Gene/Protein Disease Symptom Drug Enzyme Compound
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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)

We investigated the interaction between human lung cancer cells, laminin, and several differentiating agents. When grown on laminin coated substrate eight out of 11 small cell lung cancer (SCLC) cell lines exhibited attachment to laminin and three had extensive outgrowth of long neurite-like processes. Of seven non-small cell lung cancer cell lines, selected for their in vitro anchorage-independent growth, attachment was observed in only three cell lines, and process formation was far less extensive than in SCLC cell lines. Among several differentiating agents, only dcAMP, which alone induced attachment and some process formation, increased laminin-mediated attachment and process formation of two SCLC cell lines, NCI-N417 a variant cell line, and NCI-H345, a classic cell line. The expression of several neuroendocrine and neuronal markers was investigated in these two SCLC cell lines. The expression of the light subunit of neurofilaments increased in NCI-N417 within 3 to 4 days of seeding, while NCI-H345 exhibited approximately 5 fold increase in expression of the GRP gene and a 3 fold increase expression of the beta-actin gene. The expression of a number of other neuroendocrine and neuronal markers did not change following growth on laminin. The doubling times remained unchanged independent of the presence of and attachment to laminin while topoisomerase II gene expression levels in NCI-N417 cells decreased approximately 5 fold when cells were growing on laminin.
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PMID:Increased expression of differentiation markers can accompany laminin-induced attachment of small cell lung cancer cells. 132 26

An immunohistochemical study has been carried out on fibre optic-biopsy specimens from patients with small cell lung cancer (SCLC) who had either died within 3 months, or who had survived more than 2 years. Long term survivors (LTS) were identified from completed clinical trials at major UK centres and were matched for age and sex within the trial with short term survivors (STS). The panel of immunohistochemical markers included those previously reported to be associated with prognosis, and reagents representative of both neuroendocrine and epithelial differentiation. A preliminary screen of 17 antibodies identified 11 as consistently reactive on paraffin-embedded material using streptavadin-biotin immunoperoxidase. Of 186 identified patients, 110 biopsy samples were retrieved. Of these, 70 gave sufficient material for analysis. All sections were scored by three observers without knowledge of the prognosis. The analysis failed to identify any antigen whose expression was correlated with prognosis. We conclude that, in fibre-optic biopsy specimens, immunohistochemical analysis does not add prognostic information in SCLC.
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PMID:An immunohistochemical investigation of diagnostic biopsy material taken from short and long term survivors with small cell lung cancer. 132 28

Seventy-two consecutive patients were eligible for a study of clinical determinants of response and response duration in small cell lung cancer (SCLC). Pretreatment values of routine laboratory parameters, and three tumour markers: neuron specific enolase (NSE), carcinoembryonic antigen (CEA), and acidic glycoprotein (AGP) were measured. Descriptive clinical variables as performance status (PS), extent of disease, age and sex were also included in the study. All variables were analysed for influence on the type and duration of response. The complete remission probability was only related to pretreatment extent of disease. In a multivariate analysis (Cox) of response duration, only NSE and type of response had significant influence. Consequently, measurements of NSE before therapy will be useful in future clinical trials on SCLC especially in situations, where responding patients are submitted to specific treatment strategies.
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PMID:Serum neuron specific enolase (NSE) is a determinant of response duration in small cell lung cancer (SCLC). 132 29

We have previously reported that a human small cell lung cancer (SCLC) cell line (COR L103) that expresses the proopiomelanocortin (POMC) gene and secretes ACTH precursor peptides is relatively resistant to glucocorticoid regulation. Using this model, we have now examined alternative regulatory mechanisms of the POMC gene and found that both the mRNA and ACTH precursor peptides were stimulated four- and two-fold, respectively, after 48 h incubation with db-cAMP. Next, we examined the dopamine agonist, bromocriptine, which acts predominantly through D2 receptors linked to adenyl cyclase to cause a reduction in intracellular cAMP. Bromocriptine suppressed cAMP levels and inhibited precursor peptide secretion within 24 h in a dose-dependent manner (0.15-15 microM). At the highest dose, peptide secretion was inhibited from 95 to 53 pmol/mg protein, and POMC mRNA was reduced by 50%, while beta-actin mRNA remained unchanged. This effect could not be mimicked by incubation of cells with the alpha-adrenergic antagonist, phenoxybenzamine, suggesting that the alpha-adrenergic effects of bromocriptine were not responsible for this observation. These cells also secrete estradiol, but the secretory rate was unaffected by bromocriptine, suggesting, with the beta-actin data, that the POMC inhibition was not a cytotoxic effect. No recovery in precursor peptide secretion was seen in a 48-h period after the removal of bromocriptine. However, when the postchallenge incubation was extended to 8 d, there was a recovery in secretory potential between day 3 and day 8 and normal growth kinetics in the 4 d after removal of the drug. In contrast to these findings, the mouse corticotroph cell line, AtT20, showed no response to bromocriptine, in keeping with reports that this agonist has no effect on anterior lobe corticotrophs. We conclude that bromocriptine effectively inhibits POMC expression in SCLC cells, and that this phenomenon might be of useful clinical application.
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PMID:Bromocriptine inhibits pro-opiomelanocortin mRNA and ACTH precursor secretion in small cell lung cancer cell lines. 132 94

We assessed the outcome in 65 patients with limited small cell lung cancer (SCLC) treated from 1980 through 1989 with combination chemotherapy and chest and cranial irradiation. Of the 65 patients, 32.3% (21/65) achieved a complete remission (CR) prior to radiation therapy; six additional cases achieved a CR after radiotherapy with an improvement of 10% in the incidence of CR. In our group, 8 patients were alive and free of disease at 30 months (12.3%). We think that a combination of local thoracic irradiation in SCLC limited disease plus chemotherapy yields more CR and improves survival, especially in the group of patients who obtained the CR after initial induction chemotherapy.
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PMID:Limited small cell lung cancer of the lung treated with combination chemotherapy and radiotherapy: a retrospective analysis. 132 39

One hundred and eleven previously untreated patients with extensive small cell lung cancer were included in a prospective randomized study with the aim to assess the efficacy and tolerance of high-dose epirubicin (120 mg/m2) in combination with either cyclophosphamide (800 mg/m2; arm 1) or cisplatin (60 mg/m2; arm 2). Ninety-six patients were evaluable for response and toxicity and additional 12 patients for toxicity only. The overall response rate (CR+PR) in arm 1 and 2 were 61.4 (27/44) and 67.3% (35/52), respectively. The mean duration of remission was 4.4 months (arm 1) and 4.9 months (arm 2). The mean survival time was 6.6 months in arm 1 and 7.7 months in arm 2. WHO grade 4 toxicity was encountered in 25.5 and 15.8% of patients in arm 1 and 2, respectively. One case of cardiotoxicity resulting in the patient's death was observed in arm 1. Both combinations showed considerable antitumor activity. Toxicity was acceptable.
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PMID:Randomized phase II trial of high-dose 4'-epi-doxorubicin + cyclophosphamide versus high-dose 4'-epi-doxorubicin + cisplatin in previously untreated patients with extensive small cell lung cancer. 132 34

Epirubicin 110 mg/m2 was administered intravenously every 3 weeks to 41 elderly and/or unfit, previously untreated patients with small cell lung cancer (SCLC). There were three complete responses, 16 partial responses and 14 treatment failures, with a response rate of 57% in 33 evaluable patients. The main toxicity was haematological, characterised by leukopenia and, less frequently, thrombocytopenia and anaemia. There were three toxic deaths due to infection occurring during leukopenia. Non-haematological side effects were alopecia, nausea, stomatitis and diarrhoea. WHO grade 2 cardiac toxicity was seen in 3 patients after a cumulative dose of more than 740 mg/m2. In conclusion epirubicin is an active agent in untreated SCLC.
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PMID:Epirubicin in previously untreated patients with small cell lung cancer: a phase II study by the EORTC Lung Cancer Cooperative Group. 132 19

