The value of tumour marker CA 125 in surgical pathology

CA 125 is a tumour marker located primarily on non-mucinous epithelial ovarian tumours and which is recognized by the monoclonal antibody OC 125. In this study the value of CA 125 in surgical pathology was assessed. In fresh frozen material, the expression of CA 125 was demonstrated in 82% of 83 epithelial ovarian neoplasms using the indirect immunoperoxidase technique. In addition, all adenocarcinomas of cervix (n = 5) and endometrium (n = 15) tested expressed CA 125, and 25 of 111 (22%) non-gynaecological malignant tumours were positive. The positive cases included 20 breast carcinomas, one carcinoma of the stomach and one of the colon. Using a commercial kit on routinely fixed, paraffin embedded material, CA 125 positivity was demonstrated in 29 of 36 (80%) serous cystadenocarcinomas after pronase pre-treatment of the sections, in contrast to 100% (n = 25) positivity on frozen tissue sections. CA 125 can, therefore, be demonstrated in routinely fixed paraffin embedded material, although the number of positive results is less than in fresh frozen sections.     

Somatic spectrum of cancer-associated single basepair substitutions in the TP53 gene is determined mainly by endogenous mechanisms of mutation and by selection

The spectrum of somatic TP53 single basepair substitutions detected in 955 cancers was compared with that of 2,224 different germline mutations in 279 different human genes (other than TP53), reported as the cause of inherited disease. This comparison reveals that, disregarding a relatively small subset (12%) of TP53 mutations that probably result from the action of exogenous mutagens, both the relative rates and the nearest-neighbor spectra of single basepair substitutions are similar in the two datasets. This spectral resemblance suggests that a substantial proportion of cancer-associated somatic TP53 mutations result from endogenous cellular mechanisms. The likelihood of clinical observation of a particular mutation type differs, however, between tumors and genetic diseases, when the chemical properties of the resulting amino acid substitutions are considered. Together with a sixfold higher observation likelihood for mutations at evolutionary conserved residues, this finding argues that selection is a critical factor in determining which TP53 mutations are found to be associated with human cancer. © 1995 Wiley-Liss, Inc.     

Stage, survival and delays in lung, colorectal, prostate and ovarian cancer: comparison between diagnostic routes

BACKGROUND: Very few studies have reported cancer outcomes of patients referred through different routes, despite the prominence of current UK cancer urgent referral guidance. AIM: This study aimed to compare outcomes of cancer patients referred through the urgent referral guidance with those who were not, with respect to stage at diagnosis, survival, and delays in diagnosis. Design of study: Analysis of hospital records. SETTING: One hospital trust in England. METHOD: The records of 889 patients diagnosed in 2000-2001 with one of four types of cancer were analysed: 409 with lung cancer; 239 with colorectal cancer; 146 with prostate cancer; and 95 with ovarian cancer. Outcome measures were diagnostic stage, survival, referral and secondary care delays. RESULTS: For lung cancer, urgent referrals had more advanced TNM (tumor, node, metastasis) stage than patients diagnosed through other routes (P = 0.035) and poorer survival (P = 0.020). There was no difference in stage or survival for the other cancers. For each cancer, a higher proportion of urgent referrals was seen within 2 weeks. Secondary care delays for lung and colorectal cancer were shorter for inter-specialty referrals. CONCLUSION: For patients with lung cancer, the guidance appears to be prioritising those in the more advanced stages of disease. This was not the case for the other three cancers. Referral delays were shorter for patients urgently referred, as is the intention of the guidance. The avoidance of delays in outpatient diagnostics probably accounts for shorter secondary care delays for inter-specialty referrals.     

Production of CA125 by human lung cancer cell lines

CA125, which until recently was considered an ovary specific tumor marker, is elevated in the serum of patients with many pathological conditions, including lung cancer. In order to investigate the production of CA125 by human lung cancer cell lines, cell culture and immunochemical staining were performed in three cell lines. Our results showed the cell surface expression of CA125 in both adenocarcinoma and large cell carcinoma cell lines and the production of CA125 in culture medium. This is considered as evidence for in vitro production of CA125 by human lung cancer, and suggests that CA125 elevation is not only the result of ovarian cancer but may be due to other pathological conditions, including lung cancer.     

大肠癌患者VEGF和NO血清水平及其与恶变程度的关系

目的:研究血清中血管内皮生长因子(VEGF)和一氧化氮(NO)表达水平及其与大肠癌恶变程度的关系。方法:分别采用酶联免疫吸附法(ELISA)测定和分光光度法检测46例大肠癌患者术前和30例健康人血清中VEGF和NO的含量。结果:大肠癌患者血清VEGF和NO表达水平均较健康人明显增高(P<0.01),且随着大肠癌浸润深度增加、有淋巴结转移以及Dukes分期愈晚者而显著增高(P<0.01)。血清VEGF与NO含量呈明显正相关(r=0.8152,P<0.01)。结论:VEGF和NO与大肠癌的发生、发展及转移调控过程有关,术前检测血清VEGF和NO含量对判断大肠癌的浸润转移以及Dukes分期具有重要价值。     

Localization of CEA,HCG, Lysozyme,alpha-1-antitrypsin,and alpha-1-antichymotrypsin in gastric cancer and prognosis

Summary Carcinoembryonic antigen (CEA),-human chorionic gonadotropin (HCG), alpha-1-antichymotrypsin (ACT), alpha-1-antitrypsin (AAT) and Lysozyme (LYS) were traced by immunoperoxidase staining in gastric carcinomas. The immunohistological results were evaluated in relation to histological types (WHO and Laurén), stage of disease, grade and survival time. CEA was demonstrated in 96% of the tumours, HCG in 34%, ACT in 78%, AAT in 42%, and LYS in 71%. Comparing the staining patterns of the antigens and the intensity of staining some differences were notable. Except for signet-ring cell carcinomas, all of which were intensively positive, CEA expression decreased significantly with loss of differentiation. This observation was not seen with the other marker substances. None of the tested markers was characteristic for one particular histological type, nor could they be correlated with the tumour stage or grade. The marker positivity of CEA, ACT and LYS was not related to survival time. For HCG only, a correlation between tissue expression and a restricted survival time was established. Patients with AAT positive carcinomas had a significantly better survival probability.     

NG-硝基-L-精氨酸对大鼠内毒素性肺线粒体损伤的影响

目的： 观察非选择性一氧化氮合酶(NOS)抑制剂NG-硝基-L-精氨酸(L-NA)对急性肺损伤大鼠肺线粒体功能的影响，并探讨其改善急性肺损伤的作用机制。方法: 将SD大鼠随机分为空白对照组、急性肺损伤组、L-NA治疗组，采用舌静脉注射脂多糖(LPS)复制大鼠急性肺损伤模型，于大鼠急性肺损伤3h后给L-NA治疗3h，断头放血处死大鼠，迅速取出肺脏，匀浆器混匀后，低温差速离心法提取肺线粒体，测定线粒体总ATP酶、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）、总一氧化氮合酶（T-NOS）、诱生型一氧化氮合酶（iNOS）、结构型一氧化氮合酶（cNOS）的活性，以及线粒体肿胀度、膜流动性和线粒体一氧化氮（NO）、丙二醛（MDA）含量；电镜观察大鼠肺线粒体超微结构的改变及治疗药对此改变的影响。结果: 在大鼠内毒素性急性肺损伤后，肺脏组织中线粒体表现为肿胀、膜流动性降低，线粒体中的T-NOS和iNOS活性显著升高，线粒体NO生成明显增加，而cNOS活性无明显变化；线粒体总ATP酶、SOD、GSH-Px活性均明显下降，线粒体MDA含量明显升高。急性肺损伤3h给予L-NA治疗3h,与急性肺损伤组相比，一氧化氮合酶活性有所改变，NO生成显著下降，总ATP酶、SOD、GSH-Px活性均显著升高，MDA含量下降。电镜结果显示内毒素性急性肺损伤后肺脏组织细胞水肿，线粒体肿胀、嵴断裂、溶解、消失；L-NA能改善内毒素性急性肺损伤引起的细胞水肿、线粒体肿胀和空泡化。结论: L-NA能明显抑制急性肺损伤后线粒体一氧化氮合酶活性，减少NO生成，改善线粒体能量供应，增加线粒体抗氧化作用，从而减轻急性肺损伤。     

食管癌细胞膜提取物体外诱导胚胎胸腺细胞抗癌效应的研究

本文探讨增强胚胎胸腺细胞抗肿瘤效应的方法。采用食管癌细胞膜抗原体外诱导培养的胚胎胸腺细胞 ;用3 H TdR掺入法检测其对食管癌细胞的细胞毒效应 ;用SP 免疫组化法检测其经诱导后细胞表面抗原的变化。结果经食管癌细胞膜抗原诱导 3～ 9d的胚胎胸腺细胞对食管癌细胞的杀伤率明显大于未经诱导的胚胎胸腺细胞 ;胚胎胸腺细胞经诱导后CD4 + /CD8+ 细胞无明显变化 ,但诱导后出现少量CD5 6细胞。食管癌细胞膜抗原体外诱导胚胎胸腺细胞可增强其对食管癌细胞的细胞毒作用     

心包内处理肺静脉根部或切除部分左房在晚期肺癌手术中的应用

目的:探讨切开心包处理肺静脉或切除部分左心房对提高晚期肺癌患者的外科手术切除率及提高手术疗效的作用.方法:对21例晚期肺癌患者施行肺叶或全肺切除时,在心包内处理肺静脉或切除部分左心房.其中左肺下叶切除6例、左全肺切除4例、右肺中下叶切除6例、右肺下叶切除3例、右全肺切除2例.结果:21例均手术顺利;术后并发心律失常2例,肺炎2例,均治愈.本组1年生存率61.9%(13/21)、3年生存率38.1%(8/21),其中2例生存＞5 a.结论:晚期肺癌累及肺静脉根部或左心房时,通过切开心包处理肺静脉或同时切除部分左心房可提高肿瘤的根治率.     

Chemokine receptor CXCR4 expression in breast cancer as a potential predictive marker of isolated tumor cells in bone marrow

Interactions between the CXCR4 chemokine receptor in breast cancer cells and the ligand CXCL12/SDF-1α are thought to play an important role in breast cancer metastases. In this pilot study, CXCR4 expression along with other biomarkers including HER2-neu and EGFR, were measured in primary tumor samples of patients with operable breast cancer to test whether any of these biomarkers alone and in combination could indicate breast cancer with high likelihood of metastasizing to bone marrow. Cytokeratin (CK) positive cells in bone marrow were identified by flow-cytometry following enrichment with CK 7/8 antibody-coupled magnetic beads. Primary tumors (n = 18) were stained with specific antibodies for CXCR4, HER2-neu, EGFR, and PCNA using an indirect avidin–biotin horseradish peroxidase method. The majority of the patients had T2/T3 tumors (72%), or lymph node involvement (67%) as pathologic characteristics that were more indicative of high-risk breast cancer. High CXCR4 cytoplasmic expression was found in 7 of 18 patients (39%), whereas 6 of 18 patients (33%) were found to have CK positivity in bone marrow. The median number of CK⁺ cells was 236 (range, 20–847) per 5 × 10⁴ enriched BM cells. The presence of CK⁺ cells in bone marrow was found to be associated with increased expression of CXCR4 alone or in addition to EGFR and/or HER2-neu expression (P = 0.013, P = 0.005, and P = 0.025, respectively) in primary tumors. Furthermore, three patients with high CK positivity (>236 CK⁺ per 5 × 10⁴ enriched bone marrow cells) in bone marrow exclusively expressed high levels of CXCR4 with EGFR/HER2-neu (P = 0.001). Our data suggest that high CXCR4 expression in breast cancer may be a potential marker in predicting isolated tumor cells in bone marrow. CXCR4 coexpression with EGFR/HER2-neu might further predict a particular subset of patients with high CK positivity in bone marrow.