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Reduction of mitomycin C resistance in human bladder cancer T24 cells by knocking-down ras oncogene

Cancer Drug Resistance 2018年第1期1卷 59-71页

作者： Osama Sharaf Eldin Abdel-Motaal Fouda Amany R.Youssef Peter Hamilton Perry Maxwell Kate E.Williamson Weston General Hospital Weston-super-Mare BS234TQUK Faculty of Medicine Mansoura UniversityMansoura 35516Egypt Centre for Cancer Research and Cell Biology Queen's UniversityBelfast BT97AEUK

Aim:Mitomycin C(MMC)is a commonly used as intravesical treatment for superficial bladder ***,its role in combination with ras inhibition has not been *** aim of this study was to explore the role of ras in MMC-induced apoptosis in T24 bladder cancer cells and to determine the efficacy of combination therapy in ***:We measured the effects of various doses of MMC on apoptosis induction as well as on ras,ERK and Ki-67 protein expression by T24 cell line using immunocytochemistry,flow cytometry and Western *** also tested the effect of siRNA on ras employed singly or in combination with ***:T24 cells expressed high level of ras *** treatment increased the level of ras and ERK protein expression after 24 h,and decreased these levels after 72 *** siRNA(100 nmol/L)caused massive apoptosis associated with a marked decrease in ras expression in T24 *** combined with low doses of MMC,ras siRNA(50 nmol/L)sensitized T24 cells to apoptosis and decreased their expression of *** effect of combined therapy was higher than that of either compound used *** levels of ERK,a downstream target of ras,declined following combination ***:ras siRNA in combination with low dose MMC is a possible treatment strategy for patients with ras-positive bladder tumors.

关键词： Mitomycin C ras oncogene T24 cells bladder cancer siRNA

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C-Ha-ras oncogene in Oral Leukoplakia Tissues

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Journal of Huazhong University of Science and Technology(Medical Sciences) 1996年第1期16卷 58-60页

作者：程鹏李辉奉杨平谭云 Department of Stomatology Tongji Hospital Tongji Medical University Wuhan

The amplification and the G-T mutation at codon 12 of the C-Ha-ras oncogene in oral leukoplakia tissues were analyzed by using polymerase chain reaction (PCR) and molecular biologic technique. The results showed that these tissues had no amplification of Ha-ras oncogene. Only one case harbored G-T mutation in 11 oral leukoplakias, but this mutation was absent in 10 normal oral mucosal tissues. The possible role and significance of C-Ha-ras oncogene in oral precancerous lesions were also discussed.

关键词： oral leukoplakia ras oncogene mutation amplification

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Alterations of level of total genomic DNA methylation and pattern of c-myc, c-Ha-ras oncogene methylation in human gastric carcinogenesis

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中华医学杂志(英文版) 1996年第10期109卷 791-791页

作者： J Fang S Zhu S Xiao Y Shi S Jiang X Zhou L Qian Shanghai Second Medical University Shanghai Institute of Digestive Disease.

OBJECTIVE To investigate the status of DNA methylation in gastric *** We analysed methylation pattern of c-myc, c-Ha-ras oncogenes by southern blot hybridization. DNA from cancerous, paracancerous and non-cancerous area of surgically resected samples in 21 cases of advanced gastric cancer were digested withMspI/HpaII and hybridized with the two genomic32P labelled probes. In addition, the level of total genomic DNA methylation was measured by incubating DNA with3H-S-Adenosylmethionine (3H-SAM) in the presence of a methylase which methylates all the cytosine residues that are in the double CpG (cytosine-guanine).RESULTS The results indicated that both c-myc and c-Ha-ras oncogene fragments containing CCGG sequence were hypomethylated in DNA samples from cancerous (10/21 and 5/10) and paracancerous (13/21 and 4/10) areas. Moreover, the level of total genomic DNA methylation in cancerous tissue was significantly lower than that in non-cancerous and paracancerous mucosa tissues (Pras oncogenes fragments containing CCGG sequence was abnormal in gastric mucosa tissue from gastric cancerous and paracancerous areas.

关键词： DNA ras oncogene Methylation DNA Methylation oncogenes oncogene myc Methyltransferases Carcinogenesis

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Study on the Association Between Helicobacter Pylori Infection and the Pathogenesis of Gastric Cancer by Using Molecuar Biological Techniques

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Journal of Huazhong University of Science and Technology(Medical Sciences) 1994年第2期14卷 65-70页

作者：于君 1. Department of Gastroenterology Xiehe Hospital Tongji Medical University China

Recent epidemiological observations have indicated that the role of Helicobacter pylori (HP) infection in the pathogenesis of gastric cancer is an important but unresolved issue. We used the polymerase chain reaction, a sensitive and specific assay, to detect the HP infection in gastric biopsy specimens and examined the corrclations between HP infection and point mutation at 12 codon of H-ras oncogeneHras oncogene is higher in the group with HP infection than in those without HP infection. Furthermore, there is strong evidence that HP infection is associated with the increased expression of ras p21 protein , which suggested that HP infection increased the risk of ras oncogene activation. It is also noted that a significant relationship between infection with HP and the increase of DNA content and s% phase cells, indicated that rapid turnover of cells resulting from infection injury increases the risk of DNA damage.

关键词： helicobacter pylori ras oncogene expression of p21 protein DNA ploidy

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Proteomic analysis of hepatic tumor in Hras12V transgenic mice

Proteomic analysis of hepatic tumor in Hras12V transgenic mi...

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2017年第十五届中国北方实验动物科技年会

作者： Zhuona Rong Tingting Fan Huiling Li Juan Li Fujin Wang Jingyu Wang Aiguo Wang Laboratory animal center Dalian Medical University

Male prevalence is an outstanding characteristic of hepatocellular carcinoma（HCC）,and the underlying mechanisms for this have remained largely *** the present study,Hras12 V transgenic mice,in which hepatocyte-specific expression of the ras oncogene induces male-biased hepatic tumorigenesis,were studied,and altered proteins were detected by two-dimensional fluorescence difference gel electrophoresis（2 D-DIGE）.Protein samples from hepatic tumor tissues（T） and peri-tumor tissues（P） of transgenic males and females and the corresponding normal liver tissues（Wt） of non-transgenic males and females were subjected to pairwise comparisons based on proteomic *** 2381 auto-detected protein spots,more than1600 were differentially expressed based on a pairwise comparison（|ratio| ＞= 1.5,p ＜= 0.05）.Of these,180 spots were randomly selected for matrix-assisted laser desorption ionization tandem time-of-flight mass spectrometry（MALDI-TOF/TOF MS） identification;finally,89 distinct proteins were *** these 89 proteins,7 and 50 proteins were further validated by Western blotting and literature investigation,***,compared to Wt,the altered proteins were relatively concentrated in T in transgenic females but in P in transgenic ***,the levels of p-ERK and p-mTOR were significantly higher in the T of females compared to that of *** pathway enrichment assay showed that 5 pathways in males but only 1 in females were significantly altered in terms of the up-regulated proteins in T compared to *** data indicate that female hepatocytes are disturbed by oncogenes with great difficulty,whereas male hepatoctyes readily do *** addition,33 proteins were genderdependently altered in hepatic ***,4%DNA packaging and 4%homeostasis-related functional proteins were found in females but not in males,and more nucleus proteins were found in females（8%） than in males（3%）.In conclusion,the proteomic data and compar

关键词： Hepatic tumor ras oncogene Gender-dependent Proteomics Two-dimensional fluorescence difference gel electrophoresis(2D-DIGE)

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Metabolomic analysis for hepatic tumors of Hras12V transgenic mice

Metabolomic analysis for hepatic tumors of Hras12V transgeni...

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2017年第十五届中国北方实验动物科技年会

作者： Tingting Fan Zhuona Rong Juan Li Fujin Wang Jingyu Wang Aiguo Wang Laboratory animal center Dalian medical University

Activation of the ras/MAPK pathway is prevalently involved in the occurrence and development of hepatocellular carcinoma（HCC）.However,its effects on the deregulated cellular metabolic processes involved in HCC in vivo remain *** the present study,a mouse model of HCC induced by hepatocyte-specific expression of the Hras12 V oncogene was investigated using an integrative analysis of metabolomics and transcriptomics *** with the phenotype of abundant lipid droplets in HCC,the lipid biosynthesis in HCC was significantly enhanced by（1） a sufficient supply of acetyl-CoA from enhanced glycolysis and citrate shuttle activity;（2） a sufficient supply of NADPH from enhanced pentose phosphate pathway（PPP） activity;（3） upregulation of key enzymes associated with lipid biosynthesis;and（4） down-regulation of key enzymes associated with bile acid *** addition,glutathione（GSH） was significantly elevated,which may result from a sufficient supply of 5-oxoproline and L-glutamate as well as an enhanced reduction of the process of GSSG being turned into GSH by *** high level of GSH along with elevated Bcl2 and Ucp2 expression may contribute to a normal level of reactive oxygen species（ROS） in *** conclusion,our results suggest that the lipid metabolism,glycolysis,PPP,tricarboxylic acid（TCA） cycle,citrate shuttle activity,bile acid synthesis,and redox homeostasis in the HCC induced by ras oncogene are significantly perturbed,and these altered metabolic processes may play crucial roles in the carcinogenesis,development and pathological characteristics of HCC.

关键词： ras oncogene Hepatocellular carcinoma Metabolomics Transcriptomics

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