survivin、VEGF在非小细胞肺癌中的表达及相关性研究

目的研究survivin、VEGF基因（血管内皮生长因子）在非小细胞肺癌中的表达及其之间的相关性。方法采用免疫组化法检测72例非小细胞肺癌组织和20例肺良性组织中survivin、VEGF基因的表达。结果survivin、VEGF基因在非小细胞肺癌组织中表达水平为61．1％（44／72）、79．2％（57／72）显著高于肺良性组织10．0％（2／20）、15．0％（3／20）（P〈0．05）。survivin基因表达与肺癌患者的细胞分化程度,TNM分期和五年生存率密切相关（P〈0．05）。VEGF基因的表达与肺癌患者的细胞分化程度,TNM分期,五年生存率和淋巴结转移状态密切相关（P〈0．05）。survivin、VEGF基因在非小细胞肺癌组织中表达具有相关性（P〈0．05）。结论survivin、VEGF的表达与非小细胞肺癌的临床病理学特征密切相关,二者的检测将助于肺癌的诊断、评估肺癌患者的恶性程度和预后。     

人脑胶质瘤中凋亡相关基因survivin和p53的表达研究

目的探讨凋亡相关基因survivin和p53在人脑胶质瘤发生发展中的作用及其相互关系。方法采用免疫组化S-P法检测10例正常脑组织及75例脑胶质瘤标本中survivin、p53的表达情况并分析二者之间的关系。结果survivin在正常对照组和胶质瘤组中的阳性表达率为0％和45．3％，差异有显著性（P〈0．05）。胶质瘤Ⅰ级、Ⅱ级和Ⅲ，Ⅳ级，survivin的阳性表达率分别为15．0％、33．3％、74．2％，差异有极显著性（P〈0．001）。p53在正常脑组织和人脑胶质瘤组织中阳性表达率为0％和41、3％，差异有显著性（P〈0．05）。胶质瘤Ⅰ级、Ⅱ级和Ⅲ-Ⅳ级，p53的阳性表达率0％、41．7％、67．7％，差异有极显著性（P〈0．001）。75例胶质瘤组织中survivin与p53共阳性23例，共阴性33例，二者的表达呈正相关（rs=0．438，P〈0．01）。结论1）survivin的阳性表达率随胶质瘤恶性程度而升高；2）突变型p53蛋白的活性表达与肿瘤的组织病理类型、分化程度有关，p53基因的突变参与脑胶质瘤的发生发展；3）p53的突变与survivin的激活在胶质瘤的发生发展中可能起协同作用。     

uPARAP/Endo180在鼻咽癌中的表达及其意义

目的：探讨尿激酶型纤维蛋白溶酶原激活剂相关蛋白（uPAR—associated protein，uPARAP／Endo180）、uP—AR和VEGF在鼻咽癌组织中的表达及临床意义方法：采用免疫组化SP法检测58例鼻咽癌组织和30例慢性鼻咽炎组织中uPARAP、uPAR和VEGF蛋白的表达，分析其与鼻咽癌临床病理特征的关系，结果：鼻咽癌组织中uPARAP的阳性表达见于肿瘤间质的成纤维细胞和巨噬细胞，定位于胞膜和胞质，呈棕黄色颗粒状分布：uPAR阳性染色定位于肿瘤细咆与间质细胞胞浆内；VEGF阳性染色定位于肿瘤细胞胞浆内。鼻咽癌组织中uPARAP、uPAR和VEGF的阳性表达率分别为75．9％、81.0％和77．6％；与慢性晕咽炎比较，uPARAP、uPAR和VEGF在鼻咽癌组织中的阳性表达率有显著性差异（P〈0．05）；鼻咽癌组织中uPARAP表达与uPAR、VEGF的表达水平呈明显正相关（P〈0．05）：uPARAP在角化型鳞癌、非角化型癌和未分化癌的阳性表达率分别为42．9％、66．7％和86．1％随着肿瘤组织类型分化程度的下降，uPARAP，表达水平有上升趋势（P〈0．05）不同组织学类型之间进行两两比较发现，uPARAP的表达也有显著性差异（P〈0．05）uPARAP蛋白的表达与鼻咽癌组织病理分级、颈部淋巴结转移、临床分期密切相关（P〈0．05），而与患者的年龄、性别等因素无关结论：uPARAP、uPAR和VEGF在鼻咽癌组织中协同表达对促进鼻咽癌的扩散转移可能起重要作用，联合检测这些指标有望戍为判断鼻咽癌恶性程度和估计患者预后的重要生物学标志。     

