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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability of monoclonal antibody (MAb 108), an immunoglobulin G (IgG)2a against the epidermal growth factor receptor (EGF-R), to interact with lung cancer cell lines was investigated. 125I-EGF bound with high affinity to non-small-cell lung cancer (NSCLC) cells, and MAb 108 inhibited specific binding of nine NSCLC cell lines in a dose-dependent manner (IC50 = 0.3-3 micrograms per ml). 125I-MAb 108 bound with high affinity (kd = 2 nM) to a single class of sites (Bmax = 70,000 per cell) using NSCLC neuroendocrine cell line NCI-H460. Specific 125I-MAb 108 binding was inhibited with high affinity by MAb 108 but not by a control antibody IgG using large-cell carcinoma cell line NCI-H1299. 125I-MAb 108 binding was not internalized at 37 degrees C using NSCLC neuroendocrine cell line NCI-H460 and adenocarcinoma cell line NCI-H23. Also, 1 microgram per ml of MAb 108 but not of a control IgG inhibited the clonal growth of NCI-H23 and squamous cell carcinoma cell line NCI-H157 in vitro. Also, MAb 108 inhibited xenograft formation of cell lines NCI-H460, NCI-H157, and NCI-H727 in nude mice in vivo. After a palpable tumor had formed using NCI-H460 cells, injection of 100 micrograms of MAb 108 (intraperitoneally three times weekly) inhibited xenograft volume in nude mice by approximately 50%. These data suggest that MAb 108 may interact with EGF receptors on lung cancer cell lines and inhibit NSCLC proliferation.
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PMID:Epidermal growth factor receptor monoclonal antibodies inhibit the growth of lung cancer cell lines. 132 29

We describe studies defining several molecular events in human non-small-cell lung cancer (NSCLC). These include increased growth factor and growth factor receptor expression and oncogene alterations. The epidermal growth factor receptor (EGFR) and erbB2 are expressed by NSCLC cells. Transforming growth factor-alpha (TGF-alpha) is produced by NSCLC and may mediate autocrine growth stimulation. Specific inhibition of K-ras oncogene expression by an antisense K-ras construct reduces the growth rate and tumorigenicity of NSCLC cells. Studies with antisense p53 in NSCLC with a homozygous p53 mutation suggest that the presence of the mutant form contributes to the transformed state.
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PMID:Molecular approaches to prevention and therapy of aerodigestive tract cancers. 132 31

The c-erbB-2/neu gene encodes a transmembrane protein of 185 kDa (p185) with tyrosine kinase activity and extensive sequence homology to epidermal growth factor receptor. Amplification and overexpression of the c-erbB-2/neu gene has been shown in certain human tumors and is postulated to be important in human carcinogenesis. High levels of expression of the c-erbB-2/neu gene have been reported in non-small-cell lung cancer (NSCLC) cell lines and primary tumors from the United States. Since geographical and cultural factors may contribute to the development of certain types of cancer, we examined p185 examined p185 expression in 120 tumors from Chinese patients with lung cancers of different cell types and used immunohistochemical staining to determine the extent and general significance of p185 expression in human primary lung cancer. Our results demonstrate that 58.8% of the NSCLCs expressed p185 and that expression of p185 was observed only in NSCLC and not in small-cell lung cancers. Thirty-three of 41 adenocarcinomas and 24 of 55 squamous cell carcinomas among the NSCLCs examined were found to express p185 at levels different from those of normal lung. For the squamous cell carcinomas, p185 expression was correlated with lymph node metastasis (P less than 0.01), but for the adenocarcinomas, it was not (P greater than 0.05). In addition, expression of p185 in NSCLC was significantly more frequent in patients in advanced clinical stages. Our findings indicate that p185 expression is a frequent event and a general phenomenon in NSCLC and is correlated with poor clinical prognostic indicators, suggesting that expression of p185 may be of potential prognostic importance in NSCLC.
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PMID:Overexpression of the c-erbB-2/neu-encoded p185 protein in primary lung cancer. 135 Jan 98

A cytogenetic analysis was performed on direct preparations and short-term cell cultures of lung tumor and normal bronchial epithelium of 19 patients carrying either a first or a second primary lung cancer. In 9 tumors (6 squamous cell carcinomas, 1 adenocarcinoma, 1 mucoepidermoid carcinoma, and 1 small cell lung carcinoma) successfully analyzed, pseudodiploid and hyperdiploid karyotypes were observed with a heterogeneous pattern of chromosome abnormalities but with a consistent involvement (5 cases) of the short or the long arm of chromosome 3. The normal bronchial epithelial cells had a normal karyotype in 11 patients, whereas in 6 patients clonal and nonclonal chromosomal abnormalities were observed. Involvement of chromosome 7 was present in 4 cases. In addition, overexpression of the growth factor receptors, epidermal growth factor receptor and HER-2/neu, was found in 9 of 18 tumors and in 6 of 13 bronchial epithelium samples. These findings suggest that early genetic lesions could be present in the normal bronchial epithelial cells that are the target of further complex and multiple genetic changes occurring during the pathogenesis of lung cancer.
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PMID:Cytogenetic abnormalities and overexpression of receptors for growth factors in normal bronchial epithelium and tumor samples of lung cancer patients. 167 Sep 93

Class-switched monoclonal antibody SV2-61r recognized the extracellular domain of c-erbB-2 protooncogene products separate from the epidermal growth factor receptor. We studied the potential of SV2-61r for evaluating the amplification of c-erbB-2 protooncogene on cancer cells, which has been reported to have prognostic value in adenocarcinoma patients. Radiolabeled SV2-61r specifically bound to various adenocarcinoma cells in addition to c-erbB-2-transfected NIH-3T3 cells (A4) with the affinity constant of 4.4 x 10(8) M-1. SV2-61r injected i.v. localized well to A4 cells xenografted in nude mice. Tumor uptake and localization index of radioiodinated SV2-61r were lower than those of 111In-labeled SV2-61r, probably due to the internalization and dehalogenation of formed antibody-antigen complexes. Biodistribution and specificity of targeting were assessed by comparison among three cells, A4, lung cancer SBC-3 (c-erbB-2 weakly positive) and B-lymphoblastoid Manca cells (c-erbB-2 negative). Tumor:blood ratios, obtained 48 h after injection, were 5.63, 1.45, and 0.68, respectively, indicating the potential of 111In-labeled SV2-61r for evaluating the amplification of c-erbB-2 protooncogene on cancer cells. Because of its close relationship with carcinogenesis and the uniform expression, c-erbB-2 protooncogene products seem to be the optimal target of imaging and therapy of adenocarcinoma patients.
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PMID:Scintigraphic detection of overexpressed c-erbB-2 protooncogene products by a class-switched murine anti-c-erbB-2 protein monoclonal antibody. 167 Oct 1

The content of the epidermal growth factor receptor (EGFr) and its relation to tissue CEA and NSE were examined in 22 intracranial neoplasms (18 primary intracranial tumors and 4 metastasis from lung cancer). The EGFr was measured by a radioligand assay on crude plasma membrane preparations. The tissue tumor markers (CEA and NSE) were measured on the high speed supernatant of tissue homogenates. In the primary intracranial tumors the EGFr was positive in 68%, CEA in 43% and NSE in 47% of all cases examined. As it concerns the metastasis from lung cancer the positivity was 75% for EGFr while for CEA and NSE was 50% and 32% respectively. These results suggest that the routine measurement of EGFr, associated with the determinations of tissue CEA and NSE could provide useful information on the type of the intracranial neoplasms.
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PMID:Epidermal growth factor receptor and tissue tumor markers in human intracranial neoplasms. 196 99

With the development of molecular biological techniques the search for genetic alterations in cancer cells has resulted in the beginning of a molecular description of cellular transformation. Most of these genetic changes occur in genes which have a role in the control of cellular growth and development, the proto oncogenes. In the last decade, it has become clear that the myc and ras oncogene families are important in the carcinogenesis of human lung cancers. The myc oncogenes are usually found to be altered in small cell lung cancer (SCLC), and these alterations appear to correlate with rapid growth and progression. Mutations in the Kras gene are specific for adenocarcinoma, a subclass of non small cell lung cancer (NSCLC). Kras gene mutations are closely associated with tobacco smoking, since all were found in adenocarcinomas from patients with a history of smoking. The erbB oncogene, which encodes the epidermal growth factor receptor, is often highly expressed in epidermoid carcinomas. The roles for other oncogenes, such as raf or myb, as well as those of "suppressor" genes remain to be investigated, but may be of paramount importance. The study of alterations in proto oncogenes may aid in the (sub)classification and diagnosis of lung cancer, and may yield useful prognostic information in the near future.
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PMID:The molecular genetics of human lung cancer. 260 91

