目的:探索直肠癌新辅助放化疗的敏感性分子特征。方法:前瞻性收集局部进展期中、低位直肠癌30例患者的临床病理资料,包括一般情况、放化疗前影像学资料、放化疗前活组织病理检查资料、肿瘤分化程度等9项指标,分析其与直肠癌放化疗后肿...目的:探索直肠癌新辅助放化疗的敏感性分子特征。方法:前瞻性收集局部进展期中、低位直肠癌30例患者的临床病理资料,包括一般情况、放化疗前影像学资料、放化疗前活组织病理检查资料、肿瘤分化程度等9项指标,分析其与直肠癌放化疗后肿瘤消退分级(tumor regression grading,TRG)的相关性。收集这30例患者新辅助治疗前结肠镜活检冰冻标本,进行转录组二代测序和生物信息学分析,筛选可能驱动直肠癌放化疗敏感性的基因。结果: 30例直肠癌患者中,病理完全缓解9例,部分缓解12例,缓解差9例。直肠癌放化疗后病理TRG缓解程度与肿瘤术前MRI的T分期呈负相关( P =0.046),与术前MRI直肠癌壁外血管侵犯(extramural vascular invasion, EMVI )呈正相关( P =0.003)。转录组二代测序对所获取的 P <0.05的217条转录本进行信号通路富集分析,可以发现多条与抗原呈递相关的细胞信号转导通路,其中HSPA1A、HSPA1B和EXOSC2的高表达和术后病理缓解差呈正相关( P <0.05),DNMBP、WASH8P、FAM57A和SGSM2等的高表达和术后病理缓解良好呈正相关( P <0.05)。结论:直肠癌术前MRI检测肿瘤EMVI阳性的患者放化疗后病理完全缓解率明显优于EMVI阴性者。HSPA1A、HSPA1B和EXOSC2高表达的患者术后病理缓解差,而DNMBP、WASH8P、FAM57A和SGSM2高表达的患者术后病理缓解良好。基于直肠癌放化疗敏感性分子特征,尝试阻断或增强与直肠癌放化疗敏感性相关的分子通路,可进一步探索能增加直肠癌放化疗敏感性的候选治疗靶点。展开更多
Background The continual and rapid development of techniques which are used for diagnosis and treatment makes management of colorectal cancer more difficult depending on single discipline.Colorectal cancer multidiscip...Background The continual and rapid development of techniques which are used for diagnosis and treatment makes management of colorectal cancer more difficult depending on single discipline.Colorectal cancer multidisciplinary team （MDT） working model is recommended by UK and other countries,but there is little information on the impact of MDT working on management of colorectal cancer in China.The aim of this study was to assess the effect on management of colorectal cancer after the inception of an MDT.Methods A total of 595 consecutive colorectal cancer patients were referred to the Department of Gastroenterological Surgery,the pre-MDT cohort include 297 patients,recruited from January 1999 to November 2002,and the MDT cohort had 298 patients enrolled from December 2002 to September 2006.Information recorded included：TNM stage from histological reports,degree of differentiation,the number of examined lymph nodes and CT TNM staging performed or not,and its accuracy,including local and distant recurrence.Results The number of examined lymph nodes and the accuracy of TNM staging by CT in the MDT group were significantly more than those in pre-MDT group.CT TNM staging was more accurate in the MDT group compared to the pre-MDT group （P=-0.044）.The rate of tumor recurrence in the MDT group was lower than pre-MDT group （log-rank test,P 〈0.001）.Multivariate analysis revealed that age （P=0.001）,management after inception of the MDT （P=0.002）,degree of differentiation （P=0.003）,number of examined lymph nodes （P=0.002）,and TNM stage （P=0.000） were important factors that independently influence overall survival.Conclusions The inception of MDT working improved the diagnostic accuracy and overall survival of colorectal cancer patients.MDT working promoted communication and cooperation between disciplines and ensured high-quality diagnosis,evidence-based decision making,and optimal treatment planning.展开更多
Background Cyclooxygenase （COX） is the rate-limiting enzyme in the production of prostanoids from arachidonic acid. COX-2 is the inducible enzyme in the COX family, together with the prostanoids forms the COX-2/pros...Background Cyclooxygenase （COX） is the rate-limiting enzyme in the production of prostanoids from arachidonic acid. COX-2 is the inducible enzyme in the COX family, together with the prostanoids forms the COX-2/prostanoid pathway. Research showed that the COX-2/prostanoid pathway is activated in hepatic diseases and liver stress reaction, such as fibrogenesis, portal hypertension, carcinogenesis, and