epidermal-growth-factor and Bronchial-Neoplasms

Topics: Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Chromosomes, Human, Pair 7; Epidermal Growth Factor; ErbB Receptors; Erlotinib Hydrochloride; Genes, erbB-2; Genes, ras; Humans; Mutation; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Quinazolines; Respiratory Mucosa

Gefitinib (Iressa, ZD 1839; AstraZeneca) is a selective Epidermal Growth Factor receptor tyrosine kinase inhibitor. In two randomized phase II trials (IDEAL 1 and IDEAL 2), it has demonstrated an activity against NSCLC, showing partial response and symptoms improvement rates respectively in about 20% and 40% of patients. Multivariate analyses revealed that being a woman, a non-smoker and having an adenocarcinoma was associated with response rate.. We describe a retrospective study of patients receiving Gefitinib as a third line compassionate treatment of NSCLC.. We enrolled 37 patients (29 men, 8 women). Tumors included 25 adenocarcinoma, 4 squamous cell carcinoma, 7 large cell carcinoma, and 1 neuroendocrine carcinoma. Partial response rate was 8.1%, and stable disease rate 27.0%. The 3 responders were all non-smoker women, with an histological type of adenocarcinoma. Symptoms improvement was observed in 59.5% of patients. Main toxicities were diarrhoea and skin reactions. We observed that responding patients had more adverse drugs-related reactions than stable or non-responding patients.. Gefitinib is a meaningful active therapy in NSCLC with a favorable toxicity profile. We suggest that being a woman, a never-smoker and having an adenocarcinoma may be clinical predictive factors of response to Gefitinib.

Topics: Adult; Aged; Antineoplastic Agents; Bronchial Neoplasms; Carcinoma, Bronchogenic; Carcinoma, Non-Small-Cell Lung; Epidermal Growth Factor; Female; Gefitinib; Humans; Male; Middle Aged; Palliative Care; Protein-Tyrosine Kinases; Quinazolines; Retrospective Studies; Sex Factors; Smoking

Transgenic mouse models were established to study tumorigenesis of bronchiolo-alveolar adenocarcinomas derived from alveolar type II pneumocytes (AT-II cells). Transgenic lines expressing the murine oncogene c- myc under the control of the lung-specific surfactant protein C promoter developed multifocal bronchiolo-alveolar hyperplasias, adenomas and carcinomas respectively, whereas transgenic lines expressing a secretable form of the epidermal growth factor (IgEGF), a structural and functional homologue of transforming growth factor alpha (TGF alpha), developed hyperplasias of the alveolar epithelium. Since the oncogenes c- myc and TGF alpha are frequently overexpressed in human lung bronchiolo-alveolar adenocarcinomas, these mouse lines are useful as models for human lung bronchiolo-alveolar adenocarcinomas. The average life expectancies of hemizygous and homozygous c- myc transgenics were 14.25 months and 9.2 months, respectively, suggesting that a dosage effect of c- myc caused an accelerated bronchiolo-alveolar adenocarcinoma formation. First analyses of double transgenics, hemizygous for both c- myc and IgEGF, show that these mice develop bronchiolo-alveolar adenocarcinomas at the average age of 9 months, indicating that these oncogenes cooperate during the lung cancer formation. Our results demonstrate that c- myc and EGF are directly involved and cooperate with one another during formation of bronchiolo-alveolar adenocarcinomas in the lung.

Topics: Adenocarcinoma; Animals; Bronchial Neoplasms; Cloning, Molecular; Epidermal Growth Factor; Gene Expression; Genes, myc; Lung Neoplasms; Mice; Mice, Transgenic; Phenotype; Pulmonary Alveoli

Vascular endothelial growth factor (VEGF) plays a crucial role in physiological and neoplastic angiogenesis. Moreover, VEGF has been found to be upregulated by conditions associated with the generation of free radicals and reactive oxygen intermediates. In patients with cancer, studies to evaluate VEGF as a measure of tumour activity were carried out. We tested the hypothesis that VEGF is additionally affected by oxidative stress due to anticancer therapy. Moreover, the suitability of epidermal growth factor (EGF) to estimate tumour activity was studied.. 60 patients with non-small cell lung cancer (NSCLC) covering different therapy progress and modalities underwent bronchoalveolar lavage. VEGF-, EGF-, albumin- and total protein-concentrations in bronchoalveolar lavage fluid (BALF) and VEGF-levels in blood plasma were studied.. BALF VEGF-levels were increased in patients with advanced NSCLC before and in anticancer therapy. In patients who had received radiotherapy to the lung prior to chemotherapy, VEGF concentrations were noticeably higher than under sole chemotherapy. Pulmonary endothelial hyperpermeability was found in patients with recently diagnosed tumours and patients undergoing anti-cancer therapy. Evaluation of EGF-levels in BALF revealed no significant influence of tumour activity or cancer therapy on this parameter.. BALF-levels of VEGF are affected by tumour activity and oxidative stress due to anticancer therapy.