VEGF在鼻咽癌中的表达及其与预后关系

[目的]研究血管内皮生长因子（VEGF）在鼻咽癌中的表达与鼻咽癌患者预后的关系。[方法]通过组织芯片技术与免疫组织化学方法回顾性研究1990～2002年期间200例有临床随访资料的鼻咽癌组织中VEGF蛋白的表达情况，应用卡方检验分析鼻咽癌组织VEGF蛋白表达与临床病理参数之间的关系，并通过生存分析计算鼻咽癌组织内VEGF不同表达组的总生存率。[结果]VEGF在鼻咽癌组织中阳性表达主要位于肿瘤细胞胞浆内。VEGF在鼻咽癌组织中的表达与鼻咽癌患者的TNM分期、复发及远处转移呈正相关（P〈0．05）。VEGF表达阳性及阴性患者5年生存率分别为40．11％和67．75％，两组生存率存在显著性差异（P〈0．01）。[结论]VEGF的表达与鼻咽癌患者TNM分期、复发及远处转移呈明显正相关，其高表达提示预后不良。     

VEGF、CD31及MVD在卵巢上皮癌中临床意义

[目的]评价VEGF、CD31和MVD在卵巢癌中的表达及临床意义。[方法]卵巢上皮癌40例及正常卵巢组织20例标本采用免疫组织化学方法检测VEGF和CD31的表达，并计数MVD。[结果]卵巢癌中VEGF阳性表达率为67．5％，明显高于对照组的15．0％。有淋巴结转移者的VEGF和MVD明显高于无转移者（P〈0．05）：Ⅲ～Ⅳ期病例的VEGF和MVD也明显高于Ⅰ～Ⅱ病例（P〈0．05）。[结论]VEGF、CD31在卵巢癌的发生发展中起着重要的作用。MVD与肿瘤的浸润和转移相关。     

COX-2和survivin在B细胞非霍奇金淋巴瘤中的表达及意义

目的探讨COX-2和survivin在B细胞非霍奇金淋巴瘤（B—NHL）中的表达及临床意义。方法采用免疫组化S-P法检测43例B—NHL和10例良性淋巴结病变组织中COX-2和survivin的表达。结果COX-2和survivin在B—NHL中的阳性表达率分别为55．8％（24／43）和69．8％（30／43），与对照组相比差异具有显著性（P〈0．05）。Ⅲ／Ⅳ期B—NHL患者COX-2蛋白的表达高于Ⅰ／Ⅱ期患者（P〈0．05）。survivin的表达与B—NHL的组织病理学等级和国际预后指数（IPI）具有相关性（P〈0．05）。Spearman相关分析表明COX-2的表达与survivin的表达呈正相关（r=1．000，P=0．030）。结论COX-2和survivin在B-NHL中表达上调以及两者之间的阳性表达密切相关，表明COX-2和survivin在B-NHL的发生和发展中具有协同作用。     

VEGF在非小细胞肺癌中的表达及临床意义

[目的]探讨血管内皮生长因子（VEGF）在非小细胞肺癌（NSCLC）中的表达及其临床意义。[方法]应用免疫组化法检测30例肺癌组织和25例癌旁组织中VEGF表达。[结果]NSCLC组织中VEGF阳性表达率为70．00％,癌旁组织中的阳性表达率为20．00％（Х^2=11．745,P=0．001）;在腺癌、鳞癌、大细胞癌中VEGF阳性率差异无统计学意义（P〉0．05）;Ⅲ～Ⅳ期NSCLC中的VEGF阳性表达率为88．24％,高于Ⅰ～Ⅱ期的46．15％（Х^2=4．37,P=0．037）;VEGF在淋巴结转移组的阳性率为78.26％,在无淋巴结转移组中为42．86％,两组比较差异有显著性（Х^2=5．06,P=0．024）。[结论]VEGF在NSCLC组织中高表达;VEGF表达与NSCLC淋巴结转移、TNM分期呈正相关．而与NSCLC的组织学分类无关。     

肾癌组织中血管内皮生长因子表达的意义

目的 探讨肾癌组织中血管内皮生长因子（VEGF）的表达及与临床病理的关系。方法 应用免疫组织化学方法,对6例肾癌组织中的VEGF进行检测。结果 肾癌组织中VEGF阳性表达率为73．9％,阳性着色于细胞质和细胞膜,VEGF表达与肿瘤大小、细胞类型和病理分级均无关（P＞0．05）,Ⅲ＋Ⅳ期强阳性表达率明显高于Ⅰ Ⅱ期（P＜0．05）,VEGF阳性表达者5年生存率明显低于阴性表达者。结论 VEGF表达与肾癌生物行为有重要影响,其可能成为预测肾癌转移和预后的指标。     

Survivin在宫颈鳞癌组织中的表达及其与p53基因表达及HPV感染相关性

背景与目的：survivin基因是凋亡抑制蛋白（IAP）家族的新成员，其组织分布具有明显的细胞选择性，即仅表达于胚胎及胎儿组织及大多数癌瘤组织中，而不表达于终末分化的成人组织。本研究探讨survivin在宫颈鳞癌组织中的表达及其与HPV-16感染及p53表达的相关性。方法：应用免疫组织化学链霉素抗生物素蛋白过氧化酶连接法（S—P法）检测survivin、HPV-16、053基因在21例正常宫颈组织、23例CIN及72例宫颈鳞癌组织中的表达。结果：survivin基因在正常宫颈组织中不表达，在23例CIN中4例表达阳性，占17．39％，与正常宫颈组比较，差异有显著性（P〈0．01，x^2=9．210），在72例宫颈鳞癌组织中52例表达阳性，占72．22％，其中病理分级为G1级的宫颈鳞癌中survivin基因表达阳性率为61．3％，（17／35），G2／G3级为89．19％（33／37），两者比较，差异有显著性（P〈0．01，x^2=9．5211）。临床分期Ⅰ期的宫颈鳞癌的survivin基因表达阳性率为31例中有16例，占51．61％，临床分期Ⅱ期的宫颈鳞癌的survivin基因表达阳性率为28例中有24例，占85．71％，Ⅲ期者为92．30％（12／13），两两比较，Ⅰ期与Ⅱ期，Ⅰ期与Ⅲ期差异均有显著性（P〈0．01），Ⅱ期与Ⅲ期差异无显著性（P〉0．05）。survivin基因表达阳性率与宫颈鳞癌的病理分级和临床分期呈正相关。宫颈鳞癌组织中P53蛋白表达阳性、阴性者中survivin基因表达阳性率分别为84．78％（39／46），50．00％（13／26），两者比较，差异有显著性（P〈0．05）。HPV-16表达阳性、阴性者中survivin基因表达率分别为81．4％（35／43），58．6％（17／29），两者比较，差异有显著性（P〈0．05）。survivin基因表达阳性率与宫颈鳞癌组织中053及HPV-16表达有相关性。结论：①survivin基因的表达与宫颈鳞癌的临床分期、病理分级及患者预后密切相关，其高表达提示宫颈鳞癌预后不良。②survivin基因的表达与宫颈鳞癌组织中p53突变及HPV-16感染呈正相关。     

MMP-9、LMP-1蛋白在鼻咽癌中的表达及其与远处转移的相关性研究

目的：研究基质金属蛋白酶-9（MMP-9）、潜伏膜蛋白-1（LMP-1）在鼻咽癌中的表达及其对鼻咽癌远处转移的影响。方法：收集83例鼻咽癌患者的临床资料及鼻咽部瘤体活检组织蜡块。采用免疫组化s—P法检测标本中MMP-9、LMP-1的表达。结果：MMP-9阳性表达率为65％（54／83）,其表达与颈淋巴结转移、远处转移关系密切（P〈0．05）。LMP-1阳性表达率为57％（47／83）,其表达与颈淋巴结转移、远处转移关系密切（P〈0．05）;且与MMP-9表达呈显著正相关（rJ=0．327,P〈0．05）。鼻咽癌远处转移的危险因素是临床分期（Ⅲ、Ⅳ期）、颈淋巴结N,阳性、MMP-9阳性表达、LMP-1阳性表达（P〈0．05）。MMP-9、LMP-1均为阳性表达者远处转移风险更高（P〈0．05）。结论：MMP-9、LMP-1阳性表达与远处转移明显相关,可作为鼻咽癌远处转移的预测指标。     

