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

To identify mechanisms that allow p185HER2 expression in lung cancer, we performed Western, Southern, and Northern blot analyses of 14 cell lines derived from human non-small cell lung carcinomas and one cell line derived from a human mesothelioma. Human bronchiole epithelial cells and rat type II pneumocytes were found to express p185HER2 at low to undetectable levels by Western blot technique. In contrast, 13 lung cancer cell lines expressed p185HER2, and eight of these 13 expressed p185HER2 at levels at least 2-fold higher than that found in normal bronchiole epithelial cells or type II pneumocytes. Genomic Southern analysis showed that amplification of the HER2 gene was present in only one of the eight cell lines that expressed p185HER2 at these higher levels. Increased levels of steady-state HER2 mRNA occurred in the remaining seven cell lines. We conclude that in human non-small cell lung carcinoma cell lines the most common mechanism resulting in increased p185HER2 expression is due to mechanisms that increase HER2 mRNA levels, with HER2 gene amplification occurring less commonly.
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PMID:Mechanisms of p185HER2 expression in human non-small cell lung cancer cell lines. 131 50

DNA was prepared from normal tissue and 19 lung cancer cell lines. Using probes which detect restriction fragment length polymorphisms at both the topoisomerase II alpha and beta loci, heterozygosity was detected at a frequency of 0.17 and 0.37 for the alpha and beta loci, respectively. Southern blot analysis of DNA extracted from lung cancer cell lines detected amplification of both the topoisomerase II alpha and ERBB2 genes in the adenocarcinoma line Calu3. These results indicate that topoisomerase II alpha and ERBB2 may be closely linked on chromosome 17 and coamplified during adenocarcinoma progression. Since topoisomerase II is a target for several anticancer drugs, it will be of interest to study alterations to topoisomerase II genes during tumour development, as these may in part determine the response of the tumour to chemotherapy.
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PMID:Amplification of the topoisomerase II alpha gene in a non-small cell lung cancer cell line and characterisation of polymorphisms at the human topoisomerase II alpha and beta loci in normal tissue. 137 18

Forty-four patients with previously untreated advanced lung cancer were randomized to receive radiochemotherapy (RC) or radiochemotherapy plus MER/BCG (RCM). Prior to immunotherapy administration cutaneous reactivity to 5 log dilutions of MER/BCG was determined starting at 100 micrograms per injected site to 10 sites. Reactive patients were injected with 10, 1.0, or 0.1 micrograms while anergic patients were given 200 or 100 micrograms to each of 10 cutaneous sites, the dose being inversely related to the strength of the pretreatment reaction. Injected doses were subsequently further increased or decreased to achieve tolerable local erythema and induration. This modification resulted in a marked reduction in cutaneous toxicity previously observed, and made it possible to nearly double the mean number of MER courses per patient. It is suggested that intradermal MER/BCG may prove to be a considerably more useful therapeutic agent if doses are adjusted to patients' individual cutaneous responsiveness.
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PMID:Novel approach to MER/BCG administration in cancer patients. 358 Sep 42

Thirty-eight patients with small-cell carcinoma were treated with cyclophosphamide, Adriamycin, and VP16-213 + or - MER. Response and survival of the six patients who received radiotherapy prior to entering the study were inferior compared with patients who received chemotherapy alone. Of 32 previously untreated patients, 13 had limited and 19 had extensive disease. Ninety-seven percent of these 32 responded and 63% achieved complete remission (CR). All patients with limited disease had a response and 77% achieved CR. Patients with extensive and limited disease had 91/2 months (range 1-26 months) and 14 months (range 31/2 -42 + months) median survival, respectively. The median survival for all complete responders irrespective of extent of disease was 16 months (range 6 - 42 + months). Three patients with limited disease are disease free more than 34 + months and off all therapy 10 + to 18 + months. Eighteen of 38 patients required antibiotics for fever during neutropenia. Eight patients had MER fevers and nine had serious infections. There were four drug-related deaths. MER therapy did not influence response rate, drug toxicity, or survival, but did add morbidity. This combination chemotherapy alone is an effective treatment for previously untreated small-cell lung cancer patients regardless of extent of disease.
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PMID:Chemotherapy versus chemoimmunotherapy for small-cell undifferentiated carcinoma of the lung. 625 48

