AIM：To study the nuclear microsatellite instability (nMSI) at BAT26 and mitochondral microsalellite instability (mtMSI) in the occurrence and development of hepatocellular carcinoma and the relationship between nMSI ...AIM：To study the nuclear microsatellite instability (nMSI) at BAT26 and mitochondral microsalellite instability (mtMSI) in the occurrence and development of hepatocellular carcinoma and the relationship between nMSI and mtMSI.METHODS: nMSI was observed with PCR and mtMSI with PCR-SSCP in 52 cases of hepatocellular carcinoma.RESULTS:mtMSI was detected in 11 out of the 52 cases of hepatocellular carcinoma (21.2%). Among the 11 cases of hepatocellular carcinoma with mtMSI, 7 occured in one locus and 4 in 2 loci. The frequency of mtMSI in the 52 cases of hepatocellular carcinoma showed no correlation to sex, age,infection of hepatitis B, liver cirrhosis as well as positive AFP of the patients (P>0.05). In addition, nMSI was detected in 3 out of 52 cases of hepatocellular carcinoma (5.8%) and there was no correlation of the incidence of mtMSI to that of nMSI (P>0.05).CONCLUSION:mtMSI may be involved in the coccurrence and development of hepatocellular carcinoma and it is independent of nMSI.展开更多
Unstable repeats are associated with various types of cancer and have been implicated in more than 40 neurode-generative disorders. Trinucleotide repeats are located in non-coding and coding regions of the genome. Stu...Unstable repeats are associated with various types of cancer and have been implicated in more than 40 neurode-generative disorders. Trinucleotide repeats are located in non-coding and coding regions of the genome. Studies of bacteria, yeast, mice and man have helped to unravel some features of the mechanism of trinucleotide expansion. Looped DNA structures comprising trinucleotide repeats are processed during replication and/or repair to generate deletions or expansions. Most in vivo data are consistent with a model in which expansion and deletion occur by different mechanisms. In mammals, microsatellite instability is complex and appears to be influenced by genetic, epigenetic and developmental factors.展开更多
Here, we provide data suggesting that the absence of silencing of the ectopic reprogramming factors used to reprogram somatic cells to induced pluripotent stem cells （iPSCs） may predispose iPSCs to genomic instabili...Here, we provide data suggesting that the absence of silencing of the ectopic reprogramming factors used to reprogram somatic cells to induced pluripotent stem cells （iPSCs） may predispose iPSCs to genomic instability. We encourage stem cell scientists to undertake an extensive characterization and standardization of much larger cohorts of iPSC lines in order to set up rigorous criteria to define safe and stable bonafide iPSCs.展开更多
There is an increasing understanding of the roles that microsatellite instability （MSI） plays in Lynch syndrome （by mutations） and sporadic （by mainly epigenetic changes） gastrointestinal （GI） and other cancer...There is an increasing understanding of the roles that microsatellite instability （MSI） plays in Lynch syndrome （by mutations） and sporadic （by mainly epigenetic changes） gastrointestinal （GI） and other cancers. Defi- cient DNA mismatch repair （MMR） results in the strong mutator phenotype known as MSI, which is the hall- mark of cancers arising within Lynch syndrome. MSI is characterized by length alterations within simple repeated sequences called microsatellites. Lynch syn- drome occurs primarily because of germline mutations in one of the MMR genes, mainly MLH1 or MSH2, less frequently MSH6, and rarely PMS2. MSI is also observed in about 15% of sporadic colorectal, gastric, and en-dometrial cancers and in lower frequencies in a minor- ity of other cancers where it is often associated with the hypermethylation of the IVlLH1 gene. miRNAs are small noncoding RNAs that regulate gene expression at the posttranscriptional level and are critical in many biological processes and cellular pathways. There is accumulating evidence to support the notion that the interrelationship between MSI and miRNA plays a key role in the pathogenesis of GI cancer. As a possible new mechanism underlying MSI, overexpression of m/R-IEE has been shown to downregulate expression of MLH1, IVlSH2, and MSH6. Thus, a subset of MSI-positive （MSI＋） cancers without known MMR defects may result from m/R-1E5 overexpression. Target genes of frameshift mutation for MSI are involved in various cellular func- tions, such as DNA repair, cell signaling, and apoptosis. A novel class of target genes that included not only