1.Correlation of TS, ERCC1,β-tubulin-Ⅲ and RRM1 expressions with EGFR mutations in non-small cell lung cancer
Ze XING ; Qun HU ; Wuyun SU ; Haiyan ZHAO ; Hua WANG ; Chenxin ZHANG
Journal of Medical Postgraduates 2017;30(3):275-278
Objective Currently , the targeted therapy is the first-choice treatment of advanced non-small cell lung cancer (NSCLC) in with epidermal growth factor receptor (EGFR) mutations, but few studies have been reported on the relationship between immunohistochemical markers and the EGFR mutation.The aim of this study is to analyze the relationship of the EGFR mutation with the ex-pressions of thymidylate synthetase (TS), excision repair cross-com-plementation group 1 ( ERCC1 ) , β-tubulin-III, and ribonucleofide reductase large subunit-l ( RRM1) in NSCLC. Methods We retro-spectively analyzed 336 cases of NSCLC treated in the Department of Medical Oncology , the Affiliated Hospital of Inner Mongolia Medical University, from June 2014 to December 2015 and examined 29 EGFR mutations.We divided the patients into a mutation and a non-mutation group, performed immunohistochemical staining of the TS, ERCC1,β-tubulin-III and RRM1 proteins and compared their expressions in the NSCLC tissue between the two groups . Results EGFR mutations were found in 138 ( 41.07%) of the 336 NSCLC patients but not in the other 198 ( 58.93%) .The expression of TS was significantly lower in the mutation than in the non-mutation group (9.42%vs 39.39%, P<0.05), and so was that of β-tubulin-III (44.2%vs 60.1%, P<0.05).EGFR mutations were correlated with decreased expressions of TS (r=-0.332, P<0.05) andβ-tubulin-III (r=-0.157, P<0.05).Multivariate regression analysis showed that the risk of EGFR mutations was 2.109 times higher in the fe-male patients than in the males (OR=2.109, 95%CI:1.268-3.509), 24.265 times higher in the adenocarcinoma than in the adeno-squamous carcinoma patients (OR=24.265, 95%CI:3.508-167.845), 15.2 times higher in the squamous carcinoma than in the ade-nocarcinoma patients (OR=15.200, 95%CI:4.480-51.569), 2.364 times higher in the lung biopsy specimens than in the surgically treated patients (OR=2.364, 95%CI:1.266-4.413), and 6.171 times higher in the patients with lowly expressed than in those with highly expressed TS (OR=6.171, 95%CI: 3.145-12.109). Conclusion The decreased expressions of TS and β-tubulin-Ⅲ in NSCLC indicate the mutation of the EGFR gene.
2.Research progress of sphingosine kinase and sphingosine-1-phosphate (S1P) /S1P receptor signaling in tumor microenvironment
Xi-hua WEI ; Ze-qun WANG ; Jing-jing CHEN ; Yan PAN
Acta Pharmaceutica Sinica 2023;58(3):571-580
Sphingosine kinase (SphK), sphingosine-1-phosphate (S1P) and S1P receptor (S1PR) are involved in the tumor biological processes such as tumor cell proliferation and migration, and play an important role in the development of cancer. In recent years, researchers have increasingly focused on the interaction between cancer cells and the tumor microenvironment. The tumor microenvironment is genetically stable and can be induced to an antitumor phenotype, which has significant therapeutic advantages. Studies have shown that SphK/S1P/S1PR can regulate multiple aspects of the tumor microenvironment. This review summarizes the effects of SphK and S1P/S1PR signaling on the tumor microenvironment from four perspectives: tumor immune microenvironment, cancer associated fibroblasts, tumor angiogenesis and tumor hypoxic microenvironment, and also outlines potential drug research related to these signal molecules, aiming to elucidate the role of SphK/S1P/S1PR in tumor occurrence and development and provide new ideas for the research of anti-tumor drugs.
3.Efficacy comparison between two kinds of vitrectomy in proliferative diabetic retinopathy
Ze-Hua, ZHANG ; Hui, XU ; Xiao-Hua, MO ; Ying-Fen, LI ; Hai-Lian, LI ; Yan-Qun, WANG
International Eye Science 2017;17(6):1174-1177
AIM:To compare the clinical effect of 23G and 25G+ vitrectomy for treatment of proliferative diabetic retinopathy (PDR).METHODS: A total of 128 PDR patients (195 eyes) requiring vitrectomy in our hospital from November 2013 to May 2016 were randomly divided into 25G+ group and 23G group, 64 cases (97 eyes) in 25G+ group and 64 cases (98 eyes) in 23G group.In 25G+ group, patients were treated by 25G+ vitrectomy.In 23G group, patients were treated by 23G vitrectomy.The visual acuity, as well as intraocular pressure (IOP), iatrogenic injury and complications in two groups were recorded before and 1d, 1wk, 1mo after treatment.The operation time was compared between two groups.RESULTS: The operation time in 25G+ group was lower than that in 23G group (P<0.05).The postoperative visual acuity at 1mo of two groups were improved compared with before surgery (P<0.01).However, visual acuity between two groups in the same period had no significant difference (P>0.05).IOP in 25G+ group before surgery had no significant difference compared with those after surgery at 1d,1wk, and 1mo(P>0.05), which it was the same in 23G group.IOP of two groups in the same period had no significant difference (P>0.05).The incidence rate of iatrogenic injury in 25G+ group was 4.1%, which was significant lower than that of 23G group (13.3%) (P<0.05).The incidence rate of complication in 25G+ group was 3.1%, which was significant lower than that of 23G group (11.2%) (P<0.05).CONCLUSION: Both 23G and 25G+ vitrectomy are safe and effective treatment for PDR.However, 25G+ vitrectomy is the better choice for PDR for the shorter operation time, lower incidence rate of iatrogenic injury and fewer surgical complications.
4.Research progress of new mumber HHLA2 of B7 family
Chinese Journal of Immunology 2018;34(5):790-793
HHLA2 is a newly discovered B7 family member.HHLA2 appears to have limited expression in normal tissues.TMIGD,one of the receptors HHLA2 is established.Similar to HHLA2,TMIGD2 is absent in mouse and rat while it is found in human and higher primates.HHLA2 with inhibition of CD4 and CD8 T cell proliferation,but also can inhibit the role of T cells secrete some cytokines.HHLA2 protein is absent in most normal tissues,but mainly expressed on epithelial cells of a few tissues.But HHLA2 is widely expressed in various human cancers such as lung cancer,breast cancer and osteosarcoma et al,that make HHLA2 might be a new target for human cancers immunotherapy.
5.Clinical questionnaires about benign prostatic hyperplasia.
Xiang-hua ZHANG ; Xin LI ; Zhang-qun YE ; Ze-yu SUN ; Ying-hao SUN ; Guang SUN ; Jian-ye WANG ; Yan-qun NA
Chinese Journal of Surgery 2008;46(15):1153-1155
OBJECTIVEs To assess the understanding degree of urologists for benign prostatic hyperplasia (BPH) and the clinical characteristics of BPH patients.
METHODSThe questionnaires was distributed to urologists and patients in 119 hospitals over the country, respectively. The urologist survey was mainly focused on the questions of BPH progression and therapeutic model. The patient survey was mainly focused on the questions of patient's age, symptom features and the preference to receiving treatment.
RESULTSThe evaluations based on 289 completed urologist questionnaires and 4253 completed patient questionnaires showed that 98.6% of urologists agreed that BPH was a progressive disease but there were still some differences in understanding the risk factors for BPH progression. Additionally, 98.1% of patients were diagnosed to be moderate or severe BPH, nocturia was the most frequent symptom. In the treatment for BPH, both the urologists and patients concerned about how to improve the system rapidly.
CONCLUSIONSThis study is the first questionnaires specifically to the urologists and BPH patients, the results would reflect the situations of BPH diagnosis and treatment in China and would be helpful to the development of BPH guideline.
Adult ; Aged ; Aged, 80 and over ; Health Knowledge, Attitudes, Practice ; Humans ; Male ; Middle Aged ; Patients ; Physicians ; Prostatic Hyperplasia ; Surveys and Questionnaires
6.Treatment of CCl4 induced chronic liver injury with bone marrow mesenchymal stem cells overexpressing hepatocyte growth factor.