ischemic/repeffusion injury. But there was no report on visceral pain induced liver stress. This study was to investigate the role of the COX-2/prostanoid pathway in liver stress response in rat acute colitis visceral pain liver stress model.Methods Fifty-three male SD rats were randomly divided into Naive, Model, NS398 treatment, and Morphine treatment groups. The rat acute colitis visceral pain liver stress model was established under anesthesia by the colonic administration of 0.5 ml of 6% acetic acid using a urethral catheter. NS398 and morphine were administrated 30 minutes prior to model establishment in NS398 and Morphine treatment groups respectively. Spontaneous activities and pain behavior were counted and the extent of colonic inflammation was assessed histologically. Liver tissue levels of Glutathione-S-Transferase （GST） activity, COX-2 mRNA, prostaglandin E2 （PGE2）, thromboxane B2 （TXB2） and 6-Ketone-prostaglandin F1α （6-K-PGF1α） contents were assessed.Results Thirty minutes after the colonic administration of acetic acid, a significant decrease in spontaneous activities and an increase in pain behaviors were observed in Model group （P〈0.01 and P〈0.05 respectively）, accompanied by colonic inflammation. Liver GST activity levels significantly dropped （P〈0.05）. Liver COX-2 mRNA expressi.on significantly increased, accompanied by an increase in liver concentrations of PGE2 and TXB2, but no obvious change in 6-K-PGF1α concentrations. NS398 and morphine both ameliorated post-stress liver GST activity （P〈0.05 and P〈0.01 respectively）, decreased stress-induced COX-2 expression, decreased PGE2 and TXB2 production, but increased liver 6-K-PGF1α levels. Morphine attenuation in colonic tissue inflammation was apparent at 24 hours （P〈0.05）.Conclusions Acute colitis visceral pain liver stress can induce liver injury. Liver injury might have occurred through the activation of the COX-2/prostanoid pathway and increased production of PGE2 and TXB2. Effective analgesia might offer protective effect during visceral pain stress.展开更多
文摘目的:探索直肠癌新辅助放化疗的敏感性分子特征。方法:前瞻性收集局部进展期中、低位直肠癌30例患者的临床病理资料,包括一般情况、放化疗前影像学资料、放化疗前活组织病理检查资料、肿瘤分化程度等9项指标,分析其与直肠癌放化疗后肿瘤消退分级(tumor regression grading,TRG)的相关性。收集这30例患者新辅助治疗前结肠镜活检冰冻标本,进行转录组二代测序和生物信息学分析,筛选可能驱动直肠癌放化疗敏感性的基因。结果: 30例直肠癌患者中,病理完全缓解9例,部分缓解12例,缓解差9例。直肠癌放化疗后病理TRG缓解程度与肿瘤术前MRI的T分期呈负相关( P =0.046),与术前MRI直肠癌壁外血管侵犯(extramural vascular invasion, EMVI )呈正相关( P =0.003)。转录组二代测序对所获取的 P <0.05的217条转录本进行信号通路富集分析,可以发现多条与抗原呈递相关的细胞信号转导通路,其中HSPA1A、HSPA1B和EXOSC2的高表达和术后病理缓解差呈正相关( P <0.05),DNMBP、WASH8P、FAM57A和SGSM2等的高表达和术后病理缓解良好呈正相关( P <0.05)。结论:直肠癌术前MRI检测肿瘤EMVI阳性的患者放化疗后病理完全缓解率明显优于EMVI阴性者。HSPA1A、HSPA1B和EXOSC2高表达的患者术后病理缓解差,而DNMBP、WASH8P、FAM57A和SGSM2高表达的患者术后病理缓解良好。基于直肠癌放化疗敏感性分子特征,尝试阻断或增强与直肠癌放化疗敏感性相关的分子通路,可进一步探索能增加直肠癌放化疗敏感性的候选治疗靶点。
文摘Background The continual and rapid development of techniques which are used for diagnosis and treatment makes management of colorectal cancer more difficult depending on single discipline.Colorectal cancer multidisciplinary team （MDT） working model is recommended by UK and other countries,but there is little information on the impact of MDT working on management of colorectal cancer in China.The aim of this study was to assess the effect on management of colorectal cancer after the inception of an MDT.Methods A total of 595 consecutive colorectal cancer patients were referred to the Department of Gastroenterological Surgery,the pre-MDT cohort include 297 patients,recruited from January 1999 to November 2002,and the MDT cohort had 298 patients enrolled from December 2002 to September 