Denosumab in patients with cancer and skeletal metastases: A systematic review and meta-analysis

Background

We conducted a systematic review of the literature to determine the efficacy and safety of denosumab in reducing skeletal-related events (SRE) in patients with bone metastases.

Methods

A literature search using MEDLINE, EMBASE, Web of Science and The Cochrane Collaboration Library identified relevant controlled clinical trials up-to-March 14, 2012. Two independent reviewers assessed studies for inclusion, according to predetermined criteria, and extracted relevant data. The primary outcomes of interest were SRE, time to first on-study SRE, and overall survival. Secondary outcomes included pain, quality of life, bone turnover markers (BTM), and adverse events.

Results

Six controlled trials including 6142 patients were analyzed. Compared to zoledronic acid, denosumab had lower incidence of SRE with a risk ratio (RR) of 0.84 (95% confidence intervals (CI) 0.80–0.88), delayed the onset of first on-study SRE (RR 0.83; 95% CI 0.75–0.90) and time to worsening of pain (RR 0.84; 95% CI 0.77–0.91). No difference was observed in overall survival with pooled hazard ratio of 0.98 (95% CI 0.90–1.0). For total adverse events, denosumab was similar to zoledronic acid (RR 0.97; 95% CI 0.89–1.0). No significant differences were observed in the frequency of osteonecrosis of the jaw (RR 1.4; 95% CI 0.92–2.1). Patients on denosumab had a greater risk of developing hypocalcemia (RR 1.9; 95% CI 1.6–2.3).

Conclusions

Denosumab was more effective than zoledronic acid in reducing the incidence of SRE, and delayed the time to SRE. No differences were found between denosumab and zoledronic acid in reducing overall mortality, or in the frequency of overall adverse events.     

洛铂联合多西他赛行肿瘤细胞减灭术加腹腔热灌注化疗治疗腹膜癌的临床观察

目的 分析洛铂联合多西他赛行肿瘤细胞减灭术（cytoreductive surgery, CRS）加腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy, HIPEC）治疗腹膜癌（peritoneal carcinoma, PC）的围手术期安全性及疗效。 方法 PC患者行CRS+HIPEC治疗,药物为洛铂50 mg/m2、多西他赛60 mg/m²,加入12 000 ml 0.9%氯化钠溶液加热至（43±0.5）℃持续灌注60 min。记录术后6天体温和心率变化、围手术期不良事件、血常规及血生化指标、术后患者恢复情况及生存结果。结果 90例PC患者行95次CRS+HIPEC,手术时间180~450 min (中位数485 min）;术后6天最高体温、心率分别为36.4℃~38.6℃（中位数37.5℃）、76~124 bpm（中位数100 bpm）,严重不良事件16例,包括围手术期死亡2例。中位生存期20.8月（95%CI: 13.1~25.8月）,1、3、5年生存率分别为75.6%、45.6%、43.3%。 结论 洛铂联合多西他赛进行CRS+HIPEC治疗PC安全性可接受,有助于延长患者生存期。     

MNP和MVP方案治疗非小细胞肺癌的临床研究

目的　比较MNP和MVP方案治疗晚期非小细胞肺癌 (NSCLC)的疗效和不良反应。方法　 12 6例晚期NSCLC患者随机分为A和B组 ,A组采用MNP(丝裂霉素 去甲长春花碱 顺铂 )方案化疗。B组采用MVP(丝裂霉素 长春酰胺 顺铂 )方案化疗。至少连用 2个周期后评价疗效。结果　A组有效率为 5 4.0 % ( 3 4/63 ) ,B组有效率为 3 4.9% ( 2 2 /63 ) ,无显著性差异 (P>0 .0 5 ) ;其中对腺癌有效率A组为 44 .4% ( 16/3 6) ,B组为 3 3 .3 % ( 12 /3 6)。A组静脉炎发生率为 2 8.6% ( 14 /4 9) ,B组为 0 (P <0 .0 5 ) ,其它不良反应 2组无显著性差异。结论　MNP方案为治疗晚期NSCLC较为有效和安全的化疗方案     

