lncRNAXIST/miR-34a-5p/SIRT6 分子轴调控口腔鳞癌细胞的增殖及转移

[摘要] 目的：探究lncRNA XIST/miR-34a-5p/SIRT6 分子轴调控口腔鳞癌细胞增殖和转移及其分子机制。方法：收集2013年3 月至2018 年3 月在青岛市口腔医院就诊的OSCC患者47 例癌组织和癌旁组织标本,采用qPCR检测OSCC患者组织及细胞系中lncRNA XIST、miR-34a-5p、SIRT6 mRNA 的表达,WB检测OSCC 患者组织及细胞系中SIRT6、Ki67、pcDNA、cleaved-caspase3、cleaved-caspase8、E-cadherin、Vimentin 蛋白的表达,采用CCK-8 实验检测敲降lncRNA XIST对Cal-27 及Tca-8113 细胞增殖的影响,Transwell 小室法检测Cal-27 及Tca-8113 细胞迁移及侵袭;流式细胞术检测Cal-27 及Tca-8113 细胞凋亡情况,双荧光素酶报告基因检测lncRNA XIST与miR-34a-5p、miR-34a-5p 与SIRT6 靶向结合关系。结果：lncRNA XIST和SIRT6 在OSCC患者癌组织及细胞系中高表达（均P<0.05）,miR-34a-5p 则呈低表达（P<0.01）;敲降lncRNA XIST抑制OSCC细胞的增殖、迁移及侵袭并促进细胞凋亡（均P<0.01）,同时转染miR-34a-5p 抑制剂或pcDNA-SIRT6 载体作用则相反;敲降lncRNA XIST 促进OSCC细胞中增殖及转移相关蛋白表达（均P<0.01）,同时转染miR-34a-5p 抑制剂或pcDNA-SIRT6 载体作用则相反;lncRNA XIST 与miR-34a 靶向结合,miR-34a 与SIRT6 靶向结合;lncRNA XIST 通过靶向miR-34a-5p 上调SIRT6 表达（P<0.01）。结论：lncRNA XIST/miR-34a-5p/SIRT6 分子轴能够调控OSCC细胞增殖及转移,为OSCC治疗提供潜在靶点。     

lncRNA FLJ26245 通过 miR-200a-3p/PTPRG 轴调控前列腺癌 PC-3 细 胞的增殖与迁移

目的：探讨lncRNA FLJ26245在前列腺癌组织和细胞中的表达及其对PC-3细胞增殖与迁移能力的影响及其分子机 制。方法：选用2017年3月至2019年5月在洛阳中心医院手术切除的52例前列腺癌及相应的癌旁组织标本,以及前列腺细胞系 LNCaP、C4-2B、PC-3、DU-145和正常前列腺上皮细胞RWPE-1,用qPCR法检测前列腺癌组织和细胞中FLJ26245的表达水平。分 别将FLJ26245 mimic和阴性对照质粒（lncR-NC）转染到PC-3细胞中,用MTT法、细胞划痕愈合实验分别检测细胞的增殖和迁移 能力。生物信息学技术预测和双荧光素酶基因报告实验验证FLJ26245与miR-200a-3p、酪氨酸磷酸酶受体G（PTPRG）三者之间 的靶向关系。用qPCR 和 WB 法分别检测 FLJ26245 下游基因及增殖与迁移相关蛋白的表达。结果：FLJ26245 在前列腺癌组 织和细胞中的表达水平分别显著低于癌旁组织（P<0.01）和 RWPE-1细胞（P<0.01或P<0.05）,以PC-3细胞中的表达水平为最低（P<0.01）。FLJ26245过表达可明显抑制PC-3细胞的增殖和迁移能力（P<0.05或P<0.01）。FLJ26245可与miR-200a-3p靶向结 合,miR-200a-3p可与PTPRG靶向结合（均P<0.01）。FLJ26245过表达的PC-3细胞中miR-200a-3p表达水平显著降低（P<0.01）、PTPRG mRNA和蛋白表达水平均明显升高（均P<0.01）,细胞中增殖和迁移相关蛋白cyclin A、CDK2和Twist、N-cadherin均显著 降低（均P<0.01）。结论：FLJ26245在前列腺癌组织及细胞中均低表达,其可能通过miR-200a-3p/PTPRG轴调控前列腺癌PC-3 细胞的增殖与迁移能力。     