Between 1968 and 1974, 348 patients with lung cancer were primarily treated with radiation therapy. There were 66 such patients (19%) who survived a minimum of 18 months and are the subject of this report. Of this group, 30 patients have no evidence of disease from 18-96 months, with a median follow-up of 38 months. Thirty-three patients are dead of disease. The five-year actuarial survival of the total group of 348 patients was 5.6%. There were 14 stage I and II patients who survived a minimum of 18 months, of whom 11 had no evidence of disease. Of the 42 Stage III patients, 18 presently show no evidence of disease. There were 13 patients who failed with locally recurrent disease; in this group a dose-response relationship was demonstrated. A local failure rate of 50% (4/8) was observed for patients who received fewer than 5000 rad, 22% (6/27) for patients receiving 5000-5500 rad, 18% (2/11) in patients receiving 5500-5900 rad, and 5% (1/20) for patients who received more than 5900 rad. Radiotherapeutic technique was a significant variable in local failure. Forty-six percent (6/13) of those patient failures may have been eliminated with the use of careful treatment planning with simulation. A statistically significant difference in dose was noted for patients with central recurrence, mean dose 4725 rad, 1561 RET, 81 TDF, when compared with patients with control of gross disease with radiation, mean dose 5740, 1880 RET, 108 TDF. There were four patients with marked early complications (6%) and eight patients with late complications (12%). There were no deaths attributable to radiation. Although most patients with advanced lung carcinoma die of distant disease, a significant number of patients can achieve long-term survival when radically treated with high-dose radiation therapy.
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PMID:The characteristics of long-term survivors of lung cancer treated with radiation. 626 35

One-hundred-three patients with extensive non-small-cell lung cancer were entered into a prospective, randomized trial to determine the value of MER as an adjuvant to chemotherapy. Patients were stratified according to histology and performance status. All patients received CCNU, methotrexate, and Adriamycin with 48 patients also receiving MER. All patients had a performance status of 2 or less (less than 50% bedridden), 49% had prior radiation therapy, only one patient had prior chemotherapy, and all had extensive disease. Of the patients, 42% had epidermoid cancer, 21% had large cell cancer, 32% had adenocarcinoma, and 4% had mixed adenosquamous or undifferentiated carcinoma. The response rates and response durations of the two treatment regimens were similar. Of the patients, 18% had an objective response; in 4% it was complete. An additional 29% had a stable response. Median duration of response ranged from 21 to 23 weeks. Median survival rates for non-MER and MER treatment groups were 21.5 and 18.6 weeks, respectively. The four complete responders have a survival of 24, 85, 86+, and 129 weeks. MER did not improve response for hematopoietic tolerance, was associated with significant morbidity, and was poorly tolerated. The value of immunotherapy in lung cancer remains to be established.
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PMID:Combination chemotherapy with and without the methanol-extracted residue of bacillus Calmette-Guerin (MER) in extensive non-small-cell lung cancer: a prospective randomized study for the Piedmont Oncology Association. 626 42

The HER2/neu (c-erbB2) protooncogene, which encodes a transmembrane receptor (p185neu), contributes to tumor cell invasion/metastasis through mechanism(s) which are, at present, poorly defined. Since basement membrane degradation is a prerequisite for tumor progression, we undertook a study to determine if the expression of urokinase, a key protease implicated in extracellular matrix proteolysis, was regulated by this oncogene. Stable overexpression of a cDNA encoding HER2/neu in H460 lung cancer cells led to elevated secretion of urokinase which was a consequence of a higher level of protease mRNA. Transfection of the HER2/neu-overexpressing B 104-1 cells with a CAT reporter construct driven by the urokinase promoter, gave rise to increased CAT activity when compared with parental NIH3T3 cells, which have low levels of HER2/neu, suggesting that the protooncogene can enhance urokinase promoter activity. Since the enhanced expression of HER2/neu results in increased tumor invasion/metastasis (1), these data suggest that, at least in vitro, HER2/neu-induced expression of urokinase may contribute to tumor progression in p185neu-positive cancers.
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PMID:Up-regulation of urokinase-type plasminogen activator expression by the HER2/neu proto-oncogene. 765 95

p185HER2, the product of the c-erbB-2 or HER2 gene, is a membrane-bound tyrosine kinase that has structural similarity to the epidermal growth factor receptor. Functionally, interaction of HER2 with its ligand or p185HER2 antibodies affects the growth and differentiation of HER2-expressing breast cancer cell lines. As p185HER2 is also expressed in human lung cancers and human lung cancer cell lines, we hypothesized that these cell lines would also respond to p185HER2 antibodies. To test this hypothesis, we cultured human non-small cell lung cancer cell lines in the presence of a p185HER2 monoclonal antibody called 4D5. 4D5 inhibited the growth of p185HER2-expressing cell lines in a dose-dependent fashion. In addition, BEAS.2B, a p185HER2-nonexpressing bronchial epithelial cell line, was transfected with the HER2 cDNA, resulting in high-level p185HER2 expression, and growth of BEAS.HER2 was now inhibited by 4D5 exposure. Mechanistically, 4D5 appeared to have a weak agonist effect on the tyrosine kinase function of p185HER2, as exposure of p185HER2-expressing cell lines to 4D5 resulted in increased p185HER2 phosphorylation. Furthermore, inhibition of tyrosine kinase function with Genistein reversed the 4D5-induced growth inhibition. Therefore, 4D5 can regulate the growth of p185HER2-expressing lung cancer cell lines through agonist effects on p185HER2.
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PMID:Inhibition of human lung cancer cell line growth by an anti-p185HER2 antibody. 810 37

Human topoisomerase II enzymes are targets for a number of widely used anticancer agents. We have analysed a lung adenocarcinoma cell line CALU3, which has co-amplified topoisomerase II alpha and ERBB2 sequences, for the structure of the amplicon and for expression of both topoisomerase II alpha and beta. The region of chromosome 17q amplified in CALU3 also includes the retinoic acid receptor alpha locus and is therefore similar to the amplicon observed in breast cancers carrying amplified topoisomerase II alpha and retinoic acid receptor sequences. The use of fluorescence in situ hybridisation localises the amplified topoisomerase II alpha sequences to a cluster on one chromosome with single copies localised to others. CALU3 express high levels of topoisomerase II alpha is determined by Western blot, immunofluorescence and enzyme activity. The enzyme activity extracted from CALU3 is sensitive to inhibition by the topoisomerase II poison etoposide. Topoisomerase II beta expression was observed in three lung cancer cell lines including CALU3 and was confined to the nucleoli. Thus, the CALU3 cell line is an ideal model to study the amplification and expression of topoisomerase II alpha in adenocarcinomas.
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PMID:Expression of topoisomerase II alpha and beta in an adenocarcinoma cell line carrying amplified topoisomerase II alpha and retinoic acid receptor alpha genes. 839 10

In an attempt to define the type and temporal sequences of somatic genetic changes that precede the onset of invasive lung cancer, and to search for biological markers useful in screening multiple primary tumors of the upper aerodigestive tract, we have performed a cytogenetic and genetic study using normal bronchial epithelium and primary tumor specimens of 68 patients undergoing pulmonary resection for early stage lung cancer, and normal bronchial epithelium of 5 controls with metastatic sarcomas. Of the 68 lung cancer cases, 31 had a single tumor and 37 displayed multiple synchronous or metachronous tumors. Cytogenetic alterations were observed in 59% (23/39) of the evaluable tumor specimens with complex rearranged karyotypes, particularly involving chromosomes 3 (70%), 17 (39%), 11 (26%), 8, 9, 12 (22%), and 7 (17%). Gene alterations were also detected including overexpression of epidermal growth factor receptor (EGFR) in 63% (36/57), HER2/NEU in 21% (12/56), and p53 mutations in 50% (12/24). The overall frequency of genetic changes (any type) in the tumors was 76% (52/68). In the normal bronchial mucosa, we identified a rearranged karyotype in 20% of the evaluable cases (13/63); particularly simple rearrangements involving chromosomes 3p (6 cases), 7 (6 cases), 17 (3 cases), 9, 11 (2 cases), 8 (1 case); as well as overexpression of EGFR in 39% (20/51) and of HER2/NEU in 14% (7/51). The overall frequency of genetic changes (any type) in the normal epithelium was 46% (30/65). The presence of a rearranged karyotype in the bronchial mucosa was associated with a rearranged karyotype in the tumor sample. Other statistically significant correlations were found between histopathologic and clinical features and the occurrence of the different cytogenetic and genetic changes both in tumors and in the normal bronchial mucosa. No genetic abnormalities were found in the bronchial epithelium of the 5 controls.
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PMID:Genetic changes in lung cancer. 841


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