Brinjal or eggplant (Solanum melongena L.) is severely affected by bacterial wilt caused by Ralstonia solanecearum in Andaman and Nicobar Islands. Resistant varieties are most suitable option to reduce crop losses fro...Brinjal or eggplant (Solanum melongena L.) is severely affected by bacterial wilt caused by Ralstonia solanecearum in Andaman and Nicobar Islands. Resistant varieties are most suitable option to reduce crop losses from bacterial wilt but knowledge of resistance mechanism and its inheritance is important to develop resistant varieties. Further, majority of germplasm from mainland India showed susceptible reaction under Andaman conditions. Thus, the present study was done during 2010-2012 to understand the genetic behaviour of bacterial wilt resistance in brinjal “CARI-B-1” (R) × “Pusa Purple Long” (S) in hot humid tropical climate of Andaman Islands. For this, the population from single F<sub>1</sub> fruit was advanced to F<sub>2</sub> and F<sub>3</sub> and recorded the reaction of segregating population in the sick plots. The results revealed that there is preponderance of recessive gene family wherein more than one gene acts in additive mode. Another cross between S. torvum (R) × Diglipur local collection (S) also showed the recessive gene action for resistance as observed in F<sub>2</sub> generation. Besides, the study also advocated that mechanisms of resistance, escape with early resistance and progressive escape have been found to be operating in individuals of segregating population.展开更多
Objective: To determine the relationship between nucleosome positions and formation of differential methylation of the reported region A, B, C, and D within the MLH1 CpG island. Methods: Methylation of the MLH1 prom...Objective: To determine the relationship between nucleosome positions and formation of differential methylation of the reported region A, B, C, and D within the MLH1 CpG island. Methods: Methylation of the MLH1 promoter was analyzed by combined of bisulfite restriction assay. Chromatin of RKO and MGC803 cells were extracted and digested by MNase. Mononucleosomal DNA fragment was isolated and used as templates for detection of nucleosomal distribution by a battery of quantitative PCRs covering the full MLH1 promoter region. Results: The MLH1 was methylated in RKO and unmethylated in MGC803. At the region B, where methylation of CpG sites did not correlated with transcription of this gene well, qPCR product of the M-3 (-599nt ~ -475nt) fragment was amplified in both RKO and MGC803 cells. However, at the region C and D within the core promoter, where methylation of CpG sites correlated with loss of MLH1 transcription well, the M-7 (-257nt ~ -153nt) and M-8 (-189nt ~ -71nt) fragments were amplified remarkably only in RKO cells. Conclusion: Nucleosome may be the basic unit for both CpG methylation and methylation-related regulation of gene transcription. Methylation status of CpG sites within the same nucleosome may be homogeneous; between different nucleosomes, homogeneous or heterogeneous.展开更多
AIM:To evaluate the clinical significance of CpG island methylator phenotype(CIMP) in plasma and its asso-ciation with hepatocellular carcinoma(HCC) progress.METHODS:CIMP status of 108 HCC patients wasanalyzed using a...AIM:To evaluate the clinical significance of CpG island methylator phenotype(CIMP) in plasma and its asso-ciation with hepatocellular carcinoma(HCC) progress.METHODS:CIMP status of 108 HCC patients wasanalyzed using a methylation marker panel in tumortissues and plasma with methylation-specific poly-merase chain reaction. Fifteen samples of non-neo-plastic liver tissues and 60 of plasma from healthy persons were examined simultaneously. Examinedgenes included APC,WIF-1,RUNX-3,DLC-1,SFRP-1,DKK and E-cad .RESULTS:The frequencies of high-level methylation in HCC tissue and plasma were at least 15% forthe seven genes:APC,48/108,44.44% in tissue and26/108,24.07% in plasma;WIF-1,53/108,49.07% intissue and 35/108,32.41% in plasma;RUNX-3,52/108,48.14% in tissue and 42/108,38.89% in plasma;DLC-1,38/108,35.18% in tissue and 23/108,21.30%in plasma;SFRP-1,40/108,37.04% in tissue and31/108,28.7% in plasma;DKK,39/108,36.1% in tis-sue and 25/108,23.14% in plasma;and E-cad,37/108,34.3% in tissue and 18/108,16.67% in plasma. CIMP+(≥ 3 methylated genes) was detected in 68(60.2%) tumor tissue samples and 62(57.4%) plasma samples.CIMP was not detected in non-neoplastic liver tissuesor plasma of healthy persons. CIMP status in tumortissues differed significantly in gender,hepatitis Bsurface antigen,alpha-fetoprotein,and tumor-node-metastasis stage(P < 0.05) . Similar results were obtained with plasma samples(P < 0.05) . There was nodifference in CIMP status in age,presence of hepatitis C virus antibody,cirrhosis,number of nodes,numberof tumors,tumor size,or Edmondson-Steiner stage. Aone-year follow-up found that the metastatic rate and recurrence rate in the CIMP+ group were significantly higher than in the CIMP- group as assessed with plasma samples(P < 0.05) .CONCLUSION:Plasma DNA can be a reliable samplesource for CIMP analysis. CIMP in plasma may serve asa molecular marker of late-stage and poor-prognosis HCC.展开更多
AIM:To investigate the association between the CpG island methylator phenotype(CIMP) and serum Helicobacter pylori(H.pylori) levels for clinical prediction of gastric cancer(GC) progression.METHODS:We analyzed the ser...AIM:To investigate the association between the CpG island methylator phenotype(CIMP) and serum Helicobacter pylori(H.pylori) levels for clinical prediction of gastric cancer(GC) progression.METHODS:We analyzed the serum CIMP status of 75 patients with GC using a methylation marker panel and a methylation-specific polymerase chain reaction.Serum samples from 40 healthy persons were examined at the same time.The genes examined were APC,WIF-1,RUNX-3,DLC-1,SFRP-1,DKK and E-cad.H.pylori infection in serum was assayed with an anti-H.pylori immunoglobulin G antibody test and a rapid urease test.RESULTS:The frequencies of high-level methylation in GC tissues for the seven genes were:48% for APC,57.33% for WIF-1,56% for RUNX-3,50.67% for DLC-1,52% for SFRP-1,54.67% for DKK,and 48% for E-cad.The frequencies in GC serum were 30.67% for APC,34.67% for WIF-1,37.33% for RUNX-3,29.33% for DLC-1,33.33% for SFRP-1,32% for DKK,and 26.67% for E-cad.CIMP+(defined as ≥ 3 methylated genes) was associated with 47(62.67%) GC tissue samples and 44(58.67%) GC serum samples.CIMP+ was not associated with non-neoplastic mucosal tissues or the serum of healthy persons.Of the 75 GC cases,51(68%) were H.pylori +,and 24(32%) were H.pylori-.Of the 51 H.pylori + cases,36 were CIMP+ and 15 were CIMP-.In contrast,for the 24 H.pylori-cases,11 were CIMP+,and 13 were CIMP-.The difference was significant between the H.pylori + and H.pylori-groups(χ 2 = 4.27,P < 0.05).Of the 51 H.pylori + GC patients,34 were CIMP+ and 17 were CIMP-,while among the 24 H.pylori-GC cases,10 were CIMP+ and 14 were CIMP-.The difference was significant between the H.pylori+ and H.pylori-groups(χ 2 = 4.21,P < 0.05).A 2-year follow-up showed significant difference in the rates of metastasis and recurrence between H.pylori +/CIMP+ cases and the H.pylori +/CIMP-cases or CIMP-cases associated with H.pylori assayed in serum(P < 0.05).However,there were no significant differences in survival rates between the two groups.CONCLUSION:H.pylori +/CIMP+ cases are associated with higher rates of metastasis and recurrence than H.pylori +/CIMP-cases.Serum may be useful for examining CIMP status.展开更多
AIM To identify whether Cp G island methylator phenotype(CIMP) is predictive of response to neoadjuvant chemoradiotherapy(NACRT) and outcomes in rectal cancer.METHODS Patients undergoing NACRT and surgical resection f...AIM To identify whether Cp G island methylator phenotype(CIMP) is predictive of response to neoadjuvant chemoradiotherapy(NACRT) and outcomes in rectal cancer.METHODS Patients undergoing NACRT and surgical resection for rectal cancer in a tertiary referral centre between 2002-2011 were identified. Pre-treatment tumour biopsies were analysed for CIMP status(high, intermediate or low) using methylation specific PCR. KRAS and BRAF status were also determined using pyrosequencing analysis. Clinical information was extracted from case records and cancer services databases. Response to radiotherapy was measured by tumour regression scores determined uponhistological examination of the resected specimen. The relationship between these molecular features, response to NACRT and oncological outcomes were analysed.RESULTS There were 160 patients analysed with a median followup time of 46.4 mo. Twenty-one(13%) patients demonstrated high levels of CIMP