1.Inhibition of c-Myc by 10058-F4 overcomes imatinib resistance in chronic myeloid leukemia cells
Zijie LONG ; Zhigang FANG ; Xiaona PAN ; Ruifang FAN ; Dongjun LIN
Chinese Journal of Pathophysiology 2014;(9):1590-1594
AIM: To investigate the effect of c-Myc inhibitor 10058-F4 on human chronic myeloid leukemia ( CML) K562 cells and imatinib-resistant K562/G cells.METHODS: The protein expression of c-Myc was detected by Western blotting .Cell proliferation was evaluated by MTT assay and colony formation assay .PI staining was used to deter-mine the cell cycle distribution .Annexin V-PI staining was applied for apoptosis detection .RESULTS:Imatinib-resistant K562/G cells displayed lower sensitivity to imatinib than K 562 cells with high expression of c-Myc.Treatment with specific c-Myc inhibitor 10058-F4 inhibited the cell proliferation in a dose-and time-dependent manner , and K562/G displayed more sensitivity to 10058-F4 than K562 cells.10058-F4 also induced cell cycle arrest in G 0/G1 phase and induced apoptot-ic cell death in the 2 cells.Importantly, 10058-F4 suppressed the colony formation ability in K 562 and K562/G cells. CONCLUSION:c-Myc is a novel target to overcome imatinib-induced drug resistance , and c-Myc inhibitor provides a new approach in CML therapy .
2.Effect of G-CSF on the apoptosis induced by Ara-c in HL-60 leukemic cells
Dongjun LIN ; Renwei HUANG ; Jun FAN ; Dongning WANG ; Yongmei FU
Chinese Journal of Pathophysiology 2000;0(11):-
AIM: To investigate the effect of granulocyte colony stimulating factor (G-CSF) on arabinosyl cytosine (Ara-C)-induced apoptosis in HL-60 leukemia cells. METHODS: The proliferation of HL-60 leukemia cell was observed by hemopoietic cell culture. Apoptosis was measured by the morphology of apoptosis cell , the quantitation of DNA fragmentation with the diphenylamine reaction. The change in drug sensitivity was measured by “MTT”. RESULTS: G-CSF could stimulate the proliferation of HL-60 leukemia cell and colonies of cell increased to 76.5?18.0, compared to the control group (46.5?13.5. P
3.Telmisartan inhibits proliferation and induces apoptosis in U937 cells
Yamei LEI ; Ruifang FAN ; Yichuan XU ; Wenxing LAI ; Dongjun LIN
Chinese Journal of Pathophysiology 2017;33(4):669-675
AIM: To demonstrate the effects of telmisartan on the proliferation and apoptosis of U937 cells.METHODS: The proliferation ability of the U937 cells was assessed by CCK-8 assay and colony formation test with methylcellulose.The CD11b expression rate of the U937 cells was identified by flow cytometry.The apoptotic rate was analyzed by flow cytometry with Annexin V-PI double staining and Hoechst 33342 staining.The protein levels of cleaved PARP and cleaved caspase-3 were determined by Western blot.RESULTS: The results of CCK-8 assay confirmed that the viability of U937 cells was inhibited by telmisartan.The colony formation capacity of U937 cells was also significantly inhibited by telmisartan.The differentiation of U937 cells was induced by telmisartan with the expression of CD11b.The results of flow cytometry analysis with Annexin V-PI double staining and Hoechst 33342 staining identified that the apoptosis of U937 cells was induced by telmisartan in dose-dependent and time-dependent manners with the up-regulation of cleaved PARP and cleaved caspase-3 proteins.CONCLUSION: Telmisartan inhibits the proliferation and induces the differentiation of U937 cells.Telmisartan also induces the apoptosis of U937 cells through the caspase pathway.
4.Zoledronic acid inhibits proliferation and induces apoptosis in U937 cells
Ruifang FAN ; Lingling LIU ; Ling ZHANG ; Xiaoyan GUO ; Xiaozhen WANG ; Dongjun LIN
Chinese Journal of Pathophysiology 2016;32(7):1221-1226
[ ABSTRACT] AIM:To study the antiproliferation and proapoptotic effects of zoledronic acid ( ZOL) on human a-cute myeloid leukemia cell line U937.METHODS:The viability of U937 cells was detected by CCK-8 assay.The cell cy-cle of the U937 cells was analyzed by flow cytometry with PI staining.Apoptotic rate was assessed by flow cytometry with Annexin V-PI and Hoechst 33342 staining.Mitochondrial membrane potential was detected by JC-1 assay.Methylcellulose was used to assess colony formation.The protein levels of p21, Bcl-2 and Bax were determined by Western blot.RE-SULTS:ZOL inhibited the viability of U937 cells.ZOL induced S-phase cell cycle arrest in the U937 cells.The results of flow cytometry analysis with Annexin V-PI and Hoechst 33342 staining showed that ZOL also induced apoptosis in a dose-and time-dependent manner.Mitochondrial membrane potential assay was also used to verify the apoptosis.The apoptotic rate was consistent with the reduction of mitochondrial membrane potential.Colony formation assay showed that ZOL signifi-cantly inhibited the colony formation capacity of the U937 cells.This was achieved by the induction of S-phase cell cycle arrest, and up-regulation of Bax and p21, and down-regulation of Bcl-2.CONCLUSION:ZOL inhibits cell proliferation by regulating the expression of cell cycle-related protein, and induces apoptosis via the mitochondrial apoptotic pathway.
5.Changes in the expression of Bcl-2 and Fas in HL-60 cells treated with cyclosporine A
Dongjun LIN ; Renwei HUANG ; Jun FAN ; Dongning WANG ; Guizhen LIN ; Xudong LI
Chinese Journal of Pathophysiology 2000;0(11):-
AIM: To investigate the changes of the expression of Bcl-2 and Fas protein and the apoptosis in HL-60 cells induced by cyclosporine A. METHODS: The expression of Bcl-2 and Fas protein and apoptosis in (HL-60) cells were measured by immunohistochemistry analysis and flow cytometric analysis. RESULTS: There was strong expression of Bcl-2 in HL-60 cells, treatment with cyclosporine A (CsA) for 8-10 h down-regulated the expression of Bcl-2. Fas protein expression in HL-60 cells was very low, CsA induced apoptosis of HL-60 cells, but didn't induce Fas protein expression. CONCLUSION: CsA induces apoptosis in HL-60 cells by down-regulating Bcl-2 expression. [
6.Protein expression of TIMP3 and RUNX3 in bone marrow mononuclear cells from acute leukemia patients
Ruifang FAN ; Zhigang FANG ; Xiangfu LIU ; Yongjiang ZHENG ; Binbin LIU ; Dongjun LIN
Chinese Journal of Pathophysiology 2010;26(2):293-296
AIM: To detect the protein expression of TIMP3 and RUNX3 in bone marrow mononuclear cells (BMMCs) from acute leukemia (AL) patients and to investigate the relationship between the methylation status of genes and their expressional levels. METHODS: Protein expression of TIMP3 and RUNX3 in 50 samples of BMMCs and 10 samples of peripheral blood mononuclear cells (PBMCs) from healthy volunteers was detected by Western blotting. The prognostic factors related to AL and data from methylation specific polymerase chain reaction were also analyzed. RESULTS: The expression level of RUNX3 with methylation was less than that without methylation in BMMCs from AL patients. The complete remission (CR) rate was related to RUNX3 expression and blasts in bone marrow (BM). BMMCs from patients with silencing of RUNX3 and higher blasts in BM had a lower CR rate. CONCLUSION: Absence of RUNX3 protein expression resulting from methylation of RUNX3 promoter probably plays a role in the pathogenesis of AL and is of value in prognosis. No relationship between methylation of TIMP3 promoter and the pathogenesis of AL is observed.
7.A multi-center and retrospective analysis of missed diagnosis of colorectal polyps
Jinfeng WU ; Xiqiu YU ; Keyun CHEN ; Dongjun FAN ; Jianwei WU ; Yuqing GUO ; Xuming HUANG ; Guangchao YANG ; Jintao LIU
Chinese Journal of Digestive Endoscopy 2017;34(5):318-321
Objective To study the missed diagnosis of colorectal polyps during colonoscopy and its risk factors.Methods Data of 655 patients who underwent repeated co]onoscopy in 3 months (90 days) were analyzed in three endoscopy centers in Shenzhen.Miss rates of polyps and patients were calculated.Logistic regression analysis was used to identify the suspected risk factors associated with the miss rate including gender,age,symptoms of patient and number,shape,location of polyps.Results A total of 459 polyps(20.47%,459/2 242) in 224 patients(34.20%,204/655) were missed in overall 1 783 polyps within 655 patients.The patient miss rate increased with the polyp count increasing from 1 to 4,but with no significant differences.Polyp count of more than 5 was the independent risk factor for patient miss rate during colonoscopy(OR=4.98,P=0.00).Polyps in males were easier to be missed than those in females (OR =1.76,P =0.00).Size less than 5 mm was the independent risk factor for missed diagnosis during colonoscopy(OR=2.94,P=0.00).The flat type(Yamada Ⅰ,Ⅱ) was also the independent risk factor(OR=2.72,P=0.01;OR=3.23,P=0.00 respectively).Conclusion The miss rate of polyps is related to gender,basic polyp count,the size and shape of polyp.Male with multiple polyps and polyps with flat type and small size tend to be missed.
