1.Research progress of IL-17+Foxp3+T cells
Hua ZHAO ; Hui LI ; Xiubao REN
Tianjin Medical Journal 2015;(11):1342-1344
Recently, it is reported that regulatory T cells (Tregs) can be reprogrammed into a novel population [interleu?kin (IL)-17+Foxp3+T cells] phenotypically and functionally resembling Th17 cells under complicated cytokine circumstanc?es. IL-17+Foxp3+T cells are characterized by production of IL-17 and expression of retinoic acid receptor related orphan re?ceptor (ROR)γt, demonstrating dual functions in immune response and providing novel insight into the interconnection be?tween Tregs and Th17 cells. In this review, we lay emphasis on the phenotype features, origination, differentiation and the pleiotropic functions of IL-17+Foxp3+T cells. Furthermore, we summarized the functions of IL-17+Foxp3+T cells in inflam?matory disease and tumor microenvironment.
2.Clinical significance of FoxP3 and the correlation of FoxP3 expression with epithelial-mesenchymal transition in breast cancer
Lili HUO ; Hui LI ; Feng WEI ; Hua ZHAO ; Xiubao REN
Chinese Journal of Clinical Oncology 2014;(3):158-161
Objective: This study aims to investigate the correlation between the expression of FoxP3, TGF-β1, and epitheli-al-mesenchymal transition (EMT) in breast cancer and to determine the clinical significance of FoxP3. Methods: The expression of FoxP3, TGF-β1, E-Cadherin, N-Cadherin, Vimentin, and Fibronectin protein were detected in the cancer cells of 74 cases with breast carcinoma via immunohistochemistry. The correlation of FoxP3 protein with clinico-pathologic features of breast carcinoma and the re-lationships among the expressions of FoxP3, TGF-β1, and epithelial-mesenchymal transition (EMT) were analyzed. Results:The ex-pression rates of FoxP3, TGF-β1, and EMT are 36.5%(27/74), 39.2%(29/74), and 40.5%(30/74), respectively. The FoxP3 protein ex-pression in breast cancer is correlated with lymph node metastasis (P<0.05) but not with other clinico-pathological features (P>0.05). The expression of FoxP3 is also correlated with the expression of TGF-β1. Furthermore, TGF-β1 can induce EMT (P<0.05). Conclu-sion:The expression of FoxP3 is correlated with lymph node metastasis and EMT in breast cancer. Therefore, FoxP3 may be a marker for predicting metastasis.
3.Effects of Genistein-magnetic-nanoparticles on the Expression of FAK in Human Hepatocellular Carcinoma Cell line HepG2
Gongping WANG ; Dongpeng LI ; Xiubao LIU ; Yuyuan ZHAO ; Xiaoshan FENG
Journal of Medical Research 2009;38(8):25-27,封3
Objective To study the effects of Genistein - magnetic - nanoparticles at different concentrations on the growth and ex-pression of focal adhesion kinase (FAK) in human hepatocellular carcinoma cell line HcpG2. Methods Activities of HepG2 cells treated by Genistein - magnetic - nanoparticles were examined by MTT assay. The expression of FAK mRNA and protein was respectively detected by immunohistochemistry staining and reversed transcriptase polymerase chain reaction (RT - PCR) . Results Genistein - magnetic -nanoparticles at a concentration of 10 -80mg/L inhibited the proliferation of HepG2 cells, with obvious concentration - dapendent and time - dependent effect relationships (P < 0.05). After treatment with various concentrations of Genistein - magnetic - nanoparticles for 48h, the relative level of FAKmRNA of Genistein - magnetic - nanoparticles and control groups was 1.242 ± 0.031,1.213 ± 0.443,0.834 ± 0.044,0.652 ± 0.039,0.446 ± 0.041, and 1.443 ± 0.053 (F = 21.97 ,P < 0.05), respectively. The expression of FAK protein in the cells was decreased, which showed an obvious a concentration - effect relationship. Conclusion Genistein - magnetic - nanoparticles can reduce the mRNA and protein expressions of FAK and inhibit the proliferation of HepG2 cells.