methylation(CIMP-H) and this was significantly associated with increased risk of extramural vascular invasion(EMVI) compared with CIMP-L [8/21(38%) vs 15/99(15%), P = 0.028]. CIMP status was not related to tumour regression after radiotherapy or survival, however EMVI was significantly associated with adverse survival(P < 0.001). Intermediate CIMP status was significantly associated with KRAS mutation(P = 0.01). There were 14(9%) patients with a pathological complete response(pC R) compared to 116(73%) patients having no or minimal regression after neoadjuvant chemoradiotherapy. Those patients with pC R had median survival of 106 mo compared to 65.8 mo with minimal regression, although this was not statistically significant(P = 0.26). Binary logistic regression analysis of the relationship between EMVI and other prognostic features revealed, EMVI positivity was associated with poor overall survival, advanced "T" stage and CIMP-H but not nodal status, age, sex, KRAS mutation status and presence of local or systemic recurrence.CONCLUSION We report a novel association of pre-treatment characterisation of CIMP-H with EMVI status which has prognostic implications and is not readily detectable on pre-treatment histological examination.展开更多
AIM: To investigate the functions of promoter hypermethylation of O6-methylguanine-DNA methyltransferase (MGMT) gene in colorectal tumorigenesis and progression.METHODS: The promoter hypermethylation of MGMT gene was ...AIM: To investigate the functions of promoter hypermethylation of O6-methylguanine-DNA methyltransferase (MGMT) gene in colorectal tumorigenesis and progression.METHODS: The promoter hypermethylation of MGMT gene was detected in 27 sporadic colorectal adenomas,62 sporadic colorectal carcinomas and 20 normal colorectal mucosa tissues by methylation-specific PCR. At the same time, the expression of MGMT protein was carried out in the same samples using immunohistochemistry. Mutantallele-specific amplification was used to detect K-rasG to A point mutation in codon 12.RESULTS: None of the normal colorectal mucosa tissues showed methylated bands. Promoter hypermethylation was detected in 40.7% (11 of 27) of adenomas and 43.5% (27 of 62) of carcinomas. MGMT proteins were expressed in nucleus and cytoplasm of normal colorectal mucosa tissues. Loss of MGMT expression was found in 22.2% (6 of 27) of adenomas and 45.2% (28 of 62) of carcinomas. The difference between them was significant (P = 0.041). In the 6 adenomas and 28 carcinomas losing MGMT expression, 5 and 24 cases presented methylation,respectively (P = 0.027, P<0.001). Thirteen of the 19 colorectal tumors with K-rasG to A point mutation in codon 12 had methylated MGMT(P = 0.011). The frequencies of K-rasG to A point mutation were 35.3% (12 of 34) and 12.7% (7 of 55) in tumors losing MGMT expression and with normal expression, respectively.CONCLUSION: Promoter hypermethylation and loss of expression of MGMT gene were common events in colorectal tumorigenesis, and loss of expression of MGMT occurs more frequently in carcinomas than in adenomas in sporadic patients. Hypermethylation of the CpG island of MGMT gene was associated with loss of MGMT expression and K-ras G to A point mutation in colorectal tumor. The frequency of K-ras G to A point mutation was increased in tumors losing MGMT expression. It suggests that epigenetic inactivation of MGMT plays an important role in colorectal neoplasia.展开更多
Over the last two decades, cancer-related alterations in DNA methylation that regulate transcription have been reported for a variety of tumors of the gastrointestinal tract. Due to its relevance for translational res...Over the last two decades, cancer-related alterations in DNA methylation that regulate transcription have been reported for a variety of tumors of the gastrointestinal tract. Due to its relevance for translational research, great emphasis has been placed on the analysis and molecular characterization of the CpG island methylator phenotype(CIMP), defined as widespread hypermethylation of CpG islands in clinically distinct subsets of cancer patients. Here, we present an overview of previous work in this field and also explore some open questions using crossplatform data for esophageal, gastric, and colorectal adenocarcinomas from The Cancer Genome Atlas. We provide a data-driven, pan-gastrointestinal