2006.Information recorded included：TNM stage from histological reports,degree of differentiation,the number of examined lymph nodes and CT TNM staging performed or not,and its accuracy,including local and distant recurrence.Results The number of examined lymph nodes and the accuracy of TNM staging by CT in the MDT group were significantly more than those in pre-MDT group.CT TNM staging was more accurate in the MDT group compared to the pre-MDT group （P=-0.044）.The rate of tumor recurrence in the MDT group was lower than pre-MDT group （log-rank test,P 〈0.001）.Multivariate analysis revealed that age （P=0.001）,management after inception of the MDT （P=0.002）,degree of differentiation （P=0.003）,number of examined lymph nodes （P=0.002）,and TNM stage （P=0.000） were important factors that independently influence overall survival.Conclusions The inception of MDT working improved the diagnostic accuracy and overall survival of colorectal cancer patients.MDT working promoted communication and cooperation between disciplines and ensured high-quality diagnosis,evidence-based decision making,and optimal treatment planning.
文摘Background Cyclooxygenase （COX） is the rate-limiting enzyme in the production of prostanoids from arachidonic acid. COX-2 is the inducible enzyme in the COX family, together with the prostanoids forms the COX-2/prostanoid pathway. Research showed that the COX-2/prostanoid pathway is activated in hepatic diseases and liver stress reaction, such as fibrogenesis, portal hypertension, carcinogenesis, and ischemic/repeffusion injury. But there was no report on visceral pain induced liver stress. This study was to investigate the role of the COX-2/prostanoid pathway in liver stress response in rat acute colitis visceral pain liver stress model.Methods Fifty-three male SD rats were randomly divided into Naive, Model, NS398 treatment, and Morphine treatment groups. The rat acute colitis visceral pain liver stress model was established under anesthesia by the colonic administration of 0.5 ml of 6% acetic acid using a urethral catheter. NS398 and morphine were administrated 30 minutes prior to model establishment in NS398 and Morphine treatment groups respectively. Spontaneous activities and pain behavior were counted and the extent of colonic inflammation was assessed histologically. Liver tissue levels of Glutathione-S-Transferase （GST） activity, COX-2 mRNA, prostaglandin E2 （PGE2）, thromboxane B2 （TXB2） and 6-Ketone-prostaglandin F1α （6-K-PGF1α） contents were assessed.Results Thirty minutes after the colonic administration of acetic acid, a significant decrease in spontaneous activities and an increase in pain behaviors were observed in Model group （P〈0.01 and P〈0.05 respectively）, accompanied by colonic inflammation. Liver GST activity levels significantly dropped （P〈0.05）. Liver COX-2 mRNA expressi.on significantly increased, accompanied by an increase in liver concentrations of PGE2 and TXB2, but no obvious change in 6-K-PGF1α concentrations. NS398 and morphine both ameliorated post-stress liver GST activity （P〈0.05 and P〈0.01 respectively）, decreased stress-induced COX-2 expression, decreased PGE2 and TXB2 production, but increased liver 6-K-PGF1α levels. Morphine attenuation in colonic tissue inflammation was apparent at 24 hours （P〈0.05）.Conclusions Acute colitis visceral pain liver stress can induce liver injury. Liver injury might have occurred through the activation of the COX-2/prostanoid pathway and increased production of PGE2 and TXB2. Effective analgesia might offer protective effect during visceral pain stress.