epi- genetic modifier genes, such as HDAC2, but also miRNA processing machinery genes, including TARBP2 and XPO5, were found to be mutated in MSI＋ GI cancers. Thus, a subset of MSI＋ colorectal cancers （CRCs） has been proposed to exhibit a mutated miRNA machinery phenotype. Genetic, epigenetic, and transcriptomic dif- ferences exist between MSI＋ and MSI- cancers. Mo- lecular signatures of miRNA expression apparently have the potential to distinguish between MSI＋ and MSI- CRCs. In this review, we summarize recent advances in the MSI pathogenesis of GI cancer, with the focus on its relationship with miRNA as well as on the potential to use MSI and related alterations as biomarkers and novel therapeutic targets.展开更多
Objective: In order to elucidate the molecular mechanisms that might be responsible for hepatocarcinogenesis, we examined microsatellite instability (MSI), mismatch repair gene hMLH1 mutation and methylation in hepato...Objective: In order to elucidate the molecular mechanisms that might be responsible for hepatocarcinogenesis, we examined microsatellite instability (MSI), mismatch repair gene hMLH1 mutation and methylation in hepatocellular carcinoma. Methods: Fifty-two cases of surgically resected sporadic hepatocellular carcinoma (HCC) were studied. hMLH1 mutation was examined by two-dimensional electrophoresis and DNA sequencing; hMLH1 methylation was determined by methylation-specific PCR(MSP); and MSI at BAT26 was analyzed by PCR-based methods. Results: MSI at BAT26 was found in 3 of 52 cases (5.8%) of the tumors analyzed. No hMLH1 mutation or hypermethylation was found in these 52 cancerous tissues. No correlation existed between MSI and clinico-pathological characteristics of the patients. Conclusion: Our results suggest that MSI at BAT26 is rarely associated with carcinogenesis of chinese HCC. The genesis of sporadic HCC may occur in an alternative pathway that is probably different from MSI pathway.展开更多
Accidentally or occupationally exposures to ionizing radiation generally involving the partial-body exposures and this may pose significant health hazards that are indicated by chromosome aberration （CA） induction. ...Accidentally or occupationally exposures to ionizing radiation generally involving the partial-body exposures and this may pose significant health hazards that are indicated by chromosome aberration （CA） induction. In this experiment, the quantification of the frequencies of CA was carried out based on cytogenetic analyses of peripheral blood samples obtained from 4 healthy volunteers as a result of simulation of partial-body exposures. The percentages of mixtures of blood samples irradiated in vitro with 2 Gy of gamma rays were 10, 25, 50, 75 and 100.0%. Lymphocytes were cultured and first-division metaphase cells were collected after culture times of 48 h and then harvested with standard procedures. The results showed that frequencies of unstable CA were depended on the percentage/portion of irradiated blood. All frequencies of observed CA was lower than that of calculated from 100% exposed blood, except in one case, indicating a phenomena of＂dilution＂ of unirradiated into irradiated lymphocytes though there could be a bystander effects taken place. The increasing in frequency for 25-100% portions was also comparable with other similar experiments. The quantification of CAs in lymphocytes is an important methodology of dose assessment for partial-body exposure to ionizing radiation, however, the scenario of exposure should be determined.展开更多
We present the particle-in-cell(PIC) simulation results of the interaction of a high-energy lepton plasma flow with background electron-proton plasma and focus on the acceleration processes of the protons. It is found...We present the particle-in-cell(PIC) simulation results of the interaction of a high-energy lepton plasma flow with background electron-proton plasma and focus on the acceleration processes of the protons. It is found that the acceleration follows a two-stage process. In the first stage, protons are significantly accelerated transversely(perpendicular to the lepton flow) by the turbulent magnetic field "islands" generated via the strong Weibel-type instabilities. The accelerated protons shows a perfect inverse-power energy spectrum. As the interaction continues, a shockwave structure forms and the protons in front of the shockwave are reflected at twice of the shock speed, resulting in a quasi-monoenergetic peak located near 200 Me V under the simulation parameters. The presented scenario of ion acceleration may be relevant to cosmic-ray generation in some astrophysical environments.展开更多
基金Supported by the National-Natural Science Foundation of China,No.30070043
文摘AIM：To study the nuclear microsatellite instability (nMSI) at BAT26 and mitochondral microsalellite instability (mtMSI) in the occurrence and development of hepatocellular carcinoma and the relationship between nMSI and mtMSI.METHODS: nMSI was observed with PCR and mtMSI with PCR-SSCP in 52 cases of hepatocellular carcinoma.RESULTS:mtMSI was detected in 11 out of the 52 cases of hepatocellular carcinoma (21.2%). Among the 11 cases of hepatocellular carcinoma with mtMSI, 7 occured in one locus and 4 in 2 loci. The frequency of mtMSI in the 52 cases of hepatocellular carcinoma showed no correlation to sex, age,infection of hepatitis B, liver cirrhosis as well as positive AFP of the patients (P>0.05). In addition, nMSI was detected in 3 out of 52 cases of hepatocellular carcinoma (5.8%) and there was no correlation of the incidence of mtMSI to that of nMSI (P>0.05).CONCLUSION:mtMSI may be involved in the coccurrence and development of hepatocellular carcinoma and it is independent of nMSI.
文摘Unstable repeats are associated with various types of cancer and have been implicated in more than 40 neurode-generative disorders. Trinucleotide repeats are located in non-coding and coding regions of the genome. Studies of bacteria, yeast, mice and man have helped to unravel some features of the mechanism of trinucleotide expansion. Looped DNA structures comprising trinucleotide repeats are processed during replication and/or repair to generate deletions or expansions. Most in vivo data are consistent with a model in which expansion and deletion occur by different mechanisms. In mammals, microsatellite instability is complex and appears to be influenced by genetic, epigenetic and developmental factors.
文摘Here, we provide data suggesting that the absence of silencing of the ectopic reprogramming factors used to reprogram somatic cells to induced pluripotent stem cells （iPSCs） may predispose iPSCs to genomic instability. We encourage stem cell scientists to undertake an extensive characterization and standardization of much larger cohorts of iPSC lines in order to set up rigorous criteria to define safe and stable bonafide iPSCs.
基金Supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan
文摘There is an increasing understanding of the roles that microsatellite instability （MSI） plays in Lynch syndrome （by mutations） and sporadic （by mainly epigenetic changes） gastrointestinal （GI） and other cancers. Defi- cient DNA mismatch repair （MMR） results in the strong mutator phenotype known as MSI, which is the hall- mark of cancers arising within Lynch syndrome. MSI is characterized by length alterations within simple repeated sequences called microsatellites. Lynch syn- drome occurs primarily because of germline mutations in one of the MMR genes, mainly MLH1 or MSH2, less frequently MSH6, and rarely PMS2. MSI is also observed in about 15% of sporadic colorectal, gastric, and en-dometrial cancers and in lower frequencies in a minor- ity of other cancers where it is often associated with the hypermethylation of the IVlLH1 gene. miRNAs are small noncoding RNAs that regulate gene expression at the posttranscriptional level and are critical in many biological processes and cellular pathways. There is accumulating evidence to support the notion that the interrelationship between MSI and miRNA plays a key role in the pathogenesis of GI cancer. As a possible new mechanism underlying MSI, overexpression of m/R-IEE has been shown to downregulate expression of MLH1, IVlSH2, and MSH6. Thus, a subset of MSI-positive （MSI＋） cancers without known MMR defects may result from m/R-1E5 overexpression. Target genes of frameshift mutation for MSI are involved in various cellular func- tions, such as DNA repair, cell signaling, and apoptosis. A novel class of target genes that included not only epi- genetic modifier genes, such as HDAC2, but also miRNA processing machinery genes, including TARBP2 and XPO5, were found to be mutated in MSI＋ GI cancers. Thus, a subset of MSI＋ colorectal cancers （CRCs） has been proposed to exhibit a mutated miRNA machinery phenotype. Genetic, epigenetic, and transcriptomic dif- ferences exist between MSI＋ and MSI- cancers. Mo- lecular signatures of miRNA expression apparently have the potential to distinguish between MSI＋ and MSI- CRCs. In this review, we summarize recent advances in the MSI pathogenesis of GI cancer, with the focus on its relationship with miRNA as well as on the potential to use MSI and related alterations as biomarkers and novel therapeutic targets.
文摘Objective: In order to elucidate the molecular mechanisms that might be responsible for hepatocarcinogenesis, we examined microsatellite instability (MSI), mismatch repair gene hMLH1 mutation and methylation in hepatocellular carcinoma. Methods: Fifty-two cases of surgically resected sporadic hepatocellular carcinoma (HCC) were studied. hMLH1 mutation was examined by two-dimensional electrophoresis and DNA sequencing; hMLH1 methylation was determined by methylation-specific PCR(MSP); and MSI at BAT26 was analyzed by PCR-based methods. Results: MSI at BAT26 was found in 3 of 52 cases (5.8%) of the tumors analyzed. No hMLH1 mutation or hypermethylation was found in these 52 cancerous tissues. No correlation existed between MSI and clinico-pathological characteristics of the patients. Conclusion: Our results suggest that MSI at BAT26 is rarely associated with carcinogenesis of chinese HCC. The genesis of sporadic HCC may occur in an alternative pathway that is probably different from MSI pathway.
文摘Accidentally or occupationally exposures to ionizing radiation generally involving the partial-body exposures and this may pose significant health hazards that are indicated by chromosome aberration （CA） induction. In this experiment, the quantification of the frequencies of CA was carried out based on cytogenetic analyses of peripheral blood samples obtained from 4 healthy volunteers as a result of simulation of partial-body exposures. The percentages of mixtures of blood samples irradiated in vitro with 2 Gy of gamma rays were 10, 25, 50, 75 and 100.0%. Lymphocytes were cultured and first-division metaphase cells were collected after culture times of 48 h and then harvested with standard procedures. The results showed that frequencies of unstable CA were depended on the percentage/portion of irradiated blood. All frequencies of observed CA was lower than that of calculated from 100% exposed blood, except in one case, indicating a phenomena of＂dilution＂ of unirradiated into irradiated lymphocytes though there could be a bystander effects taken place. The increasing in frequency for 25-100% portions was also comparable with other similar experiments. The quantification of CAs in lymphocytes is an important methodology of dose assessment for partial-body exposure to ionizing radiation, however, the scenario of exposure should be determined.
基金supported by the National Basic Research Program of China(Grant No.2013CBA01500)the National Natural Science Foundation of China(Grant Nos.11421064,11220101002,11129503 and 11135012)
文摘We present the particle-in-cell(PIC) simulation results of the interaction of a high-energy lepton plasma flow with background electron-proton plasma and focus on the acceleration processes of the protons. It is found that the acceleration follows a two-stage process. In the first stage, protons are significantly accelerated transversely(perpendicular to the lepton flow) by the turbulent magnetic field "islands" generated via the strong Weibel-type instabilities. The accelerated protons shows a perfect inverse-power energy spectrum. As the interaction continues, a shockwave structure forms and the protons in front of the shockwave are reflected at twice of the shock speed, resulting in a quasi-monoenergetic peak located near 200 Me V under the simulation parameters. The presented scenario of ion acceleration may be relevant to cosmic-ray generation in some astrophysical environments.