miR-19a-3p 靶向细胞黏附分子2 阻断AKT通路抑制肾癌细胞786-O 的增殖和迁移

[摘要] 目的：探讨肾癌组织高表达的miR-19a-3p 靶向调控细胞黏附分子2（cell adhesion molecule 2,CADM2）并通过AKT信号通路影响肾癌细胞增殖和迁移的机制。方法：收集2012 年4 月至2017 年11 月苏州大学附属第一医院肾内科收治的42 例资料完整的肾癌患者手术切除的肾癌组织和癌旁组织标本。采用qPCR检测肾癌组织和786-O等4 种肾癌细胞系中miR-19a-3p 的表达水平,CCK-8、Transwell 和免疫荧光法检测miR-19a-3p 敲减对肾癌786-O 细胞增殖、侵袭和上皮间质转化的影响,双荧光素酶报告基因验证miR-19a-3p 与CADM2 的靶向关系。采用Wb 检测miR-19a-3p 通过CADM2 对AKT信号通路的调控作用。结果：miR-19a-3p 在肾癌组织及细胞系中均高表达（均P<0.01）。敲减miR-19a-3p 可显著抑制786-O 细胞增殖、迁移和上皮间质转化,且miR-19a-3p 靶向作用CADM2 并下调其表达水平（P<0.05 或P<0.01）。敲减miR-19a-3p 通过靶向上调CADM2 并阻断AKT信号通路进而显著抑制786-O细胞增殖、迁移和上皮间质转化（均P<0.05 或P<0.01）,从而缓解肾癌发生发展。结论：肾癌组织中miR-19a-3p 高表达,敲减miR-19a-3p 可显著抑制肾癌细胞的增殖、迁移和上皮间质转化,其机制可能是通过miR-19a-3p/CADM2/AKT分子轴起作用。     

微小RNA-380-5p 在宫颈癌组织及细胞中的表达及其通过下调RHOA抑制C33A细胞的增殖和迁移

[摘要] 目的：检测微小RNA-380-5p（miR-380-5p）在人宫颈癌组织和细胞系中的表达,探讨其抑制宫颈癌C33A细胞增殖和迁移的作用机制。方法：收集2016 年12 月至2017 年7 月同济医学院附属武汉中心医院妇产科手术切除的16 例宫颈癌患者癌组织和对应的癌旁组织标本,以及宫颈癌细胞系HCC94、C33A、Hela、SiHa 和人子宫颈上皮永生化细胞H8,用qPCR 法检测miR-380-5p 在癌及癌旁组织、4 种宫颈癌细胞及H8 细胞中的表达。用脂质体转染技术将miR-380-5p mimic（实验组）和miR-NC（阴性对照组）瞬时转染C33A细胞,用qPCR法检测转染后细胞中miR-380-5p 表达,CCK-8 法和Transwell 小室法分别检测转染细胞的增殖和迁移能力。用生物信息学软件TargetScan 预测miR-380-5p 的下游基因,用双荧光素酶报告基因实验验证miR-380-5p 对下游基因Ras 同源基因家族成员A（Ras homolog gene family member A,RHOA）的结合作用,qPCR 法和Western blotting 检测miR-380-5p 下游基因RHOA的表达。结果：宫颈癌组织中miR-380-5p 表达水平明显低于癌旁组织（P<0.01）,宫颈癌细胞系中miR-380-5p 表达水平均明显低于H8 细胞（P<0.05）,以C33A细胞中的表达水平最低（P<0.01）。与阴性对照组比较,转染miR-380-5pmimic 能显著抑制C33A细胞的增殖（P<0.05）和迁移能力（P<0.01）,且下调RHOA、ROCK1、ROCK2、CDK2和N-cadherin蛋白的表达（均P<0.01）。生物信息学软件预测RHOA可能为miR-380-5p 的调控基因,双荧光素酶报告基因实验结果显示miR-380-5p 可与RHOA 3’-非编码区（UTR）特异性结合,miR-380-5p 可明显下调RHOA基因的表达（P<0.01）。结论：miR-380-5p 在宫颈癌组织及细胞系中低表达,过表达miR-380-5p 可能通过下调RHOA及其下游蛋白的表达抑制宫颈癌C33A细胞的增殖和迁移。     

敲减lncRNA RP1-261G23.7抑制胶质瘤细胞增殖和迁移及其机制探讨北大核心

目的:探讨长链非编码RNA(long non-coding RNA,lncRNA)RP1-261G23.7对人胶质瘤细胞增殖及迁移的影响及可能的调控机制。方法:采用GEPIA数据库分析RP1-261G23.7在胶质瘤组织中的相对表达。采用qRT-PCR检测RP1-261G23.7在4种胶质瘤细胞系(U87MG、SNB-19、U251、LN382)中的相对表达。采用Lipofectamine3000向胶质瘤细胞U87MG中单独转染si-RP1-261G23.7质粒(si-RP1-261G23.7组)和si-NC对照质粒(si-NC组)。采用CCK-8实验和细胞划痕实验检测转染后U87MG细胞的增殖及迁移能力。采用生物信息学、qRT-PCR和双荧光素酶报告基因实验研究RP1-261G23.7和miR-525-5p表达的关系。Western blotting检测NF-κB信号通路蛋白的表达。结果:与正常组织相比,RP1-261G23.7在胶质瘤组织中表达上调(P<0.01)。与人脑星型胶质正常细胞系(HEB)相比,RP1-261G23.7在四种胶质瘤细胞系中表达均上调(P<0.01),U87MG细胞中RP1-261G23.7相对表达量最高(P<0.01)。与si-NC组相比,敲减RP1-261G23.7显著抑制了U87MG细胞的增殖(P<0.05)和划痕愈合(P<0.01)。RP1-261G23.7能够直接互补结合miR-525-5p(P<0.01)。与si-NC组相比,敲减RP1-261G23.7表达显著促进了U87MG细胞中miR-525-5p的表达(P<0.01),NF-κB信号通路蛋白表达显著下降(P<0.01)。结论:胶质瘤组织和细胞系中RP1-261G23.7表达明显上调,敲减RP1-261G23.7通过促进miR-525-5p表达、干扰NF-κB信号通路活化,抑制胶质瘤U87MG细胞的增殖和迁移,可能为胶质瘤的靶向治疗开辟新的路径。     

