1.Anticancer effects of heparinized mesoporous silicon nanoparticles drug carrier system on H22 tumor-bearing mice and its liver and kidney toxicity
Ruifang LI ; Qiang WU ; Xinli XU ; Heyang LIU ; Junmin FU ; Xiangguan FENG
Chinese Journal of Pharmacology and Toxicology 2016;(1):61-67
OBJECTIVE To investigate the antitumor effect and toxicity of doxorubicin-heparinized mesoporous silicon nanoparticles drug carrier system (DOX-HMSN) on H22 hepatoma mice. METHODS An experimental animal model of H22 hepatoma mice was established. Fifty male Kunming mice were divided into five groups:model control group,HMSN 8 mg?kg-1 group,DOX-HMSN 4,8 mg?kg-1 groups, and DOX 2 mg?kg-1(once every other day)group. Continuous intravenous injection was given once a day for 14 d. Tumor was completely stripped and weighed,and tumor inhibitory rate was determined. Pathological change of tumor tissue was observed by HE staining in H22 mice. White blood cell count was performed and the thymus index and spleen index were calculated. Levels of serum creatinine (Scr),blood urea nitrogen(BUN),glutamic pyruvic transaminase(GPT)and glutamic-oxalacetic transaminase(GOT)in serum were determined. BCL-2,BAX and vascular endothelial growth factor (VEGF)expression of tumor tissue were analyzed using Western blot. RESULTS The inhibitory rate of tumor was 20.5%,40.4%,54.8%,and 67.5%,respectively,in HMSN 8 mg?kg-1 group,DOX-HMSN 4, 8 mg?kg-1 group and DOX 2 mg?kg-1 group(P<0.01). HE results showed that HMSN 8 mg?kg-1,DOX-HMSN 4,8 mg?kg-1and DOX 2 mg?kg-1 induced tumor necrosis and nuclear dissolution of the tumor cells in H22 mice. The white blood cell count,thymus index and spleen index of mice were not signifi?cantly different between control group and HMSN group or DOX-HMSN 4 and 8 mg?kg-1 group. The levels of Scr and BUN of mice did not change obviously in HMSN 8 mg?kg-1or DOX-HMSN 4,8 mg?kg-1 groups. Compared with the model control group,the level of GPT and GOT of mice increased in the DOX 2 mg?kg-1group but decreased in HMSN 8 mg?kg-1 and DOX-HMSN 4 and 8 mg?kg-1 group(P<0.05). Compared with the control,the BAX/BCL-2 ratio(from 0.49 ± 0.06 to 0.79 ± 0.08,1.23 ± 0.14 and 1.04±0.14)increased but the VEGF expression of tumor(from 1.39±0.14 to 1.13±0.12,0.75±0.08 and 0.94 ± 0.09)decreased significantly in DOX-HMSN 4,8 mg?kg-1 and DOX 2 mg?kg-1 group(P<0.05). CONCLUSION DOX-HMSN can inhibit the tumor growth of H22 tumor-bearing mice and its antitumor mechanism might be related to inducing tumor cell necrosis and apoptosis and inhibiting tumor angiogenesis.
