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

Paraneoplastic limbic encephalitis (PLE) is a rare disorder characterized by personality changes, irritability, depression, seizures, memory loss and sometimes dementia. The diagnosis is difficult because clinical markers are often lacking, and symptoms usually precede the diagnosis of cancer or mimic other complications. The frequency of antineuronal antibodies in patients with PLE has not been investigated. We examined the neurological symptoms and the causal tumours in 50 patients with PLE to determine the utility of paraneoplastic antibodies and other tests. The diagnosis of PLE required neuropathological examination or the presence of the four following criteria: (i) a compatible clinical picture; (ii) an interval of <4 years between the development of neurological symptoms and tumour diagnosis; (iii) exclusion of other neuro-oncological complications; and (iv) at least one of the following: CSF with inflammatory changes but negative cytology; MRI demonstrating temporal lobe abnormalities; EEG showing epileptic activity in the temporal lobes. Of 1047 patients with neurological symptoms, whose sera or CSF were examined for paraneoplastic antibodies, 79 had the presumptive diagnosis of limbic encephalitis, dementia, cognitive dysfunction, or confusion. Fifty of these patients fulfilled our criteria for PLE. Pathological confirmation was obtained in 12 patients. The commonly associated neoplasms were of the lung (50%), testis (20%) and breast (8%). Neurological symptoms preceded the cancer diagnosis in 60% of patients (by a median of 3.5 months). Twenty-five of 44 (57%) patients with MRI studies had signal abnormalities in the limbic system. Thirty (60%) patients had antineuronal antibodies (18 anti-Hu, 10 anti-Ta, 2 anti-Ma), and 20 were antibody-negative or had uncharacterized antibodies (n = 4). The combination of symptoms, MRI findings and paraneoplastic antibodies established the diagnosis of PLE in 78% of the patients. Patients with anti-Hu antibodies usually had small-cell lung cancer (94%), multifocal neurological symptoms (78%) and a poor neurological outcome. Patients with anti-Ta (also called anti-Ma2) antibodies were young men with testicular tumours (100%), frequent hypothalamic involvement (70%) and a poor neurological outcome. In the group of patients without anti-Hu or anti-Ta antibodies, the tumour distribution was diverse, with cancer of the lung the most common (36%); 57% had positive MRI. Fifteen of 34 (44%) patients with a median follow-up of 8 months showed neurological improvement. Treatment of the tumour appeared to have more effect on the neurological outcome than the use of immune modulation. Improvement was observed in 38% of anti-Hu patients, 30% of anti-Ta patients and 64% of patients without these antibodies.
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PMID:Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. 1086 59

The randomized clinical trial, LU19, conducted by the Medical Research Council Lung Cancer Working Party, was designed to compare ACE (doxorubicin, cyclophosphamide and etoposide) chemotherapy plus G-CSF (granulocyte colony-stimulating factor) at 2-week intervals versus ACE chemotherapy alone at standard 3-week intervals in patients with small-cell lung cancer. This trial investigated whether more intensive administration of ACE would improve overall survival and affect the quality of life of patients. The report on overall survival and other outcome measures will be published in the Journal of Clinical Oncology. In this paper we focus on methods of analysing aspects of data reflecting quality of life. Twelve symptoms of lung cancer and its treatment - cough, haemoptysis, pain, nausea, vomiting, hoarse voice, sore mouth, rash, lethargy, lack of appetite, alopecia, and dysphagia - were scheduled to be assessed on seven occasions for the ACE arm and on eight occasions for the ACE+G-CSF arm by clinicians during the first 18 weeks of the treatment period. However, in practice the number of assessment forms completed per patient ranged from 1 to 9, and assessment time-points were very different from those planned. These 'messy' longitudinal data are explored by both a summary measure approach, in which experience of a symptom is summarized by a single value, and an extensive model-based statistical approach, which explicitly takes into account correlation within repeated measures. These analyses provide a clear picture of symptom comparisons between the two treatments. The application of various methods offers not only an approach to assessing the robustness of the results but also a basis for investigating reasons for inconsistency of results across methods. We conclude that except lethargy, which is worse in the ACE+G-CSF arm, all symptoms are similar across the two arms during the treatment period.
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PMID:Analysis of messy longitudinal data from a randomized clinical trial. MRC Lung Cancer Working Party. 1098 40

Human neutrophil peptides (HNPs) 1, 2 and 3 are antimicrobial peptides localized in the azurophil granules of neutrophils. We investigated the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the biosynthesis of HNPs 1-3 using a sensitive radioimmunoassay and Northern blot analysis. Seven patients with lung cancer were first treated with various anticancer agents for 3 days (days 1-3) followed by treatment with rhG-CSF (2 microgram/kg weight/day) for 7 days (days 8-14). Chemotherapy caused neutropenia but the neutrophil count increased biphasically between days 8 and 14. Chemotherapy did not change the baseline plasma concentration of HNPs 1-3 (74.1+/-2.1 pmol/ml) but the concentration increased from day 12, 5 days after commencement of rhG-CSF therapy, to reach a peak value of 430.8+/-57.0 pmol/ml on day 15, 1 day after the last administration of rhG-CSF. Baseline HNPs 1-3 content per neutrophil was 0.59+/-0.02 fmol, decreased to 0.30+/-0.07 fmol on day 9, then increased to 0.78+/-0.07 fmol on day 15. Analyses of peripheral blood neutrophils by Northern blot and reverse-phase high-performance liquid chromatography showed that the amounts of HNPs 1-3 mRNA and precursors of HNPs 1-3 markedly increased in response to rhG-CSF. Our results indicate that recombinant hG-CSF does not only increase neutrophil count but stimulates HNPs 1-3 biosynthesis in neutrophils, thus enhancing the host defense system of compromised hosts with neutropenia.
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PMID:Recombinant granulocyte colony-stimulating factor induces production of human neutrophil peptides in lung cancer patients with neutropenia. 1106 37

The present study was designed to ascertain whether or not the pleural effusion and serum cytokine levels (granulocyte-macrophage colony-stimulating factor [GM-CSF], interleukin-10 [IL-10], and interferon-gamma [IFN gamma]) in lung cancer patients differ from tuberculous (TB) pleural effusion, in which a strong cellular immune reaction is found; and, whether cytokine levels are a prognostic factor in lung cancer patients with malignant effusion. A total of 202 lung cancer patients with malignant pleural effusion and 26 patients with TB pleural effusion were studied consecutively between 1995 and 1998. Serum and effusion cytokine levels were analyzed with ELISA assays. The results showed that pleural effusion GM-CSF and IL-10 levels were significantly higher than serum levels in both cancer and TB patients. Pleural effusion IFN gamma levels were significantly higher than serum levels in TB patients. IFN gamma levels in both pleural effusion and serum were significantly higher in TB patients than in those with cancer. No significant difference was found, between TB and cancer patients, in the serum or pleural effusion levels of either IL-10 or GM-CSF. The ratio of pleural effusion IFN gamma to serum IFN gamma, effusion IFN gamma to effusion IL-10, and effusion IL-10 to serum IL-10, were all significantly higher in TB than in cancer patients, suggesting a higher cellular activity and T-helper 1 (Th1) reaction in TB pleural effusion than in malignant effusions, which were predominantly Th2 type. Survival analysis showed no significant difference in lung cancer patients with different levels of these cytokines. It was concluded that lung cancer patients with malignant pleural effusion had poorer immune profiles than those with TB pleurisy, both locally and systemically; and the cytokine profiles were not prognostic factors for lung cancer patients with malignant pleural effusion.
Lung Cancer 2001 Jan
PMID:An analysis of cytokine status in the serum and effusions of patients with tuberculous and lung cancer. 1116 63

Animal studies suggest that the kidney is involved in the elimination of recombinant human granulocyte colony-stimulating factor (rhG-CSF), which is used for patients with neutropenia during cancer chemotherapy. Since anticancer drugs induce nephrotoxicity, it is important to clarify the role of the kidney in the pharmacokinetics of rhG-CSF in cancer patients. Our study was designed to evaluate the relationship between the pharmacokinetics of rhG-CSF and renal function in lung cancer patients compared to the absolute neutrophil count (ANC). The pharmacokinetic studies were conducted with 25 lung cancer patients. Following chemotherapy using platinum-based compounds, a bolus 5 microg of rhG-CSF/kg of body weight was intravenously injected from the first day of leukopenia or neutropenia. Pharmacokinetic parameters were estimated by fitting the concentration in serum-time data to a two-compartment model according to the population pharmacokinetics and the Bayesian method. Creatinine clearance (CL(CR)) was predicted by the Cockcroft-Gault formula. rhG-CSF clearance (CL(G-CSF)) correlated significantly with the ANC (r = 0.613; P < 0.001) and CL(CR) (r = 0.632; P < 0.001). Multiple linear regression analysis showed that the combination of the ANC and CL(CR) accounted for 57.4% of the variation of CL(G-CSF). In patients with an ANC of <1,000/microl, CL(CR) accounted for 72.9% of the variation of CL(G-CSF) (P < 0.001). Our findings suggest that renal function and neutrophil counts correlate with CL(G-CSF) and that the role of renal function in eliminating rhG-CSF is important in lung cancer patients with neutropenia.
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PMID:Effects of renal function on pharmacokinetics of recombinant human granulocyte colony-stimulating factor in lung cancer patients. 1140 6

We have investigated the serum level of granulocyte-colony stimulating factor (G-CSF) and macrophagecolony stimulating factor (M-CSF) in non-small-cell lung cancer (NSCLC), in relation to the control group and commonly accepted tumor markers, such as carcinoembryonic antigen (CEA) and cytokeratin fragment 19 (CYFRA 21-1). Additionally, we have defined the diagnostic sensitivity, specificity, positive predictive value, negative predictive value and receiver-operating characteristics (ROC) curve of G-CSF and M-CSF. Serum levels of cytokines were measured in 61 patients with NSCLC and in 20 healthy subjects. G-CSF and M-CSF were determined using ELISA. CYFRA 21-1 was measured by radioimmunoassay and CEA by microparticle enzyme immunoassay. There were significant increases in the level of circulating G-CSF in the lung cancer patients compared to the control group. Moreover, the diagnostic sensitivity of G-CSF was higher (56%) than the sensitivity of CYFRA 21-1 (51%), but lower than the CEA sensitivity (62%). The diagnostic specificity of G-CSF was higher (70%) than the M-CSF specificity (40%) and the G-CSF predictive values were higher in relation to the predictive values of M-CSF. These results suggest a potential role of G-CSF as a tumor marker for NSCLC.
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PMID:Granulocyte-Colony stimulating factor and macrophage-colony stimulating factor in patients with non-small-cell lung cancer. 1143 84

Six mAbs were raised against human "functionally inactive" recombinant IL-18, ELISA for determination of "functionally inactive" forms of IL-18 were established using two of these mAbs (#21 and #132), and inactive species of IL-18 protein were examined with human blood plasma and macrophages (Mp). In 6-day GM-CSF-treated monocytes, namely Mp, the mAb #21 recognized the IL-18 proform (24 kDa) and a 48 kDa dimer by immunoblotting. In contrast, only the 24 kDa species was detected as a relatively faint band with a commercial mAb against "active" IL-18. No IL-18 species was detected in premature monocytes. Thus, the dimeric IL-18 was produced in Mp and detectable with the mAb we established. In blood plasma of normal subjects and patients, the #21-recognizable IL-18 was also detected by ELISA, the levels of which were not consistent with those obtained with the commercially available kit for determination of "functionally active" IL-18. We designated the former as type 2 and the latter as type 1. Strikingly, IL-18 type 1 was detected in all volunteers while type 2 was detected in approximately 30% of healthy subjects, and the levels of type 2 were high (10-100 ng/ml) compared to those of type 1 (0.02-0.55 ng/ml) in their blood plasma. In patients with atopic dermatitis, the mean value of type 1 was high (200 ng/ml) compared to those of normal subjects (0.122 ng/ml) and patients with lung cancer (0.113 ng/ml). Production of high type 1 may be associated with an immunomodulatory state in atopic dermatitis. The levels and frequencies of IL-18 type 2 were not significantly changed among these populations. Hence, large amounts of type 2 species are produced in monocyte-Mp differentiation, and their levels and frequencies are unchanged in blood plasma irrespective of the levels of type 1.
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PMID:Protein polymorphism of human IL-18 identified by monoclonal antibodies. 1160 32

In this study, we investigated the generation of dendritic cells (DCs) from blood monocytes and mature macrophages from untreated primary lung cancer patients. Blood monocytes were separated by adherence from blood mononuclear cells (MNC) from ten lung cancer patients and ten control subjects, and cultured for 7 days in medium with granulocyte/macrophage colony-stimulating factor (GM-CSF) plus interleukin (IL-) 4. In all cases examined, DCs with typical characteristics were obtained even in lung cancer patients after 7 days culture with these cytokines, and there was no significant difference in phenotype and stimulatory activity in allogeneic lymphocyte proliferation between DCs derived from monocytes from lung cancer patients and those from control subjects. Next, we examined whether alveolar and pleural macrophages in malignant pleural effusion separated by magnetic beads could differentiate to immunostimulatory DCs. Conventional culture conditions with GM-CSF and IL-4 did not induce efficient numbers of DCs from mature macrophages, whereas the addition of tumor necrosis factor-alpha (TNF-alpha) to GM-CSF and IL-4 effectively contributed to generate DCs. These findings suggest that both mature macrophages and blood monocytes from lung cancer patients could differentiate to DCs, and might be a useful source of DCs for immunotherapy.
Lung Cancer 2001 Nov
PMID:Efficient generation of dendritic cells from alveolar and pleural macrophages as well as blood monocytes in patients with lung cancer. 1167 78

Doxorubicin is the most widely studied agent for the treatment of malignant mesothelioma. In conventional doses, the response rate is approximately 17%. Higher dose doxorubicin has been successfully employed in other tumor types. Dexrazoxane has been demonstrated to reduce the cardiac toxicity associated with long term, chronic use of doxorubicin. Based upon phase I data generated by the Cancer and Leukemia Group B (CALGB) indicating that doxorubicin at a dose of 120 mg/m(2) when combined with dexrazoxane and GM-CSF could be safely administered, the CALGB undertook a phase II study of high-dose doxorubicin in patients with malignant mesothelioma. Toxicity was excessive, necessitating protocol modification and ultimately protocol termination. There were no objective responses observed. We conclude that high-dose doxorubicin administered with dexrazoxane is unacceptably toxic in this patient population.
Lung Cancer 2001 Nov
PMID:High-dose doxorubicin, dexrazoxane, and GM-CSF in malignant mesothelioma: a phase II study-Cancer and Leukemia Group B 9631. 1167 88

Lung cancer is biologically and clinically classified as non-small-cell lung cancer (NSCLC) or small cell lung cancer (SCLC). NSCLC is accounting for about 80% of lung cancers. Serum tumour markers may be helpful in diagnostic of this cancer and in monitoring of the tumour growth or tumour volume reduction. Recent studies have focused on a new family of markers--hematopoietic cytokines, defined also hematopoietic growth factors (HGFs). It has been shown that the actions of HGFs are not limited to hematopoietic cells but can also affect the proliferation of nonhematopoietic cells. Some clinical investigations have shown cell surface receptors for macrophage--colony stimulating factor (M-CSF) in cancer cells and autologous production of M-CSF in various human cell lines derived from cancer. The purpose of this investigation was to compare serum levels of M-CSF in NSCLC patients to a control group, to assess pre- and post treatment levels of M-CSF in relation to levels of commonly accepted tumour markers such as carcinoembryonic antigen (CEA) and cytokeratin fragment 19 (CYFRA 21-1), and to define the diagnostic sensitivity of G-CSF in NSCLC. In this study, the serum levels of tumour markers were measured in 34 patients with NSCLC and in 20 healthy subjects. Serum samples were drawn before surgery and 10, 30, 90, 180 and 270 days after surgery. M-CSF and CEA were assayed using ELISA system and CYFRA 21-1 was measured by radioimmunoassay (RIA). The serum level of M-CSF was significantly increased in cancer patients relative to the control group on the 10th day after operation. Concentrations of CYFRA 21-1 were decreased on the 10th day, CEA on the 30th day and M-CSF on the 90th day after surgery. The diagnostic sensitivity of M-CSF was 55%, CEA--62% and CYFRA 21-1-51%. The diagnostic sensitivity and the serum level of M-CSF were related to the stage of NSCLC. These results suggest that M-CSF may be useful in diagnostic and monitoring of NSCLC, but it needs further studies.
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PMID:[Macrophage-colony stimulating factor (M-csf) in diagnostic and monitoring of non-small-cell lung cancer (NSCLC)]. 1168 Feb 64


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