In small cell lung cancer, combination chemotherapy including agents such as etoposide, teniposide, cisplatin, doxorubicin, vincristine and cyclophosphamide continues to be the backbone of therapy. Epipodophyllotoxin derivatives, together with cisplatin, are used increasingly as part of the initial therapy. Complete plus partial responses to combination chemotherapy still occur in 80-90% of all patients with a median duration of 9-11 months. Median survival in these studies is at present 11-16 months depending on the initial tumour stage. Deaths from small cell lung cancer continue to occur until 7 years after diagnosis, but rarely thereafter. At this point, overall survival is around 5% and include a small fraction of patients (1%) initially presenting with extensive disease. The optimum duration of treatment is still uncertain. For patients with extensive disease, the use of alternating chemotherapy has been shown in a couple of randomized studies to yield the best results, as judged by long-term survival. The results of several phase II studies stress the importance of dose scheduling of etoposide in small cell lung cancer, with continuous treatment of 5 days' duration or more being superior. The therapeutic results for epidermoid, adenoid, large cell carcinoma and mesothelioma are essentially unchanged. The treatment of patients with these types of lung cancer should continue to be considered experimental, since no standard chemotherapy has as yet been developed, neither when given as single modality nor in combination with surgery or radiotherapy. One single study comparing induction chemotherapy before irradiation vs irradiation alone has resulted in an improvement of median survival of 4 months and doubled the number of long-term survivors. Since three-fourths of the patients with locoregional disease will die within 3 years, further improvements in both systemic and local treatment are needed.
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PMID:Lung cancer. 132 45

Etoposide has been in clinical trials for over 2 decades. From the inception of these investigations, both the oral and intravenous routes have been employed. The oral route has been shown to be convenient, safe, and effective in the trials of diseases such as small cell lung cancer and lymphomas. A recent resurgence of interest has surfaced with its oral application in the elderly and in protracted dosing schedules. Investigations are now under way assessing the relative value of the protracted oral dosing schema in a variety of diseases.
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PMID:Oral etoposide in oncology: an evolving role. 132 83

We have developed panels of human lung cancer cell lines with acquired and inherent resistance to cisplatin. Three parental cell lines, NCI-H69/P (small cell), COR-L23/P (large cell), and MOR/P (adenocarcinoma), were grown in increasing concentrations of cisplatin over a period of 6-9 months. This resulted in the development of sublines, H69/CPR, L23/CPR, and MOR/CPR which were 3- to 8-fold resistant to cisplatin as determined by a 6-day 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. None of the resistant sublines showed a significant change in cellular glutathione content or sensitivity to cadmium chloride (an indicator of metallothionein content), although changes in glutathione-S-transferase activity were seen. The sublines each showed cross-resistance to melphalan. Cisplatin accumulation was unchanged in H69/CPR, 1.3-fold reduced in L23/CPR, and 2.0-fold reduced in MOR/CPR compared with their respective parent lines. In a panel of 10 small cell lung cancer cell lines, there was a 16-fold range of sensitivities to cisplatin. The panels have been used to examine cross-resistance between cisplatin, carboplatin, iproplatin, tetraplatin, and a series of 10 novel ammine/amine dicarboxylate platinum(IV) compounds. Whereas H69/CPR and MOR/CPR showed little or no cross-resistance to any of the other compounds, L23/CPR was generally cross-resistant to all of them. In the panel of small cell lines, whereas the ranking of sensitivity to carboplatin and cisplatin were similar, each of the other compounds provided individual patterns of sensitivity. There was always a wide range of sensitivities among the panel, ranging from 8- to 28-fold. Among the dicarboxylate compounds, there was a great range of potencies, with two compounds (JM273 and JM274) being approximately 100-fold more potent than cisplatin.
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PMID:Sensitivity to novel platinum compounds of panels of human lung cancer cell lines with acquired and inherent resistance to cisplatin. 132 13


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