4.Timing of tracheostomy in ICU patients with mechanical ventilation support
Xiubao ZHAO ; Yongqiang WANG ; Huiyun ZHANG ; Fangchao YAO ; Bin WANG
Chinese Journal of Emergency Medicine 2017;26(2):194-196
Objective To assess the influence of timing of tracheostomy performed on ICU patientswith mechanical ventilation support for long-term.Methods A retrospective study was carried out in 94 patients under mechanical ventilation support with tracheostomy from January 2012 to October 2014.The patients were divided into early stage group (group A) in which the tracheostomy was done within 7 days after endotracheal intubation and late stage group (group B) in which the tracheostomy was performed at above 7 days after endotracheal intubation.The differences in lengths of mechanical ventilation support (MVS),ICU stay,and hospital stay,incidence of ventilator-associated pneumonia (VAP) and mortality were compared between two groups using nonparametric statistics.Results Compared with group B,there were statistically significant reduction in duration of mechanical ventilation (7d vs.17 d;P < 0.05),shorter length of ICU stay (10 d vs.19 d;P < 0.05),and lower incidence of VAP (21.05% vs.36.84%;P < 0.05) in group A.There were no significant differences in hospital stay and mortality between two groups (P >0.05).There was a correlation between the duration of mechanical ventilation and timing of tracheostomy (R2 =0.680) and a correlation between the length of ICU stay and the timing of tracheostomy (R2 =0.662) was found.Conclusions Early tracheostomy has a significant positive impact on critically ill patients hospitalized in this ICU.These results support the tendency to balance the risk-benefit analysis in favor of early tracheostomy.
5.Effects of Genistein-magnetic-nanoparticles on the Expression of FAK in Human Hepatocellular Carcinoma Cell line HepG_2
Gongping WANG ; Dongpeng LI ; Xiubao LIU ; Yuyuan ZHAO ; Xiaoshan FENG
Journal of Medical Research 2006;0(08):-
Objective To study the effects of Genistein-magnetic-nanoparticles at different concentrations on the growth and expression of focal adhesion kinase(FAK) in human hepatocellular carcinoma cell line HepG2.Methods Activities of HepG2 cells treated by Genistein-magnetic-nanoparticles were examined by MTT assay.The expression of FAK mRNA and protein was respectively detected by immunohistochemistry staining and reversed transcriptase polymerase chain reaction(RT-PCR).Results Genistein-magnetic-nanoparticles at a concentration of 10-80mg/L inhibited the proliferation of HepG2 cells,with obvious concentration-dapendent and time-dependent effect relationships(P
6.Proliferation of rats' osteoblasts promoted by mechanical strain via the protein kinases Cξ protein path-way
Zhijun LI ; Xinlong MA ; Xin FU ; Jianxiong MA ; Huafeng ZHANG ; Xiaolei SUN ; Hongyan LI ; Xiubao ZHAO
Chinese Journal of Orthopaedics 2012;32(5):494-499
ObjectiveTo investigate the proliferation of rat's osteoblasts promoted by mechanical strain via the protein kinases C ξ(PKCξ) protein path-way.MethodsOsteoblasts were retrieved from SD rats' skulls in the sterilized environment.BioDynamic testing instrument was used to exert 2% and 0% mechanical strain on rats' osteoblasts for 180 min on the each group(2% mechanical strain was experimental group and 0% mechanical strain was control group); and the same method was applied on the rats' osteoblasts which pretreated with the classical PKC ξ inhibitor with 2% mechanical strain (inhibitor group).The cell cycles of rats' osteoblasts were measured by flow cytometry; and Western blotting and immunofluorescence were used to detect expression of protein PKC ξ and phosphorylationed PKC ξ in the rats' osteoblasts.ResultsThe mechanical strain obviously increased the ratio of S period in the cell cycles.Compared to the control group and inhibitor group,a significant increase of the expression of protein PKC ξ and phosphorylationed PKC ξ in the osteoblasts was detected in the mechanical strain experimental group.ConclusionPKCξ can respond to the stimulus of the mechanical strain,which promotes the proliferation of osteoblasts through PKCξ pathway.And it plays an important role in the process of signal conduction.
7.Radiochemotherapy combined with adoptive immunotherapy with cytokine-induced killer cells for locally advanced non-small cell lung cancer:a preliminary study
Shuai WANG ; Xiubao REN ; Feng WEI ; Yang CHEN ; Jing LUO ; Lujun ZHAO
Chinese Journal of Radiation Oncology 2016;25(4):345-350
Objective To investigate and compare the clinical effects of radiochemotherapy alone or in combination with adoptive immunotherapy with cytokine-induced killer ( CIK) cells in patients with locally advanced non-small cell lung cancer (NSCLC).Methods The clinical data of 125 patients with locally advanced NSCLC who were admitted from 2011 to 2012 and did not undergo surgery were analyzed retrospectively, and among these patients, 102 received radiochemotherapy alone ( control group) , and 23 received radiochemotherapy combined with adoptive immunotherapy with CIK cells ( multimodality therapy group) .The two groups were matched at a ratio of 1:2 using propensity score matching, and the factors considered included tumor stage, radiochemotherapy regimen, and outcome after radiochemotherapy.Then 59 patients ( 22 from the multimodality therapy group and 37 from the control group) were enrolled, and survival and tumor control were compared between the two groups.The Kaplan-Meier method was used to calculate survival rates and the log-rank test was used for survival difference analysis and univariate prognostic analysis.Results The 1-, 2-, and 3-year overall survival ( OS) rates were 73%, 32%, and 16%, respectively, in the control group, and 91%, 59%, and 41%, respectively, in the multimodality therapy group ( P=0.030) .The 1-, 2-, and 3-year progression-free survival rates were 61%, 21%, and 17%, respectively, in the control group, and 45%, 10%, and 10%, respectively, in the multimodality therapy group ( P=0.538) .As for the patients with stage ⅢB NSCLC, those in the multimodality therapy group had a significantly higher 3-year OS rate than those in the control group (47%vs.11%, P=0.026). In the patients receiving sequential chemoradiotherapy, those in the multimodality therapy group had a significantly higher 3-year OS rate than those in the control group ( 46%vs.11%, P=0.003) .As for the
patients with squamous cell carcinoma, those in the multimodality therapy group had a significantly higher 3-year distant metastasis-free survival rate than those in the control group ( 73%vs.22%, P=0.029) .The two groups showed similar incidence rates of adverse events, and compared with the control group, the multimodality therapy group had a lower incidence rate of radiation pneumonitis (9%vs.15%, P=0.889) and a higher incidence rate of radiation esophagitis (12%vs.7%, P=0.097).Conclusions Some patients with locally advanced NSCLC can benefit from radiochemotherapy combined with adoptive immunotherapy with CIK cells, but the intended population, timing, and dose safety still need further investigation.
8.The Expression of TSLP and Its Relationship with the Number of Infiltrating Regulatory T Cells in Lung Cancer
Hua ZHAO ; Hui LI ; Jinpu YU ; Yanjun SU ; Lili YANG ; Feng WEI ; Xiumei AN ; Fang XU ; Dongsheng YUE ; Xiaoliang ZHAO ; Xiubao REN
Chinese Journal of Clinical Oncology 2010;37(3):126-130
Objective: To investigate the expression of TSLP in human lung cancer tissue and the correla-tion between TSLP expression and number of regulatory T cells (Tregs). Methods: The expression of TSLP mRNA and protein was detected in different pathological lesions of the lung by Q-RT-PCR and immunohisto-chemistry. Immunohistochemistry was used to detect Foxp3+ Tregs. The correlation of TSLP with the number of Tregs was analyzed. Results: TSLP gene was expressed in tumor tissues (n=37), latero-tumor tissues (n=29) and non-tumor lung tissues (n=24), without statistical difference (P=0.148). TSLP protein was expressed in the cytoplasm and was observeed in 69.57% of tumor tissues, 13.33% of benign lesions and 30.00% of non-tumor lung tissues, with a significant difference (P<0.05). The expression of TSLP protein was correlated with tumor size (P=0.000) and lymph node metastasis (P=0.018). The number of Tregs in TSLP positive group was more than that in TSLP negative group (P<0.05). Conclusion: The expression of TSLP in lung tu-mor tissues is increased and is correlated with the number of Tregs, indicating that TSLP could induce Treg to play an important role in tumor immunotolerance.
