Molecular advances support the existence of an alternative pathway of colorectal carcinogenesis that is based on the hypermethylation of specific DNA regions that silences tumor suppressor genes. This alternative path...Molecular advances support the existence of an alternative pathway of colorectal carcinogenesis that is based on the hypermethylation of specific DNA regions that silences tumor suppressor genes. This alternative pathway has been called the serrated pathway due to the serrated appearance of tumors in histological analysis. New classifications for colorectal cancer(CRC) were proposed recently based on genetic profiles that show four types of molecular alterations: BRAF gene mutations, KRAS gene mutations, microsatellite instability, and hypermethylation of Cp G islands. This review summarizes what is known about the serrated pathway of CRC, including CRC molecular and clinical features, prognosis, and response to chemotherapy.展开更多
目的:利用微滴数字PCR(droplet digital PCR,DD-PCR)技术进行CpG岛甲基化表型(CpG island methylation phenotype,CIMP)结直肠癌分型,并探讨以血浆游离DNA进行CIMP分型的可行性。方法:收集2008到2012年在长海医院行结直肠癌手术的患者21...目的:利用微滴数字PCR(droplet digital PCR,DD-PCR)技术进行CpG岛甲基化表型(CpG island methylation phenotype,CIMP)结直肠癌分型,并探讨以血浆游离DNA进行CIMP分型的可行性。方法:收集2008到2012年在长海医院行结直肠癌手术的患者216例,抽提肿瘤组织DNA和血浆游离DNA,重亚硫酸盐处理后,利用DD-PCR进行CIMP分型。CIMP分型选用CACNA1G、IGF2、NEUROG1、RUNX3、SOCS1五个基因的甲基化位点,利用免疫组织化学技术(IHC)检测P53突变情况,以巢式PCR测序方法检测K-RAS和BRAF突变。结果:216例肿瘤中17例(7.9%)存在BRAF突变,96例(44.4%)存在K-RAS突变和112例(51.9%)P53-IHC(+)。31.5%(68/216)的结直肠癌为CIMP(+)(5个基因位点中高甲基化位点数目≥3),82.3%(14/17)的BRAF突变属于CIMP(+),而只有9.4%(9/96)的K-RAS突变和7.1%(8/112)的P53突变属于CIMP(+)。除了K-RAS,BRAF和P53突变外,同CIMP(-)结直肠癌相比,CIMP(+)肿瘤还具有独特的临床病理特征:肿瘤更易发生在结直肠的近端位置,黏液性癌比例偏高,分化程度较高,CIMP(+)患者生存时间显著短于CIMP(-)患者。利用血浆游离DNA进行分型和利用肿瘤组织进行分型的一致性为93.4%、灵敏度为87.2%、特异性为100%。结论:CIMP(+)结直肠癌具有独特的临床病理特征,且预后较差;在缺乏肿瘤组织的情况下,利用DD-PCR对血浆游离DNA进行CIMP分型是可行的。展开更多
Climate change predictions for the Pacific Northwest region of the United States of America include increasing temperatures, intensification of winter precipitation, and a shift from mixed snow/rain to rain-dominant e...Climate change predictions for the Pacific Northwest region of the United States of America include increasing temperatures, intensification of winter precipitation, and a shift from mixed snow/rain to rain-dominant events, all of which may increase the risk of soil erosion and threaten agricultural and ecological productivity. Here we used the agricultural/environmental model SWAT with climate predictions from the Coupled Model Intercomparison Project 5 (CMIP5) “high CO2 emissions” scenario (RCP8.5) to study the impact of altered temperature and precipitation patterns on soil erosion and crop productivity in the Willamette River Basin of western Oregon. An ensemble of 10 climate models representing the full range in temperature and precipitation predictions of CIMP5 produced substantial increases in sediment yield, with differences between yearly averages for the final (2090-2099) and first (2010-2019) decades ranging from 3.9 to 15.2 MT·ha-1 among models. Sediment yield in the worst case model (CanESM2) corresponded to loss of 1.5 - 2.7 mm·soil·y-1, equivalent to potentially stripping productive topsoil from the landscape in under two centuries. Most climate models predicted only small increases in precipitation (an average of 5.8% by the end of the 21st century) combined with large increases in temperature (an average of 0.05°C·y-1). We found a strong correlation between predicted temperature increases and sediment yield, with a regression model combining both temperature and precipitation effects describing 79% of the total variation in annual sediment yield. A critical component of response to increased temperature was reduced snowfall during high precipitation events in the wintertime. SWAT characterized years with less than basin-wide averages of 20 mm of precipitation falling as snow as likely to experience severe sediment loss for multiple crops/land uses. Mid-elevation sub-basins that are projected to shift from rain-snow transition to rain-dominant appear particularly vulnerable to sediment loss. Analyses of predicted crop yields indicated declining productivity for many commonly grown grass seed and cereal crops, along with increasing productivity for certain other crops. Adaptation by agriculture and forestry to warmer, more erosive conditions may include changes in selection of crop kinds and in production management practices.展开更多
文摘Molecular advances support the existence of an alternative pathway of colorectal carcinogenesis that is based on the hypermethylation of specific DNA regions that silences tumor suppressor genes. This alternative pathway has been called the serrated pathway due to the serrated appearance of tumors in histological analysis. New classifications for colorectal cancer(CRC) were proposed recently based on genetic profiles that show four types of molecular alterations: BRAF gene mutations, KRAS gene mutations, microsatellite instability, and hypermethylation of Cp G islands. This review summarizes what is known about the serrated pathway of CRC, including CRC molecular and clinical features, prognosis, and response to chemotherapy.
文摘目的:利用微滴数字PCR(droplet digital PCR,DD-PCR)技术进行CpG岛甲基化表型(CpG island methylation phenotype,CIMP)结直肠癌分型,并探讨以血浆游离DNA进行CIMP分型的可行性。方法:收集2008到2012年在长海医院行结直肠癌手术的患者216例,抽提肿瘤组织DNA和血浆游离DNA,重亚硫酸盐处理后,利用DD-PCR进行CIMP分型。CIMP分型选用CACNA1G、IGF2、NEUROG1、RUNX3、SOCS1五个基因的甲基化位点,利用免疫组织化学技术(IHC)检测P53突变情况,以巢式PCR测序方法检测K-RAS和BRAF突变。结果:216例肿瘤中17例(7.9%)存在BRAF突变,96例(44.4%)存在K-RAS突变和112例(51.9%)P53-IHC(+)。31.5%(68/216)的结直肠癌为CIMP(+)(5个基因位点中高甲基化位点数目≥3),82.3%(14/17)的BRAF突变属于CIMP(+),而只有9.4%(9/96)的K-RAS突变和7.1%(8/112)的P53突变属于CIMP(+)。除了K-RAS,BRAF和P53突变外,同CIMP(-)结直肠癌相比,CIMP(+)肿瘤还具有独特的临床病理特征:肿瘤更易发生在结直肠的近端位置,黏液性癌比例偏高,分化程度较高,CIMP(+)患者生存时间显著短于CIMP(-)患者。利用血浆游离DNA进行分型和利用肿瘤组织进行分型的一致性为93.4%、灵敏度为87.2%、特异性为100%。结论:CIMP(+)结直肠癌具有独特的临床病理特征,且预后较差;在缺乏肿瘤组织的情况下,利用DD-PCR对血浆游离DNA进行CIMP分型是可行的。
文摘Climate change predictions for the Pacific Northwest region of the United States of America include increasing temperatures, intensification of winter precipitation, and a shift from mixed snow/rain to rain-dominant events, all of which may increase the risk of soil erosion and threaten agricultural and ecological productivity. Here we used the agricultural/environmental model SWAT with climate predictions from the Coupled Model Intercomparison Project 5 (CMIP5) “high CO2 emissions” scenario (RCP8.5) to study the impact of altered temperature and precipitation patterns on soil erosion and crop productivity in the Willamette River Basin of western Oregon. An ensemble of 10 climate models representing the full range in temperature and precipitation predictions of CIMP5 produced substantial increases in sediment yield, with differences between yearly averages for the final (2090-2099) and first (2010-2019) decades ranging from 3.9 to 15.2 MT·ha-1 among models. Sediment yield in the worst case model (CanESM2) corresponded to loss of 1.5 - 2.7 mm·soil·y-1, equivalent to potentially stripping productive topsoil from the landscape in under two centuries. Most climate models predicted only small increases in precipitation (an average of 5.8% by the end of the 21st century) combined with large increases in temperature (an average of 0.05°C·y-1). We found a strong correlation between predicted temperature increases and sediment yield, with a regression model combining both temperature and precipitation effects describing 79% of the total variation in annual sediment yield. A critical component of response to increased temperature was reduced snowfall during high precipitation events in the wintertime. SWAT characterized years with less than basin-wide averages of 20 mm of precipitation falling as snow as likely to experience severe sediment loss for multiple crops/land uses. Mid-elevation sub-basins that are projected to shift from rain-snow transition to rain-dominant appear particularly vulnerable to sediment loss. Analyses of predicted crop yields indicated declining productivity for many commonly grown grass seed and cereal crops, along with increasing productivity for certain other crops. Adaptation by agriculture and forestry to warmer, more erosive conditions may include changes in selection of crop kinds and in production management practices.