Li-sha WANG ; Hai-feng DUAN ; Jiang-wei HU ; Qun-wei ZHANG ; Hua WANG ; Zhuo-zhuang LU ; Zu-ze WU ; Li-sheng WANG
Chinese Journal of Hepatology 2005;13(12):934-936
Animals
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Bone Marrow Cells
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cytology
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Carbon Tetrachloride
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Carbon Tetrachloride Poisoning
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Cell Differentiation
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Cells, Cultured
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Genetic Therapy
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methods
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Hepatocyte Growth Factor
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genetics
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pharmacology
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Hepatocytes
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cytology
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Liver Cirrhosis, Experimental
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therapy
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Male
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Mesenchymal Stem Cell Transplantation
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Mesenchymal Stromal Cells
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cytology
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Rats
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Rats, Wistar
7.Influence of hepatocyte growth factor on biological characteristics of bone marrow-derived mesenchymal stem cells.
Hong-Jun LIU ; Hai-Feng DUAN ; Zhuo-Zhuang LU ; Hua WANG ; Qun-Wei ZHANG ; Zu-Ze WU ; Li-Sheng WANG
Journal of Experimental Hematology 2005;13(6):1044-1048
Hepatocyte growth factor (HGF) is one of major growth factors in the bone marrow microenvironments with which the proliferation, differentiation and migration of bone marrow-derived mesenchymal stem cells were closely contacted. However, its roles in the regulation of proliferation, differentiation and migration of bone marrow-derived mesenchymal stem cells remain unclear. This study was aimed to investigate the effect of HGF on biological characteristics of bone marrow-derived mesenchymal stem cells. Expression of c-Met, the receptor for HGF was detected by immunohistochemistry assay, cell proliferation was determined by MTT, activity of ALP was quantitatively assayed, cell migration and anoikis-induced MSC apoptosis were analyzed. The results showed that HGF not influenced the proliferation and osteogenic differentiation of bone marrow-derived mesenchymal stem cells. Treatment of bone marrow-derived mesenchymal stem cells with recombinant human hepatocyte growth factor resulted in inhibition of anoikis-induced apoptosis. HGF significantly stimulated the migration of bone marrow-derived mesenchymal stem cells. Both PI-3 kinase and MAPK kinase were proved to be involved in HGF-induced migration. It is concluded that HGF/c-Met signal regulates the apoptosis and migration of bone marrow-derived mesenchymal stem cells.
Anoikis
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drug effects
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Bone Marrow Cells
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cytology
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drug effects
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metabolism
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Cell Movement
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drug effects
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Cell Proliferation
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drug effects
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Cells, Cultured
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Hepatocyte Growth Factor
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pharmacology
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Humans
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Immunohistochemistry
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Mesenchymal Stromal Cells
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cytology
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drug effects
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metabolism
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Proto-Oncogene Proteins c-met
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biosynthesis
8. Role of epigenetic regulation of biological clock genes in tumors
Chen-Xi WANG ; Ze-Qun WANG ; Yan PAN
Chinese Pharmacological Bulletin 2023;39(6):1001-1007
The circadian clock is regulated at the molecular level by transcriptional-translational feedback loop of clock genes, which ensures that a variety of physiological processes have a-round 24 h circadian rhythms, including cell metabolism, cell proliferation, cell apoptosis and tumorigenesis, to maintain the homeostasis. Thus, the disturbance of circadian clock will disrupt homeostasis, causing various diseases, including neoplasm, metabolic syndrome, Parkinson's disease, COPD and cardiovascular diseases. Disturbance of circadian clock is closely related with tumorigenesis, and acts on various molecules and pathways leading to tumorigenesis, including oncogene and tumor suppressor gene, cell cycle, metabolic reprogramming, immune escape, endocrine disruption, alteration of gastrointestinal microbiome. This review focuses on changes in clock genes expression which disrupt cell cycle and may play a role in tumorigenesis, and epi-geneties, an important way to regulate gene expression, which can alter clock gene expression, thus playing an important role in the process of " the alternation of clock gene expression-disruption of cell cycle-tumorigenesis".
9.Protective action of effective components of Huanglian Jiedu decoction on hypoxia and reoxygenation injury in cultured rat cerebral microvascular endothelial cells.
Zheng-zhong YUAN ; Ling-qun ZHU ; He PANG ; Ze-song SHAN ; Shuo-ren WANG ; Yong-hong GAO ; Fu-ling NIU
China Journal of Chinese Materia Medica 2007;32(3):249-252
OBJECTIVETo investigate the protective effect of geniposide, baicalin and berberine for the rat cerebral microvascular endothelial cell.
METHODThe model of hypoxia and reoxygenation injury in rat cerebral microvascular endothelial cells in vitro was established. Both normal and model cells were treated with geniposide (1.024, 0.512, 0.256, 0.128, 0.064, 0.032, 0.016, 0.008 micromol x mL(-1)), baicalin (0.224, 0.112, 0.056, 0.028, 0.014, 0.007, 0.003 micromol x mL(-1)) and berberine (0.192, 0.096, 0.048, 0.024, 0.012, 0.006, 0.003 micromol x mL(-1)). Cell activity was measured by methyl thiazolyl tetrazolium (MTT) test.
RESULTAfter hypoxia/hypoglycemia cultures for 4 hour and reoxygenation for 12 hour, geniposide (0.128, 0.064, 0.032 micromol x mL(-1)), baicalin (0.028, 0.014, 0.007 micromol x mL(-1)) and berberine (0.024, 0.012, 0.006 micromol x microL(-1) could protect the injuried cerebral microvascular endothelial cells.
CONCLUSIONAppropriate concentration of geniposide, baicalin and berberine, which are effective components of Huanglian Jiedu decoction, could protect the injuried cerebral microvascular endothelial cells.
Animals ; Berberine ; isolation & purification ; pharmacology ; Cell Hypoxia ; Cell Survival ; drug effects ; Cells, Cultured ; Cerebral Cortex ; blood supply ; Dose-Response Relationship, Drug ; Drug Combinations ; Drugs, Chinese Herbal ; chemistry ; Endothelial Cells ; cytology ; drug effects ; Flavonoids ; isolation & purification ; pharmacology ; Iridoids ; isolation & purification ; pharmacology ; Male ; Neuroprotective Agents ; pharmacology ; Oxygen ; pharmacology ; Plants, Medicinal ; chemistry ; Pyrans ; isolation & purification ; pharmacology ; Rats ; Rats, Sprague-Dawley
10.Effects of electroacupuncture at "Neiguan" (PC 6) on p38 MAPK signaling pathway in rats with cardiac hypertrophy.
Song WU ; Jia LI ; Ya-Qun HONG ; Feng-Xia LIANG ; Hong-Tu TANG ; Jian-Min LIU ; Wei HUANG ; Ze-Bin CHEN ; Hua WANG
Chinese Acupuncture & Moxibustion 2012;32(2):145-148
OBJECTIVETo discuss the mechanisms of electroacupuncture at "Neiguan" (PC 6) on p38 MAPK signaling pathway in rats with cardiac hypertrophy.
METHODSForty SD rats were randomly divided into four groups: a normal group, a model group, a model plus p38 MAPK inhibitor group, a model plus electroacupuncture group, ten rats in each group. The model rats were established by subcutaneous injection 3 mg/(kg x d) of Isoprenaline Hydrochloride; model plus p38 MAPK inhibitor group were injected 0.3 mg/(kg x d) of specific inhibitor SB 203580; model plus electroacupuncture group was treated by electroacupuncture at "Neiguan"(PC 6) with continuous-wave, 2 Hz and 1 mA for 20 minutes, once a day for 14 days. There was no treatment in other two groups. The contents of TNF-alpha and IL-1beta in heart tissue were detected by radioimmunoassay and the p38 MAPK, p-p38 MAPK by western blot.
RESULTSCompared with normal group, the contents of TNF-alpha, IL-1beta, p38 MAPK, p-p38 MAPK were significantly increased in model group (all P < 0.01). The contents of TNFalpha, IL-1beta, p38 MAPK, p-p38 MAPK were significantly decreased in model plus p38 MAPK inhibitor group and model plus electroacupuncture group, compared with model group, all P < 0.05; compared with normal group, P < 0.05, P < 0.01; but no significant difference between model plus p38 MAPK inhibitor group and model plus electroacupuncture group (P > 0.05).
CONCLUSIONElectroacupuncture at "Neiguan" (PC 6) can prevent the phosphorylation of p38 MAPK of myocardial hypertrophy, and the mechanism maybe adjust p38 MAPK signaling pathway by inhibiting the expression of TNF-alpha and IL-1beta.
Acupuncture Points ; Animals ; Cardiomegaly ; metabolism ; therapy ; Electroacupuncture ; Interleukin-1beta ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Tumor Necrosis Factor-alpha ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism