Livin蛋白和LivinmRNA在散发性大肠管状腺瘤癌变过程中的表达

目的探讨凋亡抑制蛋白Livin和LivinmRNA在散发性大肠管状腺瘤癌变过程中的可能作用。方法采用免疫组化和原位杂交方法检测87例散发性大肠管状腺瘤伴上皮不同程度异型增生及癌变组织中Livin在蛋白和mR-NA水平的表达情况。结果 Livin蛋白在正常大肠黏膜、大肠管状腺瘤伴不同异型增生及腺瘤癌变病例中的阳性表达率分别为14.3%、52.3%和77.3%,腺瘤伴异型增生组和癌变组中Livin蛋白的表达明显高于正常大肠黏膜组（P〈0.05）,且癌变组中Livin蛋白的表达高于腺瘤伴异型增生组（P〈0.05）;Livin蛋白的表达随腺瘤异型增生程度的增高而增高,但无统计学意义（P〉0.05）。大肠管状腺瘤伴异型增生组和癌变组中Livin在mRNA水平的阳性表达率分别为50.8%和81.8%,均明显高于正常大肠黏膜组,而且癌变组中LivinmRNA的表达明显高于腺瘤伴异型增生组（P〈0.05）;LivinmRNA随腺瘤异型增生程度的增高呈递增趋势,但无统计学意义（P〉0.05）。Livin在蛋白和mRNA水平的表达存在一致性（P〈0.05）。结论 Livin在大肠管状腺瘤癌变过程中可能起一定作用。     

Livin和PTEN在结直肠癌组织中的表达及意义

目的 探讨Livin蛋白和PTEN蛋白在结直肠癌组织中的表达和意义.方法 应用免疫组化法检测10例正常大肠组织,30例大肠腺瘤、息肉组织,60例结直肠癌组织中Livin蛋白和PTEN蛋白的表达.结果 PTEN蛋白在结直肠癌组织中的阳性表达率明显低于正常大肠组织及大肠腺瘤、息肉组织,差异有统计学意义(P均<0.05);Livin蛋白在正常大肠组织及结肠腺瘤、息肉组织中无表达,在结直肠癌组织中高表达,差异有统计学意义(P均<0.01).在结直肠癌组织中,随组织病理分级的增加,PTEN蛋白表达阳性率逐渐下降,Livin蛋白表达阳性率逐渐上升,差异有统计学意义(P<0.01和P<0.05);Livin蛋白和PTEN蛋白表达呈负相关(P<0.05).结论 Livin、PTEN在结直肠癌发生发展过程中起着重要的作用,联合检测可为结直肠癌的早期诊断、进一步治疗及预后提供必要的理论依据.     

Survivin和Caspase-3在人类大肠腺瘤及大肠癌中的表达以及与凋亡的关系

目的 评价大肠腺瘤及大肠癌组织中Survivin和Caspase-3的表达情况以及与细胞凋亡的关系。方法 采用免疫组化二步法，对48例无术前放、化疗史的大肠癌患者的手术标本，20例正常大肠黏膜和25例腺瘤标本。进行Survivin和Caspase-3检测，并用TUNEL法检测凋亡细胞。结果 Survivin在正常大肠黏膜中无表达，在管状腺瘤、绒毛状和混合型腺瘤及腺癌中的阳性表达分别为10％、33．3％、70．8％。Caspase-3在正常粘膜、管状腺熘、绒毛状和混合型腺瘤及腺癌中的阳性表达分别为95％、60％、53．3％、45．8％。正常黏膜组织Caspase-3的表达高于大肠腺瘤和大肠癌（P〈0．05）。Survivin和Caspaso-3在大肠癌中的表达强度随组织分化程度增高而增强；而在不同的Dukes分期间无显著差异（P〉0．05）。大肠癌组织中Survivin与Caspase-3的表达无直线相关关系，Survivin阳性组凋亡指数明显低于阴性组（P〈0．005）。结论 Survivin在大肠癌发生早期过程中表达上调，有望成为大肠癌新的早期诊断标志物。Survivin作为凋亡抑制蛋白显著抑制癌组织的细胞凋亡，但不能完全抑制Caspase-3的表达。     

Ki-67、survivin在伴鸡皮样改变大肠腺瘤中表达的临床意义

目的探讨伴鸡皮样黏膜(CSM)改变的大肠腺瘤与大肠腺瘤癌变的关系。方法采用免疫组化法(SP法)检测正常大肠黏膜、伴CSM的大肠腺瘤、不伴CSM的大肠腺瘤和大肠腺癌标本中代表细胞增殖的标志物ki-67和凋亡抑制因子survivin的表达情况,对两者的阳性表达结果进行统计学分析。结果 (1)免疫组化结果显示:在大肠腺瘤癌变组织、伴CSM的大肠腺瘤、不伴CSM的大肠腺瘤及正常大肠黏膜中ki-67的表达阳性率分别为86.4%、81.0%、36.8%、26.7%,呈递减趋势;survivin的阳性表达率分别为63.6%、61.9%、21.1%、0%,呈递减趋势。(2)据统计学分析,ki-67、survivin的阳性表达结果在伴CSM的大肠腺瘤与大肠腺癌组织间比较差异均无统计学意义(P>0.05),其在不伴CSM的大肠腺瘤与正常大肠黏膜比较差异均无统计学意义(P<0.05),其余两两比较均有统计学意义(P<0.05)。结论 ki-67、survivin在伴CSM的大肠腺瘤中及大肠癌中表达水平相近,因此伴CSM的大肠腺瘤在成人中有癌变的风险,是一种癌前病变,比不伴CSM的大肠腺瘤更容易恶变,临床诊疗过程中应予以重视,尽早切除。     

Livin与EGFR、VEGF在结直肠癌中的表达及相关性研究

【目的】探讨Livin基因在结直肠癌中的表达及其与表皮生长因子受体（EGFR ）、血管内皮生长因子（VEGF）的相关性。【方法】采用免疫组织化学染色方法检测结直肠癌、大肠正常黏膜组织各50例中Livin、EG‐FR、VEGF的表达,并分析Livin表达与EGFR、VEGF的相关性。【结果】结直肠癌组织中Livin蛋白的阳性表达率明显高于大肠正常黏膜组织（ P ＜0．01）;Livin蛋白阳性表达率与淋巴结转移及Duke分期有关,而与结直肠癌患者的年龄、性别、分化程度无关;结直肠癌组织中 EGFR蛋白的阳性表达率明显高于正常黏膜组织（ P ＜0．01）;EGFR阳性表达率与结直肠癌中肿瘤的分化程度、Duke分期及淋巴结转移密切相关,与结直肠癌患者的年龄、性别无统计学意义;大肠正常黏膜组织中VEGF的阳性表达率低于结直肠癌组织中VEGF的阳性表达率（ P ＜0．01）,其差异有统计学意义,VEGF蛋白表达与结直肠癌患者的性别、年龄、肿瘤分化程度无关,与肿瘤的Duke分期及有无淋巴结转移有关;在结直肠癌组织中Livin蛋白阳性表达与 EGFR ,VEGF蛋白阳性表达无相关性,而EGFR蛋白阳性表达与VEGF蛋白阳性表达呈正相关。【结论】Livin在结直肠癌组织中过表达,阳性表达率明显高于大肠正常黏膜组织,推测Livin促进了结直肠癌的发生、发展。EGFR、VEGF蛋白在结直肠癌组织中表达呈正相关,推测EGFR、VEGF在结直肠癌的发生发展过程中起着至关重要的作用。     

胃泌素表达与大肠肿瘤的发生和细胞增殖的关系

目的 探讨胃泌素表达与大肠肿瘤的发生和细胞增殖的关系.方法 应用免疫组化技术检测15例正常大肠组织、21例大肠腺瘤和70例大肠癌组织中胃泌素及Ki67的表达.结果 在正常大肠黏膜、大肠腺瘤和大肠癌组织中,胃泌素的阳性表达率依次为0、28.6%和25.7%,大肠癌和腺瘤组显著高于正常对照组(均P<0.05),肠癌和腺瘤组比较差异无统计学意义(P0.05);Ki67的阳性表达率依次为40.0%、76.2%和82.8%,大肠癌和腺瘤组中的表达均高于正常大肠组织(均P<0.05),而肠癌和腺瘤组之间比较差异无统计学意义(P0.05).胃泌素与Ki67之间具有相关性(P<0.05).结论 胃泌素和Ki67在大肠肿瘤中的表达均增高,胃泌素在大肠肿瘤的发生发展中可能起着重要作用,并且胃泌素可能有增强肿瘤细胞增殖活性的作用.     

Livin、缺氧诱导因子-1α在结肠癌中的表达及意义

目的 探讨Livin、缺氧诱导因子-1α(HIF-1α)在结肠癌组织中的表达及意义.方法 应用免疫组织化学染色法检测Livin、HIF-1α蛋白在30例正常结直肠黏膜,30例结直肠腺瘤,30例结直肠癌中的表达.结果 结肠癌组织中Livin、HIF-1α阳性率明显高于结肠腺瘤和结肠正常黏膜组织(P<0.05).结肠腺瘤和结肠正常黏膜组织Livin、HIF-1α阳性率无统计学差异(P>0.05).结论 Livin、HIF-1α在结肠癌的发生及发展中起着重要作用.     

核磷蛋白在大肠癌发生发展中的表达及意义

目的：探讨核磷蛋白在大肠良、恶性肿瘤组织中的表达及其临床意义。方法：应用免疫组织化学方法检测核磷蛋白在大肠腺瘤、大肠腺癌和癌旁正常组织中的表达情况。结果：核磷蛋白在大肠腺瘤、腺癌中阳性率分别为70.83％,76.92％;与癌旁正常组织阳性率38.46％比较,差异均有统计学意义(P＜0.05)。大肠腺癌核磷蛋白阳性率与腺瘤伴轻、中度不典型增生核磷蛋白阳性率比较差异有统计学意义(P＜0.05),而与腺瘤伴重度不典型增生核磷蛋白阳性率比较差异无统计学意义(P＞0.05)。大肠癌组核磷蛋白表达强度与肿瘤Dukes分期、淋巴结转移、远处转移有关(P＜0.05)。结论：核磷蛋白在大肠腺瘤和大肠癌中均表达,其参与大肠癌发生的早期阶段,并在大肠癌发展中发挥一定作用;检测核磷蛋白的表达情况可能对大肠癌早期诊断、指导治疗、改善预后有一定价值。     

蛋白激酶CβⅡ与大肠癌发生发展关系的研究

目的探讨蛋白激酶CβⅡ(PKCβⅡ)在大肠癌发生发展中的可能作用机制。方法选取1996～1999年郑州大学第一附属医院大肠癌根治性手术切除标本69例,手术切除大肠腺瘤21例,另取距肿瘤边缘大于5cm正常大肠黏膜组织标本16例。应用免疫组织化学SP(Streptavidinperoxidase)法检测PKCβⅡ在大肠正常黏膜组织,大肠腺瘤和大肠癌中的表达。结果PKCβⅡ在正常大肠黏膜呈阴性或弱阳性表达;肿瘤组织中PKCβⅡ阳性染色颗粒主要定位于肿瘤细胞胞浆内。正常大肠黏膜、大肠腺瘤和大肠癌组织PKCβⅡ阳性表达率分别为6.25%、28.57%、56.52%,大肠癌组显著高于正常大肠黏膜组和大肠腺瘤组(P<0.05);PKCβⅡ在浸润不超过肌层组和浸润超过肌层至外膜及超过外膜组阳性表达率分别为60%(12/20)和67.57%(25/37),差异有显著性(P<0.05)。有淋巴结转移组阳性率为74.19%(23/31),明显高于无淋巴结转移组42.05%(P<0.05)。Dukes分期C+D期72.72%(24/33)显著高于A+B期41.67%(15/36)。PKCβⅡ表达与大肠癌大体形态、直径大小和分化程度无关(P>0.05)。结论PKCβⅡ与大肠癌的、浸润深度、淋巴结转移、Dukes分期密切相关,PKCβⅡ可能参与了大肠癌的演进过程,是反映患者预后的敏感指标。     

大肠癌和大肠腺瘤组织中端粒酶活性表达及意义

目的:研究大肠癌组织及大肠腺瘤组织中端粒酶活性表达的差异,探讨端粒酶激活在大肠癌发生、发展中的意义.方法:采用端粒重复片段扩增方法研究了37例大肠癌、50例大肠腺瘤、20例正常大肠组织中的端粒酶活性表达.结果:(1)端粒酶活性检出率在大肠癌组织、大肠腺瘤组织分别为86.5%、20.0%,而正常大肠组织中无表达,癌组织中检出率明显高于其他组织(P＜0.001).(2)端粒酶活性与大肠癌的病理分化程度、病理分期、肿瘤大小、部位无显著相关性(P＞0.05).结论:大肠癌组织中端粒酶活性呈高表达,端粒酶在大肠癌发生发展过程中起着重要作用,有希望成为大肠癌诊断和治疗的理想标志.     

Screening, surveillance, and prevention of colorectal cancer

Colon cancer screening can be effective, but only with a high-quality program that assures adherence to all elements of the program. There is evidence in the United States of greater acceptance of screening and decreased incidence and mortality of colorectal cancer. Patient education is a key element of any effective screening program. It is hoped that future screening will develop better risk-stratification tools and enable targeting of screening to high-risk individuals.     

Molecular biomarkers in esophageal,gastric, and colorectal adenocarcinoma

Cancers of the esophagus, stomach and colon contribute to a major health burden worldwide and over 20% of all cancer deaths. Biomarkers that should indicate pathogenic process and are measureable in an objective manner for these tumors are rare and not established in the clinical setting. In general biomarkers can be very useful for cancer management as they can improve clinical decision-making regarding diagnosis, surveillance, and therapy. Biomarkers can be different types of molecular entities (such as DNA, RNA or proteins), which can be detected, in different tissues or body fluids. However, more important is the type of biomarker itself, which allows diagnostic, prognostic or predictive analyses for different clinical problems. This review aims to systematically summarize the recent findings of genetic and epigenetic markers for gastrointestinal tumors within the last decade. While many biomarkers seem to be very promising, especially if used as panels, further development is urgently needed to address practical considerations of biomarkers in cancer treatment.     

Diabetes, colorectal cancer and cyclooxygenase 2 inhibition

Diabetes is a risk factor for cancer and specifically colorectal cancer. It is also associated with increased cancer mortality. Aspirin, non-steroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase 2 (Cox-2) inhibitors have been shown to decrease the incidence of colorectal cancer. This effect may be mediated by inhibiting prostaglandin synthesis. Long-term use of high-dose aspirin and NSAIDs is associated with significant gastrointestinal side effects. Unfortunately, the use of Cox-2 inhibitors is associated with an increased incidence of acute myocardial infarction and death from cardiovascular disease. The increased risk of cardiovascular disease in patients with diabetes results in the loss of the potential to use Cox-2 inhibitors for cancer chemoprophylaxis. Until a safer type of Cox-2 inhibitor is available, or low-dose aspirin is evaluated for chemoprophylaxis, a more intense screening programme for colorectal cancer may be appropriate for patients with diabetes, especially men. Healthcare professionals managing patients with diabetes should be aware of the increased risk of this type of cancer.     

Breast, stomach and colorectal cancer screening in Korea

Some issues and activities in cancer screening in Korea are briefly described, in particular those in stomach, breast and colorectal screening. There is randomized trial evidence for the efficacy of screening for breast cancer and colorectal neoplasia. Stomach cancer screening is as yet unproven, but the disease is very common in Korea and one of the leading causes of death. There are major related issues to be addressed by the country in the near future. These include improving uptake and coverage rates, quality control and evaluation. Colorectal cancer will be a major concern as its incidence and mortality rates have been increasing rapidly in recent years.     

Update on colorectal cancer. Risk factors, diagnosis, and treatment

Colorectal cancer is more common in the Western world than in underdeveloped countries. Diet, longevity, heredity, and presence of other bowel diseases may affect the incidence. Diagnosis is based on results of routine laboratory studies and evaluation of the entire large bowel with air-contrast barium enema and colonoscopy. Surgical resection is the primary therapy for colorectal cancer. Postoperative systemic chemotherapy yields poor results, but hepatic artery infusional chemotherapy offers some benefit to patients who have only hepatic metastases. Follow-up evaluation includes physical examination and laboratory studies every 3 months for the first 2 years and colonoscopy every year.     

结直肠癌的社区筛查及早期诊治

目前虽然结直肠癌诊断及外科治疗已取得长足的进步,但近10年来其5年生存率仍徘徊于50%左右。结直肠癌的社区筛查及其早期诊治成为了提高患者生存率、改善患者生活质量的关键。本文汇总了结直肠癌社区筛查及早期治疗的策略和相关治疗技术的最新进展。期待能提高对结直肠癌筛查及早期治疗的认识,进一步降低结直肠癌的发病率及病死率。     

Population screening for colorectal cancer, the goals and means

The causes of colorectal cancer are complex and in most cases obscure, making primary prevention impossible at present. Secondary prevention by finding and treating early asymptomatic cancers may possibly reduce mortality from this very common cancer. Results from conventional treatment have changed little during recent decades and are unsatisfactory, with more than half of the patients dying from the disease. The incidence has increased during recent years in many countries, making it vital to evaluate possible benefits from screening. This review considers different methods of screening for colorectal cancer and includes an overview of continuing European controlled randomised trials with the faecal occult blood test, Haemoccult-II. No final evaluation is possible, but advantages and drawbacks of different strategies are discussed. Assuming that the goal of reducing mortality is achieved, several other problems remain unsolved: the organisation of screening, the training of doctors in endoscopy, cost benefit and cost effectiveness all of which will have to be solved before a population screening can be recommended. Present screening tools are not ideal and we have to continue the search for better markers of early colorectal cancers and even possible precursors like adenomas.     

Folate in colorectal cancer,prostate cancer and cardiovascular disease

Ratio of urinary hydroxyproline/creatinine excretion is often used as an index of bone resorption. To establish the difference between the fasting urinary content (FU-HPR/CR) and the 24-h urinary excretion (24 h-U-HPR/CR) we determined hydroxyproline and creatinine in specimens from a group of early postmenopausal women. One hundred and eighty-six early postmenopausal women were randomized into 10 groups receiving various doses of sequential female sex hormones and/or 1,25(OH)₂D₃, 0.25 μg per day, or placebo. In all groups there were parallel changes of FU-HPR/CR and 24 h-U-HPR/CR, and in all groups treated with oestrogens the values decreased significantly. The changes in FU-HPR/CR were more pronounced than in the 24-h-U-HPR/CR, which indicates that FU-HPR/CR is a more sensitive marker of changes in bone resorption. The strong correlation between the mean values of 24-h-U-HPR/CR and those of FU-HPR/CR suggests that both methods are convenient for evaluating changes during long-term studies in groups of patients. The correlation on an individual basis is weak. The substantial intraindividual variation in 24-h-U-HPR/CR, (34.6%) indicates that FU-HPR/CR (CV=17.0%) is the more valid variable for individual patients.     

Compliance, attitudes and barriers to post-operative colorectal cancer follow-up

Rationale Meta‐analyses demonstrate that surveillance following curative‐intent colorectal cancer (CRC) surgery can improve survival. Our multidisciplinary team adopted a stringent CRC follow‐up (FU) guideline in 2000. The purpose of this study was to assess adherence and barriers to FU for CRC. Methods Patients with primary CRC aged 19–75 years, treated with curative intent surgery from July 2000 to December 2002 were identified from a prospective database. Compliance with FU was assessed primarily by chart review. We also surveyed patients and providers to explore attitudes and barriers to surveillance adherence using tenets of the Health Belief Model. Results 96 patients met inclusion criteria and were appropriate for FU. Median FU was 34 months. Guideline targets were met for 70% of clinic visits; 49% of carcinoembryonic antigen (CEA) determinations; and 62% of abdominal imaging studies. Post‐operative colonoscopy did not occur in 6/93 patients. Seventy per cent of health care providers and 55% of patients completed a survey. Access to testing and confusion about which provider orders investigations were identified as important barriers to FU. Conclusion Patterns of CRC FU were widely variable despite implementation of a guideline. Despite patient and provider agreement with the principles of CRC FU, adoption was inhibited by confusion among multiple providers regarding investigation coordination.