1.Development of Ebp1 in tumor proliferation and invasion
Yuan LIU ; Fei ZHANG ; Ruifang NIU
Chinese Journal of Clinical Oncology 2014;(23):1536-1539
This work summarizes the research development and molecular mechanism of Ebp1, a member of the proliferation-associated 2G4 family, in tumor proliferation and invasion. This research serves as a basis and support for further research on the mechanism of tumor proliferation and invasion. The low expression of Ebp1 in various cancers promotes tumor proliferation and invasion. Ebp1 inhibits E2F1, cyclin D1, and cyclin E transcription by interacting with Rb, human histone deacetylase 2, and the transcriptional repressor Sin3A. This inhibition triggers cell cycle arrest and suppresses cell proliferation. Ebp1 also influences cancer invasion and migration. However, the underlying mechanisms remain unknown and require further exploration.
2.Research progress in multiple regulation pathways of STAT3 in cancer
Yi YANG ; Jie YUAN ; Ruifang NIU
Chinese Journal of Clinical Oncology 2016;43(8):352-357
The activation of the proto-oncogene STAT3 is strongly controlled under physiological conditions. However, obtained evi-dence revealed that STAT3 is persistently activated in cancer cells and contributes to cancer initiation and progression. Studies demon-strated the various functions of activated STAT3 in promoting cancer development and aggravation, including cancer cell proliferation, invasion and metastasis, drug resistance, epithelial-mesenchymal transition, regulation of the tumor microenvironment, and promo-tion of the self-renewal and differentiation of cancer stem cells. Canonically, STAT3 is regulated by signaling pathways mediated by cy-tokines and growth factors. Many studies determined that STAT3 was also regulated by G protein-coupled receptors, cadherin engage-ment, Toll-like receptors, microRNA, and acetylation. We summarized the recent developments in the research on the regulation of STAT3 activation.
3.Effect of T-lymphocyte subpopulations in peripheral blood on disease-free survival of patients with different molecular subtypes of breast cancer
Wei JI ; Yan ZHOU ; Ruifang NIU
Chinese Journal of Clinical Oncology 2014;(21):1363-1367
Objective:To determine the distribution of T-lymphocyte subpopulations in peripheral blood and its relationship with disease-free survival (DFS) of patients with different molecular subtypes of invasive breast cancer (IBC). Methods:Data and plasma samples of 372 female patients with IBC treated at Tianjin Medical University Cancer Hospital and Institute between January 2008 and August 2009 were obtained. CD4+/CD8+ratio and the amount of regulatory T cells (Treg cells) and natural killer cells (NK cells) were measured through flow cytometry. Results:A total of 133 (35.8%), 124 (33.3%), 48 (12.9%), and 67 cases (18.0%) presented luminal type A, luminal type B, HER-2 over-expression, and triple-negative type breast cancer (TNBC), respectively. In TNBC, a longer DFS was observed when the peripheral CD4+/CD8+ratio was high or when the level of Treg cells was low (CD4+/CD8+P<0.05 and Treg P<0.05). However, CD4+/CD8+and Treg are not independent prognostic factors for the DFS of TNBC cases. In other molecular subtypes of breast cancer, CD4+/CD8+ratio and the amount of Treg cells are not correlated with DFS (P>0.05). The level of NK cells is unrelated to the DFS of breast cancer with the four molecular subtypes (P>0.05). Conclusion:CD4+/CD8+ratio and the amount of Treg cells in peripheral blood may predict DFS of TNBC but are not considered as independent prognostic factors.
4.Bio-Distribution of IL-2 and Its Relation to the Therapeutic Effects
Jinghua HE ; Yan PANG ; Ruifang NIU
Chinese Journal of Cancer Biotherapy 1996;0(04):-
In this article, the plasma half life of IL-2 and its bio-distribution were studied using radio-nucleus Technetium-99M labeled IL-2. The results showed the plasma half life of IL-2 was merely 10 minutes mainly due to IL-2 distribute to its target organ such as liver, kidney etc,rather than clear out of the body. Our results indicated that IL-2 is a high organ-specific drug. It's plasma half life is short under high concentration in its target organ. So it might have advantages of high effectiveness and low whole body toxicity in treatment of tumor of liver and kidney.