miR-125a-5p通过下调BAG4表达抑制胃癌细胞迁移和侵袭

目的：探讨miR-125a-5p通过调控Bcl-2相关永生基因4（Bcl-2-associated athanogene 4,BAG4）的表达抑制胃癌细胞 迁移和侵袭的分子机制。方法：选用2014年1月至2015年12月兰州大学第一医院手术切除的82例胃癌组织标本及配对的癌旁 组织以及人胃癌细胞系MGC803、BGC823、SGC7901、HGC27及人胃黏膜上皮细胞（GES-1）,qPCR法检测胃癌组织、癌旁组织及 胃癌细胞系中miR-125a-5p的表达水平。分别将miR-125a-5p mimic、miR-125a-5p inhibitor、（si-BAG4）siRNA-BAG4及阴性对照 质粒转染至胃癌细胞,划痕愈合实验和Transwell侵袭实验分别检测miR-125a-5p/BAG4信号轴对胃癌细胞迁移和侵袭能力的影 响。WB检测胃癌细胞中BAG4蛋白的表达。荧光素酶报告基因实验验证miR-125a-5p和BAG4之间的靶向调控关系。结果： miR-125a-5p在胃癌组织和细胞系中均低表达（均P<0.01）。miR-125a-5p的表达与患者的性别（P=0.953）、年龄（P=0.772）、肿瘤 部位(P=0.867)、组织学分级（P=0.745）和肿瘤大小（P=0.088）无相关性 ,与胃癌患者的 T 分期（P=0.003）、N 分期（P=0.001）、 M分期（P=0.027）和TNM分期（P=0.035）显著相关,差异有统计学意义。miR-125a-5p低表达是胃癌患者总生存时间的独立危险 因素。过表达miR-125a-5p显著抑制胃癌细胞的迁移和侵袭能力（均P<0.01）。敲降BAG4可逆转miR-125a-5p inhibitor对胃癌细 胞迁移和侵袭能力的抑制作用。荧光素酶报告基因实验证实miR-125a-5p可与BAG4 3''非翻译区（untranslated regions,UTR）结 合抑制其表达。结论：miR-125a-5p通过靶向下调BAG4的表达水平进而抑制胃癌细胞的迁移和侵袭。的表达抑制胃癌细胞 迁移和侵袭的分子机制。方法：选用2014年1月至2015年12月兰州大学第一医院手术切除的82例胃癌组织标本及配对的癌旁 组织以及人胃癌细胞系MGC803、BGC823、SGC7901、HGC27及人胃黏膜上皮细胞（GES-1）,qPCR法检测胃癌组织、癌旁组织及 胃癌细胞系中miR-125a-5p的表达水平。分别将miR-125a-5p mimic、miR-125a-5p inhibitor、（si-BAG4）siRNA-BAG4及阴性对照 质粒转染至胃癌细胞,划痕愈合实验和Transwell侵袭实验分别检测miR-125a-5p/BAG4信号轴对胃癌细胞迁移和侵袭能力的影 响。WB检测胃癌细胞中BAG4蛋白的表达。荧光素酶报告基因实验验证miR-125a-5p和BAG4之间的靶向调控关系。结果： miR-125a-5p在胃癌组织和细胞系中均低表达（均P<0.01）。miR-125a-5p的表达与患者的性别（P=0.953）、年龄（P=0.772）、肿瘤 部位(P=0.867)、组织学分级（P=0.745）和肿瘤大小（P=0.088）无相关性 ,与胃癌患者的 T 分期（P=0.003）、N 分期（P=0.001）、 M分期（P=0.027）和TNM分期（P=0.035）显著相关,差异有统计学意义。miR-125a-5p低表达是胃癌患者总生存时间的独立危险 因素。过表达miR-125a-5p显著抑制胃癌细胞的迁移和侵袭能力（均P<0.01）。敲降BAG4可逆转miR-125a-5p inhibitor对胃癌细 胞迁移和侵袭能力的抑制作用。荧光素酶报告基因实验证实miR-125a-5p可与BAG4 3''非翻译区（untranslated regions,UTR）结 合抑制其表达。结论：miR-125a-5p通过靶向下调BAG4的表达水平进而抑制胃癌细胞的迁移和侵袭。     

miR-203a-3p 在胰腺癌组织与细胞中的表达及其对 BxPC-3 细胞增殖、 迁移和侵袭的影响

目的：探讨miR-203a-3p对胰腺癌BxPC-3细胞增殖、迁移和侵袭能力的影响。方法：运用癌症基因组图谱（TCGA） 数据库筛选胰腺癌组织和癌旁组织中差异表达的miRNA,分析miRNA高表达与低表达时胰腺癌患者的生存率和临床分期;利用 TarBase数据库分析miRNA与癌症相关的GO功能与KEGG通路,利用DIANA Tools、miRDB和TargetScan网站预测miR-203a-3p 的靶基因。将miR-203a-3p mimic及NC mimic、miR-203a-3p inhibitor及NC inhibitor转染至BxPC-3细胞,用qPCR法检测胰腺癌 细胞和胰腺正常上皮细胞HPNE中miR-203a-3p、miR-192-5p和miR-451a表达水平,以CCK-8法、Transwell小室法和克隆形成实 验分别检测BxPC-3细胞的增殖、迁移、侵袭和集落形成能力。结果：通过TCGA数据库筛选出18个胰腺癌组织中差异表达的 miRNA,其中miR-203a-3p、miR-192-5p、miR-451a具有物种保守性 ,且其与胰腺癌临床癌症分期、细胞周期和患者生存率相 关（均P<0.05）;生物信息学网站预测显示miR-203a-3p的候选靶基因是PPM1A,PPM1A与多基因存在相互作用。miR-203a-3p、 miR-192-5p和miR-451a在BxPC-3和Aspc-1细胞中均高表达（均P<0.01）。miR-203a-3p mimic组BxPC-3细胞中miR-203a-3p表 达水平以及细胞增殖、迁移和侵袭能力均显著提高（均P<0.01）：miR-203a-3p inhibitor组细胞中miR-203a-3p表达水平以及细胞 增殖、迁移和侵袭能力均显著降低（均P<0.01）。结论：miR-203a-3p在胰腺癌组织及细胞中均高表达,其表达与患者生存和临床 分期相关,可调控BxPC-3细胞的增殖、迁移和侵袭能力。     

