Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reactive nitrogen species, such as peroxynitrite, nitrogen oxides and nitryl chloride, have been implicated as a cause of diverse pathophysiological conditions, including inflammation, neurodegenerative and cardiovascular diseases and cancer. We previously reported that 8-nitroguanine is formed by reactions of guanine or calf-thymus DNA with peroxynitrite in vitro. In the present study, we have studied the formation of 8-nitroguanosine and 8-oxo-7,8-dihydroguanosine in reactions of calf-liver RNA with various reactive nitrogen species. 8-Nitroguanosine in RNA was found to be much more stable than 8-nitro-2' -deoxyguanosine in DNA, which rapidly depurinates to release 8-nitroguanine. Both 8-nitroguanosine and 8-oxo-7,8-dihydroguanosine were formed in calf-liver RNA following exposure to various reactive nitrogen species, such as synthetic peroxynitrite. They were also formed in RNA by reactive species formed from nitric oxide and superoxide anion generated concomitantly from 3-morpholino-sydnonimine (SIN-1) and those formed with myeloperoxidase or horseradish peroxidase in the presence of nitrite and hydrogen peroxide. 8-Nitroguanosine was detected by HPLC with an electrochemical detector in enzymatic hydrolyzates of RNA isolated from human lung carcinoma cells incubated with synthetic peroxynitrite. Our results indicate that 8-nitroguanosine in cellular RNA could be measured as a marker of damage caused by endogenous reactive nitrogen species in tissues and cells.
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PMID:Formation of 8-nitroguanosine in cellular RNA as a biomarker of exposure to reactive nitrogen species. 1182 6

In the course of structure-activity relationships on rebeccamycin analogues, two dimers of dechlorinated rebeccamycin were synthesised with the aim to improve the interaction with DNA and in vitro antiproliferative activities. The synthesis of two dimeric compounds obtained by joining two molecules of dechlorinated rebeccamycin via the imide nitrogen is described. Melting temperature and DNase I footprinting studies were performed to investigate their interaction with DNA. Four tumour cell lines, murine L1210 leukaemia, human HT29 colon carcinoma, A549 non-small cell lung carcinoma and K-562 leukaemia, were used to evaluate the cytotoxicity of the drugs. Their effects on the cell cycle of L1210 cells were also investigated.
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PMID:Dimers from dechlorinated rebeccamycin: synthesis, interaction with DNA, and antiproliferative activities. 1200 58

A series of analogues of NAMI-A, a reference compound active on solid tumor metastases, were synthesized (NAMI-A type complexes). They share the same chemical structure of NAMI-A, and differ from it in the nature of the coordinated nitrogen ligand, such as pyrazole, thiazole and pyrazine, which are less basic than imidazole. This modification confers to the new NAMI-A type complexes a better stability in aqueous solution compared to the parent compound, a very important characteristic for a class of compounds that, with NAMI-A, is currently completing a phase I clinical trial at the Netherlands Cancer Institute of Amsterdam. Cytotoxicity and the effects on cell cycle and invasion were investigated on TS/A, B16-F10 and MCF-7 tumor cell lines, while the inhibition of lung metastases was determined on the mouse experimental tumors Lewis lung carcinoma and MCa mammary carcinoma. The new complexes show a pharmacological activity very similar to that of the parental compound NAMI-A: in vitro they are devoid of meaningful cytotoxicity against tumor cells, and in vivo they inhibit metastasis formation and growth approximately to the same extent as NAMI-A. Thus the new NAMI-A type complexes retain the same potent characteristic of NAMI-A to selectively interact with solid tumor metastases. However, compared to NAMI-A they do not stop cell cycle progression at G2-M level and are more active in preventing the spontaneous invasion of Matrigel by tumor cells exposed for 1 h to 10(-4) M concentration. Globally, these complexes take advantage of the knowledge on NAMI-A and appear particularly interesting for future clinical handling and applications.
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PMID:Ruthenium-based NAMI-A type complexes with in vivo selective metastasis reduction and in vitro invasion inhibition unrelated to cell cytotoxicity. 1242 85

Rebeccamycin analogues containing one azaindole unit, with and without a methyl group on the imide nitrogen and with the sugar moiety coupled either to the indole nitrogen or to the azaindole nitrogen were synthesized. To increase the solubility and induce stronger interactions with the target macromolecules, a bromo or nitro substitutent was introduced on the indole unit. The DNA binding and topoisomerase I inhibition properties were investigated together with the antiproliferative activities toward nine tumor cell lines. In addition, the effect of the compounds on the cell cycle of L1210 leukemia cells was examined. The nonaza analogues were found to be cytotoxic against all cell lines of the panel whereas the aza-analogues showed a selective action toward certain cell lines. They strongly inhibited the proliferation of SK-N-MC neuroblastoma, A431 epidermoid carcinoma and NCI-H69 small cell lung carcinoma cells, but showed little or no cytotoxic effect against IGROV ovary carcinoma, HT29 colon carcinoma, and A549 non small cell lung carcinoma cells. Whatever their cytotoxicity profile, all compounds induce similar cell cycle effects, with a marked G2+M block observed with L1210 leukemia cells. The data suggest that the molecular mechanism of action of the aza-analogue derivatives is different from that of rebeccamycin.
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PMID:Syntheses and antiproliferative activities of 7-azarebeccamycin analogues bearing one 7-azaindole moiety. 1257 Mar 82

Novel platinum(II) complexes with 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidines have been synthesized and characterized by infrared and multinuclear magnetic resonance spectroscopic techniques (1H, 13C, 15N, 195Pt). The complexes are of two types: [PtCl2(L)2] and [PtCl2(NH3)(L)], where L=5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine (dptp) and 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp). Significant 15N NMR upfield shifts (92-95 ppm) were observed for N(3) atom indicating this nitrogen atom as a coordination site. The molecular structure suggest that Pt(II) ion has the square planar geometry with N(3) bonded 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidines, N-bonded second ligand (NH3 for cis-[PtCl2(NH3)(L)] or, respectively, 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidines for cis-[PtCl2L2]) and two cis chloride anions. The antiproliferative activity in vitro of complexes (1-4) have been tested against the cells of four human cell lines: SW707 rectal adenocarcinoma, A549 non-small cell lung carcinoma, T47D breast cancer and HCV29T bladder cancer. The results indicate a moderate antiproliferative activity of (4) against the cells of rectal, breast and bladder cancer and a marked and selective cytotoxic effect of (1-3) against the cells of all studied human cancer lines.
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PMID:Multinuclear NMR spectroscopy and antitumor activity of novel platinum(II) complexes with 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidines. 1465 46

The synthesis of a family of rebeccamycin analogues in which one indole unit has been replaced by a 7-azaindole moiety is described. Substitutions have been carried out on the imide nitrogen, on the carbazole framework and on the sugar part. Compounds with a lactam upper heterocycle have also been prepared. The cytotoxicities of the newly synthesized compounds toward four tumor cell lines, one murine leukemia (L1210) and three human tumor cell lines (prostate carcinoma DU145, colon carcinoma HT29, and non-small cell lung carcinoma A549) have been evaluated and compared to those of rebeccamycin and parent non-aza and aza compounds.
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PMID:Synthesis and cytotoxicities of 7-aza rebeccamycin analogues bearing various substituents on the sugar moiety, on the imide nitrogen and on the carbazole framework. 1590 47

