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

Small cell carcinoma of the lung should be viewed as a widely disseminated disease in all patients. Therefore, systemic treatment with intensive combination chemotherapy should now be considered as the primary and initial treatment modality. The role of radiation therapy for local or involved-field needs to be re-examined to determine if such localized therapy following intensive combination chemotherapy offers any benefits in response rate or survival duration. The role of immunotherapy is not established, and further controlled studies are necessary to define such a role, if any does exist. Prophylactic whole brain irradiation may be useful to avoid neurologic complications, however, it does not appear to improve response rate or survival duration. A randomized study needs to be done to see whether prophylactic whole brain irradiation following complete remission alters the occurrence rate of brain metastases. Response rates up to 100% and disease free survivals greater than one year have been reported. Therefore, a realistic potential for cure exists for some patients with this particular type of lung cancer.
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PMID:Current concepts in the management of small cell carcinoma of the lung. 20 31

Survival and histologic subtype were compared in 61 patients with small cell anaplastic lung cancer. Patients with lymphocyte-like (oat cell) and fusiform histologies treated with chemotherapy had longer median survivals than the polygonal and other varieties on the same treatment. Likewise, when detectable disease was confined to the chest and supraclavicular nodes, the patients with lymphocyte-like and fusiform types lived longer. The improved survival in the lymphocyte-like and fusiform categories accounted for most of our improved overall median survival rates with the COPP regimen in small cell lung cancer. Survival in the polygonal and other types was not appreciably different from that seen in non-small cell lung cancer (squamous and adenocarcinoma). It may be possible to refine treatment plans on the basis of cell type so as to further increase survival in small cell anaplastic lung carcinoma.
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PMID:Relationship between survival and histologic type in small cell anaplastic carcinoma of the lung. 22 3

Lung cancer arises after a series of morphological changes, which take several years to progress from normal epithelium to invasive cancer. The morphological changes progress from hyperplasia, to metaplasia, to dysplasia, to carcinoma in situ, to invasive cancer and finally to metastatic cancer. Multiple molecular changes have been documented in lung cancers, both small cell (SCLC) and non-small cell (NSCLC) types. The number of changes has been estimated to be in double digits. These changes include activation of dominant oncogenes myc family, (K-ras and neu genes), as well as loss of recessive growth regulatory genes or anti-oncogenes (p53, and RB as well as unidentified gene or genes on chromosome 3). However, cytogenetic and molecular genetic studies indicate that multiple other specific sites of actual or potential DNA loss may be present in lung cancers. Other changes may include development of drug resistance, and production of growth factors and their receptors. It is tempting to associate specific molecular changes with specific morphological changes, as has been attempted in the colon. However, because of the difficulties in serially sampling the respiratory tract, such studies have not been performed to date. Documentation of molecular changes in premalignant lesions and prospective studies of their prognostic effects will be necessary for the design of rational chemoprevention trials.
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PMID:The molecular biology of lung cancer. 130 9

The p53 gene has been implicated as a tumor suppressor gene involved in the pathogenesis of lung cancer. Our previous study revealed that the p53 gene is frequently mutated with a distinct nucleotide substitution pattern in small cell lung cancer specimens in Japanese patients. In this study, we examined 30 primary, resected non-small cell lung cancer samples in Japanese patients using complementary DNA-polymerase chain reaction and sequencing. Mutations changing the p53 coding sequence were found in 14 of 30 tumor samples (47%), while G:C to T:A transversions which are uncommon in other cancers such as colon cancer were the most frequently observed mutations, in agreement with an earlier report on non-small cell lung cancer in American patients. Furthermore, the present study shows for the first time that in univariate and multivariate analyses, the presence of p53 mutations is closely associated with lifetime cigarette consumption.
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PMID:p53 mutations in non-small cell lung cancer in Japan: association between mutations and smoking. 131 70

Gene expression of the precursor of the 67kDa-laminin receptor was examined by Northern analysis using 11 established human lung cancer cell lines and 25 lung cancer tissues obtained by operation. As a result, one transcript, the size of which was 1.2 kb was shown in all cell lines and tissues examined. An increased level of mRNA was demonstrated in cell lines which proliferated rapidly and in small cell lung cancer cell lines. It was also indicated that gene expression of the laminin receptor was up-regulated especially in small cell lung cancer tissue. In this context, 67kDa-laminin receptor appears to be a marker for biological aggressiveness of human lung cancer.
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PMID:Increased expression of the 67kDa-laminin receptor gene in human small cell lung cancer. 131 Mar 92

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 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

The EORTC Lung Cancer Cooperative group performed a randomised phase II study in patients with small cell lung cancer comparing the standard cyclophosphamide/doxorubicin/etoposide (CDE) regimen with two regimens containing the new and active cisplatin derivative, carboplatin, 400 mg/m2 in combination with ifosfamide, a drug without important myelotoxicity, at a dose of 5 g/m2 (IMP) or the non-myelotoxic drug vincristine twice 2 mg (VP). Of 178 evaluable patients, 63 received CDE [30 limited disease (LD), 33 extensive disease (ED)], 55 received IMP (22 LD, 33 ED) and 60 (26 LD, 34 ED) were treated with VP. The response duration was not statistically different: CDE 31 weeks, IMP 29 weeks and VP 21 weeks. The time to progression after CEE was 28 weeks, IMP 24 weeks and VP 17 weeks. This was significantly shorter after VP than after CDE (P = 0.017). The 60% response rate of the VP combination was low compared with CDE (83%) and IMP (77%). Toxicity of all three regimens was acceptable, and dose reduction for myelosuppression was necessary in only a minority of the patients. We conclude from this study that the combination of carboplatin, at the maximally tolerated dose of 400 mg/m2, in combination with ifosfamide 5 g/m2, is an active regimen with efficacy comparable with the standard CDE regimen.
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PMID:Comparison of two carboplatin-containing regimens with standard chemotherapy for small cell lung cancer in a randomised phase II study. The EORTC Lung Cancer Cooperative group. 131 32


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