stratification of individual samples based on CIMP status and we investigate correlations with oncogenic alterations, including somatic mutations and epigenetic silencing of tumor suppressor genes. Besides known events in CIMP such as BRAF V600 E mutation, CDKN2 A silencing or MLH1 inactivation, we discuss the potential role of emerging actors such as Wnt pathway deregulation through truncating mutations in RNF43 and epigenetic silencing of WIF1. Our results highlight the existence of molecular similarities that are superimposed over a larger backbone of tissue-specific features and can be exploited to reduce heterogeneity of response in clinical trials.展开更多
A method to improve the low-velocity impact performance of composite laminate is proposed, and a multi-island genetic algorithm is used for the optimization of composite laminate stacking sequence under low-velocity i...A method to improve the low-velocity impact performance of composite laminate is proposed, and a multi-island genetic algorithm is used for the optimization of composite laminate stacking sequence under low-velocity impact loads based on a 2D dynamic impact finite element analysis. Low-velocity impact tests and compression-after impact(CAI) tests have been conducted to verify the effectiveness of optimization method. Experimental results show that the impact damage areas of the optimized laminate have been reduced by 42.1% compared to the baseline specimen, and the residual compression strength has been increased by 10.79%, from baseline specimen 156.97 MPa to optimized 173.91 MPa. The tests result shows that optimization method can effectively enhance the impact performances of the laminate.展开更多
Random amplified polymorphic DNA (RAPD) markers were used to analyze genetic variation of Podocarpus imbricatus in Hainan Island and Mainland of China. Two populations of Dacrydium pierrei were used as comparison mate...Random amplified polymorphic DNA (RAPD) markers were used to analyze genetic variation of Podocarpus imbricatus in Hainan Island and Mainland of China. Two populations of Dacrydium pierrei were used as comparison materials. Both Podocarpus imbricatus and Dacrydium pierrei showed a low level of genetic diversity. However, Podocarpus imbricatus showed higher genetic diversity and higher population differentiation than Dacrydium pierrei. The geographic range may affect the genetic diversity of Podocarpus imbricatus and Dacrydium pierrei significantly. The UPGMA cluster tree showed that populations of Podocarpus imbricatus in Hainan Island and Guangxi Zhuang Autonomous Region were closer than those in Yunnan Province, indicating possible gene flow between Hainan Island and Guangxi Zhuang Autonomous Region. The young geological history of Hainan Island and the three times of unification and separation between Hainan Island and the Mainland may give the two species more possibilities of gene flow.展开更多
文摘Brinjal or eggplant (Solanum melongena L.) is severely affected by bacterial wilt caused by Ralstonia solanecearum in Andaman and Nicobar Islands. Resistant varieties are most suitable option to reduce crop losses from bacterial wilt but knowledge of resistance mechanism and its inheritance is important to develop resistant varieties. Further, majority of germplasm from mainland India showed susceptible reaction under Andaman conditions. Thus, the present study was done during 2010-2012 to understand the genetic behaviour of bacterial wilt resistance in brinjal “CARI-B-1” (R) × “Pusa Purple Long” (S) in hot humid tropical climate of Andaman Islands. For this, the population from single F<sub>1</sub> fruit was advanced to F<sub>2</sub> and F<sub>3</sub> and recorded the reaction of segregating population in the sick plots. The results revealed that there is preponderance of recessive gene family wherein more than one gene acts in additive mode. Another cross between S. torvum (R) × Diglipur local collection (S) also showed the recessive gene action for resistance as observed in F<sub>2</sub> generation. Besides, the study also advocated that mechanisms of resistance, escape with early resistance and progressive escape have been found to be operating in individuals of segregating population.
基金supported by the National Natural Science Foundation of China(No.30571056)the National"973"Basic Research Program of China(No.2005CB522403).