miRNA-26b-3p通过靶向STAT3调控食管鳞状细胞癌细胞的增殖和迁移

目的：观察miR-26b-3p在食管鳞状细胞癌（ESCC）组织中的表达水平及其对ESCC细胞增殖、侵袭和迁移能力的影响,并探讨其分子调控机制。方法: 选取河北医科大学第四医院2018年4月1日至2018年12月25日手术切除的ESCC组织及相应癌旁组织各60例,利用qPCR法检测ESCC组织、癌旁组织和ESCC细胞中miR-26b-3p的表达。选取miR-26b-3p表达水平较低的ESCC细胞TE1和KYSE150,转染miR-26b-3p mimic,并设立阴性对照。利用细胞增殖实验、划痕愈合实验和Transwell实验检测过表达miR-26b-3p对TE1和KYSE150细胞增殖、迁移和侵袭能力的影响。荧光素酶报告基因实验检测miR-26b-3p与STAT3的 3''UTR 靶点部位的结合情况。随后同时转染 miR-26b-3p mimic 和 pcDNA3.0-STAT3,利用细胞增殖实验、划痕愈合实验和Transwell实验检测STAT3是否可逆转过表达miR-26b-3p对细胞增殖、迁移和侵袭能力的影响。qPCR 和 WB法检测甲基化酶抑制剂5-Aza-DC对ESCC细胞甲基化的影响和miR-26b-3p与STAT3表达的影响。结果: miR-26b-3p在ESCC组织中的表达低于癌旁组织（P<0.01）,其在 ESCC 细胞TE1、KYSE150和LYSE170中表达水平显著低于人正常食管上皮细胞HEEC（均P<0.01）。与miR-26b-3p NC组相比,miR-26b-3p mimic转染可明显上调TE1和KYSE150细胞中miR-26b-3p的表达（均P<0.01）,但可明显抑制两种细胞的增殖、迁移和侵袭能力（P<0.05或P<0.01）。荧光素酶报告基因实验结果表明,在TE1和KYSE150细胞中,miR-26b-3p明显抑制了野生型STAT3载体的荧光素酶活性（P<0.05或P<0.01）,而突变型的荧光素酶活性不受影响。同时转染miR-26b-3pmimic和pcDNA3.0-STAT3可部分逆转miR-26b-3p mimic对TE1 和 KYSE150 细胞增殖、迁移和侵袭能力的抑制作用（P<0.05或P<0.01）。5-Aza-DC 处理后 ,TE1 和 KYSE150 细胞中 miR-26b-3p 表达上调（均 P<0.01）、STAT3 mRNA 和蛋白水平降低（P<0.05）,miR-26b-3p呈现去甲基化状态。结论: miR-26b-3p的启动子高甲基化导致其在ESCC组织和细胞中的表达下调,其作为抑癌因子可通过靶向STAT3而抑制ESCC细胞的增殖、侵袭和迁移能力。     

