MMP-9、MMP-14、MMP-2和VEGF-C在乳腺癌中的表达及意义

[目的]探讨MMP-9、MMP-14、MMP-2和VEGF-C在乳腺癌中的表达及意义.[方法]用组织芯片和免疫组化技术检测乳腺良性病变及乳腺癌组织中MMP-2、MMP-9、MMP-14、VEGF-C的表达水平;用D2-40标记淋巴管并计数.[结果]MMP-9、MMP-14、MMP-2与VEGF-C在乳腺癌组织中的表达率及表达强度远高于乳腺良性病变组织,并呈正相关关系(r=-0.27、0.35、0.27、0.26);浸润性乳腺癌VEGF-C阳性表达率有淋巴结转移者明显高于无淋巴结转移者,差异有统计学意义(P＜0.01).[结论] MMP-9、MMP-14、MMP-2与VEGF-C的表达与乳腺癌淋巴管生成及淋巴结转移关系密切并呈正相关.     

人乳腺癌组织中D2-40标记的微淋巴管密度与血管内皮生长因子C表达的关系

目的 探讨人乳腺癌组织中D2-40标记的微淋巴管密度(LMVD)与血管内皮生长因子C(VEGF-C)表达的关系.方法 收集102例乳腺癌、25例乳腺纤维腺瘤和10例正常乳腺组织标本,采用免疫组化SP法检测D2-40单抗标记的LMVD和VEGF-C蛋白的表达水平,采用原位杂交法检测VEGF-C mRNA的转录水平. 结果 102例人乳腺癌组织中,D2-40标记微淋巴管的阳性率为76.5%,高于乳腺纤维腺瘤组织.癌周组织的LMVD为30.1个微淋巴管/100倍视野,显著高于癌中心区、正常乳腺组织和乳腺纤维腺瘤组织的LMVD (均P＜0.01),且与乳腺癌腋窝淋巴结转移数目明显相关(r=0.964,P<0.01).102例乳腺癌组织中,VEGF-C蛋白和mRNA的阳性表达率分别为55.9%和59.8%,均高于乳腺纤维腺瘤组织(χ2=11.653,P=0.003;χ2=10.345,P=0.006),且与淋巴结转移数目、临床分期、c-erbB-2和p53基因的表达相关(均P<0.05).VEGF-C蛋白和mRNA的表达水平均与D2-40标记的LMVD相关(P<0.05),尤其见于癌周组织中(P<0.01).结论 D2-40单抗标记的LMVD与VEGF-C的表达有密切关系,VEGF-C参与的乳腺癌微淋巴管的生成在乳腺癌淋巴转移中有重要意义.     

细胞外基质金属蛋白酶诱导因子及金属蛋白酶-9在乳腺癌中的表达及其意义

背景与目的:研究细胞外基质金属蛋白酶诱导因子(EMMPRIN)和基质金属蛋白酶-9(MMP-9)的表达与乳腺癌发生和转移之间的关系.材料与方法:免疫组化法检测21例乳腺增生、10例导管内癌及68例浸润性导管癌中EMMPRIN和MMP-9的表达情况.结果:①EMMPRIN在乳腺增生、导管内癌、浸润性导管癌表达阳性率分别为4.76%(1/21)、40.00%(4/10)、73.53%(50/68),3组之间的阳性率差异均有统计学意义(P＜0.05).②MMP-9在增生乳腺、导管内癌、浸润性导管癌的表达阳性率分别为0.00%(0/21)、30.00%(3/10)、69.12%(47/68),3组之间的阳性率差异亦均有统计学意义(P＜0.05).③乳腺癌组织内的EMMPRIN与MMP-9的表达成正相关(rs=0.676,P＜0.01),而且EMMPRIN和MMP-9的过度表达与腋窝淋巴结转移及淋巴结转移数目呈正相关(P＜0.01).结论:EMMPRIN和MMP-9的过度表达可能在乳腺癌的发生发展过程中起重要作用,是促进乳腺癌发生、浸润、转移的重要因素,可作为评估乳腺癌浸润转移的重要生物学指标.     

