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Query: UMLS:C0149925 (small cell lung cancer)
 6,491 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A combination of cytogenetic and molecular studies has implicated the p21 region of human chromosome 3 as the probable site of a gene the loss of which contributes to the development of small cell lung cancer. We report here the isolation of a gene from this region which is expressed in normal lung tissue and in cell lines derived from a number of different types of tumor, but the expression of which in small cell lung cancer cell lines is undetectable by RNA blot analysis. Although the more sensitive polymerase chain reaction did detect transcripts, a novel quantitative polymerase chain reaction assay showed that their concentration in small cell lung cancer cell lines is less than 3% of that in normal lung.
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PMID:A gene from human chromosome region 3p21 with reduced expression in small cell lung cancer. 131 32

The establishment and characterization of 11 human lung cancer cell lines are described in this article. Nine of these cell lines were established over a 5-year period, from 1983 to 1988, from patients treated at the Kingston Regional Cancer Centre. These include eight definite or probable small cell lung cancer (SCLC) lines and one adenocarcinoma line. In addition, two other SCLC cell lines were characterized. All of the lines have been in continuous culture for more than 2 years. The clinical histories of the patients from whom the cell lines were derived are outlined here. Several features of the cell lines are presented, including the following: (1) a comparison of the histologic features of the cell lines with the original biopsy specimens; (2) the expression of various markers, including cytokeratin, carcinoembryonic antigen, calcitonin, and neuron-specific enolase; (3) activities of the enzymes l-dopa decarboxylase and the brain isoenzyme of creatine kinase; (4) growth characteristics; (5) cloning efficiency in soft agar; (6) tumorigenicity in nude mice; and (7) cytogenetic studies. These cell lines, obtained directly from patients with a spectrum of drug-sensitive and drug-resistant tumors, will be valuable in vitro models of sensitivity and resistance to chemotherapy in lung cancer.
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PMID:Establishment and characterization of a panel of human lung cancer cell lines. 131 80

The results of nonprotocol treatment of 232 patients with small cell lung cancer seen by a group of community-based medical oncologists over a 13-year period were evaluated. Factors associated with improved survival also were assessed. The following patient characteristics significantly improved survival: limited stage of disease at diagnosis, treatment of extensive (but not limited) disease with regimens including etoposide and cisplatin, tumor resection, age younger than 70 years, radiation therapy to the chest, and female sex (extensive disease only). Comparison of the data from this study with published results of protocol studies showed similar outcomes.
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PMID:Small cell carcinoma of the lung. Treatment in the community. 131 81

The article consists of an account of Finnish experience in the clinical use of natural, and to a lesser extent, recombinant alpha-interferon in the treatment of lung cancer, including the results of research into interferon treatment of small cell lung cancer carried out by the Lung Cancer Group at University Hospital, Helsinki.
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PMID:[Interferon treatment in small-cell lung cancer]. 131 5

Patterns of drug sensitivities in relation to topoisomerase II gene expression and activity were studied in eight human lung cancer cell lines not selected in vitro for drug resistance. The cytotoxicities of doxorubicin, etoposide, teniposide, cisplatin, camptothecin, and 5-fluorouracil were measured and, remarkably, these unselected cell lines were shown to have a common pattern of multidrug sensitivity, i.e., a multidrug sensitivity phenotype. In fact, drug sensitivities were significantly correlated with each other in the studied cell lines, the correlation being best for the topoisomerase II-targeted agents and cisplatin, less strong with camptothecin, and weak with 5-fluorouracil. Almost 1-log range difference of topoisomerase II gene expression was found in these cell lines, and this was not explained by the cell-doubling time or cell cycle distribution. The level of topoisomerase II gene expression was positively and highly correlated with the cell sensitivity to epipodophyllotoxins, doxorubicin, and cisplatin in seven cell lines. Although weaker, an association was also observed between topoisomerase II gene expression and camptothecin cytotoxicity, while no association was observed with 5-fluorouracil. However, a non-small cell lung cancer cell line with neuroendocrine properties had very low levels of expression of the topoisomerase II gene, despite being highly sensitive to all drugs tested. The levels of topoisomerase I gene expression were not found to be correlated with the cytotoxicity of any drug tested. A specific enzymatic activity assay and a teniposide-stimulated DNA cleavage assay showed that the extent of active topoisomerase II present in nuclear extracts paralleled the level of topoisomerase II gene expression. Furthermore, in addition to the normal transcript, an abnormally sized topoisomerase II message and a rearrangement of the topoisomerase II gene were detected in a poorly sensitive small cell lung cancer cell line. Therefore, low levels of topoisomerase II gene expression, and possibly mutations, may predict a reduced sensitivity of unselected human lung cancer cell lines to several drugs, including agents with a cellular target other than topoisomerase II. It is hypothesized that topoisomerase II might be involved in a common pathway of cell death induced by drugs in tumor cell lines which present a multidrug sensitivity phenotype.
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PMID:Multidrug sensitivity phenotype of human lung cancer cells associated with topoisomerase II expression. 131 95