miR-125a-5p通过靶向APAF1 增强非小细胞肺癌细胞吉非替尼耐药性

目的：探讨miR-125a-5p 在诱导非小细胞肺癌（non-small cell lung cancer，NSCLC）细胞吉非替尼（gefitinib，Gef）耐药中的作用及其机制。方法：选用人NSCLC 耐药细胞株A549/GR 和NSCLC细胞株A549，将miR-125a-5p mimic、miR-125a-5p inhibitor、pcDNA3.1-APAF1、空载体pcDNA3.1 转染至A549/GR细胞。用qPCR检测细胞中miR-125a-5p 的表达水平，用MTT法、Transwell 小室法和流式细胞术检测Gef 对细胞增殖、迁移和凋亡的影响。用双荧光素酶报告基因实验验证miR-125a-5p 与细胞凋亡蛋白酶活化因子1（apoptotic peptidase activating factor 1，APAF1）的靶向关系，用Western blotting检测A549/GR细胞中APAF1蛋白水平，用比色法测定细胞中caspase-3 及caspase-9 表达水平。结果：A549/GR 细胞中miR-125a-5p 表达水平显著高于A549 细胞（P<0.01）。敲降miR-125a-5p 显著增强Gef 对A549/GR细胞增殖、迁移的抑制作用（均P<0.05），并促进细胞凋亡（P<0.01）。双荧光素酶报告基因实验证实miR-125a-5p 靶向APAF1，并负调控其表达。进一步实验显示，miR-125a-5p 通过靶向下调APAF1 缓解Gef 对A549/G 细胞增殖、迁移的抑制作用及凋亡的促进作用（均P<0.05），减弱Gef引起的凋亡相关蛋白caspase-3及caspase-9表达的上调（均P<0.05）。结论：miR-125a-5p 促进NSCLC细胞Gef 耐药，其机制是通过靶向APAF1 而促进细胞的增殖、迁移并抑制凋亡。     

Clinicopathological study of carcinomas of the lip and the mucosa of the upper and lower lips

BACKGROUND: Lip carcinomas are rare oral tumors, and there have been few reports of lip carcinoma in Japan. METHODS: Of 914 patients with oral carcinomas treated between January 1980 and December 1998, 12 (1.3%) had lip carcinoma and 5 (0.5%) had lip mucosal carcinoma. We investigated the clinicopathological features of these 17 patients. RESULTS: Of the 12 patients with carcinoma of the lip, 10 had squamous cell carcinomas (9, external lower lip; 1 commissures) and 2 had mucoepidermoid carcinomas (external upper lip). Of the 5 patients with lip mucosal carcinoma, 3 had squamous cell carcinomas (2, mucosa of the lower lip; 1, mucosa of the upper lip), 1 had mucoepidermoid carcinoma (mucosa of the lower lip), and 1 had acinic cell carcinoma (mucosa of the lower lip). Of the 12 patients with lip carcinoma, 9 were classified as stage I, 2 as stage II, and 1 as stage III; all 5 of the patients with lip mucosal carcinoma were stage I. Five patients with lip carcinoma were treated by resection, 5 by a combination of resection and reconstruction, and 2 by radiotherapy alone. All patients with lip mucosal carcinoma were treated by resection. After the initial therapy, 3 patients without neck dissection had regional recurrences and received delayed neck dissection, and 2 died with neck regional recurrence after dissection. The 5-year cumulative survival rates of the patients with lip carcinoma and those with lip mucosal carcinoma were 82.5% and 80.0%, respectively. CONCLUSION: We suggest that early-stage carcinomas of the lip and of the mucosa of the upper and lower lips are frequent, and we found that the outcome of these patients was excellent. However, an aggressive therapeutic approach to the lip carcinoma patient with cervical metastasis appears warranted, in an attempt to improve locoregional control and ultimate survival.     

Experience in the treatment of synchronous and metachronous carcinoma of the oesophagus and the head and neck

BACKGROUND AND OBJECTIVES: Treatment of multiple primary squamous cell carcinomas of the head and neck and oesophagus is controversial. The poor prognosis of these 2 types of carcinoma taken individually and their anatomic proximity complicate the therapeutic strategy and limit the treatment choices for each location. METHODS: From 1986 to 1998, 43 patients received curative treatment for multiple synchronous (n = 30) or metachronous (n = 13) primary neoplasms of the oesophagus and head and neck. For synchronous cancers, the therapeutic strategy consisted of first curing the head and neck cancer and then planning oesophagectomy according to the type of head and neck cancer therapy. RESULTS: Ten total oesopharyngolaryngectomies and 33 subtotal oesophagectomies were performed. The postoperative mortality rate was 9.3% (4/43). The rate of anastomotic leakage was 30% (13/43), and all such leaks were cervical. Pulmonary infection occurred in 19% of cases (8/43). A past history of cervical radiation therapy or cervicotomy did not appear to be a significant risk factor for anastomotic leakage or pulmonary complications. Oesophagectomy did not affect the functional results in the 31 patients whose larynx could be preserved. CONCLUSIONS: Oesophagectomy after head and neck cancer treatment is possible with a low mortality rate and acceptable morbidity.     

