lncRNA ZFAS1通过miR-588/HMGA2轴促进肝癌HepG2细胞的增殖、侵袭和迁移

目的：探讨长链非编码RNA锌指结构反义转录本1（lncRNA ZFAS1）调控miR-588/高迁移率蛋白A2（HMGA2）轴对肝癌HepG2细胞增殖、侵袭、迁移的影响。方法：qPCR、WB法检测80例肝癌组织及对应癌旁组织（2018年1月至2019年12月在武汉第三医院首义院区手术切除标本）及人正常 肝 LO2 细 胞 和 肝 癌 HepG2、Huh7、HCCLM3 细胞中 ZFAS1、miR-588 及HMGA2表达水平;采用Kaplan-Meier进行患者生存曲线分析。将 HepG2 细胞分为空白组、si-NC组、si-ZFAS1组、si-ZFAS1+inhibitor NC组、si-ZFAS1+miR-588 inhibitor组;qPCR检测各组HepG2细胞中ZFAS1、miR-588表达水平,WB法检测各组HepG2细胞中HMGA2蛋白表达;CCK-8法、Transwell和划痕实验分别检测各组HepG2细胞的增殖、侵袭和迁移能力;双荧光素酶报告基因实验分别验证ZFAS1和miR-588、miR-588和HMGA2的靶向关系。用HepG2细胞移植瘤裸鼠模型检测敲减ZFAS1或/和miR-588 对移植瘤生长的影响。结果:在肝癌组织和肝癌细胞中,ZFAS1、HMGA2 呈高表达,miR-588 呈低表达（均 P<0.05）;ZFAS1低表达患者2年生存率高于高表达组（P<0.05）;与空白组比较 ,si-ZFAS1 组 ZFAS1、HMGA2表达水平显著降低,miR588表达水平显著升高（均P<0.05）。与si-ZFAS1组比较,si-ZFAS1+miR-588 inhibitor组中ZFAS1表达水平无显著变化（P>0.05）,HMGA2表达水平显著升高、miR-588表达水平显著降低（P<0.05）;敲减ZFAS1可抑制HepG2细胞的增殖、侵袭和迁移能力,并抑制裸鼠体内移植瘤的生长（均P<0.05）;ZFAS1靶向miR-588并抑制后者的表达,miR-588靶向HMGA2并抑制后者的表达;同时抑制ZFAS1和miR-588表达可逆转敲减ZFAS1对HepG2细胞增殖、侵袭与迁移能力及体内移植瘤生长的抑制作用（均P<0.05）。结论:敲减ZFAS1可通过促进miR-588表达来下调HMGA2表达,进而抑制肝癌HepG2细胞的增殖、侵袭与迁移能力。     

lncRNA SUMO1P3诱导肝癌HepG2细胞对索拉菲尼耐药的分子机制

目的：探讨长链非编码RNA小泛素样修饰蛋白1假基因3（lncRNA SUMO1P3）促进肝细胞癌（HCC）HepG2细胞对索拉菲尼（SR）耐药的分子机制。方法：体外培养HCC细胞HepG2,采用持续接触浓度递增诱导法建立SR耐药细胞HepG2/SR,以HepG2细胞作为对照,qPCR 法检测 HepG2/SR 细胞中 SUMO1P3 的表达。利用脂质体转染技术,在 HepG2/SR细胞中分别转染si-SUMO1P3和si-NC;在HepG2细胞中分别转染pc-SUMO1P3和pc-DNA,后经5 μmol/L的SR处理24 h,qPCR法检测转染细胞中SUMO1P3表达水平,CCK-8法、Transwell实验和FCM分别检测转染细胞的增殖、迁移和侵袭能力和凋亡水平,WB法检测细胞中cyclin D1、Bcl2、BAX、MMP-2和MMP-9的表达。结果：成功构建SR耐药细胞HepG2/SR,HepG2/SR细胞中SUMO1P3表达水平显著高于 HepG2 细胞（P<0.01）。在 HepG2/SR 细胞敲减 SUMO1P3 后 ,与 si-NC 组比较 ,si-SUMO1P3 组细胞中SUMO1P3的表达与细胞增殖、迁移、侵袭能力及cyclin D1、Bcl2、MMP-2和MMP-9表达均显著降低,细胞凋亡率和BAX的表达均显著升高（P<0.05或P<0.01）。HepG2细胞过表达SUMO1P3后,与pc-DNA组比较,pc-SUMO1P3组细胞的增殖、迁移、侵袭能力及cyclin D1、Bcl2、MMP-2和MMP-9蛋白表达均显著升高,细胞凋亡率和BAX的表达均降低（P<0.05 或 P<0.01）;与pc-DNA+SR组比较,pc-SUMO1P3+SR组HepG2细胞的增殖、迁移、侵袭能力及cyclin D1、Bcl2、MMP-2和MMP-9蛋白表达均显著升高,细胞凋亡率和BAX的表达均显著降低（P<0.05或P<0.01）。结论：lncRNA SUMO1P3可通过调控HCC细胞的周期、凋亡等多种信号通路分子诱导细胞对SR的耐药,从而影响HepG2细胞的增殖、迁移和侵袭,并抑制细胞凋亡与诱导细胞对SR的耐药。     

