1.Knockdown of Erk/Slug signals increases radiosensitivity of MDA-MB-231 cells to γ-rays by upregulating PUMA
Jiyuan HOU ; Zimin LIU ; Xingan LIU ; Guoyong SHAN ; Weihong CAO
Chinese Journal of Radiological Medicine and Protection 2014;34(7):484-488
Objective To study the role Erk/Slug signal pathway in the radiosensitivity of MDAMB-231 cells.Methods MDA-MB-231 cells were transfected with NF-κBp65 siRNA,PUMA siRNA and Slug siRNA respectively or treated with U0126 for 24h,then the cells were irradiated with 4 Gy γ-ray.At different time points post-irradiation,the expressions of Erk1/2,NF-κBp65,Slug and PUMA protein were detected.The cell survival rate and apoptotic index were detected by MTT and TUNEL methods.Resluts Compared with 4 Gy irradiated group,the expression of PUMA was reduced in NF-κB p65 siRNA/4 Gy group,the expressions of Slug and Erk1/2 were obviously decreased but PUMA increased in U0126/4 Gy group,the expression of Erk1/2 had no change but the expression of PUMA increased significantly in Slug siRNA/4 Gyγ group.Meanwhile,at 48h post-irradiation,for U0126/4 Gy group and Slug siRNA/4 Gy group,cells survival rates were decreased to 19.78 ±2.71 (F=11.39,P<0.05) and 17.41 ±4.58(F=15.31,P<0.05),cell apoptosis rates were 28.61 ±4.70 (F=9.84,P<0.05) and 27.55±6.41(F =10.31,P < 0.05),respectively.At 24 h post-irradiation,for NF-κB p65 siRNA/4 Gy group and PUMA siRNA/4 Gy group,cell survival rates approached to 85.65 ± 9.60 (F =12.31,P < 0.05) and 87.53±11.50 (F=13.68,P<0.05),and cell apoptosis rates declined to 3.28 ±0.78 (F=10.83,P < 0.05) and 3.46 ± 0.84 (F =9.92,P < 0.05).Conclusions The radiosensitivity of MDA-MB-231cells was relative to the induction of NF-κB up-regulated PUMA,and the radioresistance was caused by the up-regulation of Slug induced by Erk1/2,which inhibited the expression of PUMA.
2.Protein Components of Lewy Bodies (LBs) Identified from Synthetic Proteasome Inhibitor (PSI)-induced Inclusions in PC12 Cells by MS Analysis
Xingan LI ; Yingjiu ZHANG ; Yihong HU ; Ming CHANG ; Tao LIU ; Danping WANG ; Yu ZHANG ; Linsen HU
Chinese Journal of Biochemistry and Molecular Biology 2008;24(10):906-915
Proteomic analysis is an effective way to identify protein constituent in Lewy bedy-like inclusions (or aggresome) in vitro. Exposure to synthetic proteasome inhibitor (PSI, 10 μmol/L) for 48 hours was used to induce the formation of cytoplasmic proteineous inclusions (termed as PSi-induced inclusions) in PC12 cells.The proteomic approaches of biochemical fractionation, two-dimensional electrophoresis (2-D) and identification via peptide mass fingerprints (PMF) were deployed, and 20 protein components of LBs were identified,i ncluding 2 proteins involved in the production of synaptic neurotransmitter, 6 subunits of the 26 S proteasome,2 cytoskeleton proteins, 2 subunits of mitochondrial complexes, 1 anti-oxidant protein, and 7 chaperone proteins and (or) chaperone-like proteins. The results suggested that these LB protein components might had been recruited in PSI-induced inclusions formed in PC12 cells under the condition of proteasome inhibition.
