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)

Several water-solubilized versions of the zinc ionophore 1-hydroxypyridine-2-thione (ZnHPT), synthesized as part of the present study, have been found both to increase the intracellular concentrations of free zinc and to produce an antiproliferative activity in exponential phase A549 human lung cancer cultures. Gene expression profiles of A549 cultures treated with one of these water-soluble zinc ionophores, PCI-5002, reveal the activation of stress response pathways under the control of metal-responsive transcription factor 1 (MTF-1), hypoxia-inducible transcription factor 1 (HIF-1), and heat shock transcription factors. Additional oxidative stress response and apoptotic pathways were activated in cultures grown in zinc-supplemented media. We also show that these water-soluble zinc ionophores can be given to mice at 100 micromol/kg (300 micromol/m(2)) with no observable toxicity and inhibit the growth of A549 lung and PC3 prostate cancer cells grown in xenograft models. Gene expression profiles of tumor specimens harvested from mice 4 h after treatment confirmed the in vivo activation of MTF-1-responsive genes. Overall, we propose that water-solubilized zinc ionophores represent a potential new class of anticancer agents.
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PMID:Synthesis and anticancer properties of water-soluble zinc ionophores. 1859 33

Reaction of 4,4-biphenyl-disulfonyl chloride with aromatic/heterocyclic sulfonamides also incorporating a free amino group, such as 4-aminobenzenesulfonamide, 4-aminoethyl-benzenesulfonamide, 6-chloro-4-aminobenzene-1,3-disulfonamide or 5-amino-1,3,4-thiadiazole-2-sulfonamide afforded bis-sulfonamides which have been tested as inhibitors of the zinc enzyme carbonic anhydrase (CA, EC 4..2.1.1). The compounds were rather modest inhibitors of isozymes CA I and XII, but were more efficient as inhibitors of the cytosolic CA II and transmembrane, tumor-associated CA IX (inhibition constants in the range of 21-129 nM gainst hCA II, and 23-79 nM against hCA IX, respectively). The new bis-sulfonamides also showed inhibition of growth of several tumor cell lines (ex vivo), with GI(50) values in the range of 0.74-10.0 microg/mL against the human colon cancer cell line HCT116, the human lung cancer cell line H460 and the human breast cancer cell line MCF-7.
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PMID:Carbonic anhydrase inhibitors. Biphenylsulfonamides with inhibitory action towards the transmembrane, tumor-associated isozymes IX possess cytotoxic activity against human colon, lung and breast cancer cell lines. 1860 52

We analyzed the correlation between serum zinc levels and taste disturbance, and between patient backgrounds and serum zinc levels or taste disturbance, and evaluated the effects of polaprezinc oral disintegrating tablets on taste disturbance in 29 patients with lung cancer and one patient with malignant pleural mesothelioma who were receiving chemotherapy. Taste disturbance developed in 11 (36.7%) out of 30 patients. Serum zinc levels significantly correlated with taste disturbance (p=0.0227). Serum zinc levels were significantly lower (p=0.0235) and taste disturbance tended to be more frequent (p=0.0625) in males. Polaprezinc improved taste disturbance in 5 of 8 patients.
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PMID:[Involvement of zinc in taste disturbance occurring during treatment for malignant tumor in the chest and the effects of polaprezinc oral disintegrating tablets (a retrospective study)]. 1863 24

Oxidative stress and xenobiotic metabolizing enzymes are suspected to be related to carcinogenesis by different cellular mechanisms. Hence, our study aimed at identifying potential relationships between antioxidant defense parameters measured in blood and glutathione S-transferase (GST) genetic polymorphisms of four GST izoenzymes in lung cancer patients and reference individuals. The case-control study included 404 lung cancer patients and 410 non-cancer subjects as controls, matched by age, gender and place of living (central Poland). In control subjects with GSTM3*A/*A, GSTT1 null, GSTM1 null + GSTT1 null, GSTM3*A/*A + GSTT1 null genotype, glutathione peroxidase activity was significantly higher (P < 0.05) than in controls possessing respective potential protective GST genotypes. Controls with GSTM3*A/*A + GSTP1*B genotype presented significantly higher ceruloplasmin activity (P < 0.05) than GSTM3*B + GSTP1*A/*A carriers. Zinc level was significantly higher (P < 0.05) in controls and cases with GSTP1*B + GSTT1 null genotype and in cases with GSTM1 null + GSTP1*B genotype, when compared with respective potential protective GST genotypes. This case-control study indicates that particular defective GST genotypes may enhance the defense against oxidative stress. The potential relationship between the investigated antioxidative enzymes and microelements, and common functional genetic polymorphism of GST was observed mostly in control subjects.
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PMID:Antioxidant defense markers modulated by glutathione S-transferase genetic polymorphism: results of lung cancer case-control study. 1885 Jan 83