Analysis based on the complement-dependent cytotoxicity (CDC) assays using syngeneic antiserum against a Rous sarcoma virus(RSV)-induced mouse tumor(CSA1M) showed that a cross-reactive antigen with a common tumor-associated cell surface antigen(TASA) of RSV-induced mouse tumors was shared with two human tumors A431 and MDA-468 overexpressing epidermal growth factor receptor(EGFR). The TASA, however, was not expressed on four human choriocarcinomas, a human lung cancer A2182, and human embryo fibroblasts HFF. Immunofluorescent studies demonstrated that A431 does not express a src gene product detected by anti-pp60src monoclonal antibody(MoAb). Two variant clones derived from A431 reducing number of ERFR (cl-15 and cl-16) have almost same growth rate and expression of transferrin receptor(Tf-R) in comparison with parental A431 cells. These clones, however, decreased the expression of TASA. Furthermore, CDC assays and enzyme-linked immunosorbent assay(ELISA) revealed that A431 reduced the expression of the TASA by pretreatment of EGF, but not with insulin. All these findings indicate a close association between a cross reactive antigen with the TASA of RSV-induced tumors and EGFR.
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PMID:[Expression of a cross-reactive antigen on the surface of human epidermoid carcinomas overproducing EGF-receptor shared with RSV-induced tumors]. 282 11

We have determined the average gene copy numbers (AGCN) of the erbB-1 gene, encoding the epidermal growth factor receptor (EGF-R), the erbB-2 and the erbB-3 genes in breast, ovarian, oral, and lung cancer tissue by using double-differential PCR (ddPCR). The ddPCR method comprises the co-amplification of the single-copy gene HBB, the erbB-1, erbB-2 and erbB-3 oncogenes and the second single-copy reference gene SOD2 under equal reaction conditions. In a retrospective study the AGCN of the erbB genes and the time up to the appearance of metastases were subjected to life-table analysis in 128 women with primary breast cancer. Patients whose breast cancer tissue showed an AGCN for erbB-1 of less than 0.4 and greater then 1.6, as expected from the literature, for erbB-2 of greater than 2.0 and for erbB-3 of less than 1.75 had decreased disease-free survival (DFS). The quotient of erbB-1 and erbB-2 AGCN was the most significant in multivariate Cox analysis followed by nodal status and progesterone receptor status. In extensive studies a similar association between erbB AGCN and metastasis was seen in ovarian cancer and oral cancer, though erbB oncogene aberrations in those entities were not as frequent as in breast cancer. The AGCN of erbB oncogenes may not be of prognostic value in untreated lung cancer patients.
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PMID:Prognostic relevance of aberrations in the erbB oncogenes from breast, ovarian, oral and lung cancers: double-differential polymerase chain reaction (ddPCR) for clinical diagnosis. 760 71

Gene expression of growth factors including epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), epidermal growth factor receptor (EGFR), oncogenes such as c-myc, N-ras, c-erbB2 and tumor suppressor gene P53 were studied in 4 human lung cancer cell lines using Northern blot technique. Among these cell lines were 2 adenocarcinoma cell lines, one large cell carcinoma cell line and one small cell carcinoma cell line. Expression of EGF and TGF alpha mRNAs were found in all 4 cell lines and EFGR mRNA was seen in 3 out of 4 cell lines. Among these cell lines, 2 cell lines with weaker expression of EGF and TGF alpha, expressed c-myc mRNA. Another 2 cell lines had no c-myc but expressed large amounts of EGF and TGF alpha mRNA. No expression of N-ras, c-erbB2 and p53 were found in these cell lines. The results indicate the presence of autocrine loop of growth factors in these cancer cells. The autostimulation of growth factors may be the main cause for the uncontrolled growth of cancer cells. After treating the cancer cells with EGF, anti-EGF and anti-EGFR antibodies, EGF was found to exert a mild stimulating effect on the growth of one cell line, but no effect on the other cell lines. Anti-EGF and anti-EGFR antibodies inhibited the cell growth on all cell lines. These results provided further evidence for the presence of autocrine loop of growth factors in these lung cancer cell lines.
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PMID:[Gene expression of growth factors, growth factor receptor and oncogenes in human lung cancer cell lines]. 778 Nov 11


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