1.The role of speckle-type POZ protein in the occurrence and development of malignant tumors
HE Yan ; ZHANG Shuang ; PENG Xingchen
Chinese Journal of Cancer Biotherapy 2018;25(10):1060-1063
恶性肿瘤居中国各类疾病死因之首,发病率与病死率呈逐年上升趋势。近几年来靶向治疗已广泛应用于临床,显示 出良好的抗肿瘤效果,新靶点的探索和鉴定在靶向药物研发过程中起着重要作用。E3泛素连接酶斑点型锌指结构蛋白(speckletype POZ protein,SPOP)作为治疗选择的潜在靶点,能特异性识别底物,使底物发生泛素化降解,广泛参与机体内多种生理、病理 过程。研究发现SPOP基因突变或表达水平改变,通过调控AR/ERG、Akt-mTORC1、Hedgehog/Gli2等多种信号通路影响恶性肿 瘤的发生发展,并与前列腺癌、肾癌、结直肠癌等多种恶性肿瘤细胞增殖及远处转移密切相关。目前,SPOP影响恶性肿瘤发生发 展的相关研究为靶向治疗恶性肿瘤奠定了基础,综述SPOP在恶性肿瘤的最新进展对抗肿瘤研究具有重要的意义。
2.Construction and expression of secretary recombinant adenovis vectors carrying mPSMA
Dongmei ZHANG ; Shaojun WANG ; Xingchen PENG ; Li YANG
Basic & Clinical Medicine 2006;0(12):-
Objective To construct secretary recombinant adenoviral vector carrying the mouse prostate-specific membrane antigen gene through AdEasy vector system and the immunological outcome was assessed.Methods mPSMA was amplified from plasmid pCR-BluntII-TOPO by PCR and subcloned into transfer vector pAdenoVator CMV5,The signal peptide DNA sequence of hIL-2 was fused to 5′terminal of mPSMA gene to construct a secretary Ad-mPSMA.pAdv-mPSMA was co-transformed with pAdenoVator ?E1/E3 through homologous recombination.The recombinant adenoviruses were packaged,amplified and purified in HEK293 cells.HeLa cell was infected by recombinant adenovirus Ad-mPSMA and the expression of mouse prostate-specific membrane antigen gene was detected by RT-PCR and Western blot.The recombinant adenovirus had been immuned mice,sera antibody against mPSMA from immunized mice was detected by ELISA.Results The secretary pAd-mPSMA was constructed successfully and typical cytopathic effect(CPE) was observed.The titer of the recombinant adenovirus was 1.32?1011IU/mL and expression of mPSMA was confirmed by RT-PCR and Western blot.The specific antibody against mPSMA had been foundin serum of the immunized mice.Conclusion mPSMA gene recombinant adenovirus was constructed successfully,which provide a basis for further study on the anti-tumor immunotherapy role of PSMA.
3.Inhibition Function of Dominant-negative Mutant Gene Survivin-D53A to SPC-A1 Lung Adenocarcinoma Xenograft in Nude Mice Models.
Min YU ; Xingchen PENG ; You LU ; Meijuan HUANG
Journal of Biomedical Engineering 2015;32(3):624-628
Survivin-D53A (SVV-D53A) is a dominant-negative mutant survivin, which represents a potential promising target for cancer gene therapy. The present study was designed to determine whether SVV-D53A plasmid encapsuled by DOTAP: Chol liposome would have the anti-tumor activity against SPC-A1 lung adenocarcinoma, and to detect the possible mechanisms. In our experiment, SPC-A1 cells were transfected in vitro with SVV-D53A plasmid and examined for protein expression by Western blot, then flow cytometric analysis was used to detect apoptosis. SPC-A1 lung adenocarcinoma xenografts were established in vivo in the nude mice, which received the i. v. administrations of SVV-D53A plasmid/liposome complexes. After mice were sacrificed, the paraffin-embedded tumor tissue sections were used for proliferating cell nuclear antigen (PCNA) expression and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Compared with the control group, the mice treated with SVV-D53A plasmid had an obviously reduced tumor volume, with high level of apoptosis and decreased cell proliferation in tumor tissue. The research results proved that the administration of SVV-D53A plasmid resulted in significant inhibition of SPC-A1 cells both in vitro and in vivo. The functional mechanism is that the anti-tumor response causes and induces tumor cell apoptosis.