2.Relationship between rapid-eye-movement sleep behavior disorder and synucleinopathies
Honglin HAO ; Xiuqin LIU ; Yan HUANG ; Heyang SUN ; Han WANG ; Zhenxin ZHANG ; Zhizheng ZHANG ; Liying CUI ; Qiong MENG
Chinese Journal of Neurology 2010;43(8):572-576
Objective To investigate the incidence rate, onset time and electrophysiological characteristics of rapid eye movement sleep behavior disorder (RBD) and the relationship between RBD and synucleinopathies as well as the electrophysiological diagnostic criteria of RBD in Parkinson' s disease (PD) and multiple system atrophy (MSA). Methods Sleep survey and night video-polysomnography (NPSG)were used to study sleep disturbance of PD and MSA. (1) Subjective sleep assessments: All subjects,including 66 PD patients, 65 age and sex matched healthy controls and 30 MSA patients, completed the sleep questionnaires, and the RBD incidence rate and onset time were got. (2) Objective sleep assessments: 8 PD patients, 13 MSA patients, and 15 age and sex matched healthy controls underwent video-NPSG recording on two consecutive nights. Sleep architect were analyzed. The NPSG characteristics of RBD accompany with PD and MSA were analyzed, and the electrophysiological diagnostic varameters of it were determined. Results Patients with PD or MSA had a higher prevalence of RBD. RBD was found in 59. 1% (39/66) PD patients and 86. 6% (26/30) MSA patients, among those, 46. 2% ( 18/39 ) and 84.6% (22/26) had the waking symptoms of MSA and PD. The main NPSG characteristics of RBD of PD or MSA were chin REM without atonia (RWA) and increased movement. Conclusions The relatively higher RBD prevalence in MSA and PD patients indicates that RBD has close relationship with PD and MSA.Part of patients with RBD preceding neurology disease indicates that RBD may be the early marker of PD and MSA. The main NPSG characteristics of RBD accompany with PD and MSA are chin RWA and the motor manifestations. RWA and phasic EMG activity density are supposed to be the NPSG diagnostic parameters.
3.Value of a combined ultrasound imaging radiomics model to predict progression-free survival in endocrine therapy for prostate cancer
Heyang LIU ; Qian LIU ; Hua HONG ; Diansheng JIN ; Huimin GAO ; Senlin BAO ; Wen LI
Chinese Journal of Ultrasonography 2024;33(11):992-999
Objective:To investigate the value of the combined ultrasound imaging radiomics model for predicting progression-free survival in endocrine therapy for prostate cancer.Methods:A total of 283 prostate cancer patients who received endocrine treatment at the Inner Mongolia Autonomous Region People′s Hospital and the First Hospital of Hohhot from July 2018 to January 2023 were retrospectively collected, of which 198 patients from the Inner Mongolia Autonomous Region People′s Hospital were randomly divided into the training set and the validation set according to the ratio of 7∶3, and 85 patients from the First Hospital of Hohhot served as an independent external test set. They were classified into a progression group and a non-progression group based on whether the patients progressed to desmoplasia-resistant prostate cancer 18 months after the start of endocrine treatment.Based on the two-dimensional ultrasound images, the imaging radiomics features were extracted and the imaging radiomics score (Rad-score) were constructed, the immunopathology and other clinical data were analysed, and three prediction models were constructed using logistic regression: the clinical model, the ultrasonography model, and the ultrasonography-clinical combined model, respectively. The predictive efficacy and clinical utility of the models were assessed by the ROC curves and clinical decision curves.Results:Five ultrasonographic features were included in the ultrasound model; the prostate-specific antigen nadir, the neutrophil-to-lymphocyte ratio before treatment, and the expression level of tumour proliferating cell nuclear antigen 67 (Ki-67) were incorporated into the clinical model; and the Rad score computed from the output of the ultrasound model for the screening features, together with the prostate-specific antigen nadir (PSA nadir), the neutrophil to lymphocyte ratio (NLR) before treatment, and the expression level of Ki-67 were used to construct the ultrasound-clinical joint model. The joint model achieved the highest predictive performance in both the training and validation sets of the three groups of models, with the area under the curve of 0.85 and 0.84, and the clinical decision curve showed good clinical benefit.Conclusions:The combined ultrasound-clinical model constructed in this study based on two-dimensional ultrasound images of prostate cancer before endocrine therapy can predict progression-free survival of endocrine therapy for prostate cancer more accurately.