siRNA 干扰胰岛素样生长因子1 受体表达对缺氧环境下肝癌HepG2 细胞周期及凋亡的影响

目的：探讨siRNA技术干扰胰岛素样生长因子-1受体（insulin-like growth factors-1 receptors, IGF-1R）表达对缺氧环境下肝癌HepG2 细胞周期和凋亡的影响。方法：采用氯化钴处理制备实验所需的肝癌缺氧细胞模型。设计并合成3 对siRNA序列和1 对阴性对照序列，转染缺氧的肝癌HepG2 细胞24 h 后以荧光显微镜观察转染效果，采用WB法检测IGF-1R蛋白表达筛选出干扰效率最高的siRNA序列。选用该序列再次转染缺氧肝癌细胞，以流式细胞术、MTT法检测细胞的周期、凋亡和增殖变化，以WB法检测HepG2 细胞中CDK1、CDK2 和Caspase-3 蛋白的表达。结果：成功建立缺氧HepG2 细胞模型，siRNA转染缺氧HepG2 细胞后以IGF-1R-siRNA-2 转染效率最高且敲减IGF-1R表达最明显（均P<0.01）。IGF-1R-siRNA-2 转染的HepG2 细胞的增殖被明显抑制（P<0.05 或P<0.01）、细胞周期被阻滞在G0/G1（P<0.05）、细胞凋亡率明显增加至（25.3±1.3）%（P<0.01），同时发现敲减IGF-1R后缺氧HepG2 细胞中CDK1、CDK2 蛋白表达明显降低而Caspase-3 表达则明显增加（P<0.05或P<0.01）。结论：siRNA干扰IGF-1R表达通过调控细胞周期和凋亡相关蛋白而抑制缺氧环境中HepG2细胞的恶性生物学行为，IGF-1R可能是HCC潜在的治疗靶点。     

miR-124通过调节Jagged1/Notch信号通路影响肾细胞癌OS-RC-2细胞 的恶性生物学行为

目的：探讨miR-124通过调节Jagged1（JAG1）/Notch信号通路对肾细胞癌（RCC）细胞增殖、凋亡、迁移和侵袭的影响。方法：收集2018年6月至2021年10月在武汉市第三医院治疗的38例RCC患者的RCC组织和癌旁组织标本,并体外培养RCC细胞（Caki-2、A498、ACHN、786-O、OS-RC-2）和人正常肾细胞（293T）,采用免疫组织化学法、qPCR和WB法检测miR-124和JAG1蛋白在RCC组织和细胞中的表达水平。选择miR-124表达与293T细胞差异最大的OS-RC-2细胞进行转染,按转染物不同分为Control组、NC mimic组、miR-124 mimic组、miR-124 mimic+pcDNA组和miR-124 mimic+pc-JAG1组。采用双荧光素酶报告基因实验验证miR-124与JAG1的关系;qPCR法检测miR-124、JAG1 mRNA表达;免疫组化法分析JAG1蛋白表达;WB法检测JAG1、凋亡相关蛋白（cleaved caspase-3、BAX 和 Bcl2）和 Notch 信号通路相关蛋白（NICD、HES1 和 HES5）的表达;MTT 法检测OS-RC-2细胞增殖;Transwell 检测 OS-RC-2 细胞迁移和侵袭;流式细胞术检测OS-RC-2细胞凋亡。结果：与癌旁组织比较,RCC组织中miR-124表达降低,JAG1 mRNA和蛋白表达均升高（均 P<0.01）;与 293T 细胞比较,Caki-2、A498、ACHN、786-O、OS-RC-2细胞中miR-124水平降低,JAG1 mRNA和蛋白表达均升高（均P<0.05）;miR-124直接负调控JAG1。与Control组和NC mimic组比较,miR-124 mimic组miR-124表达水平、细胞凋亡率以及cleaved caspase-3和BAX蛋白表达均升高,JAG1 mRNA和蛋白表达均降低,细胞活力（24、48、72 h）下降,迁移、侵袭细胞数减少,Bcl2及NICD、HES1、HES5蛋白表达降低（均P<0.05）;与miR-124 mimic+pcDNA 组和 miR-124 mimic 组相比,miR-124 mimic+pc-JAG1 组 miR-124 表达水平、细胞凋亡率以及 cleaved caspase-3和BAX蛋白表达均降低,JAG1 mRNA和蛋白表达均升高,细胞活力（24、48、72 h）增加,迁移、侵袭细胞数增多,Bcl2及NICD、HES1、HES5蛋白表达均增加（均P<0.05）。结论：miR-124通过下调JAG1抑制Notch信号通路,降低RCC OS-RC-2细胞的增殖、迁移和侵袭能力,促进细胞凋亡。     

