Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To assess the clinical utility of measuring the number of asbestos bodies (AB) present in bronchoalveolar lavage fluid (BALF), we counted the number of AB in BALF from 119 subjects using light microscopy. The results were analyzed according to occupational histories, radiological findings of asbestos-induced lung and pleural changes, and asbestos-related diseases. The 94 subjects in group 1 had a history of dust exposure, whereas group 2 subjects (n = 25) had no dust exposure. Group 1 was subdivided into subjects with obvious exposure to asbestos (group 1A, n = 61), and subjects with no known exposure to asbestos (group 1B, n = 33). The distribution of AB counts per ml of BALF (means +/- SEM) differed significantly between groups 1 and 2 (38.8 +/- 17.4 vs 0.06 +/- 0.04, p < 0.0001). The AB counts were significantly different between groups 1A and 1B (57.9 +/- 26.6 vs 3.4 +/- 1.2, p = 0.01). Subject, exposed to dust who had radiological evidence of pleural thickening had significantly higher AB counts than subjects in whom pleural thickening was absent (66.0 +/- 31.1 vs 5.1 +/- 4.2, p = 0.03). In group 1, the BALF was positive for AB in 7 of 14 patients with pulmonary fibrosis, 4 of 5 patients with lung cancer, all 6 patients with malignant mesothelioma, and all 4 patients with benign asbestos pleural effusion. We conclude that AB counts in BALF are useful for evaluating both the history of asbestos exposure in a population exposed to dust, as well as patients having asbestos-related diseases.
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PMID:[The clinical utility of asbestos body counts in bronchoalveolar lavage fluid]. 949 46

Increased levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) have been reported in various diseases, including lung cancer. The role of the soluble form of the IL-6 receptor (sIL-6R) remains to be explored. We therefore measured IL-6, IL-8 and sIL-6R in effusion fluid and blood serum of 10 lung cancer patients with carcinomatous pleurisy (5 men, 5 women, age 64.3 +/- 4.4 years) by enzyme-linked immunosorbent assays. Serum levels of healthy individuals served as control. Concentrations of sIL-6R were much higher in serum compared to pleural effusion fluids of tumor patients (25,698 +/- 1,993 vs. 9,438 +/- 1,407 pg/ml: p < 0.0001). In contrast, IL-6 and IL-8 were found at high concentrations in carcinomatous pleural effusions in comparison to serum (IL-6: 964 +/- 176 vs. 10.2 +/- 1.3 pg/ml, p < 0.0001; IL-8: 319 +/- 85 vs. 9.6 +/- 9.6 pg/ml, p < 0.0001). The serum concentrations of IL-6 were not significantly increased in lung cancer patients (10.2 +/- 1.3 pg/ml) in comparison to controls (7.3 +/- 1.0 pg/ml). IL-8 was detected in the serum of only 1 patient and in low levels in the serum of controls (8.0 +/- 1.5 pg/ml; all values are mean +/- SEM). We conclude from this study that decreased levels of sIL-6R, but increased levels of IL-6 and IL-8, are found in pleural effusion fluid of patients with lung cancer and carcinomatous pleurisy. The low sIL-6R levels in the presence of high IL-6 levels in pleural effusions and the high sIL-6R levels in the presence of low IL-6 levels in serum may suggest a downregulation of sIL-6R expression of sIL-6R shedding in the presence of excessive amounts of IL-6.
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PMID:Proinflammatory cytokine levels in patients with lung cancer and carcinomatous pleurisy. 967 Feb 98

The sulfone derivative of the non-steroidal anti-inflammatory drug (NSAID), sulindac, has been reported to inhibit mammary and colon tumor formation in rodent models of chemically-induced carcinogenesis. Unlike its parent compound, this metabolite lacks cyclo-oxygenase inhibitory activity. A tumor induction protocol, consisting of NNK administration in the drinking water over several weeks to model chronic human exposure, was used to test whether the sulfone (called FGN-1) could inhibit the formation of primary lung tumors in mice. A total of 150 female, AIN76A-fed, A/J mice received 9 mg of NNK each. Concentrations of FGN-1 that had been previously determined not to affect body weight gain were added to the food at levels of 0, 250, 500 and 750 mg/kg of diet (30 mice/group) starting 2 weeks before NNK administration and continuing for 22 weeks. At that time pleural surface tumors were counted. Tumor incidence decreased significantly from 96 % in the control diet and 93% in the 250 FGN-1 mg/kg diet to 63 and 67% in the 500 and 750 mg FGN-1/kg diet groups, respectively (P < 0.001 by chi-square analysis). Lung tumor multiplicity decreased from 18.1+/-3 tumors/ mouse (mean+/-SEM, control diet) to 12.3+/-3 (250), 5.3+/-1 (500) and 2.1+/-1 (750) (P < 0.0005 by post hoc ANOVA). In previous studies using this carcinogenesis protocol, the maximum tolerated dose of sulindac inhibited lung tumor multiplicity by no more than 50% with no effect on incidence. This dose-dependent reduction in tumorigenesis by a non-toxic dose of FGN-1 indicates a strong chemopreventive activity against experimental induction of lung carcinogenesis. The greater potency of the sulfone over sulindac and its lack of toxic side effects because of its inability to affect cyclo-oxygenase activity suggests that clinical testing in individuals at high risk for lung cancer should be considered.
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PMID:Inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced mouse lung tumor formation by FGN-1 (sulindac sulfone). 974 28

Interleukin (IL)-10 is known to be an autoregulatory factor of functions of monocyte macrophages. The purpose of this study was to determine whether IL-10 production by alveolar macrophages (AMs) is altered in patients with lung cancer. AMs were obtained by bronchoalveolar lavage from 25 patients with lung cancer and 14 control patients. The production of IL-10 by AMs was quantitated by enzyme immunoassay with or without stimulation with lipopolysaccharide (LPS). No significant difference in spontaneous and LPS-stimulated IL-10 production by AMs was observed between lung cancer patients and control patients (mean +/- SEM; 288.0 +/- 56.7 vs. 249.6 +/- 58.4 pg ml-1). IL-10 production of LPS-stimulated AMs was not impaired even in lung cancer patients with systemic metastasis. IL-4 failed to suppress LPS-induced production of IL-10 by AMs both in control patients and in lung cancer patients. In eight patients with lung cancer, IL-10 production by AMs was estimated before and after systemic chemotherapy and IL-10 production by LPS-stimulated AMs tended to increase after systemic chemotherapy from 152.3 +/- 51.9 to 278.0 +/- 112.8 pg ml-1. As IL-10 is a potent inhibitor of tumour angiogenesis, an important process of tumour progression, these results suggest that, even in advanced cancer patients, macrophages can produce potent angiogenesis inhibitor and systemic chemotherapy may augment this inhibitory activity in the lung.
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PMID:Production of interleukin-10 by alveolar macrophages from lung cancer patients. 1054 82

The purpose of this study was to examine the level of smoking-related aromatic DNA adducts and oxidative DNA damage in current smokers from a lung cancer case-control study in African Americans and Mexican Americans. In addition, mutagen sensitivity (bleomycin-induced chromatid breaks), a marker of genetic susceptibility, was assessed in these patients and correlated with the level of DNA damage. Lymphocyte DNA from cases and age-, sex-, and ethnicity-matched controls was analyzed for aromatic DNA adducts (43 cases and 47 controls) and the level of 7, 8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG) was determined in 46 cases and 48 controls using (32)P-postlabeling. Overall, lung cancer cases had significantly (P < 0.05) higher levels of aromatic DNA adducts and 8-oxo-dG (mean+/-SEM; 6.03+/-1.16/10(8) nucleotides and 5.82+/-0.77/10(5) nucleotides, respectively) compared to the controls (2.80+/-0.36/10(8) nucleotides and 3.65+/-0.56/10(5) nucleotides, respectively). The case-control differences for these two biomarkers were especially evident in current smokers. Both male and female lung cancer cases had higher levels of aromatic DNA adducts compared to the corresponding controls but only in men was the difference statistically significant (P=0.002). Cases who started smoking at earliest age had highest levels of aromatic DNA adducts and 8-oxo-dG. The level of aromatic DNA adducts in lung cancer cases, but not controls, was positively correlated with bleomycin-induced chromatid breaks (P=0.011). In contrast, the level of 8-oxo-dG was not correlated with mutagen sensitivity in either cases or controls or with the level of aromatic DNA adducts. The data suggest that levels of both aromatic DNA adducts and 8-oxo-dG may be useful in predicting risk of lung cancer in these minority populations. The correlation between aromatic DNA adducts and mutagen sensitivity in lung cancer cases and the trend for higher levels of DNA damage in cancer cases who started smoking earliest are particularly interesting and merit further study.
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PMID:Analysis of aromatic DNA adducts and 7,8-dihydro-8-oxo- 2'-deoxyguanosine in lymphocyte DNA from a case-control study of lung cancer involving minority populations. 1064 35

