survivin在人宫颈癌前病变和宫颈浸润癌组织中的定量分析及其临床价值的评估

目的 检测survivin在人宫颈癌前病变和宫颈浸润癌组织中的表达,探讨其与宫颈癌发生发展的关系,评估其临床应用价值。方法 采用免疫组化技术和实时荧光定量PCR技术检测30例宫颈浸润癌、15例癌前病变和10例宫颈炎组织中survivin的表达。结果 （1）survivin蛋白和survivin mRNA在宫颈炎组织中仅微量表达,在宫颈癌前病变和宫颈癌组织的表达依次显著增强（P＜0.05和P＜0.01）, survivin mRNA在宫颈癌前病变和浸润癌组织中的表达量分别是宫颈炎组的11.0倍和22.6倍。（2）在宫颈癌前病变、宫颈浸润癌组织中survivin mRNA和蛋白两者的表达量均呈正相关（P=0.02和P=0.01）,而在宫颈炎组织中两者无明显相关性。结论 survivin与宫颈癌的发生发展密切相关,是一个具有重要临床意义的特异性肿瘤标记物,应用实时荧光定量PCR技术检测survivin可做为宫颈癌早期诊断的可靠方法。     

宫颈鳞癌及癌前病变组织中VEGF、nm23表达及微血管密度研究

目的　探讨宫颈鳞癌及癌前病变组织中VEGF、nm 2 3表达情况及MVD与宫颈鳞癌发展浸润的关系。方法　采用免疫组化方法对 5 0例宫颈鳞癌、2 8例CIN和 12例正常宫颈组织进行VEGF、nm 2 3和CD3 4检测 ,计数癌组织MVD ,并结合临床资料进行统计分析。结果　宫颈鳞癌VEGF阳性表达率明显高于正常组织和CINⅠ、Ⅱ级组织 ,VEGF表达与癌组织MVD、肿瘤浸润、转移和临床分期密切相关 ;癌组织MVD与肿瘤转移密切相关 ;正常宫颈组织nm 2 3均呈阳性表达 ,而宫颈浸润癌组织nm 2 3表达率明显降低 ,但nm 2 3表达与肿瘤浸润、转移和临床分期无明显相关性。结论　宫颈鳞癌组织VEGF呈高表达、nm 2 3呈低表达 ,可能在宫颈鳞癌血管生长、肿瘤浸润转移过程中起重要作用     

整合素α2β1和CD44V4与早期宫颈鳞癌淋巴结转移的关系

摘 要：［目的］ 探讨整合素α2β1和CD44V4与早期宫颈鳞癌淋巴结转移的关系。［方法］ 收集我院宫颈鳞癌Ⅰb1期标本81份,正常宫颈组织20份和宫颈鳞状细胞原位癌组织20份。采用实时定量PCR和免疫组化法分别检测组织中整合素α2β1和CD44V4的表达,另外采用免疫组化法检测标记D2-40标记的淋巴管密度（LVD）。采用Pearson分析检验整合素α2β1、CD44V4和LVD相关性。［结果］ 宫颈癌组织中整合素α2β1和CD44V4 mRNA的相对表达量分别为1.1±0.2和1.3±0.1,均高于正常宫颈组织［(0.1±0.0)和（0.1±0.0）］和鳞状细胞原位癌组织［(0.3±0.1)和（0.3±0.1）］（P＜0.05）。宫颈癌组织中整合素α2β1和CD44V4蛋白的阳性表达率分别为87.7%和85.2%,均高于正常组织（5.0%和10.0%）和鳞状细胞原位癌组织（70.0%和40.0%）（P＜0.05）。高中分化宫颈癌患者整合素α2β1和CD44V4阳性率均低于低分化患者,且有淋巴结转移患者高于无转移患者（P＜0.05）。宫颈癌组织 LVD均高于鳞状细胞原位癌组织和正常组织,高中分化和有淋巴结转移的宫颈癌组织LVD较高（P＜0.05）。宫颈癌组织中整合素α2β1和CD44V4表达呈正相关（r=0.687,P＜0.05）,整合素α2β1表达与LVD呈正相关（r=0.559,P＜0.05）,CD44V4表达与LVD呈正相关（r=0.612,P＜0.05）。［结论］ 整合素α2β1和CD44V4可促进早期宫颈鳞癌的发生、发展和淋巴结转移,两者可能发挥协同作用。     

宫颈鳞状细胞癌发生和演进中Maspin表达及其意义的研究

目的:观察肿瘤转移抑制基因Maspin(mammary-serpin)在宫颈鳞状细胞癌和癌前病变组织中的表达,探讨其在宫颈鳞癌发生、演进中的作用及其意义.方法:运用免疫组织化学Envision二步法检测Maspin在正常宫颈组织、宫颈上皮内瘤变(CIN)和宫颈鳞癌组织的表达情况,进行统计学分析,并比较与宫颈鳞癌临床病理特征的关系.结果:Maspin在正常宫颈组织、CIN和宫颈鳞癌中阳性表达率分别为100.0%、87.5%、50.0%,表达呈逐级下降,宫颈鳞癌与前两者间差异有统计学意义,P＜0.01.正常宫颈组织和CIN以细胞质表达为主,宫颈鳞癌以胞核、胞质表达为主,在部分高级别CIN和微小浸润性宫颈癌表达呈异质性,基底区和浸润灶组织阳性信号减弱或缺失.Maspin的表达与宫颈癌的临床分期,肿瘤浸润深度、淋巴结转移及患者的生存时间呈负相关.结论:Maspin表达的下调可能在宫颈鳞癌的发生和演进过程中起一定作用,是观察宫颈CIN进展的一种潜在的有用标志,并与宫颈鳞癌浸润转移和生存密切相关,有望作为判断宫颈癌预后有价值的生物学指标.     

宫颈鳞状细胞癌及宫颈上皮内肿瘤组织中HPVl6感染与端粒酶hTERT表达的关系

目的探讨HPV16感染与端粒酶hTERT表达在人宫颈鳞状细胞癌及其癌前病变中的关系.方法应用组织芯片技术结合原位杂交技术和免疫组织化学方法研究正常宫颈组织、宫颈上皮内肿瘤组织和宫颈鳞癌组织中HPV16感染以及hTERT表达的情况.结果 CINⅡ级、CINⅢ级、浸润性鳞癌组织中HPV16杂交信号阳性率显著高于正常宫颈组织(P<0.05),浸润癌HPV16阳性率也显著高于CIN(P<0.05);hTERT在CINⅡ级、CINⅢ级、浸润性鳞癌组织中的表达都显著高于正常宫颈组织(P<0.05),浸润癌也显著高于CIN(P<0.05);HPV16感染与hTERT表达之间呈正相关(P<0.05,r=0.339).结论宫颈鳞癌的形成与HPV16的感染、hTERT过度表达有重要关系.宫颈鳞癌及其癌前病变组织中HPV16感染与hTERT表达之间呈正相关,两者联合检测配合细胞学检查可能利于提高宫颈癌及其癌前病变的诊断率.组织芯片技术是高效的研究基因及其表达产物的技术平台.     

MIF、MMP-9在宫颈鳞癌组织中的表达及与微血管密度的关系

目的:分析宫颈组织上皮内瘤样病变(cervical intraepithelial neoplasm,CIN)和宫颈鳞癌(squamous carcinoma of cervix,scc)中巨噬细胞移动抑制因子(macrophage migration inhibitory factor,MIF)和金属蛋白酶-9(MMP-9)与微血管密度(microvessel density,MVD)的表达情况及意义.方法:选择SCC组织标本51份、CIN标本41份,正常宫颈组织(normal cervical epithelium,NCE)标本32份,采用免疫组化SP法检测各组MIF和MMP-9的表达和MVD(CD44标记)情况.结果:SCC、CIN组中MIF和MMP-9阳性率和MVD值均明显高于对照NCE组(P＜0.05),但MIF阳性表达在CIN组和SCC组中差异无统计学意义(P＞0.05).MIF、MMP-9在SCC组织中的阳性表达均与组织分化程度、有无淋巴结转移相关,但与临床分期无关(P＞0.05),在SCC组织中二者表达呈正相关.SCC组中MIF和MMP-9阳性者的MVD值明显高于其阴性者(P＜0.05),在SCC淋巴结转移组织中MIF和MMP-9阳性者的MVD值明显高于无淋巴结转移组(P＜0.05),MIF和MMP-9的表达与MVD值存在显著正相关性(P＜0.05).结论:MIF和MMP-9在SCC的发生、发展、浸润及转移中起重要作用.SCC组织学分化越差,MIF和MMP-9阳性表达率越高及MVD值越高,且MIF和MMP-9的表达呈正相关.提示二者联合检测对评估SCC严重程度有一定的参考价值.     

TLR-9在宫颈鳞癌组织中的表达及其与MVD和VEGF的关系

目的检测宫颈鳞癌组织中Toll样受体-9（TLR-9）表达及其与微血管密度（MVD）和血管内皮生长因子（VEGF）的关系。方法 采用免疫组织化学SP法检测48例宫颈鳞癌和20例正常宫颈上皮组织中TLR-9表达,用CD34单克隆抗体标记微血管并计算MVD,同时采用酶联免疫吸附法检测宫颈鳞癌组织中VEGF水平。采用受试者工作特征曲线评价TLR-9表达诊断宫颈鳞癌的效能。结果 宫颈鳞癌组织中TLR-9受体的阳性表达率为83.3％（40/48）,组织MVD和VEGF水平分别为36.8±7.25和（25.58±3.49）ng/mg,均高于正常宫颈上皮组织（P＜0.05）;TLR-9受体的高表达与肿瘤的临床分期和基质金属蛋白酶9表达有关（P＜0.05）,与组织学分级及淋巴结转移无关（P＞0.05）;TLR-9受体表达阳性者的MVD和VEGF水平明显高于阴性者（P＜0.05）。组织TLR-9表达在宫颈鳞癌诊断中的效能较好,其AUC、灵敏度和特异度分别为0.830、82.7％和76.1％。结论 TLR-9高表达可能参与宫颈鳞癌的发生发展及浸润转移,并与宫颈鳞癌的微血管新生密切相关。     

S100A4蛋白在宫颈鳞痛中的表达及意义

目的研究S100A4蛋白在宫颈鳞癌组织中的表达及其临床意义.方法应用免疫组织化学SP法检测65例宫颈鳞癌组织和10例正常宫颈组织中S100A4蛋白.结果在正常宫颈组织中S100A4蛋白不表达;在宫颈鳞癌组织中S100A4蛋白的表达率为35.4%(23/65);与正常宫颈组织比较,差异具有显著性(P＜0.01).S100A4蛋白在宫颈鳞癌中的表达与临床分期和淋巴结转移有关(P＜0.01),与组织学分级无关(P＞0.05);阳性细胞在血管平滑肌细胞以及淋巴细胞中亦有表达.结论S100A4蛋白和宫颈鳞癌的侵袭和转移密切相关;S100A4蛋白可作为判定宫颈鳞癌临床病理特征的重要指标.     

RIZ1蛋白表达与宫颈鳞状细胞癌临床病理参数及放疗敏感性的相关性研究

目的 探讨宫颈鳞状细胞癌组织中Rb蛋白结合锌指结构基因1(RIZ1)的表达及其与宫颈癌患者临床病理参数及放疗敏感性的关系。方法 采用免疫组化法观察RIZ1在159例宫颈鳞癌(Ⅱ b、Ⅲ a 期)患者及20例正常宫颈组织中的表达情况,分析RIZ1在宫颈鳞癌组织中不同组间的差异表达情况,及其与宫颈癌放疗敏感性的相关性。结果 与正常宫颈组织相比,RIZ1蛋白在宫颈鳞癌组织中的表达水平明显下降(P＜0.001);RIZ1蛋白的表达水平与宫颈癌的放疗敏感性密切相关(P=0.012),并与FIGO分期(P=0.004)、深肌层浸润(P=0.026)、盆腔淋巴结转移(P=0.021)以及放疗后复发(P=0.005)密切相关,Logistic回归结果提示RIZ1蛋白高表达是宫颈癌放疗敏感性的独立预测因素(P=0.045)。结论 RIZ1可能参与宫颈鳞癌的发生与发展过程,并可能成为评估宫颈鳞癌放疗敏感性的候选标志物。     

Gankyrin在喉鳞癌组织中的表达及临床意义

目的:研究Gankyrin在喉鳞癌组织中的表达及Gankyrin的表达水平与其临床病理特征间的关系.方法:应用qRT-PCR及Western Blot技术检测16例新鲜喉鳞癌组织、相应癌旁组织中Gankyrin mRNA及Gankyrin蛋白的表达;免疫组织化学方法检测Gankyrin蛋白在50例喉鳞癌组织蜡块及癌旁组织中的表达,并分析其与临床病理参数的关系.结果:16例新鲜喉鳞癌组织与癌旁组织相比,Gankyrin mRNA及Gankyrin蛋白在喉鳞癌组织表达增加(均P ＜0.05).50例喉鳞癌组织蜡块中Gankyrin蛋白表达阳性率(34/50,68％)明显高于相应癌旁组织(6/50,12％),差异有统计学意义(P＜0.05).喉鳞癌组织中的Gankyrin蛋白表达水平与肿瘤病理分化程度、临床分期相关(均P＜0.05).结论:Gankyrin在喉鳞癌组织高表达且与喉鳞癌的发生发展密切相关.     

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.