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)

We herein report an extremely rare case of a 55-year-old Japanese woman with a primary malignant melanoma of the esophagus associated with adenocarcinoma of the lung. The patient was admitted to our hospital with a malignant melanoma of the lower esophagus. The chest X-ray and computed tomography (CT) findings revealed an incidental abnormal shadow in the left lung, which was diagnosed to be adenocarcinoma of the lung by means of a CT-guided needle biopsy. After administering systemic chemotherapy with dacarbazine (DTIC), vincristine sulfate (VCR), and nimustine hydrochloride (ACNU) plus interferon-beta, the esophageal tumor markedly decreased in size. Subsequently, the patient underwent a radical resection of both the malignant melanoma of the esophagus and lung cancer via a left thoracotomy and laparotomy.
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PMID:Primary malignant melanoma of the esophagus associated with adenocarcinoma of the lung. 959 Jul 6

We describe an interesting case of adenocarcinoma of the lung accompanying sarcoidosis with diffuse myocardial involvement. A 69-year-old man had a tumor shadow on chest X-ray films of the right upper lung field. Bronchofiberscopy was performed in Jan. 1997. Because transbronchial biopsy specimens disclosed granuloma, the patient was treated with isoniazid, rifampicin, and streptomycin sulfate for tuberculosis, but did not show any improvement. In March 1997, the patient was examined by an ophthalmologist for blurred vision. He was given a diagnosis of uveitis and referred to us for evaluation because his serum ACE and lysozyme levels were elevated. Bronchofiberscopy was performed again, and a diagnosis of lung cancer accompanying sarcoidosis was made based on the findings of transbronchial biopsy and bronchoalveolar lavage. The disease progressed rapidly, and the patient died 47 days after admission. Autopsy disclosed sarcoid granulomas in cardiac muscle tissue and lung tissue. There have been very few reports on the co-existence of sarcoidosis and lung cancer, and the relationship between the two diseases is unclear.
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PMID:[Lung cancer accompanying sarcoidosis with diffuse myocardial involvement]. 1006 64

Cobalt sulfate is a water-soluble cobalt salt with a variety of industrial and agricultural uses. Several cobalt compounds have induced sarcomas at injection sites in animals, and reports have suggested that exposure to cobalt-containing materials may cause lung cancer in humans. The present studies were done because no adequate rodent carcinogenicity studies had been performed with a soluble cobalt salt using a route relevant to occupational exposures. Groups of 50 male and 50 female F344/N rats and B6C3F1 mice were exposed to aerosols containing 0, 0.3, 1.0, or 3.0 mg/m3 cobalt sulfate hexahydrate, 6 h/day, 5 days/week, for 104 weeks. Survival and body weights of exposed rats and mice were generally unaffected by the exposures. In rats, proteinosis, alveolar epithelial metaplasia, granulomatous alveolar inflammation, and interstitial fibrosis were observed in the lung in all exposed groups. Nonneoplastic lesions of the nose and larynx were also attributed to exposure to all concentrations of cobalt sulfate. In 3.0 mg/m3 male rats and in female rats exposed to 1.0 or 3.0 mg/m3, the incidences of alveolar/bronchiolar neoplasms were increased over those in the control groups. Lung tumors occurred with significant positive trends in both sexes. The incidences of adrenal pheochromocytoma in 1.0 mg/m3 male rats and in 3.0 mg/m3 female rats were increased. Nonneoplastic lesions of the respiratory tract were less severe in mice than in rats. In mice, alveolar/bronchiolar neoplasms in 3.0 mg/m3 males and females were greater than those in the controls, and lung tumors occurred with significantly positive trends. Male mice had liver lesions consistent with a Helicobacter hepaticus infection. Incidences of liver hemangiosarcomas were increased in exposed groups of male mice; however, because of the infection, no conclusion could be reached concerning an association between liver hemangiosarcomas and cobalt sulfate. In summary, exposure to cobalt sulfate by inhalation resulted in increased incidence of alveolar/bronchiolar neoplasms and a spectrum of inflammatory, fibrotic, and proliferative lesions in the respiratory tracts of male and female rats and mice. Adrenal pheochromocytomas were increased in female rats, and possibly in male rats.
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PMID:Inhalation toxicity and carcinogenicity studies of cobalt sulfate. 1036 42