The prognostic role of lymphovascular invasion and lymph node metastasis in perihilar and intrahepatic cholangiocarcinoma

IntroductionCholangiocellular carcinoma (CCA) is an aggressive malignancy with a dismal prognosis. Among curative treatment options for CCA, radical surgical resection with extrahepatic bile duct resection, hepatectomy and en-bloc lymphadenectomy are considered the mainstay of curative therapy. Here, we aimed to identify prognostic markers of clinical outcome in CCA-patients who underwent surgical resection in curative intent.Material and methodsBetween 2011 and 2016, 162 patients with CCA (perihilar CCA (pCCA): n = 91, intrahepatic CCA (iCCA): n = 71) underwent surgery in curative intent at our institution. Preoperative characteristics, perioperative data and oncological follow-up were obtained from a prospectively managed institutional database. The associations of overall- (OS) and disease-free-survival (DFS) with clinico-pathological characteristics were assessed using univariate and multivariable cox regression analyses.ResultsThe median OS and DFS were 38 and 36 months for pCCA and 25 and 13 months for iCCA, respectively. Lymphovascular invasion (LVI) and lymph node metastasis as well as surgical complications as assessed by the comprehensive complication index (CCI) and tumor grading were independently associated with OS for the pCCA (LVI; RR = 2.36, p = 0.028; CCI; RR = 1.04, p < 0.001) and iCCA cohorts (N-category; RR = 3.21, p = 0.040; tumor grading; RR = 3.75, p = 0.013; CCI, RR = 4.49, p = 0.010), respectively. No other clinical variable including R0-status and Bismuth classification was associated with OS.ConclusionMajor liver resections for CCA are feasible and safe in experienced high-volume centers. Lymph node metastasis and LVI are associated with adverse clinical outcome, supporting the role of systematic lymphadenectomy. The assessment of LVI may be useful in identifying high-risk patients for adjuvant treatment strategies.     

蛋白激酶C的下调与KBV200细胞多药耐药性的关系

目的　探讨蛋白激酶C (PKC)在肿瘤多药耐药 (MDR)中的作用。方法　3 2 P掺入法测定PKC的活性 ;Westernblot法检测KBV2 0 0细胞株PKC亚型的表达和亚细胞分布 ;实验组用十字孢碱 (SP)预孵育KBV2 0 0细胞 ;MTT法检测耐药株KBV2 0 0细胞的耐药性。结果　SP可下调膜组分和浆组分的PKC活性及总活性 ;使PKCα膜组分和浆组分的表达均降低 ,PKCβ的膜组分消失 ,浆组分PKCβ的表达稍增强 ,PKCε的膜组分和浆组分表达无变化 ;SP可降低VCR、ADR对KBV2 0 0细胞的IC50 值 (P <0 0 1)。结论　SP使KBV2 0 0细胞耐药性降低 ,可能与下调PKC有关。     

食管、贲门、胃肿瘤手术前后胆总管及胆囊内径值的对比及其意义

本文对１８０例食管、贲门、胃肿瘤手术前后ＣＢＤ及ＧＢ进行了检测和对比，发现３组病人手术后ＣＢＤ平均值均较手术前增大（Ｐ＜０．０５）。胃癌组变化明显，贲门组次之，后为食管癌组。胃癌组手术后胆囊平均值较术前增大（Ｐ＜０．０１）。结果提示：食管、贲门、胃肿瘤手术后ＣＢＤ与ＧＢ的改变可能与手术中迷走神经的损伤有关。     

Oxygen for relief of dyspnoea in mildly- or non-hypoxaemic patients with cancer: a systematic review and meta-analysis