8.Haploidentical transplantation has a superior graft-versus-leukemia effect than HLA-matched sibling transplantation for Ph- high-risk B-cell acute lymphoblastic leukemia
Menglin FAN ; Yu WANG ; Ren LIN ; Tong LIN ; Fen HUANG ; Zhiping FAN ; Yajing XU ; Ting YANG ; Na XU ; Pengcheng SHI ; Danian NIE ; Dongjun LIN ; Zujun JIANG ; Shunqing WANG ; Jing SUN ; Xiaojun HUANG ; Qifa LIU ; Li XUAN
Chinese Medical Journal 2022;135(8):930-939
Background::Compared with human leukocyte antigen (HLA)-matched sibling donor (MSD) transplantation, it remains unclear whether haploidentical donor (HID) transplantation has a superior graft-versus-leukemia (GVL) effect for Philadelphia-negative (Ph-) high-risk B-cell acute lymphoblastic leukemia (B-ALL). This study aimed to compare the GVL effect between HID and MSD transplantation for Ph- high-risk B-ALL.Methods::This study population came from two prospective multicenter trials (NCT01883180, NCT02673008). Immunosuppressant withdrawal and prophylactic or pre-emptive donor lymphocyte infusion (DLI) were administered in patients without active graft-versus-host disease (GVHD) to prevent relapse. All patients with measurable residual disease (MRD) positivity posttransplantation (post-MRD+) or non-remission (NR) pre-transplantation received prophylactic/pre-emptive interventions. The primary endpoint was the incidence of post-MRD+.Results::A total of 335 patients with Ph- high-risk B-ALL were enrolled, including 145 and 190, respectively, in the HID and MSD groups. The 3-year cumulative incidence of post-MRD+ was 27.2% (95% confidence interval [CI]: 20.2%-34.7%) and 42.6% (35.5%-49.6%) in the HID and MSD groups (P = 0.003), respectively. A total of 156 patients received DLI, including 60 (41.4%) and 96 (50.5%), respectively, in the HID and MSD groups ( P= 0.096). The 3-year cumulative incidence of relapse was 18.6% (95% CI: 12.7%-25.4%) and 25.9% (19.9%-32.3%; P = 0.116) in the two groups, respectively. The 3-year overall survival (OS) was 67.4% (95% CI: 59.1%-74.4%) and 61.6% (54.2%-68.1%; P = 0.382), leukemia-free survival (LFS) was 63.4% (95% CI: 55.0%-70.7%) and 58.2% (50.8%-64.9%; P= 0.429), and GVHD-free/relapse-free survival (GRFS) was 51.7% (95% CI: 43.3%-59.5%) and 37.8% (30.9%-44.6%; P= 0.041), respectively, in the HID and MSD groups. Conclusion::HID transplantation has a lower incidence of post-MRD+ than MSD transplantation, suggesting that HID transplantation might have a superior GVL effect than MSD transplantation for Ph- high-risk B-ALL patients.Trial registration::ClinicalTrials.gov: NCT01883180, NCT02673008.