4.Study of sleep disorders in patients with limbic encephalitis associated with anti leucine rich glioma inactivated protein 1 antibody
Heyang SUN ; Honglin HAO ; Qing LIU ; Qiang LU ; Hongzhi GUAN ; Haitao REN ; Yan HUANG ; Liying CUI
Chinese Journal of Neurology 2018;51(8):565-569
Objective To identify the spectrum of sleep disorders in the patients diagnosed with limbic encephalitis associated with anti leucine rich glioma inactivated protein 1 (LGI1) antibody.Methods Thirteen patients were identified with limbic encephalitis associated with LGI1 antibody in the Department of Neurology,Peking Union Medical College Hospital between December 2012 and August 2017.The characters of the 13 cases were studied from several aspects such as clinical presentation,imaging,polysomnography,cerebrospinal fluid and serum.Results Serum test and/or cerebrospinal fluid test showed LGI1 antibody positive in all the 13 patients.Clinical presentation included:cognitive impairment,seizures,neuropsychiatric features.Sleep disorders presented in all patients,including insomnia,dream enactment behaviors,hypersomnia,involuntary movement.Polysomnogram in the 13 patients revealed that sleep efficiency decreased in 10 patients (< 80%),N3 sleep decreased in 10 patients,rapid eye movement sleep decreased in 13 patients;period limb movement disorder was identified in seven patients,period limb movement index was 15.6-224.4/h,four of the seven patients also had frequent irregular motor activity;six patients had frequent faciobrachial dystonic seizures (20-83 times throughout the night);rapid eye movement sleep behavior disorder (RBD) was diagnosed in three patients.Sleep disorder resolved almost completely in 10 of 13 patients who received immunotherapy.Conclusions Sleep disorders are cardinal manifestations of limbic encephalitis associated with LGI1 antibody,including insomnia,RBD,hypersomnia,involuntary movement.They may respond favorably to immunotherapy.
5.Study of negative feedback between wild-type BRAF or RAFV600E and Mps1 in melanoma.
Ling ZHANG ; Chanting HE ; Yanghui BI ; Feng LIU ; Heyang CUI ; Juan WANG ; Bin SONG ; Ruyi SHI ; Bin YANG ; Fang WANG ; Zhiwu JIA ; Zhenxiang ZHAO ; Jing LIU ; E-mail:liujing5585@163.com.
Chinese Journal of Pathology 2015;44(4):274-277
OBJECTIVETo study the effect of Mps1 on BRAFWT/MEK/ERK pathway in the presence of wild type BRAF or BRAFV600E in melanoma.
METHODSMelanoma cells harboring BRAFWT genotype were transfected either with pBabe-puro-GST-BRAF-WT and/or pBabe-puro-GFP-Mps1-WT or pBabe-puro-GST-BRAFV600E and/or pBabe-puro-GFP-Mps1-WT, followed by Western blot to detect Mps1 and p-ERK expression. The melanoma cells harboring BRAFWT and BRAFV600E genotype were infected with pSUPER-Mps1 retrovirus to knockdown the endogenous Mps1 protein, followed by Western blot to detect Mps1 and p-ERK expression. Meanwhile, melanoma cells harboring BRAFV600E genotype were infected with pBabe-puro-GFP-Mps1 and Western blot was performed to detect Mps1 and p-ERK expression.
RESULTSIn melanoma cells harboring BRAFWT genotype and transfected with pBabe-puro-GST-BRAF-WT and pBabe-puro-GFP-Mps1-WT, phospho-ERK levels were notably reduced as compared to either negative control or empty vector. However, cells transfected with pBabe-puro-GST-BRAFV600E and pBabe-puro-GFP-Mps1-WT, phospho-ERK levels did not change significantly compared with either negative control or empty vector. Knockout of Mps1 in BRAF wild-type cell lines led to an increased ERK activity. However, there was no significant change of ERK activity in BRAFV600E cell lines in the absence of Mps1. The expression of p-ERK in BRAFV600E mutant cell lines infected with pBabe-puro-GFP-Mps1-WT did not show any significant difference from either negative control or empty vector.
CONCLUSIONSBased on these findings, it suggests that there exists an auto-regulatory negative feedback loop between the Mps1 kinase and BRAFWT/ERK signaling. Oncogenic BRAFV600E abrogates the regulatory negative feedback loop of Mps1 on the MAPK pathway.
