凋亡酶激活因子与p53及Ki-67在结直肠癌和结直肠腺癌组织中的表达

目的探讨凋亡酶激活因子1（Apaf-1）、p53和Ki-67在结直肠腺瘤、结直肠癌组织中的表达情况。方法采用SP染色法,检测结直肠癌、腺瘤组织中Apaf-1、p53和Ki-67的表达情况。结果结直肠癌淋巴结转移组中,Apaf-1、p53、Ki-67阳性表达率分别为22.7%、31.8%和90.9%,无淋巴结转移组分别为43.6%、89.7%和61.5%,差异均有统计学意义（均P〈0.05）。结直肠癌A、B期的Apaf-1、p53、Ki-67阳性表达率分别为43.6%、89.7%和61.5%,C、D期的Apaf-1、p53、Ki-67阳性表达率分别为27.7%、31.8%和90.9%。结直肠癌组织中Apaf-1阳性率（39.0%）低于腺瘤（88.0%）,p53阳性率（77.0%）和Ki-67阳性率（68.0%）均高于腺瘤（分别为49.0%、26.0%）,差异均有统计学意义（P〈0.05）。Apaf-1阳性表达与p53、Ki-67阳性表达均呈负相关（r1=-0.358,r2=-0.361,P〈0.01）。结论 Apaf-1、p53与Ki-67表达在结直肠癌、腺瘤的发生、发展与转移过程中有一定影响,对诊断结直肠癌有重要意义。     

p53和Ki67在结直肠癌中的表达及其临床意义

目的探讨p53蛋白、Ki67在结直肠管状腺瘤和结直肠癌中的表达及意义。方法采用免疫组化法分别对71例结直肠癌,16例结肠腺瘤,进行了p53蛋白和Ki67的检测。结果①结直肠癌组织中p53蛋白、Ki67的阳性表达率分别为40.85%(29/71)、77.46%(55/71),均显著高于腺瘤组织,差异均有统计学意义(P=0.019,P=0.000)。②在结直肠癌组织中p53蛋白的阳性表达与结直肠癌的临床分期、浸润深度、组织学分化程度和淋巴结转移有关(P<0.05);结直肠癌中Ki67的表达阳性率与结直肠癌的临床分期和浸润深度有关(P<0.05),与组织学分化程度和淋巴结转移无关(P>0.05)。③p53蛋白和Ki67共同阳性者26例,共同阴性者13例,相关性分析显示,两者之间呈正相关(γ=0.508,P=0.000)。结论 p53蛋白和Ki67在结直肠癌中的表达明显升高,可作为判断结直肠癌恶性程度及预后的重要参考指标。     

结直肠癌中循环肿瘤细胞的表达及与Ki-67的关系研究

目的 探讨结直肠癌中循环肿瘤细胞(CTC)及其分型的表达,并分析其与Ki-67表达的关系.方法 选取230例结直肠癌患者,收集临床资料,利用CanPatrolTM二代检测技术检测CTC及其分型[上皮型CTC(eCTC)、混合型CTC(bCTC)和间质型CTC(mCTC)]的表达情况;采用免疫组化法检测结直肠癌患者结直肠癌组织中Ki-67的表达情况,分析结直肠癌患者CTC及其分型的表达与Ki-67表达的关系.结果 230例结直肠癌患者中,CTC阳性率为69.13％(159/230),Ⅰ、Ⅱ、Ⅲ期结直肠癌患者CTC阳性率分别为55.56％、64.58％、76.64％,mCTC阳性表达率分别为51.85％、66.71％、79.44％,CTC、mCTC阳性表达率随临床分期的升高而逐渐升高.不同分化程度、淋巴结转移情况、TNM分期结直肠癌患者CTC阳性表达率、mCTC阳性表达率及Ki-67表达情况比较,差异均有统计学意义(P<0.05).Ki-67≥60％结直肠癌患者mCTC阳性表达率为73.85％,高于Ki-67<60％患者的57.14％(P<0.05).结论 随着结直肠癌的进展,CTC、mCTC阳性表达率逐渐升高,且mCTC可能参与结直肠癌血行转移过程;Ki-67表达水平与mCTC的阳性表达可能有关,二者对结直肠癌的发展、转移及预后评估有重要意义.     

结直肠锯齿状腺瘤、传统腺瘤及结直肠癌中端粒酶、p53及Ki-67的表达比较

背景与目的：结直肠锯齿状腺瘤(serrated adenoma,SA)是2000年被WHO正式命名为独立的一种疾病,与传统腺瘤(traditional adenoma,TA)和结直肠癌(colorectal carcinoma,CRC)比较有其独特的性质。本研究通过对锯齿状腺瘤、传统腺瘤和结直肠癌组织中端粒酶、p53及Ki-67的免疫组化表达比较,探讨锯齿状腺瘤与普通腺瘤的恶性潜能异同及与大肠腺癌的关系。方法：运用免疫组化MaxVision法对37例锯齿状腺瘤、36例传统腺瘤,34例结直肠癌组织标本进行端粒酶、p53及Ki-67检测。结果：端粒酶在锯齿状腺瘤、传统腺瘤和结直肠癌组间差异有统计学意义(P<0.05),结直肠癌组阳性率高于锯齿状腺瘤组(P<0.05),锯齿状腺瘤组高于传统腺瘤组(P<0.01);Ki-67在锯齿状腺瘤与传统腺瘤两组差异无统计学意义(P>0.05),结直肠癌组的阳性率则明显高于锯齿状腺瘤和传统腺瘤组(P<0.01);结直肠癌组p53阳性率高于传统腺瘤组(P<0.01),传统腺瘤组高于锯齿状腺瘤组(P<0.01)。结论：端粒酶、p53及Ki-67检测显示：锯齿状腺瘤是一种具有较强活性的腺瘤,端粒酶的激活可能在其癌变过程中起一定作用。     

结直肠癌中p53蛋白和Ki67的表达及临床意义

目的 探讨p53蛋白和Ki67在结直肠癌中的表达及临床病理学意义.方法 应用免疫组织化学的方法 检测80例结直肠癌和癌周黏膜组织中p53蛋白和Ki67表达.结果 p53蛋白和Ki67在结直肠癌中表达阳性率分别为(85%,90%),癌旁组织阳性率分别为(88.2%,88.2%);正常结直肠组织中p53无蛋白表达,Ki67蛋白可见表达.p53蛋白在结直肠癌中的表达与分化程度有显著差异(P<0.01),具有统计学意义,Ki67在结直肠癌中表达与分化程度无显著差异(P>0.05),不具统计学意义.结论 p53蛋白的表达与结直肠癌的发生发展有关,表达强度与癌组织的分化程度、浸润深度、转移及预后有关,Ki67的表达与结直肠癌的发生发展有关,表达强度与癌组织的分化程度浸润深度转移及预后无相关性.p53蛋白可作为评估患者预后的指标,Ki67是评估细胞增殖的较好指标,并不能作为评估患者预后的指标.     

Ki-67、p53及HER-2在结直肠癌组织中表达的临床意义

目的:了解Ki-67、p53及HER-2在结直癌组织中表达的临床意义.方法:采用免疫组化法,观察Ki-67、p53、HER-2在39例结直肠癌组织中的表达特点,并与Dukes分期、组织分化等临床病理特征进行研究探讨.结果:Ki-67、p53及HER-2在结直肠癌组织中的阳性表达率分别为82.1％、56.4％及10.3％;在结直肠癌中,Ki-67在年龄大小和有无淋巴结转移表达中有显著差异(P＜0.05);p53和HER-2在患者性别、年龄、部位、分化程度、Dukes分期、淋巴结转移表达无明显差异(P＞0.05);结直肠腺癌组织中Ki-67与p53的表达呈正相关.结论:联合检测Ki-67和p53在结直肠腺癌中的表达有利于对结直肠腺癌恶性程度及患者预后进评估;而HER-2基因在结直肠肿瘤的表达及相关性治疗,仍需要进一步研究、探讨及验证.     

E-cadherin和Ki-67在结直肠癌组织中的表达及意义

 目的 探讨E-cadherin和Ki-67在结直肠癌中的表达及意义。方法 应用免疫组化SP法检测48例结直肠癌、23例结肠腺瘤和20例正常结肠组织中E-cadherin及Ki-67的表达,并分析其与结直肠癌临床病理特征的关系。结果 结直肠癌、结肠腺瘤和正常结肠组织中E-cadherin异常表达率分别为77.1%、24.0%和5.0%,结直肠癌E-cadherin异常表达率明显高于结肠腺瘤和正常结肠组织,组间比较差异有显著性（P〈0.01）。Ki-67阳性指数在结直肠癌、结肠腺瘤及正常结肠组织中分别为（67.60±2.52）%、（38.44±3.59）%及（8.65±1.10）%。结直肠癌的Ki-67阳性指数明显高于结肠腺瘤和正常结肠组织,组间两两比较差异有统计学意义（P〈0.01）。E-cadherin表达与浸润深度和有无淋巴转移有关（P=0.020和P=0.013）,而与患者的年龄、性别、大体形态、分化程度无关。Ki-67表达与患者性别和有无淋巴转移有关（P=0.011和P=0.043）,而与患者的年龄、大体形态、分化程度、浸润深度无关。E-cadherin正常表达组和异常表达组的Ki-67阳性指数分别为（67.30±18.87）%和（68.64±11.99）%。E-cadherin异常表达组Ki-67阳性指数略高于正常表达组,但无统计学意义。结论 E-cadherin和Ki-67是结直肠癌发生发展过程中的重要因子,并与结直肠癌浸润转移有关,可作为评估结直肠癌预后、指导治疗的指标,但两者在结直肠癌发生、发展、侵袭和转移过程中没有协同作用。     

骨桥蛋白和p21蛋白在结直肠癌中表达的相关意义

目的:探讨骨桥蛋白(OPN)和p21在原发性结直肠癌组织中的表达及转移中的作用。方法:采用免疫组化SP法检测60例结直肠癌组织中OPN和p21的表达情况。结果:OPN和p21的阳性表达主要定位于癌细胞的细胞浆;OPN和p21在60例结直肠癌组织中阳性表达率分别为66.7%(40/60)和61.7%(37/60)。在发生转移的结直肠癌组织中OPN和p21阳性表达率分别为83.3%(25/30)和80.0%(24/30),高于无转移的结直肠癌组织中OPN(50.0%,15/30)和p21(43.3%,13/30)的阳性表达率,差异具有显著性,(P<0.05)。两者均阳性表达的33例结直肠癌有24例(72.7%)已发生转移,与两者均阴性表达的8例结直肠癌仅有1例(12.5%)发生转移相比较,差异有显著性,(P<0.05),提示OPN和p21均阳性表达与肿瘤转移的发生密切相关。OPN和p21的表达与肿瘤的大小、肿瘤的分化、分期、性别、年龄等因素无关,但与肿瘤侵袭的发生有关,(P<0.05)。OPN和p21的表达成显著正相关(r=0.286,P<0.05)。结论:OPN和p21的表达与结直肠癌侵袭转移的发生密切关系,两者均阳性表达时对预测结直肠癌已发生转移具有指导意义。     

结直肠癌COX-2、p53、PCNA和ki-67表达

[目的]探讨环氧化酶-2(COX-2)、p53、增殖细胞核抗原(PCNA)和ki-67蛋白在结直肠癌中表达的意义.[方法]采用SP方法进行免疫组化染色,观察Cox-2、p53、PCNA和ki-67在84例结直肠癌中表达.[结果](1)肿瘤》5 cm、有淋巴结转移LN( )及Dukes'D期结直肠癌病例的COX-2过表达率分别显著高于肿瘤≤5 cm、LN(-)及Dukes'A B C期病例的表达(90.3%,79.4%,100.0%vs.66.0%,52.0%,73.1%,P均《0.05);(2)p53染色阳性率于LN( )及Dukes'D期结直肠癌病例分别高于LN(-)和Dukes'A B C期病例的表达(55.9%,83.3%vs.40.0%,48.7%;P均《0.05);(3))LN( )结直肠癌病例的PCNA阳性染色比LN(-)病例的表达显著增强(88.1%vs.60.0%,P《0.05);(4)LN( )及Dukes'D期结直肠癌病例的ki-67表达率分别比LN(-)和Dukes'A B C期病例的表达显著增强(84.7%,100%vs.40.0%,69.0%,P均《0.05).[结论]结直肠癌COX-2、p53、PCNA和ki-67表达与结直肠癌淋巴结转移和疾病进展等密切相关.     

p53蛋白和Ki-67在恶性纤维组织细胞瘤组织中的表达及意义

目的:研究p53蛋白和Ki-67在恶性纤维组织细胞瘤(malignant fibrous histi-ocytoma,MFH)组织中的表达及其临床意义。方法:应用免疫组化SP法检测50例MFH中p53和Ki-67的表达。结果:p53蛋白和Ki-67在MFH中表达阳性率分别为32·0%(16/50)和56·0%(28/50);在有复发转移的患者中,p53蛋白和Ki-67的阳性率分别为48%(12/25)和68%(17/25);在无复发转移的患者中,p53蛋白和Ki-67的阳性率分别为16·0%(4/25)和40·0%(10/25);生存期<5年的患者中,p53蛋白和Ki-67的阳性率分别为48·1%(13/27)和70·4%(19/27),生存期>5年的患者中p53蛋白和Ki-67的阳性率分别为17·4%(4/23)和39·1%(9/23)。p53蛋白和Ki-67与患者的复发转移及生存期显著相关,P<0·05。p53蛋白与Ki-67的表达关系密切,P<0·05。结论:p53蛋白和Ki-67的高表达与MFH的复发转移及患者生存期相关,两者的表达关系密切,并可作为MFH患者预后判断的两个指标。肿瘤防治杂志,2005,12(19):1492-1494     

Insulin and colon cancer

Some factors related to Westernization or industrialization increase risk of colon cancer. It is believed widely that this increase in risk is related to the direct effects of dietary fat and fiber in the colonic lumen. However, the fat and fiber hypotheses, at least as originally formulated, do not explain adequately many emerging findings from recent epidemiologic studies. An alternative hypothesis, that hyperinsulinemia promotes colon carcinogenesis, is presented here. Insulin is an important growth factor of colonic epithelial cells and is a mitogen of tumor cell growth in vitro. Epidemiologic evidence supporting the insulin/colon-cancer hypothesis is largely indirect and based on the similarity of factors which produce elevated insulin levels with those related to colon cancer risk. Specifically, obesity—particularly central obesity, physical inactivity, and possibly a low dietary polyunsaturated fat to saturated fat ratio—are major determinants of insulin resistance and hyperinsulinemia, and appear related to colon cancer risk. Moreover, a diet high in refined carbohydrates and low in water-soluble fiber, which is associated with an increased risk of colon cancer, causes rapid intestinal absorption of glucose into the blood leading to postprandial hyperinsulinemia. The combination of insulin resistance and high glycemic load produces particularly high insulin levels. Thus, hyperinsulinemia may explain why obesity, physical inactivity, and a diet low in fruits and vegetables and high in red meat and extensively processed foods, all common in the West, increase colon cancer risk.This research was supported by research grant number CA 55075 from the US National Institutes of Health, and Special Institution Grant No. 18 from the American Cancer Society.     

A superficial colon tumor model involving subcutaneous colon translocation and orthotopic transplantation of green fluorescent protein-expressing human colon tumor

The orthotopic transplantation model of human tumor has been demonstrated to be more patient-like animal tumor model. However, observations of tumor progression and metastasis are limited by the deep location of the colon or limited deep penetration ability of fluorescence through tissue. The purpose of this study is to establish a superficial orthotopic model to allow easier real-time visualization and more sensitive monitoring of fluorescent orthotopic colon tumor. Human colon cancer HT-29 cells were transduced with a pLPCX expression retroviral vector containing green fluorescent protein and neomycin resistance genes. For superficial orthotopic transplantation model, the cecum was identified and pulled out of the peritoneal cavity, the space between the cecum and peritoneum was sutured, the cecum was pulled to subcutaneous tissue, and incision was made on the cecal serosa followed by the implantation of a 1-mm tumor tissue to the cecum. For comparison, a conventional orthotopic transplantation model was established in a separate group of mice simultaneously. When tumor sizes reached 5 mm in diameter, half the mice in each model received 5-FU treatment. Primary tumor and metastases were monitored by fluorescent imaging or caliber measurement. Tumor fluorescence was observed as early as 3 days (median time of 4.7 ± 1.3 days) post-transplantation in the superficial orthotopic transplantation model, which was much earlier than 21 days (median time of 26.2 ± 9.9 days) in conventional orthotopic transplantation model. Although tumor growth of 5-FU-treated mice in conventional orthotopic model was lower than those of the untreated mice, the difference was not significant. However, in superficial orthotopic model, tumor growth was significantly inhibited in 5-FU-treated mice relative to the untreated mice. Fluorescence imaging showed similar metastasis incidence between the superficial and conventional orthotopic transplantation models. The fluorescent superficial orthotopic transplantation colon model allows easier real-time visualization and more sensitive monitoring of tumor growth as well as convenient repeated sampling. It is a valuable orthotopic implantation model for study of colon cancer and evaluation of new anti-cancer therapy.     

Vitamin D and colon cancer

Calcitriol, 1α, 25-dihydroxyvitamin D3(1,25(OH)2D3), the most active form of vitamin D, is a pleotropic hormone with a wide range of biological activities. Due to its ability to regulate calcium and phosphate metabolism, 1,25D3 plays a major role in bone health. In addition, 1,25D3 binds to the vitamin D receptor and thereby regulates the expression of a number of genes which control growth, differentiation and survival of cancer cells. In agreement, the levels of vitamin D3 appear to be an essential determinant for the development and progression of colon cancer and supplementation with vitamin D3 is effective in suppressing intestinal tumorigenesis in animal models. Vitamin D3 has been estimated to lower the incidence of colorectal cancer by 50%, which is consistent with the inverse correlation between dietary vitamin D3 intake or sunlight exposure and human colorectal cancer. Several studies confirmed that increasing vitamin D3 lowers colon cancer incidence, reduces polyp recurrence, and that sufficient levels of vitamin D3 are associated with better overall survival of colon cancer patients. Vitamin D regulates the homeostasis of intestinal epithelium by modulating the oncogenic Wnt signaling pathway and by inhibiting tumor-promoting inflammation. Both activities contribute to the ability of 1,25D3 to prevent the development and progression of colon cancer.     

Reproductive factors and colon cancers

In Los Angeles County, the age-adjusted incidence rate of colon cancer in men is almost 30% higher than that in women; however, in the descending and sigmoid colon, age-specific incidence rates for women are higher than those for men before age 55. Since menstrual and/or reproductive factors may be involved in producing this crossover in age-specific rates, they were examined in a population-based case-control study involving 327 white women with adenocarcinoma of the colon and age-, race- and neighbourhood-matched controls. After adjustment for other factors associated with colon cancer in this study (family history of large bowel cancer, total fat intake, calcium, weight and activity level), ever having been pregnant was protective (RR = 0.56, 95% CI = 0.33-0.97). For one to two pregnancies, the RR was 0.76 (CI = 0.42-1.37); for three or more pregnancies, the RR was 0.45 (CI = 0.25-0.81). However, the relationship between the number of pregnancies and colon cancer risk was actually U-shaped, with risk decreasing with successive pregnancies up to four and then increasing with additional pregnancies. The U-shaped relationship was present for incomplete as well as for full-term pregnancies and was more striking for cancers occurring in the distal (descending and sigmoid) than proximal (caecum to splenic flexure) colon. Risk was not related to age at menarche or use of exogenous oestrogens, but delayed natural menopause was weakly protective in the proximal but not distal colon. The crossover in incidence rates in the distal colon can be completely accounted for by the pregnancy effect. The U-shape of the pregnancy curve suggests the possibility of competing factors, some protective, especially after one or several pregnancies, and others conferring increasing risk with successive pregnancies, regardless of the pregnancy outcome.     

Tobacco use and colon cancer

Smoking cigarettes has been consistently associated with adenomatous polyps. However, only a few studies have reported associations between smoking cigarettes or using other forms of tobacco and colon cancer. A population-based case-control study of colon cancer was conducted in 3 areas in the United States: northern California, Utah and Minnesota. We observed approximately a 50% increase in colon cancer risk from smoking over a pack of cigarettes per day among both men and women. Those who stopped smoking remained at increased risk, even if they stopped over 10 years ago. Our data suggest that the amount smoked may be a more important factor than the total number of years smoked. Smoking neither cigars nor pipes was associated with an increased risk of colon cancer. Among female participants only, those who smoked over 20 cigarettes per day and had a large body mass index were at greater risk of colon cancer than participants who smoked the same amount but were smaller (p for interaction among women = 0.04). Int. J. Cancer, 70:259–264, 1997. © 1997 Wiley-Liss, Inc.     

Laparoscopic colon and rectal surgery

There are disparate variables available to appraise the quality of the laparoscopic colorectal surgery. Currently available data suggest that laparoscopic colectomy can be completed safely in most cases. It is feasible and offers patient-related benefits similar to those described for other laparoscopic procedures. The framework, within which the quality of laparoscopic colon and rectum surgery is appraised and judged, is discussed with an emphasis on diverse outcomes used to measure quality.