胆囊结石及胆囊切除与结直肠癌的关系探讨

目的 探讨胆囊结石及胆囊切除与结直肠癌的关系.方法 回顾性分析347例结直肠癌及608例其他消化道癌的临床资料.结果 结直肠癌患者胆囊结石发生率及既往胆囊切除率显著高于对照组(P<0.05).结论 胆囊结石及胆囊切除可能是结直肠癌的高危因素.     

Comparison of the Efficacy and Safety of Ceftibuten and Cefaclor in the Treatment of Pneumonia and Bronchiectasis

Summary

In a multicentre, international study of 187 adult patients with bacterial pneumonia or bronchiectasis, the safety and efficacy of a regimen of 200 mg ceftibuten administered twice-daily was compared with cefaclor given in a dosage of 500 mg three times a day. Of the 94 evaluable patients, 66 received ceftibuten and 28 received cefaclor. The overall bacteriological response was similar in the two treatment groups with elimination of the original pathogen in 91% and 89% of the patients receiving ceftibuten and cefaclor, respectively. The overall clinical response mirrored the bacteriological results with a successful clinical outcome in 92% of ceftibuten-treated patients compared with 93% in patients receiving cefaclor. Adverse experiences were, in general, few and mild, being reported in 8% and 17% of patients receiving ceftibuten and cefaclor, respectively.     

The relation between the aging of the steroid generating system and the geneses of cancers of the stomach, the breast and the uterine cervix

The purpose of the present study is to test the validity of the steroid carcinogenesis hypothesis in humans by investigating the problem whether or not a cancer-specific change of the hormonal milieu emerges at a specified stage of life where the growth rate of cancer risk is at its zenith. A case-control study of 14 urinary steroid excretions was conducted for each of 3 human neoplasias. The identification and the size (in parenthesis) of the population units used in this study were,given as follows: a) the male gastric cancer group (421); b) the male control group (104); c) the female breast cancer group (245); d) the cervical cancer group (345); e) the female control group (127). Two kinds of steroid parameters were employed for the statistical analysis of hormonal data: a) the logarithm of a steroid excretion figure (mu g/day), as expressed by log x; b) the logarithm of a relative weight of a given steroid to tetrahydrocortisol, as expressed by log x/THF. The case-control difference for each parameter was expressed in terms of a t-value of Student's t-test. The steroid deviation profile was prepared for each neoplasia and for each of the log x data set and the log x/THF data set. The results obtained are as follows: a) the 2 steroid parameters (log x and log x/THF) for each of 14 urinary steroids were both subject to change with the progress of host age. The rate of age-dependent change was different for each steroid parameter and for each population unit. b) The above differential age dependency of the steroid parameters gave rise to a continual transition of the steroid deviation profile in the course of aging. c) The hormonal traits of male gastric cancer, female breast cancer and cervical cancer were described each as a complex of androgen depression and glucocorticoid stimulation (male gastric cancer), a sequential emergence of premenopausal progestin depression and postmenopausal predominance of glucocorticoid over androgen (female breast cancer), and a complex of androgen-glucocorticoid depression over progestin (cervical cancer). d) The emergence of the above cancer-specific steroid disorders chronologically coincided with the quasiexponential growth phase of cancer risk (and slow growth phase of cancer risk in postmenopausal breast cancer). e) The usefulness of the log x/THF type deviation profile for the assessment of the hormonal milieu of the host was verified by both theoretical approach to the problem and its application to the real data of a case-control study. f) The age dependent decline of androgens was generally much faster in their progressions than that of glucocorticoids - a finding to suggest the possibility that the production of a cancer-specific steroid deviation profile might have taken the form of the stress shift of Hans Selye, since both phenomena share depletion of gonadal steroids relative to glucocorticoid in common. The etiological relevancy of the 3 cancer-specific steroid changes to the geneses of 3 cancers:was discussed in the light of the experimental pathology studies in our laboratory as well as in other laboratories.     