Ezrin在乳腺癌发生发展中的表达及意义

目的:探讨Ezrin在乳腺癌发生、发展中的作用,研究其在乳腺癌中的表达及临床意义.方法:应用免疫组化SP法测定Ezrin的表达,所有实验数据录入计算机,用SPSS13.0进行统计学分析.结果:Ezrin异常阳性表达率在乳腺普通导管增生、不典型导管增生、导管内癌、浸润性导管癌中分别为21.4%、25.0%、44.4%、70.3%,差异有显著统计学意义(P＜0.01).比较普通导管增生组(21.4%)与不典型增生组(25.0%),差异无统计学意义(P>0.05).而导管内癌组(44.4%)与浸润性导管癌组(70.3%)间差异有统计学意义(P＜0.05).乳腺增生组(23.1%)与乳腺癌组(64.6%)比较,差异有显著统计学意义(P＜0.01).在浸润性导管癌中,Ezrin高表达与患者年龄无关(P>0.05),与原发肿瘤大小、组织学分级、临床TNM分期、腋淋巴结转移均有关(P＜0.05),同时随着淋巴结转移数目增多,Ezrin异常阳性表达率增高(P＜0.05).结论:Ezrin高表达参与乳腺癌的发生、发展,与原发肿瘤大小、组织学分级、临床TNM分期、腋淋巴结转移等预后指标有关,提示检测Ezrin可作为判定乳腺癌发生、发展及预后的可靠指标.     

乳腺浸润性导管癌中AKT和VEGF-C的表达及其与淋巴道转移的相关性

目的：探讨AKT、p-AKT、AKT2及VEGF-C表达与乳腺浸润性导管癌淋巴结转移的关系,以及乳腺浸润性导管癌中AKT、p-AKT和AKT2与VEGF-C表达的关系。方法：采用RT-PCR法检测17例乳腺浸润性导管癌新鲜组织中AKT2和VEGF-C mRNA的表达;用免疫组织化学SP法检测74例乳腺浸润性导管癌石蜡标本中AKT、p-AKT、AKT2和VEGF-C蛋白的表达,用Western blot法检测17例乳腺浸润性导管癌新鲜标本中AKT、p-AKT、AKT2和VEGF-C蛋白的表达。 结果:AKT2 mRNA在淋巴结转移组中的表达高于无淋巴结转移组（U=14.000,P=0.043）,VEGF-C mRNA在两组乳腺浸润性导管癌组织中表达水平差异无统计学意义（U=29.000,P=0.601）;AKT2和VEGF-C蛋白在有淋巴结转移组中的表达均高于无淋巴结转移组（P<0.05）,而AKT及p-AKT的表达在两组间差异无统计学意义（P>0.05）;p-AKT、AKT2及VEGF-C蛋白在淋巴结转移组中表达均高于无淋巴结转移组;在乳腺浸润性导管癌中VEGF-C与AKT,VEGF-C与p-AKT的表达均呈显著正相关（r分别为0.283和0.328,P值分别为0.015和0.004）,VEGF-C与AKT2的表达无相关性（r＝0.072,P＝0.543）。 结论:AKT2及VEGF-C与乳腺浸润性导管癌淋巴结转移密切相关,可作为乳腺浸润性导管癌淋巴结转移的预测因子。     

人乳腺癌中D2-40标记的微淋巴管密度与淋巴结转移关系的研究

目的:探讨人类乳腺癌组织中D2-40标记的微淋巴管的形态特征及微淋巴管密度(Lymphatic mlcroves-sel density,LMVD)与乳腺癌淋巴结转移的关系.方法:收集沈阳军区总医院2003年1月～2006年10月手术切除的乳腺癌术后组织石蜡标本102例,另选取乳腺纤维腺瘤标本25例为对照组.采用单标及双标免疫组织化学法分别检测D2-40和CD31的表达,计数D2-40阳性微淋巴管密度(LMVD),分析其与乳腺癌淋巴结转移的关系.结果:102例乳腺癌组织中D2-40阳性率为76.5%(78/102),25例对照组D2-40阳性表达率为24.0%(6/25),显著低于乳腺癌组织(X2=24.685,P=0.000).102例浸润性乳腺癌组织中D2-40阳性的微淋巴管中位LMVD为21.61(19.72±5.11)个微淋巴管/100倍视野,且癌周组织中位LMVD显著高于瘤内(P<0.05).单因素方差分析和Pearson相关性分析显示腋淋巴结转移数目和乳腺癌瘤周D2-40标记淋巴管密度有关(P＜0.01.r=0.964).而与瘤内D2-40标记的淋巴管密度无统计学相关(P>0.05).结论:D2-40可以特异性标记乳腺癌组织中微淋巴管内皮细胞,其标记的癌周微淋巴管密度与乳腺癌的淋巴结转移数目密切相关,因此抑制癌周微淋巴管生成有望成为抗肿瘤治疗新的靶点.     

肿瘤相关糖蛋白72和葡萄糖调节蛋白94在乳腺良恶性病变组织中的表达及其意义

目的:研究乳腺良恶性病变组织中肿瘤相关糖蛋白72(tumor-associated glycoprotein, TAG72)和葡萄糖调节蛋白94(glucose-regulated protein 94, GRP94)的表达及其临床病理意义.方法:采用免疫组织化学法检测60例乳腺癌组织和30例乳腺良性病变组织中TAG72和GRP94的表达,并进行评分.应用Kaplan-Meier法对乳腺癌患者进行生存分析.结果: 乳腺癌组织中TAG72和GRP94表达的阳性率分别为68.3%和63.3%,其总评分分别为2.53±1.86和2.73±2.23;乳腺良性病变组织的TAG72和GRP94表达阳性率分别为10.0%和13.3%,其总评分分别为0.37±1.13和0.47±1.22;乳腺癌组织与乳腺良性病变组织相比,差异均有统计学意义(P = 0.000).导管内癌、组织学分级为Ⅰ或Ⅱ级、肿瘤最大径≤3 cm、无淋巴结转移、雌激素受体阳性、p53阴性及CA15-3阴性乳腺癌患者的TAG72和GRP94表达阳性率及其评分均明显低于浸润性导管癌(P＜0.05)、组织学分级Ⅲ级(P＜0.01)、肿瘤最大径＞3 cm(P＜0.05)、淋巴结转移(P＜0.01)、雌激素受体阴性(P＜0.05)、p53阳性(P＜0.01)和CA15-3阳性(P＜0.01)的乳腺癌患者.TAG72和GRP94表达阳性的乳腺癌患者及两者均表达阳性的乳腺癌患者的术后生存期明显短于阴性表达者(P＜0.01).COX多因素分析结果显示,TAG74和(或)GRP94表达阳性均与术后生存率呈负相关,与死亡率呈正相关,均是独立的预后因素.结论:TAG72和GRP94表达在乳腺癌的发生、发展、临床生物学行为及预后方面可能具有重要作用,TAG72和(或)GRP94表达阳性的乳腺癌患者预后不良.     

血管内皮生长因子-C mRNA和微血管密度与乳腺癌预后相关性关系的探讨

目的:探讨乳腺癌组织内血管内皮生长因子-C mRNA(VEGF-C mRNA)的表达及微血管密度(MVD),分析MVD和VEGF-CmRNA表达与乳腺癌患者预后的意义.方法:采用原位杂交技术观察92例乳腺浸润性导管癌(IDC)组织中VEGF-C mRNA的表达;CD105(细胞膜糖蛋白)标记乳腺癌组织中微血管并观察MVD.结果:不同组织学分级乳腺IDC组织中VEGF-C mRNA表达差异有统计学意义,P<0.05;在淋巴结转移组VEGF-CmRNA表达明显高于淋巴结未转移组,P<0.01;VEGF-C mRNA表达阳性组MVD明显高于VEGF-C mRNA表达阴性组,P<0.001;淋巴结转移组乳腺癌组织中MVD高于淋巴结未转移组,差异有统计学意义(P<0.001),VEGF-C mRNA表达阳性组(高MVD组)较VEGF-C mRNA表达阴性组(低MVD组)5年生存率低,差异有统计学意义,P<0.05.结论:VEGF-C mRNA表达与乳腺癌淋巴结转移及MVD密切相关,检测乳腺癌组织中VEGF-C mRNA表达及观察MVD可能预测乳腺癌预后.     