5.The research about bcl-2/bax/fas/fasL mRNA of splenic lymphocytes in HIBD rat model
Rui YAN ; Guilan CHU ; Rongxiu ZHENG ; Ruifang NIU ; Fei ZHANG
Chinese Journal of Microbiology and Immunology 2010;30(10):937-941
Objective To obtain the change of bcl-2/bax/fas/fasL in splenic lymphoctyes with different lasting time of hypoxicischemic brain damage (HIBD). Methods The newborn rat were divided into 6 groups by the time of being HIBD model randomly, includes 1/6/12/24/48/72 hour(s) (8 for every group),and control groups were established at the same time point. The following four apoptosis related genes bcl-2/bax/fas/fasL were tested by real time PCR. Results ( 1 ) bcl-2: the mRNA expressions of HIBD groups were lower than control groups at the same time ( P<0.01 ). Eliminated the control effects, the mRNA expressions of HIBD groups were differernt by the modeling time(P <0.01 ). (2)bax: the mRNA expressions of HIBD groups were higher than control groups at the same time( P <0.01 ), and in control group the expression of 6 h was much higher than any other groups (P<0.01 ). Eliminated the control effects, the mRNA expressions of H IBD groups were different by the modeling time( P<0.01 ). (3)bcl-2/bax: the ratios of HIBD groups were lower than control groups at the same time( P <0.05 ), the ratios in control groups were higher than 1 ( except for 1 h); while in HIBI) groups the ratios were lower than 1; Eliminated the control effects, the ratios were different in all the groups. (4)fas: the mRNA expressions of HIBD groups were higher than control groups at the same time ( P <0.01 ), and both were maximum at 6 h. (5)fasL: the mRNA expressions of HIBD groups were higher than control groups in 1 h and 6 h ( P<0.01 ), while lower than control group at other time points( P<0.01 ),the expression of 24 h was the maximum of control groups and 12 h was the maximum of HIBD groups. (6)fas/fasL: the ratios of HIBD groups were higher than control groups( P <0.01 ) (except for 6 h), and the ratios in control groups were lower than 1 ( P<0.01 ) ( except for 6 h), and not concentrated, while in HIBD groups were higher than 1 ( except for 24 h), between 0.69 to 5.65. Conclusion Pro-apoptosis genes ( include bax/fas/fasL) were promoted by HIBD, while anti-apoptosis gene(bcl-2) was inhibited. The maximum of pro-apoptosis genes became early in HIBD. Both the pro- and anti-apoptosis genes got their maximum at 6 h and 12 h of HIBD. The apoptosis suppression was the main effects in control groups from the ratio of bcl-2/bax, which was lower than 1. The apoptosis promotion was the main effects in HIBD groups from the ratio of bcl-2/bax, which was higher than 1, especially at 12 h. Thefas/fasL effect which is the major way of lymphocytes apoptosis was strengthened in HIBD.
6.The Effects of Recombinant Adenovirus-Mediated Wild Type p53 cDNA on Human Colorectal Cancer Cell Lines with Different p53 Status
Zhao YAN ; Wen LI ; Ruifang NIU ; Yurong SHI ; Xishan HAO ;
Chinese Journal of Cancer Biotherapy 1994;0(01):-
Objective: To explore the inhibition effects of ectogenic wild type p53 cDNA(Ad wtp53) on colorectal carcinoma cell lines with different p53 gene status and search for the role of wild type p53 tumor suppressor gene in occurrenc and progress of malignant tumor. Methods: MTT process was taken to choose optimal transfection titre. Three kinds of cell lines(p53 gene deletion, mutation and nomal) were transferred by Ad wtp53 in optimal titre. The inhibition effects of these cell lines were observed and compared. Results: The best titre is 1000 MOI and p53 gene deletion cell line (THC 8908) shew the highest sensitivity. G 1 S transition period blocking effects occurred in all cell lines and G 2 M phase regulation effects were not coincidence in three colorectal cell lines. Conclusions: Recombinant adenovirus mediated wild type p53 gene observably inhibited colorectal carcinoma cell lines growth and proliferation, blocked cell cycle in G 0 /G 1 phase and displayed obvious different actions on G 2 M phase among cell lines with different p53 status.
7.Reversal of Multidrug Resistance by IFN-? in KBv200 Cell Lines
Yan LIANG ; Xiyin WEI ; Kai LI ; Yi YANG ; Ruifang NIU
Chinese Journal of Cancer Biotherapy 1995;0(03):-
Objective: To explore the effects of various concentrations IFN-? on human oral epidermic cancer cell line KB and its multidrug resistant counterpart KBv200.Methods: The toxicity of IFN-? and/or VCR was assayed by MTT method; intracellular rhodamin123 concentration and p-glycoprotein expression were measured by flow cytometry; mdr-1 mRNA was assayed by RT-PCR. Results: High-dose IFN-?(10 000 IU/ml) had significant antiproliferative effects on KB/KBv200 cell lines. Low-dose IFN-? did not have any significant effect on growth of KB/KBv200 cells, but did increase the cytotoxic effect of VCR and the accumulation of Rhodamine123 in KBv200 cell line and had no effect on parent VCR-sensitive KB cell line. IFN-? down-regulated expression of P-gp and mdr-1mRNA . Conclusions: IFN-? has significant effect on the reversal of multidrug resistance of KBv200 cell line via a mechanism of P-gp and mdr1 mRNA down-regulation.
