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Objective:To study the expression and clinical significance of collagen type Ⅰ alpha 2 chain (COL1A2) in glioma , and its effect on the migration and invasion of glioma cell lines.Methods:Through in-depth mining of the data related to COL1A2 in the Oncomine database, meta-analysis of its expression in different types of tumors, different grades and different molecular types of glioma, and then through the Chinese glioma genome map project (Chinese Glioma Genome Atlas, CGGA) database to explore the relationship between its expression level and the prognosis of glioma patients. The COL1A2 gene was functionally annotated by gene ontology (GO) and Pathway analysis. The annotation content includes cell components, biological processes, molecular functions and related signal pathways.Results:A total of 426 research results on COL1A2 in different types of tumors were collected in the Oncomine database, 114 of which were statistically different, 103 studies with increased COL1A2 expression, and 11 studies with decreased expression; the analysis shows there were 22 studies on high expression of COL1A2 in tumors, and no studies on low expression. Analysis of different grades of glioma and different molecular types of glioma Compared with the control group, COL1A2 was highly expressed in various types of glioma. Through the analysis of the gene chip data of the CGGA database, it was found that in glioblastoma, low expression levels of COL1A2 were significantly associated with an improved prognosis in patients with glioma ( P<0.05). Next, through GO and Pathway annotations, it was found that COL1A2 was involved in the biological processes of NAD metabolic salvage pathway, cell and cell signal transduction, circadian rhythm regulation and so on. Finally, through the construction of overexpression and knockdown cell lines in glioblastoma cell lines U87 and T98, scratch experiments and transwell cell function experiments confirmed that COL1A2 can significantly promote the migration and invasion of glioblastoma cell lines. Conclusions:Low expression levels of COL1A2 were significantly associated with improved prognosis in patients with glioma. Knockdown and overexpression of COL1A2 on glioblastoma cell lines U87 and T98 manifested that COL1A2 can promote glioblastoma cell lines migration and invasion ability. Based on the above results, COL1A2 may be used as an indicator for judging the prognosis of glioblastoma and as a potential biological target for therapy.
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OBJECTIVE@#To establish a mouse model bearing orthotopic temozolomide (TMZ)-resistant glioma that mimics the development of drug resistance in gliomas @*METHODS@#Seventy-eight adult C57BL/6 mice were randomly divided into 6 groups (@*RESULTS@#The mouse models bearing TMZresistant glioma was successfully established. The cells from the high-dose induced group showed a significantly higher colony-forming rate than those from the high-dose control group (@*CONCLUSIONS@#Progressive increase of TMZ doses in mice bearing orthotopic gliomas can effectively induce TMZ resistance of the gliomas.
Subject(s)
Animals , Mice , Antineoplastic Agents, Alkylating/pharmacology , Brain Neoplasms/drug therapy , Cell Line, Tumor , Disease Models, Animal , Drug Resistance, Neoplasm , Glioma/drug therapy , Mice, Inbred C57BL , Temozolomide/therapeutic useABSTRACT
The aim of study was to determine relationship between cagA and genetic characterization of metronidazole [MTZ] resistant H. pylori strains from a region at high risk of gastric cancer. 