C4ORF7编码产物在浸润性乳腺导管癌中的表达及意义

背景与目的C4ORF7(chromosome 4 open reading frame 7,四号染色体开放读码框7)编码产物在癌细胞和管腔内皮细胞(包括血管内皮和淋巴内皮)均可能表达,本文探讨C4ORF7编码产物在浸润性乳腺导管癌组织中表达及与浸润性乳腺导管癌发生和淋巴道转移的关系.方法采用免疫组织化学supervision法检测15例正常乳腺组织、15例乳腺良性病变组织、42例浸润性乳腺导管癌组织中C4ORF7编码产物和VEGFR3(vascular endothelial growth factor receptor-3,血管内皮生长因子受体3)在淋巴内皮细胞的表达情况.结果C4ORF7编码产物主要表达于癌细胞、乳腺良性病变的导管上皮细胞和管腔内皮细胞.在浸润性乳腺导管癌原发灶中,C4ORF7编码产物在癌细胞和管腔内皮细胞中表达的阳性率分别为66.7%和73.8%;在乳腺良性病变组织中,C4ORF7编码产物在导管上皮细胞和管腔内皮细胞中表达的阳性率均为33.3%,前者明显高于后者(P＜0.05).在正常乳腺组织中,C4ORF7编码产物呈阴性表达.在浸润性乳腺导管癌中,C4ORF7编码产物在管腔内皮细胞中的表达与肿瘤大小有关,与临床分期及淋巴结转移个数无关.C4ORF7编码产物和VEGFR3在浸润性乳腺导管癌癌周淋巴管内皮细胞中的表达呈显著正相关(γ=0.526,P＜0.02).因此,C4ORF7编码产物在管腔内皮细胞中的表达,主要为淋巴管内皮细胞(LEC)中的表达.结论C4ORF7编码产物在乳腺癌的发生及淋巴道转移过程中发挥一定的作用,检测C4ORF7编码产物的表达可能对评价乳腺癌的预后有参考价值.     

胃癌组织COX-2、VEGF-C表达与淋巴结转移及预后关系的研究

目的:探讨环氧化酶-2(cyclooxygenase-2,COX-2)、血管内皮生长因子C(VEGF-C)在胃癌组织中的表达及其与淋巴管生成、淋巴结转移及预后的关系.方法:采用免疫组织化学SABC法检测 51例胃癌及相应的癌旁组织COX-2、VEGF-C及受体VEGFR-3表达,计数肿瘤内淋巴管密度(LVD),并结合临床病理特征和随访资料进行分析.结果:胃癌组织COX-2、VEGF-C表达阳性率分别为62.8%(32/51),60.7%(31/51).COX-2表达与VEGF-C(r=O.74,P＜0.05)、临床分期(r=0.34,P＜0.05)、淋巴管密度(r=0.69,P＜0.01)和淋巴结转移(r=0.57,P＜0.01)呈正相关,与病理分化呈负相关(r=-0.58,P＜0.01).VEGF-C表达与淋巴管密度(r=0.45,P＜0.01)、淋巴结转移呈正相关(r=0.46,P＜0.05).随访5年,胃癌组织COX-2表达与生存率呈负相关,COX-2表达阴性组5年生存率(36.8%)显著高于COX-2表达阳性组(15.6%)(P＜0.05).结论:在胃癌组织中,COX-2、VEGF-C高表达,COX-2与VEGF-C、淋巴管密度、淋巴结转移呈正相关.推测COX-2通过诱导VEGF-C表达参与淋巴结转移.胃癌组织COX-2检测可能对推测预后具有重要意义.     

Bacteria and cancer--antagonisms and benefits

There is considerable historical and recent evidence concerning the antagonisms between acute bacterial infections or their toxins and cancer and allied diseases. These data provide renewed incentives to undertake clinical programmes with mixed bacterial vaccines in many countries at the present time.     

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.     

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。     

Renal irradiation and the pharmacology and toxicity of methotrexate and cisplatinum

We used a rat model to study the effects of renal irradiation on the pharmacology of methotrexate (MTX) and cisplatinum (cis-Pt). Unanesthetized rats were given bilateral kidney irradiation (20 Gy in 9 fractions). At 9 months after irradiation, 3% of the animals had died and survivors showed moderately impaired renal function. At 15 months, 30% of the animals had died and survivors showed severely impaired renal function. Some animals were given i.v. MTX 1 week to 15 months after irradiation. In irradiated rats, the area under the MTX plasma clearance curve equaled that of controls through 6 months, and was significantly above controls from 9 months on. Other animals were given i.p. cis-Pt 1 week to 9 months after irradiation. The acute toxicity of cis-Pt was the same in control and irradiated rats when cis-Pt was given immediately before or after irradiation. Beginning 3 months after irradiation there was a progressive increase in cis-Pt toxicity and a simultaneous decrease in urinary platinum excretion. Irradiated animals that survived cis-Pt treatment showed increased radiation nephritis; the greatest effect occurred when cis-Pt was given 3 months or more after irradiation. MTX and cis-Pt clearance decreased when renal dysfunction was first observed and changes in renal function preceded changes in drug clearance and toxicity.     

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.     

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.