8.Experimental studies on apoptosis imaging of 153Sm-Annexin V
Jiang LIU ; Yingru ZHAO ; Jian WANG ; Leina SUN ; Ruifang NIU ; Wengui XU
Chinese Journal of Clinical Oncology 2013;(12):690-693
10.3969/j.issn.1000-8179.2013.12.002
9.The regulatory effects of HTLV-1 Tax protein on HMGB1 gene in T cells
Chenguang ZHANG ; Zhiguo NIU ; Hui WANG ; Mingmei YIN ; Yue LI ; Linlin ZHU ; Qingwei ZHAO ; Xiaohua DING ; Ruifang HUA ; Yalu PU ; Lihua HU
Chinese Journal of Microbiology and Immunology 2013;(7):501-506
Objective To explore the regulatory effects of HTLV-1 ( human T-cell leukemia virus type 1 ) Tax protein on the expression of HMGB 1 ( high mobility group box 1 ) gene in T cells .Methods Total RNA and protein were extracted from Tax +-T cells ( TaxP ) , Tax--T cells ( TaxN ) and Jurkat cells which were stably transfected with pCMV-Tax and pCMV-Neo, respectively.Then, the expression levels of HMGB1 mRNA and protein in different CD 4+T cells were analyzed by real-time PCR and Western blot (WB).By using liposome-mediated method, pGL3-HMGB1-luc reporter genes and pGL3-neo-luc were tran-siently transfected into TaxP and TaxN cells and the basal transcriptional activity was observed in different T cells.Additionally, pCMV-Tax and pGL3-HMGB1-luc reporter genes were also co-transfected into Jurkat cells and the regulatory effects of Tax protein on HMGB 1 gene was detected .The chromatin immunoprecipi-tation (ChIP) assay was used to identify HMGB1 genomic sites directly targeted by Tax .Results The ex-pression levels of HMGB1 mRNA and protein in Tax+-T cells ( TaxP) were higher than those in Tax--T cells (TaxN).The transcription regulation trends for HMGB1 gene in TaxN and TaxP cells were similar but not identical in diverse T cells.pHLuc3 (containing -504-+83 HMGB1) showed the highest transcriptional ac-tivity of HMGB1 gene in both TaxP and TaxN cells , but HMGB1 transcriptional activity of pHLuc 6 in TaxP cells was significantly stronger than that in TaxN cells .Luciferase assays also showed that Tax protein promo-ted the transcription of HMGB1 gene in a dose-dependent manner .The ChIP assay further confirmed that Tax protein enriched at the HMGB1 region of -1163--1043.Conclusion The region of nt -504--383 is essen-tial for the basal promoter activity of -1163-+83 HMGB1 gene originated from pHLuc 6 reporter plasmid , and Tax protein enriched probably at the HMGB 1 site of -1163--1043 enhances HMGB1 transcription.
10.Effect and its mechanism of Linagliptin on mild cognitive impairment in elderly type 2 diabetes mellitus patients
Ziying HU ; Huifeng ZHANG ; Yanfang WANG ; Ruizhi ZHENG ; Ruifang NIU ; Wei XIA
Chinese Journal of Geriatrics 2018;37(10):1069-1072
Objective To investigate the effect and its underlying mechanism of Linagliptin on mild cognitive impairment (MCI) in elderly type 2 diabetes mellitus (T2DM) patients.Methods Montreal Cognitive Assessment(MoCA)scale was used to prospectively screen T2DM patients for MCI in our hospital from December 2016 to June 2017,and a total of 98 elderly T2DM patients with MCI were recruited.They were randomly divided into the linagliptin group(Linagliptin + metformin,n=50)and the non-linagliptin group(gliclazide + metformin,n =48).Serum fasting plasma glucose (FPG),glycosylated hemoglobin(HbAlc),blood lipids and amyloid β-protein 1-42 (Aβ1-42) levels were determined,and MoCA score and homeostasis model assessment of insulin resistance(HOMA-IR)were calculated,and were compared between the two groups before and after 24 weeks of treatment.Results In the linagliptin group,serum FPG,HbA1c,HOMA-IR,Aβ1-42 levels were significantly decreased and MoCA score was increased after 24 weeks of treatment as compared with pre-treatment [(7.29± 1.00) mmol/L vs.(9.16 ± 1.60) mmol/L,(7.19 ± 0.99) % vs.(9.36 ± 1.07) %,(3.05 ± 1.12) vs.(4.05±1.30),(0.463±0.093)g/L vs.(0.528±0.110)g/L,(24.48± 1.18) vs.(23.22± 1.37),all P<0.05].In the non-linagliptin group as control,FPG and HbA1c levels were decreased after 24 weeks of treatment as compared with pre-treatment[(7.23±1.09)mmol/L vs.(9.20± 1.75) mmol/L,(7.23±1.03)% vs.(9.69± 1.18)%,both P < 0.05],while there was no significant difference in HOMA IR,Aβ1-42 level and MoCA score[(3.95 ± 1.00) vs.(4.19± 1.13),(0.517± 0.113)g/L vs.(0.526±0.119)g/L,(23.21±1.18) vs.(23.00±1.32),all P>0.05].It is worth to pay close attention to the key discovery of this paper that HOMA-IR and Aβ1-42 levels were significantly lower and MoCA score was significantly higher in the linagliptin group than in the non-linagliptin group after 24 weeks of treatment(all P<0.05).Conclusions Linagliptin as one of DPP-4 enzyme inhibitors can improve the cognitive function in elderly patients with T2DM,which might be relevant to reducing serum Aβ level and improving HOMA-IR.DPP-4 enzyme inhibitor may be a good option for treatment of mild cognitive dysfunction in T2DM patients in the future.