miR-195 靶向TLR4 并阻断NF-κB通路抑制肝癌细胞HepG2 增殖和转移

[摘要] 目的：探讨miR-195/Toll样受体4（TLR4）分子轴通过调控NF-κB通路对肝癌细胞增殖、侵袭和迁移的影响。方法：收集2016 年3 月至2017 年1 月昆明医科大学第二附属医院外科手术切除的25 例肝癌组织以及对应的癌旁组织标本;肝癌HepG2 细胞培养完成后分为4 组,即对照组（NC）、miR-195 mimic组(miR-195组)、TLR4 敲降组(si-TLR4 组)和miR-195 inhibitor 联合TLR4 敲降组（si-TLR4+miR-195 inhibitor 组）。采用qPCR检测miR-195 在肝癌组织和细胞系中的表达水平;采用CCK-8 法检测上述各组细胞的增殖活力,Transwell法检测各组细胞的侵袭能力,划痕愈合实验检测细胞迁移能力,双荧光素酶报告基因验证miR-195和TLR4的靶向调控关系,WB检测TLR4 和NF-κB p65 蛋白的表达。结果：miR-195 在肝癌组织中低表达（P<0.01）。相比于人肝上皮细胞（THLE-3）,miR-193 在肝癌细胞系（HepG2 和Huh-7）中低表达（P<0.01）,且HepG2 细胞中的表达水平最低。过表达miR-195 后HepG2 细胞增殖活力明显低于对照组（P<0.01）,穿膜细胞明显减少（P<0.01）,HepG2 细胞迁移能力明显下调（P<0.01）。过表达miR-195可明显抑制TLR4蛋白的表达水平（P<0.05）,且TLR4与miR-195的表达呈负相关（R2=0.602,P<0.0001）。过表达miR-195可靶向下调TLR4 并阻断NF-κB通路抑制HepG2 细胞增殖、侵袭和迁移能力（P<0.05 或P<0.01）。结论：miR-195 能够抑制HepG2 细胞增殖、侵袭及迁移能力,其机制可能与靶向调控TLR4 并阻断NF-κB 通路影响细胞生物学行为有关。     

ERK-VEGF/MMP-9信号通路对肝癌HepG2细胞不良生物学行为的调控作用

目的:探究ERK-VEGF/MMP-9信号通路对肝癌HepG2细胞不良生物学行为的调控作用。方法:体外培养人肝癌HepG2细胞,54个培养皿分为对照组,阻断组及转染组,各18。对照组不进行干预;阻断组使用特异性ERK-VEGF/MMP-9信号通路抑制剂GDC-0994;转染组转染ERK1质粒。MTT法检测HepG2细胞增殖情况;流式细胞仪检测HepG2细胞周期及凋亡变化;Transwell实验分析HepG2细胞迁移、侵袭情况;Western blot法检测ERK、VEGF以及MMP-9蛋白表达。结果:与对照组相比,阻断组细胞增殖率下降、S期及G₂/M期细胞占比增加、细胞凋亡率增加、细胞迁移及侵袭数降低(P<0.05),转染组细胞增殖率上升、S期及G₂/M期细胞占比减少、细胞凋亡率下降、细胞迁移及侵袭数增加(P<0.05)。与对照组相比,阻断组ERK、VEGF及MMP-9蛋白表达均下降(P<0.05);转染组ERK、VEGF及MMP-9蛋白表达均上升(P<0.05)。结论:阻断ERK-VEGF/MMP-9信号通路可抑制H...     

小核核糖核蛋白多肽A对肝细胞癌细胞恶性生物学行为的影响及其机制

目的：探究小核核糖核蛋白多肽A（SNRPA）在肝细胞癌（HCC）组织和细胞中的表达及其调控HCC 细胞HepG2 和Hep3B恶性生物学行为的作用及其机制。方法: 数据库分析SNRPA在泛癌组织中的表达及其与病理分期、HCC 患者预后的相关性。常规培养HepG2 和Hep3B 细胞，将si-NC ，si-SNRPA#1、si-SNRPA#2转染HepG2 和Hep3B 细胞，实验分为si-NC 组、 si-SNRPA#1 组和si-SNRPA#2 组；将SNRPA-vector 和SNRPA-oe 载体转染LO2 细胞，分为SNRPA-vector 组和SNRPA-oe 组。 qPCR法检测正常肝细胞和肝癌细胞以及转染各组HepG2和Hep3B细胞中SNRPA mRNA的表达，MTT法、Transwell 法和WB法分别检测转染后各组HepG2 和Hep3B细胞的增殖、迁移和侵袭能力以及EMT相关蛋白表达的变化。结果: 数据库分析显示，SNRPA mRNA在多数肿瘤组织中均呈高表达（均P<0.001）且与病理分期有关联（P<0.05或P<0.01）。SNRPA在HCC组织和细胞中均呈高表达（P<0.05 或P<0.01），且与HCC患者的预后有关联（P<0.01）。敲减SNRPA表达明显抑制HepG2 和Hep3B细胞增殖（P<0.05或P<0.01）而过表达SNRPA则能促进LO2细胞增殖（P<0.01），敲减SNRPA表达明显抑制HepG2和Hep3B细胞的迁移和侵袭能力（均P<0.01），明显促进E-cadherin 的表达上调（P<0.01），而抑制N-cadherin、vimentin 的表达（P<0.01）。结论: SNRPA在HCC组织及细胞中呈明显高表达，其可能通过调控上皮间质转化（EMT）进程进而促进HepG2和Hep3B细胞的增殖、迁移和侵袭。     

水蛭素对肝细胞癌HepG2细胞抑制作用机制探讨

目的 研究水蛭素对肝细胞癌（hepatocellular carcinoma,HCC,简称肝癌）HepG2细胞抑制作用及其抗肝癌的分子机制。方法 将含不同浓度（1 U/mL、2 U/mL、4 U/mL和8 U/mL）水蛭素的培养液作用于肝癌HepG2细胞,采用MTT法检测水蛭素对肝癌HepG2细胞增殖的影响,流式细胞仪检测水蛭素对肝癌HepG2细胞凋亡的影响,Transwell法检测水蛭素对肝癌HepG2细胞迁移、侵袭的影响,荧光定量PCR检测血管内皮生长因子（vascular endothelial growth factor,VEGF）基因的mRNA表达水平,Western blot检测VEGF基因的蛋白表达水平。结果 与空白对照组比较,肝癌HepG2细胞增殖抑制率随水蛭素浓度（1 U/mL、2　U/mL、4 U/mL和8 U/mL）增加及作用时间（24　h、48　h、72　h）延长而增加,呈剂量-时间依赖效应（P<0.05）。不同浓度（2 U/mL、4 U/mL和8 U/mL）水蛭素作用48 h后,肝癌HepG2细胞凋亡率分别为（28.37±1.16）%、（40.27±0.97）%、（76.17±1.5）%,细胞侵袭个数分别为（204±9）个、（163±6）个、（94±4）个,细胞迁移个数分别为（86±5）个、（54±7）个、（20±5）个,细胞凋亡率、侵袭及迁移个数随水蛭素浓度增加而增加,呈浓度依赖性（P<0.05）。VEGF mRNA、蛋白的表达量随水蛭素浓度增加而明显下调（P<0.05）。结论 水蛭素能抑制肝癌HepG2细胞增殖、凋亡、迁移及侵袭,其机制可能是通过下调VEGF表达。     