172 H. pylori strains were isolated from the patients with dyspeptic symptoms, and antimicrobial susceptibility testing for MTZ was assessed by E-test. rdxA and frxA genes were amplified using PCR among the MTZ resistant isolates. The status of the plasmid and classes 1-3 integrons were investigated in all isolates. MTZ was detected in 88 isolates [51.16%]. Variations in the rdxA gene leading to alterations of amino acids in RdxA proteins were identified in all MTZ resistant strains. FrxA contained missense alterations in 55 MTZ resistant isolates, while the premature truncation of FrxA was caused by frameshift mutations in 9 MTZ resistant strains. Plasmid was found in one MTZ sensitive strain [0.58%], and none of Class 1-3 integrases gene was detected in the studied isolates. The conservative cagA fragment was obtained from all clinical isolates of H. pylori. The sequence of cagA 3' variable region in 164 strains were obtained, including East Asian-type [122, 74.39%] and Western-type [42, 25.61%]. Prevalence of Western-type cagA 3' variable region was significantly higher in MTZ resistant [33.73%, 28/83] than those of MTZ-sensitive strains [17.28%, 14/81] [p=0.02]. A high prevalence of MTZ resistance was found in the region, and bacterial chromosome mutations in the rdxA and frxA gene still contribute to the high-level MTZ resistance. H. pylori strains characterized with West-type cagA 3' variable region tend to acquire MTZ resistance in the region
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Objective To investigate whether catalpol affects senile plaque formation and spatial learning and memory ability in the amyloid-β protein precursor/presenilin 1 (APP/PSI) double transgenic mice.Methods Three month-old APP/PS1 double transgenic mice were randomly divided into catalpoltreated and saline-treated groups (n =10),with C57 mice of the same age and genetic background as normal control group (n =10).The catalpol (in a dose of 5 mg · kg-1 · d-1) and the same amount of saline were peritoneally injected into Alzheimer' s disease (AD) model mice for 3 weeks.Immunohistochemical staining was performed to examine senile plaques in the brain of AD model mice,and Morris water maze was used to assess the spatial learning and memory abilities of the mice.Results Compared with the saline-treated AD model mice (6.0 ±0.6),the number of senile plaques of catalpol treated AD mice significantly decreased (2.3± 0.7; t =3.500,P =0.025); Mice in each groups had similar latency and path length to reach platform in visible platform test; In hidden platform test,catalpol-treated mice had a significant lesser latency and path length compared with saline-treated mice,furthermore,catalpol-treated mice had much more platform-crossing times (6.4 ± 0.8) than saline-treated mice (2.9 ± 0.4 ; t =5.592,P =0.001).Conclusion Catalpol can significantly decrease the senile plaque formation and improve the spatial learning and memory abilities of APP/PS1 double transgenic mice.
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ObjectiveTo investigate the distribution and expression of y-secretase subunit (APH-1)in the central nervous system (CNS) of APP/PS1 double transgenic Alzheimer's disease (AD) adult mouse model,and to detect the expression difference of APH-1 in developmental brain between AD model mouse and wild-type littermates in order to further clarify the relationship between APH-1 and AD. MethodsOffspring bred by APP/PS1 double transgenic AD mice were genotyped.Immunohistochemical staining was used to detect APH-1 distribution and expression in the CNS of adult APP/PS1 double transgenic AD mouse model,in the brain of AD model mouse and its wild-type littermates on postnatal day 1,7,21 and 120.Results APH-1 was widely expressed in almost all regions of the CNS,especially in the cerebral cortex,hippocampus,olfactory bulb,hypothalamus,ventral striatum,caudate putamen,raphe magnus nucleus,cerebellum,brainstem and spinal cord of the adult APP/PS1 double transgenic mice.APH-1 expression was higher in the cortex of both AD and wild type mouse on postnatal day 1 than on postnatal day 7 and 21 with increased level of APH-1 protein in adult mouse brain.APH-1 expression in the brain of AD mice was higher than in its wild type littermates at any stage(P＜0.05).Conclusions Distribution of APH-1 is ubiquitous and region-dependent in the CNS.The different distribution and expression between APP/PS1 double transgenic mouse model and its wild type littermate indicate that APH-1 may be related to AD.
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<p><b>OBJECTIVE</b>To assess the feasibility of the 10 microg recombination yeast hepatitis B vaccine in the expanded applicable population group aged 5 - 18.</p><p><b>METHODS</b>People with both HBsAg and anti-HBs negative were selected to take two-stage clinical experiment and the safety and immunogenicity were observed. Safety observation was conducted in 925 subjects, while 568 for immunogenicity. The observation group (aged 5 - 18) included 493 subjects, and (age > 18) 75 enrolled in control group. For the observation group, there were three sub-groups including a child group (141, aged 5 - 6), early youth group (177, aged 12 - 13), and youth group (175, aged 16 - 18). Both groups were administered with 10 microg recombination yeast hepatitis B vaccines with 3 doses at 0 month, 1st month, 6th month. To assess the immunogenicity, the vaccination reactions were observed during the following 4 weeks in order to assess the vaccine safety. The blood samples were taken during 4 - 6 weeks after fully vaccinated, and then anti-HBs were tested with RIA and analyzed by comparing the positive rate of anti-HBs, the geometric mean titer (GMT) and the protective rate between the two groups.</p><p><b>RESULTS</b>Both observation and control group didn't show any general reactions, adverse events following immunization (AEFI) or coincidental cases when observed at 0.5 h, 6 h, 24 h, 48 h, 72 h, 1 week, 2 weeks, 3 weeks, 4 weeks after being vaccinated. The result of serum test showed, the positive rates of child group, early youth group, youth group and control group were respectively 100.00% (141/141), 97.18% (172/177), 98.29% (172/175) and 89.33% (67/75); the GMTs of anti-HBs were respectively 440.28, 875.38, 467.80, 131.06 U/L; the protective rates were respectively 100.00% (141/141), 97.18% (172/177), 97.14% (170/175) and 86.67% (65/75). The positive rate, GMT and protective rate of the experimental group were all higher than that of control group (chi(2)(positive rate) = 12.77, 5.12, 7.99; t(GMT) = 3.89, 4.13, 5.91; chi(2)(protective rate) = 16.81, 8.60, 8.44; P < 0.05).</p><p><b>CONCLUSION</b>This vaccine could be expanded to 5 - 18 year-old population with safety and effectiveness, the positive rate and protective rate of anti-HBs were both higher than that of control group.</p>
Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Male , Hepatitis B Antibodies , Blood , Allergy and Immunology , Hepatitis B Surface Antigens , Blood , Allergy and Immunology , Hepatitis B Vaccines , Allergy and Immunology , Vaccines, Synthetic , Allergy and ImmunologyABSTRACT
<p><b>OBJECTIVE</b>To study the effect of gastrin on the mRNA and protein expression of urokinase-type plasminogen activator (u-PA) in human colon cancer cells and detect the role of p38 MAPK in this process.</p><p><b>METHODS</b>Lipofectin method was used to transfect pCR3. 1/CCK2R vector expressing gastrin receptor into a colon cancer cell line colo320. Gastrin and gastrin antagonist were used to up-regulate and down-regulate the signaling pathway, respectively. Human colon cancer colo320 cells and colo320/ CCK2,R cells were cultured and then stimulated with gastrin for different time; SB203580 was added into culture medium to prevent p38 kinase pathway before incubating with gastrin; Western blot and RT-PCR were used to examine the u-PA expression. Western blot was employed to detect p38 kinase phosphorylation.</p><p><b>RESULTS</b>Gastrin increased evidently the mRNA and protein expressions of u-PA and induced p38 kinase phosphorylation in colo320/CCK,R cells time-dependently. However, the extent of enhancement of u-PA and p38 MAPK expression in colo320 cells was much less than that in colo320/CCK2R cells. The gastrin antagonist L-365, 260 showed an effect of competitive inhibition on gastrin-induced u-PA expression and p38 kinase phosphorylation. The inhibitor SB203580 could sufficiently suppress gastrin-induced p38 kinase phosphorylation and significantly attenuate gastrin-induced u-PA mRNA and protein expressions in colo320/ CCK2 R cells in a dose-dependent manner.</p><p><b>CONCLUSION</b>Gastrin-gastrin receptor signal transduction pathway can obviously induce u-PA expression in human colon cancer cells via activating the phosphorylation of p38 kinase.</p>