Estrogen and progestin receptors in colonic cancer?

Adenocarcinomas of the large bowel in 28 consecutive patients were examined for the presence of estrogen and progestin receptor proteins. None of the specimens showed specific high affinity receptor binding. Our findings suggest that adenocarcinoma of the large bowel does not contain cytoplasmic receptor sites for estrogen and progestin. No reprints will be available.     

内皮素受体基因在心功能不全心肌中的表达

目的 :研究内皮素 (ET)受体基因亚型在心功能不全心肌中的表达 ,并探讨它和心功能分级及心肌肥大的关系。　　方法 :选取 40例行瓣膜置换术的心功能不全病人心肌 5 0 0 mg,同时取 10例健康心肌组织作为对照。提取组织总核糖核酸并逆转录为互补脱氧核糖核酸后 ,加入特定的寡聚核苷酸引物进行聚合酶链反应 ,分别观察 ET不同受体基因的表达。　　结果 :ET受体基因在正常心肌组织中未见表达 ,而在病变心肌组织中的表达较高。　　结论 :心功能不全时血浆 ET水平升高 ,其受体并不呈反应性下调 ,而是表达增多 ,并与左心收缩功能下降程度有关。     

Cyclooxygenase-2 Inhibition Prevents Migration of Colorectal Cancer Cells to Extracellular Matrix by Down-Regulation of Matrix Metalloproteinase-2 Expression

Purpose

Matrix metalloproteinases-2 hydrolyses gelatins and collagens. It has many biologic functions, including cancer cells invasion. Overexpression of cyclooxygenase-2 is known to be involved in colorectal carcinogenesis, although the mechanism is unclear. Up-regulation of matrix metalloproteinases-2 expression may be one of the mechanisms, which explains how cyclooxygenase-2 expression promotes migration of colorectal cancer cells to extracellular matrix.

Methods

Colorectal cancer cell lines HT29, CaCO2, and Colo205 were used. By using flow cytometry, their cyclooxygenase-2 expression was determined. These cell lines were modulated with NS398, a selective cyclooxygenase-2-inhibitor, and prostaglandin-E2. Western blot and enzyme-linked inmmunosorbent assay were used to determine these cells’ matrix metalloproteinases-2 expression. These cell lines’ ability to migrate into extracellular matrix was determined by Matrigel® (Millipore, Watford, UK) Invasion Chamber.

Results

HT29 expressed more cyclooxygenase-2 than CaCO2. Cyclooxygenase-2 was not detected in Colo205. Matrix metalloproteinases-2 expression is highest in HT29 and least in Colo205. Cyclooxygenase-2 inhibition by NS398 showed decreased matrix metalloproteinases-2 expression in HT29 and CaCO2, but not Colo205, reversible with prostaglandin-E2. Prostaglandin-E2 was shown to up-regulate matrix metalloproteinases-2 expression in all cell lines. Matrigel® Invasion Chamber demonstrated that many more HT29 cells migrate across the membrane than CaCO2 and Colo205, and cyclooxygenase-2 inhibition reduced cellular migration in the cyclooxygenase-2–positive cell lines. Prostaglandin-E2 promoted migration in all cell lines.

Conclusions

There is a positive relationship between cyclooxygenase-2 and matrix metalloproteinases-2 expression. The latter is modulated by prostaglandin-E2 in all cell lines and NS398 in cyclooxygenase-2–positive cells. Such modulation has a knock-on effect to the cells’ ability to invade into extracellular matrix. Cyclooxygenase-2 and matrix metalloproteinases-2 expression are potential therapeutic targets into prevention of colorectal cancer metastasis.

     

Estrogen replacement therapy and colorectal cancer risk in elderly women

PURPOSE: Colorectal cancer is the fourth most common incident cancer in the United States and causes more cancer deaths than any site except lung. Twenty-two epidemiologic studies have examined the relationship of estrogen replacement therapy and colon and rectal cancers with inconsistent results. However, recent studies suggest a reduced risk among current users. The purpose of the present study was to analyze the Leisure World Cohort for possible association of estrogen replacement therapy with colorectal cancer risk. METHODS: A cohort of 7,701 female members who were initially free of cancer and self-reported their use of estrogen replacement therapy were followed up from June 1981 through December 1995 for development of colorectal cancer. RESULTS: We observed 249 incident colorectal cancer cases and 89 colorectal cancer deaths. Women who had used estrogen replacement therapy had an age-adjusted colorectal cancer incidence rate of 2.67 per 1,000 person-years compared with 3.30 per 1,000 personyears among lifetime nonusers (relative risk =0.81; 95 percent confidence interval, 0.63 to 1.04). Among recent users the incidence was one-third lower than among lifetime nonusers (relative risk =0.66; 95 percent confidence interval, 0.44 to 0.98). Risk did not differ by duration of estrogen replacement therapy, usual dose of conjugated estrogen, or route of estrogen administration. The effects of current estrogen replacement therapy on colon cancer incidence (relative risk =0.70; 95 percent confidence interval, 0.45 to 1.09), right-sided colon cancer incidence (relative risk =0.75, 95 percent confidence interval, 0.38 to 1.48), left-sided colon cancer incidence (relative risk =0.76; 0.76; 95 percent confidence interval, 0.41 to 1.41), rectal cancer incidence (relative risk =0.52; 95 percent confidence interval, 0.21 to 1.31), and colorectal cancer mortality (relative risk =0.82; 95 percent confidence interval, 0.44 to 1.54) were similar. CONCLUSION: A reduced risk of colorectal cancer may be an additional benefit of recent estrogen replacement therapy use, which should be considered by postmenopausal women when deciding whether to use hormones.This research was funded by grants from the National Institutes of Health (CA32197), the Earl Caroll Trust Fund, and Wyeth-Ayerst Laboratories.Presented at the annual meeting of the Pacific Coast Fertility Society, Indian Wells, California, April 22 to 26, 1998.     

实验性大鼠肝纤维化模型中细胞外基质成份的变化

应用大鼠肝纤维化模型,通过光镜、电镜观察肝组织学改变,并应用放免法测定肝匀浆中Ⅲ型前胶原(PCⅢ)、透明质酸(HA)、层粘连蛋白(LN)水平和测定肝组织羟脯氨酸(Hyp)含量,结合计算机图像分析研究肝纤维化中细胞外基质成分的动态变化。结果发现,随着肝纤维化向肝硬变的发展,PCⅢ、HA、LN逐渐沉积于肝实质内,在肝纤维化早、中期以Ⅲ型胶原增长为主,在肝纤维化高峰期及肝硬变期则以Ⅰ型胶原增生为主。研究提示细胞外基质在肝纤维化发生发展中起重要作用。     

CCK-B受体mRNA在结肠癌中的表达

目的研究胃泌素受体(CCK B受体)的mRNA在结肠癌组织和对应癌旁正常组织中的表达水平,探讨CCK B受体参与结肠癌发病的可能机制。方法采用半定量RT PCR法检测23例新鲜结肠癌及相对应的癌旁正常组织CCK B受体的表达水平。结果23例结肠癌组织CCK B受体阳性表达率为87.0%,其表达平均值为0.704±0.134,对应癌旁正常组织CCK B受体阳性表达率为60.8%,其表达平均值为0.215±0.077。CCK B受体在结肠癌组的表达水平明显高于癌旁正常组织(P<0.05)。结论CCK B受体在结肠癌组织中的表达水平较正常组织明显增高,提示CCK B受体可能参与结肠癌的发病。     

TG、VLDL、0X-VLDL对L-02和HLF细胞增殖及合成细胞外基质的影响

以MTT法、透明质酸(HA)放免测定法及~3H-脯氮酸掺人法,观察4种不同浓度的甘油三酯(TG)、极低密度脂蛋白(VLDL)、氧化极低密度脂蛋白(OX-VLDL)对无血清培养正常成人肝细胞(L-02细胞)、人胚肺成纤维细胞(HLF细胞)增殖及合成细胞外基质(ECM)的影响。结果发现.TG、VLDL、OX.VLDL可影响HLF细胞和/或L.02细胞的增殖,促进其胶原蛋白和HA的合成,其中以OX-VLDL的作用最为明显。提示肝内脂质(特别是OX-VLDL)过多可通过加强脂质过氧化反应促进肝纤维化的发生和发展。     

心肌缺血时血管内皮生长因子的基因表达

目的：研究缺血对心肌血管内皮生长因子（ＶＥＧＦ）基因表达的影响。方法：提取正常兔（ｎ＝２）、假手术兔（ｎ＝２）及冠状动脉左旋支结扎后不同缺血时间的兔（ｎ＝６）心肌总核糖核酸（ＲＮＡ），用Ｎｏｒｔｈｅｒｎ杂交检测ＶＥＧＦ信使核糖核酸（ＶＥＧＦｍＲＮＡ）的表达。结果：正常及缺血兔心肌中均有３．９ｋｂ的ＶＥＧＦｍＲＮＡ表达，但缺血心肌中表达明显高于正常心肌，心肌缺血３０分钟ＶＥＧＦｍＲＮＡ表达即已明显增高，并持续增高达４小时。结论：兔心肌中有ＶＥＧＦ基因的基础表达，缺血可致其表达增加。关键词血管内皮生长因子心肌缺血信使核糖核酸表达     

Carneau白鸽血管壁细胞外基质的改变伴有自发性动脉粥样硬化症的发展

Ｃａｒｎｅａｕ白鸽（以下简称白鸽）自发性动脉粥样硬化的发生发展有遗传易感性。在６周的白鸽和ＳｈｏｗＲａｃｅｒ（ＳＲ）鸽胸主动脉和腹主动脉分支中，总羟脯氨酸和异构锁连素水平的分析结果表明，白鸽动脉组织中总胶原和交叉连接的弹性硬蛋白显著增加。斑点杂交分析结呆表明细胞外基质蛋白沉积的增加与白鸽主动脉组织ＲＮＡ中编码原α１（１）胶原和弹性硬蛋白ｍＲＮＡ回收率增加相一致，并使白鸽主动脉组织中编码细胞内γ－肌动蛋白ｍＲＮＡ回收率增加。在鸽肝脏ＲＮＡ中编玛原α１（１）胶原和弹性硬蛋白ｍＲＮＡ的稳定状态水平之间未见差异。结果表明在细胞外和细胞内蛋白质生物合成能力方面，白鸽主动脉组织中细胞数表示一种明显不同的表现型。     

Carneau白鸽血管壁细胞外基质的改变伴有自发性动脉粥样硬化症的发展

Ｃａｒｎｅａｕ白颌自发性动脉粥样硬化的发生发展有遗传易感性。在６周的白颌和ＳｈｏｗＲａｃｅｒ（ＳＲ）颌胞主动脉和腹结果表明，白颌动脉组织中总胶原和交叉连接的弹性硬蛋白显著增加。     

胃癌雌激素受体和孕激素受体的检测及临床意义

目的：为了研究雌激素受体（Ｅｓｔｒｏｇｅｎ ｒｅｃｅｐｔｏｒ,ＥＲ）的孕激素受体（Ｐｒｏｇｅｓｔｅｒｏｎｅ ｒｅｃｅｐｔｏｒ,ＰｇＲ）在胃癌中的表达以及与临床病理学之间的关系。方法：我们采用免疫组织化学法对９１例胃癌作了测定。结果：９１例胃癌的ＥＲ,ＰｇＲ阳性率分别为３９．６％,４１．８％。在９１例胃癌中,分化好的腺癌细胞ＥＲ,ＰｇＲ阳性率均为４７．９％,高于分化差的癌细胞的ＥＲ,ＰｇＲ阳性率（３     

心肌肥厚大鼠超声背向散射积分与细胞外基质重塑的相关性

目的　探讨心肌肥厚大鼠背向散射积分的变化情况 ,并结合心肌细胞外基质的病理改变及其重要影响因子基质金属蛋白酶 (MMP 9)和其生理性抑制剂 (TIMP 1)在蛋白和基因水平的表达 ,探讨其相互关系。方法　SD大鼠腹腔注射去甲肾上腺素 ( 1 0 6mg/kg·d× 15d)建立心肌肥厚的动物模型 ,测定室间隔中部心肌的背向散射参数 ,并应用免疫组化和逆转录 -聚合酶链反应法 (RT PCR)方法检测心肌总体胶原、Ⅰ型和Ⅲ型胶原的改变 ,及MMP 9、TIMP 1蛋白和mRNA的表达 ,与超声测定的结果进行对比研究。结果　 ( 1)实验组大鼠心肌胶原成分及MMP 9、TIMP 1蛋白和mR NA的表达显著高于健康对照组 (P <0 0 1)。 ( 2 )超声背向散射积分 (IBS % )在实验组较对照组增高(P <0 0 1) ,与心肌胶原、MMP 9和TIMP 1蛋白和mRNA的表达之间存在相关性。结论　大鼠心肌肥厚时IBS %升高与胶原的过渡沉积密切相关 ,而MMP 9和TIMP 1可能是引起心肌细胞外基质重塑的重要机制之一。     

Prognostic and Predictive Value of Thymidylate Synthase Expression in Colon Cancer