文摘Objective: To determine the relationship between nucleosome positions and formation of differential methylation of the reported region A, B, C, and D within the MLH1 CpG island. Methods: Methylation of the MLH1 promoter was analyzed by combined of bisulfite restriction assay. Chromatin of RKO and MGC803 cells were extracted and digested by MNase. Mononucleosomal DNA fragment was isolated and used as templates for detection of nucleosomal distribution by a battery of quantitative PCRs covering the full MLH1 promoter region. Results: The MLH1 was methylated in RKO and unmethylated in MGC803. At the region B, where methylation of CpG sites did not correlated with transcription of this gene well, qPCR product of the M-3 (-599nt ~ -475nt) fragment was amplified in both RKO and MGC803 cells. However, at the region C and D within the core promoter, where methylation of CpG sites correlated with loss of MLH1 transcription well, the M-7 (-257nt ~ -153nt) and M-8 (-189nt ~ -71nt) fragments were amplified remarkably only in RKO cells. Conclusion: Nucleosome may be the basic unit for both CpG methylation and methylation-related regulation of gene transcription. Methylation status of CpG sites within the same nucleosome may be homogeneous; between different nucleosomes, homogeneous or heterogeneous.
基金Supported by The Department of Health of Jiangsu Province,China,No.H200957
文摘AIM:To evaluate the clinical significance of CpG island methylator phenotype(CIMP) in plasma and its asso-ciation with hepatocellular carcinoma(HCC) progress.METHODS:CIMP status of 108 HCC patients wasanalyzed using a methylation marker panel in tumortissues and plasma with methylation-specific poly-merase chain reaction. Fifteen samples of non-neo-plastic liver tissues and 60 of plasma from healthy persons were examined simultaneously. Examinedgenes included APC,WIF-1,RUNX-3,DLC-1,SFRP-1,DKK and E-cad .RESULTS:The frequencies of high-level methylation in HCC tissue and plasma were at least 15% forthe seven genes:APC,48/108,44.44% in tissue and26/108,24.07% in plasma;WIF-1,53/108,49.07% intissue and 35/108,32.41% in plasma;RUNX-3,52/108,48.14% in tissue and 42/108,38.89% in plasma;DLC-1,38/108,35.18% in tissue and 23/108,21.30%in plasma;SFRP-1,40/108,37.04% in tissue and31/108,28.7% in plasma;DKK,39/108,36.1% in tis-sue and 25/108,23.14% in plasma;and E-cad,37/108,34.3% in tissue and 18/108,16.67% in plasma. CIMP+(≥ 3 methylated genes) was detected in 68(60.2%) tumor tissue samples and 62(57.4%) plasma samples.CIMP was not detected in non-neoplastic liver tissuesor plasma of healthy persons. CIMP status in tumortissues differed significantly in gender,hepatitis Bsurface antigen,alpha-fetoprotein,and tumor-node-metastasis stage(P < 0.05) . Similar results were obtained with plasma samples(P < 0.05) . There was nodifference in CIMP status in age,presence of hepatitis C virus antibody,cirrhosis,number of nodes,numberof tumors,tumor size,or Edmondson-Steiner stage. Aone-year follow-up found that the metastatic rate and recurrence rate in the CIMP+ group were significantly higher than in the CIMP- group as assessed with plasma samples(P < 0.05) .CONCLUSION:Plasma DNA can be a reliable samplesource for CIMP analysis. CIMP in plasma may serve asa molecular marker of late-stage and poor-prognosis HCC.
基金Supported by Department of Health of Jiangsu Province o China,No.H200957
文摘AIM:To investigate the association between the CpG island methylator phenotype(CIMP) and serum Helicobacter pylori(H.pylori) levels for clinical prediction of gastric cancer(GC) progression.METHODS:We analyzed the serum CIMP status of 75 patients with GC using a methylation marker panel and a methylation-specific polymerase chain reaction.Serum samples from 40 healthy persons were examined at the same time.The genes examined were APC,WIF-1,RUNX-3,DLC-1,SFRP-1,DKK and E-cad.H.pylori infection in serum was assayed with an anti-H.pylori immunoglobulin G antibody test and a rapid urease test.RESULTS:The frequencies of high-level methylation in GC tissues for the seven genes were:48% for APC,57.33% for WIF-1,56% for RUNX-3,50.67% for DLC-1,52% for SFRP-1,54.67% for DKK,and 48% for E-cad.The frequencies in GC serum were 30.67% for APC,34.67% for WIF-1,37.33% for RUNX-3,29.33% for DLC-1,33.33% for SFRP-1,32% for DKK,and 26.67% for E-cad.CIMP+(defined as ≥ 3 methylated genes) was associated with 47(62.67%) GC tissue samples and 44(58.67%) GC serum samples.CIMP+ was not associated with non-neoplastic mucosal tissues or the serum of healthy persons.Of the 75 GC cases,51(68%) were H.pylori +,and 24(32%) were H.pylori-.Of the 51 H.pylori + cases,36 were CIMP+ and 15 were CIMP-.In contrast,for the 24 H.pylori-cases,11 were CIMP+,and 13 were CIMP-.The difference was significant between the H.pylori + and H.pylori-groups(χ 2 = 4.27,P < 0.05).Of the 51 H.pylori + GC patients,34 were CIMP+ and 17 were CIMP-,while among the 24 H.pylori-GC cases,10 were CIMP+ and 14 were CIMP-.The difference was significant between the H.pylori+ and H.pylori-groups(χ 2 = 4.21,P < 0.05).A 2-year follow-up showed significant difference in the rates of metastasis and recurrence between H.pylori +/CIMP+ cases and the H.pylori +/CIMP-cases or CIMP-cases associated with H.pylori assayed in serum(P < 0.05).However,there were no significant differences in survival rates between the two groups.CONCLUSION:H.pylori +/CIMP+ cases are associated with higher rates of metastasis and recurrence than H.pylori +/CIMP-cases.Serum may be useful for examining CIMP status.
文摘AIM To identify whether Cp G island methylator phenotype(CIMP) is predictive of response to neoadjuvant chemoradiotherapy(NACRT) and outcomes in rectal cancer.METHODS Patients undergoing NACRT and surgical resection for rectal cancer in a tertiary referral centre between 2002-2011 were identified. Pre-treatment tumour biopsies were analysed for CIMP status(high, intermediate or low) using methylation specific PCR. KRAS and BRAF status were also determined using pyrosequencing analysis. Clinical information was extracted from case records and cancer services databases. Response to radiotherapy was measured by tumour regression scores determined uponhistological examination of the resected specimen. The relationship between these molecular features, response to NACRT and oncological outcomes were analysed.RESULTS There were 160 patients analysed with a median followup time of 46.4 mo. Twenty-one(13%) patients demonstrated high levels of CIMP methylation(CIMP-H) and this was significantly associated with increased risk of extramural vascular invasion(EMVI) compared with CIMP-L [8/21(38%) vs 15/99(15%), P = 0.028]. CIMP status was not related to tumour regression after radiotherapy or survival, however EMVI was significantly associated with adverse survival(P < 0.001). Intermediate CIMP status was significantly associated with KRAS mutation(P = 0.01). There were 14(9%) patients with a pathological complete response(pC R) compared to 116(73%) patients having no or minimal regression after neoadjuvant chemoradiotherapy. Those patients with pC R had median survival of 106 mo compared to 65.8 mo with minimal regression, although this was not statistically significant(P = 0.26). Binary logistic regression analysis of the relationship between EMVI and other prognostic features revealed, EMVI positivity was associated with poor overall survival, advanced "T" stage and CIMP-H but not nodal status, age, sex, KRAS mutation status and presence of local or systemic recurrence.CONCLUSION We report a novel association of pre-treatment characterisation of CIMP-H with EMVI status which has prognostic implications and is not readily detectable on pre-treatment histological examination.