Mutation of one p53 allele and loss of the normal p53 allele [loss of heterozygosity (LOH)] occur in many tumors including lung cancers. These alterations apparently contribute to development of cancer by interfering with the tumor suppressor activity of p53. We directly sequenced amplified DNA in the mutational hot spots (exons 4-8) of p53 in DNA samples from 40 lung cancers. Most (31 of 40) samples were preselected for LOH in the region of p53. We detected 23 p53 mutations within these exons in 22 lung cancers; no p53 mutations were found in normal tissue of the patients. One-half of the mutations were G to T transversions on the nontranscribed strand, consistent with mutagenesis by tobacco smoke. Mutations of C to A on the nontranscribed strand, which would result from G to T mutations on the transcribed strand, were detected only in one sample. Three of 23 mutations were nonsense mutations; to date, nonsense mutations of p53 have not been reported in lung cancer. Mutation of this p53-coding region was detected in 20 of 27 small cell lung cancer samples, representing a 70% occurrence. Mutation of the p53 gene is apparently very frequent in small cell lung cancers. When LOH in the p53 region could be determined, complete concordance occurred between a sample having both a p53 mutation and LOH in the region of p53 (18 of 18 samples). Twelve samples of lung cancer had LOH in the region of p53, but the samples had no detectable p53 mutations, suggesting either alterations outside the known mutational hot spots of p53 or alterations of another unidentified tumor suppressor gene in the region of p53.
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PMID:p53 mutations in human lung tumors. 131 96

Cis-Diamminedichloroplatinum (II) (cisplatin) is one of the key drugs in the treatment of solid tumors. Cis-Diammine-1, 1-cyclobutanedicarboxylateplatinum (II) (carboplatin) and cis-diammine (glycolato)-platinum (254-S) are second-generation platinum-coordination complexes developed in recent years not only to reduce nephrotoxicity but also to have antitumor activity equivalent or superior to cisplatin. Comparative pharmacological study among these three compounds was performed. Six different small cell lung cancer (SCLC) and six non-small cell lung cancer (NSCLC) lines were exposed to different concentration of the three platinum compounds, cisplatin, carboplatin and 254-S in colony assay. The IC50 values for cisplatin, carboplatin and 254-wS in SCLC cell lines were significantly lower than those in NSCLC cell lines. In addition, the IC50s for carboplatin were significantly higher than those for cisplatin and 254-S in both SCLC and NSCLC lines. A total of 15 patients entered the pharmacological study. In all, 80 mg/sqm cisplatin, 450 mg/sqm carboplatin, and 100 mg/sqm 254-S were each given to five patients by intravenous drip infusion over 30 min. Ultrafilterable platinum declined biexponentially for carboplatin and 254-S, whereas the free platinum of cisplatin fitted to a monoexponential equation. We reported the equation between nadir platelet count (NPC) and Ccr, by retrospective analysis in 38 "Training Set" patients; [NPC] = 2,783.4 x [Ccr.]- [NPC] = 2,783.4 x [Ccr.]- 64,264.7. To evaluate prospectively the equation in the "Test Set" patient and to refine it. Thirty four patients who entered phase II study of 254-S for NSCLC were prospectively analysed. Significant correlation was observed between observed NPC and predicted NPC which was calculated by the equation (R = 0.51). To refine the equation, all patients in both "Training Set" and "Test Set" were reanalyzed. Simple linear least model is shown as the best fit and refined equation is as follows: [NPC] = 2,201.7 x [Ccr.]-17,695.0. Bioassay was achieved by clonogenic techniques using NCI-H-69 (SCLC cell line) and PC-9 (NSCLC cell line) as target. Biological comparison was performed on the basis of the antitumor activity of patient's plasma using the antitumor index (ATI). The ATIs obtained by bioassay showed better correlation than the AUCs obtained by chemical assay with the clinical response for the three agents against SCLC and NSCLC according to the following equation: [Reported Response(%)] = 11.5668 + 0.0014 x [ATI] (r = 0.97).
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PMID:[Pharmacological approach to the platinum compounds]. 131 67

The doxorubicin-selected multidrug resistant small cell lung cancer cell line, H69AR, is cross-resistant to the Vinca alkaloids and epipodophyllotoxins, but does not overexpress P-glycoprotein, a 170 kDa plasma membrane efflux pump usually associated with this type of resistance. Monoclonal antibodies were raised against the H69AR cell line and one of these, MAb 3.186, recognises a peptide epitope on a 36 kDa phosphorylated protein that is membrane associated, but not presented on the external surface of H69AR cells (Mirski & Cole, 1991). In the present study, in vitro translation and molecular cloning techniques were used to determine the relative levels of mRNA corresponding to the 3.186 antigen. In addition, a cDNA clone containing an insert of approximately 1.4 kb was obtained by screening an H69AR cDNA library with 125I-MAb 3.186. Fragments of this cloned DNA hybridised to a single mRNA species of approximately 1.6 kb that was 5 to 6-fold elevated in H69AR cells. Partial DNA sequencing and restriction endonuclease mapping revealed identity of the cloned DNA with p36, a member of the annexin/lipocortin family of Ca2+ and phospholipid binding proteins.
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PMID:Elevated expression of annexin II (lipocortin II, p36) in a multidrug resistant small cell lung cancer cell line. 131 68

Tumour cell adhesion, detachment and aggregation seem to play an important part in tumour invasion and metastasis, and numerous cell adhesion molecules are expressed by tumour cells. Several families of cell-cell adhesion molecules have been described, of which two groups are particularly well characterised, the cadherin family and the Ig superfamily member, neural cell adhesion molecule (NCAM). We investigated expression of these two adhesion molecule families in small cell lung cancer (SCLC) cell lines and xenografts by immunoblotting. Nineteen tumours established from 15 patients with SCLC were examined. All tumours but one expressed both cadherin and NCAM. The tumours expressed one, two or rarely three cadherin bands, and different combinations of two major isoforms of NCAM with M(r)'s of approximately 190,000 and 135,000. Polysialylation of NCAM, a feature characteristic of NCAM during embryonic development, which may play a role in connection with tumour invasion and metastasis, was found in 14/18 NCAM expressing SCLC tumours. Individual tumours grown as cell lines and as nude mouse xenografts showed no qualitative differences in cadherin or NCAM expression.
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PMID:Expression of cadherin and NCAM in human small cell lung cancer cell lines and xenografts. 131 69

Serum laminin P1 was studied in patients with small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), respiratory infections, pulmonary fibrosis, and in normal subjects. The level of serum laminin P1 was elevated (greater than 1.27 U ml-1) in 58.9% of SCLC and in 11.5% of NSCLC patients. Median value in SCLC was significantly higher than that in NSCLC (P less than 0.01), respiratory infection (P less than 0.01), and in normal subjects (P less than 0.01), but not statistically different from that in pulmonary fibrosis. The levels of serum laminin P1 in SCLC were related to therapeutic response. However, no certain correlation was established between the level of laminin P1 and the clinical stage of SCLC.
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PMID:Serum laminin P1 in small cell lung cancer: a valuable indicator of distant metastasis? 131 70


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