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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemoradiation is becoming an important method of treatment of advanced lung cancer. Although many studies have demonstrated the efficacy of chemoradiation against lung tumors, the mechanism of its effect is still poorly understood. In this study, we analyzed the combined effect of cisplatin (CDDP) and irradiation on human lung cancer cell lines (PC-9 and Lu 134A) in vitro using MTT assay and isobologram analysis. To study whether the combined effect is due to induction of tumor cell apoptosis, we further quantified the nuclear fragmentation of tumor cells by flow cytometric analysis. Our study revealed that a combination of cisplatin and irradiation had an additive inhibitory effect on both PC-9 (adenocarcinoma) and Lu 134A (small cell carcinoma) tumor cell growth. Cisplatin improved the sensitivity of tumor cells to irradiation. The use of both cisplatin and irradiation doses could be reduced without decreasing the inhibitory effect. The additive inhibitory effect was correlated positively with the levels of tumor cell nuclear fragmentation. We concluded that combination treatment with cisplatin and irradiation is effective against lung tumors, not only small cell carcinoma but also non-small cell carcinoma, and the inhibitory effect was due to induction of tumor cell apoptosis.
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PMID:The inhibitory effect of cisplatin in combination with irradiation on lung tumor cell growth is due to induction of tumor cell apoptosis. 1089 52

Cyclooxygenase (COX)-2 has been reported to play an important role in carcinogenesis. Meloxicam (preferential COX-2 inhibitor) inhibits the growth of COX-2 positive and COX-1 negative colorectal cancer cells. We evaluated the effects of meloxicam on the growth of lung cancer cells. By reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis, COX-2 but not COX-1 was expressed in human non-small cell lung cancer (NSCLC) cell lines (A549 and PC14). In human small cell lung cancer (SCLC) cell line (H841), both COX-1 and COX-2 were not detected. MTT assay and prostaglandin (PG) E2 enzyme immunoassay showed that meloxicam inhibited the growth and PGE2 production of both A549 and PC14, but not H841 cells. These findings suggest that COX-2 may play an important role in the pathogenesis and progression of NSCLC, and that meloxicam may be a useful therapeutic agents in the treatment of NSCLC.
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PMID:Meloxicam inhibits the growth of non-small cell lung cancer. 1106 95

The effects of retinoic acid (RA) on lung cancer cells were investigated. Both all-trans (t-RA) and 13-cis RA (c-RA) decreased specific (125)I-VIP binding to NCI-H1299 cells in a time- and concentration-dependent manner. After 20 hr, 30 microM t-RA decreased specific (125)I-VIP binding by 60%. By Scatchard analysis, the density of VIP binding sites but not the affinity was reduced by 42%. NCI-H1299 VPAC(1) receptor mRNA was reduced by 48%. VIP caused a 3-fold elevation in the NCI-H1299 cAMP, and the increase in cAMP caused by VIP was reduced by 38% if the NCI-H1299 cells were treated with t-RA. Using the MTT assay, 3 microM t-RA and 3 microM c-RA inhibited NCI-H1299 proliferation by 60 and 23% respectively. Also, transforming growth factor (TGF)-beta2 increased after treatment of NCI-H1299 cells with t-RA whereas TGF-beta 1 mRNA was unaffected and TGF-beta 3 mRNA was decreased. These results suggest that RA may inhibit lung cancer growth by down-regulating VPAC(1) receptor and TGF-beta 3 mRNA but up-regulating TGF-beta 2 mRNA.
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PMID:Retinoic acid down-regulates VPAC(1) receptors and TGF-beta 3 but up-regulates TGF-beta 2 in lung cancer cells. 1115 Jun 43

VIP/PACAP are autocrine growth factors for lung cancer. VIP and/or PACAP mRNA is present in most lung cancer cell lines examined. Although mRNA for VPAC2-R is not common, VPAC1-R and PAC1-R mRNA is present in many lung cancer cell lines. 125I-VIP binds with high affinity to lung cancer cells and specific 125I-VIP binding is inhibited with high affinity by (Lys15, Arg16, Leu27)VIP1-7 GRF8-27, the VPAC1-R specific agonist, but not by Ro25-1553(18), the VPAC2-R specific agonist. VIP elevates cAMP and increases c-fos gene expression. The increase in cAMP and c-fos mRNA caused by VIP is inhibited by SN(VH). (SH)VH inhibited the proliferation of NCIH1299 cells in the MTT assay, which is based on cytotoxicity. In a recent cell line screen, (SN)VH inhibited the growth of 51 of 56 cancer cell lines including leukemia, lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, breast cancer, and prostate cancer (T. Moody, unpublished). It remains to be determined if (SN)VH will be useful for treatment of a wide variety of cancers.
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PMID:VPAC1 receptors and lung cancer. 1119 32