基金Supported by the Key Technologies R&D Program of Hubei Province, No. 2002AA301C84
文摘AIM: To investigate the functions of promoter hypermethylation of O6-methylguanine-DNA methyltransferase (MGMT) gene in colorectal tumorigenesis and progression.METHODS: The promoter hypermethylation of MGMT gene was detected in 27 sporadic colorectal adenomas,62 sporadic colorectal carcinomas and 20 normal colorectal mucosa tissues by methylation-specific PCR. At the same time, the expression of MGMT protein was carried out in the same samples using immunohistochemistry. Mutantallele-specific amplification was used to detect K-rasG to A point mutation in codon 12.RESULTS: None of the normal colorectal mucosa tissues showed methylated bands. Promoter hypermethylation was detected in 40.7% (11 of 27) of adenomas and 43.5% (27 of 62) of carcinomas. MGMT proteins were expressed in nucleus and cytoplasm of normal colorectal mucosa tissues. Loss of MGMT expression was found in 22.2% (6 of 27) of adenomas and 45.2% (28 of 62) of carcinomas. The difference between them was significant (P = 0.041). In the 6 adenomas and 28 carcinomas losing MGMT expression, 5 and 24 cases presented methylation,respectively (P = 0.027, P<0.001). Thirteen of the 19 colorectal tumors with K-rasG to A point mutation in codon 12 had methylated MGMT(P = 0.011). The frequencies of K-rasG to A point mutation were 35.3% (12 of 34) and 12.7% (7 of 55) in tumors losing MGMT expression and with normal expression, respectively.CONCLUSION: Promoter hypermethylation and loss of expression of MGMT gene were common events in colorectal tumorigenesis, and loss of expression of MGMT occurs more frequently in carcinomas than in adenomas in sporadic patients. Hypermethylation of the CpG island of MGMT gene was associated with loss of MGMT expression and K-ras G to A point mutation in colorectal tumor. The frequency of K-ras G to A point mutation was increased in tumors losing MGMT expression. It suggests that epigenetic inactivation of MGMT plays an important role in colorectal neoplasia.
基金funded by the Intramural program of the National Human Genome Research Institute,the National Institutes of Health
文摘Over the last two decades, cancer-related alterations in DNA methylation that regulate transcription have been reported for a variety of tumors of the gastrointestinal tract. Due to its relevance for translational research, great emphasis has been placed on the analysis and molecular characterization of the CpG island methylator phenotype(CIMP), defined as widespread hypermethylation of CpG islands in clinically distinct subsets of cancer patients. Here, we present an overview of previous work in this field and also explore some open questions using crossplatform data for esophageal, gastric, and colorectal adenocarcinomas from The Cancer Genome Atlas. We provide a data-driven, pan-gastrointestinal stratification of individual samples based on CIMP status and we investigate correlations with oncogenic alterations, including somatic mutations and epigenetic silencing of tumor suppressor genes. Besides known events in CIMP such as BRAF V600 E mutation, CDKN2 A silencing or MLH1 inactivation, we discuss the potential role of emerging actors such as Wnt pathway deregulation through truncating mutations in RNF43 and epigenetic silencing of WIF1. Our results highlight the existence of molecular similarities that are superimposed over a larger backbone of tissue-specific features and can be exploited to reduce heterogeneity of response in clinical trials.
基金Funded by the National Natural Science Foundation of China(No.51275393)the Fundamental Research Funds for the Central Universities(No.xjj2017160)
文摘A method to improve the low-velocity impact performance of composite laminate is proposed, and a multi-island genetic algorithm is used for the optimization of composite laminate stacking sequence under low-velocity impact loads based on a 2D dynamic impact finite element analysis. Low-velocity impact tests and compression-after impact(CAI) tests have been conducted to verify the effectiveness of optimization method. Experimental results show that the impact damage areas of the optimized laminate have been reduced by 42.1% compared to the baseline specimen, and the residual compression strength has been increased by 10.79%, from baseline specimen 156.97 MPa to optimized 173.91 MPa. The tests result shows that optimization method can effectively enhance the impact performances of the laminate.
基金the National Natural Science Foundation of China (Grant No.39830310)
文摘Random amplified polymorphic DNA (RAPD) markers were used to analyze genetic variation of Podocarpus imbricatus in Hainan Island and Mainland of China. Two populations of Dacrydium pierrei were used as comparison materials. Both Podocarpus imbricatus and Dacrydium pierrei showed a low level of genetic diversity. However, Podocarpus imbricatus showed higher genetic diversity and higher population differentiation than Dacrydium pierrei. The geographic range may affect the genetic diversity of Podocarpus imbricatus and Dacrydium pierrei significantly. The UPGMA cluster tree showed that populations of Podocarpus imbricatus in Hainan Island and Guangxi Zhuang Autonomous Region were closer than those in Yunnan Province, indicating possible gene flow between Hainan Island and Guangxi Zhuang Autonomous Region. The young geological history of Hainan Island and the three times of unification and separation between Hainan Island and the Mainland may give the two species more possibilities of gene flow.