After radiation therapy of lung cancer, a dense fibrotic shadow develops in the irradiated lung. Owing to this fibrosis, early detection of local recurrence after treatment is sometimes difficult even when using computed tomography (CT) and magnetic resonance imaging. We investigated the diagnostic accuracy of technetium-99m hexakis 2-methoxyisobutylisonitrile ((99m)Tc-MIBI) scintigraphy for the detection of recurrent lung cancer following definitive radiation therapy. Eighteen patients with primary non-small cell lung cancer treated with radiation therapy 1 year previously were studied with (99m)Tc-MIBI scintigraphy. They showed no evidence of local recurrence on serial chest radiographs. All single-photon emission tomography (SPET) images acquired 2 h after intravenous administration of the radiopharmaceutical were visually interpreted with knowledge of the pretreatment chest radiograph, CT and the details of radiation therapy (radiation portals and administered doses). A region of interest (ROI) analysis was also performed. In addition to the ROI ratio of tumour uptake to accumulation in contralateral normal lung (tumour/lung ratio), another semiquantitative analysis, the ratio of tumour uptake to accumulation in radiation fibrosis (tumour/fibrosis ratio), was performed to differentiate between accumulation in radiation fibrosis and the tumour uptake. The scintigraphic diagnoses were correlated with clinical outcome. The sensitivity, specificity and negative predictive value of (99m)Tc-MIBI scintigraphy for the detection of recurrent lung cancer were all 88.9% (8/9). The tumour/lung ratios (mean+/-SEM) of the nine patients with local recurrence and the other eight without local failure were 2.00+/-0.11 and 1.40+/-0.09, respectively ( P<0.01). The tumour/fibrosis ratios of the patients with and those without recurrence were 1.47+/-0.08 and 0.93+/-0.05, respectively ( P<0.01). These results suggest that (99m)Tc-MIBI scintigraphy might be of value for the detection of recurrent lung cancer, and especially of small foci in areas of radiation fibrosis that are hardly noticeable on serial chest radiographs.
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PMID:99mTc-MIBI scintigraphy for early detection of locally recurrent non-small cell lung cancer treated with definitive radiation therapy. 1273 91

The clinical value of pre- and post-operative serum carcinoembryonic antigen (CEA) concentration (mean +/- SEM, ng/ml) in surgically treated primary lung cancer patients with adenocarcinoma (n=97) was studied. Preoperative CEA in pT2 patients (18.3+/-8.0) was higher than in pT1 (10.5+/-6.4, p<0.05) but was not different from pT3 patients (19.7+/-6.7). Preoperative CEA in pN1 patients (5.9+/-1.6) was lower than in pN2 (28.2+/-13.2, p<0.05) but not different from pN0 patients (8.8+/-3.8); p-stage II patients (8.2+/-4.7) had lower values than p-stage III patients (26.7+/-10.5, p<0.05), but not p-stage I patients (7.9+/-3.9). The CEA was not different between p-stages IA and IIA (3.5+/-0.6, 6.1+/-3.2) and IB and IIB (17.0+/-11.8, 11.7+/-7.8), but was different between IA and IB (p<0.05) and IIA and IIB (p<0.05). Preoperative CEA did not differ between patients who received complete (12.7+/-4.7) versus incomplete (9.5+/-6.0) resections, nor between patients who developed recurrence after surgery (21.9+/-10.4) versus those who were disease-free (30.9+/-21.7). CEA obtained 2 months after surgery in patients who recurred or metastasized after surgery (63.1+/-47.0) was higher than in disease-free patients (4.8+/-1.6, p<0.05). The post-/pre-operative CEA ratio in patients who recurred or metastasized after surgery (146.6+/-53.3%) was also higher than in disease-free patients (91.0+/-10.9%, p=0.05). In conclusion, CEA reflected tumor size but not the tumor invasion nor hilar lymph node disease; patients with mediastinal lymph node involvement had higher CEA values. Preoperative CEA did not reflect the likelihood of complete resection nor postoperative metastasis, but postoperative CEA obtained 2 months after surgery did reflect postoperative metastasis.
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PMID:Pre- and post-operative serum carcinoembryonic antigen in primary lung adenocarcinoma. 1556 62

