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

Formation of metastasis is a multistep process involving attachment to the basement membrane, local proteolysis and migration into surrounding tissues, lymph or bloodstream. In the present study, we have analysed the correlation between in vitro invasion and presence of the epidermal growth factor receptor (EGFR) in a panel of 21 small-cell lung cancer (SCLC) cell lines. We have previously reported that ten of these cell lines expressed EGFR protein detected by radioreceptor and affinity labelling assays. In 11 small-cell lung cancer (SCLC) cell lines, EGFR mRNA was detected by Northern blot analysis. In vitro invasion in a Boyden chamber assay was found in all EGFR-positive cell lines, whereas no invasion was detected in the EGFR-negative cell lines. Quantification of the in vitro invasion in 12 selected SCLC cell lines demonstrated that, in the EGFR-positive cell lines, between 5% and 16% of the cells added to the upper chamber were able to traverse the Matrigel membrane. Expression of several matrix metalloproteases (MMP), of tissue inhibitor of MMP (TIMP) and of cathepsin B was evaluated by immunoprecipitation, Western blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR). However, in vitro invasive SCLC cell lines could not be distinguished from non-invasive cell lines based on the expression pattern of these molecules. In six SCLC cell lines, in vitro invasion was also determined in the presence of the EGFR-neutralizing monoclonal antibody mAb528. The addition of this antibody resulted in a significant reduction of the in vitro invasion in three selected EGFR-positive cell lines. Our results show that only EGFR-positive SCLC cell lines had the in vitro invasive phenotype, and it is therefore suggested that the EGFR might play an important role for the invasion potential of SCLC cell lines.
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PMID:In vitro invasion of small-cell lung cancer cell lines correlates with expression of epidermal growth factor receptor. 974 4

Overexpression of epidermal growth factor receptor (EGFr) in squamous carcinomas has been demonstrated extensively. Preliminary clinical studies have shown that radiolabeled anti-EGFr monoclonal antibodies can localize to these tumors. The aims of this study were to determine the tolerance, pharmacokinetics, and radiolocalization properties of 131I-labeled EGF in patients (n = 9) with advanced squamous lung cancer. Patients' vital signs and symptoms were monitored regularly for 3 days. Daily scintigrams and biological samples for pharmacokinetic analysis were obtained for 3-4 days. 99mTc-labeled human serum albumin was administered to patients with positive tumor scans. Six patients had positive tumor scans, and five of them had received >/=1.0 mg EGF. In all of these cases, tumors were visualized the same day of the infusion, although best tumor-background contrast was obtained at 50-74 h. There were no false-positive images. Whole-body radioactivity retention rose significantly with increasing EGF doses; most labeled EGF was eliminated by urinary excretion. Tumor:normal tissue uptake ratios increased during the course of the study. All patients presented self-limited, dose-related gastrointestinal adverse effects. In conclusion, recombinant 131I-labeled EGF administered i.v. can localize to squamous lung cancer efficiently, can be administered safely to patients, and has more advantageous pharmacokinetic properties than monoclonal antibodies. Further studies are warranted to determine more accurately the potential of EGF and EGF-related peptides in the imaging and/or therapy of EGFr-overexpressing human cancers.
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PMID:Radiolocalization of squamous lung carcinoma with 131I-labeled epidermal growth factor. 981 84

The epidermal growth factor receptor (EGFR) is thought to mediate the action of the mitogens EGF and tumour growth factor-alpha (TGF-alpha) in a variety of cancers, including those of the lung, breast and ovary. A number of new selective inhibitors of EGFR tyrosine kinase have now been developed as potential new antitumour agents. We used a potent inhibitor of this tyrosine kinase, 6-amino-4-[(3-bromophenyl)amino]-7-(methylamino)quinazoline (SN 25531; PD 156273), to determine the responses of primary cultures derived from patients with cancer of the lung, ovary, breast, cervix and endometrium. Cells were cultured in 96-well plates and proliferation assessed by incorporation of 3H-thymidine. Measured growth inhibitory concentrations IC50 values) varied from 1 nM to 14 microM with a 1000-fold differential between sensitive and resistant cultures. Results were compared with rates of proliferation, estimated using a paclitaxel-based method. We also measured the IC50 values for the tyrosine kinase inhibitor using a number of established human cell lines, and compared them with EGFR content using fluorescent antibody staining and flow cytometry. The presence of EGFR was found to be necessary, but not sufficient, for in vitro response. Only a small number of cell lines (3 of 7 for lung, 1 of 7 for ovarian, 2 of 3 squamous cell and 0 of 12 for melanoma) were sensitive to the tyrosine kinase inhibitor. In contrast, 40 of the 50 primary cultures (including 14 of 15 lung cancer samples and 14 of 19 ovarian cancer samples) were sensitive.
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PMID:Inhibition of growth of primary human tumour cell cultures by a 4-anilinoquinazoline inhibitor of the epidermal growth factor receptor family of tyrosine kinases. 984 59

Many human epithelial carcinomas are characterized by the overexpression and constitutive activation of the epidermal growth factor receptor (EGF-R) via an autocrine signaling loop. We have investigated the effects of a ligand-blocking monoclonal antibody (mAb) against the EGF-R LA1 on selected parameters of human lung cancer cell lines (H322 and H661) and normal human bronchial epithelial (NHBE) cells. Using Western blot analysis, we show that H322 and NHBE cell lines express comparable levels of EGF-R/p170erbB-1. The LA1 mAb against EGF-R inhibits growth, induces differentiation to a more epithelial phenotype, reduces the constitutive activation of EGF-R, and upregulates epithelial cadherin glycoprotein expression in H322 and NHBE cells. In contrast, LA1 had no effect on either growth, differentiation, receptor tyrosine phosphorylation, or the expression of adhesion molecules in H661 cells, which is consistent with our finding that this cell line does not express detectable levels of EGF-R. These studies demonstrate that a blocking anti-EGF-R mAb can regulate proliferation, differentiation, and the expression of cell adhesion molecules in human bronchial epithelial cells. Our findings suggest possible therapeutic avenues for the treatment of invasive carcinomas via the blockade of EGF-R with antibodies.
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PMID:Up-regulation of E-cadherin by an anti-epidermal growth factor receptor monoclonal antibody in lung cancer cell lines. 1010 Jul 22

The receptors erbB-3 and erbB-4 are members of the type 1 tyrosine kinase receptor family which also comprises epidermal growth factor receptor (EGF-R) and erbB-2. ErbB-3 and erbB-4 receptors are known to bind a family of related proteins termed heregulins. In this study, we report differential expression of P185erbB-2, P160erbB-3 and P180erbB-4, and their ligand heregulin alpha, in normal bronchial epithelial, and non-small cell lung carcinoma (NSCLC) cell lines. Expression of P185erbB-2 and P160erbB-3 vary from very low to a high level in NSCLC cell lines and a low level in normal bronchial cells. In contrast, P180erbB-4 was detected only in NSCLC cell lines but not in normal bronchial cells. Heregulin alpha is expressed at intermediate levels in the normal and cancer cell lines studied. Immunoprecipitation, using antibodies to erbB-2, erbB-3 or erbB-4 receptors, coupled to phosphotyrosine Western blot analysis indicates that these three receptors are constitutively tyrosine phosphorylated in lung cancer cell lines, but only erbB-2 and erbB-3 are autophosphorylated in normal cells. These data suggest that constitutive activation of erbB-2, erbB-3 and erbB-4 receptors could be induced by heregulin alpha via an autocrine loop mechanism, and that the active forms of erbB-4 may cooperate with the other members of the EGF-receptor family in human lung carcinogenesis.
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PMID:Expression of P185erbB-2, P160erbB-3, P180erbB-4, and heregulin alpha in human normal bronchial epithelial and lung cancer cell lines. 1022 86

A series of 6- and 7-acrylamide derivatives of the 4-(phenylamino)quinazoline and -pyridopyrimidine classes of epidermal growth factor receptor (EGFR) inhibitors were prepared from the corresponding amino compounds by reaction with either acryloyl chloride/base or acrylic acid/1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. All of the 6-acrylamides, but only the parent quinazoline 7-acrylamide, were irreversible inhibitors of the isolated enzyme, confirming that the former are better-positioned, when bound to the enzyme, to react with the critical cysteine-773. Quinazoline, pyrido[3,4-d]pyrimidine, and pyrido[3,2-d]pyrimidine 6-acrylamides were all irreversible inhibitors and showed similar high potencies in the enzyme assay (likely due to titration of the available enzyme). However the pyrido[3,2-d]pyrimidine analogues were 2-6-fold less potent than the others in a cellular autophosphorylation assay for EGFR in A431 cells. The quinazolines were generally less potent overall toward inhibition of heregulin-stimulated autophosphorylation of erbB2 (in MDA-MB-453-cells), whereas the pyridopyrimidines were equipotent. Selected compounds were evaluated in A431 epidermoid and H125 non-small-cell lung cancer human tumor xenografts. The compounds showed better activity when given orally than intraperitoneally. All showed significant tumor growth inhibition (stasis) over a dose range. The poor aqueous solubility of the compounds was a drawback, requiring formulation as fine particulate emulsions.
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PMID:Tyrosine kinase inhibitors. 15. 4-(Phenylamino)quinazoline and 4-(phenylamino)pyrido[d]pyrimidine acrylamides as irreversible inhibitors of the ATP binding site of the epidermal growth factor receptor. 1034 32