The aim of this study was to determine the efficacy of palliative oxygen for relief of dyspnoea in cancer patients. MEDLINE and EMBASE were searched for randomised controlled trials, comparing oxygen and medical air in cancer patients not qualifying for home oxygen therapy. Abstracts were reviewed and studies were selected using Cochrane methodology. The included studies provided oxygen at rest or during a 6-min walk. The primary outcome was dyspnoea. Standardised mean differences (SMDs) were used to combine scores. Five studies were identified; one was excluded from meta-analysis due to data presentation. Individual patient data were obtained from the authors of the three of the four remaining studies (one each from England, Australia, and the United States). A total of 134 patients were included in the meta-analysis. Oxygen failed to improve dyspnoea in mildly- or non-hypoxaemic cancer patients (SMD=-0.09, 95% confidence interval -0.22 to 0.04; P=0.16). Results were stable to a sensitivity analysis, excluding studies requiring the use of imputed quantities. In this small meta-analysis, oxygen did not provide symptomatic benefit for cancer patients with refractory dyspnoea, who would not normally qualify for home oxygen therapy. Further study of the use of oxygen in this population is warranted given its widespread use.     

肝细胞癌组织中VEGF、MMP-2和MVD的表达及其相关性研究

[目的]研究肝细胞癌(HCC)组织中血管内皮生长因子(VEGF)及基质金属蛋白酶-2(MMP-2)蛋白的表达及其临床意义,并探讨其与血管生成的关系.[方法]采用免疫组化法检测60例肝癌组织及癌旁肝组织中VEGF及MMP-2的表达,用CD34标记免疫组化法检测微血管密度(MVD).[结果]VEGF及MMP-2在癌组织中的阳性率分别为63.33%和60.00%,而在癌旁组织中的阳性率分别为33.33%和26.67%,癌组织与癌旁组织比较差异有显著性(P＜0.01).癌组织的MVD为54.92±8.55,癌旁组织的MVD为21.36±6.63,两者差异有显著性(P＜0.01).VEGF在人肝癌组织中的表达与术后复发、肝外转移、临床分期、门静脉癌栓、肿瘤直径相关.MMP-2在人肝癌组织中的表达与临床分期、门静脉癌栓、肝外转移及术后复发相关.在癌组织中MVD与VEGF及MMP-2的表达呈正相关,VEGF与MMP-2的表达亦呈正相关.[结论]HCC中VEGF及MMP-2的高表达与肿瘤血管形成有关,在HCC的发生、发展及术后复发过程中起重要作用.     

GF方案与TP方案一线治疗晚期非小细胞肺癌的临床对照研究

Objective  

The aim of the study was to evaluate the efficacies of initial gemcitabine plus cisplatin (GP) and paclitaxel plus cisplatin (TP) 1st-line chemotherapies for advanced non-small cell lung cancer (NSCLC) and observe their side effects.     

Interaction between gemcitabine and mitomycin-C in vitro

Both gemcitabine (2′,2′-difluorodeoxycytidine; dFdCyd) and mitomycin-C (MMC) are active against several solid malignancies. dFdCyd is an attractive agent for use in combination with drugs which damage DNA and with radiation therapy because of its ability to inhibit DNA replication and repair as well as its radiosensitizing effect. We hypothesized that the repair of MMC adducts in DNA might be inhibited by dFdCyd leading to a synergistic effect. To test this possibility, we studied the effect of combining dFdCyd and MMC in HT29 human colon carcinoma cells in vitro. The cells were exposed to a variety of drug concentration ratios and schedules, then assessed for clonogenic survival. D₅₀ values (drug concentration at which clonogenicity is inhibited by 50%) were calculated, and the interactive effects of the two drugs were evaluated using median effect analysis. In this approach, if the calculated combination index (CI) is <1, 1, or >1, it indicates synergism, additivity, or antagonism, respectively (Chou and Talalay 1984). We found that marked synergy (CI of 0.5–0.7) was produced by concurrent exposure to mitomycin and gemcitabine. In contrast, sequential treatment led only to additivity. These findings suggest that, when combined in an appropriate schedule, the chemosensitizing effect of gemcitabine may be beneficial in the treatment of malignancies which are sensitive to MMC. Received: 19 November 1998 / Accepted: 21 June 1999