Immunity to Oncogenic Proteins

Cheever, Martin A.; Disis, Mary L.; Bernhard, Helga; Gralow, Julie R.; Hand, Susan L.; Huseby, Eric S.; Qin, Hui; Takahashi, Mutsuo; Chen, Wei

doi:10.1111/j.1600-065x.1995.tb00076.x

Cited by 155 publications

(68 citation statements)

References 55 publications

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“…Overexpression of translation initiation factor (eIF)-4 gamma, as a consequence of gene amplification has been shown to correlate with an immune response in patients with squamous cell lung carcinoma (Brass et al, 1999). Similarly a serologic response to HER2/neu, an oncogene amplified in certain cancers strongly supports the notion that overexpression is sufficient to initiate a humoral immune response in some individuals (Cheever et al, 1995). Such is probably the case for p53 antibodies generated in MM patients, although the p53 status of any of the patients in this study is not known.…”

Section: Discussionsupporting

confidence: 79%

p53 autoantibodies in patients with malignant mesothelioma: stability through disease progression

et al. 2001

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Malignant mesothelioma (MM) generally occurs as a pleural tumour, related to the inhalation of asbestos fibres. It is highly aggressive and largely unresponsive to treatment. The incidence of MM is particularly high in Western Australia because of the extensive blue asbestos mining operations that occurred in the north of the state until 1966. MM is unusual in that mutations in the tumour suppressor gene p53 are rarely observed, whilst over-expression of p53 protein is common. As the level of antibodies directed against p53 is thought to be of prognostic value in some cancers and as MM is known to be immunogenic, we studied a cohort of Western Australian patients to determine the prevalence of anti-p53 antibodies and their value as diagnostic markers or prognostic indicators. 6/88 (7%) of patients had high titres (>2 SD above the mean of controls) of anti-p53 antibodies. There was no correlation between antibody titre and survival. Although 3/38 (8%) of sera obtained from patients exposed to asbestos but prior to a diagnosis of MM contained antibodies, the same proportion of sera obtained from patients exposed to asbestos but who remained disease free also contained antibodies (2/40; 8%). Sera collected sequentially demonstrated a profound temporal stability in the titre of anti-p53 antibodies in patients with MM throughout the course of their illness. These results show that anti-p53 antibodies are observed only at a low frequency in the sera of MM patients and where they do occur, their elicitation is an early event that may be unrelated to antigen load. The occurrence of anti-p53 antibodies does not serve as either a useful prognostic or diagnostic indicator in MM. © 2001 Cancer Research Campaign http://www.bjcancer.com

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Section: Discussionsupporting

confidence: 79%

p53 autoantibodies in patients with malignant mesothelioma: stability through disease progression

et al. 2001

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“…Autoantibodies to p53 in cancer were first reported in 1982 [7] and since then there have been numerous reports confirming and extending this finding [reviewed in 8]. The mechanism underlying the production of such autoantibodies are not completely understood but the available data show that many of the target antigens are cellular proteins whose aberrant regulation could lead to tumorigenesis, such as p53 [8], HER-2/neu and ras [9,10], or are proteins whose dysregulation could have tumorigenic potential including mRNA binding proteins such as p62 [5] and cell-cycle control proteins such as cyclin B1 [11,12]. In the case of p62 which is primarily expressed in fetal tissues and is absent in adult tissues, immunogenicity appears to be related to abnormal expression of p62 in tumor cells [13].…”

Section: Introductionmentioning

confidence: 99%

Antibody detection using tumor-associated antigen mini-array in immunodiagnosing human hepatocellular carcinoma