Thymidylate synthase (TS) is an enzyme responsible for DNA synthesis. Its competitive inhibition constitutes the major mechanism of the antitumor effect of 5-fluorouracil (5-FU) therapy, which significantly improves the survival rate of colon cancer patients. The aim of our study was to examine the clinical importance of TS expression in colon cancer patients and to correlate its expression with various clinicopathological parameters, tumor proliferative capacity, cell cycle-related molecules’ expression and patients’ survival. Of the 71 colon cancer patients studied, 51 (71.8%) tested positive for TS, with the positive result being statistically significantly correlated with patients’ gender (P = 0.012), tumor histological grade (P = 0.032), vascular invasion (P = 0.017) and the expression of cyclin E, pRb and p16 (P = 0.042, P = 0.001 and P = 0.001, respectively). The overall 5-year survival rate was 40% for TS-positive patients and 68.6% for TS-negative ones (P = 0.0134); in patients aged >70 years, this was 30 and 77.8%, respectively (P = 0.0008). In a multivariate analysis of survival, TS expression proved to be of prognostic significance (P = 0.0174). Our findings support evidence for the clinical importance of TS expression in colon cancer patients and define it as an independent prognostic risk factor.     

胃癌雌孕激素受体表达与幽门螺杆菌感染的关系

目的 探讨胃癌雌激素受体(ER)和孕激素受体(PgR)与幽门螺杆菌(HP)感染的关系.方法:采用S-P免疫组化染色法检测64例胃癌活检组织中ER和PgR.结果:胃癌ER和PgR的阳性表达明显高于肠化生、异型增生和慢性浅表性胃炎(P<0.01);HP阳性胃癌中ER和PgR明显高于HP阴性组(P<0.01);肠化生、异型增生ER和PgR在HP阳性和HP阴性组间均无显著性差异(P>0.05).结论:胃癌中ER和PgR表达与HP感染有相关性.     

Altered Gene Expression in Normal Colonic Mucosa of Individuals With Polyps of the Colon

PURPOSE Expression levels of many genes are altered in colon cancer, relative to normal colonic mucosa. We recently reported that such differences also exist between grossly normal colonic mucosa of individuals with and without colon cancer, and between individuals with and without a family history of colon cancer. Here we report a study of individuals with no cancer but with polyps in the transverse, ascending/descending, or rectosigmoid colon. METHODS Biopsies of grossly normal-appearing colonic mucosa from the rectosigmoid colon were taken from individuals with polyps, with or without personal/family history of colon cancer, and gene expression profiles compared with those from biopsies of control patients, with no polyps or known personal/family history. A global expression analysis was conducted of the same 15 genes used in our previous studies. RESULTS We found significant differences in gene expression in normal-appearing rectosigmoid colonic mucosa between individuals with polyps and controls, regardless of whether personal or family history of cancer was present. CONCLUSIONS Alterations in gene expression patterns in morphologically normal-appearing colonic mucosa are associated with the presence of adenomatous polyps. Prospective studies will be required to determine whether these alterations in gene expression can be used to predict risk of developing colon cancer. Supported in part by the Alden P. Yates Fund for colon cancer. Reprints are not available.     

Cyr61、VEGF在结肠癌中的表达及临床意义

目的 研究cyr61、VEGF在结肠癌肿瘤组织及癌旁正常组织中的差异表达及意义.方法 应用免疫组织化学S-P法,检测40例结肠癌肿瘤组织及15例癌旁正常组织中Cyr61、VEGF蛋白的表达.结果 (1)Cyr61在癌组织中的表达率95%(38/40)明显高于正常对照组织中的40%(6/15),P＜0.001;(2)Cyr61的表达与结肠癌的分化程度、Duke's分期、淋巴结转移有关(P=0.048,P=0.019,P=0.001);(3)VEGF在癌组织中的表达率67.5%(27/40)明显高于正常对照组织中的20%(3/15),二者之间差异具有统计学意义(P＜0.01);(4)经X2检验,结肠癌中Cyr61与VEGF表达有关(X2=5.507,P＜0.05).结论 (1)Cyr61在结肠癌中高表达,且标记癌组织的敏感性高,有望成为一种新颖的结肠癌标记物;Cyr61的表达与结肠癌的分化程度、Duke's分期、淋巴结转移有关,提示它可能参与结肠癌的演进,或许可作为结肠癌生物治疗作用的新靶点;(2)cyr61与VEGF表达相关,表明两者在调控血管生成的过程中存在协同效应,提示Cyr61通过调节VEGF表达的途径影响肿瘤血管生成.