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)

5'-O-Mesyl-2',3'-O-isopropylidene ribonucleosides (4 and 12) were converted to their 5'-substituted nucleosides in good yields by reacted with NaN3 or KI. 2',3'-O-Isopropylidene ribonucleosides (3 and 11) were prepared in good yields from ribonucleosides 1 and 2 with a reaction mixture of acetone and triethyl orthoformate instead of using acetone diethyl acetal. Compound 1 or 2 was treated with 2-acetoxyisobutyryl halide (Cl or Br) to give 1-[2-O-acetyl-3-halo-3-deoxy-5-O-(2,5,5-trimethyl-1,3-dioxolan-4-on-2-yl)-beta-D-xylofuranosyl]-1,2,4-triazole-3-carboxamide (19, 22, and 23) in high yields. Instead of using 2-acetoxyisobutyryl bromide, the mixture of 2-acetoxyisobutyryl chloride and NaBr was employed in the synthesis of 22 and 23. Treatment of 19 with an activated Zn/Cu couple and deprotection gave 2',3'-anhydro nucleoside (21), and treatment of 22 and 23 with an activated Zn/Cu couple and a little of HOAc and deprotection gave corresponding 2',3'-unsaturated triazole nucleosides (24 and 25), respectively. The biological activity of the compounds (7-10, 15-18, and 24) was examined in human liver cancer cells (A-549), lung cancer cells (BEL-7402), and Flu-A cells.
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PMID:Synthesis of triazole nucleoside derivatives. 1288 23

The ability of nonpeptide antagonists to interact with gastrin releasing peptide receptors on lung cancer cells was investigated. PD176252 (3-(1H-Indol-3-yl)-N-[1-(5-methoxy-pyridin-2-yl)-cyclohexylmethyl]-2-methyl-2-[3-(4-nitro-phenyl)-ureido]-propionamide) and PD168368 (3-(1H-Indol-3-yl)-2-methyl-2-[3(4-nitro-phenyl)-ureido]-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide) inhibited specific 125I-gastrin releasing peptide binding to NCI-H1299 cells with IC50 values of 20 and 1500 nM, respectively. Similar binding results were obtained using NCI-H157, H345 and N592 human lung cancer cells. PD176252 inhibited the ability of 1 nM bombesin to cause elevation of cytosolic calcium in Fura-2 loaded NCI-H345 or H1299 cells, whereas it had no effect on basal cytosolic calcium. PD176252 antagonized the ability of 10 nM bombesin to cause elevation of c-fos mRNA in NCI-H1299 cells. Also, PD176252 inhibited the ability of 100 nM bombesin to cause tyrosine phosphorylation of focal adhesion kinase in NCI-H1299 cells. Using a [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay, PD176252 was more potent than PD168368 at inhibiting NCI-H1299 proliferation. Also, 1 microM PD176252 significantly inhibited lung cancer colony number in vitro. PD176252 in a dose-dependent manner inhibited NCI-H1299 xenograft growth in nude mice in vivo. These results indicate that PD176252 is a gastrin releasing peptide receptor antagonist, which inhibits the proliferation of lung cancer cells.
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PMID:Nonpeptide gastrin releasing peptide receptor antagonists inhibit the proliferation of lung cancer cells. 1290 92

Survivin and XIAP are members of inhibitors of apoptosis (IAPs) family. They are upregulated in various malignancies. Inactivation of these molecules has resulted in chemosensitization. The purpose of this study was to determine whether inhibition of survivin, XIAP, or both enhances radiotherapy in a lung cancer model. Transient transfection of H460 cells with antisense oligonucleotides (ASOs) against either molecule has specifically reduced their expression, by Western analysis. Results from 3-(4,5-methylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide and clonogenic assays suggest that inhibition of survivin or XIAP greatly decreased cell survival following irradiation. A significantly increased number of apoptotic cells were detected when H460 cells were treated with either antisurvivin, anti-XIAP or both ASOs (P=0.03, 0.0003 and 0.01, respectively) plus irradiation. H460 xenografts that were treated with ASOs plus radiotherapy demonstrated growth delay beyond 15 days. Growth delay in the groups of combined treatment was greater than that in other groups. However, treatment with ASOs alone did not affect tumor growth delay in mice, but decreased the survival of H460 cells in culture. Antisense treatment did not cause any mortality or weight loss during the 32 days of study. These data suggest that inhibition of survivin or XIAP radiosensitizes H460 lung cancer cells by upregulating apoptosis and downregulating cell survival. Combination of radiotherapy and inhibition of survivin and XIAP through the antisense approach results in improved tumor control by radiotherapy in a mouse model of lung cancer.
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PMID:XIAP and survivin as therapeutic targets for radiation sensitization in preclinical models of lung cancer. 1525 65