Adenocarcinoma
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pathology
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Animals
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Apoptosis
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Apoptosis Regulatory Proteins
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metabolism
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Cell Line, Tumor
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Cell Proliferation
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Heterografts
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Humans
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Inhibitor of Apoptosis Proteins
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metabolism
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Liposomes
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Lung Neoplasms
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pathology
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Mice
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Mice, Nude
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Neoplasm Proteins
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metabolism
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Neoplasm Transplantation
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Plasmids
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Transfection
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Tumor Burden
4.Construction and expression of secretary recombinant adenovis vectors carrying mPSMA
Dongmei ZHANG ; Shaojun WANG ; Xingchen PENG ; Li YANG
Basic & Clinical Medicine 2009;29(12):1263-1267
Objective To construct secretary recombinant adenoviral vector carrying the mouse prostate-specific mem-brane antigen gene through AdEasy vector system and the immunological outcome was assessed. Methods mPSMA was amplified from plasmid pCR-BluntⅡ-TOPO by PCR and subcloned into transfer vector pAdeno Vator CMV5, The signal peptide DNA sequence of hIL-2 was fused to 5'terminal of mPSMA gene to construct a secretary Ad-mPSMA. pAdv-mPSMA was co-transformed with pAdeno Vator △E1/E3 through homologous recombination. The recombinant adenoviruses were packaged, amplified and purified in HEK293 cells. HeLa cell was infected by recombinant ade-novirus Ad-mPSMA and the expression of mouse prostate-specific membrane antigen gene was detected by RT-PCR and Western blot. The recombinant adenovirus had been immuned mice, sera antibody against mPSMA from immu-nized mice was detected by ELISA. Results The secretary pAd-mPSMA was constructed successfully and typical cytopathic effect (CPE) was observed. The titer of the recombinant adenovirus was 1.32 × 10~(11)IU/mL and expres-sion of mPSMA was confirmed by RT-PCR and Western blot. The specific antibody against mPSMA had been found in serum of the immunized mice. Conclusion mPSMA gene recombinant adenovirus was constructed successfully, which provide a basis for further study on the anti-tumor immunotherapy role of PSMA.
5.Role of mTOR signaling pathway in crizotinib-induced apoptosis of EML4-ALK fusion gene-positive lung adenocarcinoma cell line H2228
Hui DAI ; Xiangqun SONG ; Xingchen PAN ; Haiyan PENG ; Jiang WEI ; Shaozhang ZHOU
Chinese Journal of Pathophysiology 2014;(6):1103-1109
AIM:To investigate the mammalian target of rapamycin ( mTOR) signaling pathway as the center playing a role in the crizotinib-induced apoptosis of non-small cell lung cancer (NSCLC) cell line H2228, which represents positive echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene. METHODS:H2228 cells were processed according to different purposes .Fluorescence quantitative PCR is used to ob-serve the gene states .MTT assay is used to detect the cell inhibition rates .The cell apoptosis and cell cycle were analyzed by flow cytometry .The expression and activation levels of the key proteins in the mTOR signaling pathway were determined by Western blotting .RESULTS:Crizotinib promoted the apoptosis of H 2228 cells in a time-and dose-dependent manner . Crizotinib blocked the H2228 cells staying at the G1 phase.In apoptotic H2228 cells processed with crizotinib, the activa-tion level of mTOR was decreased , and the activation levels of the key proteins in upstream and downstream of mTOR path -way were both declined .The expression level of the fusion protein EML 4-ALK variant 3 was not affected , but its active form of p-ALK was significantly suppressed .CONCLUSION:mTOR signaling pathway has a certain relationship with the crizotinib-induced apoptosis of lung cancer cell H 2228, which represents positive EML4-ALK fusion gene.
6.Reflections on oncology teaching
Chinese Journal of Medical Education Research 2020;19(4):440-443
Oncology involves a wide range of knowledge and a strong expertise. In the teaching process, we should strengthen the cultivation of students' innovation ability, clinical scientific research ability, basic scientific research ability and humanistic quality. The improvement of tumor teaching is not only related to the people's health and quality of life, but also the inevitable requirement of the development of tumor medicine. However, the construction and development of oncology discipline in China are limited by the lack of a unified oncology teaching materials and syllabus, the single teaching mode and the insufficient postgraduate training mode. In the process of exploring the construction of tumor teaching, cooperation of various links is needed, which is mainly reflected in the compilation of characteristic oncology teaching materials and Outlines, adjustment of tumor teaching mode, optimization of postgraduate training mode, grasping the latest tumor progress and strengthening the cultivation of humanistic quality and other specific measures.
