Necessity of Radical Hysterectomy for Endometrial Cancer Patients with Cervical Invasion

To determine whether radical hysterectomy is necessary in the treatment of endometrial cancer patients with cervical involvement, we reviewed the medical records of women who underwent primary surgical treatment for endometrial carcinoma and selected patients with pathologically proven cervical invasion. Among 133 patients, 62 patients underwent extrafascial hysterectomy (EH) and 71 radical or modified radical hysterectomy (RH). The decision regarding EH or RH was made at the discretion of the attending surgeon. The sensitivity of pre-operative magnetic resonance imaging for cervical invasion was 44.7% (38/85). In RH patients, 10/71 (14.1%) patients had frankly histologic parametrial involvement (PMI). All were stage III or over. Eight of 10 patients had pelvic/paraaortic node metastasis and two showed extrauterine spread. In 74 patients with stage II cancer, RH was performed in 41 and PMI was not seen. Sixty-six (89.2%) patients had adjuvant radiation therapy and there were 3 patients who had developed recurrent disease in the RH group and none in the EH group (Mean follow-up: 51 months). Although these findings cannot conclusively refute or support the necessity of radical hysterectomy in patients with cervical extension, it is noteworthy that the risk of PMI seems to be minimal in patients with a tumor confined to the uterus without evidence of extrauterine spread.     

早期胃癌浸润深度判断的研究进展

胃癌是最常见的恶性肿瘤之一,准确地判断胃癌的浸润深度对治疗方式的选择和预后的判断十分重要。目前,主要通过白光内镜、超声内镜来对早期胃癌的浸润深度进行预测,但其准确性有待提高。本文通过复习相关文献,对各种判断早期胃癌浸润深度的方法进行介绍,并对其优势与不足进行分析,以期能对临床实践提供帮助。     

硫酸寡糖复合物对人结肠癌SW620细胞迁移与侵袭能力的影响

目的 探讨硫酸寡糖复合物(PI-88)对结肠癌SW620细胞迁移与侵袭的影响及机制。方法 培养人结肠癌SW620细胞,分为对照组、溶媒组和药物组;对照组细胞不做任何处理,药物组细胞给予5 μL的0.5 mol/L的PI-88,溶媒组给予细胞5 μL的磷酸盐缓冲液(PBS)。各组细胞处理后继续培养24 h,采用划痕实验检测结肠癌SW620细胞迁移距离;Transwell小室检测结肠癌SW620细胞迁移数量与侵袭数量;Western blot检测结肠癌SW620细胞中乙酰肝素酶(HPA)、血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)蛋白的表达。结果 划痕实验结果显示,药物组SW620细胞迁移距离(35.49±6.89)μm小于对照组(216.75±21.43)μm、溶媒组(227.52±17.72)μm,差异均有统计学意义(P值均＜0.05)。Transwell小室细胞迁移、侵袭实验结果显示,药物组SW620细胞迁移数目(226±37)个和侵袭数目(89±11)个均少于对照组(875±93、321±28)个和溶媒组(843±116、331±43)个,差异均有统计学意义(P值均＜0.05)。Western blot实验结果显示,药物组PHA、VEGF、bFGF蛋白相对表达量均明显低于对照组和溶媒组,差异均有统计学意义(P值均＜0.05)。结论 PI-88具有抑制结肠癌SW620细胞迁移与侵袭的作用,其作用机制可能与PI-88抑制结肠癌SW620细胞HPA、VEGF、bFGF蛋白的表达有关。     

膜联蛋白A5和CD147在喉癌组织中的表达

目的分别观察膜联蛋白A5（ANX A5）和细胞外基质金属蛋白酶诱导因子（CDl47）在癌旁正常组织和喉癌组织中的表达情况,分析喉癌组织中ANX A5和CD147表达的相关性。 方法收集2012年1月至2018年2月经川北医学院附属医院耳鼻咽喉-头颈外科手术切除,并经病理学确诊的喉癌组织标本51例和癌旁组织标本35例,运用免疫组化SP法分别检测喉癌组织标本与癌旁组织标本中ANX A5和CD147的表达情况。采用四格表χ²检验分析不同病理、临床特点喉癌患者中ANX A5、CD147的表达情况,采用Spearman等级相关分析分析喉癌组织中ANX A5和CD147表达的相关性。 结果ANX A5和CD147在喉癌组织中的表达水平均高于癌旁组织中的表达水平（χ²=6.939,P=0.008;χ²=14.722,P<0.001）。与TNM分期Ⅰ~Ⅱ期患者、喉癌组织病理学分级为低-未分化患者、无颈淋巴结转移患者相比,TNM分期Ⅲ~Ⅳ期患者、喉癌组织病理学分级为高-中分化患者、存在颈淋巴结转移患者中ANX A5的表达水平更高,差异均有统计学意义（χ²=5.298,P=0.021;χ²=3.869,P=0.049;χ²=8.419,P=0.004）;≥60岁和<60岁患者以及不同性别患者中ANX A5的表达水平差异无统计学意义（χ²=0.003,P=0.957;χ²=0.082,P=0.775）。与TNM分期Ⅰ~Ⅱ期、无颈淋巴结转移患者相比,TNM分期Ⅲ~Ⅳ期、存在颈淋巴结转移的喉癌患者中CD147具有更高的表达水平,差异具有统计学意义（χ²=14.009,P<0.001;χ²=11.004,P=0.001）;≥60岁和<60岁患者、不同性别患者以及不同病理学分级患者中CD147的表达水平差异无统计学意义（χ²=1.546,P=0.214;χ²=1.373,P=0.241;χ²=0.002,P=0.964）。Spearman等级相关分析显示喉癌组织中ANX A5与CD147的表达呈正相关（r=0.918,P<0.001）。 结论ANX A5和CD147在喉癌组织中的表达水平均高于癌旁组织,且在具有不同病理、临床特点的喉癌患者中存在表达水平的差异,提示ANX A5与CD147可能参与喉癌的发生、发展。     

Formin-like 3 regulates RhoC/FAK pathway and actin assembly to promote cell invasion in colorectal carcinoma

AIM To clarify the underlying mechanism of formin-like 3(FMNL3)in the promotion of colorectal carcinoma(CRC)cell invasion.METHODS The in vitro biological function analyses of FMNL3 were performed by gain-and loss-of function approaches.Changes in the F-actin cytoskeleton were detected by the technologies of phalloidin-TRITC labeling and confocal microscopy.The signaling pathway mediated by FMNL3 was explored by western blot,gelatin zymograph assay,co-immunoprecipitation(co-IP),immunofluorescence colocalization,and glutathione S-transferase(GST)pulldown assay.RESULTS The in vitro experimental results showed that FMNL3 significantly promoted the proliferation,invasion,and migration of CRC cells(P0.05 and P0.01).Moreover,FMNL3regulated the remodeling of actin-based protrusions such as filopodia and lamellipodia in a RhoC-dependent manner.The western blot and gelatin zymograph assay results indicated that FMNL3 was involved in the RhoC/focal adhesion kinase(FAK)pathway and acted as an effector of RhoC to activate the downstream signaling of p-FAK as well as p-MAPK and p-AKT.This resulted in the increased expression of matrix metalloproteinase 2(MMP2),matrix metalloproteinase 9(MMP9)and vascular endothelial growth factor(VEGF),and the subsequent promotion of CRC cell invasion.The results of TAE226,U0126 or Ly294002 treatment confirmed an essential role of FMNL3 in activation of the RhoC/FAK pathway and the subsequent promotion of CRC invasion.Co-IP,colocalization and GST pull-down assays showed the direct interaction of FMNL3 with RhoC in vivo and in vitro.CONCLUSION FMNL3 regulates the RhoC/FAK signaling pathway and RhoC-dependent remodeling of actin-based protrusions to promote CRC invasion.     

低氧对K562细胞侵袭转移的增强作用

［摘要］目的：研究低氧对白血病细胞株K562细胞侵袭能力和转移能力的影响。方法：细胞体外常规培养,用浓度为1%,3%,5%的氧分别处理细胞24 h,以常氧培养K562细胞为对照组,通过细胞黏附实验检测细胞黏附力,细胞迁移实验检测细胞运动力,肿瘤细胞体外侵袭实验检测细胞侵袭力,RT-PCR检测血管内皮生长因子（VEGF）,MMP-2,MMP-9 mRNA的表达,Western blot检测细胞HIF-1α蛋白的表达。结果：与对照组相比,3%和5%的氧均增强K562细胞黏附力、运动力和侵袭力(P<0.05或P<0.01),而且还能上调K562细胞HIF-1α蛋白,HIF-1α mRNA,VEGF mRNA,MMP9 mRNA,MMP2 mRNA的表达(P<0.05或P<0.01);而1%氧与对照组相比,以上各检测指标无明显变化(P>0.05)。结论：适度低氧能增强白血病细胞株K562细胞侵袭能力和转移能力,其机制可能是通过HIF-1α上调VEGF,MMP-2和MMP-9表达实现的。［中国当代儿科杂志,2009,11（7）：566-570］     

RNA激活技术介导的E—cadherin基因上调表达抑制5637膀胱癌细胞侵袭与迁移

目的探讨通过RNA激活（RNA activation,RNAa）技术上调E-cadherin基因的表达而影响人膀胱癌5637细胞的侵袭、迁移能力。方法将与E-cadherin基因启动子DNA序列互补的双链RNA分子（dsEcad）转染入5637细胞中,采用RT-PCR法及Westernblot检测E-cadherin的表达;用Transwell小室法及划痕法检测RNAa后细胞侵袭、迁移能力的改变;用细胞免疫荧光法及Western blot检测β-catenin蛋白在细胞内的重新分布结果。结果dsEcad转染5637细胞72h后E-cadherin表达显著上调,RNAa有效;5637细胞对细胞外基质的侵袭能力及迁移能力也明显下降。β-catenin在胞核及细胞质的水平明显下降并重新再分布至细胞膜上。结论RNAa技术激活E-cadherin基因表达并抑制细胞侵袭、转移等恶性行为,可作为膀胱癌或其他恶性肿瘤基因治疗的一种有效手段。     

High level of ezrin expression in colorectal cancer tissues is closely related to tumor malignancy

AIM： To investigate the ezrin expression in normal colorectal mucosa and colorectal cancer tissues, and study the correlation between ezrin expression in colorectal cancer tissues and tumor invasion and metastasis. METHODS： Eighty paraffin-embedded cancer tissue samples were selected from primary colorectal adenocarcinoma. Twenty-eight patients had well- differentiated, 22 had moderately differentiated and 30 had poorly differentiated adenocarcinoma. Forty-five patients and 35 patients had lymph node metastasis. Forty-five patients were of Dukes A to B stage, and 35 were of C to D stage. Another 22 paraffin-embedded tissue blocks of normal colorectal epithelium （〉 5 cm away from the edge of the tumor） were selected as the control group. All patients with colorectal cancer were treated surgically and diagnosed histologically, without preoperative chemotherapy or radiotherapy. The immunohistochemistry was used to detect the ezrin expression in paraffin-embedded normal colorectal mucosa tissues and colorectal cancer tissue samples. RESULTS： Ezrin expression in colorectal cancer was significantly higher than in normal colorectal mucosa （75.00% vs 9.09%, P 〈 0.01）, and there was a close relationship between ezrin expression and the degree of tumor differentiation, lymph node metastasis and Dukes stage （88.46% vs 50.00%, P 〈 0.01; 94.28% vs 51.11%, P 〈 0.01; 94.28% vs 51.11%, P 〈 0.01）. CONCLUSION： Ezrin expression is obviously higher in colorectal cancer tissues than in normal colorectal mucosa tissues, and the high level of ezrin expression is closely related to the colorectal cancer invasion and metastasis process.     