Clarithromycin (CAM) increased the median survival of patients with unresectable non-small-cell lung cancer who had received chemotherapy and/or radiotherapy [Chemotherapy 1997;43:288-296]. The present study was performed to ascertain whether CAM alone exhibits an antitumor effect against Lewis lung carcinoma (LLC) and to analyze the nature of its adjuvant effect on LLC-inoculated C57BL/6 mice. CAM at 10 mg/kg/day retarded the growth of subcutaneously inoculated LLC cells; consequently, the mean survival time of mice with LLC increased. This treatment was also effective in reducing the number of tumor nodules in the lung after intravenous inoculation with LLC cells. When tumor-bearing mice received an intravenous injection of vindesine sulfate (7 mg/kg) and cisplatin (6 mg/kg) 7 days after tumor inoculation, the chemotherapeutic effect was significantly enhanced by CAM treatment when it started 7 days after chemotherapy, but not when it started the day after chemotherapy. The delayed initiation of CAM treatment resulted in the enhancement of natural killer cell activity and CD8+ T cell cytotoxicity and increased the number of interferon-gamma-producing T cells and interleukin-4-producing T cells. These findings indicate that CAM can exhibit an antitumor effect by itself and also induce the well-balanced expansion of helper T cell subsets in tumor-bearing mice recovering from the immunosuppression caused by chemotherapy. CAM may therefore be a promising adjuvant drug in anticancer chemotherapy, and treatment with this macrolide should be initiated at some interval after basic cancer therapy.
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PMID:Adjuvant effect of clarithromycin on chemotherapy for murine lung cancer. 1060 98

In this study, ecological analysis was used to assess the relationship between ambient air pollution and human mortality. All the data on environmental measures and related factors, population size and number of deaths were collected for the city of Beijing, PR China and its eight districts for the years 1980-1992. In this study the concentration of SO(4)2- was selected as a main indicator of environmental pollution for the following reasons: (i) SO(4)2- data are available to cover all urban and suburban areas in Beijing compared with other air pollutants during the study period; (ii) SO(4)2- levels indicate the concentration of sulfide (include sulfate) and acid fog in the air, and they are significantly lower in cleaner districts than in others; and (iii) analyses showed that SO(4)2- levels are significantly correlated with daily mean concentrations of sulfur dioxide and nitrogen oxide, annual coal combustion, number of households using gas fuel, counts of motor vehicles and population density. Age-standardised mortality rates due to specific diseases were calculated using the Chinese population census data in 1990. Statistically significant correlations were observed between SO(4)2- concentration and total mortality and mortality due to cardiovascular disease, malignant tumour and lung cancer (r > 0.50 in all cases). The correlations were not only found between the current SO(4)2- concentration and these mortalities, but also for SO(4)2- levels measured up to 12 years prior to death, which may suggest long-term effects of air pollution. No significant correlations were observed for mortality from respiratory diseases and cerebrovascular diseases (r = 0.30-0.50). This study indicates that the concentration of SO(4)2- in air is a useful air pollution indicator in the areas where coal is used as the main source of energy. Areas with high levels of SO(4)2- experienced higher mortality due to a variety of chronic diseases.
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PMID:Ambient sulfate concentration and chronic disease mortality in Beijing. 1105 43

Nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) play a crucial role in the induction of lung cancer, and NNAL-O-glucuronide formation and elimination are important steps in detoxification of these compounds. In the present study, we investigated the ATP-binding cassette (ABC) protein, MRP1 (ABCC1), as a candidate transporter responsible for NNAL-O-glucuronide export. MRP1 mediates the active transport of numerous GSH-, sulfate-, and glucuronide-conjugated organic anions and can transport certain xenobiotics by a mechanism that may involve co-transport with GSH. Using membrane vesicles prepared from transfected cells, we found that MRP1 transports [3H]NNAL-O-glucuronide but is dependent on the presence of GSH (Km 39 microm, Vmax 48 pmol x mg(-1) x min(-1)). We also found that the sulfur atom in GSH was dispensable because transport was supported by the GSH analog, gamma-glutamyl-alpha-aminobutyryl-glycine. Despite stimulation of NNAL-O-glucuronide transport by GSH, there was no detectable reciprocal stimulation of [3H]GSH transport. Moreover, whereas the MRP1 substrates leukotriene C4 (LTC4) and 17beta-estradiol 17beta-(d-glucuronide) (E(2)17betaG) inhibited GSH-dependent uptake of [3H]NNAL-O-glucuronide, only [3H]LTC4 transport was inhibited by NNAL-O-glucuronide (+GSH) and the kinetics of inhibition were complex. A mutant form of MRP1, which transports LTC4 but not E(2)17betaG, also did not transport NNAL-O-glucuronide suggesting a commonality in the binding elements for these two glucuronidated substrates, despite their lack of reciprocal transport inhibition. Finally, the related MRP2 transported NNAL-O-glucuronide with higher efficiency than MRP1 and unexpectedly, GSH inhibited rather than stimulated uptake. These studies provide further insight into the complex interactions of the MRP-related proteins with GSH and their conjugated organic anion substrates, and extend the range of xenotoxins transported by MRP1 and MRP2 to include metabolites of known carcinogens involved in the etiology of lung and other cancers.
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PMID:Transport of the beta -O-glucuronide conjugate of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) by the multidrug resistance protein 1 (MRP1). Requirement for glutathione or a non-sulfur-containing analog. 1137 86