9.Research progress on tumor immune microenvironment evaluation in efficacy predic-tion
Hua ZHAO ; Feng WEI ; Xiubao REN
Chinese Journal of Clinical Oncology 2018;45(12):599-603
With the clinical applications of new immunotherapies, traditional TNM staging has been unable to meet the clinical needs of curative effect predictions. It is known that the immunological features of the tumor immune microenvironment play important roles in tumor prognosis evaluations. Recently, the immunoscore system, which is based on local immune cell distribution and density, has gradually become an important indicator for prognosis evaluations and has been verified in several tumor researches. Recently, with the application of new mass flow detection and single cell sequencing technologies, the number of immune landscape studies have also been increasing, and new tumor-specific immune cell subsets have been identified. These subtypes not only provide individ-ualized immunotherapy guidelines for patients, but also provide potential new targets for the further development of new immuno-therapy strategies. This review will introduce recent research progress in this field.
10.Analysis of the Role of PET/CT SUVmax in Prognosis and Its Correlation with Clinicopathological Characteristics in Resectable Lung Squamous Cell Carcinoma
REN HONGLIANG ; XU WENGUI ; YOU JIAN ; SONG XIUYU ; HUANG HUI ; ZHAO NING ; REN XIUBAO ; ZHANG XINWEI
Chinese Journal of Lung Cancer 2016;19(4):192-199
Background and objective Lung cancer is the leading cause of cancer death in men and women in the world, more than one-half of cases are diagnosed at a advanced stage, and the overall 5-year survival rate for lung cancer is 18%. Lung cancer is divided into non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC). Approximately 80%-85%of cases are NSCLC which includes three main types:adenocarcinoma (40%), squamous cell carcinoma (SCC) (20%-30%), and large cell carcinoma (10%). Although therapies that target driver mutations in adenocarcinomas are showing some promise, they are proving ineffective in smoking-related SCC. We need pay more attention to the diagnosis and treatment of SCC. 18F-FDG positron emission tomography (PET)/computed tomography (CT) has emerged as an accurate staging mo-dality in lung cancer diagnosis. hTe aim of this study is to investigate the role of maximum standardized uptake value (SUVmax) on PET-CT in prognosis and its correlation with clinicopathological characteristics in resectable SCC. Methods One hun-dred and eighty-two resectable SCC patients who underwent PET/CT imaging between May 2005 and October 2014 were enrolled into this retrospectively study. All the enrolled patients had underwent pulmonary resection with mediastinal lymph node dissection without preoperative chemotherapy or radiotherapy. Survival outcomes were analyzed using the Kaplan-Meier method and multivariate Cox proportional hazards model. Correlation between SUVmax and clinicopathological factors was analysed using Pearson correlation analysis and Spearman rank correlation analysis. Results hTe patients were divided into two groups on the basis of SUVmax 13.0 as cutoff value, and patients with SUVmax more than 13.0 had shorter median overall survival than patients less than 13.0 in univariate analysis (56 months vs 87 months;P=0.022). hTere was remarkable correla-tion between SUVmax and gender, tumor size, tumor-node-metastasis (TNM) stage, neutrophil, NLR, hemoglobin (P<0.05). Multivariate Cox analysis demonstrated that SUVmax (HR=1.714, 95%CI:1.021-2.876, P=0.042), TNM stage (HR=1.677, 95%CI:1.231-2.284, P=0.001) were independent predictors for survival. Furthermore, univariate survival analysis showed signiifcant difference by SUVmax in patients of stage I (P=0.045). Conclusion SUVmax may be of importance prognostic factor independent of TNM stage, which was considerable for risk stratiifcation in patients with TNM stage. Besides, there was correlation between SUVmax of primary tumor and clinicopathological characteristics.