Lung cancer remains one of the most common causes of cancer-related death worldwide. Approximately 80% is histologically non-small cell lung carcinoma (NSCLC) and in about 70% of patients it is an unresectable type. Clinical studies indicated that application of platinum derivatives caused good results and combinations of platinum with other agents could improve median survivals. In view of the central problem of sufficient efficiency of drugs in chemotherapy, efforts have focused on the development of alternative platinum-based analogues that can be more effective in cancer treatment. cis-bis(3-aminoflavone)dichloroplatinum(II) (cis-Pt(II) complex of 3-aminoflavone) represents a novel class of platinum-based potential antitumour agents. In order to evaluate the degree of apoptosis, acridine orange/ethidium bromide and Hoechst 33258/propidum iodide double staining as well as RT-PCR (P53 and BAX expression evaluation) were used in lung cancer cell line A549 after treatment with this compound in comparison with cis-diamminedichloroplatinum(II) (cis-DDP). Apoptotic cells at early and late stages and also necrotic ones were observed after usage of cis-Pt(II) complex of 3-aminoflavone and the percentage of these cells outnumbered the values obtained after cis-DDP application. The former compound induced a higher percentage of P53 and BAX expression in A549 cells in comparison with the latter one. Results indicate the beneficial properties of cis-Pt(II) complex of 3-aminoflavone as a potential antitumor drug.
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PMID:Enhanced P53 and BAX gene expression and apoptosis in A549 cells by cis-Pt(II) complex of 3-aminoflavone in comparison with cis-DDP. 1601 88

Ornithine decarboxylase (ODC), the first enzyme of polyamine biosynthesis, was found to increase in cancer cells, especially lung cancer cells. Some chemotherapeutic agents aimed at decreasing ODC gene expression showed inhibitory effects on cancer cells. In this study, we examined the effects of adenoviral transduced antisense ODC on lung cancer cells. An adenovirus carrying antisense ODC (rAd-ODC/Ex3as) was used to infect lung cancer cell line A-549. The 3-(4,5-methylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay was used to analyze the effect on cell growth. Expression of ODC and concentration of polyamines in cells were determined by Western blot analysis and high performance liquid chromatography. Terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick-end labeling was used to analyze cell apoptosis. The expression of ODC in A-549 cells was reduced to 54%, and that of three polyamines was also decreased through the rAd-ODC/Ex3as treatment. Consequently, cell growth was substantially inhibited and terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick-end labeling showed that rAd-ODC/Ex3as could lead to cell apoptosis, with apoptosis index of 46%. This study suggests that rAd-ODC/Ex3as has an antitumor effect on the human lung cancer cells.
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PMID:Antitumor effect of antisense ornithine decarboxylase adenovirus on human lung cancer cells. 1676 Oct 99

A non-small-cell lung cancer without distant metastases was incidentally found in a 77-year-old man who had suffered from myasthenia gravis (MG) without thymoma. The patient's condition was stabilized by oral pyridostigmine bromide which he had taken during the past 6 years. He simultaneously underwent thymectomy and left lower lobectomy with regional lymph node dissection. Although postoperative myasthenic crisis occurred, mechanical ventilation and intravenous steroid pulse relieved the patient and the symptoms improved thereafter. Cases of operable lung cancer with non-thymomatous MG have rarely been reported and the appropriate therapeutic strategy for such cases remains to be debated. Their causal association remains to be identified, whereas some studies have implied that immune disorder due to the abnormal thymus might possibly enhance the oncogenesis of extrathymic malignancies. Myasthenic crisis should also be taken into account in postoperative management of MG patients who simultaneously undergo thymectomy and lobectomy for synchronous lung cancer.
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PMID:Non-small-cell lung cancer associated with non-thymomatous myasthenia gravis. 1676 10

Most human tumors overexpress or ectopically express peptide hormone/neurotransmitter receptors, which are being increasingly studied as a means to selectively deliver cytotoxic agents. Although a number of peptide ligand-constructs demonstrate tumor cytotoxicity, the role of specific tumoral receptor interaction in its mediation is unclear. To address this question, we synthesized camptothecin (CPT) bombesin (Bn) analogs, in which CPT was coupled via a novel carbamate linker, L2 [N-(N-methyl-amino-ethyl)-glycine carbamate], that were chemically similar but differed markedly in their potency/affinity for human Bn receptors. We then examined their ability to interact with Bn receptors and cause in vitro and in vivo tumor cytotoxicity. CPT-L2-[D-Tyr(6),beta-Ala(11),D-Phe(13),Nle(14)] Bn (6-14) (BA3) bound with high affinity and had high potency for all three human Bn receptor subtypes, whereas CPT-L2-[D-Tyr(6),beta-Ala(11), D-Phe(13),Nle(14)] Bn (6-14) [D-Phe-CPT-L2-BA3] had >1400-fold lower affinity/potency. (125)I-CPT-L2-BA3 but not (125)I-D-Phe-CPT-L2-BA3 was internalized by Bn receptor subtype-containing cells. CPT-L2-BA3 displayed significantly more cytotoxicity than D-Phe-CPT-L2-BA3 toward NCI-H1299 lung cancer cells in both 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide and clonogenic assays and more potently inhibited H1299 xenograft growth in nude mice. CPT-L2-BA3 was also metabolically more stable than its parent peptide and inhibited growth of a number of other tumor cell lines in vitro and in vivo. These results demonstrate that specific tumoral receptor interaction is important in mediating the ability of peptide ligand-cytotoxic constructs to cause cytotoxicity. Because many tumors overexpress Bn receptors, these results also demonstrate that CPT-L2-BA3 will be a useful agent for delivering receptor-mediated cytotoxicity to many different human tumors.
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PMID:In vitro and in vivo antitumor effects of cytotoxic camptothecin-bombesin conjugates are mediated by specific interaction with cellular bombesin receptors. 1676 20