阻断FAK表达对涎腺腺样囊性癌细胞SACC—LM的侵袭行为的影响

目的：研究探讨阻断黏着斑激酶（focal adhesion kinase,FAK）表达对涎腺腺样囊性癌肺转移亚系细胞（salivary adenoid cystic carcinoma-Lung metastasis,SACC—LM）侵袭行为的影响及相关机制。方法：应用酪氨酸蛋白激酶抑制剂Genistein处理体外培养的SACC-LM细胞,应用transwell小室观察Genistein对SACC—LM细胞侵袭的影响,并应用RT-PCR法检测FAK和细胞外信号调节激酶（extracellular signal—regulated kinase,ERK）mRNA的表达。所得实验数据采用SPSS10．0统计软件t检验进行分组分析。结果：Genistein使SACC-LM细胞侵袭能力减弱;检测到随着Genistein抑制剂浓度的增高和作用时间的延长,FAK和ERK mRNA的表达水平均降低。结论：阻断FAK表达导致SACC-LM细胞侵袭能力减弱,原因可能是FAK和ERK表达水平的改变。     

GAS5对骨肉瘤U2OS细胞增殖、迁移和侵袭的影响

目的:观察生长停滞特异性转录因子5(GAS5)对骨肉瘤U2OS细胞增殖、迁移和侵袭的影响,探讨其机制。方法:在人骨肉瘤U2OS细胞和人正常成骨hFOB 1.19细胞中,采用实时定量PCR(qRT-PCR)检测GAS5和微小RNA (miR)-221的表达,Western blot检测基质金属蛋白酶抑制物-2 (TIMP2)蛋白的表达。转染pcDNA-GAS5重组质粒后,采用噻唑蓝(MTT)法和Trasnwell小室法检测GAS5对U2OS细胞增殖、迁移和侵袭的影响,qRT-PCR检测GAS5对miR-221表达的影响。利用Starbase软件预测和双荧光素酶报告基因实验验证GAS5与miR-221以及miR-221与TIMP2的靶向关系。转染miR-221模拟物和miR-221抑制剂后,观察miR-221过表达对GAS5调控的U2OS细胞增殖、迁移和侵袭的影响以及miR-221对TIMP2蛋白表达的影响。结果:与正常hFOB 1.19细胞相比,U2OS细胞中GAS5和TIMP2蛋白的表达水平明显降低,而miR-221表达水平显著升高(GAS5:P=0.0001;TIMP2:P=0.0003;miR-221:P=0.0004)。GAS5过表达可抑制U2OS细胞增殖、迁移和侵袭(增殖48h:P=0.0005;增殖72h:P=0.0002;迁移:P=0.002;侵袭:P=0.001),而miR-221过表达可明显逆转GAS5对U2OS细胞增殖、迁移和侵袭的抑制作用(增殖48h:P=0.0002;增殖72h:P=0.0003;迁移:P=0.0001;侵袭:P=0.0001)。Starbase软件预测到miR-221存在能够与GAS5互补结合的位点,还存在能够与TIMP2 3′UTR互补结合的位点;双荧光素酶结果显示miR-221过表达后野生型GAS5(GAS5-WT)和野生型TIMP2 (TIMP2-WT)细胞的荧光素酶活性明显降低(P均为0.0003);同时,GAS5过表达后,U2OS细胞中miR-221表达水平明显降低(P=0.0001),反之miR-221明显升高(P=0.0001);miR-221过表达后,U2OS细胞中TIMP2蛋白的表达水平明显降低(P=0.0003),反之TIMP2蛋白的表达水平明显升高(P=0.0009)。结论:GAS5可通过靶向抑制miR-221促进TIMP2表达,进而抑制U2OS细胞的增殖、迁移和侵袭。