Several studies have investigated the levels of metallic elements in the pulmonary tissues of healthy subjects, patients with lung diseases and occupationally exposed subjects. The present meta-analysis was aimed at both assessing the possible contribution of metal exposure to the development of lung diseases, including lung cancer, and evaluating systematically the role and the weight of variability factors affecting the results of such studies. A literature research covering the period 1980-2007 was conducted using the public database PubMed. A standard scoring method was elaborated with a minimum score of 5 for inclusion and evaluation. Selected papers underwent a meta-analytical assessment. Fifty-eight papers were retrieved, but 21 of them could not be admitted to further analysis, due to failure to achieve the minimum score. The main limitations of individual studies included: limited sample sizes, poor control of smoking habits and differences in subjects' ages, lung tissue topography, sampling methods, storage procedures and data analysis. Copper and zinc were the most represented elements (121.96 +/- 0.74 and 12.98 +/- 0.07 microg/g dry weight, respectively). Among toxic metals, the highest concentrations were observed for chromium and lead (2.42 +/- 0.12 and 2.14 +/- 0.04 microg/g, respectively). Tissue concentrations were similar in unaffected tissues from both controls and lung cancer patients, whereas they were lower in lung tumor samples. A considerable intra- and inter-individual variability was noted. Such a variability of measures, combined with the very low metal concentrations calls for the definition and use of standardized procedures of sample collection, storage, and analysis.
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PMID:Metallic elements in lung tissues: results of a meta-analysis. 1892 10

Cadmium (Cd), a by-product of zinc production, is one of the most toxic elements to which man can be exposed at work or in the environment. Once absorbed, Cd is efficiently retained in the human body, in which it accumulates throughout life. Cd is primarily toxic to the kidney, especially to the proximal tubular cells, the main site of accumulation. Cd can also cause bone demineralization, either through direct bone damage or indirectly as a result of renal dysfunction. In the industry, excessive exposures to airborne Cd may impair lung function and increase the risk of lung cancer. All these effects have been described in populations with relatively high exposures to Cd in the industrial or in heavily polluted environments. Recent studies, however, suggest that the chronic low environmental exposure to Cd now prevailing in industrialized countries can adversely affect the kidneys and bones of the general population. These studies show consistent associations between various renal and bone biomarkers and the urinary excretion of Cd used to assess Cd body burden. The public health impact of these findings are still unknown. Further research is needed to ascertain that these associations are truly causal and not secondary to parallel changes in Cd metabolism and in the bone or kidney function occurring because of ageing or diseases unrelated to Cd exposure.
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PMID:Cadmium & its adverse effects on human health. 1910 47

Raman microspectroscopy allows probing subcellular compartments and provides a unique spectral fingerprint indicative of endogenous molecular composition. Although several spectroscopic cell studies have been reported on fixed samples, only few attempts concern single growing cells. Here, we have tested different optical substrates that would best preserve cell integrity and allow direct measurement of Raman spectra at the single living cell level. Calu-1 lung cancer cells were used as a model and their morphology and growth were assessed on Raman substrates like quartz, calcium fluoride, and zinc selenide. Data show that quartz was the most appropriate taking into consideration both cell morphology and proliferation rate (47% on quartz vs. 55% of BrdU-positive cells on conventional plastic). Using quartz, 40 cells were analysed and Raman spectra were collected from nuclei and cytoplasms using a 785 nm laser excitation of 30 mW at the sample, in the spectral range of 580-1750 cm(-1), and an acquisition time of 2 x 10 sec/spectrum. Discriminant spectral information related to nucleus and cytoplasm were extracted by multivariate statistical methods and attributed to nucleic acids, lipids, and proteins. Finally, Raman spectral imaging was performed to show the distribution of these components within the cell.
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PMID:Raman spectral imaging of single living cancer cells: a preliminary study. 1923 92

Matrix metalloproteinases (MMPs) are zinc-endopeptidases responsible for degradation of the extracellular matrix (ECM) components including basement membrane collagen, interstitial collagen, fibronectin, and various proteoglycans, during normal remodeling and repair processes. The turnover and remodeling of ECM must be tightly regulated since excessive or inappropriate expression of MMPs may contribute to the pathogenesis of tissue destructive processes associated with lung inflammation and disease. Despite the fact that our knowledge in the field of MMP biology is rapidly expanding, the role of MMPs in the pathogenesis of lung diseases is still not clear. The aim of the present review is to present the basic principles of MMP biology and, subsequently, to focus on the clinical and experimental evidence related to MMP activity in various lung disorders, including lung cancer, pleural effusions, chronic obstructive pulmonary disease, asthma, acute respiratory distress syndrome and interstitial lung diseases.
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PMID:Matrix metalloproteinases in respiratory diseases: from pathogenesis to potential clinical implications. 1935 80

A heavy-metal-free luminescent quantum dot (QD) based on doped zinc sulfide (ZnS), conjugated with a cancer-targeting ligand, folic acid (FA), is presented as a promising bio-friendly system for targeted cancer imaging. Doped QDs were prepared by a simple aqueous method at room temperature. X-ray diffraction and transmission electron microscopy studies showed the formation of monodisperse QDs of average size approximately 4 nm with cubic (sphalerite) crystal structure. Doping of the QDs with metals (Al(3+)), transition metals (Cu(+), Mn(2+)) and halides (F(-)) resulted in multi-color emission with dopant-specific color tunability ranging from blue (480 nm) to red (622 nm). Luminescent centers in doped QDs could be excited using bio-friendly visible light >400 nm by directly populating the dopant centers, leading to bright emission. The cytotoxicity of bare and FA conjugated QDs was tested in vitro using normal lung fibroblast cell line (L929), folate-receptor-positive (FR+) nasopharyngeal epidermoid carcinoma cell line (KB), and FR-negative (FR-) lung cancer cell line (A549). Both bare and FA-conjugated ZnS QDs elicited no apparent toxicity even at high concentrations of approximately 100 microM and 48 h of incubation. In contrast, CdS QDs prepared under identical conditions showed relatively high toxicity even at low concentrations of approximately 0.1 microM and 24 h of incubation. Interaction of FA-QDs with different cell lines showed highly specific attachment of QDs in the FR+ cancer cell line, leaving others unaffected. The bright and stable luminescence of the QDs could be used to image both single cancer cells and colonies of cancer cells without affecting their metabolic activity and morphology. Thus, this study presents, for the first time, the use of non-toxic, Cd-, Te-, Se-, Pb- and Hg-free luminescent QDs for targeted cancer imaging.
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PMID:Bio-conjugated luminescent quantum dots of doped ZnS: a cyto-friendly system for targeted cancer imaging. 1941 70

GLI family members are zinc-finger transcription factors, which are involved in embryogenesis and carcinogenesis through transcription regulation of GLI1, CCND1, CCND2, FOXA2, FOXC2, RUNX2, SFRP1, and JAG2. GLI1 transcription is upregulated in a variety of human tumors, such as basal cell carcinoma, lung cancer, breast cancer, gastric cancer, pancreatic cancer, and esophageal cancer. Hedgehog signaling via Smoothened cascade and receptor tyrosine kinase (RTK) signaling via PI3K-AKT cascade induce stabilization of GLI1 protein, whereas G-protein coupled receptor (GPCR) signaling via Gs-PKA cascade induces degradation of GLI1 protein. Here we report integrative genomic analyses of the GLI1 gene. The GLI1 and ARHGAP9 genes are located in a tail-to-tail manner with overlapping 3'-ends. ARHGAP9 was expressed in bone marrow, spleen, thymus, monocytes, and macrophages, whereas GLI1 was almost undetectable in normal tissues or cells with predominant ARHGAP9 expression. Because overlapping sense and anti-sense transcripts are annealed to each other to give rise to double-stranded RNAs functioning as endogenous RNAi, GLI1 expression might be negatively regulated by ARHGAP9 transcripts. GLI-binding element with one base substitution at the +1589-bp position from the transcriptional start site (TSS) of the human GLI1 gene was completely conserved in chimpanzee GLI1, mouse Gli1, and rat Gli1 genes. Ten Smad-binding elements, double E-boxes for EMT regulators, and double N-boxes for HES/HEY family members within intron 1 of the human GLI1 gene were also conserved in mammalian GLI1 orthologs. GLI1 transcription is upregulated due to Hedgehog, and TGFbeta signaling activation, whereas GLI1 transcription is downregulated due to Snail/Slug, and Notch signaling activation. Together these facts indicate that Hedgehog, TGFbeta, and RTK signals positively regulate GLI1, and that Notch, and GsPCR signals negatively regulate the GLI1.
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PMID:Integrative genomic analyses on GLI1: positive regulation of GLI1 by Hedgehog-GLI, TGFbeta-Smads, and RTK-PI3K-AKT signals, and negative regulation of GLI1 by Notch-CSL-HES/HEY, and GPCR-Gs-PKA signals. 1951 67


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