性激素受体与VEGF、EGFR及COX-2在结直肠癌肝转移中的作用
摘要
背景:结直肠癌是我国常见的消化道恶性肿瘤,近年来其发病率呈增高趋势,肝脏是结直肠癌最常见的转移部位,是结直肠癌患者死亡的主要原因。流行病学调查结果显示,各年龄段女性结直肠癌的患病率均低于男性,结直肠癌肝转移(CRC LM)患者男女性别比例为1.9:1,绝经后的妇女患结肠癌的风险较绝经前妇女高,应用雌激素替代疗法可以减少绝经期妇女患结肠癌的风险30%～40%。目前已经发现性激素参与调节肠粘膜细胞的分化和成熟,且雌激素受体(estrogen receptor, ER)和孕激素受体(progestogen receptor, PR)在大肠正常组织和肿瘤组织中均有表达,提示雌激素及孕激素可能影响这些肿瘤的发生与发展提供了客观依据。另外雌激素(单用或联用孕激素)替代疗法在临床上作为治疗结直肠癌的一种手段已取得一定疗效,由此推测CRC LM可能与性激素水平有关。
目的:研究雌激素受体α、雌激素受体β、雄激素受体、孕激素受体在肠癌灶、正常肠粘膜及肝转移灶中的表达,探讨其在结直肠癌肝转移中的作用。
材料和方法:病例入选标准:术前未经过放疗、化疗,术前一年之内无服用性激素药物史;剔除标准:切除的肝转移灶小,不能同时满足病理检查和实验研究需要量,收集2000年3月至2008年12月间CRC伴肝转移、并且除肝脏外无其他器官转移的病例,共43例,设为实验组,同时随机选取同期住院接受手术治疗的单纯性CRC病例43例,设为对照组,应用免疫组化SP法和SuperPicTureTM Polymer二步法测定———肠癌灶、正常肠粘膜及肝转移灶中雌激素受体(ERα、ERβ)、孕激素受体(PR)、雄激素受体(AR)的表达。另外收集2005年6月至2008年12月间住院手术治疗的结直肠癌肝转移病例和单纯性结直肠癌病例各30例,应用RT-PCR检测结直肠癌肿瘤组织和正常粘膜组织中ERβmRNA的表达情况。统计学方法:所得资料采用两样本率比较、Fisher确切概率法、χ2分割法计算多样本率的两两比较以及两小样本均数比较t检验处理,检验水准取α=0.05,由SPSS13.0 for windows软件包完成统计工作。
结果:肠癌灶、正常肠粘膜及肝转移病灶均未检测到ERα蛋白表达。肝转移灶表达ERβ蛋白,其表达率13.2%(5/43),低于肠癌病灶ERβ蛋白表达率36.0%(31/86),差异有统计学意义(P<0.05),与肝转移组正常肠粘膜ERβ蛋白表达率60.5%(26/43)比较,差异有统计学意义(P<0.05)。实验组和对照组肠癌灶ERβ蛋白表达率分别为34.9% ,37.2% ,二者差异无统计学意义,P>0.05,两组正常肠粘膜ERβ蛋白表达率分别为60.5% ,62.8% ,二者差异无统计学意义,P>0.05。实验组和对照组肠癌灶ERβ蛋白表达率均明显低于正常肠粘膜,P<0.05。肝转移灶PR蛋白表达率4.7%(2/43),低于肠癌病灶PR蛋白表达率40.7%(35/86),差异有统计学意义(P<0.05),与肝转移组正常肠粘膜PR蛋白表达率55.8%(19/43)比较,差异有统计学意义(P<0.05)。实验组和对照组肠癌灶PR蛋白表达率分别为39.5%(17/43),41.9%(18/43),二者差异无统计学意义,P>0.05,两组正常肠粘膜PR蛋白表达率均为55.8%(14/43),无差异。实验组和对照组肠癌灶PR蛋白表达率均明显低于正常肠粘膜,P<0.05。肝转移灶中AR蛋白表达率7.0%低于肠癌病灶AR蛋白表达率27.9%(24/86),差异有统计学意义(P<0.05),与同组正常肠粘膜AR蛋白表达率23.3%比较,差异无统计学意义(P>0.05)。实验组和对照组肠癌灶AR蛋白表达率分别为23.3%(10/30),32.6%(14/30),二者差异无统计学意义,P>0.05,两组正常肠粘膜AR蛋白表达率分别为23.3%(10/30)和37.2%(16/30),差异无统计学意义。实验组和对照组肠癌灶和正常肠粘膜AR蛋白表达率差异无统计学意义。ERβmRNA在实验组肠癌组织中的表达率为33.3%(10/30),低于其该组正常肠粘膜中的表达率60%(18/30),差异有统计学意义,P<0.05,ERβmRNA在对照组肠癌组织中的表达率为43.3%(13/30),低于其该组正常肠粘膜中的表达率73.3%(22/30),差异有统计学意义,P<0.05,ERβmRNA在实验组和对照组肠癌灶或正常肠粘膜间表达差异无统计学意义,P>0.05。
结论:ERβ蛋白是CRC肝转移灶中的优势ER,CRC肝转移灶和肠癌癌灶均未发现ERα蛋白表达。实验组中,肝转移灶、肠癌灶和正常肠粘膜的ERβ蛋白和PR蛋白表达率呈依次升高的趋势,ERβmRNA在结直肠癌与相应正常肠粘膜中的的表达也有类似趋势。随着肿瘤进展,ERβmRNA表达降低,由此所致ERβ蛋白逐渐减少,推测ERβ对于结直肠癌肝转移是保护因子。PR可能协同作用于ERβ并对结直肠癌肝转移起保护性作用。AR在结直肠癌中有低表达,其在结直肠癌肝转移中的作用尚不明确。
背景:结直肠癌是常见消化道恶性肿瘤,发病率在男性恶性肿瘤中排第四位,女性排第三位,近年来,随着我国生活条件和饮食习惯的改变,结直肠癌发病率呈逐年上升趋势,且75%的病例发生于普通人群。虽然随着研究的深入和诊疗技术的提高,结直肠癌的早期诊断率和术后生存率有所提高,但仍未取得突破性进展,总体状况仍难令人满意。转移和复发是影响CRC预后的主要原因,肝脏是CRC最常见的转移部位,初诊时已有20%～40%的病人发生肝转移,此后20%～25%的患者发生异时性肝转移。提高CRC早期诊断率和治愈率是目前面对的一大难题,选择有效的预防药物及初步探讨其作用机制成为当前一项十分迫切的任务。
目的:探讨VEGF和EGFR在结直肠癌肝转移中的作用及其与临床病理特征之间的关系。
方法:按第一部分选择和剔除标准,随机选择43例结直肠癌肝转移患者作为实验组,43例结直肠癌无他处转移的患者作为对照组,取手术切除原发肠癌病灶和相应癌旁正常肠粘膜组织及肝转移组织,应用免疫组织化学检测VEGF和EGFR蛋白的表达情况,统计分析VEGF和EGFR在两组病例中肝转移病灶、肠癌病灶及正常肠粘膜中的表达差异,及其与肿瘤临床病理特征的关系。统计学方法:所得资料采用两样本率比较、Fisher确切概率法、χ2分割法计算多样本率的两两比较,不同组间阳性率差异比较用χ2检验,相关分析采用Spearman等级相关分析,检验标准P<0.05有统计学意义,用SPSS13.0 for windows软件包完成统计学分析。
结果:(1)VEGF蛋白在实验组中肠癌病灶的阳性表达率为76.7%(33/43),高于该组的肝转移病灶的58.1%(25/43)和正常肠粘膜的9.3%(4/43),差异有统计学意义,P<0.05;实验组肠癌病灶VEGF蛋白的阳性表达率高于对照组的53.5%(23/43),差异有统计学意义,P<0.05;实验组和对照组正常肠粘膜VEGF蛋白率都比较低,分别为9.3%和0,差异无统计学意义,P>0.05;(2)EGFR蛋白在实验组中肠癌病灶的阳性表达率为79.1%(34/43),高于该组的肝转移病灶的48.8%(21/43)和正常肠粘膜的11.6%(5/43),差异有统计学意义,P<0.05;实验组肠癌病灶EGFR蛋白的阳性表达率高于对照组的58.1%(25/43),差异有统计学意义,P<0.05;实验组和对照组正常肠粘膜EGFR蛋白率都比较低,分别为11.6%(5/43)和0,差异无统计学意义,P>0.05;(3)将两组病例综合,分析VEGF和EGFR蛋白表达率与结直肠癌临床病理特征的关系,发现VEGF和EGFR蛋白表达与性别、年龄、肿瘤部位、组织类型、浸润深度无相关性,与肿瘤分化程度呈负相关,与肝转移和淋巴结转移呈正相关,且两者有相关性。
结论:(1)VEGF和EGFR异常表达是结直肠癌发生肝转移中的一个重要环节。(2)VEGF和EGFR可作为结直肠癌有无转移的生物学指标,有助于预测CRC肝转移的发生和判断CRC肝转移的预后。
目的:应用免疫组织化学技术检测COX-在结直肠癌发生肝转移病例中的表达情况,探讨COX-2对结直肠癌肝转移的影响。
方法:按照论文第一部分的入选标准和剔除标准,收集43例结直肠癌肝转移病例作为实验组,同时随机选取单纯性结直肠癌病例作为对照组。免疫组化SuperPic Ture TMPolymer二步法检测——肝转移灶、肠癌灶和正常肠粘膜内COX-2蛋白的表达情况。统计学方法:所得资料采用两样本率比较、Fisher确切概率法、χ2分割法计算多样本率的两两比较,不同组间阳性率差异比较用χ2检验,相关分析采用Spearman等级相关分析,检验标准P<0.05有统计学意义,用SPSS13.0 for windows软件包完成统计学分析。
结果:肝转移灶中有较高COX-2蛋白表达率,为44.2%(19/43),但低于肠癌灶的79.1%(34/43),差异有统计学意义(P<0.05),实验组肠癌灶的蛋白表达率79.1%(34/43)远高于正常肠粘膜的11.6%(5/43),差异有显著意义,P<0.05,实验组肠癌灶COX-2蛋白表达率与对照组肠癌灶COX-2蛋白表达率65.1%(28/43)比较,无明显差异,P>0.05。将两组病例综合,分析COX-2蛋白表达率与临床病理因素的关系,发现COX-2蛋白过表达与肿瘤分化程度呈负相关,与淋巴结转移和肝转移呈正相关,而与性别、年龄、肿瘤部位、组织类型和浸润深度无明确相关关系。
结论:COX-2蛋白在结直肠癌组织中过表达,尤其以肝转移组结直肠癌组织中的COX-2蛋白表达为高,可能在结直肠癌的发生发展中起到重要作用。
1. COX-2蛋白表达水平与肿瘤的分化程度和淋巴结转移呈正相关。
2. COX-2蛋白表达水平与患者的性别、年龄、肿瘤部位及浸润深度无明确相关性。
3.可以根据COX-2的表达情况判断肿瘤的恶性程度,它在结直肠癌肝转移中的表达为其靶向治疗提供了理论依据,调控COX-2蛋白表达以防止肿瘤的应用前景更加普遍。
BACKGROUND: Colorectal cancer is a common gastrointestinal cancer and the incidence was increasing in China now. Liver is the most common metastatic site of colorectal cancer and the main reason of death from colorectal cancer. Epidemiological investigation showed that the incidence of colorectal cancer in women are lower than that in men(1.9:1). The risk of sufferring colon cancer in postmenopausal women is higher than in premenopausal women. Application of estrogen replacement therapy in postmenopausal women can reduce the risk of colon cancer by 30% ~ 40%. It has been found that sex steroid hormones regulated cell differentiation in intestinal mucosa and mature, and estrogen receptor and progesterone receptor express in normal colorectal tissue and tumor tissue. All of these indicate estrogen and progesterone affect these tumors’occurrence and development. In addition, estrogen (alone or combination with progesterone) replacement therapy in the clinical treatment of colorectal cancer have achieved a certain effect. It can be Speculated that CRC LM may associated with the level of sex hormones.
OBJECTIVE: Study the expression of estrogen receptorα, estrogen receptorβ, androgen receptor, progesterone receptor in colorectal cancer tissues, normal tissues adjacent to cancer and liver metastasis tissues, discuss the roles play in colorectal cancer.
Materials and Methods:Selection criteria: No pre-operative radiotherapy, chemotherapy. No taking hormone drugs within 1 year;Excluding criteria: lesions’size were too small to fit pathological examination and experimental studies. 43 cases of CRC with liver metastases and no metastasis in other organs from March 2000 to December 2008 were collorected as the experiment group, 43 cases of CRC with no metastases were colorected randomly at the same time as the control group, immunohistochemical SP method and the determination SuperPicTure TM Polymer two-step were used in the primary lesion of colorectal cancer, adjacent normal mucosa and estrogen receptor of liver metastasis (ERα, ERβ), progesterone receptor (PR ), androgen receptor (AR) expression. Statistical methods: The data were analyzed use a two-sample comparison, the fourfold table Fisher exact test,χ2 diverse segmentation method was used to calculate each two rates of varied rates, and t test comparing was used for two relatively small samples, the standard of admission testα= 0.05, by SPSS13.0 for statistical work has been completed windows package. The dates were analyzed using statistical software SPSS version13.0.
RESULTS:No expression of ERαprotein were detected in colorectal lesions, normal mucosa and liver lesions. ERβprotein expression in liver lesions were 13.2% (5 / 43), less than in colorectal lesions 36.0% (31 / 86), the difference was statistically significant (P <0.05), and the rate of ERβprotein expression in normal mucosa was 60.5% (26/43, liver metastasis group), the difference was statistically significant (P <0.05). ERβprotein expression in colorectal cancer lesions between experimental and control group were 34.9%(15/43), 39.5%(17/43), the difference was not significant (P> 0.05), and in normal lesion were 60.5%(16/43), 62.8 %(27/43), the difference was not significant (P> 0.05). However, it was significant differencer between colorectal cancer and normal mucosa (P <0.05). PR protein expression in liver lesions were 4.7% (2 / 43), less than in colorectal lesions 40.7% (35/86), the difference was statistically significant (P <0.05), and the rate of PR protein expression in normal mucosa was 55.8% (24/43, liver metastasis group), the difference was statistically significant (P<0.05). PR protein expression in colorectal cancer lesions between experimental and control group were 39.5% (17/43), 41.9% (18/43), the difference was not significant (P> 0.05), and in normal lesion both group were 55.8% (24/43), there was no difference. However, it was significant differencer between colorectal cancer and normal mucosa (P <0.05). AR protein expression in liver lesions were 7.0% (3/43), less than in colorectal lesions 27.9% (24/86), the difference was statistically significant (P <0.05), and the rate of AR protein expression in normal mucosa was 23.3% (10/43, liver metastasis group), the difference was not significant (P> 0.05). AR protein expression in colorectal cancer lesions between experimental and control group were 23.3% (10/43), 32.6% (14/43), the difference was not significant (P> 0.05), and in normal lesion were 23.3% (10/43), 37.2 % (16/43), the difference was not significant (P> 0.05). H0were, there was no significant difference between colorectal cancer and nomarl mucosa. In experiment group, ERβmRNA expression in colorectal cancer lesions were 33.3% (10/30), less than in normal mucosa 60%(18/30), the difference was statistically significant (P <0.05). In control group, ERβmRNA expression in colorectal cancer lesions were 43.3%(13/30), less than in normal mucosa 73.3%(22/30), the difference was statistically significant (P <0.05). However, for ERβmRNA expression in colorectal cancer lesions or in normal mucosa, there were no difference between experiment group and control group (P>0.05).
CONCLUSION:ERβprotein is the mainly ER in CRC liver metastasis. ERβprotein expressions were not found in CRC liver metastases and primary lesions. In experimental group, ERβprotein and PR protein expression rates was ascending in liver lesions, cancer lesions and normal mucosa orderly. Which indicated that ERβprotein is more invasive, ERβis a protective factor for colorectal liver metastases. PR synergized with ERβand plays a protective role in liver metastasis. AR had low expression in colorectal cancer.
Background: Colorectal cancer is a common digestive tract cancer, the incidence of malignant tumors in men ranked fourth and women ranked the third in recent years, with the living conditions and dietary habits change, the incidence of colorectal cancer showed an upward trend year after year, and 75% of the cases occurred in the general population. Although the study with the depth and the improvement of medical technology, the early diagnosis of colorectal cancer and post-operative survival rate has increased, but has yet to achieve a breakthrough, the overall sentiment satisfactory situation. Metastasis and recurrence is the main reason for the impact of CRC prognosis, liver is the most common metastatic sites from CRC, more than 20%~40% of patients with synchronous liver metastases, and 20%~25% of patients with metachronous liver metastases . To improve the early diagnosis of CRC and the cure rate is currently a major problem, select an effective drug prevention and to explore its role in the mechanism has become a very urgent task.
Objective: To investigate the VEGF and EGFR in liver metastases from colorectal cancer and its relationship with clinicopathological characteristics.
Materials and Methods: According to the first part of the selection and exclusion criteria, 43 cases of randomly selected patients with liver metastases of colorectal cancer as the experimental group, 43 cases of colorectal cancer with no metastases as a control group, immunohistochemical detection of VEGF and EGFR protein expression were presented in primary cancer lesions and the corresponding adjacent normal mucosa and liver organization, statistical analysis of VEGF and EGFR in the two groups its relationship with tumor clinicopathological characteristics were performed. Statistical methods: The data were analyzed use a two-sample comparison, Fisher’s exact test,χ2 diverse segmentation method was used to calculate each two rates of varied rates,χ2 test was used for the comparison of the positive rate of different groups,correlation analysis Spearman correlated test , statistical significance was accepted at P<0.05, SPSS13.0 for statistical work has been completed windows package. The dates were analyzed using statistical software SPSS version13.0.
Results: (1) VEGF protein in colorectal cancer lesions in the experimental group were 76.7 % (33/43), higher than the liver lesions and normal mucosa which were 58.1% (25/43) of 9.3% (4/43) ( P <0.05); VEGF protein expression in experimental group were higher than in control group at lesions of colorectal cancer (P <0.05); however, there were no significan difference at the normal mucosa between experimental group and control group (P> 0.05); (2) EGFR protein in colorectal cancer lesions in the experimental group were 79.1 %(34/43), higher than the liver lesions and normal mucosa which were 48.8% (21/43) of 11.6% (5/43) ( P <0.05); EGFR protein expression in experimental group were higher than in control group(58.1%, 25/43) at lesions of colorectal cancer(P <0.05); however, there were no significan difference at the normal mucosa between experimental group and control group(P> 0.05) ; (3) The relationship between VEGF and EGFR protein expression and clinicopathological characteristics found that VEGF and EGFR protein expression with gender, age, tumor site, histological type, depth of invasion associated with tumor differentiation was negatively correlated with liver metastasis and lymph node metastasis was positively correlated, and both are related to each other.
Conclusions: (1) VEGF and abnormal expression of EGFR is the occurrence of liver metastasis of colorectal cancer in an important part. (2) VEGF and EGFR in colorectal cancer can be used as biological indicators, and can help to predict the occurrence of liver metastasis of CRC or CRC liver metastases to determine the prognosis for the future treatment of a new idea.
Objective: to detect the affect of COX-2 in liver metastasis from colorectal cancer.
Materials and Methods:43 cases with liver metastasis from colorectal cancer were selected as experimental group, and no-metastases cases of colorectal cancer were randomly selected as control group. Immunohistochemistry were used to discover the COX-2 protein expression in liver lesions, primary cancer and adjacent normal mucosa. Statistical methods: The data were analyzed use a two-sample comparison, Fisher’s exact test,χ2 diverse segmentation method was used to calculate each two rates of varied rates,χ2 test was used for the comparison of the positive rate of different groups,correlation analysis Spearman correlated test , statistical significance was accepted at P<0.05, SPSS13.0 for statistical work has been completed windows package. The dates were analyzed using statistical software SPSS version13.0.
Results: The liver lesions in the experimental group was in a higher COX-2 protein expression rate (19/43,44.2%), but lower than colorectal cancer lesions (79.1%, 34/43,), the difference was statistically significant (P <0.05), and expression of COX-2 protein at colorectal cancer site were higher than at normal mucosa (11.6%, 5/43), the difference was significant( P <0.05). there were no significant difference between experimental group and control group at colorectal cancer site(65.1%, 28/43,control group ) (P> 0.05). Two cases will be a comprehensive analysis of COX-2 protein expression rate and the relationship between clinicopathological factors and found that COX-2 protein expression and tumor differentiation was negatively correlated with lymph node metastasis and liver metastasis was positively correlated with gender, age, tumor site, histological type and depth of invasion is no clear correlation.
Conclusion: 1.COX-2 protein in colorectal cancer over-expressed, in particular colorectal cancer liver metastases group of COX-2 protein expression was higher in colorectal cancer may be the occurrence and development play an important role.
2. COX-2 protein expression level and the degree of tumor differentiation and lymph node metastasis was positively correlated.
3. COX-2 protein expression level and patient gender, age, tumor location and depth of invasion is no clear correlation.
4. COX-2 expression can be the basis to determine liver metastasis from colorectal cancer and provides a theoretical basis for regulation and control COX-2 protein expression to prevent tumor metastases.
目的:研究雌激素受体α、雌激素受体β、雄激素受体、孕激素受体在肠癌灶、正常肠粘膜及肝转移灶中的表达,探讨其在结直肠癌肝转移中的作用。
材料和方法:病例入选标准:术前未经过放疗、化疗,术前一年之内无服用性激素药物史;剔除标准:切除的肝转移灶小,不能同时满足病理检查和实验研究需要量,收集2000年3月至2008年12月间CRC伴肝转移、并且除肝脏外无其他器官转移的病例,共43例,设为实验组,同时随机选取同期住院接受手术治疗的单纯性CRC病例43例,设为对照组,应用免疫组化SP法和SuperPicTureTM Polymer二步法测定———肠癌灶、正常肠粘膜及肝转移灶中雌激素受体(ERα、ERβ)、孕激素受体(PR)、雄激素受体(AR)的表达。另外收集2005年6月至2008年12月间住院手术治疗的结直肠癌肝转移病例和单纯性结直肠癌病例各30例,应用RT-PCR检测结直肠癌肿瘤组织和正常粘膜组织中ERβmRNA的表达情况。统计学方法:所得资料采用两样本率比较、Fisher确切概率法、χ2分割法计算多样本率的两两比较以及两小样本均数比较t检验处理,检验水准取α=0.05,由SPSS13.0 for windows软件包完成统计工作。
结果:肠癌灶、正常肠粘膜及肝转移病灶均未检测到ERα蛋白表达。肝转移灶表达ERβ蛋白,其表达率13.2%(5/43),低于肠癌病灶ERβ蛋白表达率36.0%(31/86),差异有统计学意义(P<0.05),与肝转移组正常肠粘膜ERβ蛋白表达率60.5%(26/43)比较,差异有统计学意义(P<0.05)。实验组和对照组肠癌灶ERβ蛋白表达率分别为34.9% ,37.2% ,二者差异无统计学意义,P>0.05,两组正常肠粘膜ERβ蛋白表达率分别为60.5% ,62.8% ,二者差异无统计学意义,P>0.05。实验组和对照组肠癌灶ERβ蛋白表达率均明显低于正常肠粘膜,P<0.05。肝转移灶PR蛋白表达率4.7%(2/43),低于肠癌病灶PR蛋白表达率40.7%(35/86),差异有统计学意义(P<0.05),与肝转移组正常肠粘膜PR蛋白表达率55.8%(19/43)比较,差异有统计学意义(P<0.05)。实验组和对照组肠癌灶PR蛋白表达率分别为39.5%(17/43),41.9%(18/43),二者差异无统计学意义,P>0.05,两组正常肠粘膜PR蛋白表达率均为55.8%(14/43),无差异。实验组和对照组肠癌灶PR蛋白表达率均明显低于正常肠粘膜,P<0.05。肝转移灶中AR蛋白表达率7.0%低于肠癌病灶AR蛋白表达率27.9%(24/86),差异有统计学意义(P<0.05),与同组正常肠粘膜AR蛋白表达率23.3%比较,差异无统计学意义(P>0.05)。实验组和对照组肠癌灶AR蛋白表达率分别为23.3%(10/30),32.6%(14/30),二者差异无统计学意义,P>0.05,两组正常肠粘膜AR蛋白表达率分别为23.3%(10/30)和37.2%(16/30),差异无统计学意义。实验组和对照组肠癌灶和正常肠粘膜AR蛋白表达率差异无统计学意义。ERβmRNA在实验组肠癌组织中的表达率为33.3%(10/30),低于其该组正常肠粘膜中的表达率60%(18/30),差异有统计学意义,P<0.05,ERβmRNA在对照组肠癌组织中的表达率为43.3%(13/30),低于其该组正常肠粘膜中的表达率73.3%(22/30),差异有统计学意义,P<0.05,ERβmRNA在实验组和对照组肠癌灶或正常肠粘膜间表达差异无统计学意义,P>0.05。
结论:ERβ蛋白是CRC肝转移灶中的优势ER,CRC肝转移灶和肠癌癌灶均未发现ERα蛋白表达。实验组中,肝转移灶、肠癌灶和正常肠粘膜的ERβ蛋白和PR蛋白表达率呈依次升高的趋势,ERβmRNA在结直肠癌与相应正常肠粘膜中的的表达也有类似趋势。随着肿瘤进展,ERβmRNA表达降低,由此所致ERβ蛋白逐渐减少,推测ERβ对于结直肠癌肝转移是保护因子。PR可能协同作用于ERβ并对结直肠癌肝转移起保护性作用。AR在结直肠癌中有低表达,其在结直肠癌肝转移中的作用尚不明确。
背景:结直肠癌是常见消化道恶性肿瘤,发病率在男性恶性肿瘤中排第四位,女性排第三位,近年来,随着我国生活条件和饮食习惯的改变,结直肠癌发病率呈逐年上升趋势,且75%的病例发生于普通人群。虽然随着研究的深入和诊疗技术的提高,结直肠癌的早期诊断率和术后生存率有所提高,但仍未取得突破性进展,总体状况仍难令人满意。转移和复发是影响CRC预后的主要原因,肝脏是CRC最常见的转移部位,初诊时已有20%～40%的病人发生肝转移,此后20%～25%的患者发生异时性肝转移。提高CRC早期诊断率和治愈率是目前面对的一大难题,选择有效的预防药物及初步探讨其作用机制成为当前一项十分迫切的任务。
目的:探讨VEGF和EGFR在结直肠癌肝转移中的作用及其与临床病理特征之间的关系。
方法:按第一部分选择和剔除标准,随机选择43例结直肠癌肝转移患者作为实验组,43例结直肠癌无他处转移的患者作为对照组,取手术切除原发肠癌病灶和相应癌旁正常肠粘膜组织及肝转移组织,应用免疫组织化学检测VEGF和EGFR蛋白的表达情况,统计分析VEGF和EGFR在两组病例中肝转移病灶、肠癌病灶及正常肠粘膜中的表达差异,及其与肿瘤临床病理特征的关系。统计学方法:所得资料采用两样本率比较、Fisher确切概率法、χ2分割法计算多样本率的两两比较,不同组间阳性率差异比较用χ2检验,相关分析采用Spearman等级相关分析,检验标准P<0.05有统计学意义,用SPSS13.0 for windows软件包完成统计学分析。
结果:(1)VEGF蛋白在实验组中肠癌病灶的阳性表达率为76.7%(33/43),高于该组的肝转移病灶的58.1%(25/43)和正常肠粘膜的9.3%(4/43),差异有统计学意义,P<0.05;实验组肠癌病灶VEGF蛋白的阳性表达率高于对照组的53.5%(23/43),差异有统计学意义,P<0.05;实验组和对照组正常肠粘膜VEGF蛋白率都比较低,分别为9.3%和0,差异无统计学意义,P>0.05;(2)EGFR蛋白在实验组中肠癌病灶的阳性表达率为79.1%(34/43),高于该组的肝转移病灶的48.8%(21/43)和正常肠粘膜的11.6%(5/43),差异有统计学意义,P<0.05;实验组肠癌病灶EGFR蛋白的阳性表达率高于对照组的58.1%(25/43),差异有统计学意义,P<0.05;实验组和对照组正常肠粘膜EGFR蛋白率都比较低,分别为11.6%(5/43)和0,差异无统计学意义,P>0.05;(3)将两组病例综合,分析VEGF和EGFR蛋白表达率与结直肠癌临床病理特征的关系,发现VEGF和EGFR蛋白表达与性别、年龄、肿瘤部位、组织类型、浸润深度无相关性,与肿瘤分化程度呈负相关,与肝转移和淋巴结转移呈正相关,且两者有相关性。
结论:(1)VEGF和EGFR异常表达是结直肠癌发生肝转移中的一个重要环节。(2)VEGF和EGFR可作为结直肠癌有无转移的生物学指标,有助于预测CRC肝转移的发生和判断CRC肝转移的预后。
目的:应用免疫组织化学技术检测COX-在结直肠癌发生肝转移病例中的表达情况,探讨COX-2对结直肠癌肝转移的影响。
方法:按照论文第一部分的入选标准和剔除标准,收集43例结直肠癌肝转移病例作为实验组,同时随机选取单纯性结直肠癌病例作为对照组。免疫组化SuperPic Ture TMPolymer二步法检测——肝转移灶、肠癌灶和正常肠粘膜内COX-2蛋白的表达情况。统计学方法:所得资料采用两样本率比较、Fisher确切概率法、χ2分割法计算多样本率的两两比较,不同组间阳性率差异比较用χ2检验,相关分析采用Spearman等级相关分析,检验标准P<0.05有统计学意义,用SPSS13.0 for windows软件包完成统计学分析。
结果:肝转移灶中有较高COX-2蛋白表达率,为44.2%(19/43),但低于肠癌灶的79.1%(34/43),差异有统计学意义(P<0.05),实验组肠癌灶的蛋白表达率79.1%(34/43)远高于正常肠粘膜的11.6%(5/43),差异有显著意义,P<0.05,实验组肠癌灶COX-2蛋白表达率与对照组肠癌灶COX-2蛋白表达率65.1%(28/43)比较,无明显差异,P>0.05。将两组病例综合,分析COX-2蛋白表达率与临床病理因素的关系,发现COX-2蛋白过表达与肿瘤分化程度呈负相关,与淋巴结转移和肝转移呈正相关,而与性别、年龄、肿瘤部位、组织类型和浸润深度无明确相关关系。
结论:COX-2蛋白在结直肠癌组织中过表达,尤其以肝转移组结直肠癌组织中的COX-2蛋白表达为高,可能在结直肠癌的发生发展中起到重要作用。
1. COX-2蛋白表达水平与肿瘤的分化程度和淋巴结转移呈正相关。
2. COX-2蛋白表达水平与患者的性别、年龄、肿瘤部位及浸润深度无明确相关性。
3.可以根据COX-2的表达情况判断肿瘤的恶性程度,它在结直肠癌肝转移中的表达为其靶向治疗提供了理论依据,调控COX-2蛋白表达以防止肿瘤的应用前景更加普遍。
BACKGROUND: Colorectal cancer is a common gastrointestinal cancer and the incidence was increasing in China now. Liver is the most common metastatic site of colorectal cancer and the main reason of death from colorectal cancer. Epidemiological investigation showed that the incidence of colorectal cancer in women are lower than that in men(1.9:1). The risk of sufferring colon cancer in postmenopausal women is higher than in premenopausal women. Application of estrogen replacement therapy in postmenopausal women can reduce the risk of colon cancer by 30% ~ 40%. It has been found that sex steroid hormones regulated cell differentiation in intestinal mucosa and mature, and estrogen receptor and progesterone receptor express in normal colorectal tissue and tumor tissue. All of these indicate estrogen and progesterone affect these tumors’occurrence and development. In addition, estrogen (alone or combination with progesterone) replacement therapy in the clinical treatment of colorectal cancer have achieved a certain effect. It can be Speculated that CRC LM may associated with the level of sex hormones.
OBJECTIVE: Study the expression of estrogen receptorα, estrogen receptorβ, androgen receptor, progesterone receptor in colorectal cancer tissues, normal tissues adjacent to cancer and liver metastasis tissues, discuss the roles play in colorectal cancer.
Materials and Methods:Selection criteria: No pre-operative radiotherapy, chemotherapy. No taking hormone drugs within 1 year;Excluding criteria: lesions’size were too small to fit pathological examination and experimental studies. 43 cases of CRC with liver metastases and no metastasis in other organs from March 2000 to December 2008 were collorected as the experiment group, 43 cases of CRC with no metastases were colorected randomly at the same time as the control group, immunohistochemical SP method and the determination SuperPicTure TM Polymer two-step were used in the primary lesion of colorectal cancer, adjacent normal mucosa and estrogen receptor of liver metastasis (ERα, ERβ), progesterone receptor (PR ), androgen receptor (AR) expression. Statistical methods: The data were analyzed use a two-sample comparison, the fourfold table Fisher exact test,χ2 diverse segmentation method was used to calculate each two rates of varied rates, and t test comparing was used for two relatively small samples, the standard of admission testα= 0.05, by SPSS13.0 for statistical work has been completed windows package. The dates were analyzed using statistical software SPSS version13.0.
RESULTS:No expression of ERαprotein were detected in colorectal lesions, normal mucosa and liver lesions. ERβprotein expression in liver lesions were 13.2% (5 / 43), less than in colorectal lesions 36.0% (31 / 86), the difference was statistically significant (P <0.05), and the rate of ERβprotein expression in normal mucosa was 60.5% (26/43, liver metastasis group), the difference was statistically significant (P <0.05). ERβprotein expression in colorectal cancer lesions between experimental and control group were 34.9%(15/43), 39.5%(17/43), the difference was not significant (P> 0.05), and in normal lesion were 60.5%(16/43), 62.8 %(27/43), the difference was not significant (P> 0.05). However, it was significant differencer between colorectal cancer and normal mucosa (P <0.05). PR protein expression in liver lesions were 4.7% (2 / 43), less than in colorectal lesions 40.7% (35/86), the difference was statistically significant (P <0.05), and the rate of PR protein expression in normal mucosa was 55.8% (24/43, liver metastasis group), the difference was statistically significant (P<0.05). PR protein expression in colorectal cancer lesions between experimental and control group were 39.5% (17/43), 41.9% (18/43), the difference was not significant (P> 0.05), and in normal lesion both group were 55.8% (24/43), there was no difference. However, it was significant differencer between colorectal cancer and normal mucosa (P <0.05). AR protein expression in liver lesions were 7.0% (3/43), less than in colorectal lesions 27.9% (24/86), the difference was statistically significant (P <0.05), and the rate of AR protein expression in normal mucosa was 23.3% (10/43, liver metastasis group), the difference was not significant (P> 0.05). AR protein expression in colorectal cancer lesions between experimental and control group were 23.3% (10/43), 32.6% (14/43), the difference was not significant (P> 0.05), and in normal lesion were 23.3% (10/43), 37.2 % (16/43), the difference was not significant (P> 0.05). H0were, there was no significant difference between colorectal cancer and nomarl mucosa. In experiment group, ERβmRNA expression in colorectal cancer lesions were 33.3% (10/30), less than in normal mucosa 60%(18/30), the difference was statistically significant (P <0.05). In control group, ERβmRNA expression in colorectal cancer lesions were 43.3%(13/30), less than in normal mucosa 73.3%(22/30), the difference was statistically significant (P <0.05). However, for ERβmRNA expression in colorectal cancer lesions or in normal mucosa, there were no difference between experiment group and control group (P>0.05).
CONCLUSION:ERβprotein is the mainly ER in CRC liver metastasis. ERβprotein expressions were not found in CRC liver metastases and primary lesions. In experimental group, ERβprotein and PR protein expression rates was ascending in liver lesions, cancer lesions and normal mucosa orderly. Which indicated that ERβprotein is more invasive, ERβis a protective factor for colorectal liver metastases. PR synergized with ERβand plays a protective role in liver metastasis. AR had low expression in colorectal cancer.
Background: Colorectal cancer is a common digestive tract cancer, the incidence of malignant tumors in men ranked fourth and women ranked the third in recent years, with the living conditions and dietary habits change, the incidence of colorectal cancer showed an upward trend year after year, and 75% of the cases occurred in the general population. Although the study with the depth and the improvement of medical technology, the early diagnosis of colorectal cancer and post-operative survival rate has increased, but has yet to achieve a breakthrough, the overall sentiment satisfactory situation. Metastasis and recurrence is the main reason for the impact of CRC prognosis, liver is the most common metastatic sites from CRC, more than 20%~40% of patients with synchronous liver metastases, and 20%~25% of patients with metachronous liver metastases . To improve the early diagnosis of CRC and the cure rate is currently a major problem, select an effective drug prevention and to explore its role in the mechanism has become a very urgent task.
Objective: To investigate the VEGF and EGFR in liver metastases from colorectal cancer and its relationship with clinicopathological characteristics.
Materials and Methods: According to the first part of the selection and exclusion criteria, 43 cases of randomly selected patients with liver metastases of colorectal cancer as the experimental group, 43 cases of colorectal cancer with no metastases as a control group, immunohistochemical detection of VEGF and EGFR protein expression were presented in primary cancer lesions and the corresponding adjacent normal mucosa and liver organization, statistical analysis of VEGF and EGFR in the two groups its relationship with tumor clinicopathological characteristics were performed. Statistical methods: The data were analyzed use a two-sample comparison, Fisher’s exact test,χ2 diverse segmentation method was used to calculate each two rates of varied rates,χ2 test was used for the comparison of the positive rate of different groups,correlation analysis Spearman correlated test , statistical significance was accepted at P<0.05, SPSS13.0 for statistical work has been completed windows package. The dates were analyzed using statistical software SPSS version13.0.
Results: (1) VEGF protein in colorectal cancer lesions in the experimental group were 76.7 % (33/43), higher than the liver lesions and normal mucosa which were 58.1% (25/43) of 9.3% (4/43) ( P <0.05); VEGF protein expression in experimental group were higher than in control group at lesions of colorectal cancer (P <0.05); however, there were no significan difference at the normal mucosa between experimental group and control group (P> 0.05); (2) EGFR protein in colorectal cancer lesions in the experimental group were 79.1 %(34/43), higher than the liver lesions and normal mucosa which were 48.8% (21/43) of 11.6% (5/43) ( P <0.05); EGFR protein expression in experimental group were higher than in control group(58.1%, 25/43) at lesions of colorectal cancer(P <0.05); however, there were no significan difference at the normal mucosa between experimental group and control group(P> 0.05) ; (3) The relationship between VEGF and EGFR protein expression and clinicopathological characteristics found that VEGF and EGFR protein expression with gender, age, tumor site, histological type, depth of invasion associated with tumor differentiation was negatively correlated with liver metastasis and lymph node metastasis was positively correlated, and both are related to each other.
Conclusions: (1) VEGF and abnormal expression of EGFR is the occurrence of liver metastasis of colorectal cancer in an important part. (2) VEGF and EGFR in colorectal cancer can be used as biological indicators, and can help to predict the occurrence of liver metastasis of CRC or CRC liver metastases to determine the prognosis for the future treatment of a new idea.
Objective: to detect the affect of COX-2 in liver metastasis from colorectal cancer.
Materials and Methods:43 cases with liver metastasis from colorectal cancer were selected as experimental group, and no-metastases cases of colorectal cancer were randomly selected as control group. Immunohistochemistry were used to discover the COX-2 protein expression in liver lesions, primary cancer and adjacent normal mucosa. Statistical methods: The data were analyzed use a two-sample comparison, Fisher’s exact test,χ2 diverse segmentation method was used to calculate each two rates of varied rates,χ2 test was used for the comparison of the positive rate of different groups,correlation analysis Spearman correlated test , statistical significance was accepted at P<0.05, SPSS13.0 for statistical work has been completed windows package. The dates were analyzed using statistical software SPSS version13.0.
Results: The liver lesions in the experimental group was in a higher COX-2 protein expression rate (19/43,44.2%), but lower than colorectal cancer lesions (79.1%, 34/43,), the difference was statistically significant (P <0.05), and expression of COX-2 protein at colorectal cancer site were higher than at normal mucosa (11.6%, 5/43), the difference was significant( P <0.05). there were no significant difference between experimental group and control group at colorectal cancer site(65.1%, 28/43,control group ) (P> 0.05). Two cases will be a comprehensive analysis of COX-2 protein expression rate and the relationship between clinicopathological factors and found that COX-2 protein expression and tumor differentiation was negatively correlated with lymph node metastasis and liver metastasis was positively correlated with gender, age, tumor site, histological type and depth of invasion is no clear correlation.
Conclusion: 1.COX-2 protein in colorectal cancer over-expressed, in particular colorectal cancer liver metastases group of COX-2 protein expression was higher in colorectal cancer may be the occurrence and development play an important role.
2. COX-2 protein expression level and the degree of tumor differentiation and lymph node metastasis was positively correlated.
3. COX-2 protein expression level and patient gender, age, tumor location and depth of invasion is no clear correlation.
4. COX-2 expression can be the basis to determine liver metastasis from colorectal cancer and provides a theoretical basis for regulation and control COX-2 protein expression to prevent tumor metastases.
引文
1. Garcia M, Jemal A,Ward EM, et al. Global Cancer Facts & Figures 2007.Atlanta, GA: American Cancer Society, 2007.
2.李连弟,饶克勤,张思维,等.中国12市县1993年-1997年肿瘤发病及死亡登记资料统计分析.中国肿瘤,2002,11:497-507.
3. Liu LX, Zhang WH, Jiang HC. Current treatment for liver metastases from colorectal cancer. World J Gastroenterol, 2003,9(2): 193-200
4.张森,万德森,潘志忠,等.结直肠癌肝转移的多因素分析.中华肿瘤杂志,2002,24(4):307-309.
5.万德森.大肠癌肝转移的治疗.万德森,潘志忠主编.大肠癌.北京:中国医药科技出版社,2004,240-247.
6.张振书,张亚历.中国大肠癌研究进展.世界华人消化杂志,2001,9(5):489-494.
7.周志伟,万德森,王国强,等.结直肠癌雌激素受体及孕激素受体的定量研究.癌症, 2004,23(7): 851-854.
8. Castagnetta L, Traina A, Campisi I, et al. Androgen receptor status in nontumoral and malignant human colorectal tissues. Ann N Y Acad Sci,2002,963: 322-325.
9. Nanda K, Bastian LA, Hasselblad V, Simel DL. Hormone replacement therapy and the risk of colorectal cancer: a meta-analysis. Obstet Gynecol,1999,93(5Pt2): 880-888.
10. Chlebowski RT, Waitawski-wende,Ritenbaugh C, et al. Estrogen plus progestin and colorectal cancer in postmenopausal women. N Engl J Med,2004,350(10): 991-1004.
11. Taylor AH, AI-Azzawi F. Immunolocation of oestrogen receptor beta in human tissue. Journal of Molecular Endocrinology,2000,24: 145-155.
12. Campbell-Thompson Martha, Lynchi. Jeanette, Bhardwa, J Bhavna. Expression of estrogen receptor(ER) subtypes and ERβisoforms in colon cancer. Cancer Res,2001,61: 632-640.
13.刘莹,刘明,胡维诚.大肠癌组织雄激素受体的表达及意义.山东医药,2003,43(12)49-50.
14. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med, 2003,9(6): 669- 676.
15. Kerbel R, Folkman J. Clinical translation of angiogenesis inhibitors. Nat Rev Cancer, 2002,2(10): 727-739.
16. Buckler P,Reber HA,Buckler M,et al. Hypoxia indueible factor1 regulates vascular endothelial growth factor expression in human panere atiecancer pancreas,2003, 26(1): 56-64.
17.任学群,景红,傅侃达.血管内皮生长因子的表达和微血管密度与结直肠癌侵袭转移的关系.中国医师杂志,2004,6(5):582-584.
18. Klapper LN, Kirschbaum MH, Sela M et al. Biochemical and clinical implications of the ErbB/HER signaling net work of growth factor receptors. Adv Cancer Res, 2000,77: 25-79.
19. CasanovaML, Larcher F, Casanova B, et al. A critical role for ras- mediated, epidermal growth fact or receptor-dependent angiogenesis in mouse skin carcinogenesis. Cancer Res, 2002,62(12): 3402-3407.
20. Watson AJ. ChemoPreventive effects of NSAIDs against colorectal caneer: regulation of apoptosis and mitosis by COX-1 and COX-2.Histo Histopat, 1998,13(2): 591-597.
21. Yamauchi T , Watanabe M , Kubota T , et al. Cycloxygenase-2 expression as a new marker for patients with colorectal cancer. Dis Colon Rectum, 2002,45 (1): 98-103.
22. Fujita T, Matsui M, Takaku K, Uetake H, Ichikawa W, Taketo MM, et al. Size and invasion-dependent increase in cycloxygenase 2 levels in human colorectal carcinomas. Cancer Res,1998,58: 4823-4826.
23. Kawasaki H, Altieri DC, Lu CD, Toyoda M, Tenjo T, Tanigawa N. Inhibition of apoptosis by Survivin predicts shorter survival rates in colorectal cancer. Cancer Res, 1998, 58(22) : 507l-5074.
24. Sinicrope FA, Ruan SB, Cleary KR, et a1. Bcl-2 and p53 onco protein expression during colorectal tumorigenesis. Cancer Res, 1995, 55: 237-241.
25. GosPodarowiez MK,Miller D,Groome PA,et al. The Process for Continuous improvement of the TNM classification. Cancer,2004,100(1):1-5.
26. Kin-Mang Lau, Mark LaSpina, John Long, and Shuk-Mei Ho. Expression of Estrogen Receptor (ER)-αand ER-βin Normal and Malignant Prostatic Epithelial Cells: Regulation by Methylation and Involvement in Growth Regulation. Cancer Res, 2000, 6(15): 3175-3182.
27. Menasee LP,White GR,Harrison CJ,et al. Localization of the estrogen receptor locus (ESR) to chromosome 6q25.1 by FISH and a simple post-FISH banding technique Genomies,1993,17:263-265.
28. EnmarkE,Pelto-Huikko M,GrandienK,et al. Human estrogen receptor beta-gene Structure Chromosomal localization,and expression pattern,J Clin Endoerinol. Metab,1997,(82):4258-4265.
29. Dardes RC,Jordan VC. Novel agents to modulate estrogen action. Br Med Bull,2000,56 (3): 773-786.
30. Ali S,Metzger D,Bomert JM,et al. Modulation of transcriptional activation by 1igand-dependent Phosphorylation of the human oestrogen receptor A/B region. EMBO,1993,12 (3): 1153-1160.
31. Katzenellenbogen BS. Estrogen receptors: bioactivities and interaetions with cell signaling pathays. Biology of Reprodution,1996, 54(2): 287-293.
32. Slattery ML,Sweeney C,Murtaugh M,et al.Associations between ER alpha,ER beta,and AR genotypes and colon and rectal cancer. Caneer Epidemiol Biomarkers Prev, 2005,14(12): 2936-2942.
33. Waliszewski P,Blaszezyk M,Wolinska-Witort E,et al. Molecular study of sex steroid receptor gene expression in human colon and in colorectal carcinomas. J Surg Oneol,1997,64(1): 3-11.
34. Campbell-Thompson M,Lyneh IJ,Bhardwaj B. Expression of estrogen receptor (ER) subtypes and ER beta isoforms in colon cancer. Cancer Res,2001,61(2): 632-640.
35. Fiorelli G,Pieariello L,Martineti V,et al. Functional estrogen receptor beta in colon cancer cells. Biochem Biophys Res Commun. 1999,261: 521-527.
36. Arai N, Strom A, RaafterJJ,et al. Estrogen receptor beta mRNA in colon cancer cells: growth effects of estrogen and genistein. Biochem Biophys Res Commun,2000,270: 425-431.
37. Qiu Y,Waters CE,Lewis AE,et al. Oestrogen-induced apoptosis in colonocytes expressing oesteogen receptor beta. J Emdrocrinol,2002, 174: 369-377.
38. Foley EF, Jazaeri AA, Sjupnik MA, et al. Selective loss of estrogen receptor beta in malignant human colon. Camcer Res,2000,60(2):45-248.
39. Witte D,Chirala M,Younes A,et al. Estrogen receptor beta is expressed in human colorectal adenoeareinoma. Hum Pathol, 2001,32 (9): 940-944.
40. Jassam N,Bell SM,Speirs V,et al. Loss of expression of oestrogen receptor beta in colon cancer and its assoeiation with Dukes,staging. Oneol Rep,2005,14 (1): 17-21.
41. Konstantinopoulos PA,Kominea A,Vandoros G,et al. Oestrogen receptor beta (ER beta is abundantly expressed in normal colon mueosa,but declines in colon adenocarcinoma paralleling the tumour’s dedifferentiation. Eur J Cancer,2003,39 (9): 1251-1258.
42. Lagendijk JH, Mullink H, VanDiest PJ, et al. Immunohisochemical differentiation between primary adenocarcinomas of the ovary and ovarian metastases of colonic and breast origin.Comparison between a statistical and an intuitive approach.J Clin Pathol,1999,52: 283-290.
43. Nash J W, Morrisson C, Frankel WL. The utility of estrogen receptor and progesterone receptor immunohistochemistry in the distinction of metastatic breast carcinoma from other tumor in the liver. Arch Pathol Lab Med,2003,127(12): 1591-1595.
44. Paech K, Webb P, Kuiper GG, et al. Differential ligand activation of estrogen receptors ER alpha and ER beta at AP1 sites. Science,1997, 277:1508-1510.
45. Zhang S, Li X, Burghardt R, Smith R, et al. Role of estrogen receptor (ER) alpha in insulin-like growth factor (IGF)-I-induced responses in MCF-7 breast cancer cells. J Mol Endocrinol,2005,35(3): 433-47.
46. Newton ACS Wong, Roger DG Malcomson, Duncan Jodrell, et al.ERβisoform expression in colorectal carcinoma: an in vivo and vitro study of clinicopathological and molecular correlates. J Pathol,2005,207: 53-60.
47. Milgrom E, Atger M, Baulieu EE. Progesterone in uterus and plasma IV progesterone receptor(s) in guinea piguterus cytosol. Steroids, 1970, 16 (6): 741-754.
48.方力,薛晓东,段笃文,等.雌孕激素受体在直肠癌中存在意义的讨.黑龙江医药科学, 2001,24(3): 67-68.
49. Lindhe B, Porsch Hallstrom I, Gustafaaon et al. Effect of neonatal and adult castration and of testosterone substitution in male rata on growth enzyme-alterer hepatic foci in the resistant hepatogyte model. Cancer Res,1990,50: 2679-2682.
50. Seiji Marayama, Nafumi Nagame. Preventive effect of FK143, a 5α-reductase inhibitor n chemical hepatocarcinogenesis in rats. Clinical Cancer Res. 2001, 7: 2096-104
51.葛旭鹏,王有德,王忠毅.性激素受体在大肠癌及其癌前病变组织中的表达.中华试验外科杂志,1998,15(4):302-303
52.张志超,韩刚,孙亚欣,等.血清VEGF水平与结直肠癌肝转移相关性的临床研究.中国老年学杂志,2006,l0(26):1340-1341.
53.唐宗江,甘嘉亮,高枫.血管内皮生长因子-A、C在大肠癌及淋巴结转移中的表达及其意义.中华试验外科杂志,2005,22(3):319-320.
54.江忠清,朱凤川,曲军英.肿瘤血管生成及其与宫颈癌的关系.中国误诊学杂志, 2003,3 (11) : 1648.
55.潘贻飞,李权,卢山珊,等.直肠癌中HER-2、VEGF与CXCR4的表达及相关性.肿瘤学杂志,2008,14(4):270-273.
56.张晓雨,周建农,张彤. Survivin、VEGF及Ki67在结直肠癌中的表达及其临床意义.肿瘤防治研究,2007,34(1):35-38.
57. Weich HA, Bando H, Brokelmann M, et al. Quantification of vascular endothelial growth factor-C (VEGF-C) by a novel ELISA. J Immunol Methods, 2004,285:145-155.
58. Uner A, Ebinc FA, Akyrek N, et al. Vascular endorhelia growth factor, c-erB-2 and c-erB-2 expression in colorectal adenoma and adenocarcinoma. Exp Oncol,2005,27(3): 225-8.
59. Italiano A, Saint Paul MC, Caroli-Bosc FX, et al. Epidermal growth factor receptor (EGFR) status in primary colorectal tumors correlates with EGFR expression in related metastatic sites: biological and clinical imp lications. Ann Oncol, 2005, 16 (9): 1503-1507.
60. Spano JP, Lagorce C, Atlan D, et al. Impact of EGFR expressionon colorectal cancer patient prognosis and survival. Ann Oncol, 2005,16 (1): 102-108.
61. Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl JMed, 2004,351 (4): 337-345.
62. Saif MW, Cohenuram M. Role of panitumumab in the management of metastatic colorectal cancer. Clin Colorectal Cancer, 2006,6 (2): 118-124.
63. Saltz LB, Meropol NJ, Loehrer PJ Sr, et al. PhaseⅡtrial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol, 2004,22 (7): 1201-1208.
64. Yarden Y. Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol,2001,2: 127-137.
65. Moniola AO,Neve RM,Lane HA,et al. The erbB signalingnetwork: receptor heterdimerization in development and cancer. EMBOJ,2000, 19(13): 3159-3167.
66. Mendels J, Baselga J. Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J Clin Oncol, 2003, 21(14): 2787-2799.
67. Mayer A, Takimoto M, Fritz E, et al. The prognostic significance of proliferating cell nuclear antigen, epidermal growth factor receptor, and mdr gene expression in coloreetal cancer. Cancer , 1993, 71(8): 2454-2460.
68. McKay JA, Murray LJ, Curran S, et al. Evaluation of the epidermal growth factor receptor (EGFR) in colorectal tumours and lymph node metastases. Eur J Cancer, 2002, 38(17): 2258-2264.
69. Gramont A. Adjuvant therapy of stageⅡandⅢcolon cancer. Semin Oncol, 2005, 32(6Suppl8): 11-14.
70. Klapper LN, Kirschbaum MH, Sela M, et al. Biochemical and clinical implications of the ErbB/HER signaling net work of growth factor receptors. Adv Cancer Res, 2000,77: 25-79.
71. Casanova ML, Larcher F, Casanova B, et al. A critical role for ras- mediated, epidermal growth factor receptor-dependent angiogenesis in mouse skin carcinogenesis. Cancer Res, 2002,62(12): 3402-3407.
72. Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev, 1997,18 (1): 4-25.
73. Folprecht G, Lutz MP, Schoffski P, et al. Cetuximab andirinotecan/5 -fluorouracil/folinic acid is a safe combination for the first-line treatment of patients with epidermal growth factor receptor expression metastatic colorectal carcinoma. Ann Oncol, 2006,17 (3):450-456.
74. Ohji Y, Yao T, Eguchi T, et al . Evaluation of risk of liver metastasis in colorectal adenocarcinoma based on the combination of risk factors including CD10 expression: multivariate analysis of clinicopathological and immunohistochemical factors. Oncol Rep, 2007,17 (3):525-530.
75. Rao M, Yang W, Seifalian AM, et al. Role of cycloxygenase-2 in the angiogenesis of colorectal cancer. Int J Colorectal Dis, 2004,19 (1): 1-11.
76. Sheng H, Shao J, O’Mahony CA, et al. Transformation of intestinal epithelial cells by chronic TGF21 treatment results in Down regulation of the type II TGF-receptor and induction of cyclooxygenase-2. Oncogene, 1999,18(4): 855-867.
77. Hamada J,Cavanaugh PG, Lotan O. Separable growth and migration factors for large-cell lymphoma factors secreted by microvascular endothelial cells derived from target organs for metastasis. Br J Cancer,1992,66(2): 349-354.
78. Lin DT,Subbaramaiah K,Shah JP,et al. Cyelooxygenase-2: a novel molecular target for the prevention and treatment of head and neck cancer. Head Neck,2002,24(8): 792-799.
79.罗伟仁,陈小毅.环氧化酶-2与肿瘤的关系.肿瘤防治研究, 2006,33 (1) : 62-64.
80.汪洋,林从尧,周夏.大肠癌中β-catenin表达及与COX-2、VEGF表达的关系.肿瘤防治研究, 2006,33(1): 20-22.
81. Wong D, Cazabon S, Ali H, et al. Can the use of conventional silicone oil and heavy oil be a strategy for the management of proliferative vit reoretinopathy? Ann Acad Med Singapore, 2006,35(3): 181-184.
82. Hillier R J, Cazabon S J, Wong D. The emerging role of heavysilicone oil as a tamponade agent. Eyenews, 2007,(1): 14-17.
83. Sirimaharaj M, Balachandran C, Chan WC, et al.Vitrectomy with short term postoperative tamponade using perfluorocarbon liquid for giant retinal tears. BrJ Opht halmol, 2005, 89(9): 1176-1179.
84. Rofail M, Lee LR. Perfluoro-n-octane as a postoperative vitreoretina tamponade in the management of giant retinal tears. Retina, 2005, 25(7): 897-901.
85. Wetterqvist C, Wong D, Williams R, et al. Tamponade.efficiency of Perfluoro.hexyloctane and Silicone Oil Solutionsin a Model Eye Chamber. Br J Opht halmol, 2004, 88(5): 692-696.
86. Tognetto D, Minutola D, Sanguinetti G, et al. Anatomical and functional outcomes after heavy silicone oil tamponade in viteoretinal surgery for complicated retinal detachment. Ophthalmology, 2005, 112(9): 1574-1582.
87. Sasson AR, Sigurdson ER. Surgical treatment of liver metastases. Semin Oncol, 2002, 29 (2): 107-118.
88. Tatsuguchi A, Matsui K, Shinji Y, et al. Cyclooxygenase-2 expression correlates with angiogenesis and apoptosis in gastric cancer tissue. Hum Pathol, 2004, 35 (4): 488-495.
89. Yamauchi T, Watanabe M, Kubota T, et al. Cyclooxygenase-2 expression as a new marker for patients with colorectal cancer. Dis Colon Rectum, 2002, 45 (1): 98-103.
90. Sheehan KM, Sheahan K, O’donoghue DP, et al. The relationship between cycloxygenase-2 expression and colorectal cancer. JAMA, 1999, 282 (13): 1254 - 1257.
91.童强,王国斌,卢晓明,等.胃癌组织中核因子2κB , ICAM 21和COX -2的表达及其临床意义.中国普通外科杂志, 2005, 14(10): 736-739.
92.汪斐,莫烨,周世权,等. COX-2和HER-2在结直肠癌中的表达及其意义.中国普通外科杂志, 2007, 7(167):693-695
93. Signh-Ranger G, Kirkpatrick KL, Clark GM, et al. Cyclooxygenase-2(COX-2) mRNA expression corelates with progesterone receptorpositivity in human breast cancer. Curr Med Res Opin, 2003, 19(2): 131-134.
94. Kundu N, Fulton AM. Selective cyclooxygenase(COX-1) or COX-2 inhibitors control metastatic disease in a murine model of breast cancer1. Cancer Res, 2002, 62(8): 2343-2346.
95. Nakamoto N, Higuchi H, Kanamori H, et al. Cyclooxygenase-2 inhibitor and interferon-βsynergistically induce apoptosis in human hepatoma cells in vitro and in vivo. Int J Oncol, 2006, 29(3): 625-35.
96. Wiese FW, Thompson PA, Kadlubar FF. Carcinogen substrate specificity of human COX-1 and COX-2. Carcinogenesis, 2001, 21(1):5-10.
1. Ahmedin Jemal, DVM, PhD; Rebecca Siegel, MPH; Elizabeth Ward, PhD;et al. Cancer Statistics, 2008. CA Cancer J Clin, 2008,58:71–96
2.李连弟,饶克勤,张思维,等.中国12市县1993年-1997年肿瘤发病和死亡登记资料统计分析.中国肿瘤,2002, 11: 497-507.
3. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2006. CA Cancer J Clin,2006,56:106–130.
4. Liu LX, Zhang WH, Jiang HC. Current treatment for liver metastases from colorectal cancer. World J Gastroenterol , 2003,9(2) :193-200
5. Elias D, Sideris L, Pocard M , et al. Results of RO resection for colorectal liver metastases associated with extrahepatic disease. Ann Surg Oncol, 2004, 11 (3): 274-280.
6. Curley SA. Outcomes after surgical treatment of colorectal cancer liver metastases. Semin Oncol, 2005, 32 (6 Suppl 9): 109-111.
7.万德森.大肠癌肝转移的治疗.万德森,潘志忠,主编.大肠癌.北京:中国医药科技出版社,2004,240-247.
8.张振书,张亚历。中国大肠癌研究进展.世界华人消化杂志,2001,9(5):489-494.
9 Zhu JW, Yu BM, Ji YB, Zheng MH, Li DH. Upregulation of vascular endothelial growth factor by hydrogen peroxide in human colon cancer. World J Gastroenterol,2002,8(1): 153-157.
10 Shen LZ, Wu WX, Xu DH, Zheng ZC, Liu XY, Ding Q, Hua YB, Yao K. Specific CEA-producing colorectal carcinoma cell killing with recombinant adenoviral vector containing cytosine deaminase gene. World J Gastroenterol,2002,8(2): 270-275.
11. Xiang DB, Wu XH, Li ZP, et al. Expression of -catenin, cyclin D1and c-myc in colorectal carcinoma. Shijie Huaren Xiaohua Zazhi, 2002,10: 305-308.
12. Yu LL, Yu JP, Ran ZX, et al. Relationship between nuclear factor-kappa B, apoptosis and proliferation in colorectal neoplasia. Shijie Huaren Xiaohua Zazhi,2002,10(3): 309-312.
13. Fang XM, Yu JP, Luo HS. Relationship between hTERT and P16 gene expe ssions and telomerase activity in colorectal cancer. Shijie Huaren Xiaohua Zazhi, 2002, 10(1): 12-14.
14. He FT, Nie YZ, Chen BJ, et al. Expression and identification of recombinant soluble single-chain variable fragment of monoclonal antibody MC3. World J Gastroenterol, 2002, 8(2): 258-262.
15. Wu BP, Zhang YL, Zhou DY, et al. Microsatellite instability, MMR gene expression and proliferation kinetics in colorectal cancer with famillial predisposition. World J Gastroenterol, 2000, 6(6): 902-905.
16. Zhou XD, Yu JP, Ran ZX, et al. Expression of cFLIP short/long and p53 mutation in colon adenocarcinoma. Shijie Huaren Xiaohua Zazhi, 2002, 10(5): 536-539.
17. Li XG, Song JD, Wang YQ. Differential expression of a novel colorectal ancer differentiation related gene in colorectal cancer. World J Gastroenterol, 2001, 7(4): 551-554.
18. Luo MJ, Lai MD. Identification of differentially expressed genes in normal mucosa, adenoma and adenocarcinoma of colon by SSH. World J Gastroenterol, 2001, 7(5): 726-731.
19. Zhang J, Lai MD, Chen J. Methylation status of p16 gene in colorectal carcinoma and normal colonic mucosa. World J Gastroenterol, 1999, 5(5): 451-454.
20. Singh S, Langman MJ. Oestrogen and colonic epithelial cell growth. Gut, 1995, 37(6):737-739.
21. Di Leo A,Messa C,Cavallini A,Linsalata M. Estrogens and colorectal cancer. Curr Drug Targets Immune Endocr Metabol Disord 2001, 1(1):1-12.
22. al-Azzawi F,Wahab M. Estrogen and colon cancer:current issues. CIimacteric,2002, 5(1):3-14.
23. Grodstein F,Newcomb PA,Stampfer MJ. Postmenopausal hormone therapy and the risk of colorectal cancer: A review and meta-analysis. Am J Med, 1999,106(5):574-582.
24. Moghissi KS. Hormone replacement therapy for menopausal women. Compr Ther, 2000, 26(29):197-202.
25. M. Gambacciani, P. Monteleone,A. Sacco,etal. Hormone replacement therapy and endometrial,ovarian and colorectal cancer. Best Pract & Res Clin Endocrinol Metab, 2003, 17(1): 139-147.
26. Burkman RT. Reproductive hormones and cancer:ovarian and Colon cancer. Obstet Gynecol Clin North Am, 2002, 29(3):527-540.
27. Giovannucci E. Obesity, gender,and colon cancer. Gut,2002, 51(2):147.
28. Adlercreutz H . Phyto-oestrogens and cancer.Lancet oncol,2002, 3(6): 364-373.
29. Elizabeth Barrett-Connor,Cynthia A Stuenkel.Hormone replacement therapy (HRT)- risks and benefits.Int J Epidemiof,2001, 30:423-426.
30. Franceschi S, Gallus S, Talamini R, et al. Menopause and Colorectal cancer. Br J Cancer,2000, 82(11): 1860-1862.
31. Nanda K, Bastin LA, Hasselblad V, et al. Hormone replacementtherapy and the risk of colorectal: a meta-analysis. Obstet Gynecol, 1999, 93 (5Pt2): 880-888.
32. Harrison JD, Watson S, Morris DL, et al. The effect of sex hormone and tamoxifen on the growth of human gastric and colorectal cancer cell lines. Cancer, 1989, 63 (11): 2148-2151.
33. Ziv Y, Gupta MK, Milson JW, et al. The effect of tamoxifen and fenretinide on hunman colorectal cancer cell lines in vitro. Anticancer Res. 1994, 14 (5A): 2005-2009.
34. Rita C Dardes, V Craig Jordan. Novel agents to modulate oestrogen action. Br Med Bull, 2000,56(3):773-786.
35. Mark A English, Kate F Kane, Nell Cruickshank, et al. Loss of estrogen inactivation in colonic cancer. J Clin Endocrinol Metab .1999, 84 (6): 2080-2085.
36. Martha L. Slattery, Wade S. Samowitz, Joseph A. Holder. Estrogen and progesterone receptors in colon tumors. Am J Clin Pathol, 2000, 113 (3): 364-368.
37. Dawson P M, Shousha S, Blair S D, et al. Oestrogen receptors in colorecta carcinoma. J Clin Pathol,1990, 43: 149-51.
38.Sietse Mosselman, Jan Polman, Rein Dijkema. ERβ: Identification and characterization of a novel human estrogen receptor. FEBS Letters, 1996, 392 (1): 49-53.
39. Eugene F. Foley, Amir A. Jazaeri, Margaret A. Shuprik, et al. Selective Loss of Estrogen Receptorβin Malignant Human Colon. Cancer Res, 2000, 60: 245-248.
40. Martha Campbell-Thompson, L. Jeanette Lynch, Bhavna Bhardwaj. Expression of Estrogen Receptor (ER) Subtypes and ERβIsoforms inColon Cancer. Cancer Res, 2001, 61: 632-640.
41. Li-Qun Xie, Jie-Ping Yu, He-Sheng Luo. Expression of estrogen receptorβin Human clorectal cancer. World J Gastroenterol, 2004, 10(2) : 214-217.
42. P. A. Konstantinopoulos , A. Kominea , G. Vandoros , et al. Oestrogen Receptor beta ( ERβ) is Abundantly Expressed in Normal Colonic Mucosa , But Declines in Colon Adenocarcinoma Paralleling the tumor’s Dedifferention. European J. Cancer, 2003, 39: 251-258.
43. Cavallini A, Notaricola M, Giannni R, et al. Oestrogen receptor-related receptor alpha (ERRalpha) and oestrogen receptors (ER alpha and ER beta) exhibit different gene expression in human colorectal tumour progression. Eur J Cancer, 2005, 41(10): 1487-1494
44. Paech K, Webb P, Kuiper GG, et al. Differential ligand activation of estrogen receptors ER alpha and ER beta at AP1 sites. Science, 1997,277 (5331): 1508-1510.
45. Monika Jakacka, Masafumi Ito, Jeffery Weiss, et al. Estrogen receptor binding to DNA is not required for its activity through the nonclassical AP-1 pathway. J Biol Chem, 2001 , 276(17) : 13615-13621.
46. Picariello L, Fiorelli G, Martineti V, et al. Growth response of colon cancer cell lines to selective estrogen receptor modulators. Anticancer Res, 2003, 23 (3B): 2419-2424.
47.陆东东.雌激素与肝癌的研究.肿瘤研究与临床,2000,12(1):141-142.
48. Rowan T. Chlebowski, Jean Wactawski-wende, Cheryl Ritenbaugh, etal. Estrogen plus progestin and colorectal cancer in postmenopausal women. N Englnd J Med,2004, 350(10): 991-1004.
49.陈雪萍,虞喜豪,陆海宇.转移性肝癌患者性激素受体变化的临床意义.河北医学,1999, 5 (1):32-33.
50. Danel L,Souweine G, Monier JC, etal. Specific estrogen binding sites in human lymphoid cells and thymic cells. J Steriod Biochem,1983, 18:559-563.
51.顾百诚,景沛.人白细胞雌二醇受体的测定.中华内分泌代谢杂志. 1986, 2 (2): 102-104.
52. Xu X, Thomas ML. Estrogen receptor-mediated direct stimulation of colon cancer cell growth in vitro. Mol Cell Endocrinol, 1994, 105(2): 197-201.
53. Kuruppu D,Christophi C, Bertram JF, et al. Tamoxifen inhibits colorectal cancer metastasis in the liver: a study in a murine model. J Castroenterol Hepatol, 1998,13(5): 521-527.
54. Werner A, Bender E, Mahaffey W, et al. Inhibition of experimental liver metastasis by combined treatment with tamoxifen and interferon. Anticancer drugs. 1996, 7(3): 307-311.
55. Castagnetta L, Traina A, Campisi L, et al. Androgen receptor status in nontumoral and malignant human colorectal tissues. Ann N y Acad Sci. 2002, 963:322-325.
56. Catalano MG, Pfeffer U, Raineri M, et al. Altered expression of androgen-receptor isoforms in human colon-cancer tissues. Int J Cancer, 2000, 86 (3): 325-330.
57.罗成华,张国华,李荣.雄激素受体对结直肠癌预后的意义.解放军医学杂志. 2001,26 (10): 773-4
58. Marugo M, Aste H, Berbasconi D, et al. Cytosolic and nuclear androgen receptors in colorectal adenomas. Anticancer Res. 1992, 12(3):705-708.
59. Lindhe B, Porsch Hallstrom I, Gustafaaon, et al. Effect of neonatal and adult castration and of testosterone substitution in male rata on growth enzyme-alterer hepatic foci in the resistant hepatogyte model. Cancer Res. 1990, 50: 2679-2682
60.张森,万德森,潘志忠等.结直肠癌肝转移的多因素分析.中华肿瘤杂志, 2002,24(4): 307-309.
61. Seiji Maruyama, Naofumi Nagasue, Dipok Kumar Dhar, et al. Preventive Effect of FK143, a 5α-Reductase Inhibitor, on Chemical Hepatocarcinogenesis in Rats. Clinical Cancer Res, 2001, 7: 2096-2104.
62.葛旭鹏,王有德,王忠毅.性激素受体在大肠癌及其癌前病变组织中的表达.中华试验外科杂志,1998,15(4):302-303.
1. Garcia M, Jemal A, Ward EM, etal. Global Cancer Facts & Figures 2007.Atlanta, GA: American Cancer Society, 2007.
2. J. Ferlay, P. Autier, M. Boniol, et al. Estimates of the cancer incidence and mortality in Europe in 2006,Annals of Oncology,2007,18: 581-592.
3. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin,2008,58(2): 71-96.
4. Ling Yang, D. Maxwell Parkin, Jacques Ferlay,et al. Estimates of Cancer Incidence in China for 2000 and Projections for 2005. Cancer Epidemiology Biomarkers & Prevention,2005,14 (1):243-250.
5. H. Strul & N. Arber. Fecal occult blood test for colorectal cancer screening. Annals of Oncology, 2002, 13:51-56.
6. Liu LX, Zhang WH, Jiang HC. Current treatment for liver metastases from colorectal cancer. World J Gastroenterol, 2003, 9(2): 193-200.
7. Larrivee B, Karsan A. Signaling pathways induced by vascular endot-helial growth factor (review). Int J Mol Med, 2000, 5 (5): 447- 456.
8. Narazaki M, Tosato G. Ligand-induced internalization selects use of common receptor neuropilin-1 by VEGF165 and semaphorin3A. Blood, 2006, 107 (10): 3892 - 3901.
9. Buckler P, Reber HA, Buckler M, et al. Hypoxia-inducible factor 1 regulates vascular endothelial growth factor expression in human pancreatic cancer. Pancreas,2003,26(1):56-64.
10. Takeda A,Shimada H,Imasekil,et a1. Clinical significance of serum vascular epithelial growth actor in colorectal cancer patients :correlation with clinical-pathological factors and tumor markers. Oncol Rep,2000, 7:333-8.
11. Underiner T.L,Ruggeri B,Gingrich D.E. Development of vascular endothelial growth factor receptor (VEGFR) kinase inhibitors as anti-angiogenic agents in cancer therapy: Emerging kinase targets and kinase inhibitor discovery methods. Current medicinal chemistry,2004, 11:731-45.
12. Yutaka Takahashi,Yasuhiko Kitadai,Corazon D. Bucana,et al. Expression of vascular endothelial growth factor and its receptor,KDR,correlates with vascularity,metastasis,and proliferation of human colon cancer1. Cancer Res,1995,55:3964-3968.
13.张志超,韩刚,孙亚欣,等.血清VEGF水平与结直肠癌肝转移相关性的临床研究.中国老年学杂志,2006,l0(26):1340-1341.
14. Ochiumi Takehiko, Tanaka Shinji, Oka Shiro, et al. Clinical singnificance of angiopoietin-2 expression at deepest invasive tumor site of advanced colorectal carcinoma. Int J Oncol, 2004, 24: 539-547.
15. Syed Ahmad, Wenbiao Liu, Young D Jung, et al. Differential expression of angiopoietin-1 and angiopoietin-2 in colon carcinoma A possible mechanism for the initiation of antiogeneisis, 2001, 92(5): 1138-1143.
16.梁晓宇,王涛,杨晓东,等.血管内皮生长因子和血管形成因子-2及纤连蛋白与结直肠癌肝转移的相关性研究.中华胃肠外科杂志,2005, 8(1):20-23.
17. David Wong, Sunildath Cazabon, Haslina Ali, et al. Can the Sequential Use of Conventional Silicone Oil and Heavy Oil be a Strategy for the Management of Proliferative Vitreoretinopathy? AnAcad Med Singap, 2006, 35(3): 181-184.
18. Roxane J Hillier, Sunildath J Cazabon, David Wong. The Emerging Role of Heavy Silicone Oil as a Tamponade Agent. Eyenews, 2007, (1): 14-17.
19. M Sirimaharaj, C Balachandran, WC Chan, et al. Vitrectomy with short term postoperative tamponade using perfluorocarbon liquid for giant retinal tears. Br J Ophthalmol, 2005, 89(9): 1176-1179.
20. Rofail M, Lee LR. Perfluoro-n-octane as a postoperative vitreoretinal tamponade in the management of giant retinal tears. Retina, 2005, 25(7): 897-901.
21. Wetterqvist C, Wong D, Williams R, et al. Tamponade efficiency of perfluorohexyloctane and silicone Oil Solutions in a model eye chamber. Br J Opht halmol, 2004, 88: 692-696.
22. Tognetto D, Minutola D, Sanguinetti G, et al. Anatomical and functional outcomes after heavy silicone oil tamponade in viteoretinal surgery for complicated retinal detachment: a pilot study. Ophthalmology, 2005, 112(9):1574-1582.
23.卢雪一,许剑民,钟芸诗,等.环氧合酶-2在预测结直肠癌肝转移中的价值.中华外科杂志, 2007,1(45)54-57.
24. Zhang H, Sun XF. Overexpression of cyclooxygenase-2 correlates with advanced stages of colorectal cancer. Am J Gastroenterol, 2002, 97(4): 1037-1041.
25. Yamauchi T, Watanabe M, Kubota T, et al. Cyclooxygenase-2 expression as a new marker for patients with colorectal cancer. Dis Colon Rectum, 2002, 45(1): 98-103.
26. Yarden Y, Sliwkowski MX, Unianglingtheerb B. signaling networkNatRev Mol CellBiol,2001,2 (2): 127-137.
27. Moniola AO,Neve RM,Lane HA,et al. The erB signaling network: receptor heterdimerization in development and cancer. EMBO J,2000,19(13): 3159-3167.
28. John Mendelsohn, Jose Baselga. Status of epidermal growth Factor receptor antagonists in the biology and treatment of cancer. J Clin Oncol, 2003, 21(14): 2787-2799.
29. Mayer A, Takimoto M, Fritz E, et al. The prognostic significance of proliferating cell nuclear antigen epidermal growth factor receptor, and mdr gene expression in colorectal cancer. Cancer,1993,71(8): 2454-2460.
30. MeKay JA, Murray LJ, Curran S. et al. Evaluation of the epidermal growth factor receptor (EGFR) in colorectal tumours and lymph node metastases. Eur J Cancer,2002, 38(17): 2258-2264.
31. Baretton GB, Diebold J,Christoforis G, et al. Apoptosis and immunohistoehemieal bel-2 expression in colorectal adenomas and carcinomas. Cancer,1996,77(2): 255-264.
32. A. Italiano, M.-C. Saint-Paul, F.-X. Caroli-Bosc, et al. Epidermal growth factor receptor (EGFR) status in primary colorectal tumors correlates with EGFR expression in related metastatic sites: biological and clinical implications. Ann Oncol, 2005, 16 (9): 1503-1507.
33. J.-P. Spano, C. Lagorce, D. Atlan, et al. Impact of EGFR expression on colorectal cancer patient prognosis and survival. Ann Oncol, 2005, 16 (1): 102-108.
34. J.A McKay, L.J Murray, S Curran, et al. Evaluation of the epidermal growth factor receptor (EGFR) in colorectal tumours and lymph nodemetastases. Eur J Cancer, 2002, 38(17): 2258-2264.
35. Gramont A. Adjuvant therapy of stageⅡandⅢcolon cancer. Semin Oncol, 2005, 32(6Suppl8): 11-14.
36. Klapper LN, Kirschbaum MH, Sela M, et al. Biochemical and clinical implications of the ErbB/HER signaling net work of growth factor receptors. Adv Cancer Res, 2000, 77: 25-79.
37. Casanova ML, Larcher F, Casanova B, et al. A critical role for ras-mediated, epidermal growth factor receptor-dependent angiogenesis in mouse skin carcinogenesis. Cancer Res, 2002, 62(12): 3402-3407.
38. Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev, 1997, 18 (1): 4-25.
39. Kopp R, Rothbauer E, Mueller E, et al. Reduced survival of rectal cancer patients with increased tumor epidermal growth factor receptor levels. Dis Colon Rectum, 2003, 46 (10): 1391-1399.
40. Li S, Kim JS, Kim JM,et al. Epidermal growth factor receptor as a prognostic factor in locally advanced rectal-cancer patients treated with preoperative chemoradiation. Int J Radiat Oncol Biol Phys, 2006, 65 (3): 705-712.
41.冯俊,吴云飞,徐惠绵,等. EGFR、VEGF表达与结直肠癌淋巴结及肝转移的相关性.现代肿瘤医学,2006, 16(3): 388-390.
42. Folprecht G, Lutz MP, Schoffski P, et al. Cetuximab and irinotecan / 5 -fluorouracil/folinic acid is a safe combination for the first-line treatment of patients with epidermal growth factor receptor expressing metastatic colorectal carcinoma. Ann Oncol, 2006, 17 (3): 450-456.
43. Ohji Y, Yao T, Eguchi T, et al. Evaluation of risk of liver metastasis in colorectal adenocarcinoma based on the combination of risk factors including CD10 expression: multivariate analysis of clinicopathological and immunohistochemical factors. Oncol Rep, 2007, 17 (3): 525-530.
44. Amioka T,Kitadai Y,Tanaka S,et al. Vascular endothelial growth factor-C expression predicts lymph node metastasis of human gastric carcinomas invading the submucosa. Eur J Cancer,2002,38(10): 1413-1419.
45. Tsujii M, Kawano S, Tsuji S, et al. Cyclooxygenase regulates angiogenesis induced by colon cancer cells,1998,93(5): 705-716
46. Sun Y,Tang XM,Half E,et al. Cyclooxygenase-2 over expression reduces apoptotic susceptibility by inhibiting the cytochrome c-dependent apoptotic pathway in human colon cancer cells. Cancer Res,2002,62(21): 6323-6328.
47. Weleh HA, BandoH, Brokelmaxm MJ, et al. Quantification of vascular endothelial growth factor-C (VEGF-C) by an ovel ELISA. Jimmunol Methods,2004,285: 145-155.
48. Jen-Liang Su, Jin-Yuan Shih, Men-Luh Yen, et al. Cyclooxygenase-2 Induces EP1-and HER-2/Neu-Dependent Vascular Endothelial Growth Factor-C up-Regulation: A Novel Mechanism of Lymphangiogenesis in Lung Adenocarcinoma. Cancer Res,2004,64(2): 554-564.
49. Kyzas PA, Stefailou D,Agnantis NJ,Cox-2 expression correlates with VEGF-C and lymph node metastasis in patients with head and neek squamous cell careinoma. Mod Pathol,2005,18(1): 153-160.
50.刘晋,于皆平,等.环氧合酶-2和血管内皮生长因子-与胃癌淋巴管转移.中华内科杂志,2004,43(11): 841-844.
2.李连弟,饶克勤,张思维,等.中国12市县1993年-1997年肿瘤发病及死亡登记资料统计分析.中国肿瘤,2002,11:497-507.
3. Liu LX, Zhang WH, Jiang HC. Current treatment for liver metastases from colorectal cancer. World J Gastroenterol, 2003,9(2): 193-200
4.张森,万德森,潘志忠,等.结直肠癌肝转移的多因素分析.中华肿瘤杂志,2002,24(4):307-309.
5.万德森.大肠癌肝转移的治疗.万德森,潘志忠主编.大肠癌.北京:中国医药科技出版社,2004,240-247.
6.张振书,张亚历.中国大肠癌研究进展.世界华人消化杂志,2001,9(5):489-494.
7.周志伟,万德森,王国强,等.结直肠癌雌激素受体及孕激素受体的定量研究.癌症, 2004,23(7): 851-854.
8. Castagnetta L, Traina A, Campisi I, et al. Androgen receptor status in nontumoral and malignant human colorectal tissues. Ann N Y Acad Sci,2002,963: 322-325.
9. Nanda K, Bastian LA, Hasselblad V, Simel DL. Hormone replacement therapy and the risk of colorectal cancer: a meta-analysis. Obstet Gynecol,1999,93(5Pt2): 880-888.
10. Chlebowski RT, Waitawski-wende,Ritenbaugh C, et al. Estrogen plus progestin and colorectal cancer in postmenopausal women. N Engl J Med,2004,350(10): 991-1004.
11. Taylor AH, AI-Azzawi F. Immunolocation of oestrogen receptor beta in human tissue. Journal of Molecular Endocrinology,2000,24: 145-155.
12. Campbell-Thompson Martha, Lynchi. Jeanette, Bhardwa, J Bhavna. Expression of estrogen receptor(ER) subtypes and ERβisoforms in colon cancer. Cancer Res,2001,61: 632-640.
13.刘莹,刘明,胡维诚.大肠癌组织雄激素受体的表达及意义.山东医药,2003,43(12)49-50.
14. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med, 2003,9(6): 669- 676.
15. Kerbel R, Folkman J. Clinical translation of angiogenesis inhibitors. Nat Rev Cancer, 2002,2(10): 727-739.
16. Buckler P,Reber HA,Buckler M,et al. Hypoxia indueible factor1 regulates vascular endothelial growth factor expression in human panere atiecancer pancreas,2003, 26(1): 56-64.
17.任学群,景红,傅侃达.血管内皮生长因子的表达和微血管密度与结直肠癌侵袭转移的关系.中国医师杂志,2004,6(5):582-584.
18. Klapper LN, Kirschbaum MH, Sela M et al. Biochemical and clinical implications of the ErbB/HER signaling net work of growth factor receptors. Adv Cancer Res, 2000,77: 25-79.
19. CasanovaML, Larcher F, Casanova B, et al. A critical role for ras- mediated, epidermal growth fact or receptor-dependent angiogenesis in mouse skin carcinogenesis. Cancer Res, 2002,62(12): 3402-3407.
20. Watson AJ. ChemoPreventive effects of NSAIDs against colorectal caneer: regulation of apoptosis and mitosis by COX-1 and COX-2.Histo Histopat, 1998,13(2): 591-597.
21. Yamauchi T , Watanabe M , Kubota T , et al. Cycloxygenase-2 expression as a new marker for patients with colorectal cancer. Dis Colon Rectum, 2002,45 (1): 98-103.
22. Fujita T, Matsui M, Takaku K, Uetake H, Ichikawa W, Taketo MM, et al. Size and invasion-dependent increase in cycloxygenase 2 levels in human colorectal carcinomas. Cancer Res,1998,58: 4823-4826.
23. Kawasaki H, Altieri DC, Lu CD, Toyoda M, Tenjo T, Tanigawa N. Inhibition of apoptosis by Survivin predicts shorter survival rates in colorectal cancer. Cancer Res, 1998, 58(22) : 507l-5074.
24. Sinicrope FA, Ruan SB, Cleary KR, et a1. Bcl-2 and p53 onco protein expression during colorectal tumorigenesis. Cancer Res, 1995, 55: 237-241.
25. GosPodarowiez MK,Miller D,Groome PA,et al. The Process for Continuous improvement of the TNM classification. Cancer,2004,100(1):1-5.
26. Kin-Mang Lau, Mark LaSpina, John Long, and Shuk-Mei Ho. Expression of Estrogen Receptor (ER)-αand ER-βin Normal and Malignant Prostatic Epithelial Cells: Regulation by Methylation and Involvement in Growth Regulation. Cancer Res, 2000, 6(15): 3175-3182.
27. Menasee LP,White GR,Harrison CJ,et al. Localization of the estrogen receptor locus (ESR) to chromosome 6q25.1 by FISH and a simple post-FISH banding technique Genomies,1993,17:263-265.
28. EnmarkE,Pelto-Huikko M,GrandienK,et al. Human estrogen receptor beta-gene Structure Chromosomal localization,and expression pattern,J Clin Endoerinol. Metab,1997,(82):4258-4265.
29. Dardes RC,Jordan VC. Novel agents to modulate estrogen action. Br Med Bull,2000,56 (3): 773-786.
30. Ali S,Metzger D,Bomert JM,et al. Modulation of transcriptional activation by 1igand-dependent Phosphorylation of the human oestrogen receptor A/B region. EMBO,1993,12 (3): 1153-1160.
31. Katzenellenbogen BS. Estrogen receptors: bioactivities and interaetions with cell signaling pathays. Biology of Reprodution,1996, 54(2): 287-293.
32. Slattery ML,Sweeney C,Murtaugh M,et al.Associations between ER alpha,ER beta,and AR genotypes and colon and rectal cancer. Caneer Epidemiol Biomarkers Prev, 2005,14(12): 2936-2942.
33. Waliszewski P,Blaszezyk M,Wolinska-Witort E,et al. Molecular study of sex steroid receptor gene expression in human colon and in colorectal carcinomas. J Surg Oneol,1997,64(1): 3-11.
34. Campbell-Thompson M,Lyneh IJ,Bhardwaj B. Expression of estrogen receptor (ER) subtypes and ER beta isoforms in colon cancer. Cancer Res,2001,61(2): 632-640.
35. Fiorelli G,Pieariello L,Martineti V,et al. Functional estrogen receptor beta in colon cancer cells. Biochem Biophys Res Commun. 1999,261: 521-527.
36. Arai N, Strom A, RaafterJJ,et al. Estrogen receptor beta mRNA in colon cancer cells: growth effects of estrogen and genistein. Biochem Biophys Res Commun,2000,270: 425-431.
37. Qiu Y,Waters CE,Lewis AE,et al. Oestrogen-induced apoptosis in colonocytes expressing oesteogen receptor beta. J Emdrocrinol,2002, 174: 369-377.
38. Foley EF, Jazaeri AA, Sjupnik MA, et al. Selective loss of estrogen receptor beta in malignant human colon. Camcer Res,2000,60(2):45-248.
39. Witte D,Chirala M,Younes A,et al. Estrogen receptor beta is expressed in human colorectal adenoeareinoma. Hum Pathol, 2001,32 (9): 940-944.
40. Jassam N,Bell SM,Speirs V,et al. Loss of expression of oestrogen receptor beta in colon cancer and its assoeiation with Dukes,staging. Oneol Rep,2005,14 (1): 17-21.
41. Konstantinopoulos PA,Kominea A,Vandoros G,et al. Oestrogen receptor beta (ER beta is abundantly expressed in normal colon mueosa,but declines in colon adenocarcinoma paralleling the tumour’s dedifferentiation. Eur J Cancer,2003,39 (9): 1251-1258.
42. Lagendijk JH, Mullink H, VanDiest PJ, et al. Immunohisochemical differentiation between primary adenocarcinomas of the ovary and ovarian metastases of colonic and breast origin.Comparison between a statistical and an intuitive approach.J Clin Pathol,1999,52: 283-290.
43. Nash J W, Morrisson C, Frankel WL. The utility of estrogen receptor and progesterone receptor immunohistochemistry in the distinction of metastatic breast carcinoma from other tumor in the liver. Arch Pathol Lab Med,2003,127(12): 1591-1595.
44. Paech K, Webb P, Kuiper GG, et al. Differential ligand activation of estrogen receptors ER alpha and ER beta at AP1 sites. Science,1997, 277:1508-1510.
45. Zhang S, Li X, Burghardt R, Smith R, et al. Role of estrogen receptor (ER) alpha in insulin-like growth factor (IGF)-I-induced responses in MCF-7 breast cancer cells. J Mol Endocrinol,2005,35(3): 433-47.
46. Newton ACS Wong, Roger DG Malcomson, Duncan Jodrell, et al.ERβisoform expression in colorectal carcinoma: an in vivo and vitro study of clinicopathological and molecular correlates. J Pathol,2005,207: 53-60.
47. Milgrom E, Atger M, Baulieu EE. Progesterone in uterus and plasma IV progesterone receptor(s) in guinea piguterus cytosol. Steroids, 1970, 16 (6): 741-754.
48.方力,薛晓东,段笃文,等.雌孕激素受体在直肠癌中存在意义的讨.黑龙江医药科学, 2001,24(3): 67-68.
49. Lindhe B, Porsch Hallstrom I, Gustafaaon et al. Effect of neonatal and adult castration and of testosterone substitution in male rata on growth enzyme-alterer hepatic foci in the resistant hepatogyte model. Cancer Res,1990,50: 2679-2682.
50. Seiji Marayama, Nafumi Nagame. Preventive effect of FK143, a 5α-reductase inhibitor n chemical hepatocarcinogenesis in rats. Clinical Cancer Res. 2001, 7: 2096-104
51.葛旭鹏,王有德,王忠毅.性激素受体在大肠癌及其癌前病变组织中的表达.中华试验外科杂志,1998,15(4):302-303
52.张志超,韩刚,孙亚欣,等.血清VEGF水平与结直肠癌肝转移相关性的临床研究.中国老年学杂志,2006,l0(26):1340-1341.
53.唐宗江,甘嘉亮,高枫.血管内皮生长因子-A、C在大肠癌及淋巴结转移中的表达及其意义.中华试验外科杂志,2005,22(3):319-320.
54.江忠清,朱凤川,曲军英.肿瘤血管生成及其与宫颈癌的关系.中国误诊学杂志, 2003,3 (11) : 1648.
55.潘贻飞,李权,卢山珊,等.直肠癌中HER-2、VEGF与CXCR4的表达及相关性.肿瘤学杂志,2008,14(4):270-273.
56.张晓雨,周建农,张彤. Survivin、VEGF及Ki67在结直肠癌中的表达及其临床意义.肿瘤防治研究,2007,34(1):35-38.
57. Weich HA, Bando H, Brokelmann M, et al. Quantification of vascular endothelial growth factor-C (VEGF-C) by a novel ELISA. J Immunol Methods, 2004,285:145-155.
58. Uner A, Ebinc FA, Akyrek N, et al. Vascular endorhelia growth factor, c-erB-2 and c-erB-2 expression in colorectal adenoma and adenocarcinoma. Exp Oncol,2005,27(3): 225-8.
59. Italiano A, Saint Paul MC, Caroli-Bosc FX, et al. Epidermal growth factor receptor (EGFR) status in primary colorectal tumors correlates with EGFR expression in related metastatic sites: biological and clinical imp lications. Ann Oncol, 2005, 16 (9): 1503-1507.
60. Spano JP, Lagorce C, Atlan D, et al. Impact of EGFR expressionon colorectal cancer patient prognosis and survival. Ann Oncol, 2005,16 (1): 102-108.
61. Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl JMed, 2004,351 (4): 337-345.
62. Saif MW, Cohenuram M. Role of panitumumab in the management of metastatic colorectal cancer. Clin Colorectal Cancer, 2006,6 (2): 118-124.
63. Saltz LB, Meropol NJ, Loehrer PJ Sr, et al. PhaseⅡtrial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol, 2004,22 (7): 1201-1208.
64. Yarden Y. Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol,2001,2: 127-137.
65. Moniola AO,Neve RM,Lane HA,et al. The erbB signalingnetwork: receptor heterdimerization in development and cancer. EMBOJ,2000, 19(13): 3159-3167.
66. Mendels J, Baselga J. Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J Clin Oncol, 2003, 21(14): 2787-2799.
67. Mayer A, Takimoto M, Fritz E, et al. The prognostic significance of proliferating cell nuclear antigen, epidermal growth factor receptor, and mdr gene expression in coloreetal cancer. Cancer , 1993, 71(8): 2454-2460.
68. McKay JA, Murray LJ, Curran S, et al. Evaluation of the epidermal growth factor receptor (EGFR) in colorectal tumours and lymph node metastases. Eur J Cancer, 2002, 38(17): 2258-2264.
69. Gramont A. Adjuvant therapy of stageⅡandⅢcolon cancer. Semin Oncol, 2005, 32(6Suppl8): 11-14.
70. Klapper LN, Kirschbaum MH, Sela M, et al. Biochemical and clinical implications of the ErbB/HER signaling net work of growth factor receptors. Adv Cancer Res, 2000,77: 25-79.
71. Casanova ML, Larcher F, Casanova B, et al. A critical role for ras- mediated, epidermal growth factor receptor-dependent angiogenesis in mouse skin carcinogenesis. Cancer Res, 2002,62(12): 3402-3407.
72. Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev, 1997,18 (1): 4-25.
73. Folprecht G, Lutz MP, Schoffski P, et al. Cetuximab andirinotecan/5 -fluorouracil/folinic acid is a safe combination for the first-line treatment of patients with epidermal growth factor receptor expression metastatic colorectal carcinoma. Ann Oncol, 2006,17 (3):450-456.
74. Ohji Y, Yao T, Eguchi T, et al . Evaluation of risk of liver metastasis in colorectal adenocarcinoma based on the combination of risk factors including CD10 expression: multivariate analysis of clinicopathological and immunohistochemical factors. Oncol Rep, 2007,17 (3):525-530.
75. Rao M, Yang W, Seifalian AM, et al. Role of cycloxygenase-2 in the angiogenesis of colorectal cancer. Int J Colorectal Dis, 2004,19 (1): 1-11.
76. Sheng H, Shao J, O’Mahony CA, et al. Transformation of intestinal epithelial cells by chronic TGF21 treatment results in Down regulation of the type II TGF-receptor and induction of cyclooxygenase-2. Oncogene, 1999,18(4): 855-867.
77. Hamada J,Cavanaugh PG, Lotan O. Separable growth and migration factors for large-cell lymphoma factors secreted by microvascular endothelial cells derived from target organs for metastasis. Br J Cancer,1992,66(2): 349-354.
78. Lin DT,Subbaramaiah K,Shah JP,et al. Cyelooxygenase-2: a novel molecular target for the prevention and treatment of head and neck cancer. Head Neck,2002,24(8): 792-799.
79.罗伟仁,陈小毅.环氧化酶-2与肿瘤的关系.肿瘤防治研究, 2006,33 (1) : 62-64.
80.汪洋,林从尧,周夏.大肠癌中β-catenin表达及与COX-2、VEGF表达的关系.肿瘤防治研究, 2006,33(1): 20-22.
81. Wong D, Cazabon S, Ali H, et al. Can the use of conventional silicone oil and heavy oil be a strategy for the management of proliferative vit reoretinopathy? Ann Acad Med Singapore, 2006,35(3): 181-184.
82. Hillier R J, Cazabon S J, Wong D. The emerging role of heavysilicone oil as a tamponade agent. Eyenews, 2007,(1): 14-17.
83. Sirimaharaj M, Balachandran C, Chan WC, et al.Vitrectomy with short term postoperative tamponade using perfluorocarbon liquid for giant retinal tears. BrJ Opht halmol, 2005, 89(9): 1176-1179.
84. Rofail M, Lee LR. Perfluoro-n-octane as a postoperative vitreoretina tamponade in the management of giant retinal tears. Retina, 2005, 25(7): 897-901.
85. Wetterqvist C, Wong D, Williams R, et al. Tamponade.efficiency of Perfluoro.hexyloctane and Silicone Oil Solutionsin a Model Eye Chamber. Br J Opht halmol, 2004, 88(5): 692-696.
86. Tognetto D, Minutola D, Sanguinetti G, et al. Anatomical and functional outcomes after heavy silicone oil tamponade in viteoretinal surgery for complicated retinal detachment. Ophthalmology, 2005, 112(9): 1574-1582.
87. Sasson AR, Sigurdson ER. Surgical treatment of liver metastases. Semin Oncol, 2002, 29 (2): 107-118.
88. Tatsuguchi A, Matsui K, Shinji Y, et al. Cyclooxygenase-2 expression correlates with angiogenesis and apoptosis in gastric cancer tissue. Hum Pathol, 2004, 35 (4): 488-495.
89. Yamauchi T, Watanabe M, Kubota T, et al. Cyclooxygenase-2 expression as a new marker for patients with colorectal cancer. Dis Colon Rectum, 2002, 45 (1): 98-103.
90. Sheehan KM, Sheahan K, O’donoghue DP, et al. The relationship between cycloxygenase-2 expression and colorectal cancer. JAMA, 1999, 282 (13): 1254 - 1257.
91.童强,王国斌,卢晓明,等.胃癌组织中核因子2κB , ICAM 21和COX -2的表达及其临床意义.中国普通外科杂志, 2005, 14(10): 736-739.
92.汪斐,莫烨,周世权,等. COX-2和HER-2在结直肠癌中的表达及其意义.中国普通外科杂志, 2007, 7(167):693-695
93. Signh-Ranger G, Kirkpatrick KL, Clark GM, et al. Cyclooxygenase-2(COX-2) mRNA expression corelates with progesterone receptorpositivity in human breast cancer. Curr Med Res Opin, 2003, 19(2): 131-134.
94. Kundu N, Fulton AM. Selective cyclooxygenase(COX-1) or COX-2 inhibitors control metastatic disease in a murine model of breast cancer1. Cancer Res, 2002, 62(8): 2343-2346.
95. Nakamoto N, Higuchi H, Kanamori H, et al. Cyclooxygenase-2 inhibitor and interferon-βsynergistically induce apoptosis in human hepatoma cells in vitro and in vivo. Int J Oncol, 2006, 29(3): 625-35.
96. Wiese FW, Thompson PA, Kadlubar FF. Carcinogen substrate specificity of human COX-1 and COX-2. Carcinogenesis, 2001, 21(1):5-10.
1. Ahmedin Jemal, DVM, PhD; Rebecca Siegel, MPH; Elizabeth Ward, PhD;et al. Cancer Statistics, 2008. CA Cancer J Clin, 2008,58:71–96
2.李连弟,饶克勤,张思维,等.中国12市县1993年-1997年肿瘤发病和死亡登记资料统计分析.中国肿瘤,2002, 11: 497-507.
3. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2006. CA Cancer J Clin,2006,56:106–130.
4. Liu LX, Zhang WH, Jiang HC. Current treatment for liver metastases from colorectal cancer. World J Gastroenterol , 2003,9(2) :193-200
5. Elias D, Sideris L, Pocard M , et al. Results of RO resection for colorectal liver metastases associated with extrahepatic disease. Ann Surg Oncol, 2004, 11 (3): 274-280.
6. Curley SA. Outcomes after surgical treatment of colorectal cancer liver metastases. Semin Oncol, 2005, 32 (6 Suppl 9): 109-111.
7.万德森.大肠癌肝转移的治疗.万德森,潘志忠,主编.大肠癌.北京:中国医药科技出版社,2004,240-247.
8.张振书,张亚历。中国大肠癌研究进展.世界华人消化杂志,2001,9(5):489-494.
9 Zhu JW, Yu BM, Ji YB, Zheng MH, Li DH. Upregulation of vascular endothelial growth factor by hydrogen peroxide in human colon cancer. World J Gastroenterol,2002,8(1): 153-157.
10 Shen LZ, Wu WX, Xu DH, Zheng ZC, Liu XY, Ding Q, Hua YB, Yao K. Specific CEA-producing colorectal carcinoma cell killing with recombinant adenoviral vector containing cytosine deaminase gene. World J Gastroenterol,2002,8(2): 270-275.
11. Xiang DB, Wu XH, Li ZP, et al. Expression of -catenin, cyclin D1and c-myc in colorectal carcinoma. Shijie Huaren Xiaohua Zazhi, 2002,10: 305-308.
12. Yu LL, Yu JP, Ran ZX, et al. Relationship between nuclear factor-kappa B, apoptosis and proliferation in colorectal neoplasia. Shijie Huaren Xiaohua Zazhi,2002,10(3): 309-312.
13. Fang XM, Yu JP, Luo HS. Relationship between hTERT and P16 gene expe ssions and telomerase activity in colorectal cancer. Shijie Huaren Xiaohua Zazhi, 2002, 10(1): 12-14.
14. He FT, Nie YZ, Chen BJ, et al. Expression and identification of recombinant soluble single-chain variable fragment of monoclonal antibody MC3. World J Gastroenterol, 2002, 8(2): 258-262.
15. Wu BP, Zhang YL, Zhou DY, et al. Microsatellite instability, MMR gene expression and proliferation kinetics in colorectal cancer with famillial predisposition. World J Gastroenterol, 2000, 6(6): 902-905.
16. Zhou XD, Yu JP, Ran ZX, et al. Expression of cFLIP short/long and p53 mutation in colon adenocarcinoma. Shijie Huaren Xiaohua Zazhi, 2002, 10(5): 536-539.
17. Li XG, Song JD, Wang YQ. Differential expression of a novel colorectal ancer differentiation related gene in colorectal cancer. World J Gastroenterol, 2001, 7(4): 551-554.
18. Luo MJ, Lai MD. Identification of differentially expressed genes in normal mucosa, adenoma and adenocarcinoma of colon by SSH. World J Gastroenterol, 2001, 7(5): 726-731.
19. Zhang J, Lai MD, Chen J. Methylation status of p16 gene in colorectal carcinoma and normal colonic mucosa. World J Gastroenterol, 1999, 5(5): 451-454.
20. Singh S, Langman MJ. Oestrogen and colonic epithelial cell growth. Gut, 1995, 37(6):737-739.
21. Di Leo A,Messa C,Cavallini A,Linsalata M. Estrogens and colorectal cancer. Curr Drug Targets Immune Endocr Metabol Disord 2001, 1(1):1-12.
22. al-Azzawi F,Wahab M. Estrogen and colon cancer:current issues. CIimacteric,2002, 5(1):3-14.
23. Grodstein F,Newcomb PA,Stampfer MJ. Postmenopausal hormone therapy and the risk of colorectal cancer: A review and meta-analysis. Am J Med, 1999,106(5):574-582.
24. Moghissi KS. Hormone replacement therapy for menopausal women. Compr Ther, 2000, 26(29):197-202.
25. M. Gambacciani, P. Monteleone,A. Sacco,etal. Hormone replacement therapy and endometrial,ovarian and colorectal cancer. Best Pract & Res Clin Endocrinol Metab, 2003, 17(1): 139-147.
26. Burkman RT. Reproductive hormones and cancer:ovarian and Colon cancer. Obstet Gynecol Clin North Am, 2002, 29(3):527-540.
27. Giovannucci E. Obesity, gender,and colon cancer. Gut,2002, 51(2):147.
28. Adlercreutz H . Phyto-oestrogens and cancer.Lancet oncol,2002, 3(6): 364-373.
29. Elizabeth Barrett-Connor,Cynthia A Stuenkel.Hormone replacement therapy (HRT)- risks and benefits.Int J Epidemiof,2001, 30:423-426.
30. Franceschi S, Gallus S, Talamini R, et al. Menopause and Colorectal cancer. Br J Cancer,2000, 82(11): 1860-1862.
31. Nanda K, Bastin LA, Hasselblad V, et al. Hormone replacementtherapy and the risk of colorectal: a meta-analysis. Obstet Gynecol, 1999, 93 (5Pt2): 880-888.
32. Harrison JD, Watson S, Morris DL, et al. The effect of sex hormone and tamoxifen on the growth of human gastric and colorectal cancer cell lines. Cancer, 1989, 63 (11): 2148-2151.
33. Ziv Y, Gupta MK, Milson JW, et al. The effect of tamoxifen and fenretinide on hunman colorectal cancer cell lines in vitro. Anticancer Res. 1994, 14 (5A): 2005-2009.
34. Rita C Dardes, V Craig Jordan. Novel agents to modulate oestrogen action. Br Med Bull, 2000,56(3):773-786.
35. Mark A English, Kate F Kane, Nell Cruickshank, et al. Loss of estrogen inactivation in colonic cancer. J Clin Endocrinol Metab .1999, 84 (6): 2080-2085.
36. Martha L. Slattery, Wade S. Samowitz, Joseph A. Holder. Estrogen and progesterone receptors in colon tumors. Am J Clin Pathol, 2000, 113 (3): 364-368.
37. Dawson P M, Shousha S, Blair S D, et al. Oestrogen receptors in colorecta carcinoma. J Clin Pathol,1990, 43: 149-51.
38.Sietse Mosselman, Jan Polman, Rein Dijkema. ERβ: Identification and characterization of a novel human estrogen receptor. FEBS Letters, 1996, 392 (1): 49-53.
39. Eugene F. Foley, Amir A. Jazaeri, Margaret A. Shuprik, et al. Selective Loss of Estrogen Receptorβin Malignant Human Colon. Cancer Res, 2000, 60: 245-248.
40. Martha Campbell-Thompson, L. Jeanette Lynch, Bhavna Bhardwaj. Expression of Estrogen Receptor (ER) Subtypes and ERβIsoforms inColon Cancer. Cancer Res, 2001, 61: 632-640.
41. Li-Qun Xie, Jie-Ping Yu, He-Sheng Luo. Expression of estrogen receptorβin Human clorectal cancer. World J Gastroenterol, 2004, 10(2) : 214-217.
42. P. A. Konstantinopoulos , A. Kominea , G. Vandoros , et al. Oestrogen Receptor beta ( ERβ) is Abundantly Expressed in Normal Colonic Mucosa , But Declines in Colon Adenocarcinoma Paralleling the tumor’s Dedifferention. European J. Cancer, 2003, 39: 251-258.
43. Cavallini A, Notaricola M, Giannni R, et al. Oestrogen receptor-related receptor alpha (ERRalpha) and oestrogen receptors (ER alpha and ER beta) exhibit different gene expression in human colorectal tumour progression. Eur J Cancer, 2005, 41(10): 1487-1494
44. Paech K, Webb P, Kuiper GG, et al. Differential ligand activation of estrogen receptors ER alpha and ER beta at AP1 sites. Science, 1997,277 (5331): 1508-1510.
45. Monika Jakacka, Masafumi Ito, Jeffery Weiss, et al. Estrogen receptor binding to DNA is not required for its activity through the nonclassical AP-1 pathway. J Biol Chem, 2001 , 276(17) : 13615-13621.
46. Picariello L, Fiorelli G, Martineti V, et al. Growth response of colon cancer cell lines to selective estrogen receptor modulators. Anticancer Res, 2003, 23 (3B): 2419-2424.
47.陆东东.雌激素与肝癌的研究.肿瘤研究与临床,2000,12(1):141-142.
48. Rowan T. Chlebowski, Jean Wactawski-wende, Cheryl Ritenbaugh, etal. Estrogen plus progestin and colorectal cancer in postmenopausal women. N Englnd J Med,2004, 350(10): 991-1004.
49.陈雪萍,虞喜豪,陆海宇.转移性肝癌患者性激素受体变化的临床意义.河北医学,1999, 5 (1):32-33.
50. Danel L,Souweine G, Monier JC, etal. Specific estrogen binding sites in human lymphoid cells and thymic cells. J Steriod Biochem,1983, 18:559-563.
51.顾百诚,景沛.人白细胞雌二醇受体的测定.中华内分泌代谢杂志. 1986, 2 (2): 102-104.
52. Xu X, Thomas ML. Estrogen receptor-mediated direct stimulation of colon cancer cell growth in vitro. Mol Cell Endocrinol, 1994, 105(2): 197-201.
53. Kuruppu D,Christophi C, Bertram JF, et al. Tamoxifen inhibits colorectal cancer metastasis in the liver: a study in a murine model. J Castroenterol Hepatol, 1998,13(5): 521-527.
54. Werner A, Bender E, Mahaffey W, et al. Inhibition of experimental liver metastasis by combined treatment with tamoxifen and interferon. Anticancer drugs. 1996, 7(3): 307-311.
55. Castagnetta L, Traina A, Campisi L, et al. Androgen receptor status in nontumoral and malignant human colorectal tissues. Ann N y Acad Sci. 2002, 963:322-325.
56. Catalano MG, Pfeffer U, Raineri M, et al. Altered expression of androgen-receptor isoforms in human colon-cancer tissues. Int J Cancer, 2000, 86 (3): 325-330.
57.罗成华,张国华,李荣.雄激素受体对结直肠癌预后的意义.解放军医学杂志. 2001,26 (10): 773-4
58. Marugo M, Aste H, Berbasconi D, et al. Cytosolic and nuclear androgen receptors in colorectal adenomas. Anticancer Res. 1992, 12(3):705-708.
59. Lindhe B, Porsch Hallstrom I, Gustafaaon, et al. Effect of neonatal and adult castration and of testosterone substitution in male rata on growth enzyme-alterer hepatic foci in the resistant hepatogyte model. Cancer Res. 1990, 50: 2679-2682
60.张森,万德森,潘志忠等.结直肠癌肝转移的多因素分析.中华肿瘤杂志, 2002,24(4): 307-309.
61. Seiji Maruyama, Naofumi Nagasue, Dipok Kumar Dhar, et al. Preventive Effect of FK143, a 5α-Reductase Inhibitor, on Chemical Hepatocarcinogenesis in Rats. Clinical Cancer Res, 2001, 7: 2096-2104.
62.葛旭鹏,王有德,王忠毅.性激素受体在大肠癌及其癌前病变组织中的表达.中华试验外科杂志,1998,15(4):302-303.
1. Garcia M, Jemal A, Ward EM, etal. Global Cancer Facts & Figures 2007.Atlanta, GA: American Cancer Society, 2007.
2. J. Ferlay, P. Autier, M. Boniol, et al. Estimates of the cancer incidence and mortality in Europe in 2006,Annals of Oncology,2007,18: 581-592.
3. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin,2008,58(2): 71-96.
4. Ling Yang, D. Maxwell Parkin, Jacques Ferlay,et al. Estimates of Cancer Incidence in China for 2000 and Projections for 2005. Cancer Epidemiology Biomarkers & Prevention,2005,14 (1):243-250.
5. H. Strul & N. Arber. Fecal occult blood test for colorectal cancer screening. Annals of Oncology, 2002, 13:51-56.
6. Liu LX, Zhang WH, Jiang HC. Current treatment for liver metastases from colorectal cancer. World J Gastroenterol, 2003, 9(2): 193-200.
7. Larrivee B, Karsan A. Signaling pathways induced by vascular endot-helial growth factor (review). Int J Mol Med, 2000, 5 (5): 447- 456.
8. Narazaki M, Tosato G. Ligand-induced internalization selects use of common receptor neuropilin-1 by VEGF165 and semaphorin3A. Blood, 2006, 107 (10): 3892 - 3901.
9. Buckler P, Reber HA, Buckler M, et al. Hypoxia-inducible factor 1 regulates vascular endothelial growth factor expression in human pancreatic cancer. Pancreas,2003,26(1):56-64.
10. Takeda A,Shimada H,Imasekil,et a1. Clinical significance of serum vascular epithelial growth actor in colorectal cancer patients :correlation with clinical-pathological factors and tumor markers. Oncol Rep,2000, 7:333-8.
11. Underiner T.L,Ruggeri B,Gingrich D.E. Development of vascular endothelial growth factor receptor (VEGFR) kinase inhibitors as anti-angiogenic agents in cancer therapy: Emerging kinase targets and kinase inhibitor discovery methods. Current medicinal chemistry,2004, 11:731-45.
12. Yutaka Takahashi,Yasuhiko Kitadai,Corazon D. Bucana,et al. Expression of vascular endothelial growth factor and its receptor,KDR,correlates with vascularity,metastasis,and proliferation of human colon cancer1. Cancer Res,1995,55:3964-3968.
13.张志超,韩刚,孙亚欣,等.血清VEGF水平与结直肠癌肝转移相关性的临床研究.中国老年学杂志,2006,l0(26):1340-1341.
14. Ochiumi Takehiko, Tanaka Shinji, Oka Shiro, et al. Clinical singnificance of angiopoietin-2 expression at deepest invasive tumor site of advanced colorectal carcinoma. Int J Oncol, 2004, 24: 539-547.
15. Syed Ahmad, Wenbiao Liu, Young D Jung, et al. Differential expression of angiopoietin-1 and angiopoietin-2 in colon carcinoma A possible mechanism for the initiation of antiogeneisis, 2001, 92(5): 1138-1143.
16.梁晓宇,王涛,杨晓东,等.血管内皮生长因子和血管形成因子-2及纤连蛋白与结直肠癌肝转移的相关性研究.中华胃肠外科杂志,2005, 8(1):20-23.
17. David Wong, Sunildath Cazabon, Haslina Ali, et al. Can the Sequential Use of Conventional Silicone Oil and Heavy Oil be a Strategy for the Management of Proliferative Vitreoretinopathy? AnAcad Med Singap, 2006, 35(3): 181-184.
18. Roxane J Hillier, Sunildath J Cazabon, David Wong. The Emerging Role of Heavy Silicone Oil as a Tamponade Agent. Eyenews, 2007, (1): 14-17.
19. M Sirimaharaj, C Balachandran, WC Chan, et al. Vitrectomy with short term postoperative tamponade using perfluorocarbon liquid for giant retinal tears. Br J Ophthalmol, 2005, 89(9): 1176-1179.
20. Rofail M, Lee LR. Perfluoro-n-octane as a postoperative vitreoretinal tamponade in the management of giant retinal tears. Retina, 2005, 25(7): 897-901.
21. Wetterqvist C, Wong D, Williams R, et al. Tamponade efficiency of perfluorohexyloctane and silicone Oil Solutions in a model eye chamber. Br J Opht halmol, 2004, 88: 692-696.
22. Tognetto D, Minutola D, Sanguinetti G, et al. Anatomical and functional outcomes after heavy silicone oil tamponade in viteoretinal surgery for complicated retinal detachment: a pilot study. Ophthalmology, 2005, 112(9):1574-1582.
23.卢雪一,许剑民,钟芸诗,等.环氧合酶-2在预测结直肠癌肝转移中的价值.中华外科杂志, 2007,1(45)54-57.
24. Zhang H, Sun XF. Overexpression of cyclooxygenase-2 correlates with advanced stages of colorectal cancer. Am J Gastroenterol, 2002, 97(4): 1037-1041.
25. Yamauchi T, Watanabe M, Kubota T, et al. Cyclooxygenase-2 expression as a new marker for patients with colorectal cancer. Dis Colon Rectum, 2002, 45(1): 98-103.
26. Yarden Y, Sliwkowski MX, Unianglingtheerb B. signaling networkNatRev Mol CellBiol,2001,2 (2): 127-137.
27. Moniola AO,Neve RM,Lane HA,et al. The erB signaling network: receptor heterdimerization in development and cancer. EMBO J,2000,19(13): 3159-3167.
28. John Mendelsohn, Jose Baselga. Status of epidermal growth Factor receptor antagonists in the biology and treatment of cancer. J Clin Oncol, 2003, 21(14): 2787-2799.
29. Mayer A, Takimoto M, Fritz E, et al. The prognostic significance of proliferating cell nuclear antigen epidermal growth factor receptor, and mdr gene expression in colorectal cancer. Cancer,1993,71(8): 2454-2460.
30. MeKay JA, Murray LJ, Curran S. et al. Evaluation of the epidermal growth factor receptor (EGFR) in colorectal tumours and lymph node metastases. Eur J Cancer,2002, 38(17): 2258-2264.
31. Baretton GB, Diebold J,Christoforis G, et al. Apoptosis and immunohistoehemieal bel-2 expression in colorectal adenomas and carcinomas. Cancer,1996,77(2): 255-264.
32. A. Italiano, M.-C. Saint-Paul, F.-X. Caroli-Bosc, et al. Epidermal growth factor receptor (EGFR) status in primary colorectal tumors correlates with EGFR expression in related metastatic sites: biological and clinical implications. Ann Oncol, 2005, 16 (9): 1503-1507.
33. J.-P. Spano, C. Lagorce, D. Atlan, et al. Impact of EGFR expression on colorectal cancer patient prognosis and survival. Ann Oncol, 2005, 16 (1): 102-108.
34. J.A McKay, L.J Murray, S Curran, et al. Evaluation of the epidermal growth factor receptor (EGFR) in colorectal tumours and lymph nodemetastases. Eur J Cancer, 2002, 38(17): 2258-2264.
35. Gramont A. Adjuvant therapy of stageⅡandⅢcolon cancer. Semin Oncol, 2005, 32(6Suppl8): 11-14.
36. Klapper LN, Kirschbaum MH, Sela M, et al. Biochemical and clinical implications of the ErbB/HER signaling net work of growth factor receptors. Adv Cancer Res, 2000, 77: 25-79.
37. Casanova ML, Larcher F, Casanova B, et al. A critical role for ras-mediated, epidermal growth factor receptor-dependent angiogenesis in mouse skin carcinogenesis. Cancer Res, 2002, 62(12): 3402-3407.
38. Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev, 1997, 18 (1): 4-25.
39. Kopp R, Rothbauer E, Mueller E, et al. Reduced survival of rectal cancer patients with increased tumor epidermal growth factor receptor levels. Dis Colon Rectum, 2003, 46 (10): 1391-1399.
40. Li S, Kim JS, Kim JM,et al. Epidermal growth factor receptor as a prognostic factor in locally advanced rectal-cancer patients treated with preoperative chemoradiation. Int J Radiat Oncol Biol Phys, 2006, 65 (3): 705-712.
41.冯俊,吴云飞,徐惠绵,等. EGFR、VEGF表达与结直肠癌淋巴结及肝转移的相关性.现代肿瘤医学,2006, 16(3): 388-390.
42. Folprecht G, Lutz MP, Schoffski P, et al. Cetuximab and irinotecan / 5 -fluorouracil/folinic acid is a safe combination for the first-line treatment of patients with epidermal growth factor receptor expressing metastatic colorectal carcinoma. Ann Oncol, 2006, 17 (3): 450-456.
43. Ohji Y, Yao T, Eguchi T, et al. Evaluation of risk of liver metastasis in colorectal adenocarcinoma based on the combination of risk factors including CD10 expression: multivariate analysis of clinicopathological and immunohistochemical factors. Oncol Rep, 2007, 17 (3): 525-530.
44. Amioka T,Kitadai Y,Tanaka S,et al. Vascular endothelial growth factor-C expression predicts lymph node metastasis of human gastric carcinomas invading the submucosa. Eur J Cancer,2002,38(10): 1413-1419.
45. Tsujii M, Kawano S, Tsuji S, et al. Cyclooxygenase regulates angiogenesis induced by colon cancer cells,1998,93(5): 705-716
46. Sun Y,Tang XM,Half E,et al. Cyclooxygenase-2 over expression reduces apoptotic susceptibility by inhibiting the cytochrome c-dependent apoptotic pathway in human colon cancer cells. Cancer Res,2002,62(21): 6323-6328.
47. Weleh HA, BandoH, Brokelmaxm MJ, et al. Quantification of vascular endothelial growth factor-C (VEGF-C) by an ovel ELISA. Jimmunol Methods,2004,285: 145-155.
48. Jen-Liang Su, Jin-Yuan Shih, Men-Luh Yen, et al. Cyclooxygenase-2 Induces EP1-and HER-2/Neu-Dependent Vascular Endothelial Growth Factor-C up-Regulation: A Novel Mechanism of Lymphangiogenesis in Lung Adenocarcinoma. Cancer Res,2004,64(2): 554-564.
49. Kyzas PA, Stefailou D,Agnantis NJ,Cox-2 expression correlates with VEGF-C and lymph node metastasis in patients with head and neek squamous cell careinoma. Mod Pathol,2005,18(1): 153-160.
50.刘晋,于皆平,等.环氧合酶-2和血管内皮生长因子-与胃癌淋巴管转移.中华内科杂志,2004,43(11): 841-844.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |