Circulating antibodies against c-myc oncogene product in sera of colorectal cancer patients

We developed a Western blot assay using purified human c-myc protein expressed in E. coli in order to look for circulating anti-c-myc antibodies in human sera. The presence of IgG antibodies against c-myc was observed in 25 out of 44 sera from patients with colorectal cancer diagnosed and treated at the Hǒpital Curie in Paris, compared to the sera of 46 normal donors of which only 8 samples were positive (p = 0.001).     

Aflatoxins in sera from patients with lung cancer

Sera from patients with lung cancer and from healthy donors were screened for the presence of aflatoxins. Significant differences in levels of aflatoxins between the two groups were found. Only 1 of the neoplastic patients with aflatoxins in the serum was a smoker. However the percentage of sera from lung cancer containing aflatoxins is not significant enough to provide evidence for a casual relationship between aflatoxins exposure and development of lung cancer in humans.     

Detection of tumor-specific autoantibodies in sera of patients with lung cancer

The presence of autoantibodies (AAs) in sera from two pulmonary carcinoma patients, adenocarcinoma (AD) and small cell carcinoma (SCLC) was screened by immunoblotting using cell lysate of four cell lines (LCN1, large cell neuroendocrine carcinoma (LCNEC); N231, SCLC; A549, AD; RERF-LC-AI, squamous cell carcinoma (SCC)). To identify the antigens recognized by AAs, two-dimensional gel electrophoresis was immunoblotted and target spots were cut out from the membrane and gel. After trypsin digestion, the proteins were analyzed by mass-spectrometry using a liquid chromatography-tandem mass spectrometer. By this method, cytokeratin18 (CK18) and villin1 were identified with AAs in sera from patients with AD and SCLC, respectively. Thus, the expressions of CK18 and villin1 were further immunohistochemically studied on 124 formalin-fixed and paraffin-embedded pulmonary carcinomas of various histologic types (44 AD, 27 SCC, 29 SCLC, and 34 LCNEC) using commercially available CK18 and villin1 antibodies. Positive CK18 immunostaining was observed in almost all cases with staining intensities significantly higher in AD and LCNEC than in SCC and SCLC. Villin1 was detected in 17/44 (38.6%) of AD and 21/34 (61.8%) of LCNEC, respectively, while in only one each of SCLC and SCC. Thus, villin1 and CK18 may be useful markers to distinguish LCNEC/AD from SCLC/SCC, and the present method might be useful to identify specific tumor-associated molecules in sera from pulmonary carcinoma patients with different histologic types.     

Anti-phosphoinositide auto-antibodies in sera of cancer patients: isotypic and immunochemical characterization.

High levels of circulating anti-phosphatidylinositol (PtdIns) auto-antibodies (auto-Ab) have been previously found in sera of patients with malignant tumors. Using our ELISA test, a high statistical level of immunological binding directed against PtdIns was found in a large series of sera from patients with proliferative pathologies. In contrast to tumor markers, anti-PtdIns auto-Ab did not vary whatever the histological grades, TMN classification and patient's age. These anti-PtdIns auto-Ab were immunoglobulins (Ig) of G class. Their specificity was evaluated by competition experiments in ELISA and found to be rather high. An increase of these circulating auto-Ab reflected possible disturbances in PtdIns turnover and appearance of endogenous neo-antigen with PtdIns structure.     

Detection of antibodies against the cellular protein p53 in sera from patients with breast cancer

Antibodies reacting with the host protein p53 were found in the sera of patients with primary or secondary carcinoma of the breast. Fourteen out of the 155 sera from breast cancer patients tested were positive for anti-p53 antibodies (9%) and no positives were detected among 164 control sera from normal women tested. The locations of the first metastasis in patients with positive sera were unusual, with more lung metastases and fewer bone metastases than expected. The detection of anti-p53 antibodies indicates that p53 is altered in amount, type or presentation in breast tumors so that it becomes immunogenic.     

血清中P53蛋白及其抗体的检测对肺癌诊断意义的研究

目的探讨血清中P53基因的表达产物P53蛋白和抗P53蛋白抗体的检测对肺癌患者诊断的应用价值。方法应用Westernblot方法．对28例肺癌患者和18例对照的血清中的P53蛋白和抗P53蛋白抗体进行检测。结果分别在7.14％（2／28）和14.29％（4／28）的肺癌患者的血清中检测到P53蛋白和抗P53蛋白抗体,而良性肺疾病和健康对照组血清中求检测到这两种蛋白抗体。结论检测患者血清中的P53蛋白和抗P53蛋白抗体对肺癌患者具有一定的诊断价值。     

Detection of circulating antibodies against c-myc protein in cancer patient sera

We have partially purified an archaebacterial protein of 84 kD which shares common epitopes with the human c-myc protein as shown by its cross-reactivity with a commercialized anti-human c-myc antiserum. An antiserum raised against the 84 kD protein recognizes a 60 kD protein from HL-60 nuclei. This protein is also recognized by the anti-human c-myc antiserum. Using this archaebacterial protein as antigen for Western blot analysis, we found that the human c-myc oncogene product could be immunogenic and that it is possible, in some spontaneously occurring human tumours, to detect antibodies against the c-myc gene product in the serum of cancer patients.     

Studies of the L-myc DNA polymorphism and relation to metastasis in Norwegian lung cancer patients

We studied 83 lung cancer patients and 129 controls for the EcoRI polymorphism of the L-myc gene. No association was found between the L-myc RFLP and increased risk of metastasis, either to lymph nodes or metastasis to other organs. There was no difference in survival time between the three different genotypes. The S-allele of the L-myc RFLP has been correlated to increased metastasis in lung cancer. We found no tendency towards a higher frequency of this allele in the cohort of patients with positive family history compared to the patients with no known first degree relatives with cancer. A higher frequency of the S-allele in the adenocarcinomas compared to other histological groups was found, although this difference was not statistically significant. No difference in the gene frequency of the L-myc RFLP was found between the lung cancer patients and the normal controls. These results are in contrast with a previous report. Possible explanations for the discrepancies are discussed.     

Forssman-like antibody levels in sera of patients with lung cancer.

Sera of normal individuals or patients with lung cancer were assayed for Forssman-like antibody by a quantitative and specific method using ethylenediaminetetraacetate-containing buffer to inactivate complement in the test serum. It was shown that although Forssman-like antibody levels were distributed widely, (a) the levels of young (20 to 45 years of age) normal subjects of Blood Groups A and AB were lower than those of Blood Groups O and B, (b) the levels of old (60 to 80 years of age) normal subjects were lower than those of young normal subjects of Blood Groups O and B, and (c) the levels of old lung cancer patients were lower when compared to age-matched normal individuals of their blood group.     

L-myc蛋白在小细胞肺癌组织中的表达及临床意义

目的:探讨L-myc蛋白在小细胞肺癌组织中的表达及临床意义。方法:应用免疫组化法检测142例小细胞肺癌组织标本中L-myc蛋白的表达情况,统计患者的临床资料,分析L-myc蛋白表达与小细胞肺癌患者临床病理因素的相关性,并进行预后关系分析。结果:小细胞肺癌组织中L-myc蛋白阳性染色位于细胞的胞浆和胞核中。L-myc蛋白在小细胞肺癌组织中的阳性表达率明显高于正常肺组织（25.4% vs 5.0%,P=0.043）,其表达与小细胞肺癌的临床分期、远处转移明显相关（P=0.040、P=0.037）。L-myc蛋白表达阳性患者的总生存期短于表达阴性的患者（P=0.031）。多因素分析表明,小细胞肺癌患者的独立预后因素有临床分期、L-myc蛋白的表达（P＜0.05）。结论:L-myc蛋白在小细胞肺癌组织中高表达,其表达与小细胞肺癌的发生发展、临床分期及预后关系密切,可能成为治疗小细胞肺癌的一个很有前途的靶点。     

Rearrangement and co-amplification of L-myc and rlf in primary lung cancer.

We have recently characterized a gene fusion and chimeric protein product formed by L-myc and part of a novel gene named rlf in two small-cell lung cancer (SCLC) cell lines. The rlf-L-myc fusion gene is formed by intrachromosomal rearrangements placing the regulatory region and (at least) the first exon of rlf upstream of the L-myc gene. In the characterized cases the fusion gene has also been involved in DNA amplification. Here we report on a similar in vivo rearrangement involving rlf and L-myc in a primary SCLC tumor. In addition, we have found co-amplification of L-myc and rlf without visible rearrangements in either gene in three other SCLC tumors, confirming the physical linkage of these loci.     

痰液K-ras P53基因检测对肺癌的辅助诊断价值

目的；76例疑为肺癌病人痰液中P53和K-ras最常见突变位点进行了检测，以了解分子生物学检测方法是否对肺癌的诊断具有辅助诊断价值。方法；痰液处理方法：痰液0．5毫升加入痰处理液制备细胞沉淀液，酚氯仿提取DNA；SSCP-PCR银染和RFLP-PCR方法对痰液中P53、K-ras突变情况进行检测。结果：在确诊的76例肺癌病人中，P53突变率为40．8％，K-ras突变率为25%，突变与肺癌类型，疾病分期未见明显相关．其中有29例病人痰液普通脱落细胞学检测阴性，痰液P53或K-ras突变阳性，最后经，奸支镜刷检、活检部分经过手术证实为肺癌，有12例经手术证实为1-1期的相对早期的肺癌。结论；痰液SSCP-PCR、RELP-PCR方法检测癌基因突变具有简便、实用、准确、可行的特点。对部分疑为肺癌而痰液脱落细胞学检测阴性的病人具有一定的辅助诊断价值。值得临床进一步开展深入的研究。     

肺癌C-myc基因扩增的临床意义

目的与方法:应用聚合酶链反应(PCR)技术对56例肺癌石蜡包埋标本进行C-myc基因的研究.结果:C-myc基因扩增与组织学类型、临床病理分期及淋巴结转移有密切关系(P<0.05),C-myc基因扩增者,分化程度较低,临床病理分期较晚,淋巴结转移多.同时还发现C-myc基因扩增与预后有明显关系(P<0.05),C-myc基因扩增者预后较差.结论:提示C-myc基因可以作为判断肺癌预后的检测指标之一.     

Localisation of lung cancer by a radiolabelled monoclonal antibody against the c-myc oncogene product

A set of mouse nonoclonal antibodies against the c-myc oncogene product, a 62,000 dalton nuclear binding protein involved in cell cycle control, has been constructed by immunisation with synthetic peptide fragments. One such antibody, CT14, was radiolabelled with 131I and administered to 20 patients with different malignant diseases. Good tumour localisation was observed in 12 out of 14 patients with primary bronchial carcinoma but not in patients with pulmonary metastases from primary tumours elsewhere. Successfully localised tumours were all 3 cm or more in diameter. Monoclonal antibodies against oncogene products may provide novel selective tools for the diagnosis and therapy of cancer.     

Detection of mammaglobin in the sera of patients with breast cancer.

Current procedures for the diagnosis of breast cancer are cumbersome and invasive, making detection of this disease difficult. A rapid screening test for early detection of breast cancer would allow for better management of this deadly disease. In this report, we show that, with the exception of the skin, mammaglobin mRNA is specifically expressed in mammary tissue and commonly overexpressed in breast cancer. Mammaglobin is not expressed in other types of cancer including colon, lung, ovarian, and prostate cancer. Breast-specific expression of mammaglobin protein was shown using immunohistochemical methods. Mammaglobin is secreted from both established breast cancer cell lines and primary breast carcinoma cells cultured in vitro. Using a monoclonal antibody-based assay for monitoring the presence of mammaglobin in serum, elevated levels of mammaglobin were detected in sera of patients with breast cancer, but not in healthy women. Thus, mammaglobin, which is overexpressed and secreted from breast carcinoma cells, is detectable in sera of patients with breast cancer and may provide a rapid screening test for the diagnosis and management of breast cancer.