Docetaxel (DOC) plus cisplatin (CDDP) is a novel combination chemotherapy for the treatment of advanced non-small-cell lung cancer (NSCLC). We investigated the combined effect of DOC with CDDP in sequence and the reverse schedule for NSCLC cell lines EBC-1 (squamous cell carcinoma) and RERF-LC-MS (adenocarcinoma) using an MTT assay and an improved isobologram method. The results showed that the combination of DOC and CDDP in human lung cancer cell lines was antagonistic. To investigate the possible mechanism of the antagonistic effect, we focused on the cell cycle perturbation and the inhibition of apoptosis fractions induced by chemotherapeutic agents. Pretreatment of CDDP significantly blocked the following DOC-induced apoptosis fraction. Therefore we consider that the suppression of apoptosis could be one of the mechanisms for antagonistic effects of combination chemotherapy of DOC and CDDP.
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PMID:Combined effect of docetaxel and cisplatin for non-small cell lung cancer cell lines in vitro. 1120 87

Howiinol A (GHM-10) is a kind of phenylethylene pyrone compounds isolated from Goniothalamus howii. By using the techniques of cell growth curve determination, MTT test, soft agar colony assay and experimental therapy of transplantable tumors in mice, it is found that GHM-10 exerts potent inhibitory effect on cancer cells but its influence on normal cells is relatively slight; the sensitivity of a drug-resistant cell line, KB/VCR 2000, to GHM-10 is similar to its parent cell line KB. Remarkable therapeutic effect can be seen in mice bearing H22 hepatoma and Lewis lung cancer and in mice with ascetic sarcoma 180 when GHM-10 is orally or intraperitoneally administered. The IC50s of L1210 cells treated with GHM-10 for 1 and 24 h are 6.85 and 3.32 micrograms.ml-1 respectively. The ratio of IC50 1 h and IC50 24 h is only 2.06, indicating that the action of GHM-10 is conformed to a cell cycle non-specific cytotoxic agent. By using trypan blue exclusive test and morphological examination, it is demonstrated that the main effect of GHM-10 is to inhibit the cell proliferation. Flow cytometery technique is used to analyze the cell cycle of L1210 cells. The results show that to some extent, GHM-10 blocks the cell cycle transition from G1 phase to S phase. By using [3H] labeled precursor incorporation technique, it is shown that GHM-10 significantly suppresses the biosynthesis of DNA, RNA and protein in L1210 cells, and the DNA synthesis is mostly affected. At 1 h after the cells were treated with GHM-10, these inhibitory effects have already been irreversible, suggesting that GHM-10 may cause structural damage on DNA molecules. However, GHM-10 is unable to intercalate into DNA molecules or to destroy its structure directly. By using single cell gel electrophoresis and alkaline elution technology, it is confirmed that GHM-10 causes DNA molecule damage and single strand breakage in L1210 cells. Further studies show that GHM-10 markedly inhibits DNA dehelix induced by DNA topoisomerase II both inside and outside the cells, indicating that GHM-10 is acting as an inhibitor of DNA topoisomerase II.
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PMID:Anticancer effect of Howiinol A and its mechanism of action. 1126 Dec 1

Integration of chemotherapy and radiation is the standard practice in the management of locally advanced inoperable NSCLC. To assess the biological interaction between third generation chemotherapeutic agents and radiation in non-small cell lung cancer (NSCLC) in vitro, we tested a number of different drugs (paclitaxel, docetaxel, gemcitabine, topotecan, SN-38 and cisplatin) combined with radiation, in lung cancer cell lines. Cellular chemosensitivity was determined, using the semi-automated colorimetric MTT assay, after 48, 72 and 96 h of exposure to increasing drug concentrations, (0.001-100 microM) and radiation doses (100-400 cGy). Cell lines used were the adenocarcinoma (ADK), A-549, and the squamous-cell carcinoma (SCC), LX-1. Cells were pre-treated with anticancer agents at 24, 12 and 0 h before irradiation. Cytofluorimetric cell cycle analysis was performed. A significant S-phase block or a G(2)/M block was seen with gemcitabine and topotecan or paclitaxel pre-treatment, respectively. Apoptosis was seen only after paclitaxel exposure in the A-549 cell line. Despite a similar pattern of cell-kinetic changes induced by chemotherapy pre-treatment in all cell lines, the adenocarcinoma A-549 cell line was not radiosensitized by any of the anticancer agents tested, whereas synergism was observed in the LX-1 squamous carcinoma cell line, when exposed to gemcitabine, SN-38, topotecan and cisplatin. Paclitaxel, despite a favourable cell cycle effect, was not found to be synergistic with radiotherapy in our experimental model. In conclusion, the observed synergism appears to be dose- and timing-independent and seems to be related to the histological subtype being present in SCC only. Favourable perturbation of the cell cycle is evident with all the new agents tested in both cell types, but was not sufficient to produce synergism with radiation.
Lung Cancer 2001 Jul
PMID:Interaction between novel anticancer agents and radiation in non-small cell lung cancer cell lines. 1142 93