Topics: Adult; Aged; Aged, 80 and over; Albumins; Alkaloids; Antineoplastic Combined Chemotherapy Protocols; Bronchial Neoplasms; Bronchoalveolar Lavage Fluid; Carcinoma, Non-Small-Cell Lung; Combined Modality Therapy; Deoxycytidine; Endothelial Growth Factors; Epidermal Growth Factor; Etoposide; Female; Gemcitabine; Humans; Lung Neoplasms; Lymphokines; Male; Middle Aged; Neoplasm Proteins; Neovascularization, Pathologic; Oxidative Stress; Proteins; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; Vindesine

Topics: Adenocarcinoma, Clear Cell; Aged; Bronchial Neoplasms; Epidermal Growth Factor; Female; Humans; Keratoderma, Palmoplantar

The effects of transforming growth factor beta (TGF-beta) on cell-to-cell communication were investigated in the log phase of growth in normal BE and in adenovirus-12 SV40 hybrid virus transformed BE cells (strain BEAS-2B). Gap junctions in these cells were identified immunocytochemically. Exposure of BE cells to exogenous TGF-beta (0.04-4.0 pM) in serum-free keratinocyte growth medium (KGM) for 1 or 24 h reduced the rate of fluorescent dye transfer (i.e. cell-to-cell communication) by 30-50% in BE cells. Inversely, in BEAS-2B cells, TGF-beta after 1 h induced a 2- to 10-fold increase in the rate of dye transfer. After 24 h of TGF-beta, communication among BEAS-2B cells was not significantly different from controls (no exogenous TGF-beta). The protein kinase C (PKC) inhibitor H-7 induced a dose-dependent enhancement in communication, which was even higher in the presence of TGF-beta (4 pM X 24 h). The calmodulin antagonist W-7 enhanced communication in BEAS-2B cells independently of the presence of TGF-beta. In keratinocyte basal medium (KBM) supplemented with EGF (5 ng/ml) or with TGF-beta (4.0 pM) dye transfer was reduced or enhanced respectively. The combination of EGF and TGF-beta in KBM antagonized the stimulatory effect of the latter on communication in BEAS-2B cells. In BE cells, continuous exposure (4 days) to TGF-beta in KGM induced a dose-dependent inhibition of proliferation and an increased expression of a keratinized, epidermoid phenotype. This correlated with a reduction in the expression of a mucous secretory phenotype. Increased exposure to TGF-beta (0.04-4.0 pM) decreased the labeling index in BEAS-2B cells, but the cells retained a growth advantage over normal BE cells, and did not express a keratinized epidermoid morphology. With respect to dye transfer as an index of cell-to-cell communication, we conclude (i) that an inhibition or enhancement of communication is involved in the response of bronchial epithelial cells to mitogens (e.g. epidermal growth factor) or growth inhibitors (e.g. TGF-beta), (ii) that PKC and Ca(2+)-calmodulin-dependent processes regulate dye transfer, and (iii) the effects of TGF-beta are mediated by PKC.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Bronchi; Bronchial Neoplasms; Calmodulin; Cell Communication; Cells, Cultured; Culture Media; Dose-Response Relationship, Drug; Down-Regulation; Epidermal Growth Factor; Epithelium; Humans; Isoquinolines; Piperazines; Protein Kinase Inhibitors; Sulfonamides; Time Factors; Transforming Growth Factor beta

The incidence of Syrian golden hamsters with pancreatic cancer induced by subcutaneous injections of N-nitroso-bis(2-oxopropyl)amine for 19 weeks (each 10 mg/kg) increased from 44% to 75% (p=0.016) when epidermal growth factor was also administered from week 5 through week 8 (5 mug energy three days for injections). Epidermal growth factor increased pancreatic weight and body weight. The incidence of animals with bronchial cancer doubled. Epidermal growth factor could be a cocarcinogen as a result of its mitogenic activity.

Topics: Animals; Bronchial Neoplasms; Carcinogens; Cocarcinogenesis; Cricetinae; Epidermal Growth Factor; Female; Mesocricetus; Nitrosamines; Pancreatic Neoplasms

Because epidermal growth factor (EGF) is rapidly bound and internalized into rat pancreas, stimulates uptake of tritiated thymidine, and increases pancreatic weight, a cocarcinogenic effect on pancreatic cancer seemed likely. Pancreatic adenocarcinomas were induced in 70 female Syrian hamsters by 19 weekly s.c. injections of N-nitrosobis(2-oxopropyl)amine (BOP) (10 mg/kg). From Wk 5 through Wk 8 of BOP injections, additional s.c. injections of EGF (5 micrograms every 3 days for 10 injections) were given to 45 animals, while 25 received saline solution. An additional group of 10 received EGF alone, and another 10 animals received saline solution alone (controls). Eleven wk later, the mean body weight of EGF-treated animals increased by 29% as compared with that of controls, and their mean pancreatic weight relative to body weight increased by 44% as compared with controls. The mean body weight of EGF + BOP-treated animals increased by 10%, and their pancreatic weight relative to body weight increased by 22% as compared with that of animals treated with BOP alone. The incidence of pancreatic cancer in the EGF + BOP-treated animals was 75% versus 44% in those treated with BOP alone (P = 0.016). No tumors developed in either animals treated with EGF alone or control animals. EGF augments pancreatic carcinogenesis induced by BOP. The incidence of bronchial carcinomas doubles.

Topics: Adenocarcinoma; Animals; Body Weight; Bronchial Neoplasms; Carcinogens; Cocarcinogenesis; Cricetinae; Epidermal Growth Factor; ErbB Receptors; Female; Mesocricetus; Nitrosamines; Oncogenes; Pancreatic Neoplasms; Receptors, Cell Surface; Receptors, Platelet-Derived Growth Factor