Zhang

Megliorino

Peng

et al. 2007

Journal of Hepatology

113

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Background/Aims-Previous studies have demonstrated that during transition from chronic liver disease to hepatocellular carcinoma (HCC), autoantibodies can appear which are not detected in the prior pre-malignant conditions. These antibody responses may be stimulated by cellular proteins involved in carcinogenesis. This study determines the prevalence of antibodies to a selected panel of eight tumor-associated antigens (TAAs) in sera from patients with chronic hepatitis, liver cirrhosis and HCC, and considers the possibility and usefulness of antibodies to such a panel of TAAs in differentiating between these conditions. The panel of eight TAAs includes Imp1, p62, Koc, p53, cmyc, cyclin B1, survivin and p16 full-length recombinant proteins.Methods-Enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies against eight selected TAAs in 30 sera from chronic hepatitis, 30 from liver cirrhosis, and 142 from HCC. Positive results were also confirmed by slot blot, Western blotting and immunoprecipitation assay.Results-Antibody frequency to any individual TAA in HCC varied from 9.9%-21.8%. With the successive addition of TAAs to a final total of eight antigens, there was a stepwise increase of positive antibody reactions reaching a frequency of 59.8% with whole cohort of HCC patients. This was significantly higher than the frequency of antibodies in chronic hepatitis (20%), liver cirrhosis (30%) and normal individuals (12.2%).Conclusions-This study demonstrates that malignant transition to HCC is associated with increased autoantibody responses to certain cellular proteins which might have a role in tumorigenesis, and shows that a mini-array of eight TAAs enhanced antibody detection for diagnosis of HCC. More studies in patients with HCC and precursor conditions such as chronic hepatitis, alcoholic hepatitis and liver cirrhosis using enlarged TAA mini-array panels might further improve the sensitivity and specificity of this mode of cancer immunodiagnosis. Its additional usefulness might be in the early detection of cancer in some patients with predisposing conditions.

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“…MUC-1 is another gene that is up regulated about 10-fold in 90% of breast tumors (Hadden, 1999;McKenzie and Xing, 1990). Each of these proteins has become the target for novel immunotherapy approaches in the treatment of breast cancer (Cheever et al, 1995;Ozturk et al, 1992;Apostolopoulos et al, 1996). It should be noted, however, that all genes mentioned above show expression in some normal tissues that could cause toxicity and non-speci®city when used as therapeutic and diagnostic agents.…”

Section: Introductionmentioning

confidence: 99%

Discovery of differentially expressed genes in human breast cancer using subtracted cDNA libraries and cDNA microarrays

et al. 2002

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Identifying novel and known genes that are di erentially expressed in breast cancer has important implications in understanding the biology of breast tumorigenesis and developing new diagnostic and therapeutic agents. In this study we have combined two powerful technologies, PCRbased cDNA subtraction and cDNA microarray, as a high throughput methodology designed to identify cDNA clones that are breast tumor-and tissue-speci®c and are overexpressed in breast tumors. Approximately 2000 cDNA clones generated from the subtracted breast tumor library were arrayed on the microarray chips. The arrayed target cDNAs were then hybridized with 30 pairs of¯uorescent-labeled cDNA probes generated from breast tumors and normal tissues to determine the tissue distribution and tumor speci®city. cDNA clones showing overexpression in breast tumors by microarray were further analysed by DNA sequencing, GenBank and EST database searches, and quantitative real time PCR. We identi®ed several known genes, including mammaglobin, cytokeratin 19, ®bronectin, and hair-speci®c type II keratin, which have previously been shown to be overexpressed in breast tumors and may play an important role in the malignance of breast. We also discovered B726P which appears to be an isoform of NY-BR-1, a breast tissue-speci®c gene. Two additional clones discovered, B709P and GABA A receptor p subunit, were not previously described for their overexpression pro®le in breast tumors. Thus, combining PCRbased cDNA subtraction and cDNA microarray allowed for an e cient way to identify and validate genes with elevated mRNA expression levels in breast cancer that may potentially be involved in breast cancer progression. These di erentially expressed genes may be of potential utility as therapeutic and diagnostic targets for breast cancer.

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Immunity to Oncogenic Proteins

Cited by 155 publications

References 55 publications

p53 autoantibodies in patients with malignant mesothelioma: stability through disease progression

p53 autoantibodies in patients with malignant mesothelioma: stability through disease progression

Antibody detection using tumor-associated antigen mini-array in immunodiagnosing human hepatocellular carcinoma

Discovery of differentially expressed genes in human breast cancer using subtracted cDNA libraries and cDNA microarrays

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