转录因子XBP1S对人肝癌HepG2细胞增殖及凋亡的影响

目的:探讨人剪接型X盒结合蛋白1(X-box binding protein1spliced,XBP1S)对肝癌HepG2细胞增殖和凋亡的影响。方法:应用衣霉素(tunicamycin,Tm)和毒胡萝卜素(thapsigargin,Tg)建立HepG2细胞的内质网应激(endoplasmic reticulum stress,ERS)模型。将XBP1S真核表达载体pcDNA3.1(-)-XBP1S和靶向XBP1S的RNA干扰质粒pSUPER-XBP1S转染HepG2细胞,MTT法检测细胞的增殖能力,荧光显微镜下观察细胞的形态学变化,FCM法检测细胞凋亡率,Western印迹法检测caspase12的表达。结果:转染pSUPER-XBP1S可有效抑制细胞增殖,而转染pcDNA3.1(-)-XBP1S可促进细胞增殖。荧光显微镜下可见Tm处理组细胞出现细胞凋亡的形态学改变,进一步下调XBP1S的表达可使这一改变增强。对照组、Tm组、Tm+pSUPER-XBP1S转染组和Tm+pcDNA3.1(-)-XBP1S转染组细胞的凋亡率分别为5.21%、41.51%、52.15%和35.87%,差异有统计学意义(P<0.05)。HepG2细胞中caspase12的表达,Tm组高于对照组,Tm+pSUPER-XBP1S转染组高于Tm组,Tm+pcDNA3.1(-)-XBP1S转染组低于Tm组。结论:XBP1S可以促进肝癌HepG2细胞增殖,抑制或促进XBP1S表达可调节ERS介导的细胞凋亡。     

剪接因子SF3b6通过MAPK信号通路促进胃癌细胞的增殖和迁移

目的：探讨剪接因子3b亚基6（splicing factor 3b subunit 6,SF3b6）对胃癌细胞增殖、凋亡、侵袭和迁移等的影响及其作用机制。方法：通过组织芯片检测 SF3b6 在胃癌和癌旁组织中的表达,采用 WB 和 qPCR检测SF3b6在正常永生化胃上皮细胞(GES-1)和胃癌细胞系(HGC27、AGS、BGC823、MGC803、SGC7901、MKN45)中的表达水平。选取AGS和MGC803细胞转染SF3b6-siRNA、BGC823和SGC7901细胞转染SF3b6过表达质粒进行功能实验,CCK-8实验检测SF3b6对胃癌细胞增殖的影响,Transwell迁移和侵袭实验检测SF3b6对胃癌细胞迁移和侵袭能力的影响,流式细胞术检测细胞凋亡水平,WB检测凋亡和迁移相关分子及MAPK信号分子在蛋白水平的变化。结果:SF3b6在胃癌细胞MGC803和AGS表达水平高于正常胃上皮细胞GES-1,而在BGC823和SGC7901细胞中低于GES-1细胞（P<0.05或P<0.01）。敲低SF3b6的表达抑制了胃癌细胞系AGS和MGC803的增殖、迁移和侵袭,并促进了细胞凋亡（P<0.05或P<0.01）;过表达SF3b6促进了胃癌细胞系BGC823和SGC7901的增殖、迁移和侵袭（P<0.05或P<0.01）。机制研究表明,敲低SF3b6表达促进了JNK 和 P38 的活化,以及凋亡相关蛋白 cleaved caspase-9、cleaved PARP、Bax的表达（P<0.05或P<0.01）,同时抑制胃癌细胞上皮间质转化的进程。结论：剪接因子SF3b6通过MAPK信号通路增强胃癌细胞增殖和迁移,促进胃癌的发展进程。     

Religiosity and Physical and Emotional Functioning Among African American and White Colorectal and Lung Cancer Patients

The literature suggests that religiosity helps cope with illness. The present study examined the role of religiosity in functioning among African Americans and Whites with a cancer diagnosis. Patients were recruited from an existing study and mailed a religiosity survey. Participants (N = 269; 36% African American, 56% women) completed the mail survey, and interview data from the larger cohort was utilized in the analysis. Multivariate analyses indicated that in the overall sample religious behaviors were marginally and positively associated with mental health and negatively with depressive symptoms. Among women, religious behaviors were positively associated with mental health and negatively with depressive symptoms. Religiosity was not a predictor of study outcomes for men. Among African Americans, religious behaviors were positively associated with mental health and vitality. Among Whites, religious behaviors were negatively associated with depressive symptoms. These findings suggest a mixed role of religious involvement in cancer outcomes. The current findings may have applied potential in the areas of emotional functioning and depression.     

Occupational and environmental radiation and cancer

Epidemiologic evidence on the relation between occupational and environmental radiation and cancer is reviewed. Studies of pioneering radiation workers, underground miners, and radium dial painters revealed excess cancer deaths and contributed to the setting of radiation protection standards and to theories of carcinogenesis. Occupational exposures today are generally much lower than in the past, thus any associated increases in cancer will be difficult to detect. Pooling investigations of these more recently exposed workers, however, has the potential to validate current estimates of risk used in radiation protection. New information on the effects of chronic radiation exposure also may come from studies in the former Soviet Union of Chernobyl clean-up workers and of workers at the Mayak nuclear facilities. Studies of environmental radiation exposures, other than radon, are largely inconclusive, due mainly to the difficulties in detecting the low risks associated with low dose exposures. Thyroid cancer, however, has been linked to environmental radiation from the Chernobyl accident and from nuclear weapons tests. Low-level radiation released during normal operations at nuclear plants has not been found to increase cancer rates in surrounding populations. Radon, a human carcinogen, is the most ubiquitous exposure to human populations; remediating high residential-radon levels is recommended, recognizing that the exposure can never be removed completely because it occurs naturally.     

Vitamin D and melanoma and non-melanoma skin cancer risk and prognosis: A comprehensive review and meta-analysis

Vitamin D is formed mainly in the skin upon exposure to sunlight and can as well be taken orally with food or through supplements. While sun exposure is a known risk factor for skin cancer development, vitamin D exerts anti-proliferative and pro-apoptotic effects on melanocytes and keratinocytes in vitro. To clarify the role of vitamin D in skin carcinogenesis, we performed a review of the literature and meta-analysis to evaluate the association of vitamin D serum levels and dietary intake with cutaneous melanoma (CM) and non-melanoma skin cancer (NMSC) risk and melanoma prognostic factors. Twenty papers were included for an overall 1420 CM and 2317 NMSC. The summary relative risks (SRRs) from random effects models for the association of highest versus lowest vitamin D serum levels was 1.46 (95% confidence interval (CI) 0.60–3.53) and 1.64 (95% CI 1.02–2.65) for CM and NMSC, respectively. The SRR for the highest versus lowest quintile of vitamin D intake was 0.86 (95% CI 0.63–1.13) for CM and 1.03 (95% CI 0.95–1.13) for NMSC. Data were suggestive of an inverse association between vitamin D blood levels and CM thickness at diagnosis. Further research is needed to investigate the effect of vitamin D on skin cancer risk in populations with different exposure to sunlight and dietary habits, and to evaluate whether vitamin D supplementation is effective in improving CM survival.     

New and emerging radiosensitizers and radioprotectors

The combination of chemotherapy and radiation has led to clinical breakthroughs in several disease sites, and current work continues to define optimum combinations of proven chemotherapy as well as more recently available, noncytotoxic agents. Administration of systemic therapies allows modulation of radiation response to improve tumor control (radiosensitization) or to prevent normal tissue toxicity (radioprotection). Substantial progress has been made in identifying the targets of standard chemotherapeutic radiation sensitizers and protectors as well as in the introduction of a new generation of molecularly targeted therapies in combination with radiation. We have reviewed the most recent, predominantly early phase clinical trials combining systemic agents with radiation. Although the proof of an improved schedule ultimately needs to come from well-run Phase III trials, the search among schedules could be shortened by the use of surrogate endpoints such as presence of active drug metabolites in the tumor. This has been accomplished only in a few cases and needs to become a more standard part of radiation sensitizer and protector trials.     

Fruit and vegetables and cancer risk

The possibility that fruit and vegetables may help to reduce the risk of cancer has been studied for over 30 years, but no protective effects have been firmly established. For cancers of the upper gastrointestinal tract, epidemiological studies have generally observed that people with a relatively high intake of fruit and vegetables have a moderately reduced risk, but these observations must be interpreted cautiously because of potential confounding by smoking and alcohol. For lung cancer, recent large prospective analyses with detailed adjustment for smoking have not shown a convincing association between fruit and vegetable intake and reduced risk. For other common cancers, including colorectal, breast and prostate cancer, epidemiological studies suggest little or no association between total fruit and vegetable consumption and risk. It is still possible that there are benefits to be identified: there could be benefits in populations with low average intakes of fruit and vegetables, such that those eating moderate amounts have a lower cancer risk than those eating very low amounts, and there could also be effects of particular nutrients in certain fruits and vegetables, as fruit and vegetables have very varied composition. Nutritional principles indicate that healthy diets should include at least moderate amounts of fruit and vegetables, but the available data suggest that general increases in fruit and vegetable intake would not have much effect on cancer rates, at least in well-nourished populations. Current advice in relation to diet and cancer should include the recommendation to consume adequate amounts of fruit and vegetables, but should put most emphasis on the well-established adverse effects of obesity and high alcohol intakes.     

肾上腺素能β受体与肿瘤生长及转移

大量研究表明肿瘤细胞可表达β受体，而一些神经递质、药物和社会心理因素可能通过β受体影响肿瘤的生长和转移，β受体激动剂、β受体阻滞剂以及抑郁等社会心理因素可加强或削弱这种作用。这为表达β受体肿瘤的治疗开辟了新的道路，提供了新的治疗靶点。     

VEGF及KDR在大肠腺瘤和腺癌中的表达及意义

目的：探讨VEGF和KDR在大肠腺瘤和大肠腺癌中的表达及临床病理特征的关系。方法：大肠腺瘤和大肠腺癌组织标本各100例,采用免疫组织化学染色法检测VEGF和KDR在标本中的表达情况。结果：VEGF和KDR在大肠腺癌组中的阳性表达明显高于大肠腺瘤组（P〈0.05）;在正常大肠黏膜均未见VEGF和KDR表达的阳性染色;VEGF阳性表达组中KDR的阳性表达率为70%,显著高于VEGF阴性表达组中KDR的阳性表达率16%,两组比较有统计学意义（P〈0.01）。结论：大肠腺癌组织中KDR的表达与肿瘤大小、转移情况、浸润深度密切相关;VEGF和KDR在大肠腺瘤中的表达与患者的年龄、性别及分型均无相关性,而与增生程度相关（P〈0.05）。在大肠腺癌患者中VEGF及KDR表达更高,二者具有协同效应。     

Cell and tissue interactions in carcinogenesis and metastasis and their clinical significance

This review describes a new vision for future directions in the study of metastatic cancer biology and pathology. It is based upon clinical and experimental observations on the constituent cell lineages within a neoplasm and on tumour-host interactions. The vision incorporates information from studies in population biology, developmental biology and experimental pathology as well as investigations upon human malignant disease. The assembled information reveals that invasion and metastasis are supra-cellular manifestations of "emergent behavior" among combinations of normal and malignant cell lineages in vivo. Emergent behavior is a combinatorial interactive process in which a population displays new traits which cannot be achieved by individuals acting separately and which subside when the specific population mix disaggregates. Disruption of such pathological interactions in the field of a developing primary or secondary tumour is, therefore, required to disable the malignant population and arrest progression without tissue destruction. These conclusions originate, in part, from principles which govern the sociobiology and group behavior of bees, ants, fish, birds and human societies. In all these social organisms, external factors can disrupt signaling mechanisms and induce expanding self-perpetuating rogue behavior, leading to social disintegration. These principles also apply to cellular societies composing higher animals, which likewise need intrinsic rules to maintain social order and avoid anarchy, and recognition of this is essential for advancing future research on the mechanisms involved in carcinogenesis and metastasis. Summarised evidence is presented here to support the conclusion that miscommunications between cells and tissues in the region of the developing tumour and its metastases are the main direct perpetrators of malignant disease. Genetic lesions (mutations, deletions, translocations, reduplications, etc.), commonly seen in cancers, can significantly disrupt important molecular pathways in the networks of communications needed to sustain orderly tissue/organ structure and function. However, genetic lesions can also, themselves, be induced by abnormal cell interactions initiated by extrinsic carcinogenic agents such as chemicals, viruses, hormones and radiation. The evidence shows that, irrespective of the initiating cause, it is this miscommunication in the region of a developing tumour and its metastases that is ultimately responsible for the emergence and progression of the disease. The article describes how this information collectively, provides a framework for designing specific novel therapeutic approaches targeting the cell and tissue interactions driving tumour metastasis and its manifold effects on the whole body.