Differential Expression of Cytoplasmic Carbonic Anhydrases, CA I and II, and Membrane-Associated Isozymes, CA IX and XII, in Normal Mucosa of Large Intestine and in Colorectal Tumors

This study compares the localization of carbonic anhydrase isozymes (CA) I and II and that of IX and XII in normal large intestine and in colorectal tumors. Immunohistochemical studies were performed on 69 colorectal lesions. While the normal mucosa of the large intestine showed high expression for CA I and II, the intensity of the immunostaining for both isozymes decreased in benign lesions and was very weak in malignant tumors. The reciprocal pattern of expression observed for these cytoplasmic isozymes and transmembrane CA IX and XII in intestinal tissue specimens supports the suggestion that CA IX and XII may be functionally involved in tumor progression to malignancy and/or in invasion. By contrast, while CA I and II are prominent in normal colorectal mucosa, where they play a role in regulation of pH homeostasis and water and ion transport, loss of expression of these cytoplasmic isozymes consistently accompanies progression to malignant transformation.     

p28 GANK在结肠癌中的表达及其意义

背景:结肠癌是消化系统常见恶性肿瘤之一。p28GANK促进人类多种肿瘤恶性演变,然而其在结肠癌中的作用尚未明确。目的:探讨p28GANK在结肠癌中的表达及其意义。方法:纳入2006年1月～2007年2月浙江省湖州市中心医院收治的结肠癌患者78例,应用免疫组化法检测患者癌组织及其相应癌旁非癌组织标本p28GANK的表达情况,分析其在结肠癌和癌旁组织中的表达差异,以及p28GANK表达与结肠癌临床病理特征和预后的关系。结果:p28GANK在结肠癌组织中的表达水平显著高于癌旁组织[69.2%(54/78)对15.4%(12/78)](P<0.01)。结肠癌组织p28GANK表达与肿瘤浸润深度、分化程度、淋巴结转移、Dukes分期相关(P<0.05)。p28GANK阳性表达与结肠癌患者术后生存期缩短显著相关(P<0.01)。结论:p28GANK表达与结肠癌恶性程度相关,其高表达提示患者预后不良。     

Correlation Between THSD7A Expression and Tumor Characteristics of Azoxymethane-Induced Colon Cancer Model in Rats

BackgroundThrombospondin type 1 domain-containing 7A (THSD7A) has emerged as a new potential molecular tool for multiple tumors since that THSD7A was detected to be expressed in various malignant tumor types including colorectal cancer (CRC). Thus, we investigated the correlation between THSD7A expression and pathologic determinants of azoxymethane (AOM)-induced CRC in a rat model.Methods: A total of 30 rats were included in the study (experimental group; n = 15, control group; n = 15). Azoxymethane was administered to the experimental group weekly as subcutaneous injections at a dose of 15 mg/kg bodyweight for 3 weeks. Five months later, 42 tumors were obtained in the study group and histopathologic evaluation of CRC tumors for THSD7A was performed by immunohistochemical staining. Thrombospondin type 1 domain-containing 7A expression was classified according to staining levels.Results: While 28.6% of the colonic tumors were stained as negative, mild-moderate and strong staining was determined in 61.9% and 9.5% of the tumors, respectively. Thrombospondin type 1 domain-containing 7A expression levels inversely correlated with Ki-67 expression (P < .001) and tumor grade (P =.02). Receiver operating characteristic analysis showed Ki-67 staining ≥20.5% was determined as a cut-off value for negatively stained THSD7A tumors with 91% sensitivity and 69% specificity (P = .001, area under curve: 0.822). Moreover, higher Ki-67 expression was found to be associated with higher tumor grade (P < .001), presence of lymphatic invasion (P = .003), and higher T stage (P = .003).Conclusion: Negative staining for THSD7A seems to be linked to invasive pathologic determinants in AOM-induced CRC in rats.     

Glucocorticoid Receptor (GR) Immunohistochemical Expression Is Correlated with Cell Cycle-Related Molecules in Human Colon Cancer

The aim of this study was to examine glucocorticoid receptor (GR) immunohistochemical expression in colon cancer histopathological specimens and to correlate it with clinicopathological parameters, tumor proliferative capacity, cell cycle-related molecule expression, and patients' survival. Primary tumoral samples from 91 colon cancer patients were immunostained for the detection of GR, cyclins D1 and E, Rb protein (pRb), p16, p21, and Ki-67, using the streptavidin–biotin–peroxidase technique. GR expression was correlated with tumor histopathological characteristics and proliferative capacity, cell cycle-related molecule expression, and patients' survival. GR positivity was prominent in 44 of 91 (48%) colon cancer cases and was positively correlated with the expression of cell cycle-related molecules pRb (P = 0.008) and p16 (P = 0.002), while lack of correlation was noted with cyclins D1 and E and p21. GR expression was not correlated with tumor location, grade of differentiation, Dukes' stage, lymph node and liver metastasis, venous invasion, tumor proliferative capacity (evident by Ki-67-labeling status) and patient survival. Our findings support evidence for GR participation in the biological mechanisms underlying the carcinogenic evolution in the colon, implying the use of glucocorticoids as an adjuvant treatment for cell cycle modulation in colon cancer cells.     

Right Colon, Sigmoid Colon, and Transverse Colon Diverticulitis in the Same Patient: Report of a Case

Although sigmoid colon diverticulitis is frequently seen, right colon and transverse colon diverticulitis remain rare forms of the disease. This case report examined the disease course of a 46-year-old female who first presented to our institution in 1990 with perforated right-sided diverticulitis. During the next 11 years, she developed sigmoid colon diverticulitis and then transverse colon diverticulitis. The right and sigmoid colon diverticulitis were treated with surgery and the transverse colon diverticulitis was managed conservatively. This is the first reported case of a single patient who had separate episodes of diverticulitis in the right, transverse, and sigmoid colon. The evaluation and management of this patient has mirrored a trend in the literature and clinical practice.Reprints are not available.     

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。     

Incidence of Advanced Adenomas of the Rectosigmoid Colon Three Years and Five Years After Negative Flexible Sigmoidoscopy in 4010 Patients

Flexible sigmoidoscopy is recommended for persons at average risk for colorectal cancer. A follow-up is advised in 3 to 5 years, although the outcomes are not well established. We designed a large, prospective study of an unselected population to measure the incidence of advanced adenomas at flexible sigmoidoscopy 3 and 5 years after an initial negative examination. Adenomas were considered advanced if they were villous, tubulovillous, high-grade dysplasia, adenocarcinoma, or > or = 10 mm in size. We evaluated 8121 patients referred for flexible sigmoidoscopy and 4010 met the inclusion criteria. Group 1 had flexible sigmoidoscopy between 3 and 4 years and Group 2 between 5 and 6 years after a negative examination. Group 1 included 1300 patients with an incidence rate for advanced adenomas of 0.9% (12/1300) and Group 2 included 2710 patients with an incidence rate for advanced adenomas of 1.1% (30/2710). When the two group were subdivided by the presence or absence of a family history of a first-degree relative with sporadic colorectal cancer, the incidence rates for advanced adenomas between the populations were not different. Our data indicate incidence rates of 0.9 and 1.1% for advanced adenomas at flexible sigmoidoscopy 3 and 5 years, respectively, after a negative flexible sigmoidoscopy, with no impact from a family history.     

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.     

Expression of Tissue Inhibitors of Metalloproteinases (TIMPs) in Gastric Cancer

Matrix metalloproteinases (MMPs) are one of the major classes of proteolytic enzymes involved in tumor invasion and metastasis, being inhibited by naturally occurring tissue inhibitors of metalloproteinases (TIMPs). Sixty-five patients who underwent surgery for gastric cancer in 1992 at Chonnam National University Hospital were selected for this study. The primary selection criteria were the availability of formalin-fixed and paraffin-embedded blocks and sufficient clinical follow-up for tumor-specific survival analysis. In this study, we examined the expression of TIMP-1 and TIMP-2 in human gastric cancer tissue by in situ hybridization and immunohistochemistry, and the correlation between their expression and clinicopathological parameters. TIMP-1 and TIMP-2 expressions were detected predominantly in the peritumor stromal cells rather than tumor cells themselves. Immunohistochemical stainings were concordant with the result obtained by in situ hybridization. The intensity of TIMP-1 immunohistochemical stromal staining correlated with tumor stage (P = 0.009) and patient survival (P = 0.025). However, the intensity of TIMP-2 immunohistochemical stromal staining did not correlate with tumor stage (P = 0.339) and patient survival (P = 0.474). The correlation between the increased TIMP-1 expression and cancer stage noted in this study reflects a role of TIMP-1 in predicting the aggressive behavior of gastric cancer. TIMP-2 expression did not correlate with clinicopathological parameters. However, expression of TIMP-1 and the possible additional value of TIMP-2 should be further explored in determining the prognosis of gastric cancer.     

Butyrate-Induced Differentiation of Colon Cancer Cells Is PKC and JNK Dependent

Butyric acid, a short–chain fatty acid physiologically present in human large gut, is derived from bacterial fermentation of complex carbohydrates. It has been shown to reduce the growth and motility of colon cancer cell lines and to induce cell differentiation and apoptosis. Apoptosis is considered a result of normal colonocyte terminal differentiation in vivo. The aim of this study was to characterize the cellular mechanisms regulating differentiation of colon cancer cells stimulated with sodium butyrate (NaB). The two human colon cancer cell lines Caco-2 and HT-29 were treated with NaB at physiologically relevant concentrations. Alkaline phosphatase (ALP) activity, a marker of colonocyte differentiation, was increased 48 hr after treatment with 1 mM NaB. Higher doses of NaB (5 and 10 mM) induced apoptosis of the cells and failed to stimulate the colonocyte differentiation. Therefore, we assumed that butyrate augments cell differentiation and induces apoptosis, acting via various intracellular mechanisms, and butyrate-mediated programmed cell death cannot be considered a consequence of colonocyte terminal differentiation. The effect of NaB on ALP activity was significantly attenuated in the presence of inhibitors of protein kinase C and JNK. Inhibition of MEK–ERK signal transduction pathways augmented the impact of butyrate on colonocyte differentiation. These results suggest that butyrate could influence the colonocyte differentiation via modulation of the activity of cellular protein kinases and signal transduction.     

基质金属蛋白酶组织抑制剂在心脏中的表达及意义

基质金属蛋白酶组织抑制剂在心血管疾病发生发展过程中的变化是近年来心血管领域研究的热点之一。现就基质金属蛋白酶抑制剂的分类和结构及在心肌重构、心力衰竭、心肌缺血再灌注损伤等的表达及作用作一综述。     

Effect of Age on Survival Benefit of Adjuvant Chemotherapy in Elderly Patients with Stage III Colon Cancer

OBJECTIVES: To estimate the modifying effect of age on the survival benefit associated with adjuvant chemotherapy receipt in elderly patients with a diagnosis of Stage III colon cancer.
DESIGN: Observational, retrospective cohort study using two samples: an overall sample of 7,182 patients to provide externally valid analyses and a propensity score–matched sample of 3,016 patients to provide more internally valid analyses by reducing the presence of treatment endogeneity. An interval-censored survival model with a complementary log-log link was used. Hazard ratios and 95% confidence intervals were obtained for all regressions.
SETTINGS: Data from the National Cancer Institute's Surveillance, Epidemiology and End Results database and the linked Medicare enrollment and claims database were used.
PARTICIPANTS: Selected patients were aged 66 and older and had a diagnosis of Stage III colon cancer. Patients were followed from surgery to time of death or censorship.
MEASUREMENTS: The outcome was colon cancer–specific death during the follow-up period. Receipt of adjuvant chemotherapy was measured according to the presence of a claim for 5-fluorouracil or leucovorin within 6 months after surgery.
RESULTS: All elderly patients had a significant survival benefit associated with adjuvant chemotherapy receipt, although the survival benefit of adjuvant chemotherapy was not uniform across all age groups.
CONCLUSION: These findings have important clinical and policy implications for the risk–benefit calculation induced by treatment in older patients with Stage III colon cancer. The results suggest that there is a benefit from chemotherapy, but the benefit is lower with older age.     

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.     

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.     

幽门螺杆菌感染对胃黏膜基质金属蛋白酶表达的影响及其与胃癌的关系

基质金属蛋白酶（MMPs）是一组锌依赖性内肽酶，可降解细胞外基质蛋白，有助于肿瘤细胞浸润和转移。已证实幽门螺杆菌（H．pylori）胃癌的发生有关，但其对胃癌浸润和转移的作用尚未明确。近年有研究显示H．pylori感染可使胃黏膜上皮MMPs表达增高，推测H．pylori感染可能通过MMPs而促进胃癌浸润和转移。本文就H．pylori感染对胃黏膜MMPs表达的影响及其与胃癌的关系作一综述，并对金属蛋白酶组织抑制剂（TIMPs）治疗胃癌的前景作一展望．     

MMP-28在口腔扁平苔藓中的表达及意义

目的探讨基质金属蛋白酶-28（MMP-28）在口腔扁平苔藓（OLP）形成中的机制。方法分别采用免疫组化和Western Blot法检测MMP-28蛋自在37例不同类型OLP中的表达,并与11份正常口腔黏膜标本进行比较。结果OLP息者中MMP-28表达明显高于正常口腔黏膜组织,且糜烂型表达明显高于其他类型;OLP患者中MMP-28表达与性别、年龄及病损面积无明显相关。结论MMP-28表达与OLP分型密切相关,随病变程度加重逐渐升高;检测MMP-28蛋白表达有助于预测OLP的恶性行为;抑制MMP-28有望成为OLP治疗的新途径。     

Twist1,MMP-2和MMP-9在结直肠癌组织中的表达及意义

目的:研究Twist1、MMP-2和MMP-9蛋白在结直肠癌组织中的表达及其相互关系.方法:建立组织微阵列平台,应用免疫组织化学方法检测92例结直肠癌组织Twist1、MMP-2和MMP-9蛋白的表达情况.结果:结直肠癌中Twist1的表达率为64.1%,MMP-2和MMP-9阳性率分别为66.3%和67.4%;Twi...