Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The European Lung Cancer Working Party (ELCWP) designed a 3-arm phase III randomised trial to determine the role of accelerated chemotherapy in extensive-disease (ED) small-cell lung cancer (SCLC). Eligible patients were randomised between the 3 following arms: (A) Standard chemotherapy with 6 courses of EVI (epirubicin 60 mg m(-2), vindesine 3 mg m(-2), ifosfamide 5 g m(-2); all drugs given on day 1 repeated every three weeks. (B) Accelerated chemotherapy with EVI administered every 2 weeks and GM-CSF support. (C) Accelerated chemotherapy with EVI and oral antibiotics (cotrimoxazole). Primary endpoint was survival. 233 eligible patients were randomised. Chemotherapy could be significantly accelerated in arm B with increased absolute dose-intensity. Best response rates, in the population of evaluable patients, were, respectively for arm A, B and C, 59%, 76% and 70%. The response rate was significantly higher in arm B in comparison to arm A (P = 0.04). There was, however, no survival difference with respective median duration and 2-year rate of 286 days and 5% for arm A, 264 days and 6% for arm B and 264 days and 6% for arm C. Severe thrombopenia occurred more frequently in arm B but without an increased rate of bleeding. Non-severe infections were more frequent in arm B and severe infections were less frequent in arm C. Our trial failed to demonstrate, in ED-SCLC, a survival benefit of chemotherapy acceleration by using GM-CSF support.
 ...
PMID:A three-arm phase III randomised trial assessing, in patients with extensive-disease small-cell lung cancer, accelerated chemotherapy with support of haematological growth factor or oral antibiotics. 1172 Apr 26

Chemotherapy-associated myelosuppression is a major limitation of anticancer therapy in both local advanced and metastatic NSCLC. In the past, primary prophylactic use of hematopoietic growth factors was administered in these patients to reduce the incidence of febrile neutropenia, to avoid dose reduction and dose delay, and to improve patient quality of life. However, so far, for myeloid growth factors significance is missing that response to treatment can be improved in terms of better outcome. Therefore, the routine use of primary for secondary prophylactic CSF in patients with stage III or IV NSCLC is discouraged. This is due to the fact that there is no evidence that intensified chemotherapy schedules improve patients' prognosis. The application of CSF may be considered (but not given routinely) in patients with pre-existing neutropenia due to diseases or (extensive) prior chemotherapy, poor performance status, previous radiotherapy of areas with large amounts of bone marrow reserve or a history of recurrent febrile neutropenia while receiving earlier therapy. However, none of these indications has ever been proven in randomised clinical trial. In contrast, locally advanced NSCLC is a potentially curable disease. Future schedules may combine increased dose intensity of chemotherapy with sequential or simultaneous radiotherapy, where the primary or secondary use of myeloid growth factors may be justified. Chemotherapy-associated thrombopenia: So far, no thrombopoietic factors are available for clinical use.
Lung Cancer 2002 Dec
PMID:Role of supportive care in the treatment of NSCLC: supportive care for myelotoxicity. 1246 53

We previously established two lung cancer cell lines, OKa-C-1 and MI-4, which constitutively produce abundant granulocyte-colony stimulating factor (G-CSF) and granulocyte macrophage-colony stimulating factor (GM-CSF). Inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1beta stimulated the expression of G-CSF, GM-CSF, and cyclooxygenase (COX)-2 in the two cell lines. It is known that increased COX-2 activity promotes tumor growth and induces G-CSF and GM-CSF expression in non-malignant cells, and that selective COX-2 inhibitors inhibit the growth of some types of malignant cells. Therefore, we hypothesized that inhibition of COX-2 activity might suppress constitutive production of G-CSF or GM-CSF in addition to reducing the growth of malignant cells. We confirmed that the selective COX-2 inhibitor, NS-398 suppressed the constitutive production of G-CSF and GM-CSF, and the cell growth in both OKa-C-1 and MI-4 cell lines. Prostaglandin E2 (PGE2) reversed the inhibitions of G-CSF and GM-CSF expression, as well as cell growth, by NS-398. This result confirms that the effects of NS-398 are based on the inhibition of COX activity. Some studies have indicated that nuclear factor kappa B (NF-kappaB) or MAPK (mitogen-activated protein kinase) activation is related to upregulation of G-CSF, GM-CSF or COX-2 expression in some types of cells. Therefore, we examined if the actions of NS-398 might be mediated by the MAP kinase pathway or NF-kappaB activity in OKa-C-1 and MI-4 cells. We found that NS-398 inhibits G-CSF and GM-CSF production and cell growth through an extracellular signal-regulated kinase kinase (MEK) signaling pathway in these cell lines. The prognosis of non-small cell lung cancer showing G-CSF gene expression is significantly worse. G-CSF overproduction by tumor cells is observed at an advanced clinical stage. Our findings imply that a COX-2 inhibitor might improve the prognosis of patients with lung cancer through the reduction of G-CSF or GM-CSF.
 ...
PMID:Cyclooxygenase-2 inhibitor NS-398 suppresses cell growth and constitutive production of granulocyte-colony stimulating factor and granulocyte macrophage-colony stimulating factor in lung cancer cells. 1270 93

Myelosupression is the major dose-limiting toxicity in most chemotherapeutic drugs. To evaluate the curative effect of a domestic product of rhG-CSF on chemotherapy-induced leukopenia, 132 patients with malignancies were enrolled, including 80 patients with lung cancer, 35 patients with breast cancer, 10 patients with nasopharyngeal carcinoma, 3 patients with non-Hodgkin's lymphoma, 2 patients with gastric carcinoma and 2 patients with bone metastasis. Total of 528 cycles of chemotherapy were performed. The results showed that according the grade of leukopenia, the different daily doses of the domestic product of rhG-CSF were administered: 75 micro g/d for 3 days, 150 micro g/d for 4 days and 300 micro g/d for 5 days, in grade I-II, grade III and grade IV groups, respectively, the times of recovery to normal level of white blood cells were 2.5, 4.2 and 7 days in 3 groups, respectively. In conclusion, The Chinese product of rhG-CSF shortened the duration of leukopenia and accelerated the hematologic recovery, which shows only slight side effects, so that patients receive the optimal doses of chemotherapy and completed the planned schedule on time.
 ...
PMID:[Clinical analysis of curative effect of rhG-CSF on chemotherapy-induced leukopenia in cancer patients]. 1274 50

A number of cancer vaccine and gene therapy approaches are being evaluated in patients with lung cancer. Cancer vaccine strategies include GM-CSF gene-modified cancer cells, liposomal MUC1 peptide, anti-idiotype antibody targeting GD3, Mage-3 peptide, and mutant p53 pulsed dendritic cells among others. Preliminary human trials have demonstrated immune responses as well as tumor regression in late stage disease. The largest human gene therapy experience in lung cancer is with intratumoral gene replacement therapy, predominantly with p53, but such approaches are limited to locoregional disease control. Earlier stage gene therapy programs targeting the immune system or tumor vasculature hold promise as systemic therapies for treatment of advanced, disseminated disease.
Lung Cancer 2003 Aug
PMID:Lung cancer vaccines and gene therapy. 1286 69

A phase II study of cisplatin, ifosfamide, and irinotecan with recombinant human granulocyte colony stimulating factor (rhG-CSF) support was conducted in previously untreated patients with stage IIIB or IV non-small-cell lung cancer (NSCLC). Between June 1998 and August 2001, 50 patients were registered in this phase II study. Cisplatin (20 mg m(-2)) and ifosfamide (1.5 g m(-2)) were administered on days 1-4 and irinotecan (60 mg m(-2)) was given on days 1, 8, and 15, respectively. This regimen was repeated every 4 weeks. rhG-CSF was administered subcutaneously at a dose of 50 microg m(-2) on days 5-18 except on the days of irinotecan treatment. In total, 49 patients were assessable for toxicity and response and 50 for survival. In all, 33, patients (67.3%; 95% confidence interval 57.4-77.2%) achieved an objective response. The median response duration was 192 days and the median time to progression for 49 patients was 170 days. The median survival time was 540 days with 1- and 2-year survival rates of 63.5 and 30.7%, respectively. Grade 3 or 4 neutropenia and thrombocytopenia developed in 63.3 and 38.8% of the patients, respectively. In conclusion, the combination of cisplatin, ifosfamide, and irinotecan with rhG-CSF support was highly effective for the treatment of stage IIIB or IV NSCLC with acceptable toxicities.
 ...
PMID:Phase II study of cisplatin, ifosfamide, and irinotecan with rhG-CSF support in patients with stage IIIb and IV non-small-cell lung cancer. 1296 17

Summary beta2-adrenoreceptor agonists are able to modulate various aspects of airway cell functions involved in the inflammatory and repair processes characterizing a variety of respiratory disorders. Human bronchial epithelial cells (HBECs), which can act as immune effector cells and express beta2-adrenoreceptors, were used to test the effects of different concentrations (0.1-100.0 nM) of salmeterol (Salm) on adhesion molecule expression and chemokine/cytokine release. HBECs, freshly isolated from resected bronchi at the time of surgery in ex-smokers with lung cancer, constitutively expressed over 3 times more ICAM-1 than VCAM-1 (P<0.05) and secreted greater amounts of IL-8 than of GM-CSF or RANTES (P<0.001). Stimulation of HBECs with IL-4, TNF-alpha or IL-4 plus TNF-alpha-upregulated ICAM-1 expression (P<0.05) and increased GM-CSF and IL-8 secretion (P<0.05). Similarly, VCAM-1 expression was significantly increased by IL-4 plus TNF-alpha, while RANTES release was significantly enhanced by IL-4 or by IL-4 plus TNF-alpha (P<0.05), but not by TNF-alpha alone (P>0.05). Dose-response curves showed that Salm, at concentration >1.0 nM, was effective in inhibiting adhesion molecule expression and cytokine release by HBECs (P<0.05). At a Salm concentration of 10 nM the degree of inhibition observed was similar for ICAM-1 and VCAM-1 expression (37.2 +/- 9.3% and 32.9 +/- 9.6%, respectively; P>0.05), but higher for RANTES (88.4 +/- 4.4%), as compared to IL-8 (21.8 +/- 7.0%) or GM-CSF (30.1 +/- 6.6%; P<0.05, each comparison). Thus, adhesion molecules and cytokines may be expressed/released at very different levels by unstimulated or stimulated HBECs and those activities appear to be modulated by Salm.
 ...
PMID:Cytokine release and adhesion molecule expression by stimulated human bronchial epithelial cells are downregulated by salmeterol. 1450 60

Acetaldehyde, a metabolite of alcohol and primary mediator of alcohol-induced asthma, causes bronchoconstriction via histamine release from airway mast cells. Acetaldehyde also is found in cigarette smoke and may cause airway inflammation. The purpose of this study was to determine the effect of acetaldehyde on cytokine production and nuclear factor kappa B (NF-kappa B) activation in human bronchial tissues. Human bronchi were prepared from normal parts of lung tissues resected for lung cancer (n = 11). The bronchi were cultured in the presence of 5 x 10(-4) M of acetaldehyde for 24 hours and the concentrations of eotaxin, granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin-5, interleukin-8, and regulated on activation, normal T cells expressed and secreted in cultured supernatants were determined by enzyme-linked immunosorbent assay. Tissues also were immunohistochemically stained for NF-kappa Bp65. Acetaldehyde significantly increased GM-CSF production from human bronchi and nuclear translocation of NF-kappa Bp65 in airway epithelium but had no effects on other cytokines. Our findings suggest that acetaldehyde potentially causes airway inflammation via increased GM-CSF production through nuclear translocation of NF-kappa B.
 ...
PMID:Acetaldehyde induces granulocyte macrophage colony-stimulating factor production in human bronchi through activation of nuclear factor-kappa B. 1461 38

The antitumor efficacy of EBV-induced molecule 1 ligand CC chemokine (ELC/CCL19) was evaluated in a murine lung cancer model. The ability of ELC/CCL19 to chemoattract both dendritic cells and T lymphocytes formed the rationale for this study. Compared with diluent-treated tumor-bearing mice, intratumoral injection of recombinant ELC/CCL19 led to significant systemic reduction in tumor volumes (p < 0.01). ELC/CCL19-treated mice exhibited an increased influx of CD4 and CD8 T cell subsets as well as dendritic cells at the tumor sites. These cell infiltrates were accompanied by increases in IFN-gamma, MIG/CXCL9, IP-10/CXCL10, GM-CSF, and IL-12 but a concomitant decrease in the immunosuppressive molecules PGE(2) and TGFbeta. Transfer of T lymphocytes from ELC/CCL19 treated tumor-bearing mice conferred the antitumor therapeutic efficacy of ELC/CCL19 to naive mice. ELC/CCL19 treated tumor-bearing mice showed enhanced frequency of tumor specific T lymphocytes secreting IFN-gamma. In vivo depletion of IFN-gamma, MIG/CXCL9, or IP-10/CXCL10 significantly reduced the antitumor efficacy of ELC/CCL19. These findings provide a strong rationale for further evaluation of ELC/CCL19 in tumor immunity and its use in cancer immunotherapy.
 ...
PMID:EBV-induced molecule 1 ligand chemokine (ELC/CCL19) promotes IFN-gamma-dependent antitumor responses in a lung cancer model. 1466 45

Breast cancer cells frequently metastasize to the skeleton, where they induce OCL formation and activity, resulting in extensive bone destruction. However, the mechanisms by which breast cancer cells mediate increased osteolysis remain unclear. To elucidate this point, we investigated how 3 human breast cancer cell lines, MDA-MB-231, MDA-MB-435 and MCF-7, induce OCL formation using a murine osteoblast-spleen cell coculture system and compared their effects with a human colorectal cancer cell line, HCT-15; a human lung cancer cell line, HT-1080; and a normal human breast cell line, HME. The breast cancer cell lines supported OCL formation only when osteoblasts were present in spleen cell cocultures, whilst the non-breast cancer cell lines and the normal breast cell line, HME, had no effect. Fractionation of BCCM by ultrafiltration established that osteoclastogenic activity was associated with factors having m.w. >3 kDa. Breast cancer cell lines produced primarily PTHrP, with lesser amounts of IL-6, IL-11 and TNF-alpha. The effect of BCCM on OCL formation in osteoblast-spleen cell cocultures was partially prevented by a neutralising antibody to human PTHrP and completely prevented by a neutralising antibody to either murine IL-11 or the murine IL-11 receptor; neutralising antibodies to human IL-6, IL-11 or TNF-alpha were without effect. BCCM or human PTHrP induced an increase in murine osteoblast IL-11 mRNA and protein production, effects that were prevented in the presence of a neutralising antibody to human PTHrP. The osteoclastogenic activity of IL-11 was mediated by enhancing osteoblast production of PGE(2) effects, which were abrogated by an inhibitor of cyclooxygenase. PGE(2) apparently enhanced OCL formation by downregulating GM-CSF production by spleen cells since recombinant murine GM-CSF inhibited OCL formation and a neutralising antibody to murine GM-CSF blocked these inhibitory effects. We conclude that breast cancer cells induce OCL formation by stimulating osteoblastic production of IL-11. The subsequent release of PGE(2) followed by inhibition of GM-CSF production by cells within the bone microenvironment plays an important part in mediating the effects of breast cancer cells on OCL formation and their resorptive activity.
 ...
PMID:Breast cancer cells induce osteoclast formation by stimulating host IL-11 production and downregulating granulocyte/macrophage colony-stimulating factor. 1499 70


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>