This study was undertaken to determine whether variations in concentrations of particulates in the ambient air of Montreal, Quebec, during the period 1984 to 1993, were associated with daily variations in cause-specific daily mortality. Fixed-site air pollution monitors in Montreal provided daily mean levels of various measures of particles and gaseous pollutants. Total sulfate was also measured daily (1986-1993) at a monitoring station 150 km southeast of the city (Sutton, Quebec). We used coefficient of haze (COH), extinction coefficient, and sulfate from the Sutton station to predict fine particles and sulfate from fine particles for days that were missing. We estimated associations between cause-specific mortality and PM(2.5), PM(10), predicted fine particles and fine sulfate particles, total suspended particles, coefficient of haze, extinction coefficient, and total sulfate measured at the Sutton station. We selected a set of underlying causes of death, as recorded on the death certificates, as the endpoint and then regressed the logarithm of daily counts of cause-specific mortality on the daily mean levels for the above measures of particulates, after accounting for seasonal and subseasonal fluctuations in the mortality time series, non-Poisson dispersion, weather variables, and gaseous pollutants. We found positive and statistically significant associations between the daily measures of ambient particle mass and sulfate mass and the deaths from respiratory diseases and diabetes. The mean percentage change in daily mortality (MPC), evaluated at the interquartile range for pollutants averaged over the day of death and the preceding 2 days, for deaths from respiratory diseases was MPC(COH)=6.90% (95% CI: 3.69-10.21%), MPC(Predicted PM2.5)= 9.03% (95% CI: 5.83- 12.33%), and MPC(Sutton sulfate)=4.64% (95% CI: 2.46-6.86%). For diabetes, the corresponding estimates were MPC(COH)=7.50% (95% CI: 1.96-13.34%), MPC(Predicted PM2.5)=7.59% (95% CI: 2.36-13.09%), and MPC(Sutton sulfate)=4.48% (95% CI: 1.08-7.99%). Among individuals older than 65 years at time of death, we found consistent associations across our metrics of particles for neoplasms and coronary artery diseases. Associations with sulfate mass were also found among elderly persons who died of cardiovascular diseases and of lung cancer. These associations were consistent with linear relationships. The associations found for respiratory diseases and for cardiovascular diseases, especially in the elderly, are in line with some of the current hypotheses regarding mechanisms by which ambient particles may increase daily mortality. The positive associations found for cancer and for diabetes may be understood through a general hypothesis proposed by Frank and Tankersley, who suggested that persons in failing health may be at higher risk for external insults through the failure of regulating physiological set points. The association with diabetes may be interpreted in light of recent toxicological findings that inhalation of urban particles in animals increases blood pressure and plasmatic levels of endothelins that enhance vasoconstriction and alter electrophysiology. Further research to confirm these findings and to determine whether they are causal is warranted.
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PMID:The association between daily mortality and ambient air particle pollution in Montreal, Quebec. 2. Cause-specific mortality. 1138 38