Clinical and experimental studies provide evidence that the plasminogen activation system plays a pivotal role in the pathogenesis of tumor growth and metastatic spread. The aim of the present study was to evaluate plasminogen activator inhibitor type I (PAI-1) in plasma and tumor extracts in patients with non-small cell lung cancer (NSCLC). The study group consisted of 146 patients (18 females, 128 males), aged 33-76 years with squamous cell carcinoma (107), adenocarcinoma (19), and mixed type of lung carcinoma (20) in pTNM stage I (72), stage II (30) and stage III (44) and 50 healthy volunteers as a control group (15 females, 35 males) aged 25-69 years. Blood for analysis was collected in the morning, 1-2 days before operation. Lung cancer and normal lung tissue specimens were obtained during surgery and homogenized in liquid nitrogen. The tissue extracts and plasma were assayed for concentration of PAI-1 with ELISA method. Significantly higher plasma level of PAI-1 was observed in patients with lung cancer than in control group. Concentration of PAI-1 in tumor tissues was significantly higher compared to normal lung tissue and was irrelevant from plasma level. Positive correlation between tumor level of PAI-1 and stage of lung cancer was noticed. Therefore it can be assumed that PAI-1 has an influence on the lung cancer progression.
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PMID:[Plasminogen activator inhibitor type 1 (PAI-1) in blood and tissue extracts of patients with non-small cell lung cancer]. 1602 96

Recent studies suggest that reactive oxygen (ROS) and nitrogen species (RNS) are highly associated with the pathogenesis of cigarette smoke related lung diseases but their role in the malignant conversion of bronchial epithelium is unclear. The immunohistochemical expression of inducible, endothelial and neuronal nitric oxide synthases (iNOS, eNOS and nNOS) and nitrotyrosine as a biomarker of oxidative/nitrosative stress was evaluated in 79 cases including 13 non-smokers, 20 smokers without chronic obstructive pulmonary disease (COPD), 22 with COPD and 24 with metaplasia-dysplasia-sequence of the bronchial epithelium. Normal lung of non-smokers was mainly negative for nitrotyrosine, while it was higher in the alveolar macrophages of cigarette smokers and COPD than in non-smokers (p=0.025, p<0.001), and in the alveolar epithelium of smokers and COPD than in non-smokers (p=0.049). There were no major differences in the nitrotyrosine immunoreactivity between the metaplastic/dysplastic lesions and bronchial epithelium of cigarette smokers. Inducible NOS and nNOS were mainly non-detectable or weak in the normal looking bronchial epithelium of smokers and COPD, whereas metaplasia and dysplasia showed positivity for iNOS (22/24) and nNOS (14/24) in the majority of cases. Strong immunoreactivity for iNOS and nNOS was also found more often in dysplastic than metaplastic (p=0.011 and p=0.049, respectively) specimens. Thus, smoking can cause protein nitration also in normal lung. Prominent iNOS and nNOS immunoreactivity in the metaplasia-dysplasia-lesions suggests a divergent role of NOSs in lung carcinogenesis.
Lung Cancer 2006 Mar
PMID:Nitric oxide synthases are associated with bronchial dysplasia. 1642 Sep 64

The synthesis of a new family of 7-aza-rebeccamycin analogues in which the sugar moiety is attached to the nitrogen of the pyridine ring is described. The capacity of the newly synthesized compounds to bind to DNA and to inhibit topoisomerase I has been evaluated. Their cytotoxicities toward four tumor cell lines, one murine leukemia L1210 and three human tumor cell lines, one prostate carcinoma DU145, one colon carcinoma HT29, and one non-small cell lung carcinoma A549, have been determined. Their abilities to inhibit the checkpoint kinase Chk1 have been evaluated.
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PMID:Synthesis and biological activities of 7-aza rebeccamycin analogues bearing the sugar moiety on the nitrogen of the pyridine ring. 1688 64

A 56-year-old woman, with dysgeusia in which nearly all food was felt as sweet, was admitted to our hospital seeking for treatment. Serum sodium concentration was 113 mmol/L, but serum creatinine, zinc, urea nitrogen, and potassium, as well as blood glucose, were all within normal ranges. Dysgeusia disappeared when serum sodium level was normalized, but recurred when hyponatremia relapsed. She was diagnosed as having large cell lung carcinoma. We considered that the cause of hyponatremia was inappropriate secretion of antidiuretic hormone (SIADH) due to lung carcinoma. Miraculin is one of taste-modifying substances which fits the sweet receptor site and induces a strong sweet taste. We considered that taste-modifying substances same as miraclin are involved in the pathophysiology of this disease.
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PMID:[Sweetness dysgeusia in a case of SIADH caused by lung carcinoma]. 1698 5


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