Gal alpha(1, 3) Gal (gal epitope) is a carbohydrate epitope and synthesized in large amount by alpha(1, 3) galactosyltransferase [alpha(1, 3) GT] enzyme on the cells of lower mammalian animals such as pigs and mice. Human has no gal epitope due to the inactivation of alpha(1, 3) GT gene but produces a large amount of antibodies (anti-Gal) which recognize Gal alpha(1, 3) Gal structures specifically. In this study, a replication-deficient recombinant adenoviral vector Ad5sGT containing pig alpha(1, 3) GT cDNA was constructed and characterized. Adenoviral vector-mediated transfer of pig alpha(1, 3) GT gene into human tumor cells such as malignant melanoma A375, stomach cancer SGC-7901, and lung cancer SPC-A-1 was reported for the first time. Results showed that Gal epitope did not increase the sensitivity of human tumor cells to human complement-mediated lysis, although human complement activation and the binding of human IgG and IgM natural antibodies to human tumor cells were enhanced significantly after Ad5sGT transduction. Appearance of gal epitope on the human tumor cells changed the expression of cell surface carbohydrates reacting with Ulex europaeus I (UEA I) lectins, Vicia villosa agglutinin (VVA), Arachis hypogaea agglutinin (PNA), and Glycine max agglutinin (SBA) to different degrees. In addition, no effect of gal epitope on the growth in vitro of human tumor cells was observed in MTT assay.
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PMID:Adenovirus-mediated expression of pig alpha(1, 3) galactosyltransferase reconstructs Gal alpha(1, 3) gal epitope on the surface of human tumor cells. 1145 43

After exposure of H460 cells to an increasing concentrations of cis-diammine-dichloroplatinum(II) (cisplatin, CDDP) for 6 months, cisplatin resistant cells were isolated (H460/CIS). The biologic behaviors of H460 and H460/CIS cells were tested using animal experiments. Only the resistant cells developed lung metastases despite cisplatin treatment. The characteristics of H460/CIS cells are as follows, MTT analyses revealed that H460/CIS cells were markedly resistant to cisplatin compared with their parental cells. Also, H460/CIS cells exhibited cross-resistance to DNA damaging agents such as doxorubicin (DXR) and etoposide. Cisplatin treatment dramatically increased p53 expression in parental cells but not in H460/CIS cells which expressed basal levels of p53. Without cisplatin treatment, Bcl-2 and Bax were expressed in H460/CIS cells, but not in parental cell. Our data suggested that p53, Bax and Bcl-2 were up-regulated in H460/CIS cells. These changes could explain some of the mechanisms of cisplatin resistance. Thus, H460/CIS could be useful to investigate the mechanisms of drug resistance to cisplatin including apoptotic gene expressions conferring drug resistance, thereby making progress in the treatment of cisplatin-resistant tumor cells.
Lung Cancer
PMID:In vitro establishment of cis-diammine-dichloroplatinum(II) resistant lung cancer cell line and modulation of apoptotic gene expression as a mechanism of resistant phenotype. 1155 17

Coumarin in vivo has antitumor activity in various types of cancer. In vitro, coumarin and 7-hydroxycoumarin, its major biotransformation product in humans, inhibit the proliferation of several human tumor cell lines. The molecular mechanisms of these effects are unknown. To gain information about these mechanisms, we studied the effects of coumarin and 7-hydroxycoumarin in the human lung adenocarcinoma cell line A-427 on the inhibition of: (i) cell proliferation; (ii) cell cycle progression; and (iii) expression of cyclins D1, E and A. The inhibitory concentrations 50 (IC(50)) of both compounds were estimated by cytostatic assays of tetrazolium (MTT) reduction. The effects on cell cycle progression were assayed with propidium iodide and BrdU using DNA histograms and multiparametric flow cytometry. The percentages of cells expressing cyclins D1, E, and A were estimated by means of bivariate flow cytometry using propidium iodide, and FITC-conjugated monoclonal antibodies for each cyclin. The IC(50) (+/-S.E.M. n=3) of 7-hydroxycoumarin and coumarin at 72 h exposure, were 100+/-4.8 and 257+/-8.8 microg/ml, respectively. 7-Hydroxycoumarin at the concentration of 160 microg/ml (1 mM), inhibited the G(1)/S transition of the cell cycle, an action consistent with the cytostatic effect. No significant decreases of cyclins E and A were observed. In contrast, cyclin D1 significantly decreased, which appears to indicate an action of 7-hydroxycoumarin in early events of phase G(1). However, messenger RNA of cyclin D1, assayed by RT-PCR, did not change. This suggests a posttranscriptional effect. The effects of coumarin were not significant. Cyclin D1 is overexpressed in many types of cancer, and its inhibition has been proposed as a pharmacological and therapeutic target for novel antitumor agents. Knowledge of the decrease of cyclin D1 by 7-hydroxycoumarin may lead to its use in cancer therapy, as well as to the development of more active compounds.
Lung Cancer 2001 Nov
PMID:Decrease of cyclin D1 in the human lung adenocarcinoma cell line A-427 by 7-hydroxycoumarin. 1167 77


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