Mast cells infiltrate the airway smooth muscle (ASM) of patients with asthma, an event which is likely to be a key factor in the development of this disease. Adhesion is a fundamental mechanism facilitating cellular cross-talk. We have examined whether human lung mast cells (HLMC) and ASM adhere, and have also examined the mechanism involved. Primary cultures of HLMC and confluent human ASM were cocultured for 30 min, then nonadherent HLMC were removed by centrifugation. HLMC adhered avidly to ASM monolayers (mean +/- SEM adhesion 43.2 +/- 1.2%, n = 41). Adhesion was increased to 58.8 +/- 2.7% by 1 mM Mn2+ (p = 0.015), and was reduced by EDTA and EGTA to 20.5 +/- 1.5% and 21.0 +/- 1.3%, respectively (p < 0.0001). Adhesion-blocking Abs for ICAM-1, VCAM-1, CD18, and the alpha4 and beta1 integrins had no effect on HLMC adhesion. HLMC expressed tumor suppressor in lung cancer-1 (TSLC-1) and blocking this reduced adhesion from 38.5 +/- 4.8% to 28.3 +/- 3.7% (p = 0.004, n = 7). ASM did not express TSLC-1, indicating that TSLC-1 acts as a heterophilic adhesion molecule. In summary, HLMC adhere avidly to ASM in part via TSLC-1 and in part via an as-yet-undefined Ca2+-dependent pathway. This supports the hypothesis that adhesion is important in the recruitment and retention of HLMC by the ASM in asthma, and for the functional interaction of these cells.
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PMID:Human lung mast cells adhere to human airway smooth muscle, in part, via tumor suppressor in lung cancer-1. 1639 14

This study compared airway responsiveness in vitro, as measured in isolated bronchi, with responsiveness in vivo in patients with COPD and smokers with normal lung function. In 9 patients with COPD (mean (range) FEV, 55 (30-78) %predicted) and 8 smokers with normal lung function (FEV1 101 (89-117) %predicted), who underwent surgery for lung cancer, responses to inhaled histamine and salbutamol were assessed before surgery. Bronchial specimens of 1-4 mm internal diameter were studied in the organ bath and histamine concentration-response curves assessed. All patients with COPD and none of the control individuals were hyperresponsive to inhaled histamine. Five patients with COPD and no control patient showed a bronchodilator response to salbutamol. Opposite to these findings, bronchial rings in the organ bath demonstrated a rightward shift of histamine concentration-response curves in COPD compared to controls, (p < 0.005). Accordingly, pED50 but not Emax differed statistically (p = 0.0016) between groups, mean+/-SEM values of pED50 in COPD (controls) being 4.67+/-0.08 (5.29+/-0.15) and of Emax 672+/-86 (772+/-120) mg. Patients with COPD showing hyperresponsiveness to inhaled histamine demonstrated lower responsiveness of their isolated bronchi compared to smokers with normal lung function. This suggests that in vivo hyperresponsiveness is based on other mechanisms than alterations in smooth muscle physiology.
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PMID:Isolated bronchi of patients with COPD show decreased histamine responsiveness compared to smokers with normal lung function. 1717 62

The present study was carried out in order to examine the anticancer properties of two sesquiterpene lactones, millerenolide and thieleanin, isolated from Viguiera sylvatica and Decachaeta thieleana, against cell lines in vitro, and on the growth B16/BL6 melanoma tumors in C57BL/6 mice. Millerenolide and thieleanin showed a similar pattern of cytotoxicity with the greatest effect on viability being evident with A549 human lung cancer cells (IC(50) - 40 and 32 microM respectively), and with the 3T3/HER2 cell line which are 3T3 mouse fibroblasts transfected with the HER2 oncogene (IC(50) - 16 and 28 microM respectively). The parent 3T3 cells and the B16/BL6 mouse melanoma cells were less sensitive to these compounds, with thieleanin showing an IC(50) with B16/BL6 greater than the highest dose tested (203 microM). Treatment with millerenolide (8 mg/kg, i.p. on days 0, 2 and 4 post-inoculation) significantly inhibited the growth of subcutaneous B16/BL6 tumors in C57BL/6 mice, (50% inhibition at day 25, P=0.015), as well as retarding the appearance of detectable tumor (millerenolide - day 15.2+/-0.4 vs control - day 12.8+/-0.5, mean+/-SEM, P=0.011). In contrast, treatment with thieleanin (8 mg/kg every other day up to the day of kill) neither retarded the appearance of the tumor nor its growth.
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PMID:Anticancer activities of two sesquiterpene lactones, millerenolide and thieleanin isolated from Viguiera sylvatica and Decachaeta thieleana. 1853 79


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