7.Blend sign, black hole sign and its combined signs with CT scanning for the predictive value of early hematoma enlargement in patients with intracerebral hemorrhage
Wensong YANG ; Qi LI ; Xingchen WANG ; Rui LI ; Ning ZOU ; Peng XIE
Chinese Journal of Cerebrovascular Diseases 2017;14(11):561-565,579
Objective To investigate the value of blend sign and/or black hole sign with CT scanning for predicting early hematoma enlargement in patients with primary intracerebral hemorrhage.Methods From July 2011 to July 2016,244 consecutive patients with primary intracerebral hemorrhage in the First Affiliated Hospital of Chongqing Medical University were enrolled prospectively.From the onset to the first CT time were all ≤ 6 h.They were randomly divided into either an early hematoma enlargement group (n =82) or a non-hematoma enlargement group (n =162) according to whether they had early hematoma enlargement or not.The general data of patients were collected and compared between the groups,including previous history,clinical features,Glasgow coma scale (GCS) at admission,imaging features (black hole sign,blend sign and black hole sign and/or blend sign),etc.Multivariate logistic regression analysis was performed on the factors influencing early hematoma enlargement.The predictive value of imaging signs of early hematoma enlargement was analyzed.Results (1) In patients with early hematoma enlargement,there were 27 (32.9%) patients had black hole sign,33 (40.2%) had blend sign,and 50(61.0%) had blend sign and/or black hole sign.(2) The volume of hematoma according to 1 ml,the first CT time from onset to admission according to 1 h,and GCS on admission according to 1,the black hole sign and blend sign were included in the multivariate logistic regression analysis.The results showed that both the blend sign (OR,14.04,95% CI 5.16-38.18) and the black hole sign (OR,5.69,95% CI 2.12-15.30) were the independent risk factors for early hematoma enlargement (all P < 0.01).After further adjustment,it showed that the blend sign and/or black hole sign were also the independent risk factors for early hematoma enlargement (OR,14.08,95% CI 5.99-33.08,P <0.01).(3) After the analysis of the receiver operating characteristic curve,the sensitivity,specificity,positive predictive value,negative predictive value,and Youden Index of the blend sign and/or black hole sign of predicting early hematoma enlargement were 61.0%,90.1%,76.0%,82.0%,and 0.511,respectively.Its Youden Index was closer to 1 than the black hole sign (Youden Index:0.280) and the blend sign (Youden Index:0.346).Conclusion Compared with the single sign,the blend sign combined with black hole sign has better predictive ability for early hematoma enlargement after intracerebral hemorrhage.
8.A nomogram model predicting futile recanalization in patients with acute anterior circulation large vessel occlusion after endovascular mechanical thrombectomy
Xiaojun WANG ; Zongyi WU ; Huiyuan PENG ; Duo LIN ; Xingchen LIU ; Jianheng WU ; Min YANG ; Junxiong WEN
Chinese Journal of Neuromedicine 2023;22(1):43-50
Objective:To investigate the risk factors for futile recanalization in patients with acute anterior circulation large vessel occlusion after endovascular mechanical thrombectomy (EMT), and establish a nomogram model predicting futile recanalization in these patients.Methods:One hundred and eighty-eight patients with acute anterior circulation large vessel occlusion after EMT were enrolled from Department of Neurology, Zhongshan Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine from January 2018 to December 2021. Patients were divided into futile recanalization group and effective recanalization group according to whether futile recanalization occurred; futile recanalization was defined as successful recanalization showed by immediate postoperative DSA (modified thrombolysis in cerebral infarction [mTICI] ≥2b), but poor functional outcome (modified Rankin Scale [mRS] scores>2 90 d after surgery). The clinical data were compared between futile recanalization group and effective recanalization group. Multivariate Logistic regression analysis was used to screen the risk factors for futile recanalization. R software was used to establish a nomogram model for futile recanalization. C-index was used to evaluate the differentiation of the model, and correction curve was used to evaluate the accuracy of the line graph model prediction. Receiver operating characteristic (ROC) curve was used to evaluate the predictive efficiency of the nomogram model.Results:Ninety-two patients had futile recanalization. Compared with the effective recanalization group, futile recanalization group had significantly older age, significantly higher hemoglobin A1c on admission, significantly longer time from puncture to vascular recanalization, significantly higher proportions of patients with hypertension history and poor collateral circulation, and significantly different severities of stroke and white matter hyperintensities (WMHs) and distribution of occlusive sites ( P<0.05). Multivariate Logistic regression analysis showed that age, history of hypertension, time from puncture to vascular recanalization, poor collateral circulation, severe WMHs, and moderate-severe stroke were independent risk factors for futile recanalization after EMT in patients with acute anterior circulation large vessel occlusion ( P<0.05). A nomogram model of futile recanalization was established according to the above 6 factors, with C-index of 0.862 ( 95%CI: 0.809-0.914); the calibration curve of the model was highly coordinated to the ideal model curve; area under the ROC curve of futile recanalization was 0.862 ( 95%CI: 0.809-0.914, P<0.001). Conclusions:Acute anterior circulation large vessel occlusion patients with older age, history of hypertension, longer time from puncture to vascular recanalization, poor collateral circulation, severe WMHs, and moderate-severe stroke trend to have futile recanalization after EMT. This nomogram can predict futile recanalization after EMT.