Effect of freezing the helix and the rim or edge of the human and pig ear

We have studied the effect of increasing freeze times on the normal pig's ear and on a variety of lesions of the human ear. The clinical and laboratory data suggest that cartilage necrosis secondary to cryosurgery is a dose-related phenomenon and is uncommon with the freeze times used in clinical practice. Cryosurgery is an effective and cosmetically acceptable treatment for superficial skin lesions of the ear.     

Degree of manifestation of therapeutic pathomorphosis and the nature of the change in the estrogen and progesterone receptors after the radiation and chemotherapy of breast cancer

Estradiol and progesterone receptor levels were measured in 130 patients with stage III breast tumors before treatment and following preoperative radiation or chemotherapy. The data were evaluated versus the morphologic features of posttreatment pathomorphosis of tumor. Standard fractionated radiation (total dose of 70 Gy) was followed by pronounced postradiation pathomorphosis and a decrease in the level and incidence of steroid receptors in 72.7-87.5%. The essentially unchanged receptor profile of tumor following large-fraction (total dose-20 Gy) irradiation as well as presence of estradiol and progesterone receptors in the originally receptor-negative neoplasms after chemotherapy were matched by a slight degree of pathomorphosis.     

Social inequalities in the incidence and case fatality of cancers of the lung,the stomach,the bowels,and the breast

Objective  In order to examine health inequalities in terms of incidences and case fatalities in a German health insurance population. Lung cancer, stomach cancer, intestinal carcinoma, and breast cancer were considered. Social differentiation was depicted by income and occupational position in order to examine which one is more strongly associated with incidence and case fatality. Methods  Analyses were performed using data from a statutory health insurance (n = 170,848). Incomes were divided into quintiles, and subjects were grouped according to occupational status. Results  For lung cancer incidence a gradient between the highest and the lowest 20% of the income distribution emerged. The relative risk of the lowest category was RR = 7.03, for occupational position the figure was RR = 6.98. For stomach cancer the relative risks were RR = 5.33 for income and RR = 7.11 for occupational position. For intestinal carcinoma only income was significantly related with incidence (RR = 4.37 for the lowest 20% of the income distribution), and for breast cancer incidence no social inequalities were found. For case fatality increased relative risks emerged for lung cancer, but only for income. Conclusions  Income and occupational position were associated with cancer incidence with the exception of breast cancer. Apart from lung cancer, case fatalities were unrelated to measures of social differentiation.     

一氧化氮与肿瘤的发生、发展及转移相关的研究进展

一氧化氮（NO）作为一种自由基性质的气体分子,参与了肿瘤的发生、发展、转移等过程。NO一方面介导了巨噬细胞、内皮细胞的杀瘤作用,另一方面又通过促进血管生成、增加血流量肿瘤生成。对NO的深入研究,将为探索肿瘤的发生、发展和开辟新的治疗途径带来希望。     

Urbanization and the incidence of abnormalities of squamous and glandular epithelium of the cervix

BACKGROUND: The large data bases of the Dutch cervical screening program can be exploited to establish the relation between urbanization and the incidence of abnormalities of the squamous and glandular epithelium, including mild or greater changes of the squamous and glandular epithelium of the cervix. METHODS: Six cytology laboratories in the context of the Dutch cervical screening program screened over 190,000 cervical smears. Urbanization (place of residence) data were derived from postal codes. All smears were coded with the Dutch national coding system, the Dutch national classification system KOPAC, in which squamous abnormalities are coded S4-S9, and glandular cell changes are coded G4-G9. From the scores per 1000 screened women, the relative risk (RR) of living in a large city compared with living in rural areas was calculated. To investigate a trend in incidence in relation to urbanization, the Schaafsma method was used. RESULTS: Of the smears with positive cytology, mild squamous dysplasia (S4) had the highest incidence per 1000 screened women (4.32), and the lowest incidence was found for adenocarcinoma (in situ; G7/G9; RR, 0.07). The RR for urban women ranged from 1.73 for moderate squamous dysplasia (S5) to 7.55 for adenocarcinoma (in situ; G7/G9). For smears with positive cytology for both squamous and glandular abnormalities, the Schaafsma method indicated a significant positive trend. CONCLUSIONS: The incidence of squamous and glandular abnormalities are maximal in women who live in a large city, which, in The Netherlands, is where there also is a population at high risk for human papillomavirus and bacterial vaginosis.