And 4 more authors.
Tumor Biology | Year: 2010
CpG island methylator phenotype (CIMP) involves methylation targeted toward the promoters of multiple genes. We determined a methylation profile of tumor-related genes in serum of sporadic breast cancer (SBC). The multigene methylation was examined by methylation-specific polymerase chain reaction assay in serum of 50 SBCs and 50 paired nontumors, and CIMP+ was defined as having three genes that are concordantly methylated. The methylation frequency of ten genes in serum of 50 SBCs varied from 10% in FHIT to 74% in RASSF1A. The methylation status of RASSF1A, BRCA1, p16, CDH1, ER, RARβ2, APC, and DAPK was significantly correlated with SBC and nontumor serum (P<0.05). Methylation of at least one gene was found in 92% SBC; CIMP was more frequent in SBC than nontumor serum (P<0.001). There was a significant association between CIMP and methylation of RASSF1A, BRCA1, p16, CDH1, ER, RARβ2, APC, and DAPK (P<0.05); the methylation link profile of CDH1, RASSF1A, BRCA1, and RARβ2 as breast cancer marker may contribute high sensitivity (90%) and specificity (88%). ER and RARβ2 methylation was associated with elevated serum CA153 levels in 39 SBC samples with CIMP+ (P<0.05). Multivariate analysis showed that living area of patients was found to provide independent prognostic information associated with a relative risk of tumor recurrence of 5.3. Multigenespecific methylation profile in serum was association with the recurrence risk of rural SBC, and positive correlation of CIMP can serve as a promising molecular marker of SBC. © International Society of Oncology and BioMarkers (ISOBM) 2010.