9.Research progress on clinical manifestations and mechanism of radiation-induced taste dysfunction in head and neck cancers
Zixia LI ; Xingchen PENG ; Xin XU
Chinese Journal of Radiation Oncology 2023;32(6):557-561
Taste is a critical sensory function for human as it supports sustenance and alerts the body to toxins. Taste dysfunction is a common side effect of radiotherapy for the head and neck cancers, which is often accompanied by oral mucositis in the early stage. It is associated with anorexia, anxiety and depression, leading to declined quality of life and treatment tolerance. The incidence of radiation-induced taste dysfunction is high, and its clinical manifestations include increased taste threshold, tastelessness, and persistent bitter, sour or metallic taste, which exert significant effect upon the quality of life. At present, effective therapeutic measures for radiation-induced taste dysfunction are still lacking. In this article, research progresses on clinical characteristics and the potential mechanisms of radiation-induced taste dysfunction were reviewed, aiming to provide reference for the mechanism, prevention and treatment for taste dysfunction.
10.Analysis of the real situation of medication in the population with gout achieving T2T indicators: a multicentre real-world study
Weiqin GAO ; Xuezhong GONG ; Yuanyuan ZHANG ; Xingchen DU ; Ping JIANG ; Fengyuan GUAN ; Ying LU ; Xiao SU ; Hongze JIANG ; Hongbin LI ; Yongfei FANG ; Hengli ZHAO ; Jiangyun PENG ; Mingli GAO ; Li SU ; Fang HE ; Qingwen TAO ; Chunrong HU ; Peng LI ; Zeguang LI ; Yuelan ZHU ; Ying GU ; Ming ZHANG ; Rongsheng WANG ; Ting JIANG ; Xiaolin YANG ; Qi ZHU ; Quan JIANG ; Jianyong ZHANG ; Xiaolei FAN ; Yu XUE ; Dongyi HE
Chinese Journal of Rheumatology 2023;27(6):361-367
Objective:To explore the therapeutic characteristics of population with gout achieving treat-to-target (T2T) indicators through real-world research and evaluate their safety.Methods:A total of 3 287 patients diagnosed with gout by rheumatologists in 21 first-class tertiary hospitals in 10 provinces, municipalities, and autonomous regions in China from January 2015 to December 2021 were included in this polycentric cross-sectional study. The database included patients′ general information, disease characteristics, and clinical application of traditional Chinese and Western medicine treatment measures. SPSS and Excel software were used for data analysis. Frequency analysis, cluster analysis, and factor analysis were used to summarize the characteristics and rules of treatment measures for patients with gout who achieved the target after treatment. The occurrence of adverse events (AE) was recorded during treatment.Results:After treatment, 691 visits (7%) achieved the serum urate (SUA) target, and the most frequent use of urate-lowering therapy (ULT) was febuxostat, followed by benzbromarone. The most common treatment options were following: GroupⅠ: traditional Chinese medicine (TCM) decoction-TCM external treatment-physical exercise-proprietary Chinese medicine; GroupⅡ: ferulic acid-nonsteroidal anti-inflammatory drugs (NSAIDs); Group Ⅲ: allopurinol-sodium bicarbonate-benzbromarone; Group Ⅳ: glucocorticoid-colchicine; Group Ⅴ: febuxostat. A total of 5 898 visits (60%) chieved manifestations of joint pain VAS scores target, and the most frequently used drug to control joint symptoms was NSAIDs. The frequency of use of drugs to control joint symptoms were 2 118 times (usage rate reached 35.9%), while the frequency of ULT were 2 504 times (usage rate reached 42.5%), which was higher than the joint symptom control drug. The most common treatment options were following: Group Ⅰ: proprietary Chinese medicine-TCM decoction-TCM external treatment-physical exercise; Group Ⅱ: NSAIDs-colchicine hormones; Group Ⅲ: allopurinol, Group Ⅳ: benzbromarone; Group Ⅴ: febuxostat. A total of 59 adverse events occurred during treatment.Conclusion:The proportions of gout patients who reach target serum urate level & good control of joint symptoms are both very low, and ULT and anti-inflammatory prescription patterns are very different from international guidelines, so it is necessary to strengthen the standardized management of gout patients. At the same time, life intervention measures account for a certain proportion of the treatment plans for the T2T population, and further exploration is needed.