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)

A photocrosslinkable chitosan (Az-CH-LA) aqueous solution containing paclitaxel resulted in an insoluble hydrogel within 30 s of ultrtaviolet light (UV)-irradiation. About 35-40% of the paclitaxel was released from the paclitaxel-incorporated chitosan hydrogel into phosphate buffered saline (PBS) within 1 day, after which gradual release occurred during 3 days under in vitro non-degradation conditions of the hydrogel. The paclitaxel remaining in the chitosan hydrogel retained its biological activity in vitro for at least 21 days, and was released from the chitosan hydrogel in vivo upon degradation of the hydrogel. The paclitaxel-incorporated Az-CH-LA hydrogel inhibited the growth of subcutaneously induced tumors with Lewis lung cancer (3LL) cells more effectively than those treated with only Az-CH-LA, only paclitaxel, and a non-treated group (control) for at least 11 days. Furthermore, paclitaxel-incorporated chitosan hydrogel markedly reduced the number of CD34-positive vessels in subcutaneous 3LL tumors, indicating a strong inhibition of angiogenesis. These results suggested that application of paclitaxel-incorporated Az-CH-LA hydrogel has an inhibitory activity on angiogenesis and tumor growth.
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PMID:Controlled release of paclitaxel from photocrosslinked chitosan hydrogels and its subsequent effect on subcutaneous tumor growth in mice. 1628 19

Eukaryotic protein translation elongation factor 1 alpha 2 (eEF1A2) is an oncogene that transforms mammalian cell lines and increases their tumorigenicity in nude mice. Increased expression of eEF1A2 occurs during the development of breast, ovarian, and lung cancer. Here, we report that eEF1A2 directly binds to and activates phosphatidylinositol 4-kinase III beta (PI4KIIIbeta), an enzyme that converts phosphatidylinositol to phosphatidylinositol 4-phosphate. Purified recombinant eEF1A2 increases PI4KIIIbeta lipid kinase activity in vitro, and expression of eEF1A2 in rat and human cells is sufficient to increase overall cellular phosphatidylinositol 4-kinase activity and intracellular phosphatidylinositol 4-phosphate abundance. siRNA-mediated reduction in eEF1A2 expression concomitantly reduces phosphatidylinositol 4-kinase activity. This identifies a physical and functional relationship between eEF1A2 and PI4KIIIbeta.
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PMID:Binding of elongation factor eEF1A2 to phosphatidylinositol 4-kinase beta stimulates lipid kinase activity and phosphatidylinositol 4-phosphate generation. 1708 55

Ceramide-1-phosphate (C1P) is emerging as a new addition to the family of bioactive sphingolipid metabolites. At low concentrations, C1P enhanced survival of NIH 3T3 fibroblasts and A549 lung cancer cells, while at high concentrations, it reduced survival and induced apoptosis. Apoptosis correlated with degradation of C1P to pro-apoptotic ceramide. To examine the role of endogenous C1P, expression of ceramide kinase, the enzyme that produces C1P, was downregulated, which reduced cellular proliferation, progression into S phase and enhanced apoptosis induced by serum starvation. Our results suggest that ceramide kinase determines the balance between pro-apoptotic ceramide and anti-apoptotic C1P to regulate cell fate, reminiscent of its function in plants.
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PMID:Ceramide kinase regulates growth and survival of A549 human lung adenocarcinoma cells. 1727 85

The inhalation of airborne pollutants, such as asbestos or silica, is linked to inflammation of the lung, fibrosis, and lung cancer. How the presence of pathogenic dust is recognized and how chronic inflammatory diseases are triggered are poorly understood. Here, we show that asbestos and silica are sensed by the Nalp3 inflammasome, whose subsequent activation leads to interleukin-1beta secretion. Inflammasome activation is triggered by reactive oxygen species, which are generated by a NADPH oxidase upon particle phagocytosis. (NADPH is the reduced form of nicotinamide adenine dinucleotide phosphate.) In a model of asbestos inhalation, Nalp3-/- mice showed diminished recruitment of inflammatory cells to the lungs, paralleled by lower cytokine production. Our findings implicate the Nalp3 inflammasome in particulate matter-related pulmonary diseases and support its role as a major proinflammatory "danger" receptor.
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PMID:Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. 1845 Dec 88

Hexavalent chromium [Cr(VI)] is an ubiquitous environmental contaminant and a well-known etiological agent of human lung cancer. Inside human cells, Cr(VI) is reduced to Cr(III), which can conjugate with amino acids, ascorbic acids, and glutathiones in the cytoplasm. Conjugated and unconjugated Cr(III) can enter the nucleus to form adducts with DNA and electrostatically interact with the phosphate group of DNA. It has been found that in both human and Escherichia coli systems, Cr(III) ligand-conjugated DNA ternary adducts are efficiently repaired by the nucleotide excision repair (NER) pathway. In contrast, DNA adducts formed by unconjugated Cr(III) with DNA are repaired significantly less efficiently by the NER system. These results raise the possibility that the NER system repairs Cr(III) ligand-conjugated DNA adducts and biadducts such as Cr(III)-guanine-phosphate adducts but not Cr(III)-phosphate adducts. To test this hypothesis, we determined the cutting efficiency and the mode of cutting of DNA modified with tannin-conjugated Cr(III) by the E. coli NER enzymes UvrABC. Tannin compounds, gallic acid (GA), and ethyl gallate (EGA) can reduce Cr(VI) to Cr(III) to form Cr(III)-GA 2 and Cr(III)-EGA 2, respectively, which can interact with a single guanine or adenine base but not with the DNA phosphate backbone. We found that UvrABC is able to incise Cr(III)-GA 2- and Cr(III)-EGA 2-modified plasmid DNA, and the amount of incision increased as a function of tannin concentration used for modifications. In contrast, UvrABC nuclease does not incise GA- and EGA-modified plasmid DNA. Mapping the sequence specificity of Cr(III)-GA 2- and Cr(III)-EGA 2-DNA formation in the human p53 gene sequence by UvrABC nuclease cutting, we found that the sequence specificity for both adducts is the same but is much more selective than Cr(III)-guanine-DNA adducts. Together, these results suggest that NER proteins from E. coli recognize the purine-Cr(III) adduct but not the Cr(III)-backbone phosphate complex.
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PMID:Recognition and incision of Cr(III) ligand-conjugated DNA adducts by the nucleotide excision repair proteins UvrABC: importance of the Cr(III)-purine moiety in the enzymatic reaction. 1845 13

Cigarette smoke is a complex chemical mixture that causes a variety of diseases, such as lung cancer. With the electrically heated cigarette smoking system (EHCSS), temperatures are applied to the tobacco below those found in conventional cigarettes, resulting in less combustion, reduced yields of some smoke constituents, and decreased activity in some standard toxicological tests. The first generation of electrically heated cigarettes (EHC) also resulted in increased formaldehyde yields; therefore, a second generation of EHC was developed with ammonium magnesium phosphate (AMP) in the cigarette paper in part to address this increase. The toxicological activity of mainstream smoke from these two generations of EHC and of a conventional reference cigarette was investigated in two studies in rats: a standard 90-day inhalation toxicity study and a 35-day inhalation study focusing on lung inflammation. Many of the typical smoke exposure-related changes were found to be less pronounced after exposure to smoke from the second-generation EHC with AMP than to smoke from the first-generation EHC or the conventional reference cigarette, when compared on a particulate matter or nicotine basis. Differences between the EHC without AMP and the conventional reference cigarette were not as prominent. Overall, AMP incorporated in the EHC cigarette paper reduced the inhalation toxicity of the EHCSS more than expected based on the observed reduction in aldehyde yields.
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PMID:Reduced toxicological activity of cigarette smoke by the addition of ammonia magnesium phosphate to the paper of an electrically heated cigarette: subchronic inhalation toxicology. 1846 53

Lignans are diphenolic compounds widely distributed in the plant kingdom. They are mainly localised in lignified tissues, seeds and roots. These molecules are involved in plant defence mechanisms, but are also interesting for human health. Flax lignans belonging to the phytoestrogens are metabolised after ingestion into enterolignans that may offer a protection against the onset and development of hormono-dependant cancers. In vitro studies based on mammalian cellular models tend to confirm their beneficial effects observed during epidemiological studies and give us insights about their mechanisms of action. The most studied lignan, podophyllotoxin, and its semi-synthetic derivatives (etoposide, teniposide, etoposide phosphate), are particularly interesting at a curative level due to their cytotoxic properties. These semi-synthetic derivatives are used in chemotherapy of lung cancer for example. However, the extensive use of these anticancer drugs will lead to the problem of podophyllotoxin supply. This molecule is currently extracted from the rhizomes and roots of an Indian species Podophyllum hexandrum which has subsequently become endangered. Strategies are investigated to obtain economically viable alternative sources of Podophyllotoxin from plants and in vitro cultures of several species. Among them, north american Podophyllum peltatum, Linum wild species, Hyptis, Anthriscus, Juniperus or Dysosma species which accumulate Podophyllotoxin or closely related derivatives, are good candidates. double dagger.
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PMID:[Interest of lignans in prevention and treatment of cancers]. 1846 29