3.Eukaryotic Translation Factors Resided in PSI-induced Inclusions in PC12
Xingan LI ; Yingjiu ZHANG ; Yihong HU ; Ming CHANG ; Tao LIU ; Danping WANG ; Lei ZHANG ; Yu ZHANG ; Linsen HU
Chinese Journal of Biochemistry and Molecular Biology 2008;24(1):20-29
Lewy body (LB), an eosinophilic inclusion localized in the neuronal perikaryon, consists of a wide range of proteins, including the consistent organization and the selective composition. Treatment of PC12 cells with synthetic proteasome inhibitor (PSI) at 10 μmol/L for 48 hours induced the formation of inclusions, which were detected by eosin staining and immunostaining for α-synuclein. To investigate the potential new components of PSI-induced inclusions in vitro, pure intact inclusions were successfully obtained by fractionation and subjected to two-dimensional electrophoresis (2-DE) then analyzed with unequivocal matrixassisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Eukaryotic translation initiation factor 3 subunit 5 (eIF-3ε), eukaryotic elongation factor 2 (eEF-2) and mitochondrial elongation factor Tu (EF-Tumt) were identified. The results suggest that 3 eukaryotic translation factors recruited in PSI-induced inclusions may influence formation of the intermediate organelles following the inhibition of proteasomes.
4. Efficacy and safety of apatinib in the further line treatment for patients with advanced colorectal cancer failed after standard therapy and the preliminary analysis of efficacy predictors
Lili SHI ; Xingan LIU ; Guoyong SHAN
Chinese Journal of Clinical Pharmacology and Therapeutics 2020;25(12):1388-1394
AIM: To investigate the efficacy and safety of apatinib monotherapy in the third line and further line treatment for patients with advanced colorectal cancer failed after standard therapy and the preliminary analysis of efficacy predictors. METHODS: The required sample size in this study was calculated with the PASS 15.0 software. Advanced colorectal cancer patients failed after standard therapy from May 2017 to October 2018 were included in this study. Patients enrolled in this study were given apatinib either 750 mg or 500 mg monotherapy. The objective remission rate (ORR) and disease control rate (DCR) were evaluated after 2 cycles treatment. The progression-free survival (PFS) and overall survival (OS) were evaluated at the follow-up period, and adverse events during treatment were recorded. The prognosis of patients with or without hypertension was analyzed. The primary endpoint of this study was PFS, and second endpoint was ORR, DCR, OS, safety evaluation and efficacy predictor analysis.RESULTS: Of the 51 patients included, 45 patients were available for efficacy and safety evaluation. Of the 45 advanced colorectal cancer received apatinib monotherapy, the objective response rate (ORR) was 11.11%, and the DCR was 77.78%, the median PFS was 3.95 months, the median OS was 10.3 months. And the common adverse reactions were hypertension, hand-foot syndrome, proteinuria and diarrhea. And the adverse reactions above grade 3 with higher incidence were hand-foot syndrome 6 cases (13.33%), hypertension 5 cases (11.11%), proteinuria 3 cases (6.67%) and diarrhea 3 cases (6.67%). PFS of patients with hypertension was significantly longer than that of patients without hypertension, which was statistical difference (P=0.01). CONCLUSION: Patients with advanced colorectal cancer failed the standard therapy and received apatinib treatment had potential clinical benefits, and the overall toxicity profile was manageable. Patients with hypertension might confer a better prognosis.
5.Immune effectiveness of A/H1N1 influenza vaccine immunization in 505 health care workers within three months after vaccination
Xingan LIU ; Yanming GUO ; Xiaoguang ZHANG ; Jinyan Lü ; Guixia YANG ; Qingxiang XU ; Mingjuan YANG ; Yandan DU ; Bin GUO ; Qin CAO ; Yingzhi LI ; Xuefei CHEN
Chinese Journal of Infectious Diseases 2010;28(11):677-680
Objective To investigate the immunization effect of influenza A/H1N1 vaccine in health care workers (HCW) in Inner Mongolia Greater Khingan Mountains area. Methods Five hundred and five HCW who received A/H1N1 influenza vaccination (immunized group) and 129 staffs who didn't receive the vaccination (unimmunized group) were randomly sampled for semiquantitative testing of serum H1N1 antibody (IgG) levels by enzyme-linked immunosorbent assay (ELISA).Results were analyzed and stratified by age, sex, occupation and the time interval between the time of vaccination and serum sample collection. The antibody positive rates of the two groups were compared by x2test. Results There were 401 (79. 4%) HCW whose H1N1 antibody were positive and 50 (9.9%) whose antibody were weak positive among 505 immunized HCW. While among 129 unimmunized HCW, there were 59 (45.7%) whose antibody were positive and 15 (11.6%) whose antibody were weak positive. The seroconversion rates of specific antibody were not significantly different among the different age groups after receiving A/H1N1 influenza vaccine (P> 0.05).However, there were statistical differences of the seroconversion rates among different sex groups (men 95.7% vs women 87.4% in immunized group, x2=6.40, P<0.05; and men 73.3% vs women 52.5% in unimmunized group, x2 =4.07, P<0.05) and different occupation groups (doctor 86.0% vs nurse 94.5% in immunized group, x2 = 9. 16, P<0.01; and doctor 43. 8% vs nurse 75.0% in unimmunized group, x2=12.61, P<0.01 ). The seroconversion rate was 81.5% after 80 to 89 days of vaccination, which was significantly lower than those after 30 to 39, 50 to 59 days and 60 to 69 days of vaccination, which was 100.0%, 94.7% and 93.6%, respectively (x2 =3.96, P <0.05; x2=7.15, P <0. 01; x2 = 9. 98, P<0. 01). Conclusions A/H1N1 influenza vaccination can induce effective immune response in HCW in Greater Khingan Mountains area of Inner Mongolia. However,the level of specific antibody significantly reduces after 80 to 89 days of vaccination.
6.Comparison between EUS-guided ethanol ablation and surgical treatment of benign insulinoma
Yanjuan JIANG ; Shanyu QIN ; Haixing JIANG ; Fengyan QIN ; Zhiling LIU ; Zuojie LUO ; Yingfen QIN ; Jia ZHOU ; Yuzhen LIANG ; Min LIANG ; Xinghuan LIANG ; Junqiang CHEN ; Xingan QIN
China Journal of Endoscopy 2017;23(4):8-13
Objective To evaluate the safety and efficacy of endoscopic ultrasound (EUS) guided ethanol ablation of benign insulinoma and compare its' advantages and disadvantages with surgical treatment. Methods From April 2011 to February 2016, clinical data of 38 patients with benign insulinoma treated by EUS-guided ethanol ablation or surgical treatment were retrospectively analyzed. Results 97.4% (37/38) patients had a typical clinical manifestation of Whipple's triad, and the I/G ratio of 82.9% patients (29/35) was more than 0.3 with their onset of hypoglycemia. The positive preoperative etiologic diagnosis rates of transabdominal ultrasonography, CT, MRI, PET/CT and EUS were 50.0%, 67.6%, 66.7%, 75.0%, 89.7% respectively. In the current study, 18 patients underwent EUS-guided ethanol ablation (EUS-FNI group) and 20 patients received surgicaltreatment (surgical group). Compared with the surgical group, the operation time, intraoperative hemorrhage volume, postoperative complications, length of stay and hospitalization costs were significantly reduced in the EUS-FNI group (P < 0.05). No treatment-related complications was observed in EUS-FNI group, while 40.0% (8/20) patients in surgical group had complications. During the follow-up period, all these patients maintained stable blood glucose without taking medication, and there's no recurrence of insulinoma in EUS-FNI group after the last treatment with alcohol injection; In surgical group, only 90.0% (18/20) patients had no recurrence, episode of hypoglycemia was less after the operation in 10.0% (2/20) patients. Conclusion EUS-guided ethanol ablation of benign insulinoma is safe and effective, compared with traditional surgical treatment, EUS-guided ethanol ablation is minimally invasive, costs less, recovers fast after treatment and has fewer complications.