The oncogene product epidermal growth factor receptor (EGF-R), the tumour suppressor gene product p53 and anti-p53 antibodies are detectable in the serum of certain cancer patients. Increased levels of some of these products were reported in lung cancer patients after occupational asbestos exposure and after exposure to polycyclic aromatic hydrocarbons or vinylchloride. In the first step, this study investigated the possible diagnostic value of serum EGF-R, p53-protein and anti-p53 antibodies, measured by an enzyme-linked immunosorbent assay, in lung tumour patients. In addition to being investigated on a molecular epidemiological basis, these parameters were examined as biomarkers of carcinogenesis, especially with regard to asbestos incorporation effects or of radon-induced lung cancers. Also, a possible effect of cigarette smoking and age dependence were studied. A total of 116 male patients with lung or pleural tumours were examined. The histological classification was four small-cell cancers, six large-cell cancers, 32 adenocarcinomas, 47 squamous carcinomas, 12 mixed lung carcinomas, five diffuse malignant mesotheliomas and ten lung metastasis of extrapulmonary tumours. Twenty-two lung cancers and all mesotheliomas were related to asbestos, 22 lung cancers were related to ionizing radiation and 61 patients had cigarette smoke-related lung cancer. Besides these patients 50 male patients with non-malignant lung or pleural diseases were included; of the latter eight subjects suffered from asbestosis. Controls were 129 male subjects without any lung disease. No significantly elevated or decreased serum values for p53 protein, EGF-R, or anti-p53 antibodies as a function of histological tumour type, age, or degree and type of exposure (asbestos, smoking, ionizing radiation) could be found. The utility of p53-protein, EGF-R and anti-p53 antibodies as routine biomarkers for screening occupationally derived lung cancers is limited.
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PMID:p53 protein, EGF receptor, and anti-p53 antibodies in serum from patients with occupationally derived lung cancer. 1047 Oct 51

We have conjugated the murine monoclonal antibody (528) against the human epidermal growth factor receptor (EGFR) to mammalian pancreatic ribonuclease (RNase) via N-succinimidyl-3-(2-pyridyldithio) propionate (SPDP) and 2-iminothiolene (2-IT). The conjugate showed dose-dependent cytotoxicity against EGFR-producing squamous cancer cells (A431, TE8, TE5, Ca9-22) and no detectable cytotoxicity against EGFR-deficient small-cell lung cancer cells (H69). The cytotoxicity of the conjugate was positively correlated with the EGFR numbers of each cell line. The addition of excess 528 antibody to the medium protected A431 cells from the conjugate cytotoxicity. This immunoconjugate might be useful for targeted treatment of squamous cell carcinomas hyperexpressing EGFR.
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PMID:Epidermal growth factor receptor-dependent cytotoxic effect of anti-EGFR antibody-ribonuclease conjugate on human cancer cells. 1062 69

The interaction of epidermal growth factor receptor (EGFR) and its ligand transforming growth factor-alpha (TGF-alpha) leads to an autocrine activation of the ras signaling pathway and putatively its oncogenic activity. It is thus hypothesized that the co-overexpression of EGFR-TGFalpha will be redundant hence rare in tumors with oncogenic ras mutations. To test this hypothesis, we studied by immunohistochemistry the expression of EGFR and TGF-alpha in primary non small cell lung cancers. Such putative EGFR autocrine loop activation was found in 73% of squamous cell carcinomas that rarely develop ras mutations. In contrast, EGFR-TGFalpha co-expression occurred with equal frequency in adenocarcinomas irrespective of their ras genotype. The results indicate that EGFR autocrine loop activity in adenocarcinoma may have alternative signaling activities aside from the activation of ras-MAP kinase pathway.
Lung Cancer 2000 Aug
PMID:Co-expression of epidermal growth factor receptor and transforming growth factor-alpha is independent of ras mutations in lung adenocarcinoma. 1096 46

Have we made any progress in the treatment of advanced non-small cell lung cancer (NSCLC) over the past 15 years? After hearing the Eastern Cooperative Oncology Group (ECOG) 1594 presented by Dr. Joan Schiller at the plenary session of the 36th Annual Meeting of ASCO, it is hard to be certain. SCHILLER: reported the results of one of the world's largest randomized trials in metastatic lung cancer comparing four platinum-based doublets. There were no differences in survival (primary endpoint) or response between these four regimens, although the cisplatin/gemcitabine arm had a superior time to progression. In her commentary on this study, Dr. Francis Shepherd concluded that progress in the treatment of metastatic lung cancer has occurred at "a snail's pace." Despite the disappointing results of ECOG 1594, there were notable trials describing new agents with novel mechanisms of action reported at this year's ASCO meeting. In small-cell lung cancer, the combination of cisplatin/ irinotecan was found to be superior to cisplatin/etoposide. For NSCLC, novel agents Iressa anti-epidermal growth factor receptor tyrosine kinase and anti-vascular endothelial growth factor monoclonal antibody appear promising.
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PMID:Lung cancer highlights. 1096 93


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