Human lung cancer cell lines are widely used to test anticancer drugs. These in-vitro tests, however, preclude the detection of responses to paracrine factors from surrounding stroma. We have cocultured pulmonary fibroblasts CCD-19Lu, from a healthy donor, or HLF-A, from a patient with epidermoid carcinoma of the lung, with two human pulmonary adenocarcinoma cell lines to test the hypothesis that the fibroblasts stimulate the growth of the tumor cells. Both fibroblast cell lines significantly increased the proliferation of the pulmonary adenocarcinoma cell lines in 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide assays, with HLF-A fibroblasts yielding the most pronounced responses. The proliferation of the pulmonary adenocarcinoma cell lines in coculture with fibroblasts was blocked by antibodies against the transforming growth factor-alpha and amphiregulin. In addition, reverse transcription-polymerase chain reaction showed expression of mRNA for amphiregulin and transforming growth factor-alpha in all cell lines, whereas mRNA for the epidermal growth factor was detected only in pulmonary adenocarcinoma cell lines. Western blot analysis revealed that medium containing growth factors released by each fibroblast cell line activated extracellular signal-regulated kinase 1/2 in the both tested pulmonary adenocarcinoma cell lines, but activated Akt kinase only in A549 cells. Assessment of protein levels for cyclin D1 and cyclin E by Western blots demonstrated pronounced increases of both proteins in each pulmonary adenocarcinoma cell line, whereas protein levels for cyclin-dependent kinase inhibitor p21 remained unchanged. Immunocytochemical analysis showed positive immunoreactivity for P-extracellular signal-regulated kinase 1/2, cyclin D1 and cyclin E in pulmonary adenocarcinoma cells cocultured with fibroblasts or exposed to fibroblast-conditioned media. Our data suggest that the growth of pulmonary adenocarcinoma is stimulated by amphiregulin and transforming growth factor-alpha released from pulmonary fibroblasts. This may contribute to the disappointing clinical responses to anticancer drugs, which have shown promise in tests with lung cancer cell lines.
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PMID:Pulmonary fibroblasts stimulate the proliferation of cell lines from human lung adenocarcinomas. 1692 27

It is well known that lung cancer patients with severe chronic obstructive pulmonary disease (COPD) have a higher risk of postoperative complications than patients without COPD. However, the information regarding preoperative treatment to improve pulmonary function of the lung cancer patients with severe COPD is limited. Here, we report 3 lung cancer cases with severe COPD. Although all patients received medication without tiotropium bromide in combination with pulmonary rehabilitation for 1 or 2 months, their pulmonary function did not improve and the predicted postoperative FEV1/predicted FEV1 was below 40% in all cases. After the approval in Japan for use of tiotropium bromide in the treatment of COPD, all patients were treated with tiotropium bromide. The pulmonary function in all patients improved 2-4 weeks after the start of tiotropium bromide, and we performed lobectomy safely. Currently all patients maintain good pulmonary function without recurrence of lung cancer. We propose that treatment of tiotropium bromide might be one of the effective preoperative methods to improve pulmonary function of lung cancer patients with severe COPD.
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PMID:[Successful lobectomy in 3 lung cancer cases with severe COPD after treatment with tiotropium bromide]. 1735 80

We tested whether zoledronic acid, a biphosphonate with proposed apoptotic activity, augmented the cytotoxicity of cisplatin and/or gemcitabine in A549 lung cancer cell line. This cell line was subjected to different concentrations of the above chemotherapeutic agents and zoledronic acid. Cytotoxicity was assessed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide) assay. Particularly, zoledronic acid in 100 micromolar (microM) concentration augmented the cytotoxicity by cisplatin 1microg/ml from 25% to 70% (Z=3.22, P=0.0072). A significant portion of cells underwent apoptosis with or without zoledronic acid, but more so with the combination treatment as assessed by an Annexin V-FITC apoptosis detection kit. However, 100microM zoledronic acid showed 50% cytotoxicity on its own, but failed to improve cytotoxicity by Gemcitabine. Thus, we show for the first time in a lung cancer cell line that zoledronic acid bears cytotoxic potential on its own and in conjunction with cisplatin. The clinical potential of this finding should be further studied.
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PMID:Cisplatin cytotoxicity is enhanced with zoledronic acid in A549 lung cancer cell line: preliminary results of an in vitro study. 1741 95


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