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)

Neuropeptides are increasingly implicated in the control of cell proliferation and their mechanisms of action are attracting intense interest. The early complex cascade of events initiated by peptides of the bombesin family including gastrin-releasing peptide is increasingly understood. The cause-effect relationships and temporal organization of these early signals and molecular events provide a paradigm for the study of other growth factors and mitogenic neuropeptides and illustrate the activation and interaction of a variety of signaling pathways. These peptides may also act as autocrine growth factors for certain small cell lung cancer cells. The results discussed here strongly suggest that the autocrine growth loop of bombesin-like peptides may be only a part of an extensive network of autocrine and paracrine interactions involving a variety of Ca(2+)-mobilizing neuropeptides in small cell lung cancer including bradykinin, cholecystokinin, galanin, neurotensin, and vasopressin. In this context, broad spectrum antagonists that prevent the function of multiple Ca(2+)-mobilizing receptors are of special interest. These antagonists block neuropeptide mediated signals and inhibit small cell lung cancer growth in vitro and in vivo. Thus, broad spectrum neuropeptide antagonists constitute potential anticancer agents.
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PMID:Growth of small cell lung cancer cells: stimulation by multiple neuropeptides and inhibition by broad spectrum antagonists in vitro and in vivo. 131 36

Strategies to block the effects of tumor growth factors, such as estrogen, and to recruit other regulatory elements, such as with retinoids, have focused interest on the possibility of successful tumor intervention approaches. Approaches that neutralize the effects of critical molecules that drive tumor promotion are attractive targets for evaluation as new intervention agents. Clinical intervention trials with early stage patients or with subjects from "high risk" populations impose stricter types of constraints than conventional chemotherapy approaches in advanced stage patients. The potential for short-term toxicity has to be considered, as it may affect subject accrual or compliance. The longer expected survival of intervention subjects mandates closer attention to the possibilities of unexpected long-term toxicities with chronic administration of an intervention agent. As part of a Phase I clinical trial evaluating the utility of a monoclonal antibody directed against the autocrine growth factor, gastrin-releasing peptide to block the growth of small cell lung cancer, we developed a mathematical model to predict the requisite amount of antibody to neutralize growth factor effect. This model requires knowledge of the equilibrium concentration of the secreted growth factor, specific receptor, and bioavailability of the antibody in the tumor interstitium. A range of possible target doses of antibody can be developed to address the potential for heterogeneity frequently encountered in such systems, including a range of levels for peptide production and specific receptor expression. This approach could be applied to rationally derive treatment or intervention in which specific information regarding the relevant binding parameters is available. Through refinement of this modeling approach more context-specific dosing of agonist/antagonists could be determined which may decrease side effects associated with the drug administration.
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PMID:The correct dose: pharmacologically guided end point for anti-growth factor therapy. 131 37

The usual form of chemotherapy of metastatic small cell lung cancer gives a 50% objective response with a mean survival of 7-8 months. We have tested a new antimitotic drug using pirarubicin alone in 26 patients. After the second treatment we noticed a response level of 12% with moderate toxicity. Then, we undertook classical chemotherapy using cisplatin-V16. After 3 doses the response level was 50% with a median survival of 32 weeks. In our study the use of a single drug pirarubicin in metastatic small cell cancer did not appear to worsen the chance of survival in patients if polychemotherapy was carried out immediately in cases which failed on the single drug. Our monotherapy did not appear to induce resistance to affective polychemotherapy. This method applied carefully to patients with metastatic disease with a strict follow up may be utilised in the assessment of the efficacy of the newer antimitotic drugs.
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PMID:[A phase II trial of pirarubicin in untreated disseminated small cell lung cancer. A cooperative study of the French Pneumo-Cancerology Group]. 131 4

The effect of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) was assessed in 17 patients with small cell lung cancer. GM-CSF was initially given alone by subcutaneous injection for 10 days at 50-500 micrograms/m2 per day. There was a significant rise in neutrophils and eosinophils and to a lesser extent in monocytes at all dose levels. During the next phase, patients received chemotherapy (etoposide, ifosfamide and doxorubicin), and GM-CSF was given on alternate cycles, the patients acting as their own controls, so that the amelioration of chemotherapy could be assessed. Despite partial abrogation of the neutropenia associated with chemotherapy (P = 0.04), GM-CSF failed to reduce the frequency of febrile episodes in association with neutropenia, with six episodes occurring on GM-CSF and seven while patients were not receiving GM-CSF after a total of 66 cycles of chemotherapy. After GM-CSF, there was a reduction in polymorph phagocytic ability and chemotaxis in 6/12 and 9/11 patients, respectively. Timed blood counts after GM-CSF administration showed that peak leucocytosis occurred at 8-12 h and fell to two-thirds of this level at 24 h. Toxicity consisting of lethargy, myalgia and bone pain occurred at all dose levels but was manageable. 2 patients had thromboembolism. This study failed to demonstrate a reduction in the infection risk associated with moderately intensive chemotherapy for small cell lung cancer despite the partial abrogation of neutropenia.
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PMID:Infection risk in patients with small cell lung cancer receiving intensive chemotherapy and recombinant human granulocyte-macrophage colony-stimulating factor. 131 26

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

A study of 149 light microscopic tissue slides from 147 patients with recorded initial diagnoses of small cell lung cancer (SCLC) (114 cases) and undifferentiated carcinoma (35 cases) was undertaken to test the reproducibility and prognostic impact of a new histopathologic subclassification of SCLC proposed by the Pathology Panel of the International Association for the Study of Lung Cancer (IASLC). This study was further designed to test the impact of clinical stage, age, sex, and race on survival. The tissue slides were blindly reclassified as SCLC or non-SCLC by a panel of five pathologists with no knowledge of the initial diagnosis. The SCLCs were divided into the three subtypes outlined by the IASLC pathology panel: small (classic or pure), mixed (small cell/large cell), and combined (small cell/squamous carcinoma or small cell/adenocarcinoma). Small cell lung cancer was clinically staged as local, regional, or distant. Consensus diagnosis (defined as agreement by at least three of the five pathologists) was achieved in 144 (96.6%) of the 149 cases. Of these 144 cases, 124 were reclassified as SCLC (115 [92.8%] small, five [4.0%] mixed, and four [3.2%] combined) and 20 were classified as non-SCLC. The median lengths of survival for the small, mixed, and combined subtypes were 225, 1,110, and 203 days, respectively (P = .025). Adequate staging data were available in 123 of the 124 SCLC cases. Of the 123 SCLC cases, 27 (21.9%) were local, 22 (17.9%) were regional, and 74 (60.2%) were distant stage. The median lengths of survival for the local, regional, and distant stages were 428, 251, and 111 days, respectively. This association was highly significant (P = .0001). We conclude that stage is the major determinant of survival in SCLC. Mixed subtypes had significantly longer survival times than the small or combined subtypes (P = .025). Survival times were longer for women than for men, and the survival time difference between men and women was significant (P = .0028). We found no significant differences in survival according to age or race.
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PMID:Prognostic significance of histopathologic subtype and stage in small cell lung cancer. 131 77

Cell-adhesive proteins such as laminin and fibronectin and their specific receptors play an important role in the processes of cancer proliferation, invasion, and metastasis. In the present study, we cloned the cDNA of 67 kDa-laminin receptor both from human lung cultured cell line (IMR90) and from human small cell lung cancer (SBC3), and determined the nucleotide sequences. In addition, the expression of mRNA in 11 lung cancer cell lines with various cell types was estimated by the method of Northern blot hybridization. As a result, 1.2 kb-message was detected in all cancer cell lines examined. It was also demonstrated that the mRNA level of 67 kDa-laminin receptor was inversely proportional to the population doubling time of the cell line (r = -0.80).
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PMID:[Cloning of 67 kDa-laminin receptor cDNA and its expression in various human lung cancer cell lines]. 131 18

Of 320 patients with small cell lung cancer (SCLC) entered into a clinical trial of chemotherapy between January 1983 and September 1985, 106 patients achieved a complete response. The induction chemotherapy used was lomustine 60 mg.m-2 p.o., cyclophosphamide 1 g.m-2 i.v., doxorubicin 45 mg.m-2 i.v. and etoposide 150 mg.m-2 i.v., every four weeks. Lomustine was only given for the first three cycles. Seventy nine of the 106 patients still in complete response after six chemotherapy cycles were subsequently randomized to receive either six more cycles or no more treatment until relapse. In this group of 79 patients, a difference was shown from the time of inclusion between the 51 patients with limited disease and the 28 patients with disseminated disease, with overall median survivals of 395 and 165 days, respectively, (p = 0.0002). No difference was shown between the two treatment groups: the median survival was 332 days from the time of second randomization with a two year survival rate of 28% for the patients randomized to receive six more cycles and 246 days and 22% for those randomized to receive no more treatment (add 147 days to obtain overall median survival). Continuing chemotherapy for more than six cycles to patients in complete response did not improve survival.
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PMID:Six vs twelve cycles for complete responders to chemotherapy in small cell lung cancer: definitive results of a randomized clinical trial. The "Petites Cellules" Group. 131 94

Eighteen small cell lung cancers (SCLCs), 108 non-SCLCs (67 adenocarcinomas, 29 squamous cell carcinomas and 12 large cell carcinomas) were immunohistochemically examined for expressions of cluster 1 SCLC antigen/N-CAM and chromogranin A with monoclonal antibodies NCC-Lu-243 and anti-chromogranin A. The cell membranes of all the SCLCs and three of the 67 adenocarcinomas (4.5%) were stained for cluster 1 SCLC antigen/N-CAM. Eight of the 18 SCLCs (44.4%), and three of the 67 adenocarcinomas (4.5%) were stained for chromogranin A, but no squamous cell carcinoma or large cell carcinoma was stained for both antigens. Two of the three adenocarcinomas which expressed cluster 1 SCLC antigen/N-CAM had been suspected of being either SCLC or poorly-differentiated adenocarcinoma cytologically, and were resected after chemotherapy and radiotherapy. Histologically, they were poorly-differentiated adenocarcinoma with rosette-like tubules. The remaining one was moderately-differentiated papillary adenocarcinoma resembling bronchial surface epithelial cells without mucin (BSE type adenocarcinoma). The three adenocarcinomas which expressed chromogranin A were well- to moderately-differentiated BSE type adenocarcinomas, and stained tumor cells were distributed sparsely as neuroendocrine cells in the normal bronchial mucosa. One of them also expressed cluster 1 SCLC antigen/N-CAM. In the present study, we demonstrated the usefulness of NCC-Lu-243 in the immunohistochemical detection of adenocarcinomas with neuroendocrine features.
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PMID:Immunohistochemical detection of cluster 1 small cell lung cancer antigen and chromogranin A in lung carcinomas. 131 1

The efficacy of high dose chemotherapy with autologous bone marrow rescue (ABMR) was given to 10 patients with small cell lung cancer (SCLC). Four patients received high dose methotrexate plus ABMR followed by chest irradiation. Six patients giving complete response after induction chemotherapy were given intensive chemotherapy plus ABMR only. The over-all survival of these 10 patients was 30.5 months with a range of 6-96 months. Five of them are surviving as of this writing, 3 survived for more than two years and 2 for more than 5 years. Toxic reactions were not severe. Systemic metastasis was the Leading cause of treatment failure. ABMR was effective and safe. When combined with radiotherapy ABMR could be expected to improve the result of intensive chemotherapy for limited SCLC.
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PMID:[High dose chemotherapy with autologous bone marrow rescue for small cell lung cancer]. 131 71


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