9.Retrospective gender analysis of bronchial artery embolization for massive hemoptysis
Wei FAN ; Zhuozhuo YAN ; Fenqiang LI ; Dongjun SU ; Gengxiang LI ; Lei DANG ; Yuxing PENG ; Wenhui WANG
Journal of Interventional Radiology 2024;33(6):636-641
Objective To retrospectively analyze the clinical features and prognosis of patients with massive pulmonary hemoptysis.Methods Patients with massive hemoptysis,who received bronchial artery embolization at authors'hospital between 2016 and 2018,were collected for this study.According to the gender,the patients were divided into female group(n=68)and male group(n=195).The primary disease,age at onset,length of hospital stay,bleeding site,embolization agent used,recurrence rate of hemoptysis,and mortality were calculated.SPSS.27.0 software was used to analyze the correlation between the age of onset,length of hospital stay,gender,recurrence of hemoptysis and death.RStudio4.2.2 software was used to make a normogram of patient's recurrent hemoptysis and death.Results The primary diseases in the top three were bacterial infection,bronchiectasis and old pulmonary tuberculosis,the incidences of them in the female group were 50%,22%and 15%respectively and in the male group were 43%,21%and 21%respectively.The mean age at onset in the female group was(54.6±16.8)years and in the male group was(60.1±14.0)years.The proportions of the bleeding site in the left lung,right lung,or both lungs in the female group were 6%,21%and 73%respectively and in the male group were 17%,21%and 62%respectively.The proportions of the used embolization agent of 350-560 μm PVA particles and 300-500 μm microspheres in the female group were 31%and 24%respectively and in the male group were 50%and 17%respectively.In the patients who had recurrent hemoptysis,the primary diseases in the top three were old pulmonary tuberculosis,pulmonary bacterial infection and bronchiectasis,the incidences of them in the female group were 33%,33%and 33%respectively and in the male group were 44%,34%and 10%respectively.The causes of death were much complex,in which pulmonary infection played an important role.Conclusion In patients with massive pulmonary hemoptysis,there are differences in the primary disease,bleeding site,applicable embolization agent,recurrence rate of hemoptysis,and mortality between females and males,in addition,the age is an independent influencing factor for recurrent hemoptysis and death.(J Intervent Radiol,2024,33:636-641)
10.Effectiveness and security of anisodine hydrobromide tablets in treating nonarteritic anterior ischemic optic neuropathy: a Chinese multicenter nonrandomized controlled study
Mo YANG ; Honglu SONG ; Huanfen ZHOU ; Mengying LAI ; Quangang XU ; Mingming SUN ; Ke FAN ; Hongpei CUI ; Haiyan WANG ; Xin JIN ; Chuanbin SUN ; Qing XIAO ; Ying WANG ; Zide ZHAO ; Minglian ZHANG ; Yongye CHANG ; Mengping CHEN ; Zhanxing SHEN ; Hui YANG ; Xiaoyu XU ; Zhiqing LI ; Dongjun XING ; Yu DONG ; Jinrun YANG ; Qian REN ; Li LI ; Wenfang ZHANG ; Li SUN ; Zhengpei ZHANG ; Suyan LI ; Danyan LIU ; Nalei ZHOU ; Nali LUO ; Yadong LIU ; Shihui WEI
Chinese Journal of Experimental Ophthalmology 2023;41(7):646-653
Objective:To evaluate the efficacy and safety of oral anisodine hydrobromide tablets in the treatment of nonarteritic anterior ischemic optic neuropathy (NAION).Methods:A multicenter nonrandomized controlled trial was conducted.A total of 282 acute NAION patients (282 eyes) were recruited from 16 hospitals in China from July 2020 to May 2021.Patients were divided into two groups according to treatment methods, which were control group (124 cases, 124 eyes) receiving regular treatment including citicoline sodium plus Ginkgo biloba leaf liquid extract or Ginkgo biloba leaf extract tablets plus mecobalamin, and experimental group (158 cases, 158 eyes) receiving treatment in control group plus oral anisodine hydrobromide tablets 1 mg, twice daily for 2 to 3 months.Best corrected visual acuity (BCVA), visual field index (VFI), peripapillary retinal nerve fiber layer (pRNFL) and radial peripapillary capillary vessel density (RPC) were assessed at 1, 2, 3, and 6 months after enrollment using the standard decimal visual acuity chart, 750i Humphery visual field analyzer, Cirrus HD-OCT 4000/Cirrus HD-OCT 5000, RTVue-XR optical coherence tomography respectively.The primary outcomes were BCVA and VFI, and the secondary outcomes were pRNFL, RPC, and the side effects during the follow-up.The study adhered to the Declaration of Helsinki.All patients were fully informed about the treatment and purpose of this study and voluntarily signed the informed consent form.The study protocol was approved by Chinese PLA General Hospital (No.S2020-021-01). Results:In all, 242 patients (242 eyes) completed the follow-up of BCVA, and 98 patients (98 eyes) completed the VFI follow-up.In terms of visual function, BCVA and VFI improved significantly over time in the two groups, and BCVA and VFI were better in experimental group than in control group at various follow-up time points (all at P<0.05). In terms of structure, pRNFL gradually decreased in both groups with the extension of treatment, and pRNFL was significanthy thinner in experimental group than in control group at various follow-up time points (all at P<0.05). There was no significant difference in RPC between the two groups at the last follow-up ( P>0.05). There were two cases with side effects and one case was discontinued due to side effects 25 days after enrollment. Conclusions:Oral anisodine hydrobromide can improve visual acuity and visual field in NAION and accelerate the regression of optic disc edema, with good safety.