The 190 kDa multidrug resistance protein 1 (MRP1/ABCC1) is a founding member of a subfamily of the ATP binding cassette (ABC) superfamily of transport proteins and was originally identified on the basis of its elevated expression in multidrug resistant lung cancer cells. In addition to its ability to confer resistance in tumour cells, MRP1 is ubiquitously expressed in normal tissues and is a primary active transporter of GSH, glucuronate and sulfate conjugated and unconjugated organic anions of toxicological relevance. Substrates include lipid peroxidation products, herbicides, tobacco specific nitrosamines, mycotoxins, heavy metals, and natural product and antifolate anti-cancer agents. MRP1 also transports unmodified xenobiotics but often requires GSH to do so. Active efflux is generally an important aspect of cellular detoxification since it prevents the accumulation of conjugated and unconjugated compounds that have the potential to be directly toxic. The related transporters MRP2 and MRP3 have overlapping substrate specificities with MRP1 but different tissue distributions, and evidence that they also have chemoprotective functions are discussed. Finally, MRP homologues have been described in other species including yeast and nematodes. Those isolated from the vascular plant Arabidopsis thaliana (AtMRPs) decrease the cytoplasmic concentration of conjugated toxins through sequestration in vacuoles and are implicated in providing herbicide resistance to plants.
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PMID:Toxicological relevance of the multidrug resistance protein 1, MRP1 (ABCC1) and related transporters. 1155 26

Heparan sulfate proteoglycans is a major component of the cell surface and extracellular matrix and functions as a barrier against cationic molecules and macromolecules. Heparanase is an endoglucuronidase capable of specifically degrading heparan sulfate, and its activity is associated with the metastatic potential of tumor cells. To inhibit human heparanase expression in human cancer cells, we constructed an adenoviral vector carrying a full-length human heparanase cDNA in an antisense orientation (Ad-AS/hep). Increased heparanase expression in T.Tn human esophageal cancer cells and A549 human lung cancer cells after infection with an adenovirus vector expressing the human heparanase gene (Ad-S/hep) was specifically inhibited by simultaneous infection with Ad-AS/hep in a dose-dependent manner. A modified Boyden chamber assay demonstrated that infection with Ad-AS/hep significantly inhibited in vitro invasion of A549 cells after Ad-S/hep infection. Moreover, intrathoracic administration of Ad-AS/hep reduced the number and size of heparanase-expressing A549 tumors implanted intrathoracically into BALB/c-nu/nu mice. Our results suggest that heparanase contributes to the invasive phenotype of tumor cells, and that antisense-mediated inhibition of heparanase activity may be efficacious in the prevention of pleural dissemination.
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PMID:Antisense-mediated suppression of human heparanase gene expression inhibits pleural dissemination of human cancer cells. 1169 3

Interferon-gamma-inducible protein-10 (IP-10)/CXCL10 is a CXC chemokine that attracts T lymphocytes and NK cells through activation of CXCR3, the only chemokine receptor identified to date that binds IP-10/CXCL10. We have found that several nonhemopoietic cell types, including epithelial and endothelial cells, have abundant levels of a receptor that binds IP-10/CXCL10 with a Kd of 1-6 nM. Surprisingly, these cells expressed no detectable CXCR3 mRNA. Furthermore, no cell surface expression of CXCR3 was detectable by flow cytometry, and the binding of 125I-labeled IP-10/CXCL10 to these cells was not competed by the other high affinity ligands for CXCR3, monokine induced by IFN-gamma/CXCL9, and I-TAC/CXCL11. Although IP-10/CXCL10 binds to cell surface heparan sulfate glycosaminoglycan (GAG), the receptor expressed by these cells is not GAG, since the affinity of IP-10/CXCL10 for this receptor is much higher than it is for GAG, its binding is not competed by platelet factor 4/CXCL4, and it is present on cells that are genetically incapable of synthesizing GAG. Furthermore, in contrast to IP-10/CXCL10 binding to GAG, IP-10/CXCL10 binding to these cells induces new gene expression and chemotaxis, indicating the ability of this receptor to transduce a signal. These high affinity IP-10/CXCL10-specific receptors on epithelial cells may be involved in cell migration and, perhaps, in the spread of metastatic cells as they exit from the vasculature. (All of the lung cancer cells we examined also expressed CXCR4, which has been shown to play a role in breast cancer metastasis.) CXCR3-negative endothelial cells may also use this receptor to mediate the angiostatic activity of IP-10/CXCL10, which is also expressed by these cells in an autocrine manner.
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PMID:A functional IFN-gamma-inducible protein-10/CXCL10-specific receptor expressed by epithelial and endothelial cells that is neither CXCR3 nor glycosaminoglycan. 1171 27


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