Cell Cycle Proteins ; metabolism ; Cell Line, Tumor ; Humans ; MAP Kinase Signaling System ; Melanoma ; genetics ; metabolism ; Mutation ; Phenotype ; Protein-Serine-Threonine Kinases ; metabolism ; Protein-Tyrosine Kinases ; metabolism ; Proto-Oncogene Proteins B-raf ; metabolism ; Signal Transduction ; Transfection
6.Study of negative feedback between wild-type BRAF or RAFV600E and Mps1 in melanoma
Ling ZHANG ; Chanting HE ; Yanghui BI ; Feng LIU ; Heyang CUI ; Juan WANG ; Bin SONG ; Ruyi SHI ; Bin YANG ; Fang WANG ; Zhiwu JIA ; Zhenxiang ZHAO ; Jing LIU
Chinese Journal of Pathology 2015;(4):274-277
Objective To study the effect of Mps1 on BRAFWT/MEK/ERK pathway in the presence of wild type BRAF or BRAFV600E in melanoma.Methods Melanoma cells harboring BRAFWT genotype were transfected either with pBabe-puro-GST-BRAF-WT and/or pBabe-puro-GFP-Mps1-WT or pBabe-puro-GST-BRAFV600E and/or pBabe-puro-GFP-Mps1-WT, followed by Western blot to detect Mps1 and p-ERK expression.The melanoma cells harboring BRAFWT and BRAFV600E genotype were infected with pSUPER-Mps1 retrovirus to knockdown the endogenous Mps1 protein, followed by Western blot to detect Mps1 and p-ERK expression.Meanwhile, melanoma cells harboring BRAFV600E genotype were infected with pBabe-puro-GFP-Mps1 and Western blot was performed to detect Mps1 and p-ERK expression. Results In melanoma cells harboring BRAFWT genotype and transfected with pBabe-puro-GST-BRAF-WT and pBabe-puro-GFP-Mps1-WT, phospho-ERK levels were notably reduced as compared to either negative control or empty vector.However, cells transfected with pBabe-puro-GST-BRAFV600E and pBabe-puro-GFP-Mps1-WT, phospho-ERK levels did not change significantly compared with either negative control or empty vector.Knockout of Mps1 in BRAF wild-type cell lines led to an increased ERK activity.However, there was no significant change of ERK activity in BRAFV600E cell lines in the absence of Mps1.The expression of p-ERK in BRAFV600E mutant cell lines infected with pBabe-puro-GFP-Mps1-WT did not show any significant difference from either negative control or empty vector. Conclusions Based on these findings, it suggests that there exists an auto-regulatory negative feedback loop between the Mps1 kinase and BRAFWT/ERK signaling.Oncogenic BRAFV600E abrogates the regulatory negative feedback loop of Mps1 on the MAPK pathway.
7. Function and mechanism of zinc finger protein ZNF50 in inhibiting the growth of esophageal squamous cell carcinoma cells
Juan WANG ; Yanghui BI ; Jie YANG ; Feng LIU ; Yike LI ; Heyang CUI ; Fang WANG ; Jing LIU ; Bin YANG ; Ling ZHANG
Chinese Journal of Oncology 2017;39(1):7-12
Objective:
To investigate the function and mechanism of zinc finger protein 750 (ZNF750) in esophageal squamous cell carcinoma (ESCC).
Methods:
Xenograft in nude mice was applied to detect the tumorigenesis of ZNF750-depleted ESCC cells. Western blot was performed to observe the expression of downstream target protein of ZNF750 in ESCC cell lines and xenograft tumor tissues in which ZNF750 was knocked down. 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay was used to determine the proliferation of ZNF750 stably depleted cells after restoration of its target protein.
Results:
The tumor weight of blank control, negative control and ZNF750 knockdown groups was 137±26 mg, 161±31 mg and 463±89 mg, respectively, with a statistically significant difference (