Hypoxic cells within a tumor can account, in part, for resistance to radiotherapy and chemotherapy. Indeed, the oxygenation status has been shown to be a prognostic marker for the outcome of therapy. The purpose of this study was to determine whether Tc-99m HL91 (HL91), a noninvasive imaging tracer, detects tumor hypoxia in vitro in cell culture and in vivo in a tumor model. Uptake of HL91 in vitro into human lung cancer cells (A549) and murine Lewis lung cancer cells (LL2) was investigated at oxygen concentrations of 20% O2 (normoxia), and 1% O2 (hypoxia). HL91 biodistribution was studied in four groups: severe combined immune deficiency (SCID) mice bearing A549 tumors, C57BL/6NCrj (B6) mice bearing LL2 tumors, SCID controls, and B6 controls. Accumulation of the tracer was compared between tumors treated with hydralazine or phosphate-buffered saline (PBS). Scintigraphic images were obtained for hydralazine-treated mice and PBS-treated mice in each of the four study groups. Autoradiography of tumor slices was also acquired. In vitro studies identified hypoxia-selective uptake of HL91, with significantly increased uptake in the hypoxic state than in the normoxic state. Biodistribution and scintigraphy showed increased HL91 uptake during tumor hypoxia at 0.5 hours, and there was progressively increased activity for up to 4 hours after tracer administration. HL91 accumulation in tumor hypoxia was markedly increased in mice treated with hydralazine compared with those treated with PBS. Autoradiography revealed high HL91 uptake in the peripheral areas around the necrotic regions of the tumor, which were identified by histologic examination. HL91 exhibits selectivity for tumor hypoxia both in vitro and in vivo and provides a successful imaging modality for the detection of tumor hypoxia in vivo.
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PMID:Accumulation of Tc-99m HL91 in tumor hypoxia: in vitro cell culture and in vivo tumor model. 1907 78

Urethane is a chemical carcinogen which causes lung tumorigenesis in mice with similarities to human adenocarcinoma (AC). The sphingosine 1-phosphate agonist FTY720 administered to mice in doses above 5 mg/kg/day has been able to prevent hepatocellular carcinoma and bladder cancer. We used BALB/c mice in urethane-induced lung cancer model to investigate the effects of a lower dose of FTY720 (1 mg/kg/day). The benefits of FTY720 were associated with the time point of the compound administration. FTY720 30 Group presented lower incidence and smaller area of lung nodules, decreased PCNA and increased Caspase-3 expressions. The findings in FTY720 0 Group (nodule multiplicity and area, PCNA expression) were similar to Urethane Group suggesting that the administration of the compound at early time point did not affect lung tumor development. FTY720 90 Group presented the biggest nodule area which was associated with increased PCNA and decreased Caspase-3 expressions. FTY720 (30 days and 90 days) administration decreased CD4 + splenocytes and blood lymphocytes which caused opposite effects in lung tumor development - impairment and improvement respectively.In conclusion, FTY720 in low dose did not provide lung tumor inhibition in mice but its administration 30 days after the chemical carcinogen (Urethane) injection was associated with impaired tumor development.
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PMID:Lung tumor development in the presence of sphingosine 1-phosphate agonist FTY720. 1921 84

The novel urea primaquine derivatives 3 were prepared by aminolysis of primaquine benzotriazolide 2 with several hydroxyamines and ethylendiamine, while carbamates 4 were synthesized from the same precursor 2 and alcohols. All compounds are fully chemically characterized and evaluated for their cytostatic and antioxidant activities. The most prominent antiproliferative activity was obtained by compounds 3c, 3d, 3g, and 5b (IC(50)=9-40 microM). 1-(5-Hydroxypentyl)-3-[4-(6-methoxy-quinolin-8-ylamino)-pentyl]urea (3c) showed extreme selectivity toward SW 620 colon cancer cells (IC(50)=0.2 microM) and a bit less toward lung cancer cells H 460. Hydroxyurea 3h showed the highest interaction with DPPH. Primaquine twin drug 3g showed very significant inhibition on LOX soybean (IC(50)=62 microM). Almost all the tested derivatives highly inhibited lipid peroxidation, significantly stronger than primaquine phosphate.
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PMID:Urea and carbamate derivatives of primaquine: synthesis